Speaker 1: I will say that I was a science nerd from
Speaker 1: a very young age. I actually have sitting in my
Speaker 1: office at work, tiny little child's microscope that I was
Speaker 1: given as a gift when I was, you know, very
Speaker 1: very young. And I was that kid. You know, if
Speaker 1: I cut myself, I would run into my room and
Speaker 1: put some of the blood on the slide and see.
Speaker 1: I didn't know what I was looking at. I don't
Speaker 1: think the microscope was even strong enough to really see anything,
Speaker 1: but the interest was there. That was Dr Jill Holland Back,
Speaker 1: an immuno geneticist at the University of California, San Francisco. Today,
Speaker 1: that former self described science nerd leads research into one
Speaker 1: of the mysteries of COVID, specifically why some people get
Speaker 1: the disease but show no symptoms, and what that can
Speaker 1: tell is about treating and preventing it. I'm a land
Speaker 1: ververe In. This is Seneca's one Women to Hear. We
Speaker 1: are bringing you one hundred of the world's most inspiring
Speaker 1: and history making women you need to hear. For years,
Speaker 1: Dr Hollandbach and her team at the Hollandbach Lab have
Speaker 1: focused on a set of genes called h L A
Speaker 1: and h l a's relationship to autoimmune diseases like multiple sclerosis.
Speaker 1: But since the pandemic, the Hollandbach lab has turned its
Speaker 1: attention to COVID as well. Their answer to the question
Speaker 1: of symptomless COVID may lie in the genetic mutation of
Speaker 1: h l A. Listen and learn why. Dr Jill Hollandbach
Speaker 1: is one of Seneca's One Women to Hear. I'm speaking
Speaker 1: today with immuno geneticist Dr Jill Holland and we're going
Speaker 1: to discuss her research on COVID. Welcome, Dr Holland Beck.
Speaker 1: It's really wonderful to have you with us. I know
Speaker 1: our listeners are going to be very interested in this topic.
Speaker 1: Thanks so much for having me. Now I understand your
Speaker 1: leading research into who does and who does not get
Speaker 1: COVID well, I first of all, I want to say
Speaker 1: that we're really focused on people who have tested positive
Speaker 1: for the virus that causes COVID but never had symptoms.
Speaker 1: So for those who actually have had the COVID virus
Speaker 1: but don't show any symptoms, why is that? Is it
Speaker 1: a genetic mutation? We think so, not probably not everybody,
Speaker 1: but in a proportion of the individuals that we've studied,
Speaker 1: it seems that a specific version of an immune system
Speaker 1: gene that we're interested in generally in my lab seems
Speaker 1: to make them much more likely to be symptomatic. So
Speaker 1: perhaps you can tell us more about precisely what you're
Speaker 1: looking at in your research or their implications in terms
Speaker 1: of genetic mutation. What can you tell us about what
Speaker 1: you've learned? Sure, so my lab is generally interested in
Speaker 1: a set of genes called h L A, human leukocide
Speaker 1: anergen and I think a good way to think about
Speaker 1: it is to think about the transplant settings. So when
Speaker 1: we talk about matching for a transplant, these are the
Speaker 1: genes that we match on. And in fact two UM
Speaker 1: one major component of our study involved going back to
Speaker 1: individuals who are registered as potential bone marrow downors and
Speaker 1: asking them about their COVID experience, because we already have
Speaker 1: data on the genes of interest for them. So h
Speaker 1: L A or genes that encode important immune system molecules,
Speaker 1: and the job of those molecules is to present or
Speaker 1: show to UH your effect or cells, your T cells
Speaker 1: in your immune system, pieces of foreign anigen or peptide,
Speaker 1: pieces of protein. Is probably a better way to put
Speaker 1: that better derived from things like viruses and bacteria, and
Speaker 1: then the T cells come along and they inspect those
Speaker 1: pieces of foreign protein and generate an immune response if
Speaker 1: it's something that is not supposed to be there. So
Speaker 1: the interesting thing about h l A is that they're
Speaker 1: extremely variable between people, between populations. So most genes have
Speaker 1: maybe one or a few different versions that we refer
Speaker 1: to as a leal. H l A has literally thousands
Speaker 1: and thousands of different versions that we see, you know,
Speaker 1: across the globe, and that's why it can be so
Speaker 1: hard to match somebody for a transplant, because one person's
Speaker 1: h l A looks very different from another person's h
Speaker 1: l A. So what we and and many others hypothesized,
Speaker 1: you know, very early in the pandemic, was that different
Speaker 1: versions of these genes, because they're so important in the
Speaker 1: immune response to pathogens, might be important in differential response
Speaker 1: to the virus that causes COVID nineteen and so we
Speaker 1: went out to start looking for individuals who had tested positive.
