When scientists set out to sequence the entire human genome in 1990, it was considered an undertaking on par with splitting the atom or landing on the Moon. They finished in 2003, two years ahead of schedule. Within another 10 years, researchers had harnessed a biological tool called CRISPR-Cas9 to “edit” human genes. And just three years after that, Chinese scientists deployed the same gene-editing tool in an experimental treatment for lung cancer.
Our understanding of human DNA has progressed at breakneck speed, revolutionizing forensics, revealing our ancestral connections, and launching the field of medical genetics. And with the advent of CRISPR, highly targeted gene editing has become possible. The implications are tremendous.
But as the science races forward, once-hypothetical ethical concerns are quickly becoming reality. In 2018, Chinese researcher He Jiankui shocked the world when he announced the birth of twin girls from embryos that had been gene edited in an attempt to make them immune to HIV. Though He and two of his colleagues were widely condemned and sentenced to prison, other “rogue” scientists could still follow suit.
“That should not have happened; it just shouldn’t have,” says geneticist-bioethicist Krystal Tsosie. Like so many scientists, Tsosie, a soon-to-be post-doctoral researcher at Vanderbilt University, advocates for a pause on germline editing—making genetic modifications that are passed on to a person’s offspring—at least long enough for society to ask itself some essential questions. What are we aiming for when we seek to edit life? What makes a human being “n*ormal,” “healthy,” or “ideal,” and who gets to decide what that means?
NOVA spoke with Tsosie, who is an enrolled member of the Navajo Nation, about how Indigenous culture, gene editing, and bioethics converge, and what it might take to #DecolonizeDNA.
Alissa Greenberg: Were you always interested in science and genetics? What drew you to this area of study?
Krystal Tsosie: When you’re Navajo in particular, there aren’t that many Indigenous people or Native Americans in the education pipeline and higher education. So of the higher degrees that were encouraged from people like myself growing up, either you were encouraged to become a doctor, a lawyer, an engineer, or an educator. And I was on the route of becoming a physician. I just loved understanding what it was that caused disease.
I was actually starting off in the cancer biology track, but there was a point in time where I realized if I wanted to pursue a career in cancer biology, that I would encounter the dilemma of, how do I innovate technologies that would not benefit my people? Because even if in my lifetime I were to develop something that could help somebody with cancer, chances are that…it wouldn’t be applied in a rural tribal clinic setting. Like, how can I deal with the guilt of undergoing several years of education and research and not have it benefit my people?
So I returned to Arizona State University and did a master’s in bioethics. It was an interesting time because they were dealing with the aftereffects of the Havasupai case and that fiasco.
AG: Can you say more about that case and what made it a fiasco?
KT: In the early 2000s an ASU researcher was doing work related to Type 2 diabetes markers in the Havasupai Nation. The Havasupai people are geographically isolated at the base of the Grand Canyon. And they collected blood samples from individuals and ended up using them to study other things besides diabetes, such as schizophrenia, which is a charged condition, and also started publishing their origins—stories that didn’t quite match their own cultural stories because they themselves believe that they originated in the base of the Grand Canyon.
This was in combination with a lot of other discussions that were ongoing in global Indigenous communities. As of now, for instance, the Navajo Nation has a moratorium on genetic research, as do a number of tribes in the U.S. I’m not sure if you’re familiar with UNDRIP, which is the United Nations Declaration on the Rights of Indigenous Peoples; it was a response to just the number of large-scale diversity genome projects that were ongoing in Indigenous communities, particularly in Central and South America. Over 600-plus tribal nations around the world went to the United Nations to ask them to stop these genome diversity projects.
In particular, the National Genographic Project was denounced as a “vampire project” because they would helicopter in, collect blood samples, promise medical interventions that would help these communities, but they hadn’t really returned. So kind of like vampires in the night coming and taking the blood—that’s where that imagery comes from.
And if you look at, for instance, the 1000 Genomes Projects or the Human Genome Diversity Project, these are two major large-scale diversity projects that have made their information openly accessible to researchers worldwide. It was an effort to sort of democratize research, but what has happened is that a number of major companies have utilized that information to develop commercial platforms such as AncestryDNA. There is a huge interest in collecting Indigenous biomarkers, and there’s a profit component there. The fact is that non-Indigenous entities are deriving revenue from Indigenous biomarkers, and at this point that hasn’t really translated to medical benefits to the people that have actually contributed that information.
There’s a level of expertise that has needed to be developed locally for Indigenous peoples to make these decisions for themselves, to self-determine. And we’re starting to get to that point because now we have more Indigenous scientists. But there still aren’t that many of us.
One thing I always say is that Indigenous peoples are not anti-science; we’re anti-exploitation. Science, as much as we like to idealize it, is not purely objective.
AG: In your Twitter bio you use the phrase “Decolonize DNA.” I’m curious what that phrase means to you. Is that related?
