Martin Luther King Jr and Malcolm X could not escape its tentacles. Nelson Mandela barely survived its ravages. And Adolf Hitler wiped out millions of lives using it as an excuse. The biology of racial discrimination, kept under wraps for years, casts off its ugly hood once again. And this time it has an ally in an unexpected force: modern medicine.
Last month when US drug regulators approved the world’s first race-specific medicine, called BiDil, it gave an imprimatur of scientific legitimacy to the contentious notion that differences on skin colour run deep down to the level of genes.
BiDil, a pill for treating heart failure, will be marketed solely for the African-Americans who die at a disproportionate rate from the disease, compared to white Americans. Its manufacturer ' US-based company Nitromed ' claims that the drug is three-times more effective in the blacks than in the fair-skinned counterparts because of a key biological differences between the two groups.
True, physicians sometimes prescribe medicines differently considering age, sex or body weight, but BiDil could open up a new clinical criterion ' people’s ethnic origins changing the way drugs are tested, reviewed by regulators, and finally marketed by multinationals.
BiDil’s debut has sparked off a row among physicians, geneticists and experts in medical ethics over biological justifications as well as social repercussions of the so-called race-specific drug. On the one hand, it is being touted as a stepping stone towards the new age of personalised or tailor-made medicine in which patients are given targeted drugs to ensure better response and minimum side-effects. On the other hand, it is portrayed as a dangerous precedent in which the marriage of race and genetics would distract policy-makers from social issues behind heart diseases such as poverty, malnourishment and poor access to healthcare. And there are ethicists who consider it as nothing more than a form of sophisticated marketing ploy by the pharmaceutical industry bent on targeting specific groups of population.
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“BiDil presents a new model that exploits race, not for science, but for commercial purposes,” says Prof. Jonathan Kahn of Hamline University in St Paul, Minnesota, who has been studying the legal and ethical issues of race specific drug development, in an email message to KnowHOW. “The great flaw in this model is that it is based on an assumption that the race of the [African 'American] people in the drug trial was a relevant biological component.”
BiDil’s clinical trial and its approval was shrouded in a drama. What’s known as BiDil today neither began as a racially-targeted drug nor is a novel therapy. It is a combination of two old generic drugs: isosorbide dinitrate and hydralazine. First tested for heart failure more than two decades ago, the drug was initially rejected by the US drug regulator, the Food Drug Administration (FDA), because it had “insignificant evidence of its efficacy”. The prospect of BiDil seemed doomed until its developers reanalysed the results of its earlier trial and discovered that nearly a third of the patients who had responded positively to the drug were blacks. Soon the scientists managed to get a patent for its use on African-Americans. Thus it was reborn as an ethnic drug.
Seal of approval
Shortly afterwards, it went into trials exclusively on African-Americans and its maker Nitromed found it extremely effective (43 per cent reduction in death rate for heart failures when the pill was added to standard heart medication). “BiDil has the ability to significantly extend and enhance the life of black patients with heart failure,” Nitromed’s chief executive officer Michael Loberg claims in its website. Surprisingly, the drug also managed endorsements from prominent African-American doctors’ groups which include the Association of Black Cardiologists and national Medical association. This quashed any possibility of a racial backlash. After dilly-dallying for months, the FDA gave its seal of approval to the drug on June 23. The FDA’s panel of experts cited ‘ethnicity’ or ‘race’ as a surrogate for genetic factors that make some people (re-ad blacks) respond to the drugs more readily.
Why does BiDil seem to work better in blacks than whites' Medical evidences point out that the African-Americans have a slightly higher risk of death from heart failure compared to the whites. According to Nitromed, blacks are more vulnerable to heart failure because they are deficient in nitric oxide ' a key molecule that relaxes blood vessels and eases the strain on heart’s pumping. BiDil supposedly boosts the production of nitric oxide and dilates blood vessels in black patients more efficiently.
| Arthur Caplan
‘Our notion of ethnicity or race is a mess’
Experts, however, don’t agree with Nitromed’s claims. “There is no scientific evidence to support such an assumption,” says Kahn. “There was no comparison group [comprising white Americans] in the trial to test the idea that race was relevant.”
According to him, majority of the drugs approved for the US market, until recently, were based almost exclusively on trials conducted on white populations. But those medications were never labelled as ‘white’ drugs and were allowed to be sold for everybody. “If a drug tested in white people is good enough for everyone, then a drug tested in black people should also be deemed good for everyone,” says Kahn. He feels that the race-specific approval of BiDil simply sends the message that “African-American is something less than the full category of human being.”
Other experts feel that BiDil reflects clever marketing but bad science. According to Arthur Caplan, director, Centre of Bioethics at the University of Pennsylvania, it was simply a clever marketing ploy by the company. “It’s about a drug company looking to salvage a drug that did not meet expectations,” says Caplan in an e-mail message to KnowHOW.
The issue of patent has also played an important role. If BiDil had been approved for general people ' irrespective of race ' its original patent would have expired within the next two years. But now that it has been approved as a racially-targeted drug, the patent protection will run till 2020. Caplan predicts there will be more companies which will try to use race to market drugs. Kahn says that many of them have already conducted race-specific drug trials.
But how important is the concept of race in medicine' Will doctors now begin to consider your ethnic origins while examining or treating a disease' Over the past few decades, scientific evidences show that race can explain only a small portion of genetic variations in people, including a few distinctive physical features. However, a research by Richard Lewontin, a geneticist at the Harvard University, in 1972 revealed that at the genetic level there is more variation between two individuals of the same race than between two different races. Simply put, he concluded that there is no biological basis for race.
But since then several other studies have both vindicated and contradicted his finding. And in the last decade racial notions have slowly staged a comeback.
| Jonathan Kahn
'BiDil is poor science, but smart marketing'
“It depends on what you call race,” says Aravinda Chakravarti, director of the Institute of Genetic Medicine at the Johns Hopkins University School of Medicine. If you mean that humans are separable into distinct groups and that medicines will be unique to each, then I am against it. The empirical data in medicine [or medical evidence] is simply against the notion.” Chakravarti, however, admits that individual genetic constitution (genotype) does affect clinical outcome to some extent. Doctors have long known that certain diseases are more common in some ethnic groups. And responses to a particular medicine also vary among different population groups. For instance, Puerto Ricans, one of the worst sufferers of asthma, don’t respond to the common medication salbutamol. And the Pima Indians in Arizona not only have the largest number of diabetics, but also people who poorly respond to standard diabetes medication.
This is why biomedical researchers, including Chakravarti, have begun to catalogue subtle genetic variations among population groups around the world. The consortium of human geneticists from the US, UK, Japan and China ' known as the International HapMap Project ' have already sourced blood samples from distinct population groups in four corners of the world. Launched three years ago, the colossal effort aims to pin down specific markers of genetic variations ' called Single Nucleotide Polymorphisms (SNPs).
This may explain why a person is more susceptible to a specific disease. Or why some others have robust health ' it’s because they are endowed with natural abilities to fend off infectious diseases. This, say some experts, will help physicians and drug-makers predict not only the onset of a disease in someone but also how he or she will respond to a drug. Those experts think that eventually doctors will prescribe pills which will be tailormade for the patients’ genetic makeup.
Shortcut to market
The problem with BiDil is that it has bypassed this circuitous route to a personalised drug. “There was no specific use of genetic information in BiDil except that it is known that some SNPs correlate with nitric oxide deficiency, which occurs in high frequency among African-Americans compared to non-African-Americans,” says Partha P. Majumder, head of the human genetics unit at the Indian Statistical Institute. Majumder has been able to identify a number of specific genetic variations amid several population groups in India. According to him, if a drug has to be targeted to a particular group of people ' who share a common genetic ancestry ' it has to be statistically established that the drug works on a large fraction of people in the group and doesn’t have a side effect.
So it is evident that BiDil’s manufacturer have misused the concept of ‘race’ or ‘ethnicity’ to market an old drug combination. It has also ignored the complexities and subtleties of population genetics. It turns out that BiDil is not that sought-after a personalised drug ready to redefine modern medicine. The controversy surrounding its approval has laid bare the shaky ground of our ideas of race and ethnicity. “Our ordinary notions of ethnicity and race are a mess,” says Caplan. “We will need much more fine-tuned definitions of race or ethnicity if personalised medicine is really going to work.”
| Aravinda Chakravarti
‘Individual genetic makeup affects the response of a medicine’
BiDil may have been found more effective in African-Americans because they are more vulnerable to high-blood pressure or heart failure than whites, but medical researchers working on the drug should have also considered the social and economic factors behind their susceptibility. A large number of black Americans have heart diseases not because of their colour of skin, but because of poverty and related problems such as poor education, undernutrition, minimal access to health care or even mental stress from discrimination. “Race is a powerful and volatile category. It can be used constructively in medical research and practice, but it has to be used with great care ' more care than is evident in the story of BiDil,” Kahn sums up the issue beautifully.