To really understand the American biomedical research enterprise, you need to understand its scientists in human terms: how we tick socially and psychologically. Our best-kept secret? We are an insecure group. Grappling with the most complex phenomena in the universe—living systems—we have no shared scientific identity or accepted theoretical framework. We don't even know the names of our own great discoverers (See essay on Robert Tuttle Morris). To a much greater degree than is healthy, many of us look up to, even glorify, the physical sciences and physicists.
Was our shakiness inevitable? I don't think so. Global events following World War II set the stage for the ascendancy of physics over health science. In late 1944, the U.S. Office of Strategic Services began secretly drafting more than 1,500 German physicists, radiobiologists and “doctors” under the military Operation Paperclip (1). It is ironic that the top European public health scientists who were discovering that chemical and radiological pollutants cause cancer during the 1940s had to struggle to gain entrance to the United States at all, as one of the brightest of them recalls in his memoirs.(2,3)
The last gasp for American public health science was the Nobel lecture delivered by Hermann J. Muller on December 12, 1946. Muller, explored in the prior essay Brilliant and Extremely Dangerous, warned that ‘the problem will become very important of insuring that the human germ plasm [chromosomes in sperm and egg]—the all-important material of which we are the temporary custodians—is effectively protected [from radiation and chemical pollution]...’ U.S. government policy following WWII did little either to foster the growth of public health science along lines outlined by Muller, Peller and others or to protect the public from genetic effects of pollution.
Although German physicists and radiobiologists were brought in to build better bombs, and to help conduct secret radiation experiments on human subjects at the U.S. atomic weapons laboratories (4), those scientists began to influence medical research in a variety of overt and covert ways. In fact, they helped create an entirely new hybrid discipline known as “health physics” (see Wikipedia entry). Health physics was, and still largely is, overseen by physics-trained scientists like medical radiologists who answer mainly to the U.S. energy departments, with little if any oversight by trained public health scientists.
Using their bully pulpits at the atomic weapons labs and elite universities, health physicists have leveraged both their general view of what constitutes a proper test—a perfectly controlled experiment--and specific criticisms of observational human studies suggesting low-level pollution damages DNA. To this day, a kind of caste system remains in American biomedical science. The table that follows roughly summarizes the relative influence and perceived credibility of biomedical scientists of a variety of stripes:
In the 1970s, when pitted against health physicists and others with unlimited funding from the AEC and its successor, the Energy Research and Development Administration, radiation epidemiologists like Alice Stewart, Irwin Bross and Rosalie Bertell had to fight hard to gain limited acceptance of their discovery that low level radiation is dangerous5.
Although eventually influencing public health policy, Alice Stewart's finding that X-rays of women during pregnancy eventually could cause leukemia in their children was bitterly attacked by weapons lab physicists, radiologists and molecular geneticists. Stewart had carefully searched medical histories of hundreds of children who had contracted leukemia, and the only common exposure they had all shared was a supposedly harmless dose of X-radiation delivered to their mother while the child was in utero.
In her debates with physicists and in her publications, Stewart boldly asserted the independence of biomedical science from health physics: Rejecting the idealized but unrealistic expectation of perfectly controlled experiments that are possible in physics, but not in biomedical science, Stewart wrote that medical science is more like archeology than physics in its methods of discovery.(6)
This was not an excuse for sloppy thinking but an attempt to embrace the fact that many important medical phenomena are rare—like leukemia and birth defects-- and therefore require starting with many cases that have already occurred and tracing back to likely antecedent causes, rather than beginning with a causative event like an A-bomb “experiment” and hoping that enough of each type of disease or defect will occur to be statistically detectable.
In other words, epidemiology is pure detective work.
In contrast to the prospective study of A-bomb victims at Hiroshima and Nagasaki, which promised to result in too few miscarriages and birth defects to conclusively say that genetic damage had occurred in exposed parents' eggs and sperm, top epidemiologists like Stewart in the U.K. and Dr. Abraham Lilienfeld in the U.S. had painstakingly designed their observational studies to hand-pick control groups that were as much like the leukemia cases as possible.