Speaker 1: Because the important thing in studies like this is that
Speaker 1: it's very hard to control for exposure, so it's very
Speaker 1: hard to ask the question does somebody who gets infected
Speaker 1: and who doesn't. Because there's so many variables in whether
Speaker 1: somebody is exposed to the virus, what kind of mitigation
Speaker 1: you know, are they have, they've been masking, and things
Speaker 1: like the humidity in the room at the time of exposure.
Speaker 1: There's far too many variables for us to really say
Speaker 1: for certain that somebody has or hasn't been exposed, or
Speaker 1: that their lack of infection is due to something genetic.
Speaker 1: But what the question that we can ask is, when
Speaker 1: somebody has a confirmed infection, they've tested positive for the virus,
Speaker 1: what does their disease course look like compared to the
Speaker 1: person next to them? Because we know that there's a
Speaker 1: huge range of disease course, everything from asymptomatic disease to
Speaker 1: you know, extremely bad outcomes, people becoming hospitalized, ventilated, and
Speaker 1: you know, we've had you know, tragic number of deaths,
Speaker 1: and so what we want to know is what mediates that?
Speaker 1: What you know, what is there something biological, Is there's
Speaker 1: something genetic, No, is there's something about their h l
Speaker 1: A that changes how somebody responds to the infection. And
Speaker 1: a lot of the studies up to this point that
Speaker 1: have been done thinking about not just h l A,
Speaker 1: but genetics in general have really focused on the severe
Speaker 1: outcome end of the spectrum. And there's really good reasons
Speaker 1: to do that. You know, people have gotten really sick.
Speaker 1: We want to understand why we want to prevent that.
Speaker 1: Some of the reasons that those have been the patients
Speaker 1: who have been focused on are practical because when people
Speaker 1: are in the hospital, you're more you know, it's much
Speaker 1: easier to get samples, biological samples like blood and DNA.
Speaker 1: But really, you know, the vast majority of people who
Speaker 1: experienced infection do not wind it in the hospital. They
Speaker 1: have you know what we would term, you know, relatively
Speaker 1: mild to moderate disease. And we were kind of interested
Speaker 1: in those people, and specifically the subset of people who
Speaker 1: just don't have symptoms at all, not a stuff, he knows,
Speaker 1: not a scratchy throat, nothing, And so we asked that
Speaker 1: question individuals who have in infected with the virus, did
Speaker 1: you or did you not have symptoms? And what we
Speaker 1: found was this extremely strong effect of a particular version
Speaker 1: of one of the h l A genes called h
Speaker 1: l A B that seems to really enhance somebody's chance
Speaker 1: of not having symptoms when they're infected with the virus.
Speaker 1: So fascinating, and can that be determined in advance for
Speaker 1: somebody to know if they've got that makeup that they're
Speaker 1: going to be symptomless. Well, first of all, I want
Speaker 1: to be clear, just because you have this particular version
Speaker 1: of this gene, so the gene is called h L
Speaker 1: A B and and the version that we're interested in
Speaker 1: is called h L A B fIF one doesn't mean
Speaker 1: that you absolutely will be asymptomatic. It just means that
Speaker 1: you're probably too to three times more likely to be asymptomatic.