KT: To decolonize DNA is not anti-science, and it’s not a rewriting of the fundamentals of DNA. One thing I always say is that Indigenous peoples are not anti-science; we’re anti-exploitation. Science, as much as we like to idealize it, is not purely objective. There’s subjectivity in the types of questions that we choose to pursue, the types of questions our agencies fund. And then also the decisions that we make in terms of who to include and who not to include in studies also creates subjectivity. And also how those results are interpreted. Because if they don’t properly take into account all the historical societal factors at play, then we are ignoring some key, potentially colonial factors that relate to health.
AG: Do you have an example that might illustrate that idea?
KT: Not everything is genetically mediated that causes disease. But it’s easy to think in those terms because that’s probably the easiest bit of information to collect that relates to disease—the biological factors. But disease is complex. There’s gene-environmental interactions that are at play. We know that socioeconomic factors play a huge role in disease.
Alcoholism is something that’s really charged and is an example. There have been over 230-plus publications in PubMed alone that try to look to see why Native Americans are supposedly genetically at greater risk for alcoholism. But then that totally ignores the history of harm that has been perpetrated upon us, the lack of mental health and preventative-health measures, the lack of social programs for treatment of alcoholism. That’s a perfect example of how skipping directly toward DNA as a cause for everything is potentially harmful and could lead to exacerbating negative stereotypes of a people.
Type 2 diabetes has been heavily studied in Indigenous peoples in the southwest and also in American Samoa. And a huge portion of this narrative for a long period of genetic history has been that we are genetically predisposed to this disease. But this disease didn’t exist in our communities until very recently. So there’s these other factors like a forced diet that was imposed upon us; forcible change to our ways of living and our ways of providing food for ourselves; a removal of our lands that doesn’t allow us to pursue our traditional forms of agriculture; an imposition of a westernized form of diet. These are like actual contributors of health that are being overly conflated with genetics, when in reality there could be other social, cultural, colonial factors at play.
AG: How would you apply this idea of decolonizing DNA to CRISPR?
KT: We have to be really careful that we’re not overly simplifying our narratives related to evolutionary adaptation and mutations. Like, the term “mutation” is one that’s not really well understood. A mutation is meant to be a change in the genetic code that differs from normal. But then what exactly is normal? The term that a number of us use is “polymorphism,” which is a common variation that’s existent in at least 1% of the population. And even this is problematic because right now, even with our efforts to diversify genome studies, over 81% of participants in genome-wide association studies are of European descent. When we’re talking about genome diversity, a mutation or a polymorphism might be an evolutionary adaptation for a certain group of people in response to certain environmental conditions, and it could be protective in some cases. We don’t have enough information about whether or not it’s adaptive in different conditions for different populations.
That is what I want to ask people who are such advocates of using this technology in living human beings. What is the ideal? Is there one?
I’m also really concerned about using germline editing as a solution for defining what constitutes a normal human being. These evaluating judgments ignore the rights of those with disabilities. It presents disability as something that must be corrected, when in reality, millions of people with a spectrum of conditions live healthy, fulfilling lives. That’s something that I really am proud to see in the autism spectrum community, a cognizance that what we call “normal” should probably be changed. I also love and appreciate Down syndrome patients who are really advocating for their rights to live with their own agency and autonomy as adults. Like, what is this ideal that people are looking for? That is what I want to ask people who are such advocates of using this technology in living human beings. What is the ideal? Is there one?
AG: You write frequently about biocolonialism. Is this what you mean?
KT: I use it in the context of commercial exploitation of biomarkers. To other Indigenous studies scholars, biocolonialism can also mean the forcible introduction of genetic variation that negatively impacts us. So, for instance, this could be introducing diseases that didn’t really exist in our communities. It could also mean changing our reproductive dynamics through genocidal acts.
AG: Can you explain that a little more?
KT: Basically a lot of population genetics is statistical. There’s a lot of assumptions at play there; one of the assumptions is that humans meet randomly. But things like genocide are non-random events. There are some disorders that are recessive gene mutations that can be prevalent in Indigenous communities and are probably more so now, post-genocidal events, just because a huge portion of the population is now not reproducing. I’m trying not to say just “dead,” but…yeah. Dead.
AG: So how do we do better? I read one of your papers in which you and your coauthors are talking about principles for ethical engagement in genomic research. Can you talk a little about those?
You want to be able to acknowledge that the participants involved in studies have knowledge and experiences that are informative and valuable and therefore should be included in the research process—particularly if there are risks and benefits that are going to be affecting them and not outside communities.
And this is just a way of stating that if you are going to be collecting biomarkers that not only identify an individual, but also have an effect on the community, then you really should be rethinking these ethical questions—not just at the individual level, but at the group level. In Western ethics, a lot of the questions of whether the benefits outweigh the risks are centered on the individual. But in reality, especially when it’s related to DNA—and DNA is something that’s inherited and shared by members of a similar group—then really that question should be applied to everyone in that community.
AG: You talk about the importance of cultural consistency in ethical genomics practice as well. What does that term mean? Why is it important?
KT: First, we have to acknowledge that there are thousands of Indigenous communities around the world and each one has their own cultural ethic. So what one community might decide is within their culture ethic may not be the same as a different community. And so when we work with Indigenous communities, one of the things we want to ensure is not only is this research beneficial to them, and potentially outweighs the risks—but also, are we ensuring that the research is a question that they’re culturally comfortable with, that isn’t going to impede or infringe on existing cultural beliefs?
I’ll give the example of migration stories. Many tribes along the Pacific Coast might be more amenable toward looking at population evolution involving their community, because they already have a creation story that states that they came from peoples that traveled from a distance. So they might look to genetics as a possible means of bridging their cultural knowledge with this genetic knowledge. Whereas with other groups, like the Havasupai, who believe they originated at the base of the Grand Canyon, these other narratives might be culturally conflicting.
* There is no way to ethically procure a full picture of global migration based on DNA without the explicit consent of Indigenous communities….What we think we know about global migration from DNA is still informed by archaeological, cultural, and linguistic data that may be misinterpreted or siloed within Western constructs and biases of history—and may itself be subject to scrutiny for pilfering of sacred sites and knowledge that have venerated meaning for Indigenous communities and descendants today.
As much as I find these questions related to new emerging technologies to be fascinating, we still have the fundamental challenge of just giving healthcare to people! I wish we could acknowledge that more.
AG: What does it mean to you as an Indigenous geneticist that the foundations of this area of study, and of STEM in general, are so profoundly white and male? How do you balance giving this technological power to the people and keeping it for people who have been educated about it, when there’s fundamental inequalities around who gets to be educated and what they learn?
KT: This notion of prioritizing wisdom is a colonial concept. In our communities, until very recently, we didn’t have Ph.D.s. We revered our elders and the wisdom that they conferred to us, which was derived from their cultural teachings and also their lived experiences. And we can’t discount that. We can’t just come into a community and say, “Oh, I have this Ph.D.” That’s meaningless. And that’s gonna require a humbling of the patriarchy that is in science currently.
And just as a distinct statement, I really wish that as much money as we are pushing on precision medicine initiatives in this country, I wish we could just allocate some of that money to preventative health. There was an editorial cartoon in one of our tribal newspapers. It’s a skeleton waiting in an Indian Health Services clinic. It just says “Waiting room, IHS.” And it’s true. Like, how can we talk about the next advances in precision medicine when we don’t even have enough clinics in our tribal communities and also in our Black neighborhoods? If there’s anything that COVID has shown us, it’s that there are huge inequities in healthcare. These are huge structural barriers that exist relating to inequitable access to healthcare clinics and preventative health. As much as I find these questions related to new emerging technologies to be fascinating, we still have the fundamental challenge of just giving healthcare to people! I wish we could acknowledge that more.
AG: What would it take to use technologies like CRISPR ethically in your opinion?
KT: Personally, I think CRISPR can be a powerful tool as it exists in many laboratories. But there’s a huge gap between the rate of technological advances and also how we discuss the ethical implication of those advances. We need to pause, is really my viewpoint. We need to really ask ourselves: What are the steps at which this technology can be exploited? And then how do we create guidelines to prevent that exploitation?
What I’m specifically talking about is germline editing. There’s just so much we don’t understand about the genome. There’s concerns about off-target effects. That basically means that the CRISPR system could have an effect on other genetic locations than what we originally intended. That speaks to the fact that there are genetic repeats throughout the genome that could be very similar, that we don’t quite have full information about.
There are also what’s called “bystander effects,” in which we don’t fully understand how the body’s normal base editing repair mechanisms act, because they don’t always act in a perfect way; they’re very error-prone. They can introduce mutations that we don’t intend. They can introduce multiple mutations at the site that maybe we intended but might have a different effect. We don’t know the effect on how those cell-repair mechanisms might affect the protein’s overall function and how that change to the protein might have an effect on biological pathways, which are very complex. And then there’s the simple fact that, even if it affects the one offspring, there’s other future downstream changes and effects that future offspring have to contend with.
We haven’t really spent the ethical time discussing those questions. And at this point in time, we still know very little about the genome. For instance, people who are of non-European descent, what their genomes might look like, or about gene-environment interactions. Until we have the full picture of what this could potentially look like in a live human being, I think we should pause.
AG: What do you think is missing from the conversations or ethical debates? Is there anything else that you feel like people aren’t talking about that they should be talking about?
KT: What this means for communities that are historically left out of these conversations. What this means for individuals who have disabilities. What it means socially and culturally as a society when we make a standard of “normal.”
It does lend itself to a eugenics discussion. It’s not a slippery slope argument because that argument is kind of a fallacy. There are intermediary steps that get you from point A to point Z, but we have to account for all those intermediary steps.
AG: The “slippery slope argument” that you probably hear the most in this context is designer babies. What do you make of the people who say if we keep going the way we’re going, that’s going to become standard?
KT: This is why I advocate for a pause, anticipating these situations beforehand so that we can put regulations in place to prevent those situations.
AG: So that’s the important thing, that if we’re thoughtful enough about this, then it doesn’t have to be a slippery slope? We can get some traction, basically?
*Tsosie added later via email
This interview has been edited for length and clarity.