In the largest U.S. leukemia study, a stratified random sample of a population base of 13,000,000 people was used as a control group in the famous Tri-State Leukemia Survey. That produced most of the data analyzed by Bross and his team at Roswell Park Memorial Institute (RPMI) which showed that low-dose X ray of gonads damages human DNA. (7,8) Similar genetic damage has been found more recently in nuclear workers and in radiation-exposed victims of the Chernobyl disaster.9,10,11,12
Even though nuclear physicists know little if anything about living organisms, in the 1970s when genetic damage from pollution was still being openly debated among scientists and the public, physicists’ opinions of whether radiation can damage human DNA were often taken more seriously than that of trained public health scientists. Many health physicists at the atomic weapons labs were called on to “peer review” grant applications for research on radiation hazards.
In fact, when the National Cancer Institute cut off Irwin Bross' core grant at RPMI in 1978, what rankled was not so much the lack of funding but that only one of 10 reviewers was actually a peer: a trained biostatistician and public health scientist (as the NIH critique, which I still have, documents). The others were health physicists, radiologists and molecular geneticists who contended that “genetic damage” could only be shown in isolated cells, and not in statistical studies of human beings.
In 1984, when the first study of Agent Orange and birth defects in children of Vietnam veterans was published by the Journal of the American Medical Association (13), Bross wrote a forceful letter to the Journal of the American Statistical Association highlighting the importance of statistical associations in revealing hidden genetic damage induced by low level exposure to pollutants. Although that journal refused to publish the note, he was able to publish it in a small desktop privately-circulated flyer on scientific ethics. We reproduce that essay in the following installment.
REFERENCES 1. Welsome, E. The Plutonium Files. (The Dial Press, Random House, 1999). 2. Peller, S. Quantitative Research in Human Biology and Medicine. (Bristol: John Wright and Sons, Ltd., 1967). at <https://books.google.com/books? id=KDngBAAAQBAJ&pgis=1> 3. Peller, S. Not in My Time: The Story of a Doctor. (New York Philosophical Library, 1979). 4. Moreno, J. D. Undue Risk: Secret State exxperiments on Humans. (Psychology Press, 2001). 5. H. Wasserman and N. Solomon. Killing Our Own: The Disaster of America’s Experience with Atomic Radiation. (Delacorte Press, 1982). 6. Stewart, A. An epidemiologist takes a look at radiation risks. 5, (U.S. Bureau of Radiological Health; [for sale by the Supt. of Docs., U.S. Govt. Print. Off., Washington], 1973). 7. Bross, I. D. J. Scientific Strategies to Save Your Life: A Statistical Approach to Primary Prevention. (Marcel Dekker Incorporated, 1981). at <https://books.google.com/books/about/Scientific_Strategies_to_Save_Your_Life.html?id=eekgAQAAIAAJ&pgis=1> 8. Bross, I. D. & Natarajan, N. Cumulative genetic damage in children exposed to preconception and intrauterine radiation. Invest. Radiol.15, 52–64 9. Busby, C., Lengfelder, E., Pflugbeil, S. & Schmitz-Feuerhake, I. The evidence of radiation effects in embryos and fetuses exposed to Chernobyl fallout and the question of dose response. Med. Confl. Surviv.25, 20–40 (2009). 10. Wertelecki, W. Malformations in a chornobyl-impacted region. Pediatrics125, e836–43 (2010). 11. Parker, L., Pearce, M. S., Dickinson, H. O., Aitkin, M. & Craft, A. W. Stillbirths among offspring of male radiation workers at Sellafield nuclear reprocessing plant. Lancet354, 1407–14 (1999). 12. Little, M. P. A comparison of the risk of stillbirth associated with paternal pre-conception irradiation in the Sellafield workforce with that of stillbirth and untoward pregnancy outcome among Japanese atomic bomb survivors. J. Radiol. Prot.19, 361–373 (1999). 13. Erickson, J. D. Vietnam Veterans’ Risks for Fathering Babies With Birth Defects. JAMA J. Am. Med. Assoc.252, 903 (1984).