The American Society of Human Genetics (ASHG) conference kicks off this week in Denver, CO. Before we packed our bags, GEN chatted with Bruce Gelb, MD, director of the Center for Molecular Cardiology, and professor of pediatrics and genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai. Gelb has also served as president of ASHG for one year. Because ASHG presidents serve one-year terms, Gelb says he is “on the home stretch.”
Gelb’s research interests include gene discovery, pathogenesis, and therapeutics, genetics of congenital heart disease, pediatric genomic medicine, undiagnosed diseases, newborn genome sequencing, diagnostic odyssey, and clinical implementation.
The Presidential Symposium, “Mendelian Traits: Thinking about Complexity in the World of ‘Simple’ Genetics,” represents these interests and will take place on Wednesday, November 6 at 5:30 pm MT.
The three speakers, Gregory Radick, PhD, from the University of Leeds, Athena Starlard-Davenport, PhD, at the University of Tennessee Health Science Center, and Stanislav Y. Shvartsman, PhD, at Princeton University, will discuss how to characterize genetic traits and disorders across the range from simple to complex.
Gelb shared some of the major themes that will be present at the meeting and what he, personally, is most looking forward to.
This interview has been edited for length and clarity.
LeMieux: How has your year serving as president been?
Gelb: It’s been a busy year, but I guess they are always busy years. We have had exciting things going on. We successfully recruited a new executive director or CEO, Amanda Pearl, who came on board in May. Last year, under the previous president Brendan Lee, we did strategic planning and we rolled out a new plan. So we’ve gotten busy on that. And there is a particular focus this year on getting more active in the advocacy space, particularly in terms of interactions with the U.S. government. We also have started, but not yet completed, a search for the next Editor in Chief for the American Journal of Human Genetics journal. We’ve also been able, in part through support from NHGRI, to expand some of our programs like the Human Genetics Scholars Initiative and another program with fellows that are involved in things like communication.
LeMieux: Great! We’re all heading to Denver soon. What are some of the major themes that you’ll be paying attention to—or you think attendees should be paying attention to—at the meeting?
Gelb: That’s a surprisingly difficult question for me because we don’t run the meeting thematically. I’ll start with an innovation that we started last year that was very successful. On the last day, we have the Distinguished Speaker Symposium. We will be having one again this year, entitled “The Promise and Payoff of Human Genetics and Genomics Paths from Bench to Bedside,” and there will be four speakers with fairly diverse viewpoints. It’s really about thinking about how we make the incredible progress we’ve made, in terms of understanding disease, that human genome sequencing and the human genome project, have enabled. How do we make that work for everyone everywhere, which is really ultimately the goal. It’s a huge challenge. It’s obviously inspirational and it’s a lot to accomplish. But that will be a really good session. I’m really excited about it.
The one thing (or two) that I personally have control over are my talk and the Presidential Symposium. My talk is on election day at 4:30, which is just exactly perfect (chuckling). The Presidential Symposium is the following day. Generally, the president sets up the symposium to try to match their talk. In my case, my talk is about incomplete penetrance and variable expressivity.
These topics have come into play because of what we’ve learned from studying large biobanks like UK Biobank and our biobank here at Mount Sinai called BioMe. What we’ve started to see very clearly is that our estimates of penetrance, for instance, for most Mendelian traits turn out to be wildly high based on the way we ascertain people. Traditionally it’s done by finding people who have the trait and then studying their siblings or their children. That turns out to be not representative. It’s an ascertain bias, basically. This becomes really important because of the vision that some people have that we’re going to sequence every baby at birth (or maybe even before birth) in the future.
At the Presidential Symposium, I’ve invited three speakers who are going to touch on areas of this. One is a historian who also does philosophy of science. His name is Greg Raddick. He is originally from the United States but he is at the University of Leeds in the U.K. He has a book called Disputed Inheritance, which is about this intellectual debate that happened at the turn of the 20th century. So in the early 1900s, there was an argument between William Bateson, who is a founder of genetics, and Raphael Weldon. They were arguing about complexity, which is what I’m interested in.
