American Scientist

As an assistant professor of pediatrics at Howard University, Latifa Jackson is concerned with public health, but also with evolutionary biology and the genetic signatures of selection that can affect disease outcomes. Jackson is part of an initiative at Howard’s William Montague Cobb Research Laboratory called the 1,000 African-American Genomes Project, which aims to compare samples from different populations of current and ancestral Africans to determine differing allele frequencies. Jackson spoke about her research with American Scientist’s editor-in-chief Fenella Saunders at the Sigma Xi Annual Meeting in San Francisco in October 2018, where Jackson co-presented her group’s work with Cobb Lab director and biologist Fatimah Jackson.

How did you start looking at genomes, and what kind of genomes are you researching now?

My interest in genomes really predates even my dissertation research. I studied evolutionary biology, and I was in a lab that was interested in questions about human demography and human ancestry. From that perspective, I’ve always been interested in how you identify signatures of selection, which are these perturbations in the genome, in allele frequencies. But our understanding of those fields is really constrained by the populations that we’ve studied in the past. So that’s how I became interested in these kinds of questions about non-European populations. I know, as an African American, these are fundamental questions to our community. We’ve been thinking a lot about, well, how do we, as a population, identify our ancestry? What does it mean to be an African American? How is that potentially different from being, say, a recent African immigrant? Those are the kinds of questions that I started with.

At Howard University, one of the interesting opportunities is that they have modern African-American and African genetic samples, and they also have samples back to the 16th century. That’s not just one or two individuals—as there are for the Neanderthal genome project or the Denisovan project—but 400 individuals who lived in lower Manhattan in the 1600s and 1700s, and 700 individuals who were born right before slavery ended in the United States up until 1959. Then we have more than 2,000 individuals—modern-day samples— from the Washington, DC, area. It’s super exciting to think, “Okay, if we’re talking about health disparities, you have to have a temporal component to it, because what does that really mean to talk about these kinds of issues without any temporality?” That’s kind of how I bit into the subject. As we started to partner with National Geographic and the University of Copenhagen and a company called Helix, we had more opportunities present themselves in terms of the kinds of approaches we could use and the kinds of samples that were available. It unfolded like a carpet—a red carpet.

What are some of the health implications of having better data about genomes in the age of personalized medicine?

As Americans, we’re really excited by technology, and we’re excited by the promise of precision medicine. It’s telling us we can go directly after those kinds of disorders that plague us. If you read that President Carter, when he had a brain tumor, had great precision medicine and that helped him go into remission, that’s what everybody wants. But if we don’t make the investment on the front end, you’re not going to have that on the back end.

Personalized medicine is really predicated on the idea that we have a good sense of what the genomes of a diverse group are, within what are, sort of, sociological races. And then—having a sense of that variation—we know which variation within that is potentially pathogenic or which variation is just neutral mutation. There’s all of this local adaptation that can really give us insights into the recent population history of any particular ethnic group. And so we can harness both the shared history and the unique adaptive experience in order to better understand who we were as a species across the board. Our argument has always been that if we want to understand who we are as humans, then we need to better study those populations that we haven’t traditionally studied.

We don’t currently have good genomic information for African Americans, or Spanish-speaking Americans, or Native-American populations, or Asian-American populations. And so the question is, are we a society that cares about bringing everybody in? Because diseases don’t care who they’re infecting. We as a society have progressed enough to say, “We want to make sure that we can find solutions for every population, because they’re Americans and because that’s our civic responsibility.” But then also because there might be solutions in those populations that can help individuals from other populations.

How did the 1,000 African-American Genomes Project begin?

The 1,000 African-American Genomes Project came from this desire to understand African-American population structure. Anecdotally, we know that there’s a lot of structure that exists, or that people self-report. We want to try to understand how to negotiate between this oral tradition of population structure, of selective and assortative mating, with this idea that somehow African Americans are panmictic, and so to study a genetic sample from Harlem is the same as to study one from the Mississippi Delta. The only way to start addressing that was to try to select people from different places.

Luckily, we’re at Howard, so we have a lot of undergraduates and graduate students and faculty who were super excited with the idea that they could contribute to understanding what it means to be a legacy African American versus a recent African immigrant and how those two populations, from a genetic point of view, are similar or different.

What other groups are you including in the project?

We have a new collection, of Africans who were intercepted by the British as they were coming over in Portuguese slave ships in the early 1800s and taken back to a small island called St. Helena. Over the course of about a decade, 25,000 Africans were deposited there and repatriated to South Africa and Jamaica as liberated Africans. But 8,000 of those 25,000 died immediately. There’s a huge cemetery there, and they had excavated 325 individuals in the course of building an airport. This past summer, we were able to work with the government of St. Helena to extract teeth and petrous bones, an inner ear bone that has been shown to have really high yields of DNA in ancient samples. In all, from these 325 individuals, our graduate student collected more than 5,000 samples, and she got current residents of St. Helena to also contribute samples. We’re excited at this opportunity to get at what scientists always call the missing link. We have Africans that lived in the Americas for a while and Africans currently in Africa. But for that population in between, we don’t have a lot of evidence. If the ships went down then, they were lost. But through this project, they’re not lost. It’s really exciting that communities are willing to trust us with their samples and work on research questions with us.

Can you tell us the scope of the project? How many researchers are working on it with you, and what is your time frame?

We always think that our time frame is as short as possible. We’ve sought strategic partnerships to complete particular pieces. For example, we work with the University of Copenhagen, the world leaders on ancient DNA.

We realize this is kind of the project of a lifetime, which is to say that we’ll be working on some of it ourselves, but for some of it, we’ll have to try to attract great graduate students and great postdocs to work on it, so they can continue it. In terms of the number of people, this project is headed up by the William Montague Cobb Research Lab, directed by Fatimah Jackson, with about 40 to 50 students and associate researchers. We get undergraduate students, some of whom are not even biology majors, but who have a deep love of understanding complex questions, such as what are the epigenetic effects of trauma.

What the Cobb Lab tries to do is give people opportunities to explore questions that they wouldn’t otherwise have the opportunity to explore. We also have medical students, clinicians, engineers, computer scientists, mathematicians, historians, and sociologists working with us. We’re also writing children’s books. The National Parks Service and NASA scientists are working with us. A lot of the students in the lab are funded through National Geographic Explorer Awards. We’re just really excited by the interdisciplinary nature of the work we do.

These problems are hard. There’s a reason why we answer some of these questions from a demographic and genomic point of view in populations with reduced variation, because the answers were more clear-cut. With our project, we’re introducing incredible variation, and we’re saying, “Find the answers again.” But we’re all in.