Episode 4: Future of Healthcare From a Clam

Michael Metzger  00:01

If there’s a way for an animal to be able to evolve to block cancer, I want to know what that is, and I think it definitely has the potential to be really useful for human therapies.

 

Jack Faris  00:15

Hello and welcome to our podcast, PNRI Science: Mystery and Discovery, where we go beyond the jargon to dig into the passion and people behind the science. I’m your host. Jack Faris, CEO of Pacific Northwest Research Institute, a 68-year-old genetics and genomics research institute in Seattle. I’m also a regular guy.

 

Anna Faris  00:36

Dad, no, you are not a regular guy. Oh boy, here

 

Jack Faris  00:40

we go. That’s my daughter, Anna Faris, who’s going to help me out, so to speak, with this endeavor. Anyway, I say I’m a regular guy who happens to spend his days around really smart people, and I’m here to interview pianos, brilliant scientists, to share what excites them about genetic research, what inspired them to become a scientist, and what are those myths that we would love to bust about science? Join me and Anna as we dig into the mysteries that may very well hold the key to our future health breakthroughs. Dad, that

 

Anna Faris  01:13

was great. Oh, I’m really proud of you. Dr. Michael Metzger, future of healthcare from a clam. In this episode of PNRI Science: Mystery and Discovery, my dad Jack interviews PNRI assistant investigator, Dr. Michael Metzger about contagious cancer in clams. I’m not joking. I thought my dad was nuts when he told me this, but it’s real. This contagious clam cancer is over 400 years old and might hold the key to humans resisting cancer. We might all be thanking a clam for saving us from cancer in the future. And yes, you can eat clams and not get cancer. I asked, it may

 

Jack Faris  01:56

seem unlikely that we would learn something useful about human cancer from clams. But the fact is, we’ve learned a lot about human cancer from yeast, so why not?

 

Anna Faris  02:07

So grab your shoes for a walk and enjoy the awe inspiring power of science.

 

Jack Faris  02:16

Michael, you walked in this room engaged in real time science, and I can’t help but want to know, what was that about you?

 

Michael Metzger  02:22

So first, what I was getting was messages on my phone about how many cells we had collected in the lab. My lab is currently setting up an experiment right now where we’re taking cancer cells from a clam and then injecting them into other clams to determine whether those clams are susceptible to the disease, and whether different routes of infection are able to transmit the disease better or worse, as well as if they’re if different animals from different locations have different levels of susceptibility. So what I was getting was the notification that we had enough cells to move forward with the experiment. So we had enough cancer cells from one animal to then go into this experiment and get it started.

 

Jack Faris  03:05

So, so that sounds pretty exciting, yeah, and but also it it opens a kind of a scientific Pandora’s box of questions, not in the kind of the horribleness of the Pandora phenomenon, but obviously our listeners, who perhaps have never heard of cancer that can be transmitted from one organism to another, will want to hear about that.

 

Michael Metzger  03:25

So what we’re working on is this is unusual. This is these are cancers that do transmit. They’re called contagious cancers, or transmissible cancers. These aren’t very normal in the wild or in people at all. So if when people have cancers, the cancer cells from one person do not jump into another person. There are infectious diseases that can jump from one person to another and cause cancer, things like HPV, that causes a number of different human cancers, but in that case, and in the other cases, with infectious diseases that cause cancer in humans, there a virus, or some other infectious agent that can go from person to person and then that transforms the person’s own cells into cancer? Once they have cancer, those cancer cells don’t go to other people in this way, but there are sort of three types of transmissible cancer that have been found in nature. There’s one in Tasmanian Devils that’s called the Tasmanian Devil Facial Tumor Disease. It’s actually spread by devils biting each other, where, basically small amounts of cells from one animal will engraft into the wounds of another animal. There’s one that’s actually a lot older but less well known, called the canine transmissible venereal tumor, that’s a solid tumor that’s spread through sexual contact in feral dog populations all over the world. And then there are the ones in bivalves, and that’s what I study. So these are transmissible cancers that are in soft shell clams, cockles, muscles, a whole variety of different bivalve species. And. There’s actually many of them in different species that have origin independently. So this seems like a phenomenon that’s occurring in multiple places at multiple times, all over the world. And

 

Jack Faris  05:08

is there a reason why transmissible is a better or more accurate word than contagious?

 

Michael Metzger  05:15

I think I’m fine with both. I think one of the things I’ve found with this is that a lot of the normal definitions of words don’t exactly match, and we’re kind of making up our own terminology, or using things in a different way we haven’t really thought of before. What we’re studying is it can be thought of as a cancer, and it can also even be thought of as a parasite, because it’s gone beyond the original cancer. In an animal, you can think of it as a metastasis, but instead of going from one place in one person to another place in that person, it’s going in and grafting in another animal altogether. And then you can also think of it in that it’s become a sort of single cell, asexual parasitic organism that is jumping from animal to animal, infecting other organisms. It really doesn’t fit any of the definitions that we normally have. And I think, I think that’s part of the thing that really makes it interesting to me, is that it sort of blurs the boundaries what we have, and then it that kind of gives us more insight into the fundamental way things actually work.

 

Jack Faris  06:15

So that’s an interesting general notion, that things that are exceptional or abnormal or somehow don’t fit into conventional boxes may have a particular scientific utility. Yeah,

 

Michael Metzger  06:29

I think so. And I think in addition to just being fascinating to me, I think it tells us about things that we didn’t know that happened. It tells us that sort of, our assumptions in the world of what can happen are not correct. And then also, from another point of view, it allows us to sort of use tools and methods that people don’t normally think of. There are a lot of methods that are used to analyze genomic interactions of pathogens, things like looking for positive selection, which is where, where you have what’s called genetic conflict, we have two different you host and a parasite that are in conflict with each other, and each one is sort of evolving, trying to get the upper hand. And there are tools and methods that people have developed to try to understand those host pathogen interactions. And now with this sort of other way of looking at cancer, we’re starting to use those methods on infectious cancers and so sort of, in addition to just being cool, I think it allows us to sort of use tools from different disciplines to analyze things in a different way. I’m

 

Jack Faris  07:30

sure people listening to this may be wondering, Am I okay if I eat a clam that’s got a cancerous element to it, and does it matter whether it’s cooked or raw? I may want to avoid the raw bar from this plant food. Yeah,

 

Michael Metzger  07:45

I would say you’re definitely safe. There is people are at no risk from getting this cancer. And it is definitely okay to eat, eat clams that have a small amount of this cancer, or any amount of this cancer, because it, it is actually, in almost all the cases, it’s species specific, even in the clams. So the clams have a cancer and the muscles have a cancer, but you can’t give a clam cancer to a muscle and you can’t give a muscle cancer to a clam. That genetic distance is enough that it won’t infect So humans are totally safe. There’s no reason to think that any humans could get harmed from clam cancer. I think I have probably eaten more bivalve since I started this project than than I had beforehand.

 

Jack Faris  08:32

You alluded to in this current experiment, you’re getting data or reports on right now to the notion that some in fact, it’s not just a notion. It’s an empirical fact, as I understand it, that some clams are able to resist cancerous invasion, whereas others are susceptible.

 

Michael Metzger  08:50

Yes, we know the most about the soft shell clam cancer. That’s the cancer in the clams, mostly in New England. These are soft shell steamer clams that they’re found in New England, up in Prince Edward Island, down to the Chesapeake Bay. And in the 80s and the 2000s there were large outbreaks of this cancer before people knew what the cause of it was, before they knew it was transmissible. There were reports that 90% of population, in some cases, would have this disease, the cancer, and then there’d be about a 90% population die off. There’s huge mortality caused by this. Now, when we look at those same populations, they have a very low level of disease, something like one to 5% depending on the location and then the time of year. And so it’s not killing whole populations. And when we take animals and keep them in the lab and follow them over time. If we take animals that have a low level of disease, what we found is that about half of them sort of progress to death as we’d expect, but the other half of them actually maintain this cancer at a low level, and some of them even sort of get blips where the cancer will grow and then it will regress. And so we know that a large number of these animals will actually. Actually be able to control the cancer at this point. And so we’re really interested in figuring out how they’re able to do that. These animals don’t have all invertebrates don’t have the sort of adaptive immune system that humans have, T and B cells and things. So we know it’s not that, but they must have some other mechanism where they’re able to evolve the ability to block these cancers? Is

 

Jack Faris  10:21

it imaginable that we might learn from clams and their ability of some of them to resist the deleterious effects of cancer cells, things that would help us improve our own ability to counteract or defeat or prevent cancer in our own bodies.

 

Michael Metzger  10:41

Yeah, that’s really the main big goal here, that we could use our understanding of how these clams have been able to evolve resistance, or evolve the ability to block this cancer, and then use that knowledge to sort of design different therapies to mimic that in humans, to mimic that block, whether that’s sort of identifying a specific target that we can interfere with, that cancer cells need to engraft, or figure out some other mechanism that that the hosts are using to attack or block these cancer cells. And we really don’t know what that mechanism is going to be yet. It is pretty unknown, and we don’t know, without knowing the answer, how it would be translated exactly, but, but if there’s a way for an animal to be able to evolve to block cancer, I want to know what that is, and I think it definitely has the potential to be really useful for human therapies.

 

Jack Faris  11:41

I can’t imagine that at the age of, say, 11, you were sort of thinking out into the future and thinking, I someday, I’m going to study cancer and clamps. That’s just not imaginable to me. So

 

Michael Metzger  11:54

yeah, that’s definitely not what happened. I would love to

 

Jack Faris  11:57

hear you try to chart the key events in your pathway, which I imagine is probably more of a zigzag than a straight line, to wherever middle school, high school, a young person to where you are today. I

 

Michael Metzger  12:13

was really interested for a long time in junior high and high school and biology and molecular biology and infectious diseases and viruses, in particular, when I was younger, I was really interested in what I could find on Ebola, and then HIV was a huge problem that was just starting to be known at that time, and so I was really interested in understanding how that works, and if there’s any ways that we can learn more about it and try to figure out how we can stop it. So I tried to sort of understand that side of things and understand viruses, and that was my main focus through going into college. And after I did my undergrad at Cornell, I still was interested in virology, but I didn’t know. I didn’t have a lot of trainings, specifically in virology in my undergrad, so I wanted to get a little bit more experience, so I actually joined a lab as a technician for two years that was Preston Marx’s lab at Tulane looking at SIVs. So these are simian immunodeficiency viruses, the sort of ancestral related viruses to HIV. So these are the viruses that that naturally infect primates in Africa. And there’s some interesting things with those. One of the interesting things is that, for the most part, the primates who get the SIV, the ancestors of HIV, they don’t actually get disease. That was one of the really interesting parts of that model for for it. And then we were also just at the time of trying to understand how they were related to HIV, where the jumps occurred to go from one species to the other. And so I was really interested in that. And that was a great place to really get experience. My first sort of full time experience in the lab after that, I went to the MCB program at the University of Washington, right here, the molecular, cellular biology program. And that’s a pretty broad title that actually covers a huge, huge area, and that was part of the reason I chose it, because one of the things I was noticing with virology and infectious diseases is people studying them. Sometimes they’re in the genetics department, sometimes they’re in a microbiology department, sometimes they’re in a biology department, then they can be spread all over. And so the MCB program was a program that let you choose from a large number of different faculty, and you weren’t sort of pigeonholed into one department. And so I really liked that, and I got to do rotations with a lot of really interesting people, and I did my PhD actually working sort of not on wild viruses, but on using viruses for gene therapy purposes. So that was with Dusty Miller at the Fred Hutch. Now

 

Jack Faris  14:46

that sounds like a headline. Most people think of viruses as the enemy, and so in what way can a virus participate in helping improve our genetic situation?

 

Michael Metzger  14:58

Yeah. So using. Viruses for gene therapy is really sort of taking the guts of viruses that taking their machinery, their ability to package genetic material and move it from one place to another, and get it into cells and get those cells to produce those genes. But instead of having the virus package its own genes to make more of itself, gene therapy. The main, main switch is sort of taking the packaging signal out of it and putting it on something we want. So then we put a gene that you want to have expressed in the cells, make the virus, package it and deliver it for you. It gets into the cells and then produces the gene you want in the cells of interest. So that’s the idea, and there’s been some really interesting successes, and then there’s a lot of difficulties involved in getting that to work. The main target that dusty’s lab was looking at, he was looking at lung gene therapy. So he was looking at viruses that you could use to infect lung tissue and deliver things like a repaired version of the CFTR gene, which is the gene that is mutated in cystic fibrosis. And so if you can deliver the right version of the cystic fibrosis gene into patients, then you could correct the problems in their lungs.

 

Jack Faris  16:21

We’re still on the journey towards clams. What’s next?

 

Michael Metzger  16:26

So after a postdoc with Barry Stoddard, which was a little bit more looking at the gene therapy, I wanted to get up training on more basic sciences of retroviruses. And so I went with Stephen goffe’s lab at Columbia University in New York, and I had a couple projects looking at molecular biology of retroviruses. So that’s retroviruses are the class of viruses that include things like HIV. Siv is the ancestors of HIV and a number of other things that infect mice and all sorts of other species. The shift came because there was another scientist who had known about Stephen Goff and his work, named Carol Reinisch, who’s the main person who started this. So she was primarily at MBL Marine Biological Labs in Woods Hole, and she had worked for a long time on a number of different things, but one of them was this cancer in clams that had been known since the 60s in the soft shell clams in New England, people didn’t know what was causing it, but they knew it was occurring in outbreaks. So there were a lot of different theories. Some people thought it might be pollution that was causing it. Some people thought it might be a virus, and we know that retroviruses can cause cancers, and there was some evidence that was really suggesting that there might be a retrovirus causing this cancer, but no one had been able to find it. So Carol Reinisch came to Steve Goff and asked if he could take a look and sort of find the missing retrovirus that was causing these cancers. So together with Gloria Arriagada, another postdoc, the two of us started looking for the virus that was causing this cancer, and it turned out there was none. There was no virus at all. So the whole thing started with a completely wrong hypothesis. So we had absolutely no virus at the end of it, but there were some really interesting signatures in the DNA that when we started looking at it, and after we started looking at it a bit more and sort of poking around with things that we had found. What we found instead was that it was this whole phenomenon of a transmissible cancer. So that’s where we found that the cancer cells themselves were jumping from one animal to the next and spreading through the environment. And this had been just a really not too long after the cancers in dogs and Tasmanian devils had been solidly reported. That was reported in 2006 and we figured this out in 2015 so after we found the transmissible cancers in clams, then I came to Seattle, to PNRI to start the lab here and

 

Jack Faris  18:55

where in that was the sharp turn. Yeah, I think

 

Michael Metzger  18:59

the big sharp turn was looking for a virus and finding something totally unexpected. Yeah, that was definitely not where I thought I was going to be when I started this project, but it really just opened up a whole lot of really interesting questions that I wanted to follow up.

 

Jack Faris  19:19

So back to the journey from viruses and before that, to clams and cancer. You mentioned several names. Is there someone in particular that you would hold up as a particularly excellent mentor during that process? And what makes a good mentor?

 

Michael Metzger  19:35

I think I’ve been very fortunate with having a lot of people who really have been mentors for me, I wanted to definitely mention Steve Goff because he’s been really supportive and a great mentor and helping me develop these projects, being very supportive. And he he let me fumble around a bit when we were looking at this weird clam cancer, and it turned out not to be what we wanted, but there might still be something interesting in there. And so he. Let me fumble around and try to track down what were odd retro transposon insertion sites, until we figured out what what this thing actually was. And then was supportive of me developing it into a whole new, whole project, and and taking that project with me and supporting me and setting up my own lab and developing this so and he’s been giving me the resources and the guidance on the individual questions, helping me learn how to write papers better and develop projects better. I think it was really an outstanding mentor to have. For

 

Jack Faris  20:31

those of us who haven’t been or had a particularly superb mentor, we may have a conception that a mentor tells you what to do, but in this case, you’re actually suggesting that part of the value was, is giving you the latitude and freedom to explore in a way that you didn’t have to be accountable for every every step of the way. I

 

Michael Metzger  20:52

think that that’s really a lot of I mean, if a mentor is just telling you step by step what to do, that’s not that’s not really going to help you, he would sort of help teach me to know what to do for different experiments. Tell me what things make sense. And if I would come to him with data or a figure, he would definitely tell me, like that one, that that doesn’t make sense. You need to write. Do that a different way, and it definitely helps me to learn how to develop a project, learn what’s important, and learn how to communicate things to other people, rather than having him just sort of dictate, this is what you’re going to be doing today, developing the ability and letting me run with it. Maybe it would take me a little bit longer in the first place than if he had been telling me what to do, but, but it also is really helpful to have me do it on my own, and sort of giving the space and the expertise and the knowledge on all sorts of different assays and methods. So

 

Jack Faris  21:44

at this point in your career, running a lab, leading a team, you have the opportunity to think to do some mentoring yourself. Yeah,

 

Michael Metzger  21:53

and I’m really excited for that as well, and I love that I get to be able to do that. I’ve been really proud to have Sam Hart in my lab, who’s a grad student who just defended his PhD, and he I was really excited with what he was able to do. And he just published, he was the first author on a report that we published looking at the genomic analysis of these transmissible cancers in clams. And he took some of the ideas that I had initially had with it, and and he came up with whole other things. He showed me that some of the assumptions that I had made about it were just totally wrong, and found things that I hadn’t even thought to look at. And he found that there were these, the cancers were much more unstable than we had previously thought. So the initial ideas that I was telling him he should try, they really opened up whole new avenues. And I was excited when he would come to me and show me things I really wasn’t expecting to see, and then how he’d followed up on them and come up with new ways to look at them. So that was really exciting.

 

Jack Faris  22:57

A little bit more about your brilliant new doctor, to what extent has his work helped us understand the actual evolutionary history of these clams? Yeah,

 

Michael Metzger  23:08

so he found a lot of things we we weren’t expecting when, when we were starting. One of the things he found is that these cancers were a lot more unstable, and so we have there are so many mutations that were really rearranging the genomes of these clams, that there were a lot more translocations and things like that. We had thought that there was more DNA in these cancers than in a normal cell, but we thought it was just like an even duplication. But it turned out these, these cancer genomes, are really all fragmented a lot more than we anticipated. One of the other things he found is that he was able to identify specific mutations that were occurring just in these cancers that we think was due to some sort of polymerase, which is a gene that copies DNA. There was an error prone polymerase that makes mutations in these cancers, and he was able to use that to build what we call a phylogenetic clock, or a molecular clock, and look at the number of mutations in these cancers over time in samples that were 10 years apart, and sort of backtrack to estimate how old these cancers were. And what he found was that we estimate that this cancers, that’s the one in softshell clams, was about 400 years old. And that means that the the original, sort of what we would call the founder clam, the clam that had a initially normal cancer was 400 years ago, and that these cancer cells have been jumping from animal to animal through the environment and spreading through these populations for the last several 100

 

Jack Faris  24:32

years. Wow. So the notion that cancer could emerge as recently as 400 years ago, and in geological time that’s very recent, obviously, even in terms of the time of organisms on on planet Earth, that’s very recent. It raises for nervous people like me, what of what about emerging of cancers that might not. Exist today, but might a century from now, or even sooner. I

 

Michael Metzger  25:04

think that these things have most likely just been continuing to emerge in different places and different species, particularly in clams and mussels and things like that. And there’s always the potential for them to emerge in different places. I think it’s funny that you mentioned that, because when we say 400 years ago, probably like two thirds of the people say, Wow, that’s really old. And then 1/3 of them will say, like, Oh, that’s really recent. It just really depends on whether you’re thinking in terms of an individual or you’re thinking in terms of sort of evolution of the whole species, and what kind of scale you’re thinking either way, it’s sort of a surprising number. But yeah, I think these things have continued to be evolving. So we know that, for example, the other two types of transmissible cancers are more well known, the devil, Facial Tumor Disease. There’s actually two lineages of that that’s only believed to be about, I think 30 to 40 years old was when it was first found. And that’s believed to be very recent where that arose and it started spreading. But in contrast, the transmissible cancer in dogs is thought to be about four to 6000 years old. So we know that sometimes these things are occurring recently, and then sometimes they can be much older, even much older than the soft shell clam cancer this 1000s of years old. And we know that there are these transmissible cancers, independent origins of these new transmissible cancers and other species, and we really have no idea at this point of the almost a dozen other lineages that we know of. Now. We don’t know whether we’re looking at things that arose last week or arose centuries ago, and that’s one of the things we’re trying to figure out.

 

Jack Faris  26:38

Well, for someone nervous as I am, the notion that we may discover strategies for resisting cancers, and whether they’re hundreds of years old or newly emerging, provides at least a measure of comfort. Good, okay. Let’s talk a little bit about we’ll raise ourselves above the tide beds and ask about relationships with constituents. So who cares about clams besides the people who make chowder?

 

Michael Metzger  27:17

Yeah? Well, yeah, the people who make chowder definitely do, but there’s a lot of different types of clams. The way we found out about these were that people who were collecting clams for aquaculture were noticing it. Part of the reason we think that there are a lot more of these is that we only really found them when it was in the steamer shells in New England, where they’re very popular and commercially collected. And then when there were large die offs in those populations. People started to investigate. People started to find what was wrong with the clams. Why were they diseased? Out here in Washington State, we have worked together with the Suquamish Tribe, as well as some other tribal shellfish biologists in different tribes in the area, and there’s a particular species called the basket cockle, so clinocardium nuttallii, it’s sort of it’s a cockle, but it’s a bigger one than we sort of see in the sort of more European cockles that you find in the grocery store and things. And this is a species that’s really important, both as food and culturally in the Suquamish tribe and other tribes, and the numbers have been decreasing recently, and the biologists with the Suquamish as well as some other organizations like Puget Sound Restoration Fund, have been trying to figure out how they can restore those populations. And when they started that, one of the things they found is that when they did a health screen, they found that some of the animals had cancer, and so we don’t know if that’s the main reason they’re dying off, but we’ve been working with them to try to understand the transmissible cancer that it’s in Puget Sound in these cockles, and trying to figure out how our understanding of the cancer can actually help them in restoration efforts to try to bring back the populations of these animals. So really, this has our work sort of spans all the way from trying to understand how we can use this as a model to develop human therapies for cancer, all the way to the ecological side of things, where we’re trying to understand how it’s spreading between different bodies of water and how to help the ecosystem and help aquaculture together with, like you said, the stakeholders, the people who are really interested in the clams being around, are

 

Jack Faris  29:32

there special forms of satisfaction in building these relationships with, for example, the Suquamish,

 

Michael Metzger  29:37

I think it is really great. I mean, like you said you really are sort of working with the people who really care about the animals and want them to be there. I think that’s really valuable, and it’s sort of a direct application of the work to the real world that is not always there when sort of looking at genes involved in something in the lab. And so I think that’s really. Exciting to have the connection that something you’re doing will really sort of have an impact and affect the environment and affect people who

 

Jack Faris  30:15

care about it. It may be obvious, but I want to give you a chance to be clear, we actually at PNRI have live clams that are part of the study.

 

Michael Metzger  30:24

Yes, yes, we do. We have live soft shell clams, as well as getting in cockles from a variety of different places in Puget Sound together with in a big collaborative grant that we have, together with Puget Sound Restoration Fund and Suquamish tribe shellfish biologist and a number of other organizations on the East Coast and West Coast. And

 

Jack Faris  30:47

is it easy or difficult to determine whether, as a clam comes in, it’s healthy or has cancer in it,

 

Michael Metzger  30:53

you actually can’t tell by looking at it. So you can’t just pick up a clam and say, Oh, this one has cancer. You have to actually look at the hemolymph. What we do most of the time is to use a syringe and drop a little bit of the hemolymph, which is really sort of the circulatory fluid or the blood of clams or cockles. And then we can look at those cells under a microscope and see whether they are the normal cells or the cancerous cells based on their shape. And then we also have much more specific diagnostic tools that look at PCR that amplify very small amounts of DNA that’s specific to the cancer and not to the host cells. And so we’ve developed those methods so we can really identify animals that have even a very small amount of cancer in them. And because we can do that just from a blood draw from the clam, we’re able to follow animals over time and look at the progression of cancer, because just taking a small amount of blood doesn’t kill the animal. So we can take a blood sample every two weeks and keep the animals, like you said, in tanks, in incubators in our lab, and follow the progression of disease, whether it’s natural disease or the experimental infections, where we’re inoculating the animals, injecting the animals or exposing them to cancer.

 

Jack Faris  32:11

You know, it’s, it’s interesting to hear you refer to these your subjects as animals. I think most of us, when we think of we don’t put, of course, we rationally do put them in the animal as opposed to vegetable category, but we it’s a little unusual. So it prompts me to ask quirky question, do you find yourself fond of clams?

 

Michael Metzger  32:33

I think I’m more fond of them now than I was in the past. I think kind of, I don’t

 

Jack Faris  32:41

mean just as food, I mean as organisms, friends, yeah,

 

Michael Metzger  32:45

yeah. I think, Well, I think I appreciate them a lot more. I think that I had a lot of just sort of assumptions that came along with not knowing anything about them. I grew up in Phoenix in the desert, and that’s sort of far away from any clam, so I, I didn’t know a lot about them, and I sort of probably just put them in that category of, oh, they’re invertebrates. They there’s lots of them. They make a lot of babies. They have short lifespans. It doesn’t, that doesn’t really they’re not, sort of like you said, they’re not animals in the way that we think of them. But I think they’re, they’re really interesting. It turns out that, yeah, these clams can live several years. Actually, some clams are among the oldest living organisms on the planet. So that, I believe it’s the Atlantic Quahog that can live very long time. And I think the it is the oldest reported living animal there was a at a cohort that was reported to be 504 years old. I think that’s the number of 506 something around that based on counting the layers of the shell that get laid down. So sort of goes against my initial naive view of them as just these things that make massive copies of each other. Really, there’s a whole lot of diversity and genetic differences within them. So even more diversity from one clam to another than there is from one person to another. The genetic level and there’s makes things complicated, but also makes them interesting when we’re doing the genetic analysis.

 

Jack Faris  34:18

Well, anyone who’s ever dug for razor clams will have a respect for their agility, for sure. Yes, your work as support from both the NIH, the National Institutes for Health and the National Science Foundation, which has a somewhat different charter, could you talk a little bit about how that works and whether or not that generates any strain, or whether that’s, in fact, complementary to each other.

 

Michael Metzger  34:47

Yeah, I really think they are complementary. And I think this is sort of a interdisciplinary is a big buzzword, but it is a really interdisciplinary project, because it really covers a big span, all the way from finding new transmissible cancers class. Operating with ecologists and marine biologists to find new cancers and new places, figuring out how they spread, and sort of then, from that, we figure out how whether animals are sort of resistant or or susceptible to it. And then that’s really the phenomenon. But then you can explore in more detail to understand how an animal has evolved resistance to cancer that could be really important for human health. In my mind, the big picture of what we’re looking at it all works together. And I think I know that defunding sources have particular interests of what they want to fund, and so each part of that research really has sort of different immediate implications for it, and different ways that it’s relevant when we’re understanding how the cancer spreads through the environment. And like we said before, that’s really incredibly relevant to the people who who care about those clams, who are interested in those the stakeholders in in the local populations, people who are into aquaculture, and the tribal groups and tribal shellfish biologists, as well as many other people, they’re interested in understanding how those diseases are spread, how you can deal with that, how, how we think the animals will will evolve in response to that. And then the NIH is really interested in the mission of understanding how this is important for human health. And so once we understand a model well enough to use it for that, then we can use it to for those purposes. So yeah, when I take a step back and think about the whole thing, I think they all really interconnect with each other, but in terms of their sort of immediate funders, we have to think about what is the what is the question that they want to know the answer to, and then target parts of the project that are important to them to their funding. So it’s a little bit of a juggling act to sort of just fit it together, but I think for all parts of this project, there’s someone who’s interested in it, and I think that’s the part that makes it all work, Music.

 

Jack Faris  37:00

Music. What’s your assessment of the state of the culture of science in the world today, or especially in America, when we’re

 

Michael Metzger  37:11

talking about the culture of science and how it’s being done? I think there’s a lot of things that we could do better as everyone knows a lot of the reward mechanisms are not really the best. People always talk about targeting papers to different the journals that have high impact factor and all that sort of thing. And that’s not really what has impact in society. There is definitely a difference between getting a paper out and having an impact in the real world, on having an impact on ecology, on restoration of an animal, on developing a therapy for human health. And I think the papers are really exciting, but they aren’t definitely the only thing, and it’s important to sort of try to keep that in mind. I think one of the other things that I’ve noticed in my work is that my work is really interdisciplinary, as we talked about before. It’s looking at cancer biology, but not a normal cancer. It’s looking at marine biology, but not in a normal way. And it’s looking at an infectious disease, but it’s not a normal infection. And I think in a lot of places, those different topics, and those fields are all siloed in different departments, and there’s a lot of or there’s not a lot of crosstalk between them, because things get so detailed and specific, and to be caught up on one specific field, you have to go so deeply and narrowly into it, it ends up making sort of barriers between people in different fields and different topics. And I think I was kind of naive to that when I started this project, because I had always been looking at viruses that were relevant to humans for most of the time. And I get into this project looking at transmissible cancers, and I think this is super fascinating, and then I come up with roadblocks that biologists don’t think it’s biology because it’s marine biology, and marine biologists don’t think it’s marine biology because it’s something else. And when you actually start talking to people, to people, a lot of people, yes, it’s fascinating, that’s interesting, but you’ll have these sort of institutional barriers in many cases that block it, and that made things difficult. And I think, like I said, you can always find people who are interested in it if you got to talk at individual people, but those are some sort of structural barriers that I think are kind of self imposed problems that we put on things. And I think a lot of really interesting work comes when you have people who are trained in one area go and jump into a slightly different area and sort of bring different expertise and bring different experience and ideas. And I think that can be where you can get some really interesting ideas coming in science, and there are still barriers on that. We like to say we like interdisciplinary projects in grants and things. But often it’s when people say they want something interdisciplinary. They have, they have two particular fields that they want to put together, because it is sort of a hot thing to put those two fields together right now. But really the interesting interdisciplinary one is the one that nobody’s looking at. Yeah, and I worry there’s a little bit of a sort of a streetlight effect people are looking in those fields, because that’s what they do in those fields. But I would like to see more sort of cross talk between things. And I know it’s hard to dilute your time and sort of dilute money from the funders point of view, for things that may not be a payoff, but I think it’s really a useful thing, and that’s one of the things with with PNRI is that it’s sort of a broad institution where we don’t really have a particular silo. No one came in here and said, when I was coming here and said, You can’t do this because that’s a marine organism, or you can’t do it because that’s an odd cancer model or something like that. The questions were interesting, and we were thinking sort of more, sort of horizontally, more widely, at different things that are connecting with genetics, but then could be other topics that are really interesting and have an important impact, even if they’re sort of outside of the norm of what would fit in any particular individual department in a university. Oh, I’ve heard from a lot of people that this notion that sort of science will explain away mysteries. You’ll see a mystery, and the scientists will look at it, and all of a sudden, it sort of doesn’t have value anymore. It’s not mysterious anymore. And I don’t I’ve never really understood that. I’ve always think that the more you understand things like the more wonderful and amazing the mystery is. Maybe you know more of it, but there’s still more you don’t know. There’s never an end to knowing things about about the way the world works. And I think that it’s really interesting when science can can explain mysteries, but it doesn’t sort of explain them away. I’ve never gotten that idea. And I think that’s another thing that I wish was, I wish was sort of more prevalent in society, this idea that you can sort of explain things and they become sort of more interesting and more wonderful, rather than becoming sort of, there’s no loss. I think, in my mind, when you learn more about something,

 

Jack Faris  41:59

that’s a great point to end on Michael, thank you so much. This has been a treat, and I know our listeners will enjoy learning about clams and the fundamental nature of the scientific enterprise through clams. Thank you. Thank you.

 

Anna Faris  42:15

Thank you for joining my father and me for this episode of PNRI Science: Mystery and Discovery. To learn more about PNRI and get connected to our groundbreaking science, go to pnri.org/connect. We would love for you to join us for a tour of our labs or a virtual event with our scientists. Thank you for listening, and we hope you’re inspired to learn more about genetics and chat with your friendly scientist neighbor. I’m your host. Jack Faris, CEO of Pacific Northwest Research Institute. I’m also a regular guy. Dad, what do you think? How’d I do?

 

Jack Faris 42:50
Better!