Speaker 1: So I think that it doesn't necessarily ensure that you
Speaker 1: would be. I don't know that it would be particularly
Speaker 1: helpful for somebody to know that it's UM. It's not
Speaker 1: a test that's done commonly, unless somebody happens, for example,
Speaker 1: to be a volunteer bone marrow donor they might know
Speaker 1: their type. But I don't know that that would be
Speaker 1: a particularly useful thing for somebody to know. I think
Speaker 1: that you know. For me, it's more about what this
Speaker 1: finding tells us about the immunopathology of the disease and
Speaker 1: what kind of directions it can point us to. In
Speaker 1: terms of possible vaccine design and possibly treatments. So this
Speaker 1: is ongoing research as you keep probing and coming to
Speaker 1: various conclusions along the way. Absolutely, So you know, after
Speaker 1: this initial finding we went back to the lab. We've
Speaker 1: since um and we're in the in the middle of
Speaker 1: writing this up right now, so I'm hoping that this
Speaker 1: paper will be released fairly soon. But went back into
Speaker 1: the lab to understand first of all, can we detect
Speaker 1: this in in other patient cohorts UM? And also you know,
Speaker 1: what is the the actual um functional activity of T
Speaker 1: cells in these individuals. So that's that's something that we've
Speaker 1: been looking at carefully. And UM have some really interesting
Speaker 1: new data on senecas one hundred women to hear. We'll
Speaker 1: be back after the short break. You had a research
Speaker 1: team called the Holland Buck Lab. Are there other scientific
Speaker 1: questions besides those you've just been describing that you're looking
Speaker 1: at as well trying to answer? Sure? So, my lab
Speaker 1: at UCSF is broadly focused on immuno genetics in human
Speaker 1: health and disease, So that mostly takes the form of
Speaker 1: us thinking about these h l A genes and UM. So,
Speaker 1: for example, one of the reasons that I'm in the
Speaker 1: Department of Therology at UCSF is that a particular version
Speaker 1: of h l A is also the most important predisposing
Speaker 1: gene in multiple sclerosis. And we've examined a number of
Speaker 1: neurological diseases from the point of view of this gene
Speaker 1: system Parkinson's disease, my skinia gravis for example. So that's
Speaker 1: ongoing work that we're focused on. We're very focused in
Speaker 1: on multiple sclerosis in my lab, and we're also interested
Speaker 1: in other common elements and and how different versions of
Speaker 1: h l A predispose somebody or or protect them from
Speaker 1: common illnesses as well as ubiquitous viruses like megalovirus. So
Speaker 1: we're asking those questions all the time in the lab,
Speaker 1: and that's really the main focus. And we were doing
Speaker 1: that long before COVID, but you know, once the pandemic
Speaker 1: came around, we absolutely refocused a lot of our energies,
Speaker 1: as did so many others, to ask these questions well.
Speaker 1: And they're so important obviously because they affect just so
Speaker 1: many people who still don't have the answers they'd love
Speaker 1: to have, right right I you know, I mean, on
Speaker 1: the one hand, it feels like it's been a long time,
Speaker 1: and and how are we still here? And why are
Speaker 1: we still worrying about this? Nobody I don't think anticipated
Speaker 1: this was going to go on for so long. But
Speaker 1: you know, another way to look at it is there's
Speaker 1: just been incredible, remarkable progress made in a very short
Speaker 1: period of time. I'm completely blown away by, you know,
Speaker 1: the amazing work that's been done all over the planet
Speaker 1: trying to understand this disease. And it's really just been
Speaker 1: an incredibly impressive scientific feat But I think that, you know,
Speaker 1: people like me and and my colleagues are just incredibly
Speaker 1: motivated because we're the same as everybody else. We've experienced
Speaker 1: the pandemic the same as everybody else, right, And you know,
Speaker 1: I first started putting together the project to look at
Speaker 1: this like so many other people, sitting you know, in
Speaker 1: my home office on lockdown. So I think there's you know,
Speaker 1: a lot of motivation across biomedical science to answer these questions. Well.
Speaker 1: And I think that's that's true about your mentioning MS
Speaker 1: as well. So many people are afflicted with that absolutely, yeah,
Speaker 1: And it's an extremely debilitating disease and impact you know,
Speaker 1: people in the prime of their lives. So you know,
Speaker 1: in general, this is just extreme, really gratifying work to do.
Speaker 1: And you know, I feel like I've been really fortunate
Speaker 1: to have been able to focus my my work life
Speaker 1: on on solving these problems. It definitely helps me to
Speaker 1: feel a little bit less helpless in the face of
Speaker 1: what we've all experienced. Well, it's certainly critically important. Can
Speaker 1: we talk about you a little bit you personally? I
Speaker 1: know you're an you know, geneticist. What does that mean.
Speaker 1: I mean, it's a big word, and I'm sure our
Speaker 1: listeners are wondering what does she do or what does
Speaker 1: that field represent? Sure, so it's really a sub field
Speaker 1: of genetics. I trained as an immunologist. Um I did
Speaker 1: my PhD in immunology at Berkeley, but I did my
Speaker 1: training during that time in a genetics lab, and so
Speaker 1: it's a sub field of genetics where we're focused specifically
Speaker 1: on these very variable immune response genes. And it really
Speaker 1: acquires an entirely different way of approaching genetics and thinking
Speaker 1: about genetics because of the high levels of variation, but
Speaker 1: also because it's so important to consider the structure and
Speaker 1: the function of the immune molecules while we're thinking about
Speaker 1: the genetic aspect. So it's a sub field that's generally
Speaker 1: um focused on things like transplant and autoimmune diseases, but
Speaker 1: it really has um kind of far reaching applications that
Speaker 1: is certainly wonderfully rewarding. It sounds like to be able
Speaker 1: to explore these areas. How did you get interested in
Speaker 1: this field? Was it your upbringing? Was there a moment
Speaker 1: when you really set to yourself, I want to be
Speaker 1: a scientist. Yeah. I will say that I was a
Speaker 1: science nerd from a very young age. I was interested
Speaker 1: in scientific things as far back as I can remember.
