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Scientists talk about what they do and why they do what they do. Their motivations, their trajectory, their setbacks, their achievements. They offer their personal take on science, mentoring and the many aspects that have shaped their work and their lives. Hosted by journalist Vivien Marx. Her work has appeared in Nature journals, Science, The Economist, The NY Times, The Wall Street Journal Europe and New Scientist among others. (Art: Justin Jackson)
Transcript
Note: These podcasts are produced to be heard. If you can, please tune in. Transcripts are generated using speech recognition software and there’s a human editor. But a transcript may contain errors. Please check the corresponding audio before quoting.
Vivien
Hi and welcome to Conversations with Scientists. I am science journalist Vivien Marx. Today's episode is a sneak peek of the 2024 annual meeting of the American Society of Human Genetics. It's coming up in early November in Denver, Colorado. Here is a sneak peek of the sneak peek episode. Just to give you a sense of this podcast, we will be talking about the meeting, also a range of topics connected to the meeting, for example, genetics and inclusion, biobanks, genetic testing of newborns and much more. And here is a bit with Dr Bruce Gelb, the current president of the American Society of Human Genetics as hg. He is a researcher at the Icahn School of Medicine at Mt Sinai in New York City. You'll hear more from him after this, of course.
Bruce Gelb [0:55]
If all you do while you're at the meeting is stay in your lane, so to speak, you're not really fully benefiting. And you know, people can have to choose for themselves what they're going to do, of course, but I think many people sometimes will say, You know what? That is, not something I would ever like pick up and read a journal article at you know that session, but it just sounds interesting. Let me, let me find out what's going on in evolutionary genetics. I'm not an evolutionary geneticist, but let me just hear what's going on. And sometimes, like I said, when that happens, you realize that some of the advances are indeed relevant what for what you're doing yourself and and I just think it makes you better, and I think it helps with scientific creativity. I don't think anybody's ever done a perfect job of describing what all that is about. But I think stretching your brain, which is part of what this is about, is an important part of being able to stay fresh and continue to be doing cutting edge work in whatever scientific endeavor, and it's certainly true in human genetics. So
So Vivien, one difference from last year is that I managed to get a URI on Saturday, which you can hear in my voice. So I'll do my best, but I'm not 100% for sure.
Vivien
Oh my gosh. Should we still do this? Is this okay?
Bruce Gelb
yeah, for sure.
Vivien
Ah, man.
Bruce Gelb
What are you gonna do? Life happens. I think the way we think about these things has changed because of COVID, right? Like you get a cold, you never thought about it. You just, like, went to work and did your thing and it's now you should be in a bubble suit or something, I don't know.
Vivien
Hi, everyone. Welcome. Thank you for dialing in to this sneak peek of the annual meeting of the American Society of Human Genetics. We're happy to see you, and we're happy to have some guests online. I have a co moderator today who I'll introduce shortly, but let me introduce the guest first. So there is Dr Bruce Gelb, who is the current president of the American Society of Human Genetics. And he is also at the ICANN School of Medicine at Mt Sinai. And we have Cara Flynn, who is the Senior Director of Public Engagement, communications and marketing at the American Society of Human Genetics. And my co host, Dr Mike Fletcher, where are you? Oops, I'm not seeing you.
Mike Fletcher
My name is Mike Fletcher, and I'm a senior editor at Nature Genetics.
Vivien
So we're all set. We have a pile of questions for you, but we wanted to first ask just some formalities about, how many people are you expecting? How many posters, how many talks, and will there be sort of live streams, also for people who might miss something, or who can't do the whole parallel I'm in two universes at the same time, trick so they can listen to maybe a talk afterwards. Don't know who might want to take that question.
Bruce Gelb
I can do some of it. I may need a little help from Kara on some of this. So in terms of the numbers, I think the total number of people will be in about the 8000 range. Kara, do I have that about right? The number of talks will will have roughly 15 plenary talks and almost 330 scientific talks. The number of posters I don't have in my head. Kara, can you help me with that? Do you know the numbers
Kara Flynn
Over 3000 posters.
Bruce Gelb
It's a lot, yeah, you can’t get through them all.
Vivien
I was just going to say, yes, wow. So that's filtered from all the submissions. And I'll just add here the annual meeting of the American Society of Human Genetics is not hybrid. There is no virtual part to this meeting, but some sessions and talks will be made available for streaming after the meeting. Those sessions will be the presidential address, so Bruce Gelb’s address, which will be on the day of the US election, the presidential symposium and the distinguished speakers symposium. And these are some of the events Bruce Gelb will be. Talking about here in this podcast shortly, and I will add the meeting will have childcare. You do need to register for that in advance. There is a family room and lactation room, and there is a prayer meditation room.
