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Authors: Daniel J. Fairbanks

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There is good evidence that these variants were strongly favored through natural selection in people from regions where domesticated milk-producing animals were raised. Milk and other dairy products are highly nutritious, an excellent source of calories, vitamins, and minerals, especially when food is in short supply, as it often was during ancient times. In regions where humans used domestic animals for milk, people who could consume milk and milk products as a source of food had an advantage for survival and reproduction over those who could not. Natural selection favored these variants, rapidly increasing their prevalence in milk-consuming societies, and this evolutionary pattern has repeated itself independently in several parts of the world.

For instance, in East Africa, in what is now Kenya and Tanzania, nomadic herders began using domestic animals for milk more than seven thousand years ago. A large proportion of their modern descendants, most of them still in Africa, carry a specific variant that allows the
LCT
gene to remain active into adulthood.
32
In the Arabian Peninsula, where milk use was and is common, a different variant conferred lactose persistence to people who lived there anciently and their modern descendants. Yet another variant that confers lactose persistence is common in people whose ancestry is northern European, where milk from cows and goats has long been used as a source of food. This variant is very common in North America, present in approximately 77 percent of North Americans whose ancestry is predominantly European, and accounts for the high consumption of dairy products in Europe, the United States, Canada, Australia, and other parts of the world where large proportions of people have European ancestry.

Ancient Native Americans, however, never domesticated animals for milk production. Not surprisingly, the variants that confer lactose persistence in other parts of the world are rare in Native Americans, who typically begin losing the ability to digest milk by age three. Ignorant of the high proportion of lactose-intolerant people among Native Americans, and the underlying science, officials promoting US government food assistance programs distributed surplus milk products to people living on Indian reservations, where the products made most people sick. Shirley Hill Witt, a Native American anthropologist and administrator for the US Commission on Civil Rights, described the situation on a Navajo reservation this way:

What is good for the Anglo body may not in fact be good for everyone else. This may be another mindless prejudice yet to be purged:
nutritional ethnocentrism
. To put it another way, the consequences of ethnocentrism may be more tenacious and deep-seated than we have thought. In the animal pens near Navajo hogans you can usually find the remains of milk products from the commodities program: butter, cheese, dried milk.

But as more and more investigations are reported, the fact is becoming incontrovertible that for many or most of the world's people, milk is not our most valuable food, or “nature's way,” or so say the slogans of the milk industry. These studies indicate that most of us cannot drink milk after early childhood without suffering gastric upset, cramps, bloating, diarrhea and nausea.
33

Promotion of milk and other dairy products for consumption by children in public school cafeterias likewise ignores the pervasive nature of lactose intolerance among many children who do not descend from ancient milk-reliant cultures. This is especially relevant in schools located on or near reservations. According to Witt,

In schools across the nation, children are browbeaten into ingesting vast quantities of milk whether or not they have the genetic equipment to do so. In 1972, a study I conducted in one of the New Mexican pueblos showed that only one person out of a hundred over the age of six was able to tolerate lactose without strong digestive reactions.
34

Reliable laboratory tests for lactose intolerance are available for administration under the supervision of a physician. Most are not genetic tests but, rather, tests that directly measure a person's ability to digest lactose. For those who have lactose intolerance, lactose-reduced and lactose-free dairy products are available, as are supplements that assist the body with lactose digestion, allowing a larger number of people with lactose intolerance who desire to consume dairy products to do so.

Because ancestry is closely tied to a wide variety of health issues, physicians have historically used racial categories to recommend different tests and treatments. The intent is not racial bias but, rather, a means to more efficiently direct medical interventions according to information published in the medical literature about health issues and ancestry. For instance, targeting diagnosis and genetic testing of cystic fibrosis in people with predominantly European ancestry, or sickle-cell disease in people with significant African ancestry, made economic sense to many healthcare organizations.

Simple blood tests that are inexpensive, rapid, and easy to administer can readily detect as many as twenty-nine genetic conditions in infants. Although some of the conditions they detect are more common in people whose ancestries trace to particular parts of the world, the American College of Medical Genetics has recommended
universal
screening of infants for all twenty-nine of these conditions, rather than targeted screening by ethnic group. The reasons are to avoid missed diagnoses and to treat these conditions in time to avert the most serious consequences associated with them.
35
Targeting by ethnic group inevitably misses cases because the ethnic classifications of infants are not accurate assessments of ancestry. Moreover, the history of targeted screening has shown that discrimination and stigmatization are unavoidable consequences, whether intended or not. There is no valid medical reason to consider racial or ethnic classification for such testing.

Until 2005, no medication had been approved by the US Food and Drug Administration (FDA) for treatment of any particular ethnic group. That year, a drug known as BiDil was approved in the United States for treatment of congestive heart failure specifically in African Americans, based on the results of clinical trials. An initial clinical trial for BiDil had included people of different ancestral backgrounds. The results initially showed little advantage for
the drug until the researchers revisited the data, parsing the analysis according to self-identified racial classification. They then discovered a possible benefit for subjects who self-identified as African American. This prompted another clinical trial with only African American participants. All participants were already suffering from congestive heart failure at the beginning of the study and were on other medications to treat their condition. The researchers randomly assigned each of them to receive BiDil or a placebo in addition to the medications each was currently taking. The trial was to continue for eighteen months but was terminated early because those taking BiDil had a lower rate of death. The FDA approved BiDil for use in African American patients in 2005 on the basis of this trial.

Some groups, such as the NAACP, praised this action for focusing medical research on an ethnic group that had long suffered medical discrimination. In fact, medical research targeting African Americans has an appalling historical record, exemplified by the unsubstantiated claims and outright errors made throughout the twentieth century with sickle-cell disease. Perhaps the most infamous case, however, was research conducted from 1932 through 1972 in Tuskegee, Alabama, in which African American men were misled into enrolling as participants in a study purportedly about blood disorders. The real purpose of the study, which was kept secret from the participants, was to research syphilis. The majority of the men enrolled in the study already had the disease when the study began, and others were intentionally infected without their knowledge. None were told that they had syphilis, and none were treated for it, even though penicillin was found to be an effective treatment during the early years of the study. Not only was syphilis allowed to progress unabated in these men, many of their spouses became infected, as did infants born to these women. The study was finally terminated after forty years when a whistleblower took the story to the press after being rebuffed when he reported its abuses to the responsible government agencies. In the aftermath, Congress mandated substantial changes in legal and ethical requirements for government-sponsored research.

Clinical trials for BiDil, with their exclusive focus on African Americans, seemed to offer a hint of reversal after decades of past injustices. According to company officials, “BiDil was ‘the antithesis of Tuskegee'” and “the approval
of BiDil was about putting Tuskegee to rest.”
36
However, geneticists, medical researchers, ethicists, legal experts, and a considerable number of physicians criticized the testing and release of BiDil as a marketing strategy carefully crafted to generate corporate profits. The drug was a combination of two drugs already available in generic forms, but the dose used in the study could not be easily formulated with available doses of generic alternatives. Had physicians been able to readily prescribe a generic alternative, it could have been equally effective and much less expensive. There was no research to indicate whether other doses, including those generically available, were less, more, or equally effective.

As it turned out, BiDil failed to realize market expectations. Projected prescriptions and sales to African American patients did not materialize, and the marketing campaign was disbanded in 2008. The company that marketed the drug was forced to downsize and, in 2009, was sold to another company.
37

The drug's focus on African Americans implied a genetic basis for its effectiveness divided along supposed racial boundaries. Prominent geneticists blasted this implication, arguing that if variation in the efficacy of BiDil had a genetic basis, research identifying associations between the drug's efficacy and specific variants in DNA would be a much more reliable way to target those who would most benefit, rather than using self-identified racial classification as the criterion. According to J. Craig Venter, one of the foremost scientists and business leaders in genome-based medicine, and his colleagues, “to attain truly personalized medicine, the scientific community must aim to elucidate the genetic and environmental factors that contribute to drug reactions and not be satisfied with a race-based approach.”
38
As Howard Brody and Linda M. Hunt of Michigan State University point out, there were financial disincentives that discouraged a for-profit enterprise from doing so:

To what extent would the identification of a specific genetic trait, correlated with positive therapeutic response, be likely to expand that market? As long as there is some probability that the results of that further research could cause the market to shrink, even if by a small amount, there is every incentive for the company to decline to undertake that research.
39

Brody and Hunt further argue that self-identified racial categories can be considered valid medical criteria not on the basis of genetics but, rather, for social and cultural reasons:

Family physicians, well schooled in the biopsychosocial model of health, ought especially to be concerned about an approach to research that de-emphasizes the search for social and cultural factors in disease….

For example, hypertension, one of the major risk factors for congestive heart failure, is more common within the African American community; and chronic social stress has been implicated as a possible contributor to the development of hypertension. Diet, exercise, and other environmental variables are also possible mediators.
40

In the end, BiDil turned out to be another instance of controversial attempts at racially based medicine. Although touted as the first case of
personalized medicine
—meaning genetically targeted treatments and interventions—in reality, it was not. Truly personalized medicine associates treatments with specific variants that can be directly identified in a person's DNA irrespective of racial classification.

As a more recent example, a June 2014 article with the title “Differing Effects of Metformin on Glycemic Control by Race-Ethnicity” received considerable attention in the popular press. It shows a more pronounced benefit of the diabetes medication metformin for African Americans than for European Americans based on self-identification. Although readers might assume the cause for this difference is genetic, the authors of the article point out in its concluding sentence that any such assumption is thus far inconclusive: “studies assessing the effect of genetic ancestry, rather than self-reported race-ethnicity, may help clarify whether there is a heritable component to population group differences in metformin response.”
41

For years, the majority of DNA tests available for use in medicine targeted single variants, and the tests were expensive, often not covered by insurance. But this scenario has dramatically changed. The cost of testing for DNA variants has fallen so precipitously that it is now readily affordable to large numbers of people. For example, tests that simultaneously detect thousands of
variants currently cost less than $100 and are available without a physician's prescription. Several companies offer such tests via the Internet. A person simply makes the order, paying by credit card, and a kit arrives in the mail. DNA is provided simply by swabbing the inside of the cheek or spitting into a tube, and the sample is returned by mail to the company.

After the analysis is complete, the test results are made privately available to that person online. Ancestry informative markers reveal the most probable composition of the individual's ancestry, which often is not exclusive to a particular region but is a mix of DNA segments inherited from different parts of the world. Some tests also reveal variants associated with health, including those strictly associated with genetic conditions such as cystic fibrosis, sickle-cell disease, lactose intolerance, and numerous others. The tests may also reveal statistical associations with genetic variants that confer greater-than-average susceptibility to, or protection against, other conditions, such as type 2 diabetes, alcohol dependence, coronary heart disease, Alzheimer's disease, Parkinson's disease, susceptibility to various types of cancer, and many others. The FDA, however, issued strict rules that substantially limit what health information a company can directly provide to consumers based on DNA variants, and the rulings may end up being challenged in court.
42
The raw data, including all tested variants, remain available so that health professionals who are knowledgeable regarding associations of health with DNA variants can interpret the results. Unfortunately, many physicians are not sufficiently versed in the details of how specific DNA variants are associated with susceptibilities to provide accurate information. Instead, to obtain accurate and current information, patients must consult with clinical geneticists—physicians who are specialized in medical genetics.

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