For a multitude of reasons, Black people, as well as other minorities, are underrepresented in medical research – everything from “GWAS” (Genome Wide Association Surveys) studies to look for genetic variants making people more or less susceptible to various diseases, to clinical trials testing the efficacy of various drugs. This holds true even when they’re more likely to be affected by the diseases the drugs are designed to treat, and this could have profound health effects.
Case in point, that awesome scientist I was telling you about, Dr. Namandjé Bumpus, who was recently appointed Director of the Department of Pharmacology and Molecular Sciences at John Hopkins Medical School!, has dedicated a lot of research into genetic variants in drug-processing proteins called cytochromes, which are responsible for the metabolism (chemical modification) of pharmaceutical drugs once they get inside your body. Different people have different genetic variants of these cytochromes and she’s found that one such variant, CYP3A5*1, which almost 1/2 of African Americans have 2 copies of, makes their bodies better at “detoxing” an HIV treatment & pre-exposure prophylaxis drug called maraviroc (trade name Selzentry). https://bit.ly/2VpoM06
This might sound good, but “detoxing” the drug means their livers chemically modify the maraviroc into a form which, instead of preventing or treating HIV infection by blocking HIV from getting into cells, just gets removed from the body. Basically, their cells are “too good” at getting rid of the drug. So if you give them the same dose of maraviroc as you give someone with the CYP3A5*3 version of the cytochrome gene (a genetic “dud” that is prominent in European Americans and leads to 80-90% of them not expressing functional CYP3A5 at all) the African Americans with the “good” gene will have less of the active drug in their system, leaving them less protected. And, if you only test out the drug on White people, you’re not going to figure that out during the dose-finding stage of clinical studies.
And the clinical study that maraviroc was approved based on, the MOTIVATE trials? Wanna guess how diverse they were? 85% of the people in the study were of European ancestry! 85%! And this is despite the fact that African Americans are more likely to *have* HIV than European Americans!!!!!!! https://bit.ly/2NAm9Eg
That was *not* okay with Bumpus – so she recruited volunteers with different versions of the gene, gave them marivoric & then checked their blood at various timepoints to measure levels of the active drug as well as the CYP3A5-inactivated version (metabolite), M1. She found that those with 2 copies of CYP3A5*1 (~45% of African Americans) had higher levels of M1 & lower levels of the active drug. How much lower? She found that ~1/3 had levels below the target level considered to be most effective. So, if dosed based on the dosing guidelines, 1/3 of the ~45% of African Americans with 2 copies of CYP3A5*1 could be under-treated!
Thankfully, the difference in metabolism doesn’t appear to affect patient outcomes, which we only know because Bumpus’ study drew attention to the issue and got drug manufacturers to actually look into it. https://bit.ly/2ZjED1e
And this is just one example. Bumpus and others are also raising concern that Black Americans, who are disproportionately becoming severely sick and dying from COVID-19, may be underrepresented in clinical trials for coronavirus treatments. Including for treatments that are known to affect Black populations differently. For example, consider that steroid drug you might have heard about, dexamethosone, which seems to help counter the overactive immune response called a “cytokine storm” that makes some coronavirus patients really really sick. There is some evidence that African Americans may respond less to this sort of drug. https://bit.ly/2ZiWTYA And, if we don’t include African Americans in trials of the drug at representative levels, we won’t know if they’re being treated effectively.
The NIH recently announced an initiative to expand COVID-19 research in underrepresented communities try to address some of these disparities. https://bit.ly/2AcdYuU But their roots run deep…
The history of Black participation in medical research is, well, disgustingly complicated. For years and years, they were excluded outright from official studies, with “unofficial” and highly unethical experimentation done on them, such as the “research” on vaginal fistulas performed by the “father of gynecology,” Dr. Marion Sims. He perfected his technique on unanesthetized slaves (up to 30 times on one single patient!) before he started using it on White women (with anesthesia)). https://bit.ly/2Zdr57F
When Black people *were* included in “official studies,” they were sometimes treated more like lab rats than human beings. For example, in the Tuskegee Syphilis Studies, which only ended in 1972, Black men with syphilis were denied curative treatment and were instead given fake “treatment” (for “bad blood” – they weren’t even told they had syphilis). They were monitored (through to autopsy) to determine the untreated disease’s effect on Black people, long after 1) there was a cure and 2) it was clear that the disease didn’t affect Black people differently. https://bit.ly/tuskegeeexperiment
This whole idea that Black people are almost a different “species” of human has been used for centuries to justify the racist and inhuman treatment of them in all aspects of society, including medicine. For instance, one reason Marion Sims didn’t give the slaves anesthesia is due to the prevailing myth that Black people don’t feel pain the same way as White people. This myth also allowed slave holders to make excuses for working their slaves to the bone. And it perpetuates to this day – a recent study found that many doctors *still* believe Black people feel less pain than White people, leading these doctors to be less likely to prescribe Black people adequate pain medicine. https://bit.ly/2YAXjKU
It’s important to keep this history in mind when we go to talk about disease disparities between racial groups. Because there *are* disparities – but these disparities have nothing to do with “blackness” or “brownness.”
Many of the disparities come from systemic racism leading to socioeconomic inequality undermining the health of underrepresented minorities (URMs) including Black and Hispanic Americans, as well as Indigenous Peoples and many others which I apologize for leaving out. In the game of “social determinants of health,” URMs loose big-time, thanks to centuries of White people establishing themselves (and their wealth) in America on the backs of slaves and URM laborers. For example, Black and Hispanic people are more likely to live in “food desserts” where there isn’t fresh, healthy, food available nearby, are less likely to have easy access to medical care, and are (unsurprisingly) more likely to have diseases such as obesity and diabetes.
These socioeconomic factors play a large role in disease disparity, but they don’t tell the entire story. As Bumpus’ work shows, there *are* genetic factors that can make certain people more susceptible to certain diseases, BUT these factors have nothing to do with “race.” Instead, they have to do with which genetic variants are more prominent among certain populations.
Our genetic blueprints are written in DNA, which is super duper long with stretches of DNA serving as “recipes” for things like proteins (kinda like chapters in a cookbook). Each time a cell wants to make a new cell, it first has to copy all that DNA. And sometimes it makes mistakes. Genetic variants (aka polymorphisms) are the result of random “mutations” that happen during the DNA copying in germline cells (i.e. during the egg- or sperm-making process). “Mutation” sounds scary, and in some cases, mutations *can* be scary, but the vast vast majority of the time they don’t have any harmful effect, and in some cases they can even be beneficial. If it weren’t for random mutations in single-celled organisms, then multi-celled blobby things, then all sorts of other extinct species, humans couldn’t even have evolved!
Even after humans evolved to be humans, we continue to acquire mutations, which we can pass along to our offspring. Each child inherits 2 copies of each genetic “recipe” for each protein (one from each biological parent). These “recipes” are called genes and the different versions are called alleles.
The only thing preventing alleles that are prominent among Black populations from being more prominent among White populations and vice versa is segregation – it is nothing “biological”. Segregation has led to Black people in America being more likely to have children with other Black people and White people to have children with other White people. So, if a certain mutation randomly arises in one of the White people, it will get passed along more among White people than among Black people.
And this is what happened in that HIV-drug case I was telling you about. African Americans are more likely to have copies of the “non-mutated,” fully functional, CYP3A5*1 (at least one & almost half the time 2 copies). But European Americans are way more likely to have mutated versions of CYP3A5 such as the CYP3A5*3, CYP3A5*6, or CYP3A5*7 alleles, which contain single DNA letter changes that lead to CYP3A5 being inactive or expressed at super low levels. In science jargon, we can say that these mutant versions have a higher “allele frequency” among European Americans, which leads to them make less functional CYP3A5. With less of this “detoxer,” they build up higher levels of the drug, which makes it longer-lasting. But for people who have 2 copies of the active detoxer (i.e. people who are heterozygous for the CYPSA5*1 allele), their bodies clear the drug from their system more quickly, potentially leaving the patients unprotected. And these potentially-unprotected patients are predominantly black – only 1% of White people and 5-15% of Asians have this combo
Note that, for this case, I’ve switched to speaking in terms of “African American” and “European American” instead of Black and White. This was intentional – because not all Black people are African American and not all White people are European American. Our systemically racist society tends to view all Black people as the same (both figuratively and literally – misidentifications of Black people by police, etc. are way more common than for White people because our society doesn’t invest in taking the time and energy to actually look and view them as individuals). But Black people are not all the same and there is a vast diversity among them. Including genetic diversity. Allele frequency is going to vary among different groups of Black people, depending on where the mutations arose, etc. This underscores the importance of making sure we include as much genetic diversity as possible in medical research.
At the same time, it is crucial that we address all of those social problems contributing to poorer health outcomes.
In addition to leading to worse disease prevalence & severity, socioeconomic problems can contribute to lower inclusion levels in medical research, which further compounds inequality in effective care. For example, clinical research opportunities at this time are largely centered in predominantly white-serving medical establishments. So, in addition to not being included in basic research studies to do things like look for genetic factors impacting disease outcomes & risks, URMs are less likely to have access to “groundbreaking” treatments. Other socioeconomic factors like lack of transportation or childcare make it harder for many URMs to participate in trials and, when they try to participate, they might be excluded because of preexisting health conditions https://bit.ly/2ZiWTYA
But fixing these infrastructural problems (adding more trials at minority-serving medical centers, offering transportation, etc.) isn’t enough to solve the problem. The medical field needs to build trust from the Black community, which involves true investment in the cause, including, among other things, increasing the representation of Black people among the ranks of doctors and in positions of power within the medical establishment.
Final note: It’s easy to try to compare this situation to the situation of women being underrepresented in medical research – and I’ve seen a lot of people do this. But it’s important to recognize that efforts to get more women involved did not mean that more minority women are being involved. And White females DO NOT know the discrimination faced by racial and ethnic minorities. It is not right to try to compare the two and/or use femininity as a “I know what you’re going through” type of thing – you don’t. So don’t try to “lessen” their experiences – don’t interrupt their stories of discrimination to tell your own. Listen to them. And act! Any White woman who fought for female rights and inclusion better damn well be fighting for minority rights and inclusion.
If you want to learn more about Dr. Namandjé Bumpus:
If you want to learn more about all sorts of things: #365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0