So I guess we'll just let you tell us what you're most excited about. Obviously, you've put together talks and presidential symposia, but I'm sure you've had your hand in a number of ways, so we're all ears
Bruce Gelb [5:25]
Sure. Well, first, you know, and having come through COVID, we still focus on the fact that we're able to come together. We're excited about going to Denver this year. And, you know, I think there's no question. I think this is echoed across biomedical research that coming together brings real value that virtual meetings that just don't provide. I mean, yes, it's great to hear the science from the talks and see the posters, but the ability to interact with people, to run into people you know, to catch a cup of coffee that is, is part of where, you know, the sausage gets made. If you ask me, I think that's a really important thing, probably in life, generally, but certainly in science. Y ou know, a lot of collaborations will come out of our meeting, where people realize they're working on either complimentary things or even similar things, where they can do better together than they can separately, etc. So I really think one can't underestimate that we obviously have at our meeting. You know, it is the largest meeting in human genetics every year, and that will be true this year,
Vivien
The largest globally?
Bruce Gelb
yeah, it's the biggest meeting in human genetics period.
Vivien
Cool.
Bruce Gelb
And, you know, I think that, our field has been one that is very technology-heavy for a long time, and as a result, I mean, I feel very blessed. I'm obviously later my career. If you look at what's happened over that period of time, you know, the the notion that we're now sequencing genomes for like, 200 bucks is crazy to think about, but it has enabled a lot of things. Well, the people who produce that technology, the industry partners, also have a very large presence at our meeting. And you know, I think they play a very positive role in helping the scientists who are there. I mean, many of them are scientists, too, but the academic scientists figure out how to best go about doing even more than what we've been doing in the past, and they will have scientific talks during some of their sessions in exhibit space that are very illuminating. I myself right now I'm trying to publish a paper that came with an industry group out of something that happened at an as ASHG meeting a few years ago. So that's not to be minimized either. I really think it's very important.
[7:50]
Another aspect this year is we're going to be celebrating the anniversary, the 75th anniversary, of our one of our two journals, the journal that's been around longer, of course, is the American Journal of Human Genetics. And Mike, not to get in competition with Nature Genetics, but you know, our field is big enough that we have several important journals. And I think the AJHG covers a space that's a little bit different, let's say, than the Nature Genetics. They're complimentary in some ways, and I think it's really important to our field. And, you know, I think we're excited about having there. We're going to celebrate them with a number of events. Our editor in chief is Bruce Korf, and he's done an amazing job. You know, for instance, they've had a series on sort of bold predictions on where we're going from here in human genetics. And I think mapping out what comes next is really an important part of what we need to do. So, so, so those are things that are going on.
[8:55]
Now, you alluded to the Presidential Symposium, you know. So that actually turns out to be the only thing I have control over at the meeting, actually, but it was fun to be able to
Vivien
Oh that's too bad we thought that you pick everything, every single poster go through your hands. I see,
Bruce Gelb
We have an amazing program committee. They they work super hard as a group. They're led by Beth Solomon, who's fantastic. I believe joining the board soon, I really think they've done a great job. And also it's important that we have diverse voices in the room when we're making decisions about what to present, what to highlight, and so on. And I mean diversity along many angles, scientific diversity, you know, geographical diversity, backgrounds, all of that. And I think we accomplished that with that group. But back to the presidential symposium. What the way it typically works in, the way it will be working out this year, is that the President tries to match up the Presidential symposium to pick up on the themes that he or she. Will be speaking about in the presidential address, which just happens to be on Election Day this year, which is my lucky task. So for my address, I will be speaking about two concepts in genetics that are well known, particularly for Mendelian traits or a simple gene, so called simple genetic traits, those are penetrance and expressivity, specifically incomplete penetrance and variable expressivity.
[10:30]
And so for listeners who are not deep into human genetics, what that refers to is the penetrance is about how likely is it that somebody who carries a change in a gene that we know can cause the disease, how likely is that person to actually wind up having the disease, exhibiting the trait? So that's what penetrance is about. And as it turns out, many human traits that are Mendelian are not completely penetrate and then the other related concept is variable expressivity, and that's the concept that if you take two people with the same disorder, even caused by the exact same change in the gene that results in that disorder, they turn out not to be exactly the same in terms of how they exhibit the trait, if they're exhibiting at all. And so those are very important concepts that have been with us for a while, but and the reason I chose them is because they've become increasingly important, and that you could say, in a way, is that we're the victims of our own success.
