Lessons for scientists from the All of Us Research Program backlash

Scientists are taught early in our training that criticism is a fundamental part of the job. What we are not usually trained to navigate, however, is public backlash, which is exactly what followed the publication of the comprehensive genomic sequencing results from the All of Us Research Program. The study aims to add the genomic information of 1 million volunteers from normally underrepresented genetic backgrounds to datasets that have been mostly constituted by people of European descent.

The publication faced public criticism almost instantaneously. At the heart of the matter is how the study presented the diversity of race and ethnicity in their dataset. It gets a little technical, but it focuses on the fact that the researchers used a type of graph called uniform manifold approximation and projection. UMAP reduces the complexity of a given dataset to something that can be plotted in a classic 2D graph. So UMAP is almost designed to find and exaggerate differences, creating new patterns that might not exist in the original data. In other words, the graph reinforces the misconception that races and ethnicity follow neatly distinct genetic components.

This misconception is often misused and exaggerated by people looking to validate racist or xenophobic views on the basis of “science.” Now, the discussion about UMAP has become much louder than the findings of the study, which discovered over 3,000 previously unknown mutations concerning 117 diseases.

There are sound scientific arguments both against and for using UMAP in this study, but the decision points to a much broader issue at hand: an inability of scientists to grasp the societal impacts of their research — often to the detriment of the people they attempt to help.

Discussions on how to properly handle genomic studies like All of Us are nothing new. From the moment the human genome was fully sequenced, there have been intense efforts to search for genetic causes for complex diseases. These genome-wide association studies (GWAS) have accelerated biomedical research by narrowing down specific mutations and their links to a specific pathology. But they have also been at the center of controversies — for instance, when they are misused by racist groups seeking to validate their views. There are no easy solutions for these thorny problems, but one place to start would be to bring more humanities experts into GWAS, particularly anthropologists, sociologists, and historians.

Scientific progress is often viewed as a neutral, apolitical, undogmatic endeavor made possible by researchers hyperfocused on finding answers. We see this best exemplified in initiatives prioritizing science, technology, engineering, and mathematics (STEM) above other areas of knowledge — the University of Florida recently used the unfortunate term “biomedical research evangelism.”

This narrow-minded approach, however, has and continues to pave the way for scientific racism to take place. Often rooted in flawed research, this has taken form in phrenology, justifications for slavery, and eugenics, all of which with devastating consequences.

But it can happen with good-faith, well-executed research, too. For scientists to ensure that even perfectly valid research is not co-opted and used to perpetrate violence, it is key to understand that science has been, is, and will continue to be embedded in its sociopolitical context.

My current research focuses on the epigenetics and neuroscience behind how trauma can get passed through multiple generations. Epigenetic changes affect how your DNA gets interpreted, but unlike a mutation, they do not affect the DNA sequence itself. Partially because there are no mutations to be tracked, and partially because of how it challenges our views of evolution, the idea of epigenetic inheritance by itself is still a controversial topic for certain geneticists.

Epigenetics is also a great example of research that can only be conducted appropriately by examining both the science and the humanity of traumatic experiences. Though I am still early in my project, my peers and I have discussed with other academics and engaged with our local communities to direct our scientific efforts responsibly. This has taken many forms. We talked to academics involved in the legal system about the interconnected roles of trauma and the carceral system. We’ve also engaged in lighter discussions with historians about the real legacy of Jean-Baptiste Lamarck, an 18^th-century scientist who has been in his own way misrepresented, in our understanding of evolution. We’ve even worked with artists and musicians, working to understand how trauma and intimacy might be portrayed photographically, or the connections between ancestral experiences in science and in music.

These opportunities brought up points that we might have missed by focusing only on the “hard science.” For example, if we discover markers for intergenerational trauma, would that be something that could stigmatize already excluded populations even further? Where are the lines between trauma that can cause a pathological condition and past experiences that can simply inform a generation down the line? These are for now open-ended questions, but they are essential for how we design experiments and present our findings.

I don’t know if the All of Us researchers spoke with non-STEM experts and cannot predict how the publication would have changed if they had presented the same data differently. But I imagine the reaction to it would’ve been more positive. Minimizing potential harms does not mean limiting the questions asked by scientists, especially in projects with so much potential for improving the health care of millions of people. To me, it means understanding that the same potential can be co-opted and having a critical evaluation of how that might happen. Case in point: Presenting races and ethnicities that greatly overlap based on history and society as distinct genomic “clusters” can easily lead to ideas that we are all much more different at some fundamental level, which is simply not true.

In many of the studies done on sensitive topics, the authors, editors, and publishers can all work to clarify their findings to a general audience, clearly stating that a graph is exaggerating differences, for example. In a society still grappling with dangerous debates directly related to historically excluded populations, I see in scientists not only a moral duty to minimize harm, but also the opportunity to break from a tradition of isolating ourselves from society.

Thiago Arzua is a Leon Levy Scholar at Columbia University, where he studies the neuroscience of how trauma is represented in the brain. He is also a co-founder of Black In Neuro, a registered 501(c)3 non-profit organization that aims to support Black neuroscientists across the world.