Second is a talk from somebody who’s quite involved with our society, Athena Starland Davenport, who is on faculty at the University of Tennessee. She’ll be talking about genetic modifiers of sickle cell disease. Everybody who has sickle cell disease is homozygous for the same allele, and yet the severity of sickle cell disease varies quite a lot from person to person. Understanding that is part of the complexity problem that I’m interested in. And then the final speaker is a friend of mine from Princeton, Stanislav (Stas) Shvartsman. He does quantitative genomics on Drosophila and has been studying stochasticity in genetic changes—another contributor to the kind of variation that we see in patients. So those are things that’ll be at that part of the meeting. I hope people like them. You’ll have to ask me after the fact.
I am confident that the use of AI to understand large genetic data sets will continue to be a theme at the meeting. Our data sets keep getting bigger and AI keeps getting better. Our data are very well set up to apply AI to, and there are clearly problems we need to solve. Two obvious examples: variants of unknown significance and what the heck all the non-coding variation is doing or not doing. Those are things that will be, I’m sure, emerging at the meeting as well.
LeMieux: Do any notable advances come to mind from the time that the last meeting was held to this year’s meeting? So, if you look back over the last year, what would you say have been one or two of the biggest advances in the field?
Gelb: We can’t know as we sit here today, but almost always, one or more of the companies is planning to make a major announcement of a change in their platform. There are major advances that are coming. I’m not sure what it will be, and we’ll have to see what they announce, but I think we will hear reasons that technology has either gotten a lot cheaper or a lot better, or both. That’s going to enable a lot of what we can do as we move forward. We’ll have to see what that is.
LeMieux: What do you think will be some of the big challenges in the field that we’ll hear in the lecture halls and what do you think people will be talking about?
Gelb: I think keeping an eye on how the election goes is going to be of importance. First, irrespective of who wins, there are going to be issues around NIH funding. That’s part of where we have been focusing our efforts. You could go to other meetings and hear similar conversations. We are trying to work together on that. We know very well the positive impact the investments our country has made at NIH, and how those have paid off. The ROI is really quite favorable. So the contribution to the U.S. GDP is very substantial (probably over a hundred billion and more broadly calculated over 250 billion). That’s not chump change. And I think that we have a lot of concern that there is going to be some reduction in investment. Obviously, depending on who wins, and who is controlling which house of Congress, it could be better or worse. This year, under the current administration, we were basically close to flat. Given inflation, that was actually a reduction, and that has real-world impact. So, I think that will be part of our discussion. Obviously, depending on who will be in office, I think the discussion changes because a Harris administration and a Trump admission would have relatively different stances toward things like NIH and investment in biomedical research.
It’s sort of a pivotal moment. And I do think that’s going to be an important part of our discussion. It’s out of our control. We’ll just have to be reactive, given whatever the reality will be. And we will do what we always do: we’ll roll up our sleeves and speak with advocates and make sure that the general public is aware of the impact genetics is having on people’s well-being.
What we care about as a society is that everybody who wants to vote makes sure to do so before they come to Denver. And we’ve been doing our best to make sure our members know about that. There is a very robust communication strategy to make sure that people remember to vote early.
LeMieux: What are you most looking forward to outside of the sessions?
Gelb: We’re still close enough to COVID-19 that we remember when we couldn’t meet. I think that being able to meet—more so now than pre-COVID-19—feels like an incredible privilege and blessing. In science, and maybe in life generally, there is a lot of value in the ability to meet up with people to talk to them. People will end up finding each other, whether it’s through a talk, a poster, or just a conversation. And I know that people will leave our meeting with new collaborations and new ideas about how to do their research. That’s the value of it. I’m excited about the networking component every year.
I’m also personally excited about stretching my brain. Our meeting is very broad. It’s just human genetics and genomics, but that spans in a lot of directions and most of us get exposed to things that we’re not thinking about or reading about on a day-to-day basis. I think that’s very healthy to keep us up to speed in our field in a broad sense. And that tends to get the creative juices going in a way that few other things can.
Other than that, I find other aspects quite inspirational. We’ll have events for trainees. We have events for people from diverse and underrepresented backgrounds. The notion of improving the human genetics workforce is one that our society is taking very seriously. And I think seeing how that continues to grow in very positive ways is something that makes me happy when I’m at the meeting. It’s inspirational, honestly.
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