[11:45]
So because sequencing has gotten so cheap, I mean, people are saying the day will come not too far off where, like every newborn, will have their genome sequenced, and they'll just live there. And the idea, of course, is to be able to make accurate predictions about what's going to happen to that person, that baby. In that case, as you move forward, we have the same issue, let's say, where people are contributing to bio banks, and you're sequencing them, and you're finding changes in some of them that can be associated with various traits. Well, it turns out that what we know in genetics is largely based on having studied groups of people who do have the disease, or at least are close relatives, so are more similar genetically than everybody in random and we're learning this from biobanks like the UK Biobank, other large bio banks, medical school specific bio banks. We have one here at Mt Sinai, originally bio me. Now we're doing something called the Mt Sinai million project. And there are other projects, other places as well, really good ones. So that is raising really interesting questions in our field, because we're trying to apply knowledge that was or conclusions that were reached by studying a very sort of different group of people than we're now trying to apply it to and thinking through that, and it becomes important, basically you know this whole concept of precision medicine, you want to be extremely accurate. Well, if you're going to be very accurate, you have to know what you're dealing with. So that's why I'm talking about what I'm talking to.
[13:10]
So the companion is the symposium, which is the following day. It's on the second day of our meeting, and we'll, we'll have three speakers for that. One of them is a very active member of our society, Athena Starlard-Davenport, who's at the University of Tennessee. She's an associate professor there, and she studies particularly sickle cell disease. And she'll be speaking about other genetic factors besides the gene for sickle cell disease, the hemoglobin gene that determine what sickle cell disease looks like in a given person who has the trait. So that's one, by the way, one cause of the variability I was speaking to. So she's going to speak about that. The first speaker is actually a historian and science philosopher named Gregory Radick. He's American, but he's on faculty at the University of Leeds in the United Kingdom, and has written a book recently that came out about, I don't know, a year or more ago, called disputed inheritance, which is about a very interesting sort of intellectual debate that happened as the field of Human Genetics was just starting back in the early 1900s it was in in in England, and how they thought about Mendelian traits, whether they were simple or complex, whether we oversimplify them and so on, and what the implications are down to the present about how we teach kids, and what that means about How they understand what's likely to happen to people based on their genes is, is what he'll be speaking about. And then the final speaker is Stanislav, I call him Stas. He's a friend as well. But Stas Shvartsman, who's on faculty at Princeton and he he does quantitative genetics, genomics, mostly using Drosophila, fruit flies as his model. And he has been studying the phenomena of randomness. The technical term is stochasticity. So stochastic effects are sort of random ones, and it turns out that that also explains some of the variability that we've been that I've been talking about. So that's maybe too much, but that's what we'll be doing for that session.
[15:25]
And then we are continuing this year with something we had last year that was usually successful, I would say, and and it's on the final day. It's called the Distinguished Speakers Symposium, and it's on the Saturday. And this year, the title of it is The Promise and Payoff of Human Genetics and Genomics: Paths from Bench to Bedside.” And we're going to have four speakers, some of them are in academics. Some of them are former academicians who then went into industry. And you know, all thinking, I think very deeply about, what does it mean to apply genetics to develop therapies. How do we make sure we're doing that in a way that reaches everyone everywhere, which is our goal for human genetics as a society? And I would argue it's our goal for a field. And these are a broad range of people. It includes, for instance, somebody whose training is in genetic counseling, and then, of course, PhD scientists who are doing work in the field as well. So that promises to be a super exciting event. And then, of course, we have just, you know, too many sessions and too many posters. You can't do them all, but there's a lot to choose from. And hopefully, again, the scientific interests of our attendees tends to be quite broad, and so hopefully, at all moments in the meeting that there'll be, as there to me, at least there always is, there'll be something calling to you, whether it's right in your sweet spot, or maybe forcing your brain to think about something a little further afield and get you thinking about how that might help you do what you're doing better.
Vivien [17:00]
I was just wondering, you know, with that many attendees, how do you manage this whole idea of a big tent, right? Someone who works in quantitative analysis of certain types of genetic phenomena, they maybe don't want to go to something that feels to them to be more clinical, or maybe it's something too much about sort of chromosome architecture. I'm just making this up here. How do you manage to have this interaction between people who are, you know, in very different fields and subfields?
Bruce Gelb [17:30]
Yeah, so I think it happens in a number of ways. I mean, first of all, so I'm in New York City, right? People who are in New York City is like, how do you deal with it? It's so crazy, it's so big. And if you live here, you know that it's really a series of small neighborhoods where you do actually get to know people. And I think you could think of our meeting in similar terms people. You know, there are actually interest groups, special interest groups, that break down along some of those scientific lines, that people do that. And of course, there are social occasions where people are breaking down by what institution may either train that formally or at currently. So people meet in those ways.
