In 2005 the FDA approved a pill to treat high blood pressure only in African Americans. This so-called miracle drug was named BiDil, and it became the first race-specific drug in the United States. It might sound like a good thing, but it had the unintended consequence of perpetuating the myth that race is a biological construct.
About Innate: How Science Invented the Myth of Race
“Black Pills” is Episode 7 of Innate: How Science Invented the Myth of Race, a podcast and magazine project that explores the historical roots and persistent legacies of racism in American science and medicine. Published through Distillations, the Science History Institute’s highly acclaimed digital content platform, the project examines the scientific origins of support for racist theories, practices, and policies. Innate is made possible in part by the National Endowment for the Humanities: Democracy demands wisdom.
Credits
Hosts: Alexis Pedrick and Elisabeth Berry Drago
Senior Producer: Mariel Carr
Producer: Rigoberto Hernandez
Associate Producer: Padmini Raghunath
Audio Engineer: Jonathan Pfeffer
“Innate Theme” composed by Jonathan Pfeffer. Additional music by Blue Dot Sessions
Resource List
Fatal Invention: How Science, Politics, and Big Business Re-create Race in the Twenty-first Century, by Dorothy Roberts
Oprah’s Unhealthy Mistake, by Osagie K. Obasogie
Race in a Bottle: The Story of BiDil and Racialized Medicine in a Post-Genomic Age, by Jonathan Kahn
Saving Sam: Drugs, Race, and Discovering the Secrets of Heart Disease, by Jay Cohn
The Slavery Hypertension Hypothesis: Dissemination and Appeal of a Modern Race Theory, by Jay S Kaufman, Susan A Hall
Superior: The Return of Race Science, by Angela Saini
Transcript
Lisa: An episode that aired in April 2007 Oprah Winfrey was hosting a Q and A segment with a frequent guest. Most people know him as Dr. Oz. Dr. Oz asked Oprah, “Do you know why African Americans have high blood pressure?” And she responded, “Well, African Americans who survived the slave trade’s middle passage were those who could hold more salt in their body.” And Dr. Oz responded, “That’s perfect.” Here he is talking about it in an interview.
Dr. Oz archive: So those folks that had genes that didn’t hold onto salt ended up dying. The survivors came to a new environment and actually benefited them, and they were young, that they could maintain salt ’cause with salt they can maintain water in their bodies so they can survive in inhumane conditions.
But now fast forward 200 years to a society where you don’t have those headaches anymore, now all you’ve got is a genetic limitation that leads to high blood pressure.
Lisa: The theory they’re discussing goes like this: enslaved Africans who’s bodies could hold more salt were better able to survive thirst and depravation during the trans Atlantic voyage and once that group had children, their genes, which favored holding more salt, were passed down to the next generation. This genetic superpower for holding onto salt may have served them well when trying to survive dehydration in the belly of a 17th century slave ship but now it’s leading their descendants to struggle with high blood pressure, and that theory propagated here by Dr. Oz, a former heart surgeon and failed senate candidate is known as the slavery hypertension hypothesis. It was shared during the height of Oprah’s prime time show, which commanded an audience of eight million viewers a day.
And you can see why Oprah might this theory compelling, it ties a problem afflicting the African American community to a shared history. It roots a modern struggle within a historical one. The only problem is, there’s no data to support it.
Jay Kaufman: so the, the slavery hypertension hypothesis is sort of a, like a just so story.
Lisa: This is J. Coffman, a professor of epidemiology at the University of Montreal, who’s written about the hypothesis.
Jay Kaufman: I’m referring to these, um, books for children that were written by Kiplin around the turn of the century and there’s stories about how animals came to take on their shape, you know, like the, the elephant got his long truck because an aligator pulled on it and stretched it out and it became very long. Like, these are stories that describe in some kind of a mythical way the way that, uh, nature came to take its current shape and, um, the slavery hy- hypertension hypothesis is sort of like that.
Lisa: The slavery hypertension theory emerged after a survey in the 1960s found that African Americans in the United States have nearly twice the rate of high blood pressure than white Americans, and despite a lack of evidence, this theory has endured for decades.
Jay Kaufman: The remarkable thing about it over historical time is just how pervasive and resilient this conjectury was because it ended up appearing in all kinds of textbooks and it ended up being discussed in all kinds of scientific meetings and many people described it as though it’s a, a, a respected scientific hypothesis, and yet nobody’s ever actually observed any data that would suggest any mechanism of some kind of genetic evolution that would give Black people higher blood pressure than white people. Like it doesn’t, um, the, there’s no, uh, uh, data that would suggest any reality for this story.
Lisa: The biggest issue for this hypothesis is not just that it’s wrong, but that it sends the message that the problem of hypertension is a problem created within the Black body. Framing the story this way, uh, kind of absolves society from addressing all the other systemic problems that we know can cause hypertension; not having access to healthy foods, not having safe places to exercise, outdoor spaces, and of course, stress from all the structural racism. Blaming genetics for social problems is something Jay. Kauffman calls genetic determinism.
Jay Kaufman: If I say oh, I have a, you know, gene for criminality or a gene for high blood pressure, it’s not anybody’s fault, it’s just an accident of nature, you know, it’s just, uh, it’s, it’s, it’s my fate essentially, you know? Like it, it’s beyond my control. So this operates, this kind of genetic determinism operates to absolve everybody, individual behavior, societal behavior, uh, in fact it’s, it’s mythological.
Lisa: So just to summarize, the slavery hypertension hypothesis is a way of framing the problem of hypertension as a problem within the Black body. But medicine has also tried to frame the solution the same way.
In the early 2000s, a pharmaceutical company applied this logic when it created a bill to treat hypertension only in African Americans. This so called miracle drug was named BiDil.
News Archive: Researchers announced that BiDil worked spectacularly in African Americans. We saw a 43% improvement in survival, a 33% decrease in hospitalization rate and a significant improvement in quality of life. The drug’s maker, NitroMed does not claim that BiDil can’t work in white or in Asian heart patients, only that it does work in Blacks who suffer far more heart disease than whites.
Lisa: In some ways, this sounds like a good thing, right? Well, as the old cliché goes, the devil’s in the details.
Jonathan Kahn: They are opening a Pandora’s box by using race as a means to get FDA approval for this drug.
Lisa: That was Jonathan Kahn, the author of Race in a Bottle, speaking in 2004. He documented the BiDil saga from the very beginning.
Jonathan Kahn: You open up the road to people talking about races as being genetically biologically different, which opens up a whole host of possible, um, uh, avenues for discrimination, for mistreatment.
Lisa: In a nutshell, that’s the story we’re going to tell today, the story of BiDil, how it became the first race specific drug approved in the United States and how the medical system helped perpetuate, without evidence, this myth that race is a biological construct.
Jonathan Kahn: It’s a story of people who I think are very well meaning in many respects, um, in trying to address concerns about health and health disparities, uh, but having depreciated the, uh, uh, the potential dangers of using race in biomedical context without appropriate, uh, thought being given to what a volatile category it is when you mix up race and genetics.
Lisa: Chapter one, dead in the water.
In July of 1956, J. Cohen was an internist at the Beth Israel Hospital in Boston when a man named Sam Farber was admitted into the emergency room with a heart attack. He was given oxygen and morphine for it.
Jay Cohn: And I followed him during the weeks that he re- was in the hospital recovering from the heart attack and sent him home apparently well and ready to be returned to, to activity slowly and, uh, six months later he came back to the hospital now in severe heart failure.
Lisa: In those days, there was little information as to why a heart attack could lead to a disease called heart failure. A heart attack is when blood flow is partially or completely interrupted from the heart and heart failure is a disease in which the heart cannot effectively pump blood to the rest of the body. They’re two different conditions, but they’re interrelated. We now know a heart attack damages and weakens the muscle, and therefore, a patient could develop heart failure and the prognosis is bleak. 50% of people die within five years of diagnosis.
But at the time, in 1956, no one knew that, and so Sam died on his second visit to the ER.
Jay Cohn: And no one could explain to me why he had developed heart failure because he didn’t have any new damage to his heart.
Lisa: This death sent Jay Cohan on the path to figure out how hypertension or high blood pressure, heart attacks and heart failure are all connected. He needed to figure out a way to treat them. By 1972, Cohan was a cardiologist at the University of Minnesota and at this time, there are still few ways to treat heart failure. One was a plant based medicine called Digitalis, other was through diuretics, which just make it easier for the heart to pump blood.
Cohn remembered reading that there was a chemical that could lower severe high blood pressure. He got some of it in powder form to use for testing. It wasn’t approved for medical use, but his university had permission to use it for investigations, so he began running tests on animals.
Jay Cohn: As soon as you started dripping the infusion into a vein, their blood pressure would come down so it was a remarkable way to, uh, treat high blood pressure. No one had ever used it to treat heart failure, so that was a whole new approach.
Lisa: Two problems here. One, again, this chemical is not approved for medical use to treat heart failure. Two, it’s got to be applied through a needle. Cohan wanted to have the same effect but in pill form and he figured out that he could almost replicated it by using two generic pills already on the market. One was Hydralazine, the other was Isosorbide Dinitrate. They’re both known as vasodilators and this combination later became known as BiDil. Even though it didn’t get its official name until 1992, for the purposes of this episode, we’re going to keep referring to this pill combination as BiDil.
Together, these two drugs helped the body make nitric oxide, which is a gas that widens the arteries and lets blood flow more smoothly with less of a strain on the heart.
Imagine a water pump pumping into small pipes. To get water through all the pipes, it’s probably easier to make the pipes bigger as opposed to making the pump work harder, then the water isn’t forced out at higher and higher pressure.
Jay Cohn: No longer did we focus on making the heart beat more, more strongly, but we focused on relaxing the arteries so the heart with its reduced pumping ability could empty into the arteries at a lower resistance and a lower impedance.
Lisa: In 1979, Cohan went to his old employer, the Veteran’s Administration. He got some funding to develop a test-of-theory trial for his BiDil combination drug. The first trial had 643 patients, Black and white veterans. It lasted for five years and it basically showed that BiDil worked to prevent heart failure. You’ll hear us refer to this trial as V-HeFT I. Now, this trial was promising enough to get him funding for a second trial and the second trial pitted BiDil against another drug, which is known as an ace inhibitor. These types of drugs basically suppress the part of your body that regulates blood pressure, and this trial was known as V-HeFT II.
Now, something remarkable happened during this trial. Remember we said there’s very few things to treat heart failure? Well, the ace inhibitors worked so well in this trial that this type of drug now became the go-to medication for treating heart failure, a new gold standard.
Jonathan Kahn: And, um, the outcome of that trial was that it did not appear that the BiDil drugs, uh, did any better than, um, than the ace inhibitor
Lisa: So this could have been the end of the story. The ace inhibitor was a better drug. BiDil was just a medical curiosity. But J. Cohen didn’t give up. He wanted to do one more trial. However, by this point in the late 80s, the federal money had dried up.
Undeterred, Cohen tried to get a patent. Now, the odds weren’t in his favor here. You usually can’t get a patent for two generic drugs that are already on the market, but he got the patent office to agree based on one significant difference, delivery. Because instead of taking two generics, BiDil was administered in a single pill.
Jonathan Kahn: There was no mention of race in this original patent. So at this point, in 1989, BiDil is conceived of as a drug for everybody, and indeed, uh, a lot of articles were published out of the V-HeFT studies during the 1980s, not one of ’em mentioned race. It was all just about oh, this drug seems to have a very positive impact on heart failure mortality and quality of life.
Lisa: With the patent now in hand, Cohen partners up with a company called MedCo. It’s located in the research triangle in North Carolina. MedCo takes the data from the original trial with the 643 veterans and made preparations to get FDA approval. A patent lasts for 20 years and it gives 20 years of exclusivity, meaning only the company that holds the patent can make and sell it and FDA approval is mandatory if the drug’s gonna be sold and marketed in the US.
Now, FDA approval can take years and MedCo and Cohen finally presented their application in 1996. The FDA review panels are usually 10 to 12 experts reviewing the data and they make recommendations to the FDA for approval.
This panel was mostly cardiologists and two bio statisticians. Things didn’t go according to plan. In 1997, the FDA rejected their application.
Jonathan Kahn: What the FDA said was very instructive. It said we think this drug is approvable, but the statistical data you have supplied us is insufficiently well controlled to merit approval. That’s because the original studies were conceived of as test of theory trials, not as new drug trials, so they didn’t have the appropriate controls in place and they didn’t have a data safety monitoring board or any of these kinds of things and so basically what happened, it’s very interesting when you read the transcripts of the actual review session and the cardiologists were saying, um, you know, does this drug work? Well I would give this drug to my patients, right? But the bio statisticians were saying that may be the case but the statistics are a hash, right? The statistics are a mess, um, the data’s not good enough.
And so at one point they pull the, uh, the panel and ask them whether or not they think BiDil works and, uh, essentially what, what the clinicians are saying, there’s aw- this is almost a direct quote, they say, “Do I think it works? Clinically, yes, statistically no.” Right? Which is a fantastic or, you know, fascinating kind of concept, right? And so, so they say, well, if you conduct one well controlled follow up trial, MedCo, right, clinical trial, that is controlled like a new drug trial, uh, we think it’s likely approvable.
Lisa: MedCo stock plummeted 20% after the rejection and they pulled out of the BiDil business for two reason, one, clinical trials are the most expensive part of the process, especially for a relatively small drug company like MedCo. The V-HeFT I and V-HeFT II trials were done with tax payer money so they thought they could have gotten the drug approved on the cheap.
Reason number two, by this point, the patent that J. Cohen received is already 10 years old, which means they only have 10 years left of potential profits, and on top of that, finally getting FDA approval could take a few more years, meaning that their patent life is shrinking.
Jonathan Kahn: And so it’s at that point then in 1997 that BiDil seems dead in the water and so what happens at that point is now for the first time, race enters the story.
Lisa: J. Cohen needed to save his drug so he went back to the V-HeFT I and V-HeFT II trials. He basically chopped the data up into subgroups and then divided them along racial lines. He isolated a sample of Black patients, which was 49 people.
Jay Cohn: You dutifully go through the process of looking at all the subgroups in your trial in order to see if there’s any difference and the answer always is there’s no difference, so we were blown away when we did the first analysis of, of the difference in the racial response.
Lisa: What he found is that BiDil seemed to work really well in prolonging the survival of Black patients.
Jay Cohn: And that was a revelation that, uh, opened the door to questioning whether racial distinction would help us in managing patients with heart failure.
Lisa: Cohen applied for and received another patent in 2000.
Jonathan Kahn: And the new patent ends up looking almost exactly like the old patent, except it says a method of treating heart failure in a Black patient. And, um, and the patent office grants the patent and this is a critical turning point in BiDil’s shift to becoming a racialized drug because you have the federal government giving the imprimatur to using race as in effect, a genetic category here. And what’s quite striking about the federal government’s approval here, the US Patent Office approval is that it seems to go against very directly a doctrine known as double
Lisa: Just to explain the double patenting problem, if you get a patent for using BiDil to treat heart failure in human beings writ large, which Cohen originally got in 1989, you can’t then get a second patent for using the drugs to treat heart failure in a subset of human beings, in this case, just African Americans.
Jonathan Kahn: But in America for, you know, my reading of this is sort of the power and salience of the idea of race is such here that it was the idea that oh no, this really is something different and the only way it could be conceived of as something different to warrant the issuing of a new patent would be if you conceived of Black people as somehow different from people and this is sort of the, the sort of deep conc- concern over the sort of unintended messages being sent here.
Um, but powerfully what you have here then is the shift, really, towards getting this racial patent had less to do with the science and medicine underlying, uh, the, the me- the, the sort of, uh, the mechanisms of BiDil’s efficacy and much more to do with the fact that they were turned down by the original FDA panel and the original company didn’t want to, um, conduct a follow up trial.
Lisa: By this point, Cohen now has a new pharmaceutical partner in a company called NitroMed, based in Boston. He licenses the patent to them. NitroMed likes this new patent because the old one, issued in 1989, is more than half way through its life cycle, which means that with a new patent, issued in 2000, there’s 20 more years of exclusivity.
Jay Cohn: And nobody, no drug company, uh, spends the money in doing a clinical trial unless there is a product at the end of the line that they can market and if you don’t have patent protection you can’t market the product because anyone else can make it. So of course that’s true. Uh, the incentive in the pharmaceutical industry, uh, for drug development is obviously financial. So that’s the way the pharmaceutical industry works. I don’t know why Johnathan Kahn, uh, doesn’t understand that but he [laughs] implied that he thought that was, uh, that, that was, uh, uh, strange thing for a drug company to do. Of course not, that’s what all drug companies do.
Chapter 2: A Blunt Tool
Lisa: With the patent in hand, NitroMed went to the FDA to get the drug approved. They still needed to go through the drug approval gold standard, two large, well controlled, clinical trials. Now, the FDA did something surprising here. It said that NitroMed could use the data from the previous two trials, V-HeFT I and V-HeFT II and they’d be the equivalent of one large, well controlled trial. It asked them to only do one additional trial, and just on one population, self identified African Americans. These two together would satisfy their equivalent of the gold standard. It was incredibly unusual. Up to that point, it had never happened before.
Jonathan Kahn: And that’s because the logic was, oh, well, in the initial trials, it seemed to show such great efficacy in African Americans, and the irony of that is,” this claim was based primarily on the study from V-HeFT but in that trial, the, the claim of enhanced efficacy in, or effectiveness, I should say in, uh, in the Black subjects was based on a, an enrolled population of 49 African Americans who were actually on the BiDil drugs, right? Tiny, tiny amount. Usually a clinical trial enrolls in the thousands, like you know, three to 6000 say would be a typical clinical trial. Um, this was 49 African Americans.
Lisa: Incredibly, the drug approval process was allowed to go forward thanks to just 49 people.
Jonathan Kahn: They kept calling it a signal. Um, I would argue it’s a fairly weak signal to rest an entire drug approval process on but this is testament sort of to the power of race.
Lisa: So NitroMed started working on its second trial of just African Americans in 2001. It was led by the association of Black cardiologists. The trial had 1036 self identified African American participants enrolled. This trial was called A-HeFT. Now, keep in mind those words, self identified African American ’cause a lot of what’s gonna come hinges on that.
But anyway, 1000 people is still a very small number compared to other trial, which was good for NitroMed because a smaller trial means a cheaper trial.
Jonathan Kahn: But the logic there as well, well this is an enriched population. It was the idea, it was sort of like this pseudo pharmacogenomic idea that if you have a targeted population that a drug is likely to do well in, you can enroll smaller numbers to, to get, uh, the, the effects you want.
Lisa: The enriched population in this case were the self identified African Americans and here we’re gonna point something out. This trial uses race as a proxy for genetics. The implication here is that there’s some unknown biological mechanism at work for high blood pressure in African Americans writ large. The assumption here is that they’re all genetically the same, but in fact, there can be far more genetic diversity among people within each race than between races. What’s also strange about using self identified African Americans is that this is a socially constructed term.
Jonathan Kahn: You know, they didn’t wanna get into sort of the politics of race, again, but they were very happy to get into what they se- saw as or were purporting to observe as the sort of biology of race. Right? So well, we know, yeah, they said we don’t wanna get into all these other issues, these sort of purportedly political concerns about whether ra- race is genetic, we just wanna look at the data that we’ve gathered. But the data they’re gathering is based on all sorts of prior assumptions about the sort of biological or genetic nature of socially constructed racial categories. The, they’re enrolling self identified African Americans. You know, self identification is a social process. Racial concepts themselves are, are socially, socially conditioned.
Lisa: Keith Ferdinand is a cardiologist at the Tulane School of Medicine in New Orleans and a member of the Association of Black Cardiologists. He was one of the principle investigators on the African American trial with two sights, one in the ninth ward and another at Xavier University School of Pharmacy in uptown New Orleans. He and his colleague, Charles curry, the chief cardiologist at Howard University and the founder of the Association for Black Cardiologists were concerned about this very issue, enrolling self-identified African Americans.
Keith Ferdinand: Dr. Curry was very reluctant to give the, the stamp of imprimatur of the Association of Black Cardiologists for this study ’cause he was prescient and he felt that there may be a feeling that we were endorsing a Black drug and we really didn’t see that that would happen because we say well, there’s a signal in V-HeFT and our patients have more cardiovascular deaths and hospitalizations, so if it helps, let’s study and see if it helps. That was our path.
His path was, yeah, but you don’t wanna be locked into this idea that you’re making, um, scientific discoveries on a drug that would just work in Black patients.
Lisa: Nevertheless, Ferdinand went ahead with the trial for a few reasons. One, this practice is common in medicine.
Keith Ferdinand: So if you look in medicine in general, we use the term white, Black, Hispanic, these are social terms. They’re really divorced from any true biologically genetic markers. To a large extent, it’s a very blunt tool, you can make the point that it’s an inaccurate tool and we recognize it as a marker for a whole host of things outside of just skin color and language. But it’s kind of a short hand that’s used in clinical trials.
Lisa: Reason number two, the A-HeFT trial was groundbreaking. The vast majority of medical trials in the United States are in white men. Just 5% of clinical trial participants are typically African Americans. A-HeFT had the largest number of Black women in a clinical trial at that time.
Keith Ferdinand: So we use, on a regular basis, drugs which under represent the Black population. Here, the script was flipped somewhat, we wanted to see a drug that may be beneficial in a Black population.
Lisa: The third reason is pragmatic. It’s not like he went into this trial thinking BiDil was a miracle drug. In some ways, he just wanted to give his patients good medical treatment and if this study gave him the resources to do it, he was gonna take the opportunity.
Keith Ferdinand: In our communities, we saw the heart failure hospitalization, we saw the early death, I treated these patients, I’ve had patients die in my arms. I’ve done CPR on two patients at once, so I have seen what happens when persons on the throws of heart failure and, and, can’t survive. So we said, well, you know, I understand that there’s some reluctance, but let’s just do the study and, and, and it’ll give the chance for our patients to get, uh, free medications, they get free testing, echocardiograms, which at that time were quite expensive, hundreds of dollars, whether or not they had insurance it didn’t make a difference.
Lisa: It’s helpful to understand a bit of background here. In 2002, the Institute of Medicine, a federal agency, had just published a paper called Unequal Treatment: Confronting Racial and Ethnic Disparities in Healthcare. It was an explosive paper that showed African Americans have higher rates of cardiovascular disease, heart disease, stroke, heart failure, hypertension, among others. All at higher rates than white people and essentially the source of those differences is structural racism, both within medicine and outside it.
So there’s a sense of urgency in doctors like Ferdinand who are concerned with health equity, who wanna do something about it.
Keith Ferdinand: I wanted to do something with my education that would benefit my people and I, and I knew at that time that Black people had poor healthcare, so I wanted to become a provider, and as the data started to accumulate even more that there were these cardiovascular disparities driven by hypertension, heart failure, chronic kidney disease, et cetera, I focused on cardiovascular medicine. So it wasn’t some sort of romantic love of medicine, it was a cold blooded decision what I could do to help my people.
Lisa: Ferdinand’s intent was to provide relief and care to his patients. His intent was not to send a message that Black people are biologically different.
Keith Ferdinand: We wanna do something to help our patients. We see a signal. With wanna study a drug, see if it helps our patients and if it does, then it’s something that we wanna add to our armamentarium of medications. It doesn’t mean that somehow simplistically we would say, “Eureka, we found a drug that only helps people who self identify as Black. Oh, you not? You can’t use our drug.” That… that’s illogical to me and we never had that as our intent.
Lisa: Rana Hogarth, the author of Medicalizing Blackness says that Ferdinand’s buy in for BiDil shows the problem is not the drug itself, but rather the system that created it.
Rana Hogarth: The point of health disparities and why BiDil is so thorny is that he recognized, as anyone would, that there are health disparities and he is doing what he needs to do for his community, so not only are his intentions good, his outcomes are good, but the problem is he’s trapped in a system where this is how he’s gotta do it. Like, so if you wanna say, “I’m gonna make sure they get the best care, oh yeah, and the BiDil thing, that’s incidental,” but you have to still be a part of it. That’s the issue. It shouldn’t have to be that way. They, he, his patients should not be suffering in this way.
And so the point is is that the story of the African American cardiologists who are supporting, uh, BiDil, who participate in A-HeFT is a testament to how much or how bad health disparities are and what lengths that Black physicians are gonna go to to look after their community, to say, okay, nobody else is gonna do it, here’s an opportunity that landed in our laps. We can say no on paper theoretically this is reifying the idea of race as a biological thing.
Yeah, that’s fine and good, but if you, as he says, he sees this every day. So he can say all right, that’s not great, I’m gonna make that the lesser priority and I’m gonna say what can I do for my patients today? If I sign onto this, how many people are going to have a better existence? And I think that that’s perfectly valid, that doesn’t mean that he is, you know, somehow was tricked.
Lisa: The story of BiDil is less about the drug itself and what impact it might have had on patients and more about how people used BiDil to achieve their goals.
Rana Hogarth: But I also think that there is a way that you can acknowledge both, that you can say, look, uh, this is the system that we have and I have to work within the system, just like for, um, J. Cohen, this is how I’m gonna get approval, all right, I’m gonna work in the system. The reality is that there, this is a story of people working within a system where race is given this meaning that it really ought to not have and this is the mischief that, like, falls out.
Lisa: Ferdinand expressed resentment at the fact that people have implied that he was bought to endorse a Black drug.
Keith Ferdinand: I will tell you as an investigator with two sites, member of the steering committee and a leader of the Association of Black Cardiologists, we never intended to make a Black drug and that’s a simplistic and, and somewhat a chauvinistic way to describe the efforts of people who spent a lot of effort to become a physician and then a cardiologist and then specialize in clinical trial which many of us were, some of the leading docs at the time, that we are simplistic enough in our thinking to think that we were making a Black drug. That, that just doesn’t make sense to me, but I know some feel very comfortable casting dispersions on our efforts and, and articulate that and if, if you really think on this, on the face, it doesn’t make sense that people with this degree of education and commitment, lifelong commitment are gonna somehow think that there’s a drug that should only be used in persons who self identify as Black.
Lisa: A crucial question remains, why didn’t NitroMed include a more diverse group of people in its trial to see if BiDil worked in, say, white Americans or Asian Americans, and the answer is they had a financial disincentive for finding out that BiDil worked regardless of race because their patent only applied to the drug as administered to African American patients.
Jay Cohn: It satisfied NitroMed, but it, it obviously didn’t satisfy the critics who thought that we were trying to make money on, over, off of Black people or some ridiculous claim like that as if treating Black people, uh, is not a benefit to society. Of course it is.
Lisa: The trial actually had fantastic results. In fact, the results were so good that those who were taking a placebo were given the drug instead and the trial stopped ahead of schedule. The results made national news.
New Archive: In a study released today, we learn that the drug worked particularly well on African Americans, combined with routine therapy for heart failure, it dramatically reduced the risk of dying.
It could be a turning point not only in treating heart failure but for the overall approach to developing medications. Doctors report success today in saving lives with a heart drug tested on a specific group of people, African Americans.
Lisa: The fact that the drug worked wasn’t really a surprise.
Jonathan Kahn: Indeed, it showed good results, as everybody expected because the V-HeFT trial showed good results. There’s no reason it shouldn’t have shown good results.
Lisa: But if the drug had been tested in people of other races, would it have shown similarly good results regardless of race? Some of the A-HeFT trial investigators themselves said that was the case but we’ll never know, because it was only tested in self identified African Americans. For J. Cohen, the good results were welcome news.
Jay Cohn: It was a dramatic moment. It was, uh, vindication for everything we had done over the years and for our recognition that there was pa- potential difference. We didn’t study the difference between Blacks and whites but here we had data at least that we knew this population had a dramatic benefit and it was, uh, very reassuring and exhilarating because it was a drug that we had invented and here it was helping keep people alive and, uh, the potential for its use in the Black population was so dramatic that we felt we had solved a major healthcare problem.
Lisa: With the A-HeFT trial completed and successful, BiDil was now headed to the FDA for approval.
News Arch ive: Approval for BiDil as a heart treatment for African Americans is now up to the FDA but is expected by early next year.
Lisa: Cohen was cautiously optimistic that BiDil would get its approval.
Jay Cohn: And, uh, we were suspicious of whether the FDA would follow through and, and approve the drug for, uh, one racial group. I mean, that, that was a precedent never visited before [laughs] by the FDA to approve a drug for a racial subgroup.
Chapter three, drugs aren’t racist, people are.
Lisa: Part of the process for FDA approval involves a hearing with a panel of experts. The panel gives a recommendation and the FDA basically rubber stamps it. This is a key part of the process and BiDil’s hearing was on June 16th, 2005. One of the first people to speak in favor of the drug was Dana Christensen, a physician, a member of congress, and a member of the Congressional Black Caucus.
She said that BiDil should be approved as a kind of restorative justice for African Americans for whom, “treatment has been denied and deferred for 400 years.” The support is understandable, but the drug was going to have an unintended consequence, that is labeling Black people as biologically different.
Jonathan Kahn: I think what it was though was also, uh, a failure to appreciate sort of short term versus long term goals. Um, ’cause the short term goal might be here’s a drug for Black people, the long term goal might be sort of contributing to a narrative that says health disparities which are a much bigger problem than just heart failure, that heart disparities are something that should be fixed with pills rather than with equity and social policy and justice,
I don’t, um, you know, think that the people supporting it were hypocrites or, um, simply, um, uh, greedy or anything of that sort. Um, I think, um, I think they simply, uh, did not take the care necessary to really think through the implications of what their support involved.
Lisa: Jonathan Kahn also gave testimony the day of the hearing and his testimony gets to the crux of the debate at the FDA. They weren’t trying to decide if the drug should be available at all, but rather whether it should be labeled as a pill only for Black patients.
Jonathan Kahn: But, but the main thing I was saying, and that a number of people were saying is yes, you know, the indications are this is a good drug. Uh, there’s no reason not to approve it, but there is no reason to approve it with a race specific indication. And even, you know, people from the, like, the International Society for Hypertension in Blacks and things, uh, of that sort were saying, “Oh yes, we love this drug, it’s great, but there’s no need for a race specific approval.”
Lisa: One committee member, Vivian Ota Wang who is part of Howard University’s National Human Genome Center, she had one of the same concerns we discussed earlier, the fact that the A-HeFT trial used self identified African American as equivalent to a biological marker of difference. Here’s Ota Wang appearing on PBS News Hour a day after the hearing.
News Archive: I was not convinced by the scientific evidence that actually it is effective for this broad range of a very variable group called African America. This brings up the whole issue of is race biological and I am from the, um, persuasion that it is, at this point, not biological, that in fact the self identification of, of racial identity is a complex sort of process that includes social, cultural and psychological, um, issues in that it really serves as a biological proxy in this particular study.
In short, using social categories as a proxy for genetics is basically sloppy science. Johnathan Kahn says it’s also a symptom of arrogance.
Jonathan Kahn: When, you know, if you look at your typical, um, you know, biomedical study, article published in, you know, Nature or Science or the New England Journal or something like that and especially if it involves genetics, the methods section is very detailed, going into sort of like, you know, what sequencing platform they used and what software they used and what primers they use and all this… and then when it comes to race, they simply say self identified race. Um, and the idea is that well that captures all they need to know about race.
And, they don’t think anything more about, like, how race is this fraught and complex category and what it means. When I’m speaking to, to people, you know, to doctors or, or geneticists, I say, you know, genetics is really complex but so is race. Right? And, and, in every day life, yeah, walking down the street we may say, oh yeah, you know, I know who’s Black, who’s white, who’s Asian, who’s Hispanic, whatever, um, and sort of like a, a kind of sloppy social way. Like we all live with race very day, so since we all live with race every day, we may think it’s obvious.
And maybe for everyday interactions, it by and large is, but in the world of biomedicine, it’s anything but obvious. It’s much more complicated and much more fraught because you are trying to connect race with, with what’s going on inside the body.
Lisa: The FDA Committee Chairperson Steve Nissen didn’t see it this way. He said that he wished they did know how exactly the drug worked inside the bodies of African Americans but since they didn’t know the best they had were the V-HeFT and A-HeFT trials.
Wong countered that the standard of research, those large, well controlled studies that they usually required had been lowered when it came to African Americans. What kind of message was that sending?
At the heart of their debate was how exactly does this drug work anyway? NitroMed was using the self identification as a proxy for an unknown biological marker and while it’s true that the A-HeFT trial showed BiDil as successful in treating Black patients, it didn’t give enough evidence to the FDA to approve it as a race based medicine. Neither Cohen nor NitroMed could explain how or why the drug worked biologically, specifically on Black people.
What was this strange mechanism at work?
Jay Cohn: Race, of course, is not a biological phenomenon, it is a social phenomenon according to the social scientists and it doesn’t really matter and it’s never mattered to the FDA. The FDA just wants show me the population and show me it works. And we show you the population, we don’t understand why it works. You, you don’t have to di- document that. You just have to show that this therapy, when applied to this population, produces a beneficial effect.
Lisa: You may be surprised to learn, as I was surprised to learn, that it turns out you don’t have to prove how something works, you just have to prove that it works.
Jay Cohn: Of course we all wanted to know that but, uh, the FDA only bases their approval process not on mechanism of action but on data and, uh, they were happy, all they needed was evidence that survival was improved and it was statistically sound analysis and the drug gets approved. There’s no requirement to identify a mechanism by which the drug works.
Lisa: There are multiple medications that are available without doctors understanding the scientific reason why they work. Think of it as cause and effect. Without know… oh. Think of it as cause and effect. While knowing the cause would be nice, the effect is the most important.
Keith Ferdinand: As physicians, we do the best we can with science but there’s a certain degree of art, so you look at studies, you see where patients in clinical trials may have benefit, but we may not really even understand the science of why exactly one group benefited versus another. That takes a lot of time and a lot of effort, but in medicine, we’re simple human beings with simple tools and we tend to do the best we can for our patients. We often are doing it more as an artist than a, a true scientists.
Lisa: In any case, Nissen dismissed the concern that by approving BiDil, they were sending the unintended message that Black people were biologically different. He said, “Drugs aren’t racist, people are.”
The expert panel approved BiDil.
News Archive: Now today, for the first time, an FDA panel of experts has recommended approval for a drug for one race.
Lisa: BiDil became the first race specific drug on the American market.
Jonathan Kahn: And the logic they give, the rationale I should say, they gave was well, the drug was only tested in Black people, so, that’s the population for which we have to approve it.
Lisa: There’s a weird logic at work here. Most drugs in the market today are primarily tested on white people, and this is because of a lack of diversity in clinical trials. This has long been a problem in medicine and yet those drugs are approved for everyone. So, why is it that when a drug is tested only on Black people, it’s only approved for Black patients.
Jonathan Kahn: But when the FDA was reviewing data from clinical trials conducting in white populations, they just saw human beings, right? The idea being that the category white was not raced, it was just that white equaled human and so if it works in white people, it works in everybody. The category white being coextensive with the category human. It’s only with BiDil where fe- for the first time you get somebody saying, okay, the category, it was only tested in Black people, that is a biologically salient category that is not coextensive with the category human so therefore it should only be approved in Black people.
So the message unintended but nonetheless the message being sent is tested in white people it’s good enough for everybody ’cause the category white is coextensive with the category human. You approve it in Black people, you test it in Black people, you can only approve it in Black people ’cause Black people are somehow less fully representative of humanity.
Lisa: Our producer, Rigo Hernandez asked Jay Cohen about this logic.
Rigo: So then if a drug that is only tested in African Americans, then by logic, shouldn’t it also be prescribed for everyone, or if a drug is tested only on white people, then shouldn’t it only be prescribed in white people? Like, how do you reconcile that logic?
Jay Cohn: Yeah, I don’t. I mean, I agree with you completely. It, it, it’s, uh, inconsistent and, and that’s what we wondered when the FDA reviewed the A-HeFT results, that was the one question that, uh, uh, NitroMed had, yeah, eh, are they really gonna follow through and approve the drug for one racial group or are they gonna turn around and say, “Well, the drug is effective, let’s, let’s approve it for everybody.” But they stuck to their, their promotional idea that Black people, if you study Black people then it’s good for Black people, if you study white people, it’s good for everybody. It’s obviously a fallacious reasoning but, uh, we do a lot of strange things based upon the realty of them.
Lisa: Fallacious reasoning or not, BiDil was approved. Now it would succeed or fail in the market.
Chapter four, Suspicion.
Now that BiDil had FDA approval, NitroMed could market it as a drug to treat heart failure in African Americans and with the patent at hand, it could do so exclusively for 20 years.
One financial analysis projected that the opportunity could be worth up to a billion dollars, but they could stand to make more if they prescribed it not just to African Americans, but to everyone.
Jonathan Kahn: Of course the reason NitroMed wanted the race specific approval is ’cause they needed the race specific approval from the FDA in order to protect their race specific patent. So an FDA approval says is, this drug is approved for use to treat heart failure in a Black patient.
What that means is that that drug can only be marketed to treat heart failure in a Black patient. Doesn’t mean it can’t be prescribed, it can be prescribed, doctors can prescribe it however they want.
Lisa: This is a kind of win-win for NitroMed, because while they can only market it to one group, doctors can prescribe it to everyone, meaning your market for the drug is not just limited to one group of people. Our producer Rigo Hernandez asked J. Cohen about it.
Rigo: It’s, it’s been described as, like, having your cake and eat it too.
Jay Cohn: too. Well, that’s probably true. I think, uh, but the, but the, the distinction was never made because we thought there was a fundamental difference in response. The distinction was made just so that we could do a study of modest size and get a benefit so that we could get approval and I think that’s misunderstood a little bit. There’s nothing wrong with that. That, in fact, is the only way you do clinical trials. You have to find a population that is responsive to your drug so you can accomplish a positive trial.
Lisa: With patent exclusivity, FDA approval and the endorsement of Black organizations, BiDil seemed destined to succeed, except it failed. One factor was cost. Prior to FDA approval, NitroMed was saying BiDil was going to be priced around two and a half dollars a day, but shortly after the approval, their analysis came back and said it was actually going to cost around $12 a day.
Jay Cohn: NitroMed, uh, double crossed us and raised the price of the drugs so it had an adverse effect on their sales sales.
Lisa: NitroMed justified the cost increase by saying it was going to save American healthcare a lot of money by preventing hospitalizations.
Jonathan Kahn: NitroMed simply got greedy and greedy and priced itself out of the market. NitroMed thought that the drug would essentially sell itself ’cause it’d gotten so much big media coverage as the first Black drug.
Lisa: There are multiple explanations for why BiDil failed. Hospitals and insurance companies didn’t want to pay for it because it was expensive and the two generics that made up BiDil are already widely available. Some doctors also didn’t want to add yet another pill to the many drugs their heart failure patients were already taking.
But perhaps, the most compelling reason is best illustrated by a TV show on Fox called House MD. In an episode from 2006, a Black doctor was seeing a Black patient with hypertension.
Black Doctor: There’s something new that should help you out, it combines nitrate with a blood pressure pill. It’s targeted to African Americans.
Black Patient: Targeted? I’ve had white people lying to me for 60 years.
Lisa: Later in the episode, Dr. House who is white, sees the same patient. The patient again refuses to take a drug that’s only for Black patients. He’s skeptical, distrustful.
Black Patient: I’m not buying into no racist drug, okay?
White doctor: It’s racist because it helps Black people more than white people? On behalf of my peeps, let me just say thanks for dying on principle for us.
Black patient: Look, my heart’s red, your heart’s red and it don’t make no sense to give us different drugs.
Lisa: To resolve the crisis, Dr. House writes another script for the same drug without the patient knowing.
White doctor: Fine, fine. I’ll give you the same medicine we give Republicans.
Lisa: The episode treats his fears as paranoid, but if you’ve listened this far into our season, you know it’s an earned mistrust.
Jonathan Kahn: And this was brought home to me when I was giving a talk, um, at a law school about, about BiDil, um, around this time, and, uh, a Black woman in the audience, a law professor was saying, “So you’re telling me that if I go to my doctor, she’ll tell me, ‘Oh, we’ve got this drug that’s just for you, just for Black people.'” And I say, “Yeah.” And she say, “Well, I tell you, if my doctor told me that, I’d say, ‘Please give me, give me the same drug you give the white folks, thanks very much.'” But again, there’s a lesson there about, you know, the suspicion, the, the well-earned suspicion in communities of color about exploitation at the hands of biomedical establishments.
Lisa: The BiDil patent expired in 2020. NitroMed went out of business. Ferdinand still prescribes BiDil to his patients if they don’t respond well to other treatments. As for J. Cohen, he’s retired and living in Florida. Last year, last year he received a lifetime achievement award from the American College of Cardiology. He says he has no interest in doing anymore trials or studies around race.
Jay Cohn: So I learned my lesson now to stay away from race. It’s the third rail of biological studies. [laughs] Uh, I think it’s just too, it’s too inflammatory a topic.
Lisa: Creating a drug just for Black patients doesn’t eradicate structural racism, it helps further shape it. It shifts responsibility to the individual and takes it off society at large.
Jonathan Kahn: So, the great appeal of something like BiDil is like [laughs] oh, we’ve got this messy problem of racism that everybody’s very uncomfortable dealing with or talking about, so how do we fix racism? Do we fix it with a pill or do we fix it with sort of like very fraught and contested racial pol- pol- politics, right? Well, the, the, the appeal of a pill is very powerful under these circumstances. It lets you have this sort of conflict thr- free technologically managed way to sort of address racism that lets you off the hook for dealing with any sort of more complex or messier social issues.
Lisa: An individual solution allows us to ignore the real problem, and that has real consequences.
Jonathan Kahn: When you say it’s biola- there’s biological difference, it’s never just that there’s difference, there’s always a hierarchical aspect involved and that’s where I say, you know, Black being somehow less human than whites in a sense, less representative. You know, bad things happen when race and genetics get mixed, um, in a sort of sensualizing way.
