Written by Christopher Kelly
Sept. 15, 2016
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Christopher: Hello, and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly and today I'm joined b y Leandra Brettner. Hi, Leandra.
Leandra: Hi.
Christopher: Thank you so much for coming on today. I think you're very brave. Today, we're going to talk about genetically modified organisms. Obviously, this is a contentious subject and we're going to go deep into this. Leandra is a PhD candidate at the University of Washington. We met recently at the Ancestral Health Symposium in Boulder. Leandra, can you tell us a little bit about your background and your research interest?
Leandra: Sure, yes. As a graduate, I am working in the field of synthetic biology, which is kind of like taking genetic engineering to the next level. Instead of just engineering single genes now we're like trying to engineer entire genetic circuits and systems for both the purpose of application to biotechnology. But personally, I'm more interested in using synthetic biology techniques to kind of probe biology in ways that we haven't been able to before and answer questions that are really hard to get at if you can't deconstruct the living system and then put it back together again.
I'm a PhD student at the University of Washington in the Bioengineering Department. Before that, I was a molecular and cellular biology student at the University of Arizona where I actually worked in computational evolution lab for three years. So, got kind of broad background, I guess, in biology, you could say.
Christopher: What brought you to the Ancestral Health Symposium? So, I thought you're very brave to present this poster. And the poster that we're going to be talking about in this interview, I will link to it in the show notes. If you come to the show notes of this episode, you'd be able to find the PDF document that we're going to be talking around. And there's lots of nice diagrams in here. I don't think you need to see the poster to get something out of this interview but it might be nice to have a look at it afterwards. I thought you were super brave to put this poster up in front of all these people who were all kind of -- They were all kind of crunchy, let's face it.
Leandra: Yeah. I mean, I'm pretty crunchy.
Christopher: And I should probably read that disclaimer before we go any further that we run this functional medicine practice and my wife has a Masters degree in food science and she coaches athletes with their diet. I know for a fact that she always says go organic. So, before I hang myself here with the GMO story that I should make that clear. Maybe my mind will be changed by this interview. The reason I thought you were brave is because this subject is so highly charged and I saw this firsthand when you were presenting the poster. There was a large man who was invading your personal space and starting to froth a little bit at the corners of his mouth and I'm like, oh my god.
Leandra: I wasn't really the person who he had like some aggressive contention with.
Christopher: Oh, really?
Leandra: I didn't take it personally, I guess, in the end because it turns out he just likes to be aggressive with people he doesn't agree with.
Christopher: Oh, really? I wonder if he's listening to this podcast. There's quite a number of people that listen to this podcast that attended that conference, I'm sure. I hope I'm not going to offend anyone by giving that description. Okay. So, we better dive into this. Perhaps the most important part of the conversation is definitions. Genetically modified organisms cover such a broad range of things that to be against them doesn't really make any sense. We've seen this elsewhere in biology. So, to say that low fat diet is beneficial, what do you mean? You mean low trans fat? Do you mean low omega three essential fats? What do you mean? You've got to be specific with your definition. Maybe we should start there and let me ask you what is a GMO?
Leandra: Yeah. No. So, this is actually a question that I can't really answer definitively either. So, from my perspective, especially having an evolution background, when you say genetically modified, that just means that some sort of genetic change has occurred from the ancestral genotype. And that can happen through "natural" means, like just randomly out in nature, or it can happen with the aid of the hand of humans.
Actually, so, in doing the research for this poster, because the acronym GMO is all over the place, part of the reason I wanted to present this poster, when people say they're avoiding GMOs, like what are they actually avoiding? What exactly do they want to not include in their diet? And in my research for this poster, I stopped after six organizations, and nobody, none of these organizations have a cohesive definition.
The recent congressional bill defines it to be, the one that just passed, the voluntary labeling that's been very controversial, I think it's S.764, it refers to food that has been modified through in vitro recombinant DNA techniques. And then they go on to say this modification, you have to be able to prove that this modification could not occur through conventional breeding or through mutation, natural mutations in nature.
Monsanto, interestingly enough, has a very broad definition of genetic modification to say that its plants or animals that have had their genetic makeup altered to exhibit traits that are not naturally theirs. It's like, well, okay, that's incredibly broad, which is interesting.
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Christopher: And what do you think the definition should be?