[18:25]
But I do think that we also come with the notion that if all you do while you're at the meeting is stay in your lane, so to speak, you're not really fully benefiting. And you know, people can have to choose for themselves what they're going to do, of course, but I think many people sometimes will say, You know what? That is, not something I would ever like pick up and read a journal article at you know that session, but it just sounds interesting. Let me, let me find out what's going on in evolutionary genetics. I'm not an evolutionary geneticist, but let me just hear what's going on. And sometimes, like I said, when that happens, you realize that some of the advances are indeed relevant what for what you're doing yourself and and I just think it makes you better, and I think it helps with scientific creativity. I don't think anybody's ever done a perfect job of describing what all that is about. But I think stretching your brain, which is part of what this is about, is an important part of being able to stay fresh and continue to be doing cutting edge work in whatever scientific endeavor. And it's certainly true in human genetics and genomics, and also, you know, I, again, I alluded to this before. I think we are blessed in that we are at a field, in a field that's been just sort of galloping along for a few decades now. I mean, you know, I not to dis on any group, but I think about the poor anatomists I think over my whole career, they they've discovered one new ligament in the knee, or something like that, but you know, like our field by comparison, like what we're doing today is a complete sea change compared to what we're doing before. And you know, that's we're obliged to keep up with that. But that's not easy either. And I think the meeting plays an important role in making that possible.
Mike Fletcher
If I may pick up the thread here. Vivien, You mentioned earlier, you know, you said, like we, and I completely agree, we have been in genetics. We are very lucky to have all of these genomics technologies that, as you said, in the last couple of decades, have completely transformed how we think and analyze genetics. And you know, you also alluded to, you know, your part of the aims of the conference will be discussing, what are the next steps. So what, in your view? What are the next steps required? You know, like, now that we have all of this data, or at least the ability to generate all this data, how are we going to get more understanding out of this, how we will improve people's lives? What would you say is required?
Bruce Gelb [20:40]
Yeah, so I, you know, first of all, just because I'm the president doesn't mean I have answers to all of that, of course, and nor should I be imposing my views. I would say a few things. There's still much to learn and discover. You know, I will again. I've spent most of my career not not entirely in this space, but much of it focusing on so called Mendelian traits, and the numbers continue to mount. First of all, right? We were at multiple thousands, maybe 8,000, I think now we're probably holding in on 10,000. And although we've made large numbers of discoveries, we still don't know the underlying gene for thousands of traits, right? So just take that, and that's one thing. Second point I would make is that, and it's well documented, and you know, I'm sure, Mike, you know from your journal, the field has not done a good job with its inclusivity the particularly in the common common disorders, common genetic variation model, which has been mostly GWAS, of course, you know, overwhelmingly people of European ancestry have been represented relative other people.
[21:55]
Aside from being inherently unfair, it's scientifically impoverishing, we know very well that different ancestries have different variants at different frequencies. There's some you just can't find. You can study people from European backgrounds, you know, till the cows come home. And there's some things you're never going to discover because they're just not there. And so becoming more inclusive and finding ways to study, you know, other groups as important. I think we're making important strides there, honestly. But I you know, we're clearly not there. The numbers still show we're not there. And unfortunately, because there's the sort of lead in the ancestry department, it's hard to catch up, in a way, and I think we've struggled with that. But that so, you know, that project will not end in my career. I think, I think that'll be an ongoing discussion.
[22:45]
And then I think critically, you know, sometimes you hear discussions which I think are misguided, but, and that is like, Okay, you sequenced the genome, what you know, where we actually changed human well being and, and I think there, I think we have already no question. But the truth is that we don't have therapies for many of the disorders that we have worked out pathogenesis.
The tools are getting better and better, the ability to do gene editing. You know, we've seen FDA approval just within the last 12 months of such things, and hopefully this is the beginning of what will turn into, really, just a tsunami of such therapies. But it does turn out to be, you know, hand-to-hand combat. It's not like you come up with one therapy that solves all problems. You have to keep and within things we used to think of as one trait. Think of autism as an example, right? It's a large number of traits, and I'm dubious that one therapy will it help all individuals who you know have that trait. And that's true for most traits where there are multiple genes. And so a lot of work needs to be done.
[24.00]
A lot of creativity needs to be brought to bear in order to do that, and and human genetic community as part of that, but we're also interacting with people in other scientific disciplines as well to make that happen, and it has to happen as partnerships between academia and industry to make it work. So I think those are our parts.
The last thing I'll say is that, you know, and I think this is represented our meeting. Obviously, everybody is talking about AI and machine learning as a form of AI. I do think it's going to have large impact. No question, I think we are a field that has just very, very large amounts of data, which is exactly the situation you want, if you want to bring forward AI.
But you know, to give one example, and it was one of the challenges that the AJHG spoke to, is that we continue to have the problem as we do genetic testing, that people get back results that are in that gray area that we. Refer to as variants of unknown significance, or VUSes, and that's a struggle, but I believe it's one we'll solve. And I think AI is going to play a big role in helping us get there. You know, we just saw the Nobel Prize conferred in physics, I believe, you know, and part of that was where they worked out the structure for nearly all proteins. That has, in turn, enabled us to figure out, if you change an amino acid, how likely is it to be problematic. So I think, you know, those are, those are examples, but, you know, I hope I'm not leaving anything super obvious out, but if I am, I bring it forward and I'm happy to pick up on it.
