Immunology, Tay Sachs, vaccines and the feeling of intimidation when interviewing a person who has won a Nobel prize are the topics of this episode.
Dr. Beutler, who was awarded the 2011 Nobel Prize in Physiology or Medicine with another researcher, came to Bellingham, WA in 2018 and I have a few minutes to have a discussion with him. I also enlisted the help from Spark Science veterans and WWU scientists Dr. Jackie Rose and Dr. Dahlberg to answer some of the questions I had about biology terminology and analysis of Dr. Brutler’s answers.
A big THANK YOU to WWU Chemistry for fitting Spark Science in Dr. Beutler’s schedule.
Make sure to check out Dr. Rose and Dr. Dahlberg back in Season 1.
Click Here for Transcript
Dr. Regina Barber DeGraaff: Welcome to Spark Science. This is a special episode where I enlist my colleagues to help me dissect an interview with Nobel Laureate Bruce Beutler [pronounced “Boyt-ler”]. We apologize for mispronouncing his name so many times in the beginning of this episode.
>> Here we go!
[♪ Blackalicious rapping Chemical Calisthenics ♪]
♪ Neutron, proton, mass defect, lyrical oxidation, yo irrelevant
♪ Mass spectrograph, pure electron volt, atomic energy erupting
♪ As I get all open on betatron, gamma rays thermo cracking
♪ Cyclotron and any and every mic
♪ You’re on trans iridium, if you’re always uranium
♪ Molecules, spontaneous combustion, pow
♪ Law of de-fi-nite pro-por-tion, gain-ing weight
♪ I’m every element around
Dr. Regina Barber DeGraaff: Welcome to Spark Science, where we explore stories of human curiosity. My name’s Regina Barber DeGraaff. I teach physics and astronomy here at Western Washington University, and I am here today with my two great friends and veterans of Season One of Spark Science, Dr. Lina Dahlberg and Dr. Jackie Rose. How are you doing today?
Dr. Lina Dahlberg: Super duper!
Dr. Jackie Rose: Doing great!
Dr. Regina Barber DeGraaff: So I brought you back because I had a one-day notice‒it was last minute‒and they were like, “Guess what? This guy who has won a Nobel Prize is at our university. You should interview him,” and I was like, “Okay…” and I had a very little time to prepare and I had about 15 to 20 minutes to talk to him. And I brought you two in because we’re going to listen to some clips and kind of dissect what he talked about, because I think that there was some jargon that‒I was just lost while he was talking‒but also he talks about biology and gene editing, which I know nothing about, and maybe you two do.
So listeners, you might remember Dr. Lina Dahlberg‒we were talking about the science of smell‒and Dr. Jackie Rose. We had a very fun episode about the science of the movie Inside Out, where we were just being crazy.
Dr. Jackie Rose: Yeah.
[all chuckling]
Dr. Lina Dahlberg: Super scientific!
Dr. Jackie Rose: Super scientific.
Dr. Regina Barber DeGraaff: She’s nodding. But first of all, before we get into this, the scientist I interviewed is named Dr. Bruce Beutler (I’m guessing that’s how you say his name). He won a Nobel Prize in 2011 for Physiology and Medicine, and I don’t understand what he did. So that’s why I brought you two in.
So who wants to give our listeners a quick synopsis of why he won the Nobel Prize?
Dr. Lina Dahlberg: Okay, I’ll go, okay!
[laughter]
Dr. Regina Barber DeGraaff: So this is Dr. Lina Dahlberg talking.
Dr. Lina Dahlberg: The really important thing that the Nobel Prize was awarded for‒specifically for Dr. Beutler‒was the discovery of the toll-like receptors, which are a class of proteins, and proteins are sort of molecular machines that sit on‒these ones, in particular, sit on the outside of our cells. And the protein receptors that he discovered and characterized are able to interact with pathogens. And so pathogens are things that we don’t want invading our bodies. And specifically, he found one of these receptor proteins that could bind to a lipopolysaccharide, which is a long word that means “fatty sugar molecule.”
Dr. Regina Barber DeGraaff: Okay, in our bodies?
Dr. Lina Dahlberg: Actually outside our bodies.
Dr. Regina Barber DeGraaff: Outside of our bodies.
Dr. Lina Dahlberg: …which is important. The whole idea here is if you have a nasty bacterium or fungus, it’s probably coated with these lipopolysaccharides (so, fatty sugar molecules). And one way that our bodies can be sure that we don’t let them get very far is by detecting their presence in or around our bodies. So these proteins on the outside of our cells are able to sense the presence of pathogens in our bodies by finding out which one of these greasy sugar molecules might be around. Once those molecules are sensed, then the body can launch an inflammatory response. So maybe you get the sniffles or you break out in hives or you have a fever, but all of those are defense mechanisms that our bodies have for fighting things off nonspecifically, just saying, “That is wrong! I don’t want it.”
Dr. Jackie Rose: So he studied these things. And if your system isn’t working very well‒if these detectors aren’t working‒then your immune system is compromised.
Dr. Lina Dahlberg: Compromised, right. And this is a specific part of your immune system that we call innate immunity, which means that it’s not super specific. So we’re not trying to come up with a new way to fight a new bug every minute. We’re just saying, generally speaking, if you see a lipopolysaccharide of this type or shape, it’s just bad.
Dr. Regina Barber DeGraaff: Okay.
Dr. Lina Dahlberg: We don’t ask any more questions. We just try and kill it.
Dr. Regina Barber DeGraaff: So he’s just studying these things. Like, what exactly did he do?
Dr. Lina Dahlberg: So he found‒it was understood that probably there were these receptors.
Dr. Regina Barber DeGraaff: Okay, I got it, I got it.