Speaker 1: I actually how of sitting in my office at work,
Speaker 1: tiny little child's microscope that I was given as a
Speaker 1: gift when I was, you know, very very young, and
Speaker 1: I was that kid. You know, if I cut myself,
Speaker 1: I would run into my room and put some of
Speaker 1: the blood on the slide and see. I didn't know
Speaker 1: what I was looking at. I don't think the microscope
Speaker 1: was even strong enough to really see anything, But you know,
Speaker 1: I was the interest was there. I used to you know,
Speaker 1: graph the details from my doctor's appointments and things like that.
Speaker 1: But you know, actually, when I was growing up, I
Speaker 1: didn't really understand that being a scientist was a job.
Speaker 1: I grew up in a you know, in a Jewish family,
Speaker 1: where if you were interested in science, you became a doctor.
Speaker 1: If you're interested letters, you became a lawyer. And those
Speaker 1: were the only two options that were presented to me.
Speaker 1: But you know, during the course of my education, I
Speaker 1: really kind of fell in love with immunology. That was
Speaker 1: during a period of time when I was working on
Speaker 1: my master's degree in public health. At the time, I
Speaker 1: had actually been interested in going into women's health and
Speaker 1: health policy. I had gone to work for Planned Parenthood
Speaker 1: straight out of college. UM, but I got a little
Speaker 1: bit sidetracked and fell in love with immunology. And then
Speaker 1: during the course of my PhD, I was particularly interested
Speaker 1: in h l A because my mother had rheumatoid arthritis
Speaker 1: and h l A is very important in autoimmune disease
Speaker 1: and including room toid arthritis, and that kind of sparked
Speaker 1: my interest and had an opportunity to work in a
Speaker 1: lab that was focused on these genes. And it's um,
Speaker 1: it's been quite a long time. The rest is history.
Speaker 1: Here I still am doing important work. Did your parents
Speaker 1: nurture your interest as a child in science or were
Speaker 1: there mentors along the way who inspired you. I think
Speaker 1: you know, my parents, Um, my father was was a
Speaker 1: c P A my you know, my mom had been
Speaker 1: an English teacher. They were not really stem people, so um,
Speaker 1: you know, they encouraged me, of course, but I think,
Speaker 1: you know, to be honest, you know, to the day
Speaker 1: my dad died, he used to variably describe me as
Speaker 1: a microbiologist. You know what of this that he never
Speaker 1: you know, he tried but didn't really understand what I
Speaker 1: was doing. But I certainly, you know, I had some
Speaker 1: great teachers along the way. I had a physiology teacher
Speaker 1: when I was in high school who really sparked my
Speaker 1: love for that topic, and I went on to become
Speaker 1: a physiology major at Berkeley. And then some you know,
Speaker 1: really key professors during during my time at Berkeley's so um, yeah,
Speaker 1: some great mentors along the way, and um peers and
Speaker 1: colleagues as well who have been extraored, early supportive through
Speaker 1: the years. Well, here at Seneca women we often emphasize
Speaker 1: how important it is to have women in science, and
Speaker 1: we still have to do better in that respect. I
Speaker 1: think you agree as a general proposition, but I wonder
Speaker 1: what you think about why having a women's perspective is
Speaker 1: important in your field if it is, well, I guess
Speaker 1: what I would say is, I don't know that as
Speaker 1: a woman, I necessarily have a different perspective, at least
Speaker 1: not on the science necessarily. But you know what, as
Speaker 1: a professor at a research and university, part of my
Speaker 1: job is to train the next generation of scientists, and
Speaker 1: I think that that's where, you know, having representation is
Speaker 1: really just so important. I think that, um, you know,
Speaker 1: we bring to the table a different set of life experiences, UM,
Speaker 1: A different way of having experienced the world and moved
Speaker 1: through the world, and that is really, um I think
Speaker 1: an asset when we're training not just you know, the
Speaker 1: next generation of women's scientists, but the entire next generation
Speaker 1: of scientists. I think that having that different perspective on
Speaker 1: you know, life and and life experiences is extremely important
Speaker 1: and helpful, UM as as we train young scientists. Well,
Speaker 1: I always hate this moment looking at the clock when
Speaker 1: we're nearing the end of a fascinating conversation, but I
Speaker 1: really would like to ask you before we have to
Speaker 1: take leave. You know, given that we've all collectively gone
Speaker 1: through a couple of years now of the epidemic. We've
Speaker 1: been talking about COVID, We've been talking about other viruses.
