To Reach Health Equity, We Need More Diverse Stem Cells. Here’s How We Get ThereNews
Even though modern medicine can now cure or alleviate many conditions that killed people only decades ago, the reality is that we have only gotten better at saving a subset of lives. A Black woman is 71% more likely to die of cervical cancer than a white woman, and nearly 65% of Puerto Rican children do not respond to the drugs used in asthma inhalers – examples that illustrate the racial health disparities that exist across the majority of measures of health outcomes.
“It is imperative that we do better at including and integrating the minoritized communities we have been missing, because our work is needed by a lot more people than we are effectively serving the way things are going,” noted NYSCF’s Vice President of Scientific Outreach and Diversity, Equity, Inclusion and Belonging (DEIB) Raeka Aiyar, PhD, as she kicked off a session on health equity at the 2023 NYSCF Conference.
“Ensuring disease represents the diversity of our global population is central to NYSCF’s mission and is the reason we created technology to enable stem cell research at the scale of populations,” she continued. “But having the technology isn’t enough, there are many obstacles to overcome.”
For the annual NYSCF Conference spotlight on DEIB in STEM, we convened a discussion, moderated by Dr. Aiyar, between leading geneticists, researchers, and patient advocates to talk about the obstacles, current initiatives, and society-wide benefits of diversifying stem cell biobanks. John M. Greally, DMed, PhD, FACMG (Albert Einstein College of Medicine), Ru Gunawardane, PhD (Allen Institute for Cell Science), Krystal Tsosie, PhD, MPH, MA (Arizona State University), and Teresa Wright-Johnson (Patient Advocate) emphasized the vast potential for discovery by including marginalized populations in research, as well as the cultural and ethical competencies that the biomedical research community must develop to effectively engage these communities.
Inclusion Leads to Discovery
When we don’t include ethnically diverse participants in research, we not only limit our understanding of how disease impacts different groups, but also how it impacts us all. Dr. Greally shared an example from recent research.
“I just learned an unbelievable story about families of Black men with prostate cancer. Colleagues at Louisiana State University discovered a genomic variant in a certain gene that acts as a tumor suppressor,” he shared. “If we had started studying prostate cancer in Black men, we would be calling this the gene that has to do with prostate cancer susceptibility — these variants have the same frequency as BRCA1 mutations in Ashkenazi Jewish individuals! And instead, it has taken until 2022 to come up with this insight.”
So how do we capture these critical genetic insights into disease models? Now that stem cells are so central to understanding genetics, a great opportunity lies in diversifying the stem cells we use for research. Dr. Greally is now collaborating with NYSCF to do just this.
“I started to talk to our NYSCF colleagues about how to build a possible diverse biobank. That led to the DIVERSTEM initiative that we are trying to get funded,” said Dr. Greally. “We have over 70,000 bags of cord blood cells at the New York Blood Center that represent this incredibly diverse population of individuals who were born in New York City over the last several decades. And those make ideal donor cells from which to make stem cells using the robotic technologies at NYSCF. We would like to be able to push forward on this because this will allow us to have an equitable generation of stem cells across seven ethnic groups, which represent about 95% of the US population.”
To do inclusive research, we also need better baseline measurements of human biology that account for natural human diversity when we are trying to distinguish ‘normal’ from diseased cells. Dr. Gunawardane is working to establish these baselines by ‘tagging’ all the major structures in cells and tracking them as they divide and differentiate into other cell types.
“In addition to looking at all the gene expression changes, if we can also look at intracellular organization, we can see what’s normal and what’s not,” she explained. “That way, by making these measurements and capturing the natural variation we see in normal cells we can hopefully predict pathologies much earlier than before – that’s the dream.”
“If we can all come together and create stem cell lines from diverse donors that have different genetic backgrounds, I think we can really expand what our definition of ‘normal’ is, and we’ll be able to define when certain cellular structures are outside of that distribution.”
The Humans Behind Research
All of this work is done for one reason: to help patients. If we are to do this effectively, it is paramount that we engage with patients from the very beginning, and keep them top of mind through every step from bench to bedside.
“As you are in your labs and doing your work, I just want you to realize that every cell that you’re studying, every case that you have, it’s attached to someone, it’s attached to someone’s history,” noted Ms. Wright-Johnson, a longtime patient advocate. “And I think we really need to humanize this space with faces, with stories, and with people sharing their perspectives. That’s not only to change medicine, but to change the entire healthcare ecosystem.”
