OmicsXchange Season 2, Episode 1: Together for CHANGE: sequencing the African American genome with Lyndon Mitnaul and James Hildreth Sr.

28 Feb 2024

In this first episode of season 2, we speak with James Hildreth Sr., President and CEO of Meharry Medical College, and Lyndon Mitnaul, Executive Director of Research Initiatives at the Regeneron Genetics Center. Hildreth and Mitnaul lead a new multi-institution project called Together for CHANGE, which aims to sequence the African American genome and build capacity to overcome inequities in STEM careers.

Angela Page  00:04

Welcome to the OmicsXchange. I’m Angela Page, and today we’re joined by Dr. James Hildreth Sr. who is President and CEO of Meharry Medical College, and Dr. Lyndon Mitnaul, Executive Director of Research Initiatives at the Regeneron Genetics Center. Dr. Hildreth and Dr. Mitnaul are our leaders in a new multi-institution project called Together for CHANGE [T4C], which launched in October 2023. The initiative brings together Meharry Medical College, Regeneron Genetics Center, AstraZeneca, Novo Nordisk, and Roche to create better health care and outcomes for African Americans, and to address inequities in STEM careers and research. Welcome, and thank you so much for joining us today. 

Lyndon Mitnaul  0:44

Thank you for having us. Pleasure being here. 

James Hildreth Sr. 0:48

Thank you, Angela. 

Angela Page  0:49

Dr. Mitnaul, would you like to go first and introduce yourself?

Lyndon Mitnaul  0:52

Sure. I’m Lyndon Mitnaul. I’m a part of the Regeneron Genetics Center here in Tarrytown, New York. You know, just some brief history on me, besides your lovely introduction is I’m a graduate of a Historically Black College & University (HBCU) Benedict College in Columbia, South Carolina, where, you know, I got my first exposure to research and that exposure to research and training really sparked the interest in helping to develop this initiative with Meharry and our other corporate partners.

Angela Page  01:27

And Dr. Hildreth?

James Hildreth Sr.  01:28

Thank you, Angela. I’m an immunologist by training. My research for the last almost 40 years has been focused on HIV pathogenesis. I did my undergraduate studies at Harvard and I became the first Black Rhodes Scholar from Arkansas. So I went to Oxford University, and did my PhD there with Dr. Andrew McMichael. I came back from Oxford to Johns Hopkins Medical School where I was a student, postdoc, and faculty. I came to Meharry Medical College for the first time in 2005, as the founding director of the HIV center, and I left temporarily  to go to UC Davis [University of California, Davis], as Dean of the College of Biological Sciences. And they brought me back as president in 2015. My work has been focused from the beginning on making sure that there’s diversity in research, diversity in health care, diversity in those who provide care. So, really happy to be a part of this program.

Angela Page  2:21

Thank you so much. So to start things off, could you tell us what Together for Change is and how you’re both involved.

James Hildreth Sr.  02:30

So, Together for Change is an historic partnership between an HBCU and four amazing pharma companies. Its purpose is to make sure two major things we hope to accomplish. One is to create a diverse data set of human exomes and genomes, to make sure that the amazing discoveries that will come from such datasets will benefit minorities and people of African ancestry, as well as Europeans. The other part, which I think is equally important, if not more important, is to bring diversity to STEM fields around genetics, genomics, data science, and artificial intelligence. For me, this is one of the most important things I’ve been a part of in my 40-plus-year career because it’s going to have a generational impact. And I’m so happy to be working with my colleague Dr. Mitnaul now who brought this to our— brought this opportunity to my attention almost four years ago.

Lyndon Mitnaul  3:22

Yeah, I’ll just add on to that, and emphasize — re emphasize that, you know, there’s two components to this initiative, which really differentiates this from other, you know, programs or even genetic studies ethnic studies. So, this is a genetic study, as Dr. Hildreth mentioned, we’re going to sequence the largest ever, people of African ancestry cohort, so 500,000 people of African ancestry will be sequenced. But in— in addition to doing that genetic study, and providing that data exclusively to our minority institutions, we are going to be also developing new STEM pathways, pathway programs. So you’re building a resource, and you’re actually building the scientists, so that the scientists have something to study. And that’s why this is a 10-year commitment. For this initiative, it’s not something that’s gonna you know, just change what we want. It’s not going to happen within two or three or five years. It’s a 10-year commitment here to keep communications to look for other additional opportunities. This is a starting point. But we’re hoping that we could build off of this platform and do other collaborative things together.

