Medical science and medical opinions are no exception: as scientific data accumulate, we construct theories and formulate paradigms that we inevitably and constantly alter. The evolution of the concept of ‘gender-specific medicine’ is a classic example of that principle.
The notion that all human biology, with the exception of that of our reproductive systems, is essentially the same for men and women dominated medicine for centuries. In fact, the idea that what we know about males cannot be extrapolated to females without direct testing of female subjects is less than 25 years old. Suggesting that what we found in males might only be true of one sex and could not be extrapolated without separate testing in females met with tremendous skepticism and even outright opposition. In fact, it is astounding to think that centers of medical research tolerated and indeed promulgated the idea that sex was not a significant determinant of normal function and of the experience of disease.
Thus, scientists themselves are imperfect; they do not spring fully and perfectly formed like Athena from the brow of Zeus: one’s style in shaping a method of scientific inquiry is not wholly objective: basic talent, the caliber of training, and, importantly, prejudices, all influence investigative style and substance. A whole variety of other factors impact medical investigation. Public interest is one: money drives the research engine, and the public is the source of that money and the ultimate arbiter of what it will pay for. The prevailing wisdom of the research community dictated that to repeat research protocols that had been completed in men to women seemed an unnecessary waste of funds. History is another factor: it shapes attitudes in medicine as in all sections of society. After the abuses of World War II were exposed to general scrutiny at Nuremberg, a determination to protect the more vulnerable members of society from exploitation under the guise of furthering medical knowledge was forged and dominated the American research enterprise for decades. Women, particularly premenopausal women, were considered more vulnerable than men and shielded accordingly from sharing the risk of being subjects of clinical investigation. This attitude was, however, countered by the effective lobbying of the feminist community (itself a direct result of the experience of the war), which petitioned the government to support the direct investigation of women’s physiology.
The Task Force on Women’s Health, sponsored by Dr. Edward Brandt at the Public Health Department, spearheaded an effort by the National Institutes of Health and the Congress itself to fund and support direct research on women. The Office of Research of the NIH, headed by Doctor Vivian Pinn, played a major role in guiding and shaping efforts to comply with that mandate. In the decade that followed, a dedicated coalition of feminists, physicians, and medical researchers stabilized and expanded the idea that women were significantly different from men and profited from a direct investigation of their physiology and their experience of disease. The rich bonanza of data that resulted, however, was completely unanticipated: to our growing amazement, we found that every system of the body was different in significant ways between males and females. The differences extended to the molecular level: thousands of identical genes are expressed differently in males and females [2]. Furthermore, gene expression is modified by the parent of origin in the process called imprinting and, even more significantly, the loci and number of parentally imprinted genes vary with the sex of the offspring. The impact of sex on the genome is far more extensive than was ever anticipated [3, 4].
Another revolution in our concept of gender-specific medicine was the old debate of whether our sex-specific differences are cast in biological stone or rather our environment is in fact more important in shaping the phenotype. Many have speculated that if men and women were subjected to environments that were utterly identical, sex-specific biology would disappear. This extreme view is a distortion of what is, in fact, correct: experience plays a direct and essential role in altering biological properties and cannot be ignored or separated out from what it means to be male or female. The intricate dance between our DNA, experience/environment, hormones, and developmental age is a composite of inextricably intertwined events, all of which produce the ultimate version of our phenotype. Biological sex and gender are not two separate concepts, but follow a final common path; ‘gender-specific medicine’ is a unifying term that includes and takes into account all the contributing factors that produce the functioning organism.
There are many more miles to go before we fill in the blank spots in our understanding of gender-specific science. Three members of the faculty of the Department of Obstetrics and Gynecology at the Feinberg School of Medicine at Northwestern University pointed out in a recent editorial in Nature that women still remain underrepresented in biomedical research [5]. They referred to a 2004 study surveying nine important medical journals that showed only 37% of the participants were women and only 13% of the studies analyzed data by sex [6]. It is not enough, however, to agitate for more carefully balanced investigation: women themselves must acknowledge their duty to participate wherever possible in clinical research as a matter of justice; men should not have to bear the burden of the risks involved alone.
We should be striving to give full weight to all the ingredients that determine our gender-specific function throughout our lives: from the moment of conception to our death we are the product of our biological sex, our hormones, and the impact of our environment and experiences on the very stuff and substance of which we are made. The human genome is not, as some have already pointed out, the Holy Grail, which when decoded will give us a complete understanding of each person’s unique phenotype. A fuller and more accurate understanding of who we are and how we became this way depends on a balanced view of all the components that operate throughout the lives of all of us to produce who and what we are.
References
1 Heraclitus of Ephesus (ca. 535-475 BC) quoted by Plato in: Cratylus, and by Diogenes Laertius in: Lives of the Philosophers Book IX, section 8. http://en.wikiquote.org/wiki/Heraclitus.
2 Yang X, Schadt Wang S, Wang H, Arnold AP, Ingram-Drake L, et al: Tissue-specific expression and regulation of sexually dimorphic genes in mice. Genome Res 2006;16:995–1004.
3 Gregg C, Zhang J, Butler JE, Haig D, Dulac D: Sex-specific parent-of-origin allelic expression in the mouse brain. Science 2010;329:682–685.
4 Gregg C: Parental control over the brain. Science 2010;330:770–771.
5 Kim Alison M, Tingen Candace M, Woodruff Teresa K: Nature 2010;465:688–689.
6 Geller SE, Adams MG, Carnes MJ: Womens Health 2006;15:1123–1131.
Marianne J. Legato, MD
Partnership for Gender-Specific Medicine, Columbia University
903 Park Avenue, Suite 2A
New York, NY 10075 (USA)
Tel. +1 212 737 5663, E-Mail [email protected]
