Machiavelli's Laboratory

Dirty Little Secret of Health Informatics

2011-06-27T10:16:00.000-07:00

I have just posted a new article describing another flagrant deficiency of the medical industrial complex. The title of the article is:

THE DIRTY LITTLE SECRET OF THE HEALTH INFORMATICS INDUSTRY: Without a reliable patient identifier system, electronic health records (EHRs) are worthless; And most systems are unreliable.

Seriously, patient identifiers are at the heart of the push to create electronic health records for everyone. The purpose of the article is to describe the kinds of problems that arise when patient identifiers are unreliable. Most institutions simply do not have in place a sensible system to ensure that every patient has a unique identifier, and that all of the reports for a patient are permanently "held together" by the identifier. The article also describes the features of a patient identifier system, emphasizing the essential role of identifiers in healthcare and biomedical research.

The article is available on my web site at:

http://www.julesberman.info/book/id_deid.htm

© 2011 Jules J. Berman

Tips for writing an evil grant

2011-01-30T09:56:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

The typical grant reviewer gives your grant a perfunctory once-over, looking for answers to the following simplistic questions:

1. Is the applicant a bona fide scientist? This often boils down to whether the reviewer knows the applicant or knows any of the people who the applicant has worked with, past or present. If the applicant is a complete unknown to the reviewer, it is unlikely that his application will be taken seriously by the reviewer.

2. Does the applicant have a history of completing the grant awards that he has received? If the members of the study section learn that you botched a prior grant, it's an uphill battle to get another chance of funding. One of the best ways of unloading a failing grant is to relocate to a new institution. Many grants are tied to a set of resources that are unique to the host institution. When the principal investigator leaves, the grant stays in the institution. When this happens, the principal investigator is relieved from his obligation to fulfill the grant. The home institution continues to draw down its indirect costs for the grant (i.e., the part of the grant funding that pays for the administrative and physical overhead of supporting the grant), but the incentive to follow the grant's research plan has vanished. In these cases almost everyone wins. The principal investigator has moved on to another job; he can list his severed grant as proof of his fundability, and he can apply for another grant without being held accountable for the failure of his research project. The original host institution continues to collect indirect costs for the duration of the grant. Some lucky researcher in the host institution will be assigned as the new principal investigator for the grant, and this is equivalent to winning a grant, without bothering to compete in the grant application pool. In the case of NIH grants, the only loser is the American taxpayer, who is saddled with paying for a non-productive grant, for the duration of the funding period.

3. Does the applicant have a friend on the study section? Applicants with little or no name recognition in the scientific community can redeem their credibility if they have a champion among their study section. A convivial member of a study section can exert great influence by discussing significant prior contributions from the applicant, and by prophesying the applicant's future productivity. Study section members are asked not to promote the efforts of applicants from their own institutions, but a shrewd study section member often looks for friends who live beyond his own back yard. In winter, a study section member who lives in Wisconsin, might dream of working in San Diego. An evil scientist never misses an opportunity to solidify friendships with influential academics from a desirable location. Exercising his powers of persuasion, he can push the score of a mediocre grant into the "funding" range. Once accomplished, how does the evil scientist take credit for his act? There is no effective way to maintain the confidentiality of study section discussions. It is commonplace for study section members, during their refreshment breaks, to get on their phones and spread the news. The evil scientist will place a call to the applicant, or to a close friend of the successful applicant, relating the thrilling tale of how he saved the grant, just as it was headed for oblivion.

4. Is the grant well written? Most grant applicants do not understand that a grant application is a work of literature, not a technical report. It's not sufficient to provide a correct but perfunctory response to the headings included in the template provided by the funding agency. Like all works of literature, your grant application must provide compelling reasons to read the first sentence, then the next sentence, and so on, until the grant is finished. The biggest mistake that most grant applicants make is to wait until the last possible moment to write the grant. Although it is possible to write a grant application at the last possible moment, it is impossible to re-write a grant application that was written at the last possible moment. Persuasive grants are written, then re-written, and re-written again, until the applicant is satisfied that the goals of the grant will become the goals of the reviewer. A thoughtfully crafted grant proposal is such a rare commodity that it will be likely receive a fundable score, on the basis of literary merit alone.

5. Does the grant address an important scientific problem, that has not been previously solved? This seems obvious, but many grant applications cannot meet this simple condition. A few bad grant applications address problems that have already been solved. More commonly, a grant application will address a problem that has not been solved previously, but which has no scientific importance (i.e., not much reason to solve the problem in the first place). Applicants must unburden themselves of the popular but misguided notion that all unsolved problems have potential merit. The burden of uncovering the merit in a research problem falls on the applicant. He must somehow persuade the study section that a problem that nobody has bothered to solve, throughout human history, is more worthy of funding than the projects offered by his competitors.

6. Does the grant application make any scientific sense? The "sense" of a research project is determined by the scientific paradigm that spawned the central hypothesis. For example, if you believe that there are four essences to the universe (i.e., earth, air, fire, and water), then you might find a project, that measures the power of water to overcome the power of fire, to be rather sensible. If you believe that aliens from other planets walk among us, you might want to fund a registry database that tracks the whereabouts of illegal extraterrestrials. Here's another example. In 2003, NCI set a goal of eliminating death from cancer by the year 2015 (1). In the ensuing years, NCI has not pushed back the expected delivery date. If you believe that cancer will be conquered by the year 2015, then it would make no sense to apply for a cancer research grant that extends into the year 2016 (after cancer has already been cured). For that matter, it would make no sense to fund NCI research grants awarded in the year 2011 with five years of funding; four will suffice. It's best to pander to the biases that prevail in the committee. If your reviewers believe in global warming, and that the oceans will rise 18 inches in the next decade, then you must believe the same. If they don't believe in global warming, then neither should you.

7. Is the grant budget realistic? Don't be cheap. If your grant budget is too small for the work proposed, the review committee will conclude that you don't know what you're doing (which you don't). If it's too large, they'll think the grant is simply a revenue-generating scheme (which it is). What is the correct amount of money to request for your grant? Nobody knows. If you think about it, you'll realize that it is impossible to predict the costs of research; nobody knows what techniques will work before they've actually worked. The best you can do is to plagiarize your budget with the budget of a successfully funded grant from your own institution.

Evil scientists should take note that honesty is not a criteria for grant success. It makes no sense to write a grant proposal that faithfully describes your intended research. The review committee will be composed by your competitors, who will give your grant a low score, and steal your ideas. Under these circumstances, honesty is the worst policy. Feel free to write ridiculous, misleading proposals; even if your grant if rejected, at least you'll have the satisfaction of leading your competitors astray.

Study section members are not endowed with the ability to peer into the future. They cannot determine which grants will yield major advances, and which grants will contribute nothing to science or society. The only thing that a study section member can do is to judge whether the grant meets the general criteria for a well-constructed grant (vida supra). Very few grant applications meet these criteria. Hence, very few grant applications deserve funding. Nonetheless, the available funds will be distributed to thousands of applicants. A Committee of Science and Public Policy report concluded that if you were to switch the review group for a set of grant applications, you would change the group of funded investigators by 25-30% (2). Agencies would save a great deal of money if they pooled the adequately written grants, and awarded funds by lottery. Deep down, everyone knows this.

REFERENCES

[1] Eschenbach AC. NCI sets goal of eliminating suffering and death due to cancer by 2015. Journal of the National Medical Association 95:637-639, 2003.

[2] Garfield E. Essays of an Information Scientist. Current Contents 5:3, Feb. 2, 1987.

- © 2011 Jules Berman

Free ebook update for Machiavelli's Laboratory

2011-01-26T05:18:00.000-08:00

I've just prepared an updated ebook version of Machiavelli's Laboratory. It's available for free download at:

http://www.julesberman.info/integ/machfree.htm

Just click the link under the book title, near the top of the web page.

Anyone with a ebook reader should be able to read the MobiPocket file from any mobile device.

If you have a PC, and you've been reading the HTML or the PDF version of Machiavelli's Laboratory, I would highly recommend that you try reading the MobiPocket ebook version on your PC, using freely available ebook reader software.

I personally use MobiPocket desktop reader. It's free, easy to download and install, and provides a much better reading experience than HTML or PDF. Aside from the improved esthetics, The MobiPocket reader provides navigation and search features not available on the PDF version. The MobiPocket site is:

http://www.mobipocket.com/en/downloadsoft/productdetailsreader.asp

My understanding is that there are other "readers" for the PC (usually called desktop readers) widely available on the web.

- Jules J. Berman

Conflict declarations

2011-01-15T05:50:00.001-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.This blog entry continues yesterday's blog on Acknowledgments in scientific manuscripts

Editors have a bad record when it comes to ensuring that their published articles are free from financial conflicts (1), (2). Authors seldom volunteer their conflicts of interest, and editors seldom demand disclosures (3). Ensuring integrity is a time-consuming and thankless task. No editor has ever earned a dollar for his journal by uncovering a conflict of interest in a study. Basically, editors are in the business of selling journals, not advancing science.

Until recently, editors did not ask authors to disclose conflicts that might bias a manuscript's conclusions . Nobody really cared. Today, most journals have a "Conflicts" section, but statements are prepared in such a perfunctory fashion that their value is negligible.

Here is an example of about the best "Conflicts" section that you can hope to find in a manuscript.

The author(s) declare that they have no competing interests (4).

The sentence offers a clear statement from the authors, indicating that no conflicts exist. Of course, the editor offers no corroborating statement indicating that he has made a reasonable effort to validate the author's declaration.

Among the many scientific journals, there is no standard "Conflicts" statement. Some statements are barely worth reporting. Here is an example of a statement that could bear some improvement.

The authors declare no competing financial interests (5).

Here, the authors declare that they have no competing financial interests. Whether they have competing interests of a non-financial nature is anyone's guess.

Here's another.

The author reported no potential conflicts of interest (6).

Does this mean that they authors had actual conflicts; not potential conflicts? Or perhaps the statement conveys a completely different message. It may mean that conflicts exist, but they're all so very uninteresting.

Here's another

The authors of this manuscript have no conflict of interest to declare (7).

If I say, "I have no money to give you," it may mean that I have no money whatsoever, or it may mean that none of my money is held for the purpose of giving to you. In this "Conflicts" statement, the authors may have conflicts of interest, but none that they care to declare.

For brevity, the following cannot be beaten.

Competing interests: none declared (8).

Does this mean that the authors declared that they had no conflicts, or does it mean that the authors did not declare anything at all? Perhaps they forgot to respond to the editor's "Competing interests" query.

Why can't the editors of scientific journals do a little editing of their own and compose a useful "Conflicts" statement?

REFERENCES

[1] Smith R. Journals fail to adhere to guidelines on conflicts of interest. BMJ 323:651 (inclusive), 2001.

[2] Gross CP, Gupta AR, Krumholz HM. Disclosure of financial competing interests in randomised controlled trials: cross sectional review. BMJ 326:526-527, 2003.

[3] Hussain A, Smith R. Declaring financial competing interests: survey of five general medical journals. BMJ 323:263-264, 2001.

[4] Gressner OA, Weiskirchen R, Gressner AM. Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options. Comparative Hepatology 6:7, 2007.

[5] Landgren O, Kyle RA, Pfeiffer RM. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 113:5412-5417, 2009.

[6] Slany RK. The molecular biology of mixed lineage leukemia. Haematologica 94:984-993, 2009.

[7] Odell A, Askham J, Whibley C, Hollstein M. How to become immortal: let me count the ways. Aging 2:160-165, 2010.

[8] Bauer AJ, Stratakis CA. The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumorigenesis. J Med Genet 42:801-810, 2005.

- © 2011 Jules Berman

Acknowledgments

2011-01-14T06:16:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

The Acknowledgment section of published papers provides public recognition for those people who contributed to the manuscript. It's a sort of consolation prize for people who weren't included as co-authors.

For those who have never paused to read the Acknowledgment section at the end of a research manuscript, here is a typical example:

"For advice and discussion, we thank L.F. Cai, C. F. Kim, T. Motoi, R. Hobbs, J. Clohessy, T. Yung, A. Carracedo, K. Ito, Pandolfi lab members, B. Clarkson, members of the MSKCC Lung Cancer Oncogenome Group, and members of the DF/HCC Lung Cancer Research Program. We thank M. Asher, T. Matos, and A. Egia for histology services and immunohistochemistry. We thank the MSKCC, University of Iowa, and Dana Farber Cancer Institute flow cytometry core facilities for technical assistance. This work was funded by National Institutes of Health/NCI grants (CA-64593) to P.P.P., and Steps for Breath Fund by the Society of MSKCC and the Thomas G. Labrecque Foundation to M.N." (1)

The authors acknowledged individuals, by name. They listed the laboratories and funding agencies that provided materials, funds, and other tangible support for the project. For their NIH grant, they listed the grant number, CA-64593. NIH expects grantees to reference grant numbers within their manuscripts. This permits administrators to track the research activities of their grantees.

All told, the typical Acknowledgment serves everyone but the authors. Certainly, an evil scientist should be able to turn the acknowledgment section into another opportunity for shameless self-promotion.

Let's look at a few Acknowledgment sections that work for the author.

ACKNOWLEDGMENTS. I thank students, postdocs, and colleagues for critical discussion and encouragement. I am grateful to the National Center for Biotechnology Information for providing the earliest dates associated with each NR sequence (2).

Here, the author has published an Acknowledgment wherein no person or persons are actually acknowledged. The Acknowledgment gives the impression that many people are vested in the success of the project, without actually giving credit to any individuals. By extending the effort to a large, anonymous group of professionals, the Acknowledgment adds a certain gravitas to the manuscript.

Here's an even better Acknowledgment.

ACKNOWLEDGMENTS. We thank the patients, physicians, and investigators who have contributed to our understanding of these disorders, and apologize to our colleagues whose work was not highlighted due to space constraints (3).

This Acknowledgment also fails to actually acknowledge any specific person. Instead, it provides an emotionally charged list of anonymous participants that includes every physician and investigator who has ever worked in the field, and every patient who has ever been afflicted by the investigated disease. Well done, but further improvement is possible.

ACKNOWLEDGMENTS. This work is dedicated to the many colleagues and patients who have contributed over the past several decades to advancing our understanding and treatment of amyloidosis, and to the staffs of the Amyloidosis Foundation and the International Myeloma Foundation whose work is ongoing and so often unheralded (4).

From the first sentence, the authors deftly replace their Acknowledgment with a Dedication. It's brilliant, really. With one bold stroke, the Acknowledgment is transformed from a message of indebtedness to a message of giving. As in the previous examples, no specific persons are actually mentioned in the acknowledgment. The manuscript becomes a gift given selflessly to all of the unnamed little people out there.

The Acknowledgment section has gradually evolved to a point where it's primary purpose is to serve the author and to add credibility to the manuscript. Can we dare hope to raise the level of the Acknowledgment to a higher realm? Yes, with God's help, we can.

Consider this remarkable introduction, wherein the author acknowledges God's role in the manuscript.

ACKNOWLEDGMENTS. I thank God for His grace and inspiration in this work..... (5).

The Acknowledgment continues by thanking a number of coworkers, by name. It ends by thanking the author's wife and his children "for the years of personal sacrifice that are their contribution to this project (5)". The final sentence of the Acknowledgment is another reference to God:

"May God bless them richly (5)."

How can any reviewer reject a manuscript that was inspired by God? To do so would be an act of heresy. Even the most hardened secular humanist will be moved by the years of personal sacrifice endured by the author's family.

So there we have it. The Acknowledgment section is much more than a simple afterthought, grudgingly included in the publisher's boilerplate. Always remember that a well-turned Acknowledgment can save your next manuscript from rejection.

Jump to tomorrow's blog on the Conflicts of Interest statements that appear in journal articles.

REFERENCES

[1] Berger AH, Niki M, Morotti A, et al. Identification of DOK genes as lung tumor suppressors. Nat Genet 42:216-223, 2010.

[2] Levitt M. Nature of the protein universe. Proc Natl Acad Sci USA 106:11079-11084, 2009.

[3] Levine RL, Gilliland DG. Myeloproliferative disorders. Blood 112:2190-2198, 2008.

[4] Comenzo RL. How I treat amyloidosis. Blood 114:3147-3157, 2009.]amyloid_tx.pdf

[5] Bidgood WD. Documenting the Information Content of Images. Proc AMIA Annu Fall Symp 424-428, 1997.

ACKNOWLEDGMENTS

I, Jules Berman, dedicate this blog entry to our universe, whose existence was crucial to the successful creation of this gift to humanity.

- © 2011 Jules Berman

key words: Acknowledgement, Acknowledgements

Another false first

2011-01-06T05:17:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

Stigler's law of eponymy, "No scientific discovery is named after its original discoverer."

-SM Stigler

One of the most rigid rules of scientific discovery is that the person credited with being "the first" ..... is not.

Christopher Columbus was not the first European to lead an expedition to North America. Alexander Graham Bell was not the first person to invent the telephone. Guglielmo Marconi was not the inventor of radio. Joseph Fourier was not the first mathematician to invent what is now known as the Fourier transform. Einstein did not invent the field of relativity. In all these cases, the credited "firsts" were preceded by others, who made important contributions to the "final" discoveries.

In the field of cancer research, James Ewing (1866-1943) is credited with being the first to use the term "precancer" to describe the early and treatable phase of cancer development.[1] In a 1914 paper, Ewing wrote:[2]

"If inoperable advanced cancer is incurable, and localized cancer eradicable, the disease is preventable by dealing with its preliminary stages. Precancerous lesions are not cancers. Practically they differ enormously from the established disease. They can usually be removed by trivial or safe operations, and they are sometimes amenable to less violent treatment."

Thanks to Google's ngram viewer, we can actually test this assertion by searching for the years in which the term "precancerous" appears in the English literature.

Here is the result:

Click on image for larger view

"Precancerous" was used in 1849 (before Ewing was born) and 1876 (when Ewing was 10 years old) and throughout the latter 19th century (preceding Ewing's 1914 paper).

This only goes to show that ideas percolate through scientific communities before they bubble out as a finished idea. As Carl Sagan said (but perhaps he was not the first to say so), "If you want to make an apple pie from scratch, you must first create the universe."

REFERENCES

1. Cardiff RD. Borowsky AD.Precancer: sequentially acquired or predetermined? Toxicol Pathol 2010 38:171-179, 2010.

2. Ewing J. Precancerous diseases and precancerous lesions, especially in the breast. Medical Record 86, 951-958, 1914.

- © 2011 Jules Berman

Failure overtakes success

2011-01-04T04:45:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

At the tail end of yesterday's blog, I inserted an output screen from Google's ngram viewer. Google collects an index of the occurrences of words and phrases (up to 5 words in length) found in its' collection of scanned literature. The lengths of phrases are ngrams (e.g., a 1-gram is a single word, a 2-gram is a two-word phrase, and so on).

At the ngram viewer page, anyone can enter a comma-separated list of words and phrases, and Google will produce a graph plotting occurrence frequency over time. Most of their scanned books come from the period following 1800, and Google's default starting data is 1800. You can look at earlier years, or you can confine your search to shorter periods of time.

You can use the ngram layer as a gauge of cultural honesty.

Let's look at the ngram that compares the frequency of "success" and "failure".

Click on image to see larger view

In the nineteenth century, "success" (the blue line) was about 6 times more frequent as "failure". By the end of the twentieth century, "failure" had overtaken "success" and is currently just shy of a tie.

What does this mean? It means that in the artifactual world of literature, our ancestors were somewhat reluctant to write about failure; not so today.

Are modern writers more honest than our predecessors? Have we evolved to the point where we can openly admit our failures?

Of course not. Modern writers have simply learned that they can openly criticize their competitors without incurring the scorn of their peers.

Let's look at the occurrences of the phrases "his failure" and "my failure"

Click on image to see larger view

The occurrence of "my failure" remains at a consistent and low level through the centuries. The occurrence of "his failure" enjoyed a meteoric rise through the mid-twentieth century. Basically, modern writers made the important discovery that they could blame someone else when things went wrong.

- © 2011 Jules Berman

Further work is required

2011-01-03T11:55:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

The Discussion section of any manuscript is always the dumbest section, because it includes all of the subjective, prejudiced, dogmatic, self-serving, and unscientific thoughts that motivate the authors.

Still, some reviewers may insist, quite unreasonably, that your Discussion include some conclusion, based on your findings.

How absurd!

You and the reviewer know full well that no useful conclusions can be drawn from your work. Your data can neither establish or abolish a hypothesis. Basically, you have wasted everyone's time and money on a project that has produced no meaningful results.

Just remember that all conclusions, no matter how unfounded, can reasonably benefit from further study. Write your baseless conclusions just as they they were factual. Then, add the comment: "Further work is required." This suggests that you're a humble and open-minded scientist who is willing to accept that all science is tentative. It tells the world that any final conclusion that might come from your work will require more research, and much more money. This tactic turns mindless pseudo-research into your next grant proposal; a reason for building on the preliminary findings expressed in your manuscript.

Nobody knows when scientists learned that half-baked and unfinished projects are more valuable than valid research. The Google ngram viewer permits us to look at its use throughout literary history.

Click on graph for larger view

As the graph plainly shows, the phrases "Further work is required" and "Further work is needed" have appeared with increasing frequency throughout the twentieth century. Evil science marches on.

- © 2011 Jules Berman

Free ebook update available

2010-11-25T06:03:00.000-08:00

Happy Thanksgiving!

I've taken the most recent series of blogs (on Medical Economics) and incorporated them into the latest version of Machiavelli's Laboratory (Chapter 20, Greed).

As per usual, Machiavelli's Lab (a satire on scientific ethics written from the perspective of an unethical scientist) is available for download as a free ebook at:

www.julesberman.info/integ/machfree.htm

Also, I will be taking a short hiatus from writing for the Machiavelli's Laboratory blog, so that I can focus on several other projects.

I hope to resume blogging after the New Year.

Happy Holidays,

-Jules Berman

Economics of mental illness

2010-11-24T17:22:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

This blog entry continue's yesterday's blog, "Psychiatry: slow care getting faster".

To summarize yesterday's blog, modern pharmaceuticals allow psychiatrists to treat more patients, in less time. Consequently, psychiatrists have been prescribing more and more drugs, thus bringing billions of dollars of annual sales for the big drug companies. This has helped make drug companies the most profitable of all the big industries in the U.S.

The problem for the psychiatrists is that they don't get any revenue from those prescriptions. Since 1987, the Antikickback Statute has restrained the drug companies from paying physicians for the prescriptions they write (1). Specifically, Section 1320a-7b(b) makes it a felony to solicit or receive remuneration (in the form of a kickback, bribe or rebate (directly or indirectly, overtly or covertly, in cash or in kind) for arranging an individual to receive an item (such as a prescription drug) or service for which payment may be made in whole or in part under [Medicare] or a State health care program (1).

The AntiKickback Statute may have enhanced the level of trust between patient and physician, but it has nearly destroyed the mutually beneficial relationship between physicians and drug companies. If psychiatrists couldn't receive any remuneration for their prescriptions, might they not revert to their formerly standard practice of listening to patients?

The stakes are high. When an antipsychotic medication sells well, much of the credit should go to the psychiatrists who write the prescriptions. Just two anti-psychotic medications: Zyprexa and Risperdol, each provided sales exceeding $4 billion dollars, in 2006. If psychiatrists were to engage in pharmaceutical-free psychotherapy sessions, the drug companies would lose many billions of dollars.

For drug companies, psychiatry is a chemical industry, and mental illnesses are chemical deficiencies. For example, schizophrenia can be thought of as a Quetiapine deficiency, and depression can be thought of as an Escitalopram deficiency. The chemicals that nature failed to provide are now available in convenient gel-cap or tablet form, courtesy of the American pharmaceutical industry. To sell their chemicals, the pharmaceutical companies must convince psychiatrists of the following:

Every sanity-challenged patient can benefit from pharmaceuticals.
Patients deserve the very best pharmaceuticals available, and the best pharmaceuticals are the newest pharmaceuticals (i.e., still under patent protection).
Mental illness cannot be treated overnight. Patients must be treated indefinitely, or at the very least, until their health benefits and their personal savings, are exhausted.

If hefty kickbacks cannot clarify these three self-evident principles, then some other method of persuasion is necessary. The pharmaceutical industry, resourceful to a fault, developed the marketing concept of the "physician thought leader" (2). It works something like this:

A pharmaceutical company representative seeks the "expert assistance" of a local psychiatrist. The representative explains that his company, which employs thousands of professionals and earns billions of dollars each year, is woefully lacking in the kind of "hands-on" expertise wielded by the local doctor.
The doctor is asked to serve as a thought leader for his local colleagues.
A dinner seminar is arranged wherein the local doctor presents a powerpoint demonstration (prepared by the drug company) highlighting their products. As the thought leader, he moderates a discussion in which his colleagues ask quesions and discuss their own experiences prescribing the company's drugs.
The doctor receives a generous check; the first of many.

Doctors love being consultants for the drug companies. Besides the money, it's a highly valued ego boost. Psychiatrists seem to be particularly susceptible to this kind of manipulation. Knowing very little about clinical medicine, psychiatrists are seldom taken seriously by other members of the medical profession. Few psychiatrists have the ego strength to rebuff the advances of a pharmaceutical representative who values their clinical knowledge.

It's hard to find an academic psychiatrist who has not received money from the pharmaceutical industry (examples are easily found (3)). The payouts can exceed a million dollars. A Harvard psychiatrist received $1.6 million from a pharmaceutical company but did not report much of the income to Harvard University. The payments were absolutely legal. The psychiatrist got into some trouble only because he failed to report the income to his employer, Harvard (4).

In a recent review of authors who write clinical practice guidelines, it was found that the vast majority had financial ties to pharmaceutical companies (5). It was rare for any of these conflicted authors to disclose their drug company affiliations. A survey of physicians has shown most payments received by doctors, for collaborations with pharmaceutical companies and with the medical devices industry, are deemed appropriate by their colleagues (6).

The American medical-industrial complex is profoundly mercantile. Physicians, much like pharmaceuticals, are up for sale.

REFERENCES

[1] The Medicare and Medicaid Patient Protection Act of 1987, as amended, 42 U.S.C. 1320a-7b (the "Antikickback Statute"), P.L. 100-93, January 23, 1989.

[2] Spiegel A. How To Win Doctors And Influence Prescriptions. National Public Radio October 21, 2010.

[3] Expert Interviews. Disclosures. American Academy of Child and Adolescent Psychiatry. 2010. http://www.aacap.org/cs/
expert_interviews/disclosures]phych_pharm_consultants.pdf

[4] Harris G, Carey B. Researchers fail to reveal full drug pay. The New York Times June 8, 2008.

[5] Choudhry NK, Stelfox HT, Detsky AS. Relationships between authors of clinical practice guidelines and the pharmaceutical industry. JAMA 287:612-617, 2002.

[6] Ross JS, Keyhani S, Korenstein D. Appropriateness of Collaborations between Industry and the Medical Profession: Physicians' Perceptions. AJM 122:955-960, October 2009.

- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, physician reimbursement

Psychiatry: slow care getting faster

2010-11-13T09:24:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

This blog entry continue's yesterday's blog, "Medicine: fast care and slow care".

Psychiatry is the quintessential slow care specialty. They sit for long sessions, listening to patients talk about their relationships with fathers, mothers, spouses, children. In the time that a psychiatrist devotes to a tedious tale of a disappointing childhood birthday party, a dermatologist could have fattened four pairs of lips with collagen injections.

There is a limit to the amount of money a psychiatrist can charge for a procedure-free hour filled with angst, regret and guilt.

By all rights, psychiatrists should be teetering on the verge of extinction. Surprisingly, psychiatry is a thriving field! The percentage of graduating medical schools who choose psychiatry for a career seems to be increasing (1). There is a growing demand for psychiatrists, particularly in the sub-specialty of childhood and adolescent care (2).

How do they do it?

Well, the most important trend has been the migration of psychiatry from the analyst's couch to the drugstore. Psychoanalysis has been widely abandoned by contemporary psychiatrists. The history of psychiatry has been revised, and Freud is currently relegated the role of "philosopher" (not physician). Today, the works of Sigmund Freud are read with greater interest by English literature majors than by medical students.

Basically, a "slow care" method, such as psychoanalysis, cannot meet the payroll of a modern psychiatric practice.

Today, there is a pharmaceutical treatment [distinguish treatment from cure] for the common mental aberrations: depression, anxiety, bipolar disorders, schizophrenia, obsessive-compulsive disorder. Proximate causes of disturbed behavior, such as suicide, phobias, and physical aggression, are triggered by one or more of these drug-sensitive common disorders. Nowadays, psychiatry is virtually a sub-field of pharmacology.

No longer is it necessary to listen to the same patient drone on week after week, year after year. It never helped the patient much, in any case. Freud and his coterie of psychoanalysts sought to provide patients with self-awareness. If self-awareness led to a cure, all well and good. But a cure was too simple a goal for Freud. Freud's detractors, of whom there are many, doubt that Freud cured anyone.

Drugs simplify and abbreviate the practice of psychiatry. Psychiatrists need not waste their valuable time on physical examinations. Patient and doctor will readily concede that there is nothing like a rectal exam to undermine a mutual sense of trust. Today, office visits are short and can often be consigned to the time taken to write a prescription.

The existentional challenge for modern-day psychiatrists is: "How can I make money off of writing prescriptions, when the drug revenues flow to the pharmaceutical companies?"

In the next blog, we'll discuss the answer.

REFERENCES

1. Dorsey ER, Jarjoura D, Rutecki GW. Influence of controllable lifestyle on recent trends in specialty choice by U.S. medical students. JAMA 290:1173-1178, 2003.

2. The Physician Workforce: Projections and Research into Current Issues Affecting Supply and Demand U.S. Department of Health and Human Services Health Resources and Services Administration Bureau of Health Professions, December 2008.

- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, physician reimbursement

Medicine: fast care and slow care

2010-11-10T04:51:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

This blog entry continue's yesterday's blog, "Right-sizing the physician workforce".

Just as restaurants can be divided into two broad categories: fast and slow; so can medical care.

The fast care specialties involve treating large numbers of patients with short, billable procedures. These procedure-oriented specialties include dermatology, gastroenterology, anesthesiology, radiology, and emergency medicine.

The slow care specialties require listening to the patient describe his many complaints, detailed history-taking, drawn-out and repeated instructions, and follow-up encounters. Many of the most time-consuming efforts in "slow-care" specialties are non-reimbursable. These slow-care, procedure-poor specialties include family practice, geriatric medicine, and psychiatry.

Though surgeons pride themselves as being hands-on proceduralists, their work often requires them to talk to patients before and after surgery, and to attend to a host of post-operative medical sequelae. Like it or not, surgery is a slow care specialty.

Physicians are reimbursed for procedures, with their income depending directly on the number of billable procedures they perform. It comes as no surprise that there is growing competition among recent medical school graduates for placement in the fast care specialties.

The slow care specialties, including family practice and surgery, can no longer fill their training slots with U.S. medical school graduates (1). Hence, there is a strong incentive for the slow care specialties to become "faster" (i.e. less time per patient, and more dependence on ancillary caregivers such as nurse practitioners and physician assistants).

Suppose you're a physician working in a slow care specialty, like psychiatry. How can you make your practice "faster" and increase your income? This will be the subject of tomorrow's blog, "Psychiatry: slow care getting faster".

REFERENCE

1. Dorsey ER, Jarjoura D, Rutecki GW. Influence of controllable lifestyle on recent trends in specialty choice by U.S. medical students. JAMA 290:1173-1178, 2003.

- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, physician reimbursement

Right-sizing the physician workforce

2010-11-09T08:34:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

This blog entry continue's yesterday's blog, "Physician workforce: supply and demand".

The most enduring symbol of TV doctor shows is the over-worked, chronically fatigued intern. If you believe everything you watch on TV (and who doesn't?), you will believe that the permanently-strapped-for-cash clinic has done all it can to adequately staff the ER, but there's just no money to spare for intern salaries!

Ha!

That's just not how hospital staffing works. Interns are no-cost slaves that work impossible hours. Medicare compensates hospitals for the salaries of interns, and much more! If it were up to hospital administrators, patients would need to push their way through an army of interns just to get from the parking lot to the hospital lobby.

There have always been overworked, chronically fatigued interns because that is what the U.S. economic model for physician manpower requires. It has nothing to do with cash flow problems in inner city emergency rooms; the same rules apply to poor and wealthy hospitals.

Here is a short course on graduate medical training economics in the U.S.

When students finish medical school, they enter a graduate medical education program. Interns are doctors in their first year of post-graduate training. Following internship comes residency, where doctors get training in their specialty of choice. Residency training can take anywhere from 2 years to 6 years depending on their field. After residency, some doctors enter fellowships, for even more specialized training. To make things simple, we'll refer to all post-medical schools trainees as residents.

Four government sources pay for almost every resident trained in the U.S.: Medicare, Medicaid (through State governments), the Veterans Administration, and the Department of Defense. Of these agencies, Medicare has been the number one payer since 1965 (when it was created), and currently pays about $10 billion dollars each year to support interns and residents (1-2).

Under Medicare, the Health Care Financing Administration (HCFA) gives hospitals about $100,000 for each resident. The hospital pays the resident anywhere from $20,000 to $50,000 and the hospital pockets the remainder (3). Hospitals do not generally inform their residents about their sweet deal with HCFA. The resident, unaware of the economic realities, believes that his salary comes from the hospital's general budget. When hospitals face economic shortfalls, residents generally accept salary cuts, just like everyone else. It's beautiful!

Because the government is virtually the only payer for residency slots, the government can fully control the total number of slots and the total number of trained physicians that enter the workforce each year.

In the U.S. there are about a 800,000 physicians (4). The total number of resident slots paid by Medicare each year is about 24,000 (of which about 16,000 are filled with graduates of U.S. and Canadian medical schools). This number is intended to replace the number of doctors who leave the profession each year. By keeping the number of physicians more-or-less steady, this payment system has kept the average salaries of physicians in most medical specialties from declining. It has also kept hospital administrators happy, by providing free professional labor.

The only flaw with this system is that not every hospital runs in the black. For many hospitals that run on a thin margin of financial solvency, the money received for residents is the only thing that keeps them afloat. When Medicare reduces the total number of funded residents (as they will do in a manpower oversupply year), at-risk hospitals slide into bankruptcy.

In New York State, hospitals came up with an ingenious plan to bring in Medicare funding without training an excess of residents. New York hospitals convinced HCFA to pay them for "empty" residence slots. In effect, they asked Medicare to pay them NOT to train residents (3). And it worked!

Under the New York plan, hospitals cut their resident slots by 25% but were paid as though they were filling 100% of their slots (3). Hospitals would continue to provide the same care, but with fewer residents to do the job. Financially troubled hospitals got the additional funds they needed, and the total number of newly trained doctors did not rise. The only drawback in the plan was that the flesh-and-blood residents all had to work harder to compensate for the phantom residents who were paid at the same rate.

There you have it. The reason that hospitals employ so few residents to do so much work is simple: this keeps the number of physicians released into the workforce low, thus keeping physician salaries high..

Every few years, one committee or another scrutinizes funding programs for U.S. graduate medical training. They make feeble recommendations such as the following:

"The Secretary should conduct workforce analysis to determine the number of residency positions needed in the United States in total and by specialty. In addition, analysis should examine and consider the optimal level and mix of other health professionals. This work should be based on the workforce requirements of health care delivery systems that provide high-quality, high-value, and affordable care. (1)"

Medicare has been paying resident salaries, one way or another, since 1965. How is it that in 2010, we still can't seem to match residency funding with actual healthcare needs? The answer is simple: physicians and hospitals benefit from the status quo, the public, unaware that Medicare pays the bills for residency training, doesn't want government interference in medicine. It's all good.

REFERENCES

1. Medical Planning Advisory Commision). Graduate medical education financing: focusing on educational priorities. Medpac report to the congress: aligning incentives in Medicare. Chapter 4. June 2010.
2. Rich EC, Liebow M, Srinivasan M, Parish D, Wolliscroft JO, Fein O, Blaser R. Medicare financing of graduate medical education. J Gen Intern Med 17:283-292, 2002.
3. Korcok M. New York hospitals paid to teach fewer physicians. Can Med Assoc J 157:1263-1264, 1997.
4. The Physician Workforce: Projections and Research into Current Issues Affecting Supply and Demand U.S. Department of Health and Human Services Health Resources and Services Administration Bureau of Health Professions, December 2008.

Jump to tomorrow's post, "Medicine: fast care and slow care"

- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, physician reimbursement

Physician workforce: supply and demand

2010-11-08T10:08:00.000-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

This blog entry continue's yesterday's blog, "Public Health: effective but irrelevant".

How many doctors do we need? If you read the healthcare literature, particularly the government studies pertaining to the topic of physician workforce requirements,you would think that this is a complex and subtle problem. In a 2008 report produced by the U.S. Department of Health and Human Services Health Resources and Services Administration (HRSA) Bureau of Health Professions, various technical approaches, all with many different measurement parameters, were considered: 1) a needs-based approach, 2)a demand/utilization-based approach, 3)a benchmarking approach, and 4)a trend analysis approach (1). Following 100 pages of tortured analysis, their conclusion was tentative: "HRSA’s Physician Supply Model and Physician Requirements Model, like all models, are simplified versions of a complex health care system that generalizes the millions of decisions made by physicians, patients, insurers, and other entities into probabilities that certain events will occur based on historical patterns of behavior. (1)"

None of these analyses were necessary.

Here's how the U.S. physician workforce is calculated:

If the salaries of physicians are rising, you don't have too many doctors. If you don't have too many doctors, then you don't have a problem.

That's all there is to it.

For physicians, and for the leadership of medical societies, there is only one issue to worry about: physician oversupply. If you have too many physicians, salaries will fall. That's bad.

What about undersupply? If the U.S. doesn't have enough doctors, won't people die from medical neglect?

Not likely. Currently, in the U.S., there are very few people who lack access to medical care, if they have good health insurance or sufficient personal funds (1). There are lots of sparsely populated areas in the U.S. where physicians are few and far between, but if you can afford transportation, you can gain access to a doctor.

In the U.S., access to care is a wealth issue, not a physician supply issue.

In the unlikely event that physician undersupply became a reality, the U.S. has access to an unlimited supply of foreign medical graduates who would love to have the opportunity of practicing medicine in a country with no national healthcare service (such as the U.S.).

If every medical school in the U.S. were to implode today, and if the U.S. never produced another physician, we would have an inexhaustible supply of foreign medical graduates to fill every open residency position in every medical specialty.

If that's the case, you might well ask why we pay for U.S. medical schools. The answer is simple. America is the land of opportunity, and every American parent wants his or her child to have the opportunity of becoming a U.S.-trained physician. If parents and their children had no interest in medical careers, we would import all of our doctors from foreign countries.

Don't be shocked by this news. The hard sciences (e.g., physics, mathematics, engineering) are unpopular among U.S. college undergraduates. No matter. These days, we import our American scientists, mostly from Asia.

In tomorrow's blog (Right-sizing the physician workforce), we'll discuss the simple measure that hospitals take to ensure that the supply of doctors will never be so great that the average physician salary will fall.

REFERENCE

1. The Physician Workforce: Projections and Research into Current Issues Affecting Supply and Demand U.S. Department of Health and Human Services Health Resources and Services Administration Bureau of Health Professions, December 2008

- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, physician reimbursement

Public Health: effective but irrelevant

2010-11-08T06:40:00.001-08:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

This blog entry continue's Saturday's blog on Man-Made Epidemics.

Public health measures are often much for effective and much less expensive than the pay-per-complaint practice of medicine so prevalent in the U.S. In Finland, in about 1970, the population had reached its highest incidence of cardiovascular diseases. As a result, public health measures were introduced to improve diet, exercise and other health habits (particularly smoking) in the population. The multi-decade effort, called the North Karelia project, stands as one of the greatest successes in public health intervention.

Here are the results of the North Karelia project (1).

An increased life expectancy (7 years longer for men and 6 years longer for women).
Lung cancer death rate reduced 70% in North Karelia
Heart disease mortality reduced 65% in men.

In the United States, patients hold their encounters with their private physicians with the greatest reverence. Many Americans would fight to the death (more literally than they might imagine) for the right to follow their personal physician's recommendations, even when those recommendations conflict with public health guidelines. We know that physicians commit preventable medical errors every day, accounting for up to 98,000 American deaths each year (2), but that doesn't seem to matter to most of us. We know that public health measures prevent disease, save lives, and extend our life-spans. But Americans seem oblivious of the realities.

If you don't look too closely, U.S. medicine is a simple and effective service. When you get sick, you seek the services of a highly trained doctor, who treats your illness, and you get better. In return, the doctor is paid by some third party (your health insurer or government Medicare), or you pay the doctor yourself. Nothing could be simpler, and nothing could be better.

The only problem is that U.S. medicine does not work very well. The U.S. pays more for health care than any other country in the world (by far), but the U.S. has the lowest life expectancy of any developed country.

When you try to assess overall satisfaction with medical care in the U.S., you're always working with a skewed population: survivors. About 90,000 U.S. citizens die every year from medical errors. Deceased citizens have very little say in the matter. Doctors are among the few professionals who can literally bury their mistakes.

Many of the satisfied living are lulled into a false sense of health, without receiving appropriate care for their illnesses. An obese patient with newly diagnosed type 2 diabetes, hypertension, and hyercholesterolism would probably prefer to be treated with pills than to be told that he must conform to a strict diet and a rigorous exercise program. American medicine, like any other business in America, is designed to keep the customer happy.

Essentially, U.S. medicine is run like any other American enterprise. Doctors make their decisions to maximize personal gain. They expect their patients to do the same. As the U.S. population gets sicker and sicker (and demand more services), doctors get richer and richer.

In the next few blogs, we'll discuss some of the key forces that determine: 1)the total workforce of physicians in the U.S., 2) where physicians are deployed, and 3) how physicians distribute themselves into different healthcare specialties.

REFERENCES

1. Puska P. Successful prevention of non-communicable diseases: 25 year experiences with North Karelia Project in Finland. Public Health Medicine 4:5-7, 2002.

2. To err is human: building a safer health system. Institute of Medicine, November, 1999.

Jump to tomorrow's blog

- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, physician reimbursement

Man-made epidemics

2010-11-06T10:47:00.000-07:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

This blog continues yesterday's blog on Man-Made Diseases."

In the first half of the twentieth century, three infectious diseases received the bulk of attention here in the U.S.: polio, syphilis, and tuberculosis. Every physician knew these diseases intimately. There were medical journals devoted exclusively to these diseases. Doctors specialized in these diseases and invented now-obscure names for their specific clinical presentations or variant forms (e.g., Pott's disease for tuberculosis of the spine; craniotabes for syphilis). Few of us today remember that polio was also called infantile paralysis and that its full name was poliomyelitis, or that it came in several clinical forms (e.g., bulbar polio, abortive polio).

In the mid-twentieth century, a cure for each of these diseases was discovered. Everyone was predicting that in a few years, polio, syphilis and tuberculosis would be eradicated. The predictions were accurate for polio, but they were somewhat off the mark for syphilis and wildly wrong for tuberculosis.

In the case of polio, prevention consisted of getting vaccinated. Syphilis was also easy. If you've had syphilis for less than a year, a single intramuscular injection of penicillin will cure you. Curing tuberculosis required some effort. For active cases of tuberculosis, patients were expected to swallow multiple pills, daily, for up to 18 months.

Basically, the reason that polio is virtually non-existent in developed countries, and the reason that you don't hear too much about syphilis these days, is that the cure comes in the form of one or two doses of a medication that the physician personally delivers in the office. The reason that tuberculosis is still a major public health problem is that it requires long-term treatment administered by patients.

Physicians understand, but do not always care, that patients simply do not adhere to long-term medication regimens. When groups of patients are closely monitored for medication compliance, nobody expects strict adherence to long-term therapy. Acceptable adherence is 80% compliance. But patients seldom meet acceptable levels of treatment. In a group of patients with hypercholesterolemia, only about half of the monitored group achieved 80% medication compliance for statins(1).

In the 1950s, when antiobiotics active against tuberculosis were discovered, everyone believed that this disease would soon be eradicated. They hadn't taken into account patient compliance. It was common for patients to stop their medication after a few weeks of treatment, or as soon as their symptoms abated. Not surprisingly, this practice gave the TB microbe (Mycobacterium tuberculosis) the opportunity to develop resistance to standard treatment. Within a generation, multidrug-resistant strains of tuberculosis emerged.

How did this play out in American cities? Baltimore is the home of Johns Hopkins Hospital, one of the most prestigious medical centers in the world. In Baltimore, Johns Hopkins employs more people than any other business. You would think that Baltimore would be the healthiest population in the world? It is not. In the 1970s, Baltimore had the highest tuberculosis rate of any city in the U.S. The incidence of new cases of active TB reported in Baltimore, in 1981, was 35.6 cases per 100,000 population (2). Baltimore hosts one of the greatest centers of health technology in the world, but physicians did not ensure that their TB patients followed their prescribed treatments.

The Baltimore City Health Department, in 1981, implemented directly observed therapy (DOT), a strategy wherein healthcare workers would routinely visit patients and watch them take their tuberculosis medications. The plan worked. In 2009, the incidence of TB in Baltimore was a mere 2.7/100,000 population (3). This is about 7.5% of the active TB incidence in 1981. The Public Health Department succeeded where the medical-industrial complex failed.

In the 1970s, tuberculosis re-emerged as a national health problem because the United States has a healthcare system that is disconnected from the realities that influence the incidence and severity of diseases. Currently, the healthcare system in the U.S. is faced with another, frightening, healthcare failure: the rise of new strains of staphylococcus and other common organisms that are resistant to currently available antibiotics. Like tuberculosis, antibiotic resistance arose in common organisms largely because treatment regimens were not followed to completion. Physicians worsened the problem by routinely prescribing antibiotics for people with viral syndromes (e.g. the common cold) that do not respond to antibiotics. Endogenous organisms, dwelling within those persons who receive inappropriate treatment with antibiotics, will develop resistance, over time. This is another example of a problem created by the medical-industrial complex. Like TB, the solution may come from the public health sector: making sure patients take the full treatment regimen for infections, insisting on scrupulous handwashing among hospital staff and thorough cleansing of patient rooms in clinics and hospitals. Low-tech methods, the same methods championed by Florence Nightingale (1820 - 1910), are the best weapons we have, at present, to fight drug-resistant pathogens.

It's funny the way things work out. The worse things become, disease-wise, the better things are for the medical-industrial complex. Emerging epidemics bring more patients, more severe diseases, more research funding, greater dependence on costly high-tech interventions (e.g., Intensive Care Units, non-generic antibiotics, genetic testing of microorganisms, scans, blood tests), and more revenue. The people who create public health problems are often the same people who benefit from the resulting havoc.

REFERENCES

[1] Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy 28:437-443, 2008.

[2] Chaulk CP, Moore-Rice K, Rizzo R, Chaisson RE. Eleven years of community-based directly observed therapy for tuberculosis. JAMA 274:945-951, 1995.

[3] Baltimore City Achieves Record Low Tuberculosis Case Rate as Health Department Launches Cutting-Edge Screening Program. Baltimore City Health Department (announcement) March 24, 2010.

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- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, physician reimbursement

Man-made diseases

2010-11-05T04:14:00.000-07:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

This blog continues yesterday's blog on Medical Economics."

Many physicians cannot stop themselves from dividing diseases into two broad categories: God-made diseases and Man-made diseases. God-made diseases are all the awful genetic, developmental, microbiologic, and parasitic, disorders that mankind did not create. These account for most of the diseases of infancy and childhood.

Man-made diseases are those conditions that arise from self-indulgences (over-eating, substance abuse, smoking) or follow directly from the actions of humans (motor vehicle injuries, violent assaults, safety lapses). Man-made diseases account for the vast majority of the diseases of adults.

There is also a grey-zone of diseases where there seems to be some collaboration betwen God and man. Cancer is a good example. Humans did not invent cancer, but human connivance vastly increases the number of cancer occurrences (e.g., smoking, alcohol abuse, over-eating, unsafe sex, meat-intensive diets, pollution of air and water, etc.).

All physicians know that if adults simply behaved better (calorie-restricted diets, no smoking, no substance abuse, moderate and regular exercise, vegetarian or reduced-meat diets, less pollution, defensive and attentive driving, home and occupational safety precautions, fewer wars, less assaulting, better personal hygiene) the health delivery system would shrink from the size of a fungating tumor to the size of an adolescent's pimple.

You might argue that every human will eventually get sick and die. It's just a matter of time before we all need the services of a physician. This is true, but it does not change the fact that clinics are filled with people who have made themselves sick through their own life-style choices. The individuals who have God-given diseases or who have age-related infirmities represent a small fraction of the total number of patient-physician encounters in the U.S.

From the perspective of the pharmaceutical industry and the medical device industry, the best thing about lifestyle diseases is that they persist for the duration of the patient's life. As long as the patient continues his indiscretions, he will continue to need the services of the medical-industrial complex. Most physicians and other members of the medical-industrial complex understand that they would be unemployed if their patients seriously pursued a healthy lifestyle. This is why the status quo is acceptable to so many people.

Jump to tomorrow's blog

- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, physician reimbursement

Medical Economics

2010-11-04T05:11:00.000-07:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

In the United States, there is no healthcare system. What we have is a medical technology system wherein the provision of medicine is determined almost exclusively by the method and amount of reimbursement obtained for the different technologies employed. Basically, the practice of medicine is pre-determined by money, not disease.

Here is an example. A 300 pound, 30 year old smoker comes to his private physician, complaining of difficulty breathing. After a quick history and physical examination and some simple blood work the physician finds that the patient has hypertension, hyperglycemia, a complex dyslipidemia, osteoarthritis of knees and ankles, chronic bronchitis, sleep apnea, back pain, GERD (gastro-intestinal reflux disorder), halitosis, chronic fatigue, depression, and frequent absenteeism from work.

The doctor knows that all of these problems are the direct result of the patient's morbid obesity. If the patient were put on strict diet, with exercise, all of his medical issues would soon vanish - even the halitosis (which is secondary to GERD). The most effective approach to the patient's treatment would be a lengthy discussion, with the physician, in which the doctor would explain that all of these disorders stem from dietary excess or dietary indiscretion, coupled with a lack of regular exercise, and exacerbated by smoking. If there were an effective public health system, the patient would be tracked to a personal trainer, who would plan the patient's diet and exercise program and supervise a smoking cessation program. His family would be brought into the discussion, and instructed how they must support his efforts to reduce weight. His employer would participate in his therapy program by providing a supervised period, in the morning and afternoon, when employees would engage in light exercise. Employers are happy to cooperate, when they know that a program will reduce absenteeism and enhance staff productivity. The cost of this kind of treatment is small. The benefit to society is immense. Of course, this description does not characterize the practice of medicine in the United States.

In the United States, an obese smoker with attendant ailments is a medical gold mine. The doctor tells the patient that he is a diabetic and will develop blindness and almost certainly require amputations of his legs, if he doesn't begin lifelong treatment with oral hypoglycemic agents, and, eventually, insulin. The patient will learn that his hypertension is out of control and that he will start treatment with two expensive medications. His treatment for hypertension will be a life-long process. His dysplipidemias will require life-long treatment with the most recently marketed statins. His sleep apnea would require an expensive evaluation followed, with an assistive breathing device (CPAP, Continuous Positive Airway Pressure) that would be fitted to the patient and worn through each night, for the remainder of his life. GERD will require endoscopy, esophageal biopsies, and medications to reduce the production of stomach acid. Chronic bronchitis, will require a consultation from a pulmonary medicine specialist, who will follow the patient indefinitely, providing a rich array of agents intended to cleanse airways and open bronchi, oxygen therapy as needed, and antibiotics for attendant lung infections. An orthopedic consultation will be called to evaluate the patient's knees and ankle arthritis. He will probably recommend arthroscopic procedures. Back pain will probably require various pain killers, muscle relaxants, corticosteroid treatments, and possibly surgery. Fatigue and depression will lead to psychiatric examinations and trials with various tranquilizers, anti-anxiety, anti-depressent medications. The many daily, long-term medications will interact with one another in an unpredictable, and malevolent manner, producing strange incapacitating symptoms that no doctor will be able to diagnose correctly. The patient will continue to smoke and to gain weight at a rate that is alarming, even to himself. The patient's work absenteeism will worsen, as his many doctor visits increase in frequency and his various complaints multiply with age. His employer will become obsessed with finding a way of firing the patient without violating the patient's employment contract.

In a healthcare system, the patient would be treated for the primary problems that caused all of his symptoms: over-eating and smoking. But the U.S. does not have a healthcare system. We have a health technology system, which is geared toward providing tests (e.g., laboratory tests on blood or tissue biopsies, various imaging scans), procedures (e.g., endoscopies, biopsies, surgical interventions), and medications (particularly, expensive new drugs that are protected by patent). In a health technology system, doctors are paid for the technology that they employ. In a health technology system, there is no satisfactory way to reimburse a doctor for the hours spent coaching an obese patient to participate in a healthy, effective diet. Consequently, patients are treated on a symptom-by-symptom basis. It's an expensive and ineffective way of practicing medicine, but that's the whole point. A health technology system is aimed at generating reimbursed costs.

Has this discussion been realistic? Has the American health technology system done more harm than good? Or have I irresponsibly mischaracterized the problem?

Jump to tomorrow's blog

- © 2010 Jules Berman

key words: medical-industrial complex, American healthcare, reimbursement for prevention

Linnaeus, the immortal crony

2010-11-03T05:37:00.000-07:00

Statistics: veneer of mathematical legitimacy

2010-11-02T10:14:00.000-07:00

null hypothesis (the hypothesis you want to prove or disprove): If a person is an American, then he is not a member of Congress.

You start searching through each American, checking to see if he or she is a member of Congress. Eventually, you will find an American who is a member of Congress. At that point, you will know that your null hypothesis is not true, and you will reject it.

When we project null hypothesis testing into the realm of statistics, we reach the opposite conclusion.

probabilistic null hypothesis (the hypothesis you want to prove or disprove): If a person is an American, then he is probably not a member of Congress.

Here you can choose a random sampling of Americans (a few hundred or so), and you will almost always find that none of them are members of Congress. You will then accept the probabilistic null hypothesis ("If a person is an American, then he is probably not a member of Congress"). Furthermore, you are now ready to believe the general rule that Americans are not members of Congress.

Of course, the probabilistic null hypothesis is nonsense, as all members of Congress are Americans. The probabilistic null hypothesis is accepted because there are very few members of Congress and there are many Americans. The non-probabilistic version of the same hypothesis was rejected by examining the population to which the hypothesis applied. If we began with an understanding of the rules of fitness for Congress (i.e., a Congressman must be an American), and good data on the relative numbers of Americans and Congressmen, we wouldn't have been suckered into examining a probabilistic absurdity.

Statistical testing is the closest thing the evil scientist has to sleight-of-hand deception. How does an evil scientist know when to believe a statistical conclusion? If the conclusion is consistent with your own biases, and if it furthers your own selfish agenda, you can swear on the results. Otherwise, reject the conclusion by invoking one of four popular classes of statistical error.

Type 1 error. Rejecting the null hypothesis when the null hypothesis is correct (i.e., seeing an effect when there was none).

Type 2 error. Accepting the null hypotheses when the null hypothesis is false. (i.e. seeing no effect when there was one).

Type 3 error. Rejecting the null hypothesis correctly, but for the wrong reason, leading to an erroneous interpretation of the data in favor of an incorrect affirmative statement.

Type 4 error. Erroneous conclusion based on performing the wrong statistical test.

Type 5 error. Erroneous conclusion based on bad data.

REFERENCE

1. Cohen J. The Earth Is Round (p < .05). American Psychologist 49:997-1003, 1994.1

- © 2010 Jules Berman

New blog site on Neoplasms

2010-10-11T07:54:00.000-07:00

When I'm not writing about unethical science, I'm writing about medical informatics or tumor biology.

Readers of my (currently) free ebook, Machiavelli's Laboratory, may wish to visit my two serious blog sites:

Specified Life, which covers medical informatics;

and my new blog site,

Neoplasms, which deals with tumor biology.

The Specified Life blog is three years old and has hundreds of entries listed in its web archive.

The Neoplasms book is just two days old, and will be dealing with issues that were introduced in my book, Neoplasms: Principles of Development and Diversity.

- © 2010 Jules Berman

key words: carcinogenesis, neoplasia, neoplasms, tumor development, tumour development, tumor biology, tumour biology, carcinogenesis

WNL: We Never Looked

2010-09-28T11:21:00.000-07:00

Taking a break from Machiavelli

2010-09-22T14:09:00.000-07:00

In addition to writing under the guise of an evil scientist, I also publish serious scientific literature. Yesterday, CRC press published my new book, Methods in Medical Informatics: Fundamentals of Healthcare Programming in Perl, Python,and Ruby.

If there are any blog readers interested in medical informatics, I've prepared two web pages with a book description and the table of contents.

- Jules Berman

Beware the second opinion

2010-09-19T17:05:00.000-07:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

In a recent New York Times Article, Stephanie Saul told the story of a woman who had been given the diagnosis of DCIS (ductal carcinoma in situ, or non-invasive breast cancer), who subsequently received treatment (surgery, radiation and drugs), and who was later informed that the diagnosis was incorrect: she never had breast cancer.[1]

The diagnosis of DCIS was rendered by a pathologist who was not a breast cancer specialist, but who had gone to the trouble of soliciting a second opinion, from another pathologist. The consulting pathologist, who worked at a nearby hospital, agreed with the first diagnosis of DCIS.

The misdiagnosis came to everyone's attention when the woman transferred her follow-up treatment to another hospital. Her records and pathology slides were sent to the transfer hospital, where a staff pathologist reviewed the pathology material. He found no evidence of cancer in the original biopsy or in the portion of breast that was subsequently removed at surgery. The slides were sent to several expert consultants, all of whom agreed that no tumor was present.

Not surprisingly, the case became the subject of legal action. The lawyer for the plaintiff indicated that the original pathologist [who misdiagnosed the case] could have easily sent the slides to an expert consultant [not to a non-expert pathologist from a nearby hospital.] It is likely that, should this case ever reach a courtroom, debate will center on whether the first pathologist exercised standard of care by seeking a second opinion from a pathologist who had no special expertise in breast cancer pathology.

Setting aside the specifics of the case described in The New York Times article, the broader question of expert consultants deserves the scrutiny of every evil scientist. As you shall see, the issue of choosing expert consultants has ramifications far beyond the small world of pathology.

First, you must understand that getting a second opinion is a no-win situation. If your consultant agrees with your original opinion, nothing was gained. Everyone will assume that the diagnosis must not have been very challenging. You will learn that your opinion was actually superfluous. Only the consultant's opinion carries any real weight. Eventually, after a number of consultations, your employer may wonder why you are needed at all. Why not just pay the consultant to render diagnoses on all your specimens; in which case, your position can be terminated.

Of course, if the consultant disagrees with your opinion, your life will deteriorate rapidly. Everyone will assume that you are wrong, and that the consultant is correct. Your credibility will be destroyed. You may become the center of attention in a lawsuit. You will become a pariah among your co-workers. You may lose your job. Your permanent record will be blemished. You may become unemployable.

As an evil scientist, with no great competence, and prone to committing errors, you must learn to defend yourself. Follow the following recommendations, without deviation.

1. Pick a consultant that you trust to watch your back. This will almost always be someone who asks you to be his consultant when he needs a second opinion. A reciprocal consultation agreement virtually guarantees a non-threatening opinion.

2. In any field, most tasks are routine. In the specialty of pathology, 90% of cases are trivial and can be rendered correctly, and with complete confidence, by the most marginal pathologist. The remaining 10% of cases can be handled with equivocations ("The biopsy is consistent with but not definitely diagnostic of..."), temporizations ("A final diagnosis will be rendered after special stains and molecular tests are completed."), supplementations ("A few atypical cells are noted, but there is insuffficient material for an unequivocal diagnosis. I suggest re-biopsy."), and consultations ("We are waiting for a consultative report").

3. It is best for the marginal professional to eliminate the concept of a final diagnosis, entirely. Restrict yourself to vague pronouncements. On the official report, in the space normally reserved for the "Diagnosis" field, you must substitute the heading, "Diagnostic Impression." For example, "Diagnostic impression: Neoplastic process suggestive of invasive ductal carcinoma." Astrologers and palmists have perfected this dodge. Remember that the official tree of the evil scientist is "the hedge."

When you've picked your trusted consultant, you will need to be prepared to prove that he is an expert. This really is not very difficult, because nobody really knows how to determine whether any person qualifies as an expert. If you doubt this, try to answer the following:

1. Are experts infallible? Of course not. Experts are human and can make diagnostic errors.

2. Do experts make fewer errors than non-experts? Nobody really knows. In the medical field, there is no mechanism by which the diagnoses of experts can be evaluated.

3. Do experts routinely send their difficult cases to other experts? No. People who consider themselves experts tend to have high confidence in their own diagnostic acumen. Though studies have shown that overconfidence is the most common cause of medical error, the expert assumes that this caveat only applies to non-experts.[2]

4. Do experts concentrate their efforts on a specific area, gaining expertise by seeing a large number of cases in their chosen field? Often, yes. But you must remember that simply seeing a large number of specimens does not prove that you're not an idiot. An incompetent pathologist can consistently misdiagnose a large number of specimens, just as easily as he can misdiagnose a specimen that he rarely encounters.

Basically, an expert is someone who is called an expert by others in his own field, such as yourself.

Given that experts can be mistaken, would it not be advisable to consult with more than one expert on very difficult cases? No, no, no, no. The absolutely worse thing you can do is to send a specimen to two experts. If they disagree, which expert will you believe?

Case in point. In 1993, Reggie Lewis was the 27 year old captain of the Boston Celtics. Mr. Lewis collapsed during a basketball game, and was treated by several teams of expert cardiologists. The team assembled by the New England Baptist Hospital believed that Mr. Lewis had focal cardiomyopathy, a life threatening condition requiring Mr. Lewis to retire from basketball. A second team of experts, assembled at the Brigham and Women's Hospital, disagreed. They rendered a diagnosis of vasovagal fainting, a benign condition. A third team of experts, from St. John's Hospital in Santa Monica, California, was non-committal. The Santa Monica team suggested that Mr. Lewis play basketball, but with a heart monitor attached to his body. With three discordant diagnoses, Mr. Lewis decided to take his chances, continuing his athletic career. Soon thereafter, Lewis died, quite suddenly, from cardiomyopathy, while playing basketball.[3]

References

1. Saul S. Prone to error: earliest steps to find cancer. New York Times July 19, 2010.

2. Berner ES, Graber ML. Overconfidence as a cause of diagnostic error in medicine. American J Med 121:S2-S23, May 2008.

3. Altman LK. After a highly publicized death, second-guessing second opinions. The New York Times August 3, 1993.

- © 2010 Jules Berman

key words: consultations, second opinions, diagnostic disagreement, discordant diagnoses, expert opinions, misdiagnoses, misdiagnosis, pathology error

Financial conflicts undisclosed in research papers

2010-09-14T12:07:00.000-07:00

Web of deception: DCIS misdiagnoses

2010-09-09T06:43:00.000-07:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

Everyone knows that you can't believe everything you read on the Web. But most people would imagine that you can believe authoritative knowledge that is delivered through the web. No such luck.

I came across a July, 2010, New York Times article that provided information obtained from "Susan G. Komen for the Cure," formerly known as the (previously known as the Susan G. Komen Breast Cancer Foundation). The article reports that 90,000 women may carry a breast cancer misdiagnosis.

The New York Times article is:

Saul S. Prone to error: earliest steps to find cancer. New York Times July 19, 2010.

Here are the exact words found in the article:

"In 2006, Susan G. Komen for the Cure, an influential breast cancer survivors’ organization, released a startling study. It estimated that in 90,000 cases, women who receive a diagnosis of D.C.I.S. or invasive breast cancer either did not have the disease or their pathologist made another error that resulted in incorrect treatment."

The article goes on to describe the medical community's reaction to the study.

A large number of web blogs and web services have repeated the "90,000" number provided by the Susan G. Komen for the Cure study.

See for yourself. Google the following phrase, "komen 90,000 misdiagnosed breast cancer". Google will return a large number of web pages that echo the same statement included in the New York Times article (see figure)

Here are just a few of the headings that come up on the search:

Who's responsible for the over 90000 misdiagnosed cancer cases ...

Health Beat: 50000 to 90000 American Women Incorrectly Diagnosed ..

Mammography Leads to Misdiagnosis and Unnecessary Mastectomies

More mixed messages on breast cancer Why Current Breast Pathology Practices Must Be Evaluated

Earliest Steps to Find Breast Cancer Are Prone to Error

Beyond Flip-Of-A-Coin Breast Cancer Diagnosis

Many Women Are Being Misdiagnosed With The Earliest Stage of ...

I read about a half dozen of these web reports. Most of them used the exact same language as the New York Times article, and none of them actually provided a reference for their source (other than indicating that their data came from a study done by Susan G. Komen for the Cure).

After a bit of digging, I found the Susan G. Komen white paper that was the source of the "90,000" number. Contrary to popular opinion, THERE WAS NO SUSAN G. KOMEN STUDY TO SUPPORT THE OFT-QUOTED DATA!

Here's the 2006 white paper , which is currently available the web:

"Why Current Breast Pathology Practices Must Be Evaluated Susan G. Komen for the Cure White Paper: June 2006."

Here is what the Susan G. Komen paper actually contains:

"It is exceedingly difficult to estimate the rate of major breast cancer pathology errors that occurs in the United States each year. There is no uniform process in place to capture errors, and fear of disclosure may limit reporting [Raab 2005] For all cancer specimens, the frequency of anatomic pathology errors has been reported to range from 1% to 43%.[Raab 2005] Specific to breast cancer pathology, our interviewees who routinely provide second opinions estimate that 2% to 4% of breast cancer diagnoses in the United States may be incorrect.[personal communication, Drs. Kivitz, Page, Allred]."

There was no study. The report acknowledges that it is exceedingly difficult to estimate the breast cancer error rate, so, rather than attempting an exceedingly difficult study, they simply interviewed three doctors and asked them their opinion.

Once they had their opinion (an error rate of 2% to 4%), they extrapolated and made the following summary conclusion:

"While it is exceedingly difficult to determine the incidence of incorrect breast cancer diagnoses in the United States, our consultants estimate that the error rate could be as high as 2% to 4%. If accurate, as many as 5,000 to 10,000 patients diagnosed with invasive or in-situ breast cancer each year may have been misdiagnosed and inappropriately treated (Appendix II). More than 90,000 people currently living with breast cancer may, in fact, be living (or dying) with an incorrect diagnosis (Appendix II)."

When you ask a few pathologists their opinion about error rates, and they give you an answer in terms of a range estimate (2% to 4%) this does not constitute a study. When you preface your conclusion by saying that "it is exceedingly difficult" to determine error rates, it pretty much implies that you can't determine a reliable error rate by doing something that is exceedingly simple (like asking a few pathologists for their opinions). In fact, given the difficulty of getting any accurate information, you need to wonder what the Susan G. Komen writers were thinking when they decided to just interview a few pathologists. Did they think that if something is difficult to do correctly, it must be ok to make a half-assed job of it?

For the sake of argument, let's accept that the breast cancer error rate falls somewhere in the 2% to 4% range. How did this lead the authors of the Susan G. Komen white paper to conclude that "More than 90,000 people currently living with breast cancer may, in fact, be living (or dying) with an incorrect diagnosis."

It seems to come from multiplying 4% by the estimated number of living women who carry the diagnosis breast cancer. According to the the U.S. National Cancer Institute's SEER program , "On January 1, 2007, in the United States there were approximately 2,591,855 women alive who had a history of cancer of the breast." Four percent times about 2.5 million is about 90,000. Why they didn't multiple by the lower estimate (2%) or by the average in the range (3%) is a mystery.

In any case, the Susan G. Komen for the Cure white paper is poorly worded. We have no way of knowing the total number of U.S. women living with breast cancer. We can only estimate the total number of living women who have been given the diagnosis of breast cancer. We can assume that there are many women living with breast cancer who have never received a diagnosis of breast cancer. That's the primary problem in the breast cancer field! Women may live with breast cancer, or with precancerous breast lesions, for years without receiving a diagnosis. If we could diagnose precancers and cancers as soon as they occurred (before they metastasized) we could virutally eliminate all deaths from breast cancer.

As we move to earlier and earlier diagnoses, obtained with smaller and smaller samples of tissue, pathologists are going to make more mistakes than they would make if they had large samples of advanced cancers to evaluate. That's just reality. It's easier to diagnose advanced disease then it is to evaluate the earliest manifestations of disease. In this case, it would seem that the pathologists are performing their jobs much more responsibly than are the journalists and funding organizations that report the errors.

- © 2010 Jules Berman

key words: breast cancer, precancer, misdiagnosis, dcis, misinformation, medical errors, error rates

Glossary letters V-Z

2010-08-13T06:55:00.001-07:00

Glossary letter T

2010-08-12T06:53:00.001-07:00

Glossary letter S

2010-08-11T09:40:00.001-07:00

Glossary letter R

2010-08-10T05:36:00.001-07:00

Glossary letters N-P

2010-08-09T10:57:00.001-07:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously. The ebook has been downloaded well over 10,000 times since its publication. This blog site features excerpts from the book and provides a forum for readers who would like to comment publicly.

GLOSSARY (letters N-P)

Nepotism - Nepotism is the blood-borne form of cronyism.

New idea - An old idea that you are hearing for the first time.

Obliteration by incorporation - As per Robert K. Merton (1910 - 2003), applies to ideas that are so broadly popularized that the original creator of the idea is forgotten. For example, do we know who invented the wheel, the fruit pie, or the back scratcher?

Obviousness in patents - For a device to be patented, it should be new, useful and non-obvious. In KSR v. Teleflex (April 30, 2007), the U.S. Supreme Court, in a unanimous opinion, reversed a Court of Appeals decision, and determined that a prior patent was unenforceable because it was obvious (163). The opinion discussed, at length, the principles of obviousness. In particular, the Supreme Court indicated that merely putting together prior art to make a new device can only qualify for a patent if the resulting device is unexpected by people working in the field; hence, not obvious. The decision may have raised the bar for patents, particularly patents that are built on prior art (e.g., all software and most software standards).

Off-label use - In 1962, Congress required that drug manufacturers produce scientific evidence that a marketed drug is both safe and effective for a specific use. When a drug company receives FDA approval, the approval is restricted to the specific use demonstrated in an FDA-approved clinical trial. All other uses of the drug (for populations and conditions not included in the clinical study, or for doses not deemed safe in the study) are not covered by FDA approval and cannot be marketed by the drug company. Off-label use occurs when the approved drug or device is used for a purpose other than the purpose approved by the FDA. The FDA controls drug companies, not doctors. Physicians are permitted to use drugs and devices for off-label uses, if they wish.

One field one book rule - The evil scientist does not waste time reading books in his field. At most, the number of books that an evil scientist will read is "1". Every field has a so-called bible, so named because it is contains contradictory, incredible, and merciless doctrine, often written by a committee, and altered by succeeding generations of scientists who are angry about being left out of the first edition. If you refuse to read more than one book, then you must read your field's "bible."

Orphan drug - A drug needed by a small number of people. In the past, drug companies were reluctant to manufacture drugs for rare diseases. The small population with the disease cannot produce an adequate return on investment for the manufacturer. Nowadays, drug companies produce orphan drugs charging up to thousands of times the manufacturing costs. Th idea is that third party payers (such as health insurers) will pay any fee for a medically required drug, so long as no competitors offer the same drug at a lower price.

Ownership - Ownership is a mercantile concept that bestows an entity with the right to sell. If you own a horse, that means that you alone have the right to sell the horse. If you own a tissue sample, that means that you have the right to sell the tissue sample. A long-honored tradition has prohibited the sale (hence ownership) of human tissue. This tradition was broken by a recent court ruling that assigned ownership of a collection of human tissues to Washington University (317)

Panglossian - Blind optimism, after Pangloss, the optimist in Candide (1759), by Voltaire (1694 - 1778).

Parker, Janet (1938 - 1978) - The last person on earth known to die from smallpox (100). In 1978, Janet Parker was a 40 year old photographer who lived in Birmingham, England. She worked on the floor above Henry Bedson's smallpox research laboratory. Virus particles escaped from Bedson's laboratory and infected Ms. Parker. After learning of Parker's infection, Bedson committed suicide (100).

Patent farming - Planting (usually, surreptitiously) patented intellectual property within someone else's intellectual property. The patent farmer reaps his crop by surprising users of the aforementioned intellectual property with notice that their activities rely on a patented process or device owned by the patent farmer. An example occurs when patented methods are included within technical standards. Hidden patents within standards can be asserted against anyone who implements the standard (318).

Patent holding company - Private entities that buy many patents, thus building portfolios of patents to assert intellectual property rights in strategically chosen business sectors.

Peer review - A venerable tradition, in which clueless editors, funding agencies, and awards panels ask scientists to spend their time and energy reviewing the grants and manuscripts written by their fiercest competitors. Not surprisingly, peer review provides reviewers with the risk-free opportunity to ravage their enemies and steal their ideas. Peer review has never been shown to serve a useful purpose; yet we persist (69).

Pharma - Slang for pharmaceutical industry. Used in conjunction with, and following, "big."

Ph.D. M.D. - A person who is qualified to be incompetent in two fields. If you're lucky enough to have these both degrees, you can parlay them into a lifetime of leisure. Basically, you can use your research activities to cover poor clinical acumen ("Sorry, I was busy in the lab"), and your clinical activities to cover poor research ("Sorry, I was in the clinic"). Because researchers seldom speak to clinicians, your colleagues on either side of your job will be unaware that you actually spend your afternoons in salacious trysts, with their wives.

Pilfer - Scientists don't steal from other scientists; they pilfer. Pilfering is a time-honored way of taking some scientific advancement produced by another scientist and using it to advance your own research agenda. One of the most successful acts of pilferage occurred when James Watson and Francis Crick got hold of Rosalind Franklin's X-ray photographs of DNA (without her permission). Watson and Crick have acknowledge that the photos were of critical importance in their work, which culminated in their discovery of the double-helical structure of DNA. Watson and Crick received the Nobel price. Rosalind Franklin received their gratitude. Though pilferers sometimes receive criticism from their peers, they never get into any serious trouble, because pilfering is not a crime. If you are ever accused of pilfery, the best defense comes from Isaac Newton, who famously said, "If I have seen further it is only by standing on the shoulders of giants." In other words, great science is accomplished by peering over the shoulders of your colleagues.

Plagiarism - Taking credit, through a literary device, for another person's intellectual contribution. Plagiarism is often confused with intellectual piracy. If I take an idea, developed in a book that you published, and I include it in my book, as though it were my original idea, without citing your book as the source of the idea, that would be plagiarism. Publication piracy is the copy-theft of a literary work. If I take your book, re-publish it, sell copies of the re-published work, and keep all the money paid to buy the re-published book, that's piracy. As books go, scientific works have negligible value, and are seldom pirated. Ideas are the currency of scientists, and plagiarism is rampant.

Predicting the future - The thing about predicting the future is that you need to start with a good understanding of the present. Nobody really understands what is happening in the here and now. So it is very unlikely that anyone can see the future.

Privacy - The right not to be bothered. Often confused with confidentiality, the right to keep a secret. See Confidentiality.

Proprietary Standard - A Standard that belongs to some entity and that cannot be used freely (i.e., without obligation, or restriction).

Prostitution - Currently the world's oldest profession, but at the time when it was invented, it was the world's youngest profession.

Publication dishonesty - Falsifying or fabricating data, lying about the original source of the data (e.g., plariarism), adding co-authors who did not contribute to the paper or whose contributions were marginal, failing to cite the proper precedent papers, and listing as co-authors persons who did not read and approve the final version of the paper. In the case of journal articles, duplicate publications are usually considered a form of publication dishonesty, because the appearance of the publication implies originality.

- © 2010 Jules Berman

Glossary letters J-M

2010-08-08T07:44:00.000-07:00

Glossary letters H-I

2010-08-07T06:45:00.000-07:00

Glossary letters F-G

2010-08-06T04:06:00.000-07:00

Glossary letters D-E

2010-08-05T05:50:00.001-07:00

Glossary letter C

2010-08-03T08:22:00.001-07:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a satiric discourse on scientific ethics, from the perspective of an unethical scientist. Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously. The ebook has been downloaded well over 10,000 times since its publication. This blog site features excerpts from the book and provides a forum for readers who would like to comment publicly.

GLOSSARY (letter C)

Cause of death errors - Cause of death data comes from death certificates (310). Death certificate data have many deficiencies (311), (312). The most common error occurs when a mode of death is listed as the cause of death. For example, cardiac arrest is not a cause of death, though it appears as the cause of death on many death certificates. There is not much value in a death certificate for a man who died with end-stage cancer when the listed cause of death is "cardiac arrest." An international survey has shown very little consistency in the way that death data are collected (313). Most death certificates are completed without the benefit of an autopsy. At best, death certificates express a clinician's reasonable judgment at the time of a patient's death.

Cherry-picking bias - Selecting experimental parameters that are most likely to promote your own scientific agenda, or biases. In medical science, the most common cherry-picking activity occurs during patient selection. By choosing the right patients, you can often guarantee that your protocol will produce the results that you want. Purists complain that cherry-picking is unscientific, and produces results that are misleading and unreproducible in a general patient population. Evil scientists understand that cherry-picking is no different that the legal practice of voir dire during jury selection. If lawyers are allowed to cherry-pick a jury, why can't scientists cherry pick their patients?

Citation - Among scholars, a citation is a credit given to a previously published work from within a later work. A citation comes in the form of a pointer to the author, title, and source of the prior work, as a footnote or as a numbered item in a reference section. If you use an original finding, method, or comment from a previously published work, without citing the work, you are engaging in plagiarism. The number of times that a work is cited in the literature is a rough indicator of the importance of the work.

Co-author - Short for co-opting author. A person whose name has been included on the list of persons responsible for a scientific literary work (manuscript, chapter, or book), without making any substantial contribution to the final product. In most cases, the list of co-authors is chosen to achieve some political or social agenda. Co-authorship is, in many cases, tacitly understood to be a reciprocating process ("I'll list you as a co-author on my paper if you'll list me."). There is no upper limit to the number of co-authors that may be listed on a paper. Some manuscripts have over 100 co-authors. Obviously, in these cases, the majority of the co-authors could not have seriously contributed to the paper.

Committee - A group of people with nothing better to do. An adept bureaucrat can form a committee that will function in a totally predictable manner, if he chooses committee members whose prejudices, allegiances, and work customs are known. In modern times, service on committees has essentially replaced scientific productivity as the sign of a credible scientist. Many famous scientists have built their reputations exclusively on committee work.

Common Rule - The Common Rule (Title 45 Code of Federal Regulations, Part 46, Protection of Human Subjects) is the U.S. federal regulation that describes how scientists and institutions must protect their human research subjects (210).

Competing Interest - See Conflict of Interest.

Compilation - How do you tell the difference between a book (which tells a story) and a compilation (a bunch of informative essays published as an ensemble)? In a book, you cannot change the order of the chapters without destroying the product. In a compilation, you can devise a new ordering the chapters and still have an equivalent (or maybe even an improved) product.

Confidant (alternate, Confidante) - "One entrusted by A with the secrets of B, confided by him to C." - Ambrose Bierce

Confidentiality - Keeping safe an entrusted secret concerning another person.

Conniver - One who permits a dishonest act to proceed without interference.

Consensus - Scientific consensus is the illusion that truth is achieved when everyone agrees.

Conservation of Energy, Law of - Evil scientists need to conserve their energy; let others do the work. Sir Winston Churchill distilled the Law of Conservation of Energy into basic elements; "Never stand up when you can sit down, and never sit down when you can lie down."

Contract - Had Van Gogh been a house painter, he would have had steady employment. Just about everyone needs their house painted, at one time or another. Nobody really needs an original piece of art hanging on their wall. The relationship between house painting and art is analogous to the relationship between contracts and grants. A contract is a legal agreement to acquire a service or a deliverable item for a specified remuneration. The funding agency specifies what it wants, and the contractor delivers the item. In a grant, the researcher tells the government what mysteries he would like to pursue, and the funding agency provides him with the necessary money.

Corporation - A corporation is a legal entity that conducts business, whose purpose is to sustain itself, to grow, and to profit. As a legal entity, it has many of the same rights held by humans. Corporations can own and sell property; they can hold patents and copyrights; they have rights of free speech under the first amendment, and they can use those rights to mock their political enemies; they can sue people and other corporations; they have the right to enter into contracts and advertise their products. Most importantly, corporations can lobby congress. Under the law, corporations must be motivated by profit. When you combine an existential mandate for greed, with the power to influence congress, you can understand why corporations are usually much more successful than people. Remember the maxim: laws don't protect citizens from ruthless corporations; laws protect ruthless corporations from citizens.

Cronyism - Favoritism towards friends. Crass people think of cronyism as a safe way to discriminate against everyone in the world who is not your friend. Evil scientists think of cronyism as a sort of power cooperative. Cronyism permits individuals to contribute some of their power to a general pool of power (i.e., the sum of all evils). Members of the cooperative can dip into the pool, as needed. See Nepotism.

- © 2010 Jules Berman

Glossary letter B

2010-08-02T04:06:00.000-07:00

Glossary letter A

2010-08-01T07:00:00.000-07:00

Free ebook, Machiavelli's Laboratory, updated

2010-06-14T05:26:00.001-07:00

Machiavelli's Laboratory is a free ebook that I published on April 13, 2010. It is a discourse on scientific ethics, from the perspective of an unethical scientist. This blog site features excerpts from the book and provides a forum for readers.

I took a few days off from blogging to make several improvements in the content and layout of the book. Blog readers may want to download the latest updates at:

http://www.julesberman.info/integ/machfree.htm

- © 2010 Jules Berman

key words: free ebook, Machiavelli's Lab, ethics, scientific misconduct, scientific fraud, scientific organizations, scientific societies

Corporations 3

2010-06-05T11:25:00.001-07:00

Corporations 2

2010-06-04T04:17:00.001-07:00

You are an overweight middle aged man, who leads a sedentary life. You have dangerously high blood levels cholesterol and triglycerides. Your doctor has put you on a strict diet, with instructions for daily exercise, and has prescribed simvastatin, a low-cost, generic statin, to control your dyslipidemia.

While watching TV, you see a commercial, featuring Dr. Robert Jarvik, inventor of the Jarvik artificial heart, talking about the benefits of Lipitor. The scene shifts from a close-up view of Dr. Jarvik, to a panoramic view of a man who looks like Dr. Jarvik, rowing a canoe. In the space of a short commercial, you make the following assumptions.

1. You assume that Dr. Jarvik was the inventor of the Jarvik heart.

2. You assume that artificial hearts, like artificial hips, and artificial breasts, are a practical alternative to natural hearts.

3. You assume that Dr. Jarvik was making a public service announcement, not a crass advertisement. Dr. Jarvik was paid in excess of $1 million dollars for his spot in the commercial.

4. You assume that Dr. Jarvik is a practicing physician.

5. You assume that Dr. Jarvik has expertise in the pharmacologic field relevant to lipitor (dyslipidemias and their treatment).

6. You assume that Dr. Jarvik had some professional experience with Lipitor.

7. You assume that Dr. Jarvik rowed the canoe.

8. You tell your doctor to switch your cholesterol-lowering medication from the cheap generic drug (simvastatin) to the high-priced patented drug, Lipitor. If he asks why, you tell him that Dr. Jarvik recommended Lipitor.

Your assumptions about the Lipitor ad were inaccurate (197). Let's review:

1. Dr. Jarvik was not the inventor of the Jarvik heart; at least, not the sole inventor. Remember Stigler's Law of Eponymy, "Credit always goes to the wrong person." The father of the Jarvik artificial heart was Kolff, who never commercialized his name. A large team of scientists developed the Jarvik heart. Kolff brought Jarvik into the project.

2. Artificial hearts are not practical alternatives to natural hearts. Though originally designed as a permanent replacement for failing hearts, a succession of artificial hearts, including the Jarvik, failed to do the job. Today, artificial hearts are bridge devices; they keep patients alive from the time that their natural hearts fail until the the time that they receive a transplant heart. It's more accurate to think of these devices as types of cardiopulmonary bypass machines, and not as artificial hearts.

3. Though the commercial had the appearance of a public service announcement produced by a kindly, concerned cardiologist, it was, in fact, a carefully choreographed advertisement produced by a large pharmaceutical corporation with the single goal of increasing Lipitor sales. Dr. Jarvik was paid in excess of $1 million dollars for participating in the project.

4. Dr. Jarvik received an M.D., but never pursued the post-doctoral ordeals that that qualify practicing physicians: internship, residence, fellowship. Nor did he pass any medical specialty Boards that certify competence in a particular area of patient care.

5. Dr. Jarvik has no professional expertise or experience in the dysplipidemias, or their treatment.

6. Dr. Jarvik is not a cardiologist, and has never prescribed Lipitor.

7. An actor, who looked like Dr. Jarvik from a distance, rowed the canoe.

The Jarvik commercial was caught up in a congressional investigation into false and misleading advertising by the pharmaceutical industry; the ads were pulled (197).

Did Dr. Jarvik commit any crime? No. Did the pharmaceutical company commit any crime? No. How are Lipitor sales doing? Lipitor is the number one selling statin drug. Global annual sales of Lipitor exceed $13 billion.

The Lipitor story has a moral. Corporations exist for the purpose of making money. When a corporation advertises, the purpose of the advertisement is to promote a product, and not to provide an accurate representation of reality.

[197] Saul S. Pfizer to End Lipitor Ads by Jarvik. The New York Times February 26, 2008.

--TO BE CONTINUED--

- © 2010 Jules Berman

key words: free online ebook, Machiavelli's Lab, corporate science

CORPORATIONS 1

2010-06-03T07:31:00.001-07:00

Common Errors

2010-06-02T04:14:00.000-07:00

Greed 3

2010-06-01T05:08:00.001-07:00

"There is nothing men will not do, there is nothing they have not done to recover their health and save their lives. They have submitted to be half-drowned in water, and half-choked with gases, to be buried up to their chins in earth, to be seared with hot irons like galley-slaves, to be crimped with knives like codfish, to have needles thrust into their flesh, and bonfires kindled on their skin, to swallow all sorts of abominations, and to pay for all this, as if to be singed and scalded were a costly privilege, as if blisters were a blessing and leeches a luxury" (280).

Know one knows this better than the corporations that sell drugs for the treatment of cancer. Of all the diseases inflicted upon humanity, cancer has proven itself the most lucrative. Here's why:

1. Cancer is common. One in two men; one in three women will contract cancer during their lifetime.

2. Cancer is scary. Everyone is afraid of cancer, and the public continues to lavish money on the National Cancer Institute, despite decades of imperceptible progress.

3. Cancer is chronic. Cancer doesn't kill in a day or a week or a month. Most cancer patients will languish for years of treatment (281).

4. Cancer is expensive, and insurers are obligated to foot the bill for high-priced treatments.

5. There is no simple cancer cure on on the horizon. Drug companies don't need to worry that someone will come up with an effective, cheap cancer cure that will eliminate their source of income.

Today's pharmaceutical industry cynically embraces cancer research, knowing full well that desperate patients will grasp any cancer treatment that lengthens their life, even for a few weeks, and at any expense, so long as a third party foots the bill (284). Erlotinib, sold as Tarceva by Genentech, OSI Pharmaceuticlas and Roche Pharmaceuticals, was approved by the FDA for treatment of pancreatic cancer. It costs about $3,500 per month, and will improve survival by an average of 12 days (284) (285). This 12-day miracle has been embraced by the community of oncologists. The chief executive of OSI Pharmaceuticals, projected that annual sales of Tarceva could reach $2 billion by 2011 (286).

Bevacizumab (developed and sold by Genentech as Avastin) is one of the most popular cancer drugs in the world, bringing in about $6 billion in global sales, in 2009 (287). It can easily cost $50,000 to $100,000 per year of use. Avastin does not seem to be much of a wonder drug. Recent trials have shown that Avastin does not extend the life of men with advanced stage prostate cancer (287). Ditto for gastric cancer (287). In responsive cancers, studies indicate that it extends life by up to four months (288). Why is Avastin popular? A well-marketed drug that promises hope for to desperate patients, will sell, no matter the price.

At any moment, drug companies are running more than 800 clinical trials for cancer drugs (284). They know that if they can develop a drug that improves cancer survival, even for just a few weeks, they can recoup their investments. Big pharma sinks about a billion dollars into each new drug that come to market. Their exclusive right to market the new drug lasts, at most, twenty years from the patent filing date. In view of these circumstances, consumers expect pharmaceutical companies to charge a lot for each dose of a newly developed cancer drug. Conversely, consumers expect cheap prices for generic and ancient nostrums, that are easy to manufacture in bulk quantities and for which no research investment was made. No such luck.

Matulane (sold as Procarbazine), is a drug closely related to mustard gas, and was approved for the effective treatment of Hodgkin lymphoma, way back in 1969. Cheap to synthesize, it sold for a paltry 66 cents per pill until 2005, when the price jumped to $56 per pill, an overnight 8,400% increase (289). How could this happen? Easy. The price of drugs is not regulated by the FDA or any other federal agency. In the U.S., if you happen to have a monopoly on sales, you can charge whatever the market will bear.

Today, decades after the War on Cancer was launched (1971) the cancer death rate is about the same as it was in the mid-nineteenth century. The pharmaceutical industry has not produced many new cancer drugs. The public is paying exorbitant rates for a few new therapies, most of which have only minimally effectiveness. Who is to blame? Many would blame the FDA, clearly the least likely culprit in this sordid business. Guards are now posted at the FDA's public cancer advisory meetings, to protect the FDA staff and its invited committee members (290).

We are no closer to a cure for the common, advanced cancers than we were fifty years ago. The number of people with cancer is increasing and will likely triple over the next few decades. The medical-industrial complex is counting on cancer to be a dependable revenue source for the near future.

--TO BE CONTINUED--

- © 2010 Jules Berman

key words: free online ebook, Machiavelli's Lab, cancer drugs, the cost of treating cancer

Greed 2

2010-05-31T09:50:00.001-07:00

Machiavelli's Laboratory is an ebook that is currently available at no cost. It is a satire on ethics, written from the perspective of an unethical scientist. This blog is a discussion vehicle for the book.

The ebook is available at:

www.julesberman.info/integ/machfree.htm

Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

-- EXCERPT CONTINUED FROM CHAPTER 20. GREED, FROM MACHIAVELLI'S LABORATORY

GHOST WRITERS

Behind every able man, there are always other able men."

-Chinese proverb

"Every writer I know has trouble writing."

-Joseph Heller

Of course, the best way of authoring anything is to take credit for another person's work. In the past, wealthy people were well-accustomed to paying others to for every conceivable service. In Europe, the wealthy could pay to have a seat in Parliament. In early America, the wealthy would pay to have someone serve in the army in their place. Throughout the scientific community, wealthy students would pay to have someone else write their theses and their scientific papers. People who wrote books and articles for money, without appearing as a named author, were called ghost writers. Today, the lucrative field of ghost writing has been turned on its head. Scientists are paid, very handsomely, to have teams of corporate writers publish journal articles with the scientist listed as the sole author. Corporations have found that a journal article favorable to their product, and credited to an influential and respected author, has enormous value to the company.

In August, 2009, Natasha Singer reported, for the New York Times, on ghost writing in the Pharmaceutical industry (174). Wyeth pharmaceuticals helped produce 26 scientific articles between 1998 and 2005, that emphasized the beneficial effects of hormone replacement therapy (174). In a proposal prepared for Wyeth by a firm that wrote many of the articles, the goal of the publication's initiative was to "increase physician awareness on the multitude of benefits that hormone replacement therapy provides" and "diminish the negative perceptions associated with estrogens and cancer" (175). In a process likened to medical ventriloquism, the American physican community willingly believed that hormone replacement therapies had a protective effect on the heart (175).

Wyeth's sales of hormone drugs Premarin and Prempro were about $2 billion in 2001 (174). Sales subsequently dropped after a large, NIH-sponsored clinical trial showed that combination hormonal therapies increased the risk of breast cancer, heart attacks, dementia and pulmonary emboli (175).

Here is how drug company ghost writing generally works. The pharmaceutical company chooses a set of scientific points that it would like to emphasize. A company that specializes in medical communications is generally contracted to write a series of articles suitable to the pharmaceutical company. After the articles are prepared to the satisfaction of the pharmaceutical company, respected authorities in the relevant field are approached and asked if they will permit the papers to be published listing them as authors, in exchange for a consultation fee. The paper is published. The journal editor and the journal subscribers are unaware of the arrangement. Readers falsely assume that the article was written by the listed author, without influence by the pharmaceutical industry. Pharmaceutical companies have the right to help authors write papers that highlight the benefits of their products. Likewise, pharmaceutical companies are under no obligation to emphasize, in scientific papers, the risks associated with their products; nobody is held to such a standard. Scientists have the right to accept consultation fees from pharmaceutical companies, and they have the right to publish scientific papers. Everybody wins.

When the New York Times article broke, scant attention was paid to the role of journal editors in the tangled story (174). Why weren't the editors aware that the articles were ghost-written? What had happened to the vaunted peer review system? Why had the articles not raised suspicions among the eagle-eyed peer reviewers? Isn't it the job of the editor and the peer reviewers to ensure discussion of both sides of controversial scientific topics? Why was the journal-based review system unable to detect that the articles were ghost-written by an industry-paid company commissioned to promote the beneficial effects of hormone replacement therapies?

Ghost-writing is rampant in the scientific community. In a review of 809 scientific papers, by Flanagin and coworkers, 93 articles (11%) had evidence of ghost authors (60). In a Washington Post article, a nuclear energy consultant admitted that he was paid to write pro-industry editorials and farm them to colleagues, who allowed themselves to be listed as authors (301). This method of dissemination provides the illusion of many minds, but analysis of the text usually demonstrates the same key phrases in every editorial, pointing to a single, ghostly author (301).

A 1997 paper published in the Journal of Occupational and Environmental Medicine claimed no link between drinking chromium-polluted water and cancer incidence. At the time that the paper was written, a public utility was being sued for allegedly exposing California residents to chromium pollution. The editors eventually learned that ghost writers hired by the public utility had contributed to the article that seemed to provide exculpatory scientific evidence for the utility company (302). The paper was retracted by the journal, nearly a decade after the fact (303).

Sometimes, when industry ghost-writes a document, there are too many people willing to take the credit for the same work. Lobbyists working for Genentech ghost-wrote nearly identical position statements for over a dozen members of Congress. The Congressmen published the statements, as their own, in the Congressional Record. Any citizen with the time and inclination would see that the same text, with only minimal deviation, appeared repeatedly. In all, over 40 members of Congress used, as their own, points written by lobbyists who were paid by Genentech (304). It's a pleasure to see the American political system at work.

The services of ghost writers are many. Grant applications, review articles, clinical trial summaries, legislation, committee reports, consensus guidelines, industry standards, position statements, and all manner of documents traditionally produced by groups of scientists, can be prepared by a single ghost writer, serving a corporate agenda. Whenever you read a scientific report, never assume that the persons listed as authors had much input in the finished product. So long as there is power and money, there will be ghost writers.

--TO BE CONTINUED--

- © 2010 Jules Berman

key words: free online ebook, Machiavelli's Lab, ghost writer, ghostwriter, ghostwriting

Greed 1

2010-05-30T07:46:00.000-07:00

Avoiding Ethics 7

2010-05-29T04:28:00.001-07:00

You have just pissed into a cup. You pass the cup, along with the requisition form, to a medical student, who will submit the specimen to clinical pathology. On the following day, your doctor will have the results of a complete urinalysis; part of a routine medical check-up. The medical student looks at your paperwork and pauses a moment. She turns to you and asks if you would like to participate in a medical study. You decline. She tells you that there is an ongoing study for men, aged 40 to 70 (your age range) that measures small quantities of prostate-associated proteins in urine. You decline again. She mentions that you will not be bothered in any way by the study. They can use the same urine sample that you just submitted for your annual check-up. You decline. She informs you that the results of the study may lead to a way to treat early prostate neoplasia, before it has a chance of becoming malignant. You decline again. She mentions that this treatment may be available to you within your lifetime. You thank her for the good news and decline again. She wishes you a good day. You proceed with your life.

Patients can be just as selfish as scientists. Many scientific experiments pose no hazard whatsoever to the patients involved. Often, the scientist wants to use a piece of tissue that was removed in the course of some procedure. Excess tissues removed at surgery are usually sampled by a pathologist. The pathologist saves the small tissue sample and discards the remainder. The excess tissue can sometimes be used in research projects. Hospitals usually request patients to sign a form allowing such tissues to be used for research purposes. Well over 90% of patients sign the form, happy to participate in medical research when there is no risk involved.

A subset of patients will refuse to cooperate, under any circumstance. Rarely, the objection will be based on religious grounds. For example, some native American tribes believe that bodies should be kept intact. Tissues removed at surgery are collected, saved for the duration of the patient's life. When the patient dies, his body is buried along with the all the pieces removed during life.

In some cases, patients object without any rational reason. Some will insist that their tissues must have some monetary value to the scientists. Rather than give their tissues away, they want to negotiate a contract for a piece of any profits that might result from the experiment. This tactic never works. The scientists will simply obtain their tissues from the next patient.

Even when assured that a lucrative contract is simply not in the offing, and that their excess tissues will be discarded if not used for research, some patients will refuse to sign a release for the tissues. In this case, refusing to donate excess tissues is a matter of selfishness, not greed. These patients do not like to give anything of theirs to another person. They would rather have the tissue incinerated.

The Helsinki declaration of the World Medical Association (WMA) insists that participants share the benefits that come from clinical trials: "The WMA hereby reaffirms its position that it is necessary during the study planning process to identify post-trial access by study participants to prophylactic, diagnostic and therapeutic procedures identified as beneficial in the study or access to other appropriate care. Post-trial access arrangements or other care must be described in the study protocol so the ethical review committee may consider such arrangements during its review (209)." This being the case, shouldn't those who refuse to participate be denied benefits? Every consent form should have a paragraph that reads, "I refuse to participate in this research project. I understand that I will not be permitted to use the medicines, and treatments that may become available as a consequence of this research. Further, I understand that my name will be included on a list of people who cannot receive medication or treatments developed from this research project."

Justice happens whenever a person gets what they've asked for, and then they are required to live with the consequences.

--TO BE CONTINUED--

- © 2010 Jules Berman

key words: free online ebook, Machiavelli's Lab, confidentiality, medical consent, unethical behavior, unethical behaviour

Avoiding Ethics 6

2010-05-28T09:25:00.000-07:00

Avoiding Ethics 5

2010-05-26T05:00:00.001-07:00

Machiavelli's Laboratory is an ebook that is currently available at no cost. It is a satire on ethics, written from the perspective of an unethical scientist. This blog is a discussion vehicle for the book.

The ebook is available at:

www.julesberman.info/integ/machfree.htm

Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

-- EXCERPT CONTINUED FROM CHAPTER 15. ETHICS AND THE AVOIDANCE OF SAME, FROM MACHIAVELLI'S LABORATORY

"The movies are the only business where you can go out front and applaud yourself."

-Will Rogers

Most people simply do not understand the meaning of conflict of interest, often confusing the term with payola, or bribery, or some intentionally deceitful action designed to further one's own interests. A conflict of interest is simply the condition where a person is put in a position where his decisions may be influenced by factors other than the usual and expected factors that motivate a person. Here is a good example of a conflict of interest. A physician's son is sick. The doctor decides to diagnose his child himself, without sending the child to the pediatrician. Normally, a physician who encounters a sick child has one driving interest: to render a correct diagnosis, even when that diagnosis is terrible news for the child and the parents. A father's primary interest is his child's welfare. The father-physician wants, more than anything else, for his child to have a benign illness. The father-physician has a conflict of interest, because the motivation to render a diagnosis may conflict with the motivation to have a healthy child. A conflict of interest is not necessarily a dishonest action; it is merely a situation where a person's motivations are muddled.

How pervasive are conflicts of interest in the science literature? Stelfox and colleagues reviewed papers that supported the somewhat controversial issue of drug safety of calcium channel blockers. They found that 23 out of 24 authors who defended the safety of calcium channel blockers had financial ties to the pharmaceutical companies that manufactured these drugs (218). Of 70 articles reviewed for the study, only two of the articles disclosed potential conflicts of interest (218). Studies that have looked specifically at the issue of financial disclosures by authors of research articles have shown that voluntary disclosures of conflicts are rarely reported (95). Most academic institutions have no conflict of interest policy for staff receiving commercial support (219).

Conflicts of interest accompany exercises in power, and are most likely to occur among top-level scientists. Here is an example. A university professor is a consultant for a pharmaceutical company. He relationship with the pharmaceutical company extends over several decades, during which time he has collected a considerable amount of stock in the company. He conducts clinical trials testing drugs that the pharmaceutical company has developed. Clearly, he has a conflict of interest. He wants the drug trial to succeed for a variety of reasons that are unrelated to scientific curiosity. If the trial succeeds, his stock will increase in value. If the trial fails, his stock will plummet in value. He has every reason to distort or misinterpret the findings of the trial to favor the pharmaceutical company. He has every reason to minimize, fail to report, and fail to treat adverse reactions from the drugs.

Jesse Gelsinger was a 17 year old who volunteered in a clinical trial conducted in 1999, that resulted in his death. The trial was led by James M. Wilson at the University of Pennsylvania. Accusations of misconduct resulted in an investigation, and in 2005 the U.S. Justice Department settled a civil case against Wilson and his major collaborators and with the University of Pennsylvania. As part of the settlement, Wilson was required to write an article on "lessons learned. (220)" In 2009, a decade after Jesse Gelsinger's death, an article appeared in the journal Genetics and Metabolism, written by James M. Wilson, and entitled "Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. (221)" In the article, the author reflects on the professional motivations of academic scientists, such as himself. In this case, Wilson was a founder of a biotechnology company focused on gene therapy, while he led clinical trials of gene therapeutics. Furthermore, he owned stock in Genovo, another gene therapy company. Success in Jesse Gelsinger's trial may have bolstered the value of stocks held in the gene therapy sector. Wilson wrote, "I learned it is very hard to convincingly uncouple drivers for academic success from the incentives derived from potential financial gain. (221)" Indeed.

Situations arise when an entire group of scientists are equally conflicted. For example, most scientists have membership in several different scientific agencies. The steering committee for one organization is usually populated by the same scientists who hold office in other organizations. Issues will arise that relate to the way that one organization interacts with the other organizations in the same field. Decisions are made to co-sponsor events, to send mailings to members of the other organizations, to recruit new members from the ranks of the other organizations, or to purchase services and goods from other organizations. In each case, the committee members have conflicts of interest. Which organization will their influence serve? Nobody knows, and nobody seems to care. The occurrence of conflicts among the officers in scientific organizations is so pervasive that it cannot be stopped. In most instances, these kinds of conflicts are simply ignored.

Sometimes, conflicts of interest rise to the level of criminal action. For example, a former head of the FDA, Lester M. Crawford, owned stock in companies that his agency regulated. Two months after his approval, by the U.S. Senate, as FDA Commissioner, Crawford found himself pleading guilty to a conflict of interest charge. He received a sentence of three years supervised probation and a fine (222).

[218] Stelfox HT, Chua G, O'Rourke K, Detsky AS. Conflict of interest in the debate over calcium channel antagonists. N Engl J Med 338:101-105, 1998.

[219] Ehringhaus SH, Weissman JS, Sears JL, Goold SD, Feibelmann S, Campbell EG. Responses of medical schools to institutional conflicts of interest. JAMA 299:665-671, 2008.

[220] Weiss R. U.S., Researchers Reach Deal in '99 Gene Therapy Case. The Washington Post February 10, 2005.

[221] Wilson JM. Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Genetics and Metabolism 96:151-157, April 2009.

[222] Saul S. Former F.D.A. Chief Is Charged With Conflict. New York Times October 17, 2006.

--TO BE CONTINUED--

- © 2010 Jules Berman

key words: free online ebook, Machiavelli's Lab, informed consent, medical consent, unethical behavior, unethical behaviour

Avoiding Ethics 4

2010-05-25T07:24:00.000-07:00

1. Consent is a revenue source for researchers. When consent must be obtained on thousands of patients, the consenting costs can actually exceed the costs of conducting the trial. You need to consider that the consent must be explained to the subject, by a professional staff member. The consent form can be quite long, and the time for acquiring consent can be lengthy. After consent is obtained, it must not be lost. In most cases, the consent information must be entered into a database (another cost). Patients have the right to reverse consent at any time during the clinical trial. The trialists need to have a way of flagging cases for which consent was withdrawn; not an easy task. The tasks related to the consent process cost money, without materially contributing to the research output. Because funding institutions must support consenting efforts, you can ask for and receive obscenely large grants when consenting is required.

2. Consent is itself a confidentiality risk. The moment you ask for consent, you're creating a new security risk, because the consent form spells out the procedure and the patient. The consent form must be stored, and retrieved as needed. Copies of the consent form will usually need to be attached to the patient's medical record, and other documents needed for the duration of the patient's care and during the trial follow-up period. As more and more people have access to copies of the confidential consent forms, the risk of a confidentiality breach increases. In many trials, the physical risks to the patient are minimal (e.g., obtaining a swab of the oral mucosa, drawing one extra vial of blood during a routine phlebotomy procedure). In minimal risk trials, confidentiality risks associated with the acquisition of consent may represent the greatest threat to the patient.

3. Consent diverts attention from a wide range of nefarious activities. There is a limit to the number of problems anyone can worry about. If half of your research effort is devoted to obtaining, storing, flagging, and retrieving consent forms, you're less likely to pay attention to other aspects of the project. More importantly, an IRB (Institutional Review Board) that approves a consent process will have less time to supervise your methods of treating patients, recording intended and unintended consequences of the treatment, and analyzing the resulting data.

4. Consented research data can be used for unconsented purposes. Once you've gotten permission to do a study, the results of the study can be used for purposes unrelated to the original project. Here's how it's done: when you have collected all the data for your consented research, remove the patient identifiers (names, addresses, social security numbers, and any other identifying information) from the trial records. This yields a de-identified database. Government regulations pertaining to human subject research and the uses of medical records do not apply to de-identified data (217), (208). Use the de-identified data for any purpose, commercial or non-commercial, that suits your fancy. You can combine your data with other data that you collected, or with data held by other collaborators, including pharmaceutical companies. The project for which the consent was obtained can be implemented as a ruse, the sole purpose of which is to support research that patients would not dream of consenting, otherwise.

Is it ethical to ask consent for a research effort that you never intended to pursue? Maybe not. But it may be what you need.

--TO BE CONTINUED--

- © 2010 Jules Berman

key words: free online ebook, Machiavelli's Lab, informed consent, medical consent, unethical behavior, unethical behaviour

Avoiding Ethics 3

2010-05-24T08:32:00.000-07:00

Avoiding Ethics 2

2010-05-23T04:01:00.001-07:00

AVOIDING ETHICS 1

2010-05-22T06:33:00.001-07:00

1. IRBs may not like certain research fields, finding them inherently harmful to patients, essentially stopping the career of faculty who work in the field.

2. IRBs may dislike particular researchers. Death by nitpicking is the standard punishment reserved for unpopular investigators.

3. In an effort to protect the sovereignty of the IRB, the Common Rule provides no mechanism wherein investigators can demand accountability for bad IRB decisions. Any IRB can hound any investigator to distraction, without needing to justify their actions to a higher authority.

4. IRBs have notoriously poor communication with investigators. Final judgments are issued without explaining to the investigator what he must do to submit a proposal that would be acceptable to the IRB.

5. IRBs often have nobody on the committee who can competently read the proposal. IRBs seldom try to maintain the pretense of scientific competence, taking the position that their job is to assess risks to patients, not judge the research on its scientific merits. This skirts the issue that if they do not understand the science, they cannot estimate the resulting risks. When in doubt about research risks, IRBs tend to err on the side of "no".

6. IRBs don't have a very good record regarding consistency; handing down a rejection a trial that has the same research risks as another trial that was previously accepted by the same IRB. IRB committee turnover contributes to the problem, but the overall lack of firm principles of operation probably accounts for the bulk of inconsistent judgments.

7. There is wide variability in the way that different IRBs operate. A project that is approved at one IRB can be summarily rejected by a different IRB. Some of these inter-institutional differences may be due to the many ways that the Common Rule regulation is interpreted.

8. IRBs have a tendency to be overly protective of human research subjects. Whereas the Common Rule is designed to protect research subjects from harm, many IRBs protect research subjects from any perceived annoyance or inequity, no matter how trivial or unlikely. In many cases, such protections, if enforced, would abrogate the scientific value of proposals.

9. Principle 19 of the World Medical Association's Helsinki Declaration (209) states the following: "Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research." The ugly truth is that there is never a reasonable likelihood that anyone, other than the researchers themselves, will benefit from the results of the research. Consider the field of cancer research. Despite hundreds of thousands of experimental studies, we don't have a cure for cancer, but we have produced thousands of smug, well-funded scientists. Knowing this, it would be fair to say that every future cancer study will have the same likelihood of success as all of the past experiments; that's a number pretty close to zero. If human subject research required a likely benefit for the subjects, all clinical research would come to a grinding halt.

10. IRB decisions have finality. Investigators cannot appeal decisions rendered by the IRB. The only solution for a rejected proposal is to come back to the same IRB with a new proposal.

In the U.S., the Office of Human Research Protections (OHRP) registers and regulates IRBs. You might think, that with all the angst generated by IRB decisions, the OHRP might focus its attention on the decision-making process. Not so. The OHRP is not in the habit of faulting IRBs for bad decisions. Like any government office, the OHRP is all about processes (not results) (210), (211). IRBs must ensure the OHRP that approved protocols are legitimate (the applicant did not misrepresent the study presented to the IRB), that researchers are not conflicted by financial or other interests that might lead them to harm patients, that the actual trial conforms to the submitted protocol (no bait and switch), that adverse events are reported, and that these activities are documented and organized (so they can be found), dated accurately, and saved. The job of an IRB is to develop and deploy a well-documented process for approving and following protocols. That's all.

You might think that institutions could assemble and operate a smoothly functioning IRB. It seldom happens. Here are just some of the many rituals followed by institutions that run IRBs: providing no guidance to the members of the IRB; placing lazy and unqualified staff into IRB positions, as a sort of administrative punishment; bullying IRB members into approving or disapproving protocols for reasons unrelated to human subject protection; placing staff into IRB positions who have known conflicts of interest stemming from financial arrangements with drug companies; performing no quality assurance over the general activities of the IRB, to ensure that the IRB is adequately fulfilling its responsibilities.

--TO BE CONTINUED--

- © 2010 Jules Berman

Universities and Evil Science 3

2010-05-21T04:17:00.001-07:00

Universities and Evil Science 2

2010-05-20T05:25:00.001-07:00

1. Non-human corporations invade the minds of faculty (with money) and take control of their thoughts;

2. Faculty enlist legions of students using slogans and speeches prepared by the supreme commander of the corporate forces;

3. A student uprising against the faculty is suppressed, using a diabolical super-weapon, academic freedom, that selectively destroys students.

4. The student body capitulates, and obeys the commands of the faculty.

5. Students, the subjects of non-human corporate mind-control, graduate to become the next generation of faculty.

What is the difference between science fiction and real life? It costs $8 to send your child to a science fiction movie; it costs $266,000 to send your child to four years at Harvard Medical School.

How can the faculty receive money from pharmaceutical companies and promote the interests of these companies in their lectures to students? Isn't this a flagrant conflict of interest? Of course, but there is a loophole that protects the faculty, and the loophole is called academic freedom. Academic freedom permits professors to make assertions that are unpopular. Academic freedom also provides faculty with the right to operate openly, as the shill of corporate interests. This means that academic faculty can openly promote the positions of their corporate sponsors, even when those positions have no scientific merit. The most important feature of academic freedom is that it belongs to the faculty, not the students. Students, you see, are the victims of academic freedoms exercised their instructors.

When students attempt to use the same freedoms enjoyed by their professors, the consequences can be dire. The Christian Science monitor reported the unusual fate of Petr Taborsky, who worked on a corporate-sponsored science project as a University of South Florida (USF) student (201). According to Mr. Taborsky, he developed a new way of purifying waste water while participating in the project. The USF took an interest in the research, claiming ownership of the process. A judge agreed, forbidding Mr. Taborsky to use the research data. Mr. Taborsky had other ideas, and proceeded to successfully patent the process. When he refused to sign the patents over to the university, he was sent to prison, where he served on a chain gang. Universities are ruthless, greedy entities no different from corporations. If anyone doubts this, just ask Petr Taborsky.

It's easy to exploit students. A popular tactic is to divvy up their responsibilities on a research project, keeping each participant ignorant of the others' work, and taking credit for the total product.

Here is an example of how the process might unfold:

1. A graduate student isolates a class of related chemical compounds, obtained from an herb. The herb is touted, by traditional Chinese healers, to have anti-cancer activity. The related chemical compounds have some inhibitory effect on a cellular pathway known to be activated by an oncogene.

2. Another graduate student, in the same lab, develops methods to isolate, purify, and chemically characterize the different active compounds.

3. Another graduate student, in the same lab, demonstrates that these compounds inhibit the proliferation of several different cancer cell lines.

4. The laboratory chief (a full professor in the University, and a paid consultant for 15 different pharmaceutical companies) contacts the University's Technology Transfer Office. Plans are laid to patent the class of compound as an anti-cancer treatment, based entirely on cell line studies, with no actual anti-cancer trials in any animals or in humans. Under the University's technology transfer policies, the patent will be assigned to the University. The laboratory chief will receive 25% of any patent royalties and licensing fees received by the University. The graduate students who had key roles in the discovery, will receive nothing; neither will the traditional Chinese healers.

Though universities and faculty make a big show of academic freedom, most faculty will gladly sign away their freedom to corporations; if the price is right. Thirty-five percent of agreements signed between industry and academic researchers allow the sponsor to delete information from publications; 53% allow sponsors to delay publications (202). Basically, what a professor says, and when he says it, can be determined by his industry sponsor.

--TO BE CONTINUED--

- © 2010 Jules Berman

Universities and Evil Science 1

2010-05-19T04:14:00.001-07:00

Evil Intellectual Property 4

2010-05-18T14:42:00.001-07:00

Evil Intellectual Property 3

2010-05-17T05:24:00.001-07:00

Evil Intellectual Property 2

2010-05-16T07:38:00.000-07:00

1. Patenting to suppress innovation. If you were in the oil business, and an inventor developed a source of free, unlimited energy (e.g., solar power), you might be inclined to buy the patent for his solar energy invention for the sole purpose of halting its implementation. Likewise, if you held a patent on a gene or a drug, you could assert your patent to squelch research or medical testing on your property, for the duration of the patent (159).

In the case of healthcare, there are some limits on the use of patents to suppress a scientific discovery. In 1999, Congress passed 35 U.S.C. 287 specifying conditions that would limit the damages collected by patent holders from healthcare practitioners (160). If you held the patent on a new way of tying a knot, and if a surgeon required the use the patented knot as a ligature in a surgical procedure, the patent would probably not be enforceable on the surgeon, under 35 U.S.C. 287. For the moment, patent holders cannot stop physicians from saving lives.

2. Patent farming. If you hold a patent for an algorithm or a manufacturing process that could be used in other technologies, you might benefit by "seeding" your invention into the derivative technology. When the new technology is released, you can "farm" your patent by announcing that anyone using the new technology will need to pay you royalties. For example, if a committee is creating a new software standard, you might strive to become a member of the committee. If you can insert your algorithm or subroutine into the new standard, then your patent rights will extend to the final standard. If the standard is mandatory, you can expect to collect royalties from thousands or millions of unwilling users.

3. Patent spreading. Every patent contains a set of claims that specify the intellectual components that are protected by the patent. For example, a patent for a software application may claim each of the algorithms or subroutines that are featured in the application, the graphic user interface by which the application is accessed, and novel features included in the application. An evil scientist will maximize his list of claims, effectively magnifying his intellectual property.

4. Patent holding. A shrewd capitalist can buy patents that cover fundamental processes that are necessary for a particular field. Whereas a single patent may be vulnerable to challenge, a collection of patents that insinuate their claims throughout a complex industry, might be invincible. Patent holding companies (called patent trollers by their detractors) strategically collect patents on devices and processes that are vital to an industry. When the time is ripe, after a new technology has become an indispensable component of business, the patent holding companies will assert their portfolio.

5. Patent shifting. Sometimes, a patent holder may find himself in a position where it would be unwise to assert his patent. Large corporations and patent holding companies occasionally reach agreements with their competitors to hold each other harmless from patent infringements. These kinds of agreements can save companies a vast amount of time and expense. In such cases, a corporation may choose to sell various patents to a third party (an individual, a corporation, or a holding company). The third party, unrestricted by a non-litigation agreement, can prosecute the patent. This works best if the patent is not owned directly by the company that sells the patent.

For example, if a corporation sits on a committee that is developing a new industry standard, it may need to sign an agreement promising not to prosecute patents held by the corporation and implemented by the standard. This kind of agreement is developed by standards committees to discourage patent farming. The company can simply sell the patent to a holding company. Sometime in the future, when the standard becomes entrenched in an industry, the holding company will assert the patent against all of the patent users. The corporation that developed the patent would have made its profit up front, at the time of the patent's sale to the holding company.

6. Remixing prior patents. You can re-mix prior art to make a new device that you can patent for yourself. This provision in patent law is particularly useful for software corporations; virtually all new software is made by re-mixing old software. You must be careful, though, to produce a re-mixed product that is not obvious to your peers. In KSR v. Teleflex (April 30, 2007), the U.S. Supreme Court, in a unanimous opinion, reversed a Court of Appeals decision, and determined that a prior patent was unenforceable because it was obvious (161). The opinion discussed, at length, the principles of obviousness. In particular, the Supreme Court indicated that merely putting together prior art to make a new device can only qualify for a patent if the resulting device is unexpected by people working in the field; hence, not obvious.

7. Patenting the uses of unpatented inventions. The wheel is an unpatented invention. If you were to come up with a novel, useful, and nob-obvious application of the wheel, you might be able to patent your work. This means that when you use an invention that is not covered by a patent, your use of the invention may still constitute a patent infringement. Here is an example. DICOM (Digital Imaging and Communications in Medicine) is a freely available, unpatented standard for radiologic images. Currently, there is an effort to have all medical specialties adopt DICOM as the exclusive format for all medical images. Nonetheless, there there are specific circumstances for which the DICOM standard cannot be used without infringing on patented intellectual property. U.S. Patent 6725231, issued Apr 20, 2004, to Jingkun Hu and Kwok Pun Lee and assigned to Koninklijke Philips Electronics N.V., has the following claim.

"1. A method for mapping a DICOM specification into an XML document, comprising: mapping each entry of a DICOM table of the DICOM specification into a corresponding XML element of a plurality of XML elements,outputting each XML element of the plurality of XML elements to the XML document, in an output format that conforms to at least one of: an XML document-type-definition and an XML Schema."

In addition, the patent owners have been granted a similar patent by the European Patent Office (EPO). Mapping image information from a free specification, such as DICOM, into another free specification, such as XML, is a common task for medical informaticians. Does this activity constitute an infringement on an existing "use" patent? These are the types of questions that keep patent lawyers busy.

8. Patenting life. What must it feel like to own a species of living organisms? It must be like God would feel, if God had the the Supreme Court on his side. In a 1980 5-4 ruling, the Supreme Court upheld that a living organism could be patented. The case was Diamond v. Chakrabarty and involved a dispute over a patent for a genetically modified bacterium (162), (163).

After a patent on life is awarded, the consequences can be far-reaching. For example, Monsanto developed and patented genetically engineered corn that is resistant to Monsanto's Roundup weed killer. Using Monsanto's corn seed, robust corn grows in fields that are liberally treated with Roundup. This guarantees that farmers who buy Roundup-resistant corn will also buy Roundup, at Monsanto's price. When farmers buy Roundup-resistant corn, they agree not to collect seed (from their corn crops) for replanting. This means that each growing season, they must buy new seed from Monsanto, at Monsanto's price (164). The use of genetically engineered seed is rapidly spreading. As more and more farmers use Monsanto's seed, the risk increases that genetically engineered seed will drift (from the winds, or from passing seed transport trucks) onto the fields of farmers who chose not to use genetically engineered corn. After genetically engineered corn invades a field, Monsanto can assert its seed patent on the hapless farmer, even when the farmer had not intended to use Monsanto's seed.

It is dangerous to rely on a single genetic variant of vital crop seed. A newly emerging disease that targets the crop can decimate the world's food supply. In the specific case of roundup-resistant corn, new varieties of roundup-resistant weeds may emerge. In 2010, twenty-two states were infested by multiple new species of roundup resistant weeds, essentially nullifying any benefit from the genetically engineered corn (165).

The Diamond v. Chakrabarty ruling extends "life" patents to genes and sequences of DNA. Jensen and Murray reported in 2005 that 4,382 of 23,688 human genes in National Center for Biotechnology Information had been patented (166). The two most highly patented genes were BMP7, an osteogenic factor, and CDKN2A, a tumor suppressor gene (166). These two genes are claimed in more than 20 patents.

9. Viral patenting involves asserting a patent on the manufacturer of an assembled device, and asserting the same patent on the users of the manufactured device. Viral patenting is risky for the patent owner. In a precedential case, the U.S. Supreme Court unanimously ruled that LG Electronic could not assert a patent against Intel (the manufacturer that implemented a memory-technology patent owned by LG Electronics) and on the computer makers that install Intel chips in their computers (167). The patent power to collect royalties was effectively exhausted by its first license (with Intel).

10. Royalty stacking. For a complex process, it may be possible to assert different patents on various steps in a process. For example, a medical test may involve processing cells using a patented technology, using one or more patented reagents, performing a patented analytic process, using a patented machine, and evaluating the data with patented software. After all the royalties are stacked, the totaled costs are transferred to the patient or to a third party payer (168).

11. Reaching through a patent. Savvy patent holders may issue licenses that contain an insidious "reach-through" clause. The clause may stipulate that license holders can use the patent under the condition that any future technologies, that the license holder develops with the licensed technology, will be assessed a royalty. The clause allows the patent holder to reach through into the intellectual property created by the license holder, and impose an additional royalty.

Evil Intellectual Property 1

2010-05-15T08:55:00.001-07:00

Scientific Globetrotting 5

2010-05-14T08:33:00.001-07:00

Scientific Globetrotting 4

2010-05-13T04:23:00.001-07:00

Scientific Globetrotting 3

2010-05-12T04:09:00.001-07:00

Machiavelli's Laboratory is an ebook that is currently available at no cost. It is a satire on ethics, written from the perspective of an unethical scientist. This blog is a discussion vehicle for the book.

The ebook is available at:

www.julesberman.info/integ/machfree.htm

Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

-- EXCERPT CONTINUED FROM CHAPTER 8. SCIENTIFIC GLOBETROTTING, FROM MACHIAVELLI'S LABORATORY

Today, scientists will eagerly travel the globe to attend a meeting of fellow scientists, but very few scientists make any kind of effort to discover a new species of moss. Speak to any successful scientist and ask him where he has been lately. He will rattle off a list of cities, domestic and foreign, that would be the envy of any travel writer. Scientists who do not travel are relegated to obscurity. Nobody will know their name. Their work will not influence the work of other scientists in their field.

Travel for modern scientists, in contrast to predecessors such as Spruce and Douglas, is easy, pleasurable, and fully reimbursed. Most scientists work in major metropolitan areas and have access to an international airport. In the U.S., almost anyone can fly to Chicago (a centrally located location that hosts many meetings and scientific societies) in about two hours. London-based scientists can hop on a non-stop flight from Heathrow to Las Vegas; air travel time, a tolerable nine hours.

More than a few budding scientists are drawn into their fields by the opportunity to attend lavish meetings, held in exotic locations. Young scientists enjoy the opportunity to meet bright, attractive colleagues in a socially exciting atmosphere, to network, and to enhance their careers just by being there. Senior scientists enjoy the adulation and the amenities, particularly fine wining and dining. Those with tight per diem budgets will enjoy the meeting freebies.

10:00 A.M., Tuesday morning, Venetian Hotel, Las Vegas. There is nothing quite like a scientific meeting in Las Vegas. Things that are impossible anywhere else are likely to occur here. Here, you have a chance to meet beautiful women who were well beyond your pay grade anywhere else. You march briskly through the casino aisles, barely glancing at the human residua seated night and day at the gaming tables, and you approach the vast meeting area that lies beyond. Another set of tables awaits the scientists. These are filled with trinkets brought as gifts by the laboratory vendors. The treasures consist of pens (retractable, gel-tipped, glow-in-the-dark, on-a-rope), pocket flashlights, paperweights, miniature souvenirs and keepsakes marked with a corporate logo (valuable collectors' items), key rings, t-shirts, lanyards, coffee mugs, thumb drives, nail clippers, business card holders, money clips, umbrellas, mirrors. They're all for you and they're all for free. Then come the foods: coffee, cookies, potato chips, pretzels, chocolates. If you're a VIP, you won't need to collect freebies by visiting the tables. The vendor organizers will prepare a VIP basket filled with a selection of the best freebies from all the vendors, plus special gifts selected just for you. The personal services are a nice touch. Look for 3-minute massages (to relieve the stress that comes with every meeting), and caricatures (drawn by an artist or rendered by a computer from a digital photograph). You can count on a door prize and a grand raffle, so be sure to register early on the first day. Consolation prizes will include golf clubs, and answering machines. Luckier attendees will receive computers, or free registration to next year's meeting. The top prize is $5,000 in cash. Seduced by trinkets, by meeting's end you will have fallen in love with every vendor in the room. Do you worry that once you've accepted a vendor freebie, you can no longer promote yourself as an impartial expert in your field. Nonsense. What happens in Las Vegas stays in Las Vegas.

What is the purpose of a scientific meeting? All meetings serve one purpose; to produce wealth for the meeting sponsors and power for the meeting organizers. If you have a big radiology meeting, or surgery meeting, you can bet that the meeting was supported by vendors of radiology equipment or surgery equipment. The vendors will construct elaborate booths for the purpose of selling their wares. The vendors, who are much better showmen than the scientists who attend meetings, will set the general tone of the meeting, and will greatly influence the meeting agenda. In many cases, vendor representatives will make scientific presentations, often brazen advertisements for their latest products.

You own a software company. Years ago, you were an earnest assistant professor at a major university, and you take pride in your scientific credentials and the network of scientific associates that you cultivated over the past decade. When one of your former students (now the head of the Program Committee) invites you to present a lecture on Middleware, you jump at the chance. Your company exclusively produces middleware, and there is nobody in the world who has more ground-level experience with the subject than you. Here is your chance to convince the scientific community to place their trust in your middleware product, and yours alone. You will come prepared with the slickest visuals that any of those ivy tower pundits have ever seen. You have signed a disclosure form that tells everyone that you are the President and owner of a middleware company, so you needn't worry about anyone complaining that they weren't warned. You will spend the hour hyping the importance, value, and dependability of your product. You will be very careful not to mention any of your competitors. This is your hour, not theirs. They would do the same, if they were asked to speak.

Here are the signs of a commercial agenda disguised as a scientific presentation:

1. Only the speaker's product will be mentioned by name. The speaker will only mention competitors in the context of the deficiencies of their products.

2. The speaker will refute any criticism of their commercial product, even when the criticism is fair. In many instances, they will try to discredit or marginalize all critics.

3. The speaker will not discuss any technical difficulties that members of the audience might have had with their product.

4. Open source or free products will be mocked ("Oh yes. I've heard of the freeware you're referring to. You get what you pay for.").

5. The speaker will discuss issues related to product popularity, rather than product value ("We've had 100,000 visitors to our web site").

6. The speaker will plant friendly associates in the audience, who will provide personal testimonials stressing the value of the product.

7. The speaker will often place a moderator or panel chair who will divert discussion away from criticisms ("We'll be discussing this general issue at this evening's round-table. So I'm asking you to defer this question until then.")

8. The speaker will have professional quality graphics for his presentation. The average scientist would not go to the trouble of creating impressive graphics.

9. The speaker will be attractive and well-spoken; real scientists are neither.

10. The speaker will be sincere. Real scientists seldom seem sincere because they are constantly re-examining their own assumptions and conclusions. Commercial speakers have learned to fake sincerity.

11. The speaker will use buzz words. Besides the hackney "synergy, leverage, network, enterprise," look for terms that seem out of place in a scientific venue: CIO, CFO, return on investment, workflow, user profile, enterprise, product.

12. The speaker will not give credit to prior art. This would jeopardize pending patents.

13. The speaker will be future-oriented, not past-oriented, even with regard to their own product. This will avoid criticism from members of the audience who had problems with earlier versions of their product. Also, speakers are often people who are newly hired by the company. They honestly don't know much about the history of the product.

14. The speaker may be an academic. Companies will sometimes pay a respected scientist to promote their product during a "science" lecture. Read the meeting documents. There will be a page that lists the conflicts of interest disclosed by the speakers. You will find that the speaker has been paid by a company that stands to profit from a favorable presentation.

--TO BE CONTINUED--

- © 2010 Jules Berman

Scientific Globetrotting 2

2010-05-11T04:20:00.001-07:00

Scientific Globetrotting 1

2010-05-10T03:33:00.001-07:00

Complexity 5

2010-05-09T04:44:00.001-07:00

Complexity 4

2010-05-08T03:34:00.001-07:00

Complexity 3

2010-05-07T04:20:00.001-07:00

Complexity 2

2010-05-06T05:36:00.001-07:00

Machiavelli's Laboratory Blog Archive

2010-05-05T04:30:00.000-07:00

I have created a blog archive site for Machiavelli's Lab.

It lists all of the prior blogs, by title, with direct links to the blog post.

The archive allows you to conveniently browse through the post titles and choose those topics that have a special interest to you.

- © 2010 Jules Berman

Complexity

2010-05-04T07:17:00.001-07:00

Evil Editors and Reviewers

2010-05-03T04:29:00.001-07:00

You read a fascinating journal article in the October issue of Science Life. The authors have discovered that galactic acid, secreted by tear ducts, increases the time that astronomers can stare through their telescopes without blinking. You find this article particularly interesting for two reasons; 1) in the March issue of The Science of Our Lives, you reported that galactic acid increased the time that birdwatchers could stare through their binoculars without blinking, and 2) the authors of the Science Life paper did not cite your work, that predated their work by 7 months. You write a letter to the editor of Science Life, indicating that yours was the earlier work, and that you would like to have a letter published in the very next issue of the journal, rectifying the oversight.

Three weeks later, you receive a letter from the editor's office indicating that your letter has been received and is being reviewed by an impartial referee. The letter indicates that you will be informed of the editor's decision once it has been made.

Two months pass. You call the editor's office. His assistant indicates that the editor is aware of your complaint, is working to reach a decision, and that you will be notified when a decision is reached.

A month later, hearing nothing, you call the editor's office again. This time, you reach the editor. The editor indicates that your complaint has been reviewed, and that the outside consultant had determined that the authors of the Science Life paper are innocent of plagiarism.

You inform the editor that you had not accused the other authors of plagiarism. You simply had accused them of being the second, not the first, laboratory to discover that galactic acid inhibits blinking. As such, your paper should have been cited in their paper.

The editor indicates that because there was no plagiarism, there was no scientific misconduct. If there was no scientific misconduct, there is no obligation to publish a retraction.

You indicate that you are not requesting a retraction. You are requesting that the editor publish a short statement indicating that you were the first to discover the effect of galactic acid on blink-avoidance.

The editor indicates that his journal does not embroil itself in disputations over precedence. He says that such arguments need to be settled among the authors.

You indicate that the problem is that the readers of Scientific Life were informed, incorrectly, that the October article was the first to observe the effects of galactic acid on blink-avoidance. You are simply asking for the mistake to be corrected.

The editor indicates that he is pressed for time, and the conversation ends.

Editors have their own biases and will summarily reject scientifically sound papers, if it suits them. There really is nothing that a scientist can do when an editor tells him that a flawless work, requiring years of hard work, is simply unsuitable for publication in the journal (44). Aside from asserting their many biases, editors impose a set of self-serving rules that they expect authors to obey. In a paper pompously titled, "On Exemplary Scientific Conduct Regarding Submission of Manuscripts to Biomedical Informatics Journals," a group of editors vented some of their frustrations with authors. Particularly vexing was a practice they call "journal shopping," occurring when "Authors submit a manuscript to one biomedical informatics journal, and, after peer review, it is not accepted for publication, and a critique is provided. The authors do not make any of the changes suggested by the previous review and instead submit the unchanged manuscript immediately to a second journal, without disclosing the existence or results of the previous review by the first journal."

Authors do not publish guidelines telling editors how to edit; editors should not publish guidelines telling authors how to write. If authors were to list some of the more egregious practices of journal editors, they might include the following points:

1. Accepting papers of highly questionable scientific merit when those papers come from an influential laboratory, or when those papers address a hot topic of great interest of their readers.

2. Failing to provide a timely review. Editors always blame the reviewers, but the reviewers are selected by the editor. A craftsman never blames his tools.

3. Not bothering to ask whether the reviewer or the authors have conflicts of interest. Or, asking reviewers and authors if they have conflicts of interest, but doing nothing to verify their response (89)

4. Relying on reviewers who routinely reject papers written by their competitors.

5. Failing to determine the competency of reviewers.

6. Failing to have any quality assurance program for rendered reviews. Editors should be able to show that that reviews have consistency. Editors should follow the destiny of rejected papers. If the journal's rejecta are published in competing journals, receiving praise and peer citations, then something went wrong with the original review process.

7. Failing to provide reviewers with guidelines for a fair review. When a reviewer flatly rejects a paper because it was prepared in a small font, then perhaps the reviewer could use some instruction.

8. Failing to determine if the study protected research subjects from harm.

9. Failing to determine if the paper was written by a ghost writer.

10. Failing to provide authors with the names of the peers who reviewed their papers. Criminals are allowed to confront their accusers; why don't scientists have the same rights.

11. Delaying publication of low-priority papers that have been accepted.

12. Yielding to pressure from the publisher regarding the content of the journal. For example, the marketing department may stop the publication of an accepted paper containing conclusions detrimental to the interests of advertisers (56).

Editors cannot seem to grasp the idea that scientists submit papers for the purpose of getting the paper published. Scientists do not submit papers for the purpose of learning the opinions of reviewers, or for the opportunity to mollify their complaints. Authors will take the course of action that will lead to publication. If an editor forwards scathing reviews and requires the author to repeat experiments, gather more data, provide more analysis, revise the results, pay homage to their competitors, and generally grovel to the delight of anonymous critics, the authors may not willingly comply. Editors who demand that authors adjust their behavior to serve the interests of the journal are likely to be disappointed.

Every author knows that editors routinely reject scientifically valid manuscripts if they are deemed to be of limited interest to the readers. Journals, like all publications, need to attract and maintain an active readership. Most scientists have received, at some point in their careers, the classic put-down for an otherwise adequate work of science, "Your manuscript is not of sufficient scientific interest to be published at this time." In truth, the editors are almost always correct when they deliver a "not of sufficient interest" notice. Most papers, whether published or unpublished, do not advance science. The problem is that we really have no method of distinguishing the important papers from the unimportant papers. There are many examples of Nobelists whose seminal work seemed uninteresting to editors (90). If editors had the power to stop the authors of rejected papers from submitting to another journal, scientific advancement would come to a standstill.

From the author's point of view, the problem with rejection distills down to time. After submitting a paper, an author can wait a year or longer before he receives his rejection letter (91). During that time, the author is prohibited from submitting his paper to any other journals. The editor, at his whim, can delay publication of a scientifically valid paper for reasons that are purely self-serving and without benefit to the scientific community.

Editors have a bad record of ensuring that the results published in their journals were not biased by financial interests (92), (93). Authors seldom volunteer their conflicts of interest, and editors seldom demand disclosures (94). You can never be sure whether the authors of any scientific paper have a financial interest in the results. Ensuring integrity is a time-consuming and thankless task. No editor has ever earned a dollar for his journal by uncovering a conflict of interest in a study, or a lapse in human subject protections. Basically, editors are in the business of selling journals, not advancing science.

Though editors loathe to scrutinize, they love to criticize. The chief vehicle for scientific criticism is the peer review process, and editors never miss a chance to heap praise on the process. Here is what a group of medical journal editors have said: "The peer-reviewed literature constitutes the main archival source of knowledge in biomedicine. Authors, editors, and publishers must respect reasonable, common-sense ethical and legal imperatives in order to maintain the integrity of the peer-reviewed literature as a vital and important resource. Peer review is conducted by busy professional colleagues who are experts in a given field and who are not compensated for their efforts" (87).

If these editors were asked to demonstrate the value of peer review, with the same scientific rigor they demand from the authors of journal articles, it is unlikely that their praises would be published. Peer review has never been shown to have any merit (57), (95). Peer review does not seem to improve the clarity of the papers published in scientific journals, and peer review does not seem capable of finding or reducing scientific fraud and human subject abuses. In a recent test conducted by the British Medical Journal, eight errors were deliberately inserted into a paper and sent to 420 potential reviewers: 53% responded with a review, the median number of errors spotted was two, no reviewer spotted more than five of the eight errors, and 16% found none (96). We can say that peer review greatly lengthens the interval between a paper's submission and its' subsequent publication. Otherwise, peer review has no proven effect on scientific advancement.

The silliest section of the editors' statement is that "Peer review is conducted by busy professional colleagues". The reason that editors refer to reviewers as "busy people," may stem from the excuses they hear for tardy reviews. "It took me six months to review this paper because I've been very busy." Or, perhaps, "No, I haven't reviewed the paper. I've been very busy." Or, "Has a year gone by already? I really think it is important for me to offer the authors some instructive comments, and I want to make sure that I give the paper all of the time it takes to do a helpful review. Can I have a two month extension for this review."

How long does a reviewer work on a review that takes two years to complete? About five hours; if you're working in the field it simply does not take much longer than this to read and comment on a paper. The procrastinator is not a "busy professional." He is simply a selfish person who places a higher value on five hours of his own time than on two years of the author's time. A procrastinating reviewer can easily delay the publication date of a paper by a year, two years, or even longer (91). Late reviews are almost always unfavorable reviews. After you have submitted a manuscript, each month that passes while you wait for the reviewer's comments reduces the likelihood that your reviews will be favorable.

If peer review were important, wouldn't you expect scientists to receive some training in the area. Wouldn't you expect peer reviewers to be held to a standard of conduct? It doesn't happen. When the reviewer receives your manuscript, he knows that he can handle the review exactly as he wishes. Most editors hide the identities of their peer reviewers with the same zeal that journalists hide the identities of their sources. A reviewer can kill the work of a competitor or a colleague, and nobody will ever know the name of the assassin.

As the number of journals increases, and the number of submitted papers increases, editors have an increasingly difficult time finding reviewers. If an editor asks you to review a paper, always accept. A review is your opportunity to hurt your competitors, and to stifle innovative ideas that threaten the status quo. Always remember the first rule of the journal reviewer: "Every manuscript can be justifiably rejected." If you take your job seriously, you can find a flaw in any research effort. In the event that one of the other reviewers supports the paper, over your objections, don't be discouraged. A reviewer has the power to delay the publication of any paper. If the editor instructs you to return your review in two weeks, you can take six months, without rebuke. The author will be required to submit new revision of his manuscript, responding to your criticisms. If you nitpick each successive revision of the manuscript, you can easily stretch the review process to 18 months. By the time the author has successfully responded to all of your criticisms, his innovative paper will be stripped of new ideas and transformed into a non-controversial fluff piece.

On rare occasion, you may be asked to review a truly excellent research paper. You can delay its publication for about two years. This gives you ample time to duplicate the experiment in your own lab, and publish the results in an electronic journal that offers quick publication. Don't worry about being caught stealing the author's ideas. Editors defend the anonymity of reviewers. Why do editors protect the anonymity for reviewers? The given reason for this practice is that a reviewer, fearing retribution, might be reluctant to criticize a paper written by a powerful colleague.

As a reviewer, you are the defender of your chosen field of science. It is your duty to reject any paper that challenges the integrity of your field. Simon LeVay, in his book, When Science Goes Wrong, recounts the story of fetal cell transplantation gone wrong (97). The researcher injected tissue from two sixteen-week old human fetuses into the striatum and the ventricles (of the brain) of a patient with advanced Parkinson's disease. The operation was performed by an American scientist, in China, where experiments using fetal tissue are legal. Two years later, the patient died. An autopsy showed no surviving fetal tissue in the striatum. However, the injected fetal tissue had grown into a teratomatous neoplasm, composed of bone, cartilage, skin and hair, filling the ventricles. The autopsy was restricted to an examination of the head, but the findings of teratoma in the ventricles seemed to be the logical cause of death. The pathologist who performed the autopsy submitted her findings to the New England Journal of Medicine, where her paper was rejected by a reviewer who happened to be a supporter of fetal tissue transplantation research. The manuscript was subsequently published in a neurology journal (98).

When you read a journal article, remember the following:

1. You can't assume that the paper was written by the listed author. The paper may have been written by a ghost writer paid by industry.

2. You can't assume that the co-authors contributed to the paper. They may have been listed for political or economic reasons, without contributing in any measure to the manuscript.

3. The listed authors may have undisclosed conflicts of interest, of a financial nature.

4. In the case of clinical trials, the study may have violated the rights of human subjects.

5. The conclusions may be based on falsified or fabricated data.

6. You will never have access to the raw primary data upon which the conclusions were based.

7. The Discussion section may misrepresent the data.

8. The reference section may exclude important precedent work published by the author's competitors.

9. The paper may have been accepted for publication because it confirmed the biases held by the reviewers.

10. The research may have been submitted for publication several years prior to the publication date and has no current scientific value.

11. The work described in the article may bear no relevance to the intended area of research supported by the funding sources listed at the end of the article.

12. The article may have appeared in another place and another time, in another language, with a different title and conclusion.

13. You are probably the only person on the planet who has bothered to read the published manuscript.

REFERENCES

[44] Schonemann PH. Better never than late: peer review and the preservation of prejudice. Ethical Human Sciences and Services 3:7-21, 2001.

[56] Editorial Decision Overridden By Marketing Department. January 2004 World Association of Medical Editors, January, 2004. http://www.wame.org/ethics-resources/editorial-decision-overridden-by-marketing-department, viewed December 30, 2009.

[87] Miller RA, Hasman A, Haux R, McCray AT, Safran C, Shortliffe EH. On exemplary scientific conduct regarding submission of manuscripts to biomedical informatics journals. J Am Med Inform Assoc 13:113-114, 2006.

[88] Schneier B. Crypto-gram, August 15, 2005.

[89] World Association of Medical Editors. Reviewer Conflict of Interest. September, 2002 http://www.wame.org/ethics-resources/reviewer-conflict-of-interest, viewed December 23, 2009.

[90] Campanario JM. Rejecting Nobel class articles and resisting Nobel class discoveries. http://www2.uah.es/jmc/nobel.html, viewed October 27, 2009.

[91] Dewey ME. Authors have rights too. BMJ. 1993 Jan 30;306(6873):318-320, 1993.

[92] Smith R. Journals fail to adhere to guidelines on conflicts of interest. BMJ 323:651 (inclusive), 2001.

[93] Gross CP, Gupta AR, Krumholz HM. Disclosure of financial competing interests in randomised controlled trials: cross sectional review. BMJ 326:526-527, 2003.

[94] Hussain A, Smith R. Declaring financial competing interests: survey of five general medical journals. BMJ 323:263-264, 2001.

[95] White C. Little evidence for effectiveness of scientific peer review. BMJ 326:241(inclusive), 2003.

[96] Smith R. Peer review: reform or revolution? BMJ 315:759-760, 1997.

[97] LeVay S. When Science Goes Wrong. Twelve Tales from the Dark Side of Discovery. Plume, New York, pp 160-180, 2008.

[98] Folkerth RD, Durso R. Survival and proliferation of nonneural tissues, with obstruction of cerebral ventricles, in a parkinsonian patient treated with fetal allografts. Neurology 46:1219-1225, 1996.

--TO BE CONTINUED--

- © 2010 Jules Berman

Misinterpretation in Statistics 2

2010-05-02T07:08:00.001-07:00

Misinterpretation in Statistics 1

2010-05-01T07:08:00.000-07:00

Rejection 3

2010-04-30T03:39:00.001-07:00

Machiavelli's Laboratory is an ebook that is currently available at no cost. It is a satire on ethics, written from the perspective of an unethical scientist. This blog is a discussion vehicle for the book.

The ebook is available at:

www.julesberman.info/integ/machfree.htm

Please don't take any of the advice and opinions in the book (or the excerpts featured in this blog) seriously.

-- EXCERPT CONTINUED FROM CHAPTER 6, REJECTION, FROM MACHIAVELLI'S LABORATORY

Sometimes, the best works are found amongst the rejected efforts. In mid-nineteenth century France, the Salon de Paris, the official art exhibition sponsored by the Academie des Beaux-Arts, rejected works by Monet, Manet, Pissarro, Cezanne, and many others whose concept of art conflicted with prevailing sensibilities. Complaints reached the ears of Napoleon III, who allowed rejected words to be displayed in a Salon de Refuses (a gathering of the rejected people). These exhibitions of rejected art are credited with the rise of impressionism. Today, the term "salon des refuses" refers to any exhibit of works that were rejected by a juried show.

Mathematicians have their equivalent of a Salon de Refuses. Today, mathematicians can publish their rejected papers in Rejecta Mathematica, available online at: http://math.rejecta.org/about-rejecta-mathematica. Sometimes, great ideas are not rejected; they're just ignored. Hundreds of years can pass while a deserving idea is discovered, lost, re-discovered, lost again, and so on.

In 1668, the world was modernized, in many ways. We had the fundamentals of cryptography (Viete, 1589), Pi calculated to 20 decimal places (Ludolf, 1596), logarithms (Napier, 1624), Fermat's last theorem (1637), the fundamentals of probability (Pascal, 1654), and the ability to diagnose cancers by pathologic examination (Malpighi, 1659). Differential equations were understood (1662), and the last details of integral calculus were being written, independently, by Newton and Leibnitz. Despite all of these scientific advances, the world believed that the life of very small organisms arose spontaneously, from thin air, or possibly from inanimate particles of dirt. Otherwise rational intellects were comfortable with magical thinking, and believed that life could be explained by postulating forces acting in a realm beyond human perception.

Francesco Redi, in 1668, designed an experiment to test whether maggots arose through spontaneous generation. He incubated meat in flasks; some flasks covered to stop the entry of flies, and others left uncovered, permitting flies to enter. After some time passed, Redi examined the meat in both sets of flasks. Only the meat from the open flasks contained maggots. Redi correctly concluded that maggots do not generate spontaneously from dead meat. We now know that maggots generate from tiny eggs laid by flies.

Redi's experiment had very little influence on the prevailing belief systems. Seventy-two years later, John Turberville Needham conducted his own meat-related test for spontaneous generation. He heated mutton broth in a closed container, and examined the contents a few days later. The container swarmed with micro-organisms, proving, to the satisfaction of many, that micro-organisms arise by spontaneous generation. In retrospect, we can assume that the broth was not heated sufficiently to kill all of the organisms initially present in the container, or that the container was not closed tightly. For some time, though, Needham's experiment vanquished lingering doubts regarding the validity of spontaneous generation.

In 1768, a full century after Redi's experiments, Lazzaro Spallanzani (1729 - 1799) repeated Needham's experiment, this time boiling the broth for forty-five minutes. No organisms grew in the closed container. Spallanzani's experiment should have put the kibosh on spontaneous generation, but it did not. Ninety-two years passed before the controversy was revisited. In 1860, scientists knew enough about the biology of life to infer that spontaneous generation was a needless and absurd theory. At that time, Virchow, a highly influential pathologist, argued against spontaneous generation, observing that cells arise from other cells, through cell division. In 1860, Pasteur showed that dust particles in air carried micro-organisms. If boiled meat is exposed to purified air (without dust particles), bacterial growth does not occur. Nearly two centuries were required to convince the world that Redi's experiment, disproving spontaneous generation, was valid.

Back in 1668, just as Redi was trying to convince his colleagues that living organisms cannot generate from nothing, Richard Lower was putting the finishing touches on his Tractatus De Corde: Item De Motu Et Colore Sanguinis. Lower demonstrated experimentally that venous blood pumped from the heart, into the lungs, is transformed (from venous dark red, to arterial bright red) by aeration and returned to the heart, where arterial blood is pumped to the peripheral circulation. This seems obvious today; barely worthy of explanation. But it took 1600 years to solve the mystery of heart-lung circulation.

We need to be reminded that for about 1500 years, all medical thought in Europe was dominated by one honored physician. Galen (129 - 199 C.E.) was a Greek physician who lived in Rome, and Pergamum (Turkey), and retired early to live a life of scholarship. He wrote many books, including "On Prognosis," (177 C.E.), and produced a total of about 3 million bon mots before he died (118). For the subsequent 1500 years, his words were accepted on blind faith by virtually all European physicians. To reject Galen was a type of heresy, that almost always resulted in professional ostracism.

Galen, great as he was, labored under the somewhat limited scope of second century science. Some of his most far-reaching thoughts fell into the realm of superstition. For example, Galen believed that blood was embued with natural spirts by the liver, and vital spirits by the heart. Furthermore, Galen believed that blood moved through the septum of the heart through invisible pores. The concept of a closed circulation was unknown to Galen.

Every child who rides an escalator must wonder where the steps go when they reach the top. The escalator steps seem to slink under the floor, and drop off into a hidden chamber. Meanwhile, another mysterious process creates new steps that emerge from the floor of the elevator, and rise upwards. The idea of a continuous belt of stairs seldom catches the imagination of very young children, who prefer magical thinking over mundane observations. Basically, medieval physicians accepted Galen's magic stairs version of blood circulation. Blood was constantly replaced by the liver at a rate that equaled its issuance through invisible pores in the heart. It was just fantastic.

Anatomists who gave any thought to Galen's theory of blood circulation knew that Galen could not be correct. Still, to doubt Galen was clearly unacceptable. In frustration, Henri de Mondeville, the author of Cyrurgia (1312), an early textbook of surgery, wrote, "God did not exhaust all His creative power in making Galen (118)." Andreas Vesalius (1514 - 1564) published "De Fabrica Humani Corporis," in 1543 (Figure).

Andreas Vesalius, on left. Source: Garrison FH. History of medicine. WB Saunders, Philadelphia, 1921.

Vesalius provided a detailed description of human anatomy that corrected some of the misconceptions and superstitions left by Galen (Figure). Vesalius' closest friends turned against him. Others in his profession condemned, mocked, or ignored his work. Die-hard Galen fans insisted that any discrepancies between Galen's second century human anatomy, and Vesalius' sixteenth century observations were due to naturally occurring modifications in the human condition. Sylvius, Vesalius' teacher in Paris, grumbled, "Man had changed but not for the better (118)." Vesalius departed Venice, and died alone, impoverished, ridiculed by his colleagues, shipwrecked on the Island of Zante (Zakynthos) (118).

Vesalius' drawing of the base of the brain, demonstrating a thorough understanding of brain anatomy, including the crossing of the optic nerves, the origins and course of the spinal nerves, and the relationship of the cerebellum to the brain stem. Source: Wikipedia, public domain.

Ten years later, Michael Servetus (1511 - 1553) published Restitutio Christianismi, in which he noted that the pulmonary vessels deliver blood to the heart, after the blood has mixed with air in the lungs. That same year, Servetus was burned at the stake (along with most of the copies of his book) by Calvin for a poorly written sentence that seemed heretical at the time.

By 1628, the world was ready to take a second look at some of Galen's opinions. In this year, William Harvey (1578 - 1657) published De Motu Cordis, describing the circulation of blood from heart to lungs and back, and from the heart to the periphery and back. This brings us to back to Richard Lower (1631 - 1691). In 1691, Lower published an explanation of the relationship between the peripheral and pulmonary circulations, and described the intrapulmonary aeration of venous blood. Lower's work was a complete anatomic and physiologic synthesis that has withstood the test of time.

The Italians credit Andrea Cesalpino (1524 - 1603), a professor of medicine at Pisa, for discovering the closed heart-lung circulation prior to Harvey. The point is moot. In 1242 C.E., the Arabic polymath Ibn an-Nafis (1213 - 1288) described the heart-lung role in circulation and aeration; four centuries before Cesalpino. At the time, nobody in Europe cared to listen. The moral of the story is that new ideas will be rejected if they contradict cherished beliefs.

[118] Garrison FH. History of medicine. WB Saunders, Philadelphia, 1921.

--TO BE CONTINUED--

- © 2010 Jules Berman