Angela Page  04:37

Great, and I love that it is sort of two sides of the same coin. It’s too often it’s been the first side only and not really building the capacity. Could you tell us how the project got started? Dr. Hildreth, you mentioned that Dr. Mitnaul reached out to you four years ago. And that sounds like an interesting conversation. How did this project get going? 

Lyndon Mitnaul  4:55

Yeah, yeah. So let’s go back, you know, three and a half, four years ago now, and look at where our country was and where — where science was. You know, we had the— the social justice movement happening after George Floyd’s murder. And lots of companies were looking for things to do, and including Regeneron. And, you know, the good thing about I think, Regeneron, is that we have a diverse group of scientists here and employees, that our senior leadership, actually, we have access to our senior leadership. So, you know, our senior leadership asked for what— what could we do to really make a difference? And, you know, I thought about how did I get here, coming from an HBCU going to a large pharma company. I worked at Merck for 15 years and cardiovascular diseases research, then came to Regeneron, some 10 years ago to help establish the genetics center here. And, you know, I said, How did that happen? And what were the things that were offered to me that got me here? That’s one. 

And then two, what are the tools that we uniquely have here at Regeneron, that can really make a difference. And being in the genetics research space, we all know if you’re studying genetics, that there’s not a lot of genetics of a lot of different minority groups or other groups. So— so I put the two together and said, Let’s have a program where we can build more genetics, data, as well as build more scientists to study that data, and offer them the opportunities that were offered to me. So that’s how it all came about. But then we had to find that partner and— and that’s when we looked at, you know, who could we partner with here. And Dr. Hildreth’s name easily floated to the top.

Angela Page  6:43

So this is obviously a very historic project for many reasons. And I think that last aspect that you just mentioned, is one that I’m curious about, which is, you know, pharma companies who are often in competition with one another coming together to do this. How did you make that happen? And what are sort of the unique characteristics or features of this project with respect to that commercial piece?

Lyndon Mitnaul  7:04

Yeah, it’s not easy, let me just say, and, and it continues to be not easy, but not impossible. So I think if you if we, what we did was stay focussed on the science, look for the win-win for both sides. And we have to start so with— with, as you know, with a genetic study like this, this is research based, it’s all about research here. So there’s no commercial, anything here, right? Things can come from this. But, you know, that’s downstream of the research that we’re doing here. And so you just got to find those corporate partners that are— are understanding that and most do, we have other and we have history here, where, you know, Regeneron, helped to establish the whole Exome Sequencing Consortium for the UK Biobank. So we brought companies together— eight companies together to do that. And that was a model for us. And we said, hey, we— we learned from that, let’s do that again, here. And— and you see that everyone is using the UK Biobank resource for internal research purposes. And yeah, things may come from that. But again, that’s downstream and outside of any intellectual property.

James Hildreth Sr.  8:17

And, Angela, if I might mention that, what you’ve heard from Dr. Mitnaul, that’s the reason why diversity is so important. Because when people who look like us are not sitting in the room, these kinds of things will not happen, and Dr. Lyndon did not take it upon himself, to bring this to the attention of the leadership at Regeneron. It may have happened, but the chances are that it might not have and this is why having scientists like Lyndon, in rooms where these kinds of decisions are made is important. And as— as I said at the launch of this initiative, we are determined that this time, people of African ancestry will not be on the outside looking in, when the amazing outcomes of the research from— from these datasets are brought to bear for the public good. So this story is a great example of why diversity is so very important. At all levels. 

Angela Page  9:13

Yeah, it’s a success story, for sure. So this project aims to improve health outcomes for people with African ancestry. Who will own the data in the end? Will it be those people who are contributing their own sequence data? And how will you ensure that the data feeds back into positive outcomes for the target community? So you know, we’ve talked about like, this is the goal, but what is the sort of the tangible actions that you’re going to take to make sure that that actually comes to fruition?