Leandra: I guess, it depends on what context it's being used in. Me, personally, when I think of genetic engineering, and this is strictly from the fact that this is how I work with these "in vitro recombinant DNA techniques" -- I work in yeast, the yeast that we use to make beer and bread. It's actually a very popular model organism in research. And to genetically engineer them, we basically just give them foreign DNA and through a couple of chemical processes they uptake that foreign DNA and integrate it into their chromosomes. It's carefully designed. I know, because of homologous recombination, I know exactly where that gene is going to go in the genome, I know more or less what it's going to do.
Christopher: Okay. Let's contrast that to the traditional. Can you describe the traditional method of artificial selection?
Leandra: Right. So, artificial selection is just finding some organism, plant or animal typically, that the human race has been interested in, and whether consciously or unconsciously, arguably, selecting at the trait level for interesting phenotypes. So, for example, corn, if you look at the ancestor of corn, teosinte, it's a grass. It's got this knobbly little string of seeds that doesn't look anything like modern corn. But through just selectively picking larger seed pods progressively across generations you end up with modern corn.
Probably the easiest and most widespread example of this is like dog breeding, for example. if you want to take a wolf and turn it into a Chihuahua, just progressively take the smallest of east litter and mate them together until you go from something that looks like a wolf until something that looks like a Chihuahua.
Christopher: And then let's talk about some of these DNA delivery methods then. Because these are crazy and, I think, they've changed a lot. When I thought about the DNA delivery, until I saw your poster, I thought it was some shotgun technique where you're just blasting stuff into the chromosomes and hoping for the best. That may have been true in the past but it's not true now. So, can you talk a bit more about that?
Leandra: Yeah, sure. So, there are two ways to get foreign DNA into plant tissue. One is through this naturally occurring plant pathogen called A. tumefaciens. It's a bacteria and it naturally deliver as foreign DNA to plant cells. Basically, it just attaches to the plant and then uses some proteins to breach the plant cell wall and then it delivers foreign DNA and that DNA does something beneficial for the bacteria. That's like a bacterial method and that actually only works for pretty narrow range of plants.
A lot of species are resistant to A. tumefaciens infection. They are what's called recalcitrant which just means it's hard to transform them genetically through the bacterial means, so instead it's done through something called biolistics or gene gun. Actually, so, the delivery methods are still the same. It's the integration methods that have changed. So, with a gene gun, you attach pieces of DNA to these like metal nano particles and then those are shot into the plant tissue.
And then previously, before we had really the new sequence specific nucleases, you kind of just hoped that couple of your seeds would take up that DNA and start expressing it. You'd have selection markers for this. And it would integrate, more or less, randomly into the genome. However now, with these sequence specific nucleases like zinc fingers and talens and CRISPR/Cas9, probably CRISPR/Cas9 is the one most people have heard of, if they've heard of these things, it's been in the news a lot lately, you can actually target specific sequences in the hosted genome.
And when you make a cut in that DNA, the organism has all kinds of mechanisms around to repair that -- Because you don't want broken DNA hanging out. It's not good. So, that foreign DNA that's kind of just like floating around in the plant cell, we'll typically have what's called homologous regions, which means it has overlapping sections on either end of the gene, overlaps with the insertion site into the genome.
And when the plant goes to repair that double stranded break, it can either repair it through what's called non-homologous end joining where it just kind of glues it back together. But organisms don't typically like to use that method because it often induces mutation. So, what they'll do instead is use a template from the adjacent chromosome and homologous recombination right over that break with a template, which typically would come from the sister chromosome in a diploid or multiploid organism.
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And if your foreign DNA is hanging out and it aligns with the break, it can be integrated into that specific site. And this still happens at the very low efficiency. So, even if you try to transform like, say, a thousand seeds maybe, only a couple will have a properly integrated piece of foreign DNA.
Christopher: I was just going to say you just went a little bit over my head there but that's okay because I'm going to have this interview transcribed. The transcription will be linked from the show notes. And I'm going to get back through the transcription and then read it and then I'm going to find some videos online and I'm sure I'll find some good ones on the Khan Academy to try and make sense of what you just said. I like that. That's perfect. By going over my head, you've inspired me to go learn something new. CRISPR/Cas 9 are probably the key words that you need to unlock some more information.
Leandra: Yeah. And, I think, actually, the majority of plant engineering right now is being done with something called talens. It's a similar concept. It's still just like homing nuclease, which is basically -- It's just a protein that cuts DNA. And the homing part comes from either a protein sequence or an RNA sequence that binds to specific regions of the DNA. So, these homing endonucleases haven't changed the delivery method of the DNA. You still either have to use a bacteria or this was called biolistics, these gene guns, to get the DNA into the plant cell.
