Popular science, genetic reductionism, and sincere fictions
by Joseph L. Graves, Jr.1
Dean University Studies & Professor of Biological Sciences
North Carolina A&T State University
Greensboro, NC 27411
1. Fellow, American Association for the Advancement of Science, Section G: Biological Sciences.
The authors of Helgadottir et al 2005 should have been more careful about how they allowed their research to be presented to the public.1 In the NY Times article, Dr. Stefansson gives the impression that he believes that increased myocardial infarction (heart attack) risk associated with the HapK variant of the leukotriene A4 hydrolase gene in African Americans results primarily from genetic sources.2 This is unfortunate, since the data presented in their publication do not, nor could they, address how much of the increased risk is purely genetic, purely environmental, or due to gene x environment interaction. Furthermore the discussion presented in the professional paper made it clear that these researchers clearly understand that both genetic and environmental factors could be responsible for the increased risk in African Americans who carry this allele.
The one-sided representation of risk presented in the NY Times article raises questions. Was this presentation due to an oversight on the part of the reporter? Or was it the way the researchers themselves reported their results to the journalists? In either event, scientists have an ethical and moral responsibility to try to make the press report the findings that their research results actually support. It is the obligation of scientists to accurately report what they are doing and its significance to the public. Scientists must actively resist false claims in the media.
Unfortunately, with regards to issues of race and biomedical research, there is a long history of intellectual sloppiness in both the scientific community and the media3. Not knowing all the principals involved in this case, I cannot comment on this particular case in detail, but I am troubled by the prospect of the financial gain that might arise from racializing medical treatments under US patent laws4.
In the United States, environmental risk factors associated with heart disease continue to act differentially on persons with visible African ancestry5. With this in mind, those who wish to make claims that allelic differences between European- and African-Americans also account for significant amounts of the cardiovascular (CVD) or any other disease disparity needs to present strong evidence supporting such genetic assertions. The difficulty, of course, is that to truly test a genetic hypothesis of disease disparity, the environmental circumstances of the populations in question must be equalized, including possible maternal effects, a situation that will take generations to achieve for American patient populations. The equalization of environments for persons of African and European descent in the United States has never been realized. This is a particularly vexing problem when we consider that social and cultural factors influence disease predisposition in primates, especially those with social dominance hierarchies, such as the socially-constructed racial categories of the United States6.
Some might argue that knowledge of the source of disease is less relevant than providing medical treatments for it. Thus, if a medical treatment works successfully only for a particular ethnic group, should we really be concerned with why or how it is successful in that population? Actually we should be very concerned. For example, if the differential impact of HapK or any other genetic variant is primarily due to environmental sources that have a social origin and are preventable, then it behooves us to try social interventions to remove the disparity. This does not preclude the development of drugs to help those who are afflicted by HapK-mediated risk, just as we develop drugs that treat lung cancer, even though much of lung cancer incidence can be reduced by programs to reduce both hazardous air pollutants and tobacco smoking.
But there are also basic problems of population genetics that have arisen. Consider Dr. Stefansson’s suggestion that the physiological impacts of HapK at later ages have been ameliorated in Europeans but not in persons of African ancestry. Supposedly increased disease resistance accounted for the spread of this genetic variant in European populations. This variant is associated with prolonged inflammation in arterial walls via the action of a protein LTB4, which increases heart attack risk at later ages. Stefansson goes on to speculate that, in modern Europeans, heart attack risk has been lowered by the evolution at modifier loci acting to reduce damage resulting from long-term inflammation. Thus, it follows that African Americans have fewer genetic variants mollifying the impact of HapK because of the more recent appearance of this allele in this group. Therefore, we can conclude that even if heart attack risk factors were equalized between European- and African-Americans carrying this allele, the latter would still have greater risk, due to their lack of epistatic control of HapK induced late-age physiological effects.
In their professional paper the authors suggested that the increased HapK risk in African Americans results from "a strong interaction between HapK and other genetic variants and/or non-genetic risk factors that are more common in African Americans than in European Americans and Icelanders…pg. 4." This explanation is notably absent in the Dr. Stefansson’s comments to the NY Times (it is alluded to in the Times by Dr. Charles Rotimi, Director of the National Human Genome Center at Howard University.) Their professional article did not discuss an evolutionary genetic explanation for lower risk in Europeans. This begs the question why this explanation is offered up for the popular press? This might be explained by the idea that if the public believes that the differential African American CVD risk resulting from HapK is genetic in origin, that it is reasonable or even imperative to seek a drug based intervention to reduce the disparity. Moreover, disparity resulting from genetic difference suggests that such a drug would and should be marketed to only African Americans.
However, does the author’s evolutionary genetic scenario make sense? Consider for example, that for most of human history, circulatory diseases were probably not major causes of death. In 16th century England, average life expectancy was 33.7 years, three hundred years later, in that same country, it was only 40.9 years, while in France and Sweden it was 40.1 and 42.6 respectively. In 1900, circulatory diseases only accounted for 8.3% of recorded American deaths, yet by 1986 this figure had increased to 46%.7 These figures indicate that for most of human existence, resistance to arthrosclerosis could not have been a major selective agent. Indeed, Randolph Neese and George C. Williams pointed out that this disease really is the product of modern civilizations when food became available in abundance.8 In addition, since the damage caused by this disease would have occurred long after the net reproductive value of most humans would have reached zero it is difficult to imagine a scenario that would have selected for modifier alleles at other loci to prevent HapK induced damage. Evolutionary biologists have demonstrated that the declining force of natural selection is responsible for the genetically based pathologies we experience at the end of life.9 Thus if there had been selection for the amelioration of the impact of HapK in European populations, the selective agent would have probably had little or nothing to do with preventing myocardial infarctions (heart attack) at later ages. Therefore it is possible that genetic modifiers exist in Europeans associated with the allele’s greater prevalence and history there, but there is certainly not a strong argument for their existence. Conversely, one could also explain the differential impact of HapK in African American carriers due to environmental effects that accelerate the damage caused by LTB4 biosynthetic pathways, or to other environmental effects that incapacitate various protective mechanisms. At present, the available evidence cannot distinguish between genetic/epistatic, environmental, or gene by environment based influences due to impossibility of producing experimental designs adequate to separate these influences. This is a point that most professional geneticists understand well.
This all begs the question if professional scientists understand the limitations of their research designs, why do they continually allow those sophistications to be minimized by popular science writers? It further begs the question why this problem is more pronounced in some areas of science, and not others? Biomedical research associated with the American socially constructed racial categories has been one of the worse offenders in this regard. Moreover, I predict that this problem will get worse, particularly as the financial stakes are raised by the desire to rush approval of "racial" medicines. However, it is precisely on this issue where the scientific community should require and uphold more rigorous ethical standards with regards to the reporting of results to the scientific media. We must be wary of the motives of interviewees who seem to discuss in the media results that support their most immediate financial projects and ignore those that call them into question. Furthermore we must call scientific journalists to task for continually simplifying and misrepresenting scientific results with regard to social conceptions of race, genetic variation, and biomedical research. The tragedy here is that the story they have created for public consumption has begun to influence biomedical research, clinical testing, and commercial application. Thus their not-so-sincere fictions have the effect of interfering with the pursuit of reducing health disparity, not moving it forward.
5. Clark, L.T., Issues in minority health: atherosclerosis and coronary heart disease in African Americans, Med Clin North Am. 89(5): 977-1001, 2005 and Vaccarino, V. et al., Sex and racial differences in the management of acute myocardial infarction, 1994 through 2002, N Engl J Med. 2005 Aug 18;353(7):727-9.