Vivien [25:35]
Awesome. That's quite the to do list, and we know that you're still under the influence of some microbe, so we'll let you rest for a moment, but we're going to torture you with a little word game, and then we're going to come back to all the questions, and maybe people are pondering their questions or comments right now, you've played this game before. It's in the tradition of French novelist Marcel Proust, who developed a questionnaire, and then French journalist Bernard Pivot used it for decades in his talk show. James Lipton Inside the Actor’s Studio used it or a version of it and Stephen Colbert has used it. So it's a game that we are riffing on: a word pair. We give you two words and you pick one that resonates more with you. And then we'll return to questions in human genetics and all that, although some of these word pairs have to do with genetics, of course. Mike, are you ready?
Mike
Yes.
Bruce Gelb
Do I have to explain why I picked the one I picked? Or just
no explaining? No explaining. I mean, you're welcome to if you want to, but really it's just about getting a lot of information. In a very limited amount of time and to have a little bit of fun. And as you're healing, maybe it'll be a little fun for you. So we'll just explain. So for example, we'll ask ‘coffee or tea’, you pick one, and then we'll move on. So I'll start with coffee or tea, and then Mike, and then we'll, we'll switch off, all right,
Bruce Gelb
Tea.
Vivien
Tea it is. All right. Mike, your turn
Mike
Mac or Windows?
Bruce Gelb
Mac
Vivien
Big conferences or small conferences?
Bruce Gelb
Tough one. I'm going to say small conferences.
Vivien
Okay, Mike.
Mike
How about simple traits or complex traits?
Bruce Gelb
I'm gonna say simple traits
Oonce a Mendelian, always a Mendelian Mike,
Vivien
I see, all right, yes, of course, yes, you have a Mendelian tradition, yes, yes,
Bruce Gelb
I do. I do go ahead,
Vivien
DNA or RNA,
Bruce Gelb
DNA
Mike
Coding or non coding,
Bruce Gelb
oh coding,
Vivien
poster or talk
Bruce Gelb
talk,
Mike
Master’s degree or not.
Bruce Gelb
Masters degree
Vivien
X chromosome or Y chromosome,
Bruce Gelb
X chromosome
Mike
Organoids or cell lines?
Bruce
I'll go with organoids.
Vivien [28:10]
Awesome. Thank you. I mean, we can go on for hours on this, but we'll let you go. Thank you so much for playing this. It's really interesting always to hear responses and things back to so I'm just going to check and see if anybody has any questions.
If not, we'll fire away with some things picking up on what you've previously said. I don't see any hands up yet,
Bruce
I should say, since you brought it up. I have to respond, maybe explaining why I wound up doing what I'm doing. I did not enjoy the Proust novel I had to read for one of my courses in college. I remember when I realized we were done with it, flipping it over my shoulder as I walked to class, because I just couldn't stand it any longer. I think it was a red, black or something like that, some such, right? Anyway, go ahead.
Vivien,
yeah, he's, difficult, but he’s an interesting fellow, kind of very focused on certain things only.
Bruce Gelb
Not how my brain works. Sorry,
Vivien
No, sorries needed, but you played the game anyway, which he based on the questionnaire that he invented. You mentioned earlier this, this concept that many people are now interested in hearing about simple genetics versus complex genetics and thinking about the nuance here. But I was looking and I was just wondering about pop culture a little bit, because it's in my DNA, is the name, I think, of a dog treat that's a cheese scented rubber ball with a wacky bounce. And then there's a lot of music that talks about DNA. Kendrick Lamar, of one of many singers, has a song where he says, ‘I got loyalty. I got royalty inside my DNA.’ Not sure where inside my DNA is. But what do you think about the fact that many people, I think, now feel that there are things in and inside their DNA, and that is kind of a success of your society and of genetics in general, but it might not be always a great success. I'm not sure. What do you think?
Bruce Gelb [30:10]
Yeah, so I think it is something that has a double that is a bit of a double- edged sword, right on the one hand, you know, unraveling the code book that for humans, which is what our genome, fundamentally, is. It is an incredible task and an accomplishment for mankind, for humankind. And I think we're continuing. I mean, one of my choices before was coding and non coding, and I pick coding because currently we understand it very well, but clearly we're working hard to understand the rest. And I think all of that is huge.
And I think understanding how, whether it's complex disorders or simple disorders, how those DNA bases contribute singly or in large amounts to put us at risk for various traits is useful, allows insights, but also buried in there is potential problems, right? I you know, the notion that DNA is not destiny is super important. I think we do tend to think of these things too simply, in deterministic ways that are just downright dangerous, right?
Like, you know, someone is not who they are just because of their DNA code. And you know, whether one winds up being a Nobel Prize winner, or, you know, a convicted felon. It's very complicated, and the social factors, as well as things that are part of inheritance, that aren't in the DNA code, so-called epigenetics, all of those things play into who we are and whether, around health and disease and around many traits. But we have tried to graft on this very sort of like binary thing from the DNA that that is not is not accurate.