Speaker 1: Certainly there are more on the horizon we haven't named
Speaker 1: or don't know anything about because there yet at the
Speaker 1: development stage, probably, But given all that, what makes you optimistic?
Speaker 1: What gives you hope? Because this is tough stuff, it is.
Speaker 1: But you know, as I said earlier, I realized it
Speaker 1: feels like it's it's been a long time, and that
Speaker 1: it's been you know, one step forward, two steps back
Speaker 1: through the pandemic. But you know, from where I sat,
Speaker 1: I'm just absolutely marveling at the progress that we've made.
Speaker 1: And it's really been an incredible experience to be in
Speaker 1: the middle of these research efforts and to look around
Speaker 1: me and see my colleagues at UCSF and across the
Speaker 1: country and across the world who have really come together
Speaker 1: in I think a unprecedented way. And I'll say that
Speaker 1: the levels of collegiality and collaboration that I've experienced, you know,
Speaker 1: particularly working on this topic, have just been so heartening.
Speaker 1: Um I think that there's often a lot of um,
Speaker 1: you know, competition and science and you know, trying to
Speaker 1: be very protective and and get ahead because you know,
Speaker 1: just like everybody else, we have careers that we're trying
Speaker 1: to promote and move forward, and that's really a lot
Speaker 1: of that has fallen by the wayside during the pandemic,
Speaker 1: and the the level of collaboration has has been really
Speaker 1: something to behold. And I think that the proof is
Speaker 1: in the pudding the strides that we've made. I mean,
Speaker 1: if if you just think about the vaccines alone, I mean,
Speaker 1: it's it's really just an absolutely incredible scientific accomplishment. But
Speaker 1: that's really just you know, the tip of the iceberg.
Speaker 1: What we've learned in the last two and a half
Speaker 1: years is absolutely mind blowing. And so when I think
Speaker 1: about what comes next, I mean, there's there's always going
Speaker 1: to be challenges. I really hope there's not going to
Speaker 1: be another challenge of this magnitude in my lifetime, but
Speaker 1: but who knows. But when I see how folks really
Speaker 1: apply their expertise and come together to solve these problems,
Speaker 1: and it makes me very hopeful that we'll be able
Speaker 1: to deal with whatever comes next. Well, thank you so much,
Speaker 1: Dr Jill Holland Beck for the important work that you
Speaker 1: are doing and will continue to do. It makes such
Speaker 1: a difference and I know you've made us a whole
Speaker 1: lot smartyr today listening to you. Thank you so much,
Speaker 1: Thank you so much for having me, and thanks for
Speaker 1: your interest in this work. Appreciate it. It's amazing to
Speaker 1: see how dedicated researchers like Dr Holland Beck are tackling
Speaker 1: some of the world's most pressing challenges. Here are three
Speaker 1: things things I took from that conversation. First, while COVID
Speaker 1: has been a global plague, it's also brought about incredible
Speaker 1: collaboration among scientists worldwide, and that has resulted in tremendous
Speaker 1: progress against the disease in an incredibly short time. Second,
Speaker 1: Dr Hollandback reminds us that good science requires a diversity
Speaker 1: of viewpoints and backgrounds. As she says, different people bring
Speaker 1: a different set of experiences to the table, and that
Speaker 1: diversity is crucial as we train the next generation of scientists. Finally,
Speaker 1: Dr Holland Back shows us how personally rewarding scientific research
Speaker 1: can be. She says that working to solve problems like
Speaker 1: COVID makes her feel a little bit less helpless in
Speaker 1: the face of what we've all ex variant. Tune in
Speaker 1: next time to hear about our next Featured Woman and
Speaker 1: discover why she's one of Seneca's one hundred Women to Hear.
Speaker 1: Seneca's one hundred Women to Hear is a collaboration between
Speaker 1: the Seneca Women Podcast Network and I Heart Radio, with
Speaker 1: support from founding partner PNG Have a Great Day,