Lyndon Mitnaul 9:38

Yeah, so data ownership would be through the DHGI, this new 501(c)(3) institute that was formed by Meharry— chartered by Meharry – called the Diaspora Human Genomics Institute. So this 501(c) nonprofit is the contracting, managing, organisation for Together for Change. They will contract with the different organisations that will be recruiting sites for this cohort. So, say University X is going to be recruiting, you know, 20,000— 50,000 participants, they will send that data to Regeneron, we will sequence it, but that data goes back to the DHGI. 

Angela Page  10:21

Actually, that leads nicely to my next question, which obviously, I assumed that the data are going to be consented for sharing. But how will you make sure it’s accessible first and foremost, to the African and African American research communities? Is there any kind of like measures in place to make sure that that’s the priority research population that gets to see the data at first? 

Lyndon Mitnaul  10:41

Yes, so — so through the DHGI membership, again, we’re hopeful that the majority of our HBCUs would join the DHGI. And then by joining the DHGI, and— and showing that they can ingest this data in and secure that data, they can get access to this data. We’re not making this data publicly available, like the All of Us study, for example. It is exclusive for the DHGI membership in this purpose — for we did this on purpose, because what we don’t want to happen is if other groups — major institutions get access to the data, like the All of Us study, they will analyse the data, publish on that data and bring in funding to their organisations. 

We’re providing this dataset exclusively to our HBCUs and institutions in Africa that are part of the DHGI, so that they can determine who they would like to share it with. So we’re giving ownership to the DHGI members like Meharry could share it with, say, Vanderbilt, their neighbor next door. But let’s leave that up to Meharry versus letting it be open access. And then Vanderbilt gets the data they analyse it and, and, you know, there’s no publications— no funding coming to Meharry. So it was designed this way on purpose not to keep people out. But to ensure that we have a collaborative ecosystem that’s focused on our schools that are building capacity for research and genomics research.

James Hildreth Sr.  12:18

And if I can add that one of the most important things here, I’ll just emphasise, but when Lyndon said, is to make sure that African American and minority scientists have a chance— have the first chance to use the data to advance their scholarship and also have an impact on communities. At the end of the day this is about making sure health equity is achieved when it comes to interventions, drug discovery, and other things that can come from datasets like these. And that’s why the other part of this is so important, making sure that we have programs that excite and motivate young people to pursue careers related to this, which as I said before, it’s really exciting for me.

Lyndon Mitnaul  13:02

If you really look at, you know, what is the true benefit of research, it’s having better drugs, better diagnosis, better test for— for different diseases, right. So— so pharma, the pharma industry, I believe, has to be a part of this equation, because otherwise you’re going to have this big dataset that people are studying, but nothing is being translated into, you know, helping people’s lives. So that’s where these companies— our four companies AstraZeneca, Novo Nordisk, Roche, and Regeneron have really committed to doing this. And— and really, yeah, we want to take this information, we do want to better health for people of African ancestry. 

Angela Page  13:45

Thank you. Dr. Hildreth, you mentioned, you know the STEM component of this that you’re really excited about, I wonder if you could tell us just a bit more about the opportunities that you are creating for Black students. 

James Hildreth Sr.  13:55

So there are a number of things we’re going to do one of which is to create programs related to genomics for K through 12 students. But there are also going to be opportunities for students from all 107 HBCUs to get involved in research, that’s going to be sponsored by and funded by resources through the DHGI. I’m— I’m excited to expose K through 12 children to this because one of the things that has motivated me is the understanding that students cannot get excited about something they’re not exposed to. And imagine exposing these kids to this amazing kind of research in STEM at an early age. When I was Dean at University of California Davis, I went out and visited schools to talk to kids about science and research. I was very impressed by one school I visited in which third graders were writing code. I mean, can you imagine third graders writing code completely unintimidated by it. It just— I mean, it was the most amazing thing for me, it was really an eye-opener. And I wondered how many Black and Brown kids in the third grade around the United States were getting an opportunity to learn to code, right? And these kids will not be the least bit intimidated from this point on. But anything related to that. So that’s why I’m so excited about this, because I’m sure that coming out of this will be some amazing scientists, physician-scientists, and otherwise, I wouldn’t even believe it was possible for them, except for these programs. That’s why— That’s why I’m excited.