[32.20]
And taken to its extreme, you know. And there have been times you go back to, you know, some of the horrible stuff that went on in the early 70s around intelligence and people of certain ancestries, you know, usually referred to in racial terms, that was inappropriate, and we're still hearing echoes of that down to the present, and that's very problematic. And I think our society also has an educational mission, and I think helping people understand both the you know, the magnificence of our genomes and what we can do with that information, how liberating that can be, how empowering that can be, but at the same time, making sure that we all know its limits And and things that are just untrue and unfair, and and it's a mix.
Vivien
I guess there's going to be testing and conversations in the NICU with newborns sometimes, and then also in vitro fertilization clinics are, I'm sure, not with your approval, but they're offering all kinds of strange tests. You know, polygenic genetic risk score, intelligence tests, Olympic athlete, yeah,
yeah.
Bruce Gelb [33:25]
I think we'll start with newborns on that. So I think that highlights the sort of double edged sword thing I was talking about, you know, and we'll, I know, we'll have some talks at our meeting. And it's, it's getting a lot of press. I think we spoke about it last year, Vivien.
The ability to rapidly and rapidly here is like a week or less to sequence a sick, critically ill baby's genome, to figure out why they're so sick, is unbelievable. It's transformative. And you know, it's only going to get better from here. It's changing how critical newborn care is delivered across the country and ultimately across the globe. That's empowering.
But you know the notion that you're going to sequence every baby who's born and then tell the parents whether the kid will be able to do DC calculus is ridiculous, I think, and it's not going to happen. And I'm not sure I would even want to live in that world if it could, but I'm confident that DNA is not going to tell you that, and I think that's where you know we have to be super careful.
Mike [34:40]
And just continuing on from this, I attended the European Society for Human Genetics, yeah. And I went to a very interesting talk from someone talking about the importance of the exposome and how that affects, you know, traits. So in the context, yeah, and just in the context of, you know, like genes are not destiny. How do you think, is this a topic that will be on the agenda at ASHG, is this? Is this something that we need to grapple more with? Because, of course, it's very easy to, you know, draw blood, do sequencing, and you have their genome. But of course, collecting exposure data is just environmental data is a different order of magnitude.
Bruce Gelb
So, yeah,right, yeah. So I'm well familiar with exposomics. We have quite a prominent institute here, my at Mt Sinai, that's devoted exactly to that. And for those not familiar, just like in the genome, we're talking about the entire collection of your genes. With exposomics, you're talking about the entire collection of things you're exposed to, chemicals, but also social environment and all sorts of things like that, right? So I mentioned already that variability things I was talking about, penetrance and variable. And basically the way we currently think of it now is there are three buckets that we attribute the variability to or the unpredictability, two of them I previously mentioned. One is other genetic factors. The other is the randomness thing. The third bucket is the exposure piece. And there are people we will have talks on that interaction between genetics and exposures. We call it gene by environment. The problem is that the number of possible exposures and their combinations not quite infinite, but tremendously large. And figuring we we have enough problems figuring out how to power statistically power studies to robustly look at gene by gene interactions, you then bring in. Instead, you want to look at gene by environment, where environment is like hundreds of thousands of things, it becomes nightmarish to come to clear conclusions. And I think working that out is one of the challenge moving forward a little easier for common. Traits, because you can get large numbers of people that have high blood pressure or what have you, harder for rarer traits, where I think those exposures still matter, because you can't put together collections of hundreds of thousands of people with rare disease by definition, even if you somehow manage to recruit every single person who has a you know, worldwide, so it's a struggle.
It's not going to be easy, but I think, you know, that's where we need innovation and creativity.
Vivien
I wanted to circle back, and I know that it's a bit fashionable, but when you were thinking about AI and machine learning, and as you look over the genetics field, do you sense that a lot of computational people are drawn to the field, also for jobs, but just because of interesting problems that they want to help solve, and are interested in, kind of getting involved in, whether it's consortia or even, you know, lab groups. Are you finding there's a trend now to do that?
Bruce Gelb [38:00]
I would say that this about about that question, our field, for quite some time, has been attractive to people from computational backgrounds. And, you know, we've had people, you know, with PhDs in physics, coming into human genomics, because a lot of the problems we've had and from sort of statistical mathematical backgrounds as well, because the nature of the problems draws on that AI is just really an extension of some of that sort of computational work. It is true that there are computer scientists at elite institutions that are working to develop completely new models for doing AI, but what our field needs is application of the existing models, whatever the state of art will be in it, and it does continue to evolve in order to create different models.
