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'Better Drugs, Better Health': A Human Genome Pioneer Talks About the Future of Genetics

ReachMD Healthcare Image
04/13/2023
gizmodo.com

Twenty years ago, the Human Genome Project officially wrapped up. It was a feat of collaborative science that took 13 years—from 1990 to 2003—and involved researchers from around the globe.

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In honor of the anniversary, I spoke with Richard Gibbs, founder and director of the Baylor College of Medicine Human Genome Sequencing Center in Texas, who was one of the project’s leading figures. Gibbs shared his thoughts about the early days of studying DNA, the likely future of the genetics field, and whether the science and themes of the 1997 movie Gattaca still hold up. The following conversation has been edited and condensed for clarity.

Ed Cara, Gizmodo: What was it like to study people’s genes before the project became reality?

Gibbs: There’s been lots of analogies that people have put forward—like us being Lewis and Clark. We didn’t really have a map. Another good one is to think about computational science at that time versus now. We’re talking pre-internet, almost like steam ship technology. And now, when you think about what coding is, what our access to developing code is, these amazing computer tools there for moving around and analyzing masses of data, or what ChatGPT and other AI things are doing for us right now—it’s that contrast between punching holes in computer cards compared to what you can do today.

Gizmodo: So what made it possible for you and the many scientists involved in the project to start creating that map?

Gibbs: When the project was officially declared to begin [in 1990], the technologies we had on hand were simply not adequate to do that well. So we all knew something had to evolve. What we weren’t sure of was whether there would be these single, straightforward, enabling technologies that would knock the thing out of the park in one shot, or whether there would have to be some litany of individual methods that would allow the project to get done. It really turned out to be more of the latter, but there were some major technologies that contributed.

Gizmodo: This was obviously a massive effort. Was that scale of cooperation unprecedented in science beforehand? How many people were actually working together on this?

Gibbs: If you count up all the people who will tell you that they worked on the Human Genome Project, it’s a couple thousand. And that includes everybody at all levels of engagement, people doing the technical work in the lab, etc. Now, as the project proceeded, it condensed down to a few groups. So those groups kind of became the focal point of completing the project.

As for unprecedented, the nearest thing we had back then, and still have, is in physics. You know, there are these groups that can build a giant machine to look at basic principles and physics. The difference there is that those kinds of problems tend to be more monolithic, and have single installations where people can focus and build their experiments. The problem in biology, of course, is that you have many smaller problems, and you have to solve and put them together like a jigsaw puzzle to get to the final solution. So there was a more distributed approach to tackling the Human Genome Project than what you might have imagined in physics.

And I think that’s actually a major contribution of the project—it simply changed the way that people thought that biology could be done. It built a model for team science that was not there before.

Gizmodo: Aside from the the cooperation that became possible, what happened to the study of genetics post-project? How did it evolve?

Gibbs: Well, genetics became digital—it became genomics. Back before the project, genetics and genomics were somewhat separate. Genetics is the field of study of inheritance and its consequences and its attributes, and the changes in biology that are manifest by what happens in inheritance, all the way through to evolution. It’s a big and multi-faceted area. And in the beginning, genomics was quite technical. It was about questions like, can we do DNA sequencing, can we clone DNA? What can we do to manipulate DNA and to understand little parts of it? But genomics grew and joined with genetics, and now the two are somewhat harmonized.

Gizmodo: I think many people still have this conception of genes being our destiny. But it seems like one of the many lessons we’ve learned in the past few decades is that our genes are only one factor that influences our disease risk or behavior. Were there lofty expectations or goals that you thought might have been possible 20 years ago that haven’t come to fruition?

Gibbs: One of the major ambitions of the program was to understand the components of common complex human diseases. What are the things that kill us that run in families? What is the genetic machinery responsible for that? And then what we found along the way is that the answer to that question is more complicated than we had hoped—the genetic contributions are more subtle, and there’s more of them, and the interactions are more complicated. So unraveling those components has been harder than we thought it would be. It’s not intractable, but it’s been more difficult.

Gizmodo: How do you see the field of genetics influencing our lives in the years to come?

Gibbs: Well, I think it’s the same answer as it has been since the beginning of the Genome Project, if not before then. And that is, if we can understand how to build therapeutics, we can do better therapeutics. That’s the real driver. So much of medical treatment and drug discovery is empirical; it’s not designed or thought through. But if you can have that understanding of a mechanism, that allows you to do these more designed therapeutics. And genetics is one of the best vehicles for understanding mechanism. So better drugs, better therapy, better health.

Now, the other part of that is, of course, risk prevention. Having a genetic screen early in your life; the degree to which that can tell you about your health risks will be the degree to which you can do things to avert those problems.

Gizmodo: For the longest time, the popular media that really helped the average person appreciate genetics was the movie Gattaca. But we’re all getting older now, and I’ve seen scientists complain that the younger generations aren’t as familiar with it. Is there anything since that you feel has had that same sort of inspirational effect on people—that hooks people into caring about genetics?

Gibbs: It’s been a pretty hard act to follow! I remember that, as we were wrapping up our genome factory, I took the entire group to see Gattaca at the theater. And it was quite profound. I think it influenced those who were new to the program to realize what an important part of history we were contributing to. And I also thought that Gattaca was just a wonderful representation of what the issues are. It wasn’t technical, but it certainly touched on all those important social issues, and I don’t think anything has come along since then that’s come close.

What I do think is very compelling today is the real-life stories I hear from people who have done these ancestry testing services. You know, they’ll find family or extended family that they didn’t know about. And that kind of gets them interested. So that’s a positive thing.

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Schedule30 May 2024