Lyndon Mitnaul  15:30

Yeah. And if I may add on, you know, to Dr. Hildreth’s point, I think, you know, you got to see it, to believe it to achieve it. And I think, you know, this program has an opportunity to do more of what Dr. Hildreth just— just said, in his experience, for example, we all attend conferences, right? We go to American Society of Human Genetics [ASHG] meetings, and, you know, neuroscience, and, and so forth. This program is going to say, okay, when we have the ASHG meeting and say, Colorado next year, we’re going to have some folks that are part of this initiative, to go to target schools in Colorado, to actually inspire those students— to show students that look — you know, I look like you I’ve come from communities like you, and and I’m now a scientist. And— and help build those mentorship relationships that, again, Dr. Hildreth mentioned, that is so critical to inspire the students to say you can do this too. 

So we have K to 12 programs like a National Science Fund, that’s being— that’s a part of this initiative where funding can be given to the schools to buy microscopes. $5-10,000 grant to— to schools can really make a difference to help students go to a science museum they’ve never been to because they can’t, right? So, we have— that we have the DNA Learning Center, we have the high school internship programs. Starting at Meharry. Meharry has magnet high schools in Nashville where we’re going to support students coming to Nashville, to Meharry to do hands-on biomedical research. We’re going to have the HBCU scholars internship program, we’re going to have— we have funding for the first joint genetic counselling training program of the 107 HBCUs across our nation, none of them have a genetic counselling training program. And that’s why probably less than 2% of the genetic counsellors are Black in the US. So— so that’s going to start we’re going to have the first medical genetics fellowship program at Meharry. Work, physician sci— physician-cientists and physicians at Meharry can learn about genetics and how to apply genetics and clinical practice. So there’s a lot of things here. 

And that’s why I’m saying it’s not just a genetic study. The genetic study is the bonus. But all of these other community benefit programs are going to make — I think the real difference here, and is going to build these scientists. And when these scientists come out and say 10 years, they’re going to have this resource now that they can study. 500,000 people’s sequence data linked to electronic health record and other phenotype data, that’s going to be a rich resource for them to study and build their careers.

Angela Page  18:28

So obviously, you know, scientific history has not always treated the Black community with the appropriate amount of respect. And I’m just curious how do you build trust with a group of people that has been taken advantage of so much in the past? 

James Hildreth Sr.  18:41

So, Angela, the first thing that we did, as part of this initiative, is to create an ethics advisory committee, recognizing that what you say is— is true. And Reuben Warren, who’s the former director of the Tuskegee Institute for Bioethics, he is leading our efforts in this.  We couldn’t have asked for a better person to keep us on track when it comes to ethics.

During the pandemic, one of my tasks that was assigned to me was to convince Black and Brown people, they should accept the vaccine, because of this mistrust of medical research, and people talk about the— you know, the Tuskegee initiative that was put on by the Public Health Service. It was not Tuskegee that did it, it was actually the National Public Health Service. And then there’s involuntary sterilisation of Black and Brown women. But I tell people, you can find examples of this to go all the way back to 1619 for God’s sake. So we have every reason to be mistrusting and distrusting a medical research. But I was able to show people— this— our people this time that this time was different at every level of, of, of this. 

From Kizzy Corbett [Kizzmekia S Corbett-Helaire], who was a Black woman involved in vaccine research, to the data safety monitoring boards, to the VRBPAC [Vaccines and Related Biological Products Advisory Committee] in the FDA, which I was a part of still a part of. We had a voice, we ran the table— at the table on every stage that made a difference. So it comes down to having people who can connect with culturally and otherwise, to the population, engaging them in these conversations. 