You know, often what are called foundational models to allow us to address the critical problems. I don't think that's going to be limiting for us, getting people to do it. And I, you know, I've said this already during our conversation, but the fact that our field has been such a dynamic one and advancing makes it attractive to young people thinking about what to head into, and so I'm not at all concerned that we'll have trouble with the workforce in terms of applying AI to human genetics and genomics,
Vivien
That's cool. Jobs are cool, and also interdisciplinarity is cool.
Mike. Any more questions before I keep going through my stack, and then we'll let Bruce run on to his busy day.
Mike
No please go ahead.
Vivien
I know that, and Mike and I have talked about this biobank analysis plays a big role in genetics research. And I guess the question is, how do you see not just the UK Biobank, but obviously biobanks, such as the one you have at Mt. Sinai, but also others too? How do you see the role of biobanks and biobanking? There are standards to uphold, there's metadata annotation, there's a lot of, I guess, back room things that have to happen in order for a biobank to be usable and, I guess, plunkable into papers. So what kinds of measures do you see as necessary, I guess, for biobanks to kind of be that way? I know, UK Biobank invests a lot in that kind of work, but not every biobank does. I think,
Bruce Gelb
Yeah.And I think we've seen variability across biobanks, you know, I think that they have to think deeply about how they're going to make their data available to the scientific community. And I think that, you know, the UK Biobank, I, for instance, I think has done an excellent job with that in general. I think, you know, I'm not going to call anybody out, but I think there are other bio banks where that has been less well done. I think that is, ultimately should be thought of in sort of, I don't know, living up to the promises we're making to people who are generous enough to agree to participate in the bio banks, that we're going to use the information, the data that's derived from learning about their health and upbringing and what have you, and their DNA. And if we're measuring other things, those other things too, that we owe it to them. Most of all, we owe it to them to make sure that it's used robustly. And I think, you know, we're learning as we go along. We make mistakes, and hopefully we we circle back and do it better. There's also the issue, you know, we've really evolved in terms of how we think of return of results. It you know, there was a time not so long ago in human genetics, where you were, you volunteered, you gave consent, and then you gave your tube of blood, and that was sort of the end of your engagement. And I think that that that has changed also there's an expectation level, but both just in terms of logistics and in terms of.
Vivien
oh, so does that mean, for example, people who participate are will hear back about some results and maybe risks, but also just about an analysis results.
Bruce Gelb [42:20]
Yeah. But in order to return those results, at least in the US context, the work the DNA analysis has to go on in a way that's compatible with what, what is the clinical standard, in order you know, for a clinical test. And the problem is that that standard, what we while we know what it is, turns out to be more expensive to meet. And so you have a lot of decisions about how to do your research. I mean, typically we do it, not in that way. And then when we find something we want to return, we flip over to the other side and just pay the cost for that one little piece to make it affordable. But the more you want to cover. But then there's all when you step back, there's all sorts of complicated ethical issues that come with this territory about what do you want to return?
[43:10]
And then, I mean, I happen to, I mean, I come from the pediatric background, right? So once you start talking about children who have been, frankly, left out from many of the key bio banks so far, which I find problematic, and it's that's been because there are all sorts of tough decisions, like, especially if what you're finding is a disorder that might pop up in adulthood. Do you return it now? I mean, the parents feel like they're in charge, and that's how we work in society. On the other hand, you are in essence taking away from the child their right to decide whether they want to know this or not.
You know you can't unring bells, as they say, so, like, if you tell the family about this genetic change in this child, that means, when they become an adult, it's known to them, and they may have been a person who didn't want to know that. That's complicated. And then you have to find the kids when they become adults, which in the US is age 18, and get their okay to continue to participate, which is, you know, in larger bio banks, we have like, half a million or a million people, whatever percentage it is, it's a non trivial task, and it's not free. So those are all things that we've been grappling with, with, with the bio banks.
And last thing I'll say is, I think many of the bio banks in the US, let's take all of us as an example, are doing a wonderful job of being more inclusive, and therefore the people that are in them are more diverse. But the price there is it's even more important that you get some of that stuff right in terms of, for instance, return results, because if you're not from the viewpoint of people who have been, you know, over time, systematically excluded. This looks like just another raw deal that they've just been handed, you know, like it's a bait and switch situation, so you have to be very careful and and you cannot assume that one community is the same as another.
So, you know, Native American community is not the same as the African American community and the US. We use the term Hispanic, but that's a whole series. You know, people who derive from Cuba are not the same as people from Mexico, etc, etc. So there's a lot of complexity there. Our society grapples with that. We've had position papers around some of those things over time. But those are all those all come to pay our when you're thinking about bio bank work, it's important work. It's proving incredibly you know, a wealth of discoveries are being made, using them both for complex traits and simple traits both and so it will continue. And the fact that we can sequence for less, fewer and fewer dollars makes it you know, even more so, but, but on the other hand, you know, just like we say, bigger kids, bigger problems, you know, bigger bio banks, bigger bigger headaches to deal with,
Mike [45:55]
If I may, follow up on this point. You know, you mentioned earlier the importance of partnerships with the industry. And I think in the context of bio banks, we have the, you know, the examples of how the exome and genome sequencing performed in the UK. Biobank, for example, was funded by pharmaceutical partners. And I was wondering whether you had any thoughts on how do we balance the interests of researchers, both in academia and industry, working together and also for the people, the participants, who you know, are a very important part of these studies. And I think this is especially interesting to think about in the current context, where we have 23andme as an example of, you know, not a biobank per se, but a large, well used public data set. But they're having some, you know, business issues, and now there's open questions about, will this data remain available and usable by the research field, like, how? How do we balance all of these competing, you know, interests and needs in a way that maximizes the utility for
everybody?