“We have an obligation to humanize medicine and research,” she continued. “It’s the stories of the people who we are studying that really make the difference. Cultural competency is 100% a necessity. You really have to understand who you are studying for best health outcomes.”
And while including diverse populations in research is critical, we need to get to know the communities we are researching as well, as many have undergone a long and horrific history of exploitation and abuse from the medical and research communities. Minorities are not monoliths: each community has their own unique perspective on biomedical research and hesitancies for participating in it. Dr. Tsosie’s work as an Indigenous geneticist places great emphasis on Indigenous data sovereignty, which recognizes that communities have intrinsic agency in data decisions concerning its members.
“For a very long time, we were asking people to contribute their samples and data to research, and then asked them to sign a blanket statement allowing researchers to use this for any other research that benefits humankind,” pointed out Dr. Tsosie. “Then we would turn around and use those samples and data for things that the community never consented or agreed to begin with. We never asked whether the communities are benefiting proximally from that research or whether we’ve developed trust partnerships to warrant that use in other contexts.”
“There have been many instances where cell lines have been taken from Indigenous peoples with the promise of delivering therapeutics to cure the conditions that are afflicting them. Those communities have unfortunately stated that they felt duped and exploited because they have heard that other people, like researchers and companies, are benefiting from the use of their cells before they are, sometimes in the form of commercial gain,” noted Dr. Tsosie.
Rebuilding the Lost Trust
Dr. Tsosie is seeking to build back trust amongst communities and engage them from the beginning of the research process to determine which health issues matter most to them and how to update research practices to ensure culturally-safe approaches to participating in research.
“I co-founded a non-profit organization called the Native Bio Data Consortium, which is Indigenous-led with community members and scientists. We brought high-throughput sequencing to a rural Tribal Nation for the first time. We’re talking about -omics research that looks at social and structural determinants of health along with biological factors in health. Who better than to partner with communities themselves for informing these questions that impact their health than them?”
Building back trust will need to come from a place of honesty, empathy, and a willingness to learn.
“There has to be a lot of humility in the space. I’ve done this without a PhD for a large portion of my research career, and now I have been conferred an academic-colonial status that is recognized by other researchers. Yet, I acknowledge that when I talk to an elder, they are the experts in seeing the long-term impacts of colonially-driven changes to our traditional lifestyles, not me,” shared Dr. Tsosie. “And I encourage everyone to do the same as well – approach communities with humility, openness, and without overpromising on something related to precision medicine that we cannot deliver on. That’s how we build trust moving forward.”
“First, you build trust through authenticity,” added Ms. Wright-Johnson. “You make your intention known, and you follow through with that.”
“Second, you build trust by knowing the community that you are trying to serve, by humanizing your work, by telling these communities and showing these communities that you are more than what you say, that you’re willing to go the distance.”
“Third, and I think the most important part, is to acknowledge a person’s history and the things that they’ve gone through in the past. We cannot deny the medical mistrust and the trauma that so many communities have endured. So, it doesn’t mean that you have to be responsible for the things that occurred, but you have to acknowledge it in order for us to truly move forward and not repeat the mistakes of the past.”
Looking Ahead: Engaging Stakeholders and Educating Researchers
“Another challenge that can really slow progress is people working on this in silos when we could be working together. How do we partner on this work better with all of the stakeholders in health equity to achieve what we cannot on our own?,” asked Dr. Aiyar.
“Partnerships are the key to moving forward,” remarked Ms. Wright-Johnson. “You can partner with your community advocates, with organizations who prioritize patient-centric care, with research organizations like NYSCF – there are so many opportunities out there.”
“I think that at the funder level, there is a will, but it’s not enough just yet,” added Dr. Greally. “We need to have more investments. These are not cheap things to do because we have to have an extensive layer of engagement with and oversight by community participants. That sometimes looks like ‘fluff’ on an NIH grant, but it’s actually the bedrock.”
To effectively move forward, educating ourselves on these topics is also key.
“When it comes to these topics, there’s so much we just don’t think about as scientists in our everyday lives. There’s so much opportunity to learn and educate ourselves on the broader implications of the science we do or want to do. The good news is that we scientists are very curious people,” said Dr. Gunawardane. “The discussions we’ve had in the last few months with some of you have just opened up our minds. So I think partnerships and discussions like this are hugely beneficial and we should all share what we are learning with our own scientific communities.”