For 148 years Meharry Medical College has established that it’s trustworthy when it comes to our populations. And I believe that’s part of the reason why our organisation was chosen to be the partner in this. Because we have demonstrated our commitment to the welfare of Black folks. 

Lyndon Mitnaul  20:45

When we first started this initiative, and Dr. Hildreth, who remembers this, the name was not Together for Change, it was Be the Change. And it was Be the Change on purpose to get to your point, but of the question, Angela, and that is, you know, we can’t wait for others to make this change. We have to We— the Black community has to build that trust. And we’re going to have to build that trust with the Black employees in these pharma companies and these other corporate organizations, with our schools, with our civic groups, with our faith groups, we have to drive this change. 

And I believe, if we change that perspective, in 10 years from now, we will have people talking about Together for Change versus the Public Health Study on syphilis, or the Henrietta Lacks. Okay, we were gonna say we had that. We learned from that, and then we put together for change together. And it’s not only a model for African people—  African ancestry, you know, it’s the same hesitancy with Native Indigenous people, it’s the same hesitancy with Hispanic and some Asian— South Asian communities. So this is our catalytic movement that we can have now, that could, you know, resonate across a lot of different ancestral groups.

Angela Page  22:16

This leads directly into my next and last question, which kind of trying to bring it back to GA4GH a little bit. We build tools and expand responsible use of genomic health data through standardisation. But it’s a global community. It’s an international effort. And I think, for you know, many, many reasons, it’s very difficult to get the “global” in GA4GH, to be really at the forefront. And so as you’re talking about this as a model for engaging those communities that are not necessarily present at these tables, always, I wonder what advice you have for our global community that we should consider when trying to engage these historically marginalised groups and genomic research occurred sort of across the world, when we sort of take it out to this bigger international scope.

Lyndon Mitnaul  23:06

I think everyone has their initial major concerns that are probably different across different groups, ancestral groups. So first, start by listening. And then I would say, link in with organisations that people trust. This is to our point with Dr. Hildreth and Meharry Medical College, we— we— we can’t just as Regeneron and at AZ {AstraZeneca] and Novo and Roche go and do this on our own. So I would say you have to listen to their concern. Link in with community, you know, organisations that they trust, and then start there, and then start and build, I think if we try to do everything at once, it usually is not going to work. So start small— build on it.

James Hildreth Sr.  24:04

And Angela, the partners in places like Africa need to know that you are trying to create a sustainable change. In my time at my former institutions, I witness as part of [U.S. President’s Emergency Plan for AIDS Relief] PEPFAR that investigators would go to Africa, parts of Africa, do the research they intended to do get their papers published, they come back to the US and there was none— the people that they were interacting with the none the better off for them having been there. And billions of dollars have been spent on these programs. 

So our approach is just what Lyndon said, is to listen, but also have what I call cultural humility. Many places people have answers to the problems they face — what they lack are resources and capacity. So we start with the end in mind, which is always a sustainable change that we’ve put in place we— we are present now Afri— in Zambia, and Malawi, doing HIV, preventing HIV transmission from mother to their babies. And we’ve achieved I don’t know, we’ve gotten it down to 99.5% reduction in transmission in the places that we are, which as you know, is an amazing result.

But part of it was because we got the folks in Zambia to take care of their fellow citizens and fellow community members. And that made all the difference in the world.

Angela Page  25:27

This is— this is great advice. Thank you so much. This has been an absolutely stunning conversation. I’m so— so happy to learn about what you guys are doing and really excited to see how it all plays out. I hope that we can stay in touch and maybe talk again once— once the project is kicked off and hear how it’s going.

James Hildreth Sr.  25:46

Absolutely.

Lyndon Mitnaul  25:46

Absolutely. Yep. Thank you for having us. 

Angela Page  34:19

Thank you for listening to the OmicsXchange, a podcast of the Global Alliance for Genomics and Health. The OmicsXchange is produced by Connor Graham and Stephanie Li, edited by Biljana Gaic, with music created by Rishi Nag. GA4GH is the international standards organization for genomics aimed at accelerating human health through data sharing. I’m Angela Page and this is the OmicsXchange

Resources:

Together for Change Website