Bruce Gelb [47:00]
So I would say a few things. First, I think it's important to keep some humility around this and say these, these are different. Difficult issues at best, we hope to read something approaching consensus, but there are going to be some that are very contentious and not easy to reach consensus around. I think that it's critical to have transparent conversations that involve a wide range of people. And there are, there are many, many people who deserve and hopefully are getting seats at the table for those discussions. And it, and it's certainly not just a bunch of scientists who have, frankly, interest in the in the outcome of the discussion, right?
[47:20]
And I think including ethicists and advocacy groups and so on, are all incredibly important to those discussions, I personally would put something like 23andme in a little bit of a different space, because there it was a fee for service that people decided to pay for to get information and so on. And yes, if that company goes belly up and the data go away, that'll be terrible. But somehow, to me, that's a little different than the sort of ethical obligation where we're doing consent driven research, where people volunteered, and we have a commitment to them, and we have to live up to that commitment to them. So I think they're rather different.
[48:20]
The last thing I'll say is that, and I think our field is right up near the front on this. I think that there was a time in academia where we start sort of turned our nose up at at people in industry and industry as something lesser, somehow forgetting that those used to be our colleagues within academia who at least trained with us and then went out to do it. I think there are things that industry does extremely well. They have their conflicts of interest. For sure, they are running a company. They are usually, you know, they are not non profit organizations. So I think acknowledging that and putting guardrails around that is important. On the other hand, they have enormous strengths. They have viewpoints, you know, you look at a company like Regeneron, and what they've accomplished in our in our human genetic space, I think it's fantastic, and I think we would be foolish not to all work together. And I think there are ways to do that. And I think in general, transparency is is goes a long way. I'm not saying it's going to be completely the answer to every problem, but it goes a long way to reassuring everybody. And I'll say one last thing, why I think it's so important to get all this right.
We're living in a time of unprecedented skepticism about facts, about science, right? It started, I mean, anti vaccine goes back, you know, probably a century or two, at least, from the invention of vaccines, but clearly coming out of COVID it has, shall we say, metastasized from being anti-vax to a broader anti science. And I think that is very frightening and concerning, because so much of what happens in science happens with public funds. That's true here in the United States, and that's true in Europe and in other parts of the world as well. And that can only continue if our elected representatives are who are, after all, carrying out the will of the populace all believe that this is something important for society.
And I think therefore, when it comes to biobanks, I think being very clear and very honest about what we are doing, what we're not doing, how we're doing it, listening to people to try and quell concerns that are some of them appropriate, but some of them are based on on really untruths. Is really important for maintaining the belief in the scientific enterprise.
Vivien
Wow, yes, that’s wonderful. And also thank you for the openness. Let me just check to see if people have any questions. I feel like that was an awesome closing statement. Mike, do you have any questions or comments or anything else you wanted to say? Or, Bruce, maybe you wanted to close more, but it seems really that seemed like a really nice note.
Bruce Geld
I’m happy that I just want to say thank you to both of you for hosting this, and it was really a pleasure to participate. I look forward meaning to see you at the meeting. Mike, I don't know that you're going to be there, but if not another time or at the ESHG, maybe we'll bump into each other. It's also a wonderful meeting and just a great pleasure to share the excitement that we have in human genetics and genomics and in our society. Thank you.
Vivien
That was Conversations with Scientists. Today's episode was a sneak peek of the 2024 annual meeting of the American Society of Human Genetics. The guests were Dr Bruce Gelb, current president of the American Society of Human Genetics, ASHG, And he is a researcher at the Icahn School of Medicine at Mt Sinai in New York City. Another guest was Kara Flynn, who is the Senior Director of Public Engagement, Communications and Marketing at the American Society of Human Genetics. And we'd like to thank them for taking part in this podcast.
My fabulous co-host today was Dr Mike Fletcher, senior editor at Nature Genetics.
The music in this podcast is Blue Mountain Inn by Omri Smedar, licensed from artlist.io.
I just wanted to say because there's confusion about these things sometimes. The American Society of Human Genetics didn't pay for this podcast, and nobody paid to be in this podcast. This is independent journalism that I produce in my living room. I'm Vivien Marx, thanks for listening.