However now, instead of just like hyper dosing them and getting a bunch of integrations and hoping something works, you can actually control where in the genome these things could integrate them. And with modern sequencing technologies, it's a lot easier to see if they've integrated successfully, if they're integrated into the place that you want them to be. It's sort of less concern with this off target effects of integrating all over the place.
Christopher: Okay. So, much more specific and accurate.
Leandra: Right, yeah.
Christopher: That's the integration. I thought it was worth mentioning, mutation breeding, but this sounds like an older technology. Am I right in thinking that?
Leandra: It's older than the, I guess, the genetic engineering that we're talking about now. So, I guess, after World War II, we just had, the world just had like a bunch of like radioactive stuff that they didn't know what to do with. So, they started setting up these -- they're called atomic gardens -- where they would just drop like radioactive coal bolt in the center and just plant around it. There's a picture on my poster. And you can see everything towards the center is dead but then as you get further and further away, the radiation is to a lesser degree, and then you just start getting massive mutation in these plants.
And then people just started phenotypically selected for new traits that seem interesting. Like, for example, a ruby red grapefruit. Up until then, grapefruit was like a pink, like a pale pink color. And through this, they found something with really, really dark red flesh. So, probably, obvious reasons, these atomic gardens kind of went out fashion.
Christopher: That's just straight out of the Simpsons, isn't it? Blinky the three-eyed fish.
Leandra: Although I think there's still a couple in Japan, but I might be wrong about that. Now typically, the way they do it is through mutagenic chemicals. They'll dip seeds into these DNA damaging chemicals and then grow them up and see what looks interesting. This, however, the mutation breeding, which I think this is very interesting, does not fall under the umbrella of GMOs for anybody or any organization. Nobody seems to care about this. They're almost entirely unregulated even in countries where GMOs are restricted or banned, which is kind of funny because, in this case, you have no -- At least in the genetic engineering, you have an idea of like what DNA is being transferred between organisms. But in mutation breeding, you have no idea what you're changing.
Christopher: Yeah. So, in computer science, we call this a thousand monkeys technique where you set up a thousand monkeys to work at a keyboard and eventually one of them comes up with an operating system.
Leandra: Yeah. So far, it doesn't seem -- I mean, there's something, I think the last number I saw, it was something they estimate about 3200 nutrient varietals on the market today. And, I mean, yeah, like so far we haven't come across any negative health effects. You could think of a situation where -- This is completely hypothetical. Say, you're breeding apples this way and you find a new apple that's bright orange or something fun. It turns out not only that apple orange but maybe instead of just producing cyanide in the seeds it produces cyanide like ubiquitously across the fruit but nobody would ever check for that because nobody seems to care.
Christopher: Let's move on to the safety concerns then because, I think, this is the real issue here.
Leandra: Yeah.
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Christopher: You mentioned that the companies that are producing these GMOs and I always think of Monsanto but that's not true, is it? There's lots of other companies doing it too.
Leandra: Yeah. So, right now, the last time, there was at least 20, if not more, that were actively making GMO products that are being used in actual agriculture. I think there are a lot more -- There are tons of startups that are sort of in the research and development stage because genetic engineering has kind of taken off in the years. So, yeah, this technology is starting to, it seems to be starting to move away from just these two or three companies that have a large monopoly on the system. And it seems to be spreading to include smaller companies that have, I guess, different motivations. Nobody likes Monsanto because Monsanto has a sort of revolving door situation or it's like they make these chemical herbicides and then they make seeds that are resistant to their chemical herbicide so you have to buy both.
Christopher: So, you can't just be against big corporations because there are small companies doing this too.
Leandra: Right, right. Yeah, I know. And another interesting thing that I found out in the research for this poster -- Because I don't actually work with plants. I work with yeasts. But genetic engineering is more or less the same across the board. Monsanto just recently bought Seminis. Recently as in like the last five to ten years. I don't remember exactly when they did. Which is the largest seed distribution company in the world, I think.
So, if you're trying to not, if you're avoiding GMOs because you don't want to pay, you don't want to give your dollar to Monsanto, you could be buying organic, you could be buying local organic and you still might be contributing profit to Monsanto because they own the largest seed distribution company in the world. They provide something like 40% of the country's seeds.
Christopher: And initially, I had a problem with this in that I don't like the idea of somebody owning the genome for a plant.
Leandra: Oh, absolutely. That's ridiculous.
Christopher: Yeah. But it's not new to GMOs. So, I discovered this later on that before there was any kind of human engineering of the likes that we've just been describing, that people already own the genome for the seed. This is not new.