Dr. Lina Dahlberg: In fact, one of the earliest ways that they knew about it is that there were fruit flies who didn’t have these receptors and they weren’t very healthy, and he suggested that maybe there was a similar receptor in mice. And mice are kind of like people…
[Dr. Regina Barber DeGraaff laughs]
So he went in and found this receptor in mice and was able to open up a whole new branch of what we call immunology, the study of how our bodies stay healthy.
[♪ Janelle Monae singing Wondaland ♪]
♪ Early late at night
♪ I wander off into a land
♪ You can go, but you mustn’t tell a soul
♪ There’s a world inside
♪ Where dreamers meet each other
Dr. Regina Barber DeGraaff: So I was reading up about you, and I think you went to University of San Diego. UC San Diego, not USD. That’s a different school.
Dr. Bruce Beutler: Right, that’s different.
Dr. Regina Barber DeGraaff: I mean, how did you get to San Diego? Did you want to go to UC San Diego? Was that your goal? I read that you got done very quickly. Did you like it there?
Dr. Bruce Beutler: I did like it there, but I had a focused goal in life: I wanted to be in biomedical sciences. That had been true since I was in my early teens, let’s say.
Dr. Regina Barber DeGraaff: Okay. Was there a catalyst that did that, that was like, “I want to do this?”
Dr. Bruce Beutler: My dad had a strong influence. He was a biomedical scientist, a hematologist and a geneticist. He gave me quite a lot of advice then and suggested that I should go to medical school where I’d learn physiology, pathology, pharmacology, become familiar with biological systems, and then I’d be able to do anything I wanted to in biology.
Dr. Regina Barber DeGraaff: So how old were you when he’s basically strongly encouraging these terms that you may or may not have known?
Dr. Bruce Beutler: About 14 or 15.
Dr. Regina Barber DeGraaff: Okay, okay. So you were familiar with all this stuff.
Dr. Bruce Beutler: Yes.
Dr. Regina Barber DeGraaff: Okay. Were you already kind of on that path, where you, like, “I’m looking up to my father. This looks interesting. I’m hanging out in his lab and I want to do this?”
Dr. Bruce Beutler: Very much.
Dr. Regina Barber DeGraaff: Okay.
[Dr. Regina Barber DeGraaff laughs]
Dr. Bruce Beutler: I have to say I kind of idolized my father at that time.
Dr. Regina Barber DeGraaff: Yeah? But why UCSD though? So like, were you . . . ?
Dr. Bruce Beutler: I applied to two schools: to Caltech and to UC San Diego.
Dr. Regina Barber DeGraaff: Okay.
Dr. Bruce Beutler: And I got into UC San Diego, not into Caltech.
[Dr. Regina Barber DeGraaff laughs]
Dr. Bruce Beutler: And I felt a little bit bad about that. I remember my father making a kind of analogy and saying it was as though I had a choice between two restaurants, and at one they would serve more than I could eat and at the other they would serve much more than I could eat.
Dr. Regina Barber DeGraaff: Right! And you were like, “Maybe it was for the best.”
Dr. Bruce Beutler: Yes, I think it was not a bad thing to do.
Dr. Regina Barber DeGraaff: Well, I mean your dad sounds really supportive. Was he like, “Wherever you want to apply, it’s going to be great,” or did he also have opinions on certain universities that are going to help your path?
Dr. Bruce Beutler: He had the latter view, and we didn’t any of us kids apply to a large number of universities. It was never really a consideration to go to Harvard or Yale or any of the famous eastern universities because he felt we could get a top notch education in science or in other areas . . .
Dr. Regina Barber DeGraaff: I think that is not a common thought, though. I don’t know if it was different during that time, but this idea that you can still get a really great education, that you’re getting research experience at these UC schools and other schools, instead of going to the East Coast. Was your dad’s view common at the time, or was it kind of progressive?
[Dr. Regina Barber DeGraaff laughs]
Dr. Bruce Beutler: I don’t know. I think he was certainly right.
Dr. Regina Barber DeGraaff: Yeah. I think he was right too.
Dr. Bruce Beutler: Actually, it was quite a bargain to go to UC San Diego. If I recall, the tuition was $500 a year.
Dr. Regina Barber DeGraaff: So now you’re in the sciences. You graduate pretty early. I read that you graduated when you were 18 and you were off to grad school.
Dr. Bruce Beutler: Yes.
Dr. Regina Barber DeGraaff: And so did you find anything out at the university? Because you had this great background with your dad, but was there anything surprising at university that you were surprised that you found this out, and you’re learning your craft?
Dr. Bruce Beutler: I started to learn genetics in a formal way at UCSD. I worked in the lab of Dan Lindsley, who was a drosophila geneticist, and I began to see how genetics worked, which made a big impact later on. However, in those days, of course it was very different. One could never sequence DNA, for example. One could find a phenotype, map a phenotype, get a good idea about what the gene product might be, but you couldn’t do nearly what you can do now.
Dr. Regina Barber DeGraaff: Yeah. So what was the formal process like? Can you kind of give us a short description of that?
Dr. Bruce Beutler: I do remember. I had a project that I brought to Dan Lindsley related to something my dad was working on in his lab at City of Hope at the time, where he worked in those days. This had to do with hexosaminidase. I thought, wouldn’t it be interesting to find a genetic variant of hexosaminidase, which is the enzyme missing in Tay-Sachs disease, and have a Tay-Sachs model of a fly. I proposed that I might try to find the gene for hexosaminidase in the fly. And in fact, I was able to map it.
In those days, I had to outcross the fly to a marker strain, one called rucuca, I happen to remember. And then backcross and look at visible markers to try to locate the gene on a chromosome.
Dr. Regina Barber DeGraaff: So let’s go back, because our listeners might not know about Tay-Sachs. I only know about it because I have biology friends and we talk about this in our race and inclusion workshops, where we talk about misunderstandings of which groups has Tay-Sachs and which groups don’t (this idea of—what do I want to say—stereotyping). Can you talk to our listeners about exactly what is Tay-Sachs? And then, what do you mean by that mapping?
Dr. Bruce Beutler: Okay. First about Tay-Sachs, it’s a glycolipid storage disease in which an enzyme fails to degrade a polysaccharide chain that’s hooked onto a lipid. And the lipid polysaccharide complex correspondingly accumulates in neurons.
Dr. Regina Barber DeGraaff: Okay, so this is, where exactly in your body is the neurons going to be?
Dr. Bruce Beutler: In the brain.
Dr. Regina Barber DeGraaff: In the brain.
Dr. Bruce Beutler: That’s right.
Dr. Regina Barber DeGraaff: I’m just trying to break it down for our listeners. So things are building up in the brain that shouldn’t be.
Dr. Bruce Beutler: Correct. It’s a disease that is particularly poignant because children with it are born seeming quite normal, but then they become blind and regress in their development, and it’s 100% fatal.
Dr. Regina Barber DeGraaff: Right, and it’s very quick, too, so it’s going to happen . . .
Dr. Bruce Beutler: Typically within two or three years. There may be some survivors a bit longer than that, but not many.
Dr. Regina Barber DeGraaff: Right.
Dr. Bruce Beutler: It’s one of several glycolipid storage diseases. For example, there’s also Sandhoff’s disease, Gaucher’s disease, Niemann-Pick disease. All of these are more common in Ashkenazi Jews, even though they involve different enzymes that are genetically unlinked to one another. That in itself is a very interesting observation. It’s not well understood at the present time.
Dr. Regina Barber DeGraaff: Right. We talk about in our workshops that, because of the population that, and you start linking it to genetics, people can start making bigger leaps that are not good about, “Well then, maybe people should be wary of having kids” and stuff like that. I remember talking to a biologist saying that it might not just be that population of Jewish people, but it could be the region, right? It could be the region of Eastern Europe.
Dr. Bruce Beutler: It is mostly in Ashkenazi Jews. It is also found in some areas of Moravia. Fundamentally, it appears the mutation arose in the progenitors of Ashkenazi Jews in the Rhine River Valley. It may have spread to other populations, but very little because the Ashkenazi Jews were quite isolated.
Dr. Regina Barber DeGraaff: Right. And your family is Ashkenazi Jewish, your ancestry. Has there been issues with that? Have you ever been at conferences where they come up with comments and you have to explain to them the biology?
Dr. Bruce Beutler: No, not really, no.
Dr. Regina Barber DeGraaff: Okay, good. So as you’re doing this work and you present this idea, did it actually work out? Did you talk to your advisor, and you did your project, and there were big advances?
Dr. Bruce Beutler: Not big ones. I would have to say this is part of my scientific infancy. It was a good experience for me. If I remember right, I was able to map the mutation to a point between two of the markers on chromosome 3 in the fruit fly. And I couldn’t go much farther than that. There was a way in those days to delete parts of the drosophila genome which had been invented by my preceptor Dan Lindsley. It was called segmental aneuploidy. You could cut out a part of each chromosome and walk your way along the chromosome. But I didn’t get that far.
Dr. Regina Barber DeGraaff: Okay. But that was the future. You could surgically kind of alter these things so the fruit fly wouldn’t have to have this mutation. Or it would take it out.
Dr. Bruce Beutler: It would lack one copy of the gene.
Dr. Regina Barber DeGraaff: Okay, got it. Okay.
Dr. Bruce Beutler: Yes. But I never did find a fruit fly that was completely lacking in hexosaminidase activity, so I didn’t make the Tay-Sachs fruit fly.
Dr. Regina Barber DeGraaff: Oh, okay. But you had the idea! Somebody probably did, though, right?
Dr. Bruce Beutler: You know, I bet someone has. It certainly would be possible.
Dr. Regina Barber DeGraaff: Maybe I should look that up. You are an award-winning scientist. You’ve done all these things. What do you see really is the next big advance in your field? Since you only have so much time, that’s my question.
Dr. Bruce Beutler: We’re working now with mice. In fact, I have been doing that for most of my career. The mouse is a wonderful model for human diseases of all kinds. There is a Tay-Sachs mouse, for example. In fact, many human diseases are very well modeled in the mouse. It’s been our interest to try to understand immunity in the mouse. The immune system in the mouse also is very similar to the human immune system in how it works. Our approach has been to mutate the genome of the mouse with a chemical mutagen called ENU, ethyl-nitrosourea.
Dr. Regina Barber DeGraaff: Okay. For what purpose?
Dr. Bruce Beutler: We do that to destroy genes at random, or damage them severely. And then we breed the offspring of those mice that were exposed to the mutagen to bring the mutation to homozygosity. That is, to make it so that there are two copies of the mutation in every cell of the organism. And then we screen the mice, and we look to see whether immunity functions normally.
If we find in a particular family that we’ve made of mice that there’s an abnormality of immunity, what’s really new in our lab is that we know instantly what the genetic cause is. And it used to take years, but now we’re able to assign responsibility for a phenotype to a particular mutation. At the same time, we see the phenotype.
That means that over a typical year, we might find three, four, five hundred phenotypes and know their causes, and we’re able to approach saturation of the genome, the point where every gene will have been damaged or destroyed under close observation, and we’ll know all the parts of the machine.
Dr. Regina Barber DeGraaff: Yeah, that’s really mind-boggling to me, that you’d be able to get through the whole, I mean every single part, and actually try to make some association to a disease, a disfunction of immunity.
I want to ask one last question about immunity. There’s a lot of worry. People I know, children, about immune diseases and vaccinations and people exposing their children to playing outside, antibacterial soap, all that kind of stuff. Do you get questions about that? Is this actually affecting the human immune system the more and more safe we are, the more and more sterile we are?
Dr. Bruce Beutler: I do get asked questions like that. I also get asked questions: “How can I boost my immune system?”
Professor: Exactly. That was my first question when I was reading your stuff. I’m sure you get these questions, so how do you field them? Do you say, “That’s not my field and I don’t really want to get into it?”
Dr. Bruce Beutler: No, I have definite opinions about that. If you want to boost your immune system, you get vaccinated. To people who are squeamish about vaccinating their children because they’ve heard some bit of bad science here and there that says it might be linked to autism or this or that, I say try living without it. If you consider what life was like before we could vaccinate against measles and mumps and diphtheria, et cetera, et cetera, et cetera, it was terrible! I’ll talk to this class shortly. Do you know what the median lifespan was of people in Victorian England?
Dr. Regina Barber DeGraaff: I believe it was 42, 38, something like that.
Dr. Bruce Beutler: It was 10 years.
Dr. Regina Barber DeGraaff: Ten years?
Dr. Bruce Beutler: The average baby that was born could expect to live ten years. That was when half the population had died.
Dr. Regina Barber DeGraaff: Oh, right.
Dr. Bruce Beutler: So the immune system by itself is not enough to really defend us effectively if we’re living in the wild state. If we practice good hygiene and we have immunization against those diseases we can vaccinate against and we have antibiotics, then we can live to be 80, median lifespan. It makes a big difference. Much better life quality living to 80 than living to 10.
Dr. Regina Barber DeGraaff: That’s actually a great sound bite! I really like that. We’re going to end there, and thank you so much for talking to us.
Dr. Bruce Beutler: Thank you. Pleasure.
[♪ Janelle Monae singing Wondaland ♪]
♪ Dance in the trees
♪ Paint mysteries
♪ The magnificent droid plays there
♪ Your magic mind
♪ Makes love to mine
♪ I think I’m in love, angel
♪ Take me back to Wondaland
♪ I gotta get back to Wondaland
♪ Take me back to Wondaland
♪ She thinks she left her underpants
♪ Take me back to Wondaland
♪ I gotta get back to Wondaland
Dr. Regina Barber DeGraaff: We started our interview talking about Dr. Beutler’s childhood and why he went into science, and also why he attended UC San Diego.
I what to go kind of chronologically in my interview. Basically I started talking about his background. And what I really, really liked was he started talking about how his dad really suggested that he apply to UC schools. His dad was like, “You don’t need to go to Harvard. You don’t need to go to these Ivy League schools. A UC (University of California) school is going to be just as good. So what did you think when you heard that clip?
Dr. Jackie Rose: I can’t remember what his dad did.
Dr. Lina Dahlberg: He’s a hematologist.
Dr. Jackie Rose: He’s a hematologist?
Dr. Regina Barber DeGraaff: What is that?
Dr. Lina Dahlberg: Somebody who studies blood.
Dr. Regina Barber DeGraaff: Okay.
Dr. Jackie Rose: So then he spent time in his dad’s lab, which obviously would be a lot of fun. Looking at blood cells. “Look at this!”
Dr. Regina Barber DeGraaff: He got super happy when he, when I talked about his dad.
Dr. Jackie Rose: I hope so. I mean, not every kid’s going to be happy about looking at blood in the lab.
Dr. Lina Dahlberg: Yeah, but some of them might. I really liked the quote where he applied to Caltech and UC San Diego, and the quote was something about one restaurant will serve you too much and the other will serve you WAY too much. I think, especially starting out as a college student, there’s a lot of knowledge. Just a whole lot.
Dr. Regina Barber DeGraaff: I was actually taken aback. Lina, you and I have talked about this. You have scientist parents and I don’t.
Dr. Lina Dahlberg: I sure do.
Dr. Regina Barber DeGraaff: But to see how happy it made him. He said that he looked up, you heard in the clip that he really looked up to his dad. And having that role model was just amazing. I really liked that part of him because when we think of Nobel Laureates, we think of these giants who aren’t going to spend 15 minutes talking to me. But he was really—this is going to sound so stupid—he was really human in that clip.
Dr. Jackie Rose: And in the family business.
Dr. Lina Dahlberg: I mean, the other thing is—don’t ever let my mom listen to this—but the only time I ever really worked with my mom in the lab, she set up a little experiment for me to do. I think I was in eighth grade or something. It was terrifying.
Dr. Regina Barber DeGraaff: Were you intimidated by your mother?
Dr. Lina Dahlberg: I’m still terrified by my mother. She’s a great scientist and so is my dad. And I spent a lot of time in their lab, but I never spent time being in the lab. I was not allowed into the lab. I was allowed into the research space and asked to sit sort of quietly and not get into trouble. I drew on the whiteboards a lot.
Dr. Regina Barber DeGraaff: Really?
Dr. Lina Dahlberg: Yeah.
Dr. Regina Barber DeGraaff: So what about you, Jackie?
Dr. Jackie Rose: When he was younger, I brought my son in to watch some surgeries and help out with some of the culturing.
Dr. Regina Barber DeGraaff: What kind of surgeries? What are you talking about?
Dr. Jackie Rose: So at that time, we were culturing primary hippocampal neurons. So you had to extract from the animal the neurons—I’m just going to put it that way. And then put it in a dish and grow them up.
Dr. Regina Barber DeGraaff: You mean you cut into their brains?
Dr. Jackie Rose: A little gorier. Picture gore. I don’t do that anymore. It’s all about worms.
Dr. Lina Dahlberg: Worms don’t have the hippocampus.
Dr. Jackie Rose: Worms don’t have a hippocampus.
Dr. Regina Barber DeGraaff: Don’t come and protest Jackie Rose’s lab.
Dr. Jackie Rose: Now you can mail-order a hippocampus. You don’t actually have to have the whole animal.
Dr. Regina Barber DeGraaff: You both work with worms. You work with the same worm.
Dr. Lina Dahlberg: We do.
Dr. Jackie Rose: We do. But he came in, and from that day forward he said he would never do what he called a “wet science” or an icky science (a soft science, like soft tissue science), so then he went into physics, starts at U.
Dr. Regina Barber DeGraaff: It’s not my fault.
Dr. Jackie Rose: And now he’s a mechanical engineer.
Dr. Regina Barber DeGraaff: What about your parents? Do you have early memories? What’s your earliest memory of being in a wet lab? I’ve never been in one.
Dr. Lina Dahlberg: Regina, you’ve been in a lab because you brought your daughter into my lab.
Dr. Regina Barber DeGraaff: I did. I was just about to talk about that. I took biology in high school. I didn’t take it in college. I didn’t really take chemistry in college. So I haven’t been around very many wet labs. Just a couple months ago, my daughter and I—she’s nine—we went up to Dr. Lina Dahlberg (Lina’s) lab and we looked at the worms that Jackie Rose and Lina Dahlberg works on. And I felt like a real scientist. I have a Ph.D in physics and all that, but as I was looking at the microscope, which I’ve never done with this worm before, I could see it and it was moving. I felt amazing! My daughter was so happy.
Dr. Lina Dahlberg: Awesome. I’ve met other Nobel Laureates, and a lot of them are really, really good folks. And a lot of them are good guys, so to speak.
Dr. Regina Barber DeGraaff: Yeah, he definitely was. I do want to get into the next clip that we’re going to listen to. In this next clip, he starts basically talking about a lot of jargon. We’re going to talk about Tay-Sachs in a second. He talks about that as well. He talks about gene editing and destroying genes. He kind of put a lot of biology terms in there and I was kind of lost. But again, I had a very short amount of time to talk to him so I couldn’t stop him. Let’s actually break apart this clip. I’m actually going to play it for us here.
[♪ Janelle Monae singing Wondaland ♪]
♪ Take me back to Wondaland
♪ Me thinks she left her underpants
♪ The grass grows inside
♪ The music floats you gently on your toes
♪ Touch the nose, he’ll change your clothes to tuxedos
Dr. Bruce Beutler: Okay. First about Tay-Sachs, it’s a glycolipid storage disease in which an enzyme fails to degrade a polysaccharide chain that’s hooked onto a lipid. And the lipid polysaccharide complex correspondingly accumulates in neurons.
Dr. Regina Barber DeGraaff: Okay, so this is, where exactly in your body is the neurons going to be?
Dr. Bruce Beutler: In the brain.
Dr. Regina Barber DeGraaff: In the brain.
Dr. Bruce Beutler: That’s right.
Dr. Regina Barber DeGraaff: I’m just trying to break it down for our listeners. So things are building up in the brain that shouldn’t be.
Dr. Bruce Beutler: Correct. It’s a disease that is particularly poignant because children with it are born seeming quite normal, but then they become blind and regress in their development, and it’s 100% fatal.
Dr. Regina Barber DeGraaff: Right, and it’s very quick, too, so it’s going to happen . . .
Dr. Bruce Beutler: Typically within two or three years. There may be some survivors a bit longer than that, but not many.
Dr. Regina Barber DeGraaff: Right.
Dr. Bruce Beutler: It’s one of several glycolipid storage diseases. For example, there’s also Sandhoff’s disease, Gaucher’s disease, Niemann-Pick disease. All of these are more common in Ashkenazi Jews, even though they involve different enzymes that are genetically unlinked to one another. That in itself is a very interesting observation. It’s not well understood at the present time.
Dr. Regina Barber DeGraaff: Right. We talk about in our workshops that, because of the population that, and you start linking it to genetics, people can start making bigger leaps that are not good about, “Well then, maybe people should be wary of having kids” and stuff like that. I remember talking to a biologist saying that it might not just be that population of Jewish people, but it could be the region, right? It could be the region of Eastern Europe.
Dr. Bruce Beutler: It is mostly in Ashkenazi Jews. It is also found in some areas of Moravia. Fundamentally, it appears the mutation arose in the progenitors of Ashkenazi Jews in the Rhine River Valley. It may have spread to other populations, but very little because the Ashkenazi Jews were quite isolated.
Dr. Regina Barber DeGraaff: Right.
[♪ Janelle Monae singing Wondaland ♪]
♪ Don’t you freak and hide
♪ I’ll be your secret Santa, do you mind?
♪ Don’t resist
♪ The fairy gods will have a fit
♪ We should dance
♪ Dance in the trees
♪ Paint mysteries
♪ The magnificent droid plays there
Dr. Regina Barber DeGraaff: So you’ll hear in that clip that I was trying to get at this idea of diseases and science being used to actually, I want to say, discriminate against certain races, to actually say that certain groups are much, much different than others, to have some superiority. So science was used in a not-so-great way and I was trying to get at that with Dr. Beutler, but it was not going well.
So after listening to that clip, do you two want to add anything? His definition of Tay-Sachs was pretty good. I remember you, Jackie, saying that. But was there anything else you wanted to add to how science is used to discriminate or to justify discrimination, is basically what I was trying to get at?
Dr. Lina Dahlberg: Well, what I took away from his discussion, which I thought was interesting, was that for some time it’s been clear that isolated populations—for example, the Ashkenazi Jews in Europe—those have been traditionally isolated populations. So when there are mutations or disease phenotypes, they become associated sometimes very closely with those populations.
And what I thought was really important that Dr. Beutler brought up was this idea that it’s not that Tay-Sachs is exclusively found in an Ashkenazi Jewish population, even though it has a high prevalence because of the isolation of that population of people, but he also brought up the idea that there are other isolated populations where similar diseases are found.
So for example, he brought up the idea that there’s a population of Moravian folks in the Czech Republic where you see a similar situation, where an isolated population has a higher prevalence of a disease phenotype. And I think that’s really important because those people (having lived in the Czech Republic), those people are not represented as a Jewish population. Those are a different population of Europeans that happen to be isolated within their population.
But yeah, I think what he was dancing around a little bit was if you have a population where you can start attributing phenotypes to a specific population, it can become used as a tool of discrimination. It has been used as a discriminatory tool. But I thought that it was really important that he brought up other populations that have the same disease phenotype but are different quote-unquote “populations.”
Dr. Regina Barber DeGraaff: I was trying to get at has he ever had to deal with that at a conference or with other scientists. I guess I’m just opening it up to you two, in the field of biology or neuroscience, have you actually run into people using science to—what do I want to say—support their biases? And it doesn’t have to be racial. It could be any other biases. I was trying to think, in neuroscience there might be.
Dr. Jackie Rose: Especially in neuroscience and in health in general, there’s a huge—it’s been going on for decades and we’re now addressing—the fact that a lot of animal research has always been conducted on male of the species. So we don’t know a whole lot of what female physiology looks like, in fact. I just came back from a neuroscience conference up in Vancouver a couple weeks ago where this eminent researcher—i think he works in pain—and so he had all this data for the male rats and how they process pain. And so now, because the funding agencies are insisting that they also do their experiments in female rats, and the data came out completely different. And he just kind of ended his talk with, “I don’t know.”
[laughing]
It’s like, oh my goodness. So what are we supposed to do?
Dr. Regina Barber DeGraaff: I literally want to have a show just about how science has been misused in the past (because it has) as supporting discriminatory ideas, but also how there is bias in the science we do sometimes now. And it’s kind of controversial because I think science has a bad rap sometimes in the public, being like, “You don’t really know what you’re talking about.” So I don’t want to add fuel to that fire, but I also want to say that we are human and we as humans conduct these experiments, and we all have these biases.
Dr. Lina Dahlberg: Well yeah. I mean, we bring our bias to our experiments. What are we interested in and why are we interested in it? That comes from who we are and what our experiences were. There’s no way around that.
But I think that it is really interesting to look at, that field of neuroscience is clearly up and coming. It’s true that when you write a grant you have to talk about how you’re going to address essentially sex bias in your experiments, and it becomes really important. I mean there are all sorts of other neuroscience experiments like how birds learn to sing, which has implications for how humans or other organisms learn how to talk and how to use language. But not all of the birds learn to sing the same songs from the same parent because there are two sexes in the bird families, also. Which doesn’t even get into a continuum of sex across them [laughs].
Dr. Jackie Rose: There’s always this background explanation of, people avoided doing research with female rats, say because there were fluctuating hormone levels that could affect behavioral outcomes. So to do that, you’d have to do things like ovariectomize them first and then control hormones. So it just added this layer of complexity. So researchers would just opt to, “Well we’ll just work with males.” But then it builds this whole assumption that the same would be true in females, when the whole reason why they avoided doing research in females in the first place is because it’s not the same [laughing]. It’s harder!
Dr. Lina Dahlberg: But it also brings up this idea, Dr. Beutler talked about, and mice are really similar to humans. Which is true to a point, and then it turns out that many of the studies that we’ve done on sepsis, for example, have been done in mice and it turns out that those results do not transfer very well to the human immune system or inflammatory system. So the bias against, or the correct ethical bias against doing human biology research on humans also leads to complications when we talk about how to transfer our results.
Dr. Regina Barber DeGraaff: This is all really fascinating. I wish we had more time. We will. I’m going to come back and do a biology bias or science bias episode, and you’ll come.
Dr. Lina Dahlberg: Oh we will?
[laughter]
Dr. Regina Barber DeGraaff: I’m like, “That’s an order!” So with that, let’s get to this next clip. He talks about the next big thing in his field. In this next big thing, he starts talking about this gene mapping. In that case, I think he does, I think I stopped him. There was a lot of jargon. So could either of you talk about this gene mapping?
Dr. Lina Dahlberg: We can edit this, right? This is a quote where he’s talking about mutagenizing these animals and then homozygousing them and looking for what genes there are, right? By using a chemical to make mutations in the genome of the mice and then making sure that each mouse only has one mutation in one gene (more or less), he’s able to dissect out a whole pathway because since each gene encodes a protein and since each protein has a function in the animal, when you see a defect then in the animal, you can relate it back to the mutation that happened in that animal. And that’s why—I mean it’s in many ways a very expensive process because for each gene you have to make a new mouse. You have to have a new line of mice that has that mutation in it.
Dr. Regina Barber DeGraaff: But how many do you need?
Dr. Lina Dahlberg: It depends on the pathway. The pathways he’s working on could have hundreds of genes that are related to each other in the pathway. So yeah, it’s expensive.
Dr. Regina Barber DeGraaff: Yeah, that’s a lot of mice.
Dr. Lina Dahlberg: In terms of money and mice.
Dr. Jackie Rose: I was just looking up too, so doing that there’s what he calls a “large number of genes” that they’ve found with all these single mutations that he’s able to look at. And then he challenges, basically, the immune systems of these mutant mice to see how well they respond to this virus. What he’s been able to do is—I don’t know if he calls it or if somebody else has coined this for him—the resistome [laughing] genes involved in immunity, basically. And then categorizing them into ones that are important for senses, ones that are important for the inflammation or ones that are important for other parts of the immunity process, all comprise the resistome.
Dr. Lina Dahlberg: Biologists love “-omes.”
Dr. Regina Barber DeGraaff: Really?
Dr. Lina Dahlberg: “-Omes” just means large collections of things. So the gen-ome or proteos-ome or the ribos-ome . . .
Dr. Jackie Rose: Or the connect-ome.
Dr. Lina Dahlberg: . . . Or the connect-ome. Or the transcript-ome. Lots of omes.
Dr. Regina Barber DeGraaff: I just heard resistome and I thought of a dome, actually. I thought of the Thunderdome. But go ahead.
[laughter]
Dr. Lina Dahlberg: It’s more like the Tacoma Dome, actually.
Dr. Regina Barber DeGraaff: It’s still there.
Dr. Lina Dahlberg: I know.
Dr. Regina Barber DeGraaff: So that’s good. That’s good.
Dr. Lina Dahlberg: Importantly.
Dr. Regina Barber DeGraaff: You were saying that he’s called these things…?
Dr. Jackie Rose: Like the large numbers of genes that he’s discovered that play a role in all of these different processes of immunity comprise the grander resistome [laughing].
Dr. Regina Barber DeGraaff: Got it. Got it. Okay. But this new thing of being able to actually—I mean he said it in that clip. He said that at some point we’re going to be able to figure out what every gene does. To me, that seems really ambitious. How ambitious is that? Is it realistic?
Dr. Lina Dahlberg: I think it depends on how you define gene. How helpful is that? I would say it’s not overly ambitious to say we might know what protein every gene encodes, and basically what the function of each of those proteins are. But, as we learn more and more about our genomes, we find there are more and more areas of the genome that are not encoding proteins; that are either encoding other molecules of RNAs or that are somehow not encoding things that get expressed out of our genome but are structurally important. And so understanding what every single piece of the genome does, that’s a much more ambitious and potentially unending project.
[laughter]
I’m looking at Jackie for confirmation here. I feel there are all sorts of institutes that are out there to say, “We will solve the genome,” and I’ve always been the person in the audience being like, “Really?”
Dr. Jackie Rose: And the other thing is, when you talk about RNA, we know that moment to moment what a cell is producing is changing too. Whenever you’ve got the snapshot of the genome and it’s function, it’s only the snapshot in that developmental stage or in that circumstance or that environment or signaling environment, or all the different things that change. And then it’s going to change within even the same cell under different conditions. So it’s never . . . it’s a big project!
Dr. Lina Dahlberg: Yep.
Dr. Regina Barber DeGraaff: I ended, because he was very, very busy here at Western. The last thing I asked him—I had already run over the fifteen minutes and I was like, “Wait a minute. Do people ask you about the immune system? Do they ask you things about vaccines? Do they ask you about what can I do?” He goes, “Oh yes.”
Let’s go ahead and play that clip.
[♪ Janelle Monae singing Wondaland ♪]
♪ Take me back to Wondaland
♪ I gotta get back to Wondaland
♪ (Take me back to Wondaland)
♪ (She thinks she left her underpants)
♪ Take me back to Wondaland
♪ I gotta get back to Wondaland
♪ (Take me back to Wondaland)
♪ (She thinks she left her underpants)
Dr. Bruce Beutler: If you want to boost your immune system, you get vaccinated. To people who are squeamish about vaccinating their children because they’ve heard some bit of bad science here and there that says it might be linked to autism or this or that, I say try living without it. If you consider what life was like before we could vaccinate against measles and mumps and diphtheria, et cetera, et cetera, et cetera, it was terrible! I’ll talk to this class shortly. Do you know what the median lifespan was of people in Victorian England?
Dr. Regina Barber DeGraaff: I believe it was 42, 38, something like that.
Dr. Bruce Beutler: It was 10 years.
Dr. Regina Barber DeGraaff: Ten years?
Dr. Bruce Beutler: The average baby that was born could expect to live ten years. That was when half the population had died.
Dr. Regina Barber DeGraaff: Oh, right.
Dr. Bruce Beutler: So the immune system by itself is not enough to really defend us effectively if we’re living in the wild state. If we practice good hygiene and we have immunization against those diseases we can vaccinate against and we have antibiotics, then we can live to be 80, median lifespan. It makes a big difference. Much better life quality living to 80 than living to 10.
[♪ Janelle Monae singing Wondaland ♪]
♪ (Hallelujah) This is your land
♪ (Hallelujah) This is my land
♪ We belong here
♪ Stay the night
♪ I am so inspired
♪ You touched my wires
♪ My supernova shining bright
Dr. Regina Barber DeGraaff: So he talks about, first of all he’s like, “Vaccines!” He jumps on that, right? As biologists, as a neuroscientist, do you also kind of live in the realm where you get these questions too, and what do you want to say? It’s an open forum right now.
[all laughing]
Dr. Jackie Rose: Get vaccinated.
Dr. Lina Dahlberg: Yeah! Do it! Herd immunity. It’s important.
Dr. Jackie Rose: Yeah, herd immunity.
Dr. Lina Dahlberg: Actually, that was one thing I took issue with. When he was like, “If you don’t want to be vaccinated, see how it is without it.” That’s not how it works though, right? It’s not. That one person might get sick, but we’re worried about the whole population here. So yeah, get yourself vaccinated.
But I’d say yeah, I work on a receptor protein that is orthologous, that is, that’s similar to a human receptor that’s important for learning and memory. And then I get questions about how the animals remember things and then I have to point people to Jackie.
Dr. Regina Barber DeGraaff: We live in a town—if I want to bring it back to vaccinations—we live in a town; the population is very, I think, science supportive if we talk about climate change and other things. However, the vaccination rate is not as science supportive in our community here, at least in the southern part of Bellingham. What do you do when you come into that kind of conversation in your everyday life?
Dr. Jackie Rose: Your kids are not allowed to play with my kids. I’m sorry.
Dr. Lina Dahlberg: Yeah, I mean, I also have kids. I don’t think I’ve had to have that conversation with somebody. I’ve actually worried about that a lot though when we started moving into preschool because there were some opt out clauses where I was like, “If you start that, I’m going to have to move my child because I’m not comfortable with it!”
Dr. Regina Barber DeGraaff: There’s a school in town that has like 30% not vaccinated.
[gasp]
Dr. Regina Barber DeGraaff: That’s a huge percentage.
Dr. Jackie Rose: That’s high. That’s horrible.
Dr. Regina Barber DeGraaff: I think it’s a private school, but . . .
Dr. Lina Dahlberg: So I don’t know. Related to my own science, I don’t get a lot of questions that hit that super close to home. And I no longer work directly in developmental biology, but when I did, those questions came a lot more clear. I mean, people would ask questions about developmental defects and because I was studying that, I had some ideas about ways that organisms develop.
Dr. Regina Barber DeGraaff: Right. I mean, I think he did an okay job responding to my question. But I teach a science communication course and we talk about these ideas in science that can be seen as controversial, but as you are talking, you don’t have to deal with these things at conferences. This is not a controversial topic.
[laughter]
Dr. Lina Dahlberg: Not at a conference.
Dr. Regina Barber DeGraaff: Right, in our scientific communities, we don’t have to deal with these things. But we might have to deal with them when we’re outside. So are there other controversial things that come up. I guess I’ve already kind of asked that. You talked about the gender thing. That’s not very controversial, but is there anything else that comes up in your fields that you do have to deal with?
Dr. Lina Dahlberg: Well one thing I think probably Jackie and I both deal with is we both think of ourselves as what we call basic researchers, which means that we are talking about the fundamental processes that underly how organisms work. And I would say a lot of biologists are interested in that type of research. And what that means is people can look at our research and say, “Why would we care what happens in a worm?” Right? And I do get that all the time. So, “Who cares if the worm goes that direction or that direction?”
And the upshot is I don’t care per se about that particular animal, but the knowledge that we’re gaining through those experiments really do have underpinnings for our understanding of human health. And so if we want to tie it to a human health angle, that’s one thing. But there are also plenty of examples of basic research being drivers for really fundamental leaps forward in human technologies.
Dr. Jackie Rose: Yeah, I think probably the gene editing CRISPR is a good example, starting in bacteria and understanding how that happens, not even in a multicellular with-neurons organism, but bacteria. And now it’s leading to potential quote-unquote “gene therapies” in humans. So we never would have got there by looking at the human to see how we could be able to edit genes within a human.
Dr. Lina Dahlberg: Yeah, and even off San Juan Island, GFP (which is the green fluorescent protein) was discovered at Friday Harbor Labs. And that is a jellyfish protein that we now use fundamentally throughout biology to enable us to understand how molecules in cells work.
Dr. Jackie Rose: Yeah, and we use it across species (probably not in humans), but cats, dogs. I show a video clip, or I’ve shown a video clip in previous sections of my Intro to Behavioral Neuroscience class where they have—the cat’s name is Mr. Green Genes and they turn on the black light and the cat glows green.
Dr. Regina Barber DeGraaff: Wow. Wow.
Dr. Jackie Rose: It was from a jellyfish, but once you have the genetic code, it can be applied to . . .
Dr. Lina Dahlberg: And then you can do breakthrough research in cat glowing.
[Dr. Jackie Rose laughing]
Dr. Jackie Rose: Don’t you have one?
Dr. Regina Barber DeGraaff: There was a Sherlock episode about this, I think.
Dr. Lina Dahlberg: Oh really, I missed it? But I will say that GFP can also be used for things like learning how cells, for example, how attack cells in our body can trace and follow cancer cells. So the immune therapies that we’re understanding are really powerful against cancer. Glowing cats aside, we wouldn’t be able to do that without having found this jellyfish protein.
Dr. Regina Barber DeGraaff: Well don’t put them aside. We’re using them for part of this, right?
[meowing]
Dr. Jackie Rose: And also for taking donor cells, they make them glow green and then you can find them in the recipient. So it’s pretty cool.
Dr. Regina Barber DeGraaff: That is awesome. I’m so glad we actually came to that point. We’re going to have to end it there. Thank you both for talking to me. Thank you so much for helping me kind of dissect what I went through in interviewing Bruce (who is a wonderful man). But I did not know anything about biology. So thank you for being my rocks.
[laughter]
Dr. Lina Dahlberg: You can call us anytime.
Dr. Regina Barber DeGraaff: Thank you.
Thanks for listening to Spark Science. If you missed any of this show, go to our website sparksciencenow.com. If there’s a science idea you’re curious about, send us a message on Twitter or Facebook at sparksciencenow. Spark Science is produced in collaboration with KMRE and Western Washington University. Our producer is Regina Barber DeGraaff. Our audio engineers are Natalie Moore, Andra Nordin, and Tori Highley. Our theme music is “Chemical Calisthenics” by Blackalicious and “Wondaland” by Janelle Monáe.
[♪ Blackalicious rapping Chemical Calisthenics ♪]
♪ Lead, gold, tin, iron, platinum, zinc, when I rap you think
♪ Iodine nitrate activate
♪ Red geranium, the only difference is I transmit sound
♪ Balance was unbalanced then you add a little talent and
♪ Careful, careful with those ingredients
♪ They could explode and blow up if you drop then
♪ And may hit the ground
[End of podcast.]