Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century (54 page)

Conclusion: Taking a Chance on Chance: Cultivating Serendipity

1. The NSF's 2006 research budget for the biological sciences was $586 million. Along with the Department of Energy, the NSF also funds much of the physical sciences research in the United States, a fertile source for tools and software that enable biomedical research. Examples range from functional MRI instruments and electron microscopes to DNA micro-arrays and genome sequence. These critical advances were all the products of work by physicists, engineers, chemists, and computer scientists.

2. Quoted in James Gleick,
Genius: The Life and Science of Richard Feynman
(New York: Pantheon, 1992), 382.

3. The mechanism for the assessment via peer review of the competence, significance, and originality of work submitted for publication was instituted by the first scientific journal,
Philosophic Transactions,
published by the Royal Society of London, as early as the 1600s. Robert Hooke, the Royal Society's first curator of experimenters and himself a pioneering microscopist, had the distinction of confirming Leeuwenhoek's discovery of “animalcules” or bacteria. The motto of the society,
Nullius in verba
(On the word of no one), expresses the society's insistence on verification by observation or experiment, rather than by the voice of authority or tradition.

4. E. M. Allen, “Why Are Research Grant Applications Disapproved?”
Science
132 (1960): 1532–34; D. J. Lisk, “Why Research Grant Applications Are Turned Down,”
Science
21 (1971): 1025–26; R. Smith, “Peer Review: Reform or Revolution?”
British Medical Journal
315 (1997): 759–60.

5. In 2004 Cohen and Boyer won the Albany Medical Center Prize in Medicine and Biomedical Research, the nation's largest award in the field, for their pioneering work. J. C. McKinley Jr., “Big Medical Research Prize Goes to 2 Pioneers in Genetics Work,”
New York Times,
April 24, 2004.

6. In 1994 the General Accounting Office of the U.S. Congress studied the use of peer review in government scientific grants and found that reviewers often know applicants and tend to give preferential treatment to those they know. “Peer Review: Reforms Needed to Ensure Fairness in Federal Agency Grant Selection,” General Accounting Office, June 24, 1994, GAO/PEMD-94-1. Similar evidence of cronyism as well as gender bias was found in an analysis of the peer review system of the Swedish Medical Research Council, a major funding agency for biomedical research in Sweden. C. Wennerås and A. Wold, “Nepotism and sexism in peer-review,”
Nature
387 (1997): 341–43.

7. Garrett James Hardin,
Nature and Man's Fate
(New York: Rinehart, 1959).

8. Juan Miguel Campanario, “Consolation for the Scientist: Sometimes It Is Hard to Publish Papers That Are Later Highly Cited,”
Social Studies of Science
23 (1993): 342–62; J. M. Campanario, “Commentary on Influential Books and Journal Articles Initially Rejected Because of Negative Referees’ Evaluations,”
Science Communication
16 (1995): 304–25; F. Godlee, “The Ethics of Peer Review,” in
Ethical Issues in Biomedical Publication,
ed. Anne Hudson Jones and Faith McLellan (Baltimore: Johns Hopkins University Press, 2000), 59–64.

9. Yalow, a feminist to her soul before feminism reached society's consciousness, suffered another indignity when her Nobel Prize received extensive coverage in women's magazines. In its June 1978 issue
Family Health,
a magazine that reached more than 5 million readers, headlined an article “She Cooks, She Cleans, She Wins the Nobel Prize” and introduced Yalow as a “Bronx housewife.”

10. P. C. Lauterbur, “Image Formation by Induced Local Interactions: Examples Employing Nuclear Magnetic Resonance,”
Nature
242 (1973): 190–91.

11. For a perspective on the NIH and NSF process of peer review of grant applications, see
chapter 6
, “The Problems of Peer Review,” in
The Great Betrayal: Fraud in Science
by Horace Freeland Judson (Orlando: Harcourt, 2004), 244–86.

12. Jerry Avorn,
Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs
(New York: Knopf, 2004).

13. Gregg Critser,
Generation Rx: How Prescription Drugs Are Altering American Lives, Minds, and Bodies
(Boston: Houghton Mifflin, 2005), 2.

14. D. Young, “Studies show drug ads influence prescription decisions, drug costs,”
Am J Health Syst Pharm
59 (2002): 14–16.

15. M. S. Lipsky and C. A. Taylor, “The opinions and experiences of family physicians regarding direct-to-consumer advertising,”
J Fam Pract
45 (1997): 495–99.

16. Ray Moynihan and Alan Cassels,
Selling Sickness: How the World's Biggest Pharmaceutical Companies Are Turning Us All into Patients
(New York: Nation Books, 2005).

17. The power of marketing “me-too” drugs and a recognition of its unsavory characteristics was first demonstrated with the introduction of the broad-spectrum antibiotic tetracycline in the 1950s. Pfizer produced it by chemically manipulating another antibiotic called Aureomycin, manufactured by Lederle. Both companies, as well as three other firms, claimed patent rights. Collusion led to the circumvention of the Patent Office, and the problems were resolved, in one description, in “back-rooms, boardrooms and courtrooms.” The five firms reached agreement that they all should manufacture and market tetracycline. Each extensively promoted its product, drawing distinctions not on efficacy but on such characteristics as one's more stable liquid suspensions, another's more palatable liquid forms, or another's having combined injectable forms with a superior local anesthetic. J. Goodman, “Pharmaceutical Industry,” in
Medicine in the Twentieth Century,
ed. Roger Cooter and John Pickstone (Amsterdam: Harwood Academic Publishers, 2000), 148.

18. Marcia Angell,
The Truth About the Drug Companies: How They Deceive Us and What to Do About It
(New York: Random House, 2004), 76–79.

19. Avorn,
Powerful Medicines,
208; Angell,
Truth About the Drug Companies,
62–64.

20. In
combinatorial chemistry,
small chemical building blocks are combined in every possible variation into larger molecules that together form a huge synthetic-chemical “library.” These are screened by the thousands with robotic equipment for the ability to attach to or disturb the function of validated targets in a cell-culture system.
Rational drug design
is the process of designing new compounds based on the known structure or function of the target molecule. As drug-resistant variants arise in cancer chemotherapy, for example, DNA sequencing can identify the mutations responsible and provide a rational basis for further drug development.
Pharmacogenomics,
the newest technology, could increase the number of targets by examining the genetic underpinnings of disease in order to find new drugs and tailor them to the individual patients. Enthusiasts refer to this as “personalized medicine.” Companies are finding thousands of genes that produce previously unknown proteins that might be involved in the disease.

21. Neal Pattison and Luke Warren, “2002 Drug Industry Profits: Hefty Pharmaceutical Company Margins Dwarf Other Industries,”
Public Citizen's Congress Watch,
June 2003.

22. P. Rodenhauser, “On creativity and medicine,”
Pharos
59, no. 4 (1996): 2–5.

23. Carl Sagan eloquently put the issue of unpredictability into a human dimension: “For myself, I like a universe that includes much that is unknown and, at the same time, much that is knowable. A universe in which everything is known would be static and dull…. A universe that is unknowable is not a fit place for a thinking being. The ideal universe for us is one very much like the universe we inhabit. And I would guess that is not really much of a coincidence.”
Broca's Brain: Reflections on the Romance of Science
(New York: Random House, 1979), 18.

24. Jeff Howe, “The Rise of Crowdsourcing,”
Wired,
June 2006, 176–83.

25. Jerome P. Kassirer,
On the Take: How Medicine's Complicity with Big Business Can Endanger Your Health
(New York: Oxford University Press, 2005).

26. In 1996 Juan Miguel Campanario of the University of Alcalá near Madrid attempted a systematic analysis to identify classic papers in the scientific literature whose authors reported that unsought factors played a key role in their research; see “Using
Citation Classics
to study the incidence of serendipity in scientific discovery,”
Scientometrics
37 (1996): 3–24. Of those authors in Campanario's series who retrospectively commented on some kind of accident or oversight in performing the research, in only less than a third did a careful reading of the original paper reveal hints of the involvement of unplanned factors. Even then, such hints were often indirect and written in the passive voice. Examples include: “the mixture was allowed to stand overnight,” “it was found that,” and “with the intention, originally.”

27. The phrase “the endless frontier” was coined by Vannevar Bush, who headed the federal government's Office of Scientific Research and Development in World War II. Vannevar Bush,
Science, the Endless Frontier: A Report to the President
(1945; reprinted Washington, D.C.: National Science Foundation, 1960).

28. John Barth,
The Last Voyage of Somebody the Sailor
(Boston: Little, Brown, 1991).

Selected Bibliography

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Angell, Marcia.
The Truth About the Drug Companies: How They Deceive Us and What to Do About It.
New York: Random House, 2004.

Avorn, Jerry.
Powerful Medicines: The Benefits, Risks and Costs of Prescription Drugs.
New York: Knopf, 2004.

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El-Hai, Jack.
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