Leandra: Yeah, no. So now, I think that the patent law, I'm not super familiar with it but I believe the patent law has been modified now so that if you have a patent on some sort of gene -- You can't patent entire genomes now, I believe. I know like Monsanto tried. I remember talking about this in my ethics class in biology as part of my biology degree. They wanted to patent the entire pig genome and they wanted to charge pig farmers royalties every time they bred their pigs because pig breeding involves the replication of the pig genome which they wanted to own.
I think, initially, there was -- I don't remember if they actually granted them that or it was later repealed but it seems like a lot of these sort of shenanigans have curtailed back a lot of these patent laws so that now if you want to patent any kind of genetic technology you have to be able to prove that it's novel in the context of that organ -- Yeah, it's novel in the context of that organism. If you want to patent a gene, like you can patent an organism now if it's genetically modified.
But if you want to patent a gene, I think it might actually been Monsanto, I don't remember exactly, like somebody had the patent for the BRCA1 gene, which is the breast cancer gene, and like researchers had to pay royalties if they wanted to use that gene. I don't think you're allowed to do that anymore. Now, it has to be you have to prove that this is a novel technology. Or if you patent a gene it has to be something that you made up like through protein engineering or something.
Christopher: Yeah. So, there's certainly precedence for this in software. What happens with patents is you just basically squeeze out the middleman. I own the patent for buying something with one click and that's Amazon.com and then Facebook infringes on that but that's okay because Amazon infringed on Facebook's patent for this and, of course, it's a lot more complicated than that and eventually you just end up with Facebook, Apple, Microsoft, IBM and a few big others that are all pointing guns at each other and the little guys are screwed because they kind of owe everyone, right? It ends in disaster.
Leandra: And, actually, I think a lot of times too you actually see these larger companies advocating for more regulation on themselves, which seems counterproductive. But if you look at it, they're huge so they can absorb the cost of these regulations. However, their smaller up and coming competitors cannot. So, it becomes sort of like a legal way for them to edge out any up and coming competitors.
Christopher: Let me ask you this. What are your main concerns over safety?
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Leandra: My main concern -- Yes. So, it would be on a case by case basis. Because the genetic engineering is a technology. And pretty much any technology, it can be used for good or it can be used for bad.
Christopher: Right. It's like guns. Like what are you going to use it for?
Leandra: Yeah, yeah. Or a nuclear power, online banking, pretty much everything. Typically, the technology is developed maybe not necessarily now, like the military industrial complex, but usually technology is developed for good and then someone comes along and figures out something awful to do with it. Like, I think, this is the classic Einstein case where he came up with basically the science that led to the production of the atomic bomb. He didn't want to do that but someone came along and was like, "Hey, I'm going to use your series and now we can make atomic bombs."
From my perspective, there isn't anything inherently dangerous to genetic engineering because you're just taking DNA and transferring it around which is what already happens in nature. Now, we put human intent behind it. Evolution has been changing up genomes for billions of years, even, so something called -- basically what genetic engineering is -- the asexual transfer of genes between organisms. It's horizontal gene transfer. Vertical transfer being parent to child, horizontal being like this asexual transfer between organisms.
And horizontal gene transfer actually happens pretty ubiquitously across biology. Bacteria pick up DNA from their environment, bacteria, you carry out, swap DNA back and forth. There only seems to really be controversy when you put human intent behind it. There isn't anything inherently dangerous to taking a piece of DNA from one organism and putting it another. It really depends on what that -- Because DNA is basically a physical manifestation of information.
It's like saying the printing press is inherently dangerous because you can print the Bible or you can print instructions on how to make a bomb. The printing press isn't the problem. It's the information in whatever the printing press. So, for me, my concern, yeah, would have to be on a case by case basis. It's like if you're, pretty hypothetically, if you're engineering coffee to be decaffeinated, you either like go in and just break the caffeine pathway. That I'm not really scared of. If you were to somehow stick, I don't know, small pox into bananas, that I might be a little bit more worried about.
Christopher: But could I suggest that there are some important differences between the traditional artificial selection method and the genetic engineering?
Leandra: Sure.
Christopher: As a computer scientist, again, I really understand the difference between top down and bottom up. So, the easiest way I can describe this to people who are not computer scientists is with a top down approach you might say, "A house, please." Whereas, with the bottom up approach, you might say, "A brick, and now another brick, and now some cement, and some more bricks, and some more brick." And so the process of bottom up, it takes a lot more time. And so you can think of the traditional artificial selection method, that is like a bottom up approach. That's bottom up tinkering. And any tinkering that you do is localized.
So, imagine a farmer has just -- Yesterