 And we're back with more this week in science. Yes, we are and we are joined by our guest this evening Dr. Amro Hamdoun. He is an associate professor of biology at Scripps Institution of Oceanography University of California, San Diego He has a PhD in physiology from UC Davis We were there at the same time. That was fun He also held a an NIH NRSA postdoctoral fellowship at Hopkins Marine Station of Stanford University His general interests are in the fields of developmental biology and environmental toxicology his current research focuses on the defense and survival mechanisms of embryos and the biology of the accumulation and elimination of chemicals in marine animal cells and the sea urchin is Usually your animal of choice, but in a recent paper that was published your lab found that Persistent organic pollutants in the ocean accumulate in the tissues of tuna inhibiting cellular defenses of cells and humans and mice by binding with essential transport protein proteins Fun stuff Amro. Welcome to the show. Thank you. Thanks for having me on and Amro that last bit was terrifying to me Yeah, because I am a Four to five can of tuna a week Because it is my time if you took everything on the grocery list and looked at the thing that I Consistently buying consume the most. It's tuna me too So we're doomed. That's it. This is sort of a good news bad news story. So the bad news is that there are really contaminated fish out there in the ocean and They account for about three percent of the fish that we caught that you probably don't want to eat The bad news is there's no way to know when you buy your fish at the store Which one's really contaminated or not because we don't have a really great mechanism of labeling fish from the point of capture All the way through to the supermarket where you buy the fish So I wish I could tell you which can of tuna to buy but I'm you're sort of on your own It wouldn't stop me. This is the like it'd be great to like narrow down the right can like hold it up to the light And like yeah, what's not right, but right? Three percent. I'll take those odds That's right. Well We know where some of the most contaminated places on the planet are so that's one way we can kind of reduce those fish in the food supply and We also know what the contaminants are so we can look for them So there there are there are ways to do that and one of the things we're working on now is ways to look at these contaminants more cheaply and rapidly so that anybody could do just what you're talking about hold the tuna can up to the light and determine whether the tuna that's in there is is clean or not and An important thing to add to all of this is that these contaminants are not unique to fish or seafood or tuna they're really everywhere, but Fish we focused on fish because fish tend to have the highest levels of these chemicals as compared to some of the other foods that we Consume regularly. Yeah, because fish as they swim in the ocean. They they breathe they eat they are surrounded by They're they're in a bath of anything that's around them Whereas other animals have to go searching and for specific food types And it's a little bit different at the top of the food chain there with a tuna Yeah, like with my that's the big concern with mercury right bio accumulation is huge Yeah, so the the idea the idea is that not only are they swimming around in the ocean the oceans large but The ocean has has been used sort of as a dumping ground for a lot of these environmental chemicals And of course all of our land sources of chemicals like Agriculture drain into rivers and they ultimately end up in the ocean. So we looked at fish in the Gulf of Mexico for example and Those fish have very high levels of these chemicals because the Mississippi River is a great Carrier of contaminants that would normally be on land and end up in the ocean Can we talk about the contaminants themselves for a minute? So I mentioned briefly that they're persistent organic pollutants, but what does that mean to the layperson or and to me? Well, actually the reason I came on the shows is hoping you guys could explain my paper to me Then So I think you know they basically they're chemicals that hang around and unlike you know A lot of things that are in the environment break down and after a few days or weeks or months are essentially gone Persistent pollutants are this class of chemicals. They include really famous things like DDT that really Arguably sparked the modern environmental movement Rachel Carson's work on on on pollution That the idea is that these are chemicals that don't break down And they have this really unusual tendency to move out of the environment and into living things and as a result Because we eat other animals they end up in us and humans All of the chemicals we looked at in our study are things that you can find in the blood or in a human body Every American or probably every person on the planet. So whether Whether or not, you know, you think you're you can try to avoid these chemicals, but they're really persistent They really stick around and they just sort of end up in you. Yeah, they're things like flame retardants, which are or chemicals that are put in the the foams that make up couches Or delicious I know I know of people who are working very hard to get flame retardant furniture Outlawed and to get these flame retardants taken out of our furnishings so that we won't have them in our home environments anymore But they're still gonna stick around So the state of California just passed a law that requires labeling of flame retardants on labeling of furniture that contains flame retardants and actually the person that's probably done the most work on this Or one of the people who's done a lot of work on this is Arlene Blum Who wrote the book and a perna and she is actually a chemist from UC Berkeley and pointed out that a lot of these flame Retardants the structures of these flame retardants When you ban one of them what happens is that people make another structure that's very similar and Use it and they get the sort of same outcome. So she pushed hard so that we could have kind of at least Labeling and the ability to know what it is that's in our in our furniture or in our in our house Our major exposure to some of these retardants is just household dust Just dust just household dust so you're gonna be picking up a lot of flame retardants from those Stain repellents from your carpets How many chemicals did you did you look for in your particular assay? We looked for 40 chemicals that are three major classes on pesticides flame retardants and PCBs these are legacy Electronics chemicals and then there's we also looked at some plastics related compounds like phthalates and bisphenol a Yeah, okay So what do they actually do they they attach to this transporter and how did you what's the story behind how you Figured this particular Inhibition of the transporter out like how did you how did you determine all this? So we were we were trying to understand why it is that certain chemicals are so persistent and and the idea being that if you can figure that out you can make chemicals that don't persist so That would sort of be the that'd be sort of an amazing thing to do you can make a flame retardant that keeps your laptop from bursting it into flames Right, that's that's a good thing But then it breaks down over time, but then it breaks down and it doesn't end up in you and it doesn't have any problems And what we thought was we would find some chemicals that this transporter, which is a really important cell defense would latch on to and Eliminate get rid of and that would give us some clues into which ones are safer and which ones are worse And we looked at these persistent chemicals because they're precisely the kind of thing we worry about in terms of environmental chemicals And the unexpected thing for us was that rather they so so they latch on and what we show in the paper is they actually bind right Where they should if they were going to be Expelled or eliminated by these transporters, but instead of being eliminated They sort of hold on and they prevent the transporter from actually doing its work and they actually slow it down So the the consequence is that the more of these things you get exposed to the the less Effective your body is going to be at getting rid of chemicals you would otherwise get rid of So do you have it you do you have evidence is that or are people looking for evidence of it actually Influencing immune function and having downstream effects or is this just the first study showing okay? We know that it blocks the activity of these transporters slows them down They don't work as well, and now there are chemicals getting into cells. We don't know what happens next Yeah, so the idea that this could happen is was proposed about 20 years ago by a Croatian scientist named Branko Kurleck And he suggested that maybe what makes these chemicals so persistent is rather than being pumped out or eliminated by the system They actually slow it down or bog it down And it's been shown in a variety of different organisms and cell lines and Different test scenarios that this actually occurs, but nobody really had a sense for how this occurs Does it occur through some kind of predictable binding to the drug? Transporter is this just some general effect of weakening a cell and making it not work what our our paper shows is that this occurs through a very specific binding to Residues in the transporter that are evolutionarily conserved so 15 of the residues that bind PBDE which is a flame retardant in a human our The same 15 are also present in the same transporter from a tuna and what this means is that if you Want to begin to design chemicals to be recognized and eliminated you actually have some targets that you can work with and We think you know in terms of human health impacts. We don't know you raise a good point We don't know who is going to be affected most by this, but our concern is obviously about vulnerable populations There's there's one in particular that we We thought about and that is human neonates So normally this protein pig like a protein sitting around in your gut and it's keeping nasty things that are in your diet From entering into your body Human neonates in the first six months of life tend to have relatively low levels of these protective proteins in their guts, so they're already kind of at the threshold and breast milk tends to concentrate a lot of these pollutants in fact in villages in in Africa where DDT is still used for Malaria control the concentrations of DDT and breast milk are as high as 30 micromolar And that's well within the kind of range of concentrations that we saw Causing problems for this defense system in a test tube. So we think this We think this paper should encourage our policy makers to think a little bit about this pathway as being a kind of Potential way in which chemicals can cause harm And maybe think about what are safe. We don't have exposure limits for these sorts of things think about what our safe exposure limits should be and and you know we We want analogy might be to think of these as being a bit like endocrine disruptors, right? We have chemicals that we think of as being like hormone mimics These are immune system weakening chemicals that we might want to think about How much of them we want to eat how much we want in our food How many cans of tuna Justin should eat per week? How much tuna but it's not it maybe as an adult you don't think about it as much how much how much should you feed your children tuna? Or how much you know if you're pregnant how much tuna we tell we tell pregnant women not to eat tuna because of the mercury like Blair said earlier earlier But maybe there are other reasons The list that's right Most people think of mercury as being the major contaminant to worry about in tuna and it certainly is it can be at very high levels in Very high trophic level tuna. We looked at yellowfin tuna, which are somewhere in the middle as compared to say bluefin or skipjack, which is what's in a lot of canned tuna and Even even there we we found quite a bit of these persistent pollutants in certain fish But again, the good news is you can avoid this if you know where your fish comes from and you know that it's a place where they're relatively little Human activity. I live in Portland, Oregon now And that sounds like the kind of farm-to-table activity that we joke about on shows like Portlandia Yeah, I now know the name of my tuna because I went to the And it seems like this test to that we could apply to the can Could be applied when they when they're selling this tuna to market, you know They could they could apply this then and say okay Do you want to buy one with the level of contaminants? Then you can't label it like Contaminant free you have to go to that send it to a black label tuna canning I'm kind of thinking I should just go to my own doctor and have a couple of tests and just see How full of contaminants are you Do I have Doctor turns me is like Justin you need to stop eating couches that I know So that's kind of my question too is we're talking about these contaminants and it sounds pretty scary But there's lots of things that we talk about that's in our food or in the air in our water that are also scary Where is my freak out level on this am I like a six am I at an eight am I at a three? How bad is this? Yeah, I don't think it helps to freak out ever so I Encourages zero freak out I think you know I think there are other types of food that also have these contaminants for the average American the primary route of exposure is through Meat and dairy the reason simply being that we eat a lot more meat and dairy that we then we eat fish So not eating fish is not necessarily a solution if you eat you will be exposed to these contaminants and You know, you don't really get a choice. I mean environmental chemistry is this interesting Experiment because there is no control population on the planet We all have these chemicals in our body and we don't know exactly what the effects are going to be But I think there is an important lesson there in that before we make Compounds and put them into the environment We might want to look at some of the factors that influence their bio accumulation and really avoid making chemicals that are going to enhance bioaccumulation or reduce our ability to eliminate other types of chemicals that we would normally keep out And and do we have any good contenders for for a non persistent chemical that could do some replacements? Well, we showed in our study that simply changing the Stereochemistry of a molecule can dramatically change its interaction with a drug transporter so we looked at two chemicals deildren and endren which are Stereo isomers of one another and We found that one of them acts as this very strongly inhibitory molecule And the other is 20 times less potent So I think even looking at very simple solutions like what stereo isomer of the compound you use Will help the other lesson and I think it's one that isn't really new in environmental chemistry But we see it again and again is that when we we when you take up an organic molecule And you remove all the hydrogen atoms and you replace them with halogens you really reduce the ability of metabolic enzymes to break it down and and of course, you know the reason why and Is that carbon halogen bonds are some of the most stable bonds in nature? In fact, the most stable bond in nature is the carbon-fluorine bond So non-stick chemicals are our chemicals for example where all of the hydrogens have been replaced with Fluorine atoms and that makes an incredibly slippery wonderful molecule that doesn't stick your egg It also makes one this very difficult to break down and yes So it'll be it'll be there much longer, but it won't be in our biology Yeah, yeah, this isn't trade-off But I guess that if that's you know if we're not worried about the fact that it actually exists and are worried about it being taken up in Organisms, I would think that's an excellent solution Well, and there are non-stick alternatives that don't require the use of Based on the way a material is shaped or organized that reduce how sticky something is that don't require the use of these chemicals So the question might be, you know, do we really need these things in all of the applications that we use them in is it really essential to have Stain repellent carpets or can we replace some of those carpets with other materials that might not require the use of They're still pretty stain repellent might not require the use of these Compounds When an antibacterial came it onto the market and we started putting it in everything antibacterial hands-up antibacterial sponges antibacterial everything no bacteria never Bacterial comb that was the weirdest one like yeah You're like, oh, maybe we don't need antibacterial in everything. Yeah, that's right. It's actually a bad idea Yeah Yeah, that's absolutely right and bacteria are Bacteria that the emerging kind of literature on bacteria says that they're pretty Good for you if you have the right ones And so we were constantly messing with them and creating more harm than good And I think they're I think we sort of repeat this lesson over and over again with Environmental chemistry we make something we use it before we fully understand what the consequences will be and then we sort of try to catch up with it and and change it and I The the our goal is that Environmental chemistry become a more predictive rather than reactive science Good idea So how does it feel to you? I mean you've been I know you've been working on the the environmental chemistry angle and developmental biology angle for For years and now it seems are you how do you feel about starting to push this into also the sociopolitical Sociopolitical side of things to try and actually take your research and say okay. We now need to start making some recommendations. Oh Well, that's what the FDA and EPA do and What we can do as scientists is really give them the best information available One of the things we didn't know as I mentioned before this study is whether this Transporter inhibition phenomenon occurs through some kind of predictable binding So knowing that they can now begin to look at this and and ask questions about how much of these chemicals We should be exposed to in our diet, but there are people who do that and do it very well, and that's that's their That's their job. So I I think I think giving them the information is probably our role Awesome, and what's your next step? Are you are you going further with analyses of this sort? Yeah, so we're now working with people in the Department of Pediatrics here at UCSD to get a handle on when in early life and animal might be or a human might be very Sensitive to these classes of compounds. We know that things like drug transporters, you know in an early embryo stage are not always on their periods when they turn on or off and So when they might be especially low might be windows when an exposure to a small amount of these Transporter inhibiting compounds would be problematic. So we're trying to track those developmental windows down And then we're also looking at other defense proteins We're trying to take the same model that we applied here for looking at how One chemical effect or one transporter is affected and look at the other transporters And other parts of the chemical Defense system people often use call this the chemical immunity system or the chemical defense system and see how How they might respond to these same kinds of exposures It's an interesting way to put it I mean in articles that it talked about oh this affects your immune system and so the way that we normally think of the immune system as the T cells and the in the blood and beta B cells and everything it's this is different This is like this is like skin. This is like a barrier This is a door and I think it like there's you you're quoted in several articles as calling it a cellular bouncer which Which is yeah, it's just an interesting and another interesting level of okay We have a barrier against the environment and we have to our body has to choose what it's gonna get to bring in or not And sometimes it can't yeah I think one of the things that we we now appreciate about how cells work is that in addition to having a system that protects Us against pathogens things like viruses and bacteria We also have a very elaborate system in the body to protect us against foreign chemicals and the reason for that is that you know plants and animals and Have always and bacteria have always been making molecules to defend themselves to prevent other things from eating them and and in in response their their Predators have been making Strategies or proteins evolving strategies or proteins to overcome those toxins So we actually have a very elaborate system to protect ourselves from Chemicals and it's pretty effective Against the classes of chemicals that it evolved to protect us against where it falls apart Is against things that we never see in nature like things that are highly halogenated. Yeah We're create we're creating an alien environment in a sense about one that we didn't evolve To deal with that's right. That's right Yeah, and bringing up the DDT question again now with mosquitoes making their way into the United States there is talk from many to bring DDT back into use in more areas of the world including the United States for mosquito control and so this is a This is something that if we If we need if we if we want to stop these persistent compounds from actually having developmental effects We need to figure it out one way or another Yeah DDT is a very interesting study, of course the the you know, it's still used in places where there is malaria and Malaria is a terrible disease and so Any strategy that can help reduce the human death toll to malaria certainly? valuable that said DDT is not is is not a perfect solution insects rapidly evolve resistance to DDT and As a result after a few generations of use it becomes less effective and there are other strategies Of course that are necessary in parts of the world where there's a high DDT burden There's often also poor sanitation and other issues that need to be addressed before Before you can really sort of stamp out the the problem of you know vector-borne disease, so I Think these you know, I think DDT may be part of an arsenal, but it's certainly not the Silver bullet that it's sometimes portrayed to be Are you gonna go see your chin tasting anytime soon? Breeds contempt I don't eat my research animals Oh It's an important rule of science. Yeah, Kiki. How do zebra finches taste? Yeah, never. I never had the the skewer roasted zebra finches. That wasn't quite the Like eating a teeny tiny wing or a teeny tiny jump stick just I'm sure some people might enjoy it People eat everything. I don't know. Oh My goodness Amro, this is just this is fascinating It's I think the point that the the perspective you're taking on it is a very positive action oriented perspective that I Hope is the message that's being picked up by people as opposed to the many headlines that that we see that are the fear Mongering be afraid of your tuna kind of kind of thought but rather Hey, we need just to keep working on this and there is action that can be taken as opposed to Being afraid of our food. Yeah, that's right. I I think You know as I've been asked about this and I eat tuna I think it's a it's a healthy food and there's certainly plenty of advantages to eating tuna but Think where we can go with this is to make sure we we eat the least contaminated ones And I think people are are going to want to eat less contaminated fish. Oh Yeah, that's Given the option But I know I'm curious too and this is a probably a longer different conversation about because it seems like the profit side of Chemistry is about creating the newer the better the efficient product and and is probably More so now but still less so Concerned with the environmental Downstream costs of it further further down. So so I do hope I do hope the discoveries that you're making get incorporated Into the production of new new chemistry that I'll facilitate it the brighter better more efficient future although I Because I you know because that is the profit driven segment of all of this I can see that as as being a challenge. I Think green chemicals are profitable and I think there is a demand a market for them I think the chemistry industry Recognizes that and I think it's important also not to think of these industries as single entities Some companies in the chemical industry have taken very bold moves to eliminate chemicals that are found to be persistent An example of that was the 3m company Choosing to voluntarily kind of phase out per fluoro chemicals when they found out they were persistent and other companies have not so I think you know, I think it's there's always a danger of painting with a broad brush when we're thinking about these industries and How they might react or how much they they want to do to avoid making persistent chemicals Some some are quite proactive about that and I wouldn't I mean and I'm not meaning to think that the profit side of the chemistry industry Absolutely doesn't care downstream But again and looking at like we've come up with this great new product Let's spend five ten years testing it in various ways before we release it That's the part that I find is going to be the difficult challenge But if we have things like this, you know where you can look and see how it affects this transcriptor You know if they have a set of things that they can quickly and actively test the new product on and with That might accelerate that their ability. That's absolutely right and I think they're You know the the current laws that govern these sorts of things don't Necessarily require that kind of testing you're talking about although in Europe a lot a law was passed several years ago called reach and It does require this kind of testing but the very challenge is exactly what you brought up what do you actually test with and what do you look for and This could be one of several things you could look for in addition to whether or not, you know a A you know an animal dies when you put it in the water with this thing because really we're not You know the big change in how toxicology is happening these days is we're no longer really concerned With eliminating the Incredibly toxic molecules that are going to kill something we're now looking for much more subtle effects of chemicals interfering with hormone systems affecting our You know pathogen defenses or chemical defenses and that's going to require a lot more thinking about these kinds of biological pathways that we could test Many organoids Yeah, many organoids in dishes and you Then you test it on them. Maybe that's the future of this testing. We'll see Amro, do you have any other big plans for your your research future anymore? Any other studies that you're working on that you're excited about? We're also looking at cells called primordial germ cells. These are cells that give rise to eggs and sperm We'll be happy to hear that and they're specified very early in embryonic development. These in most animals are set aside in the first five days of life and and then they they basically Hang out and wait until the gonad develops and then they migrate to the gonad and they They they begin to divide and then produce in you know, whether they're male or female eggs or sperm so One of the things we're looking at now is how these cells protect themselves because if they acquire mutations in early embryonic development Unlike mutations that will happen in any other part of the embryo Mutations in these cells, of course will be passed on to future generations So we're very interested in how those cells might defend themselves one of these transporters or other pathways to do that and how environmental exposures might affect them and then Yeah, that I think that's that that keeps me more than busy Yes, it sounds These are these are some some broad directions to go in and some there's a lot of research a lot of experiments I'm sure you're coming up with Yeah, yeah, the people in the lab wish I would come up with fewer. I Remember being a grad student in a postdoc one. Yeah, that's enough. That's okay Yeah, I still yeah, that's right Once upon a time many suggestions All right, I won't keep you any later tonight unless you would like to stay with us for the end of the show We've got a few more science stories that we're going to cover on the way out of the show But thank you so much for your walk tonight. I talk about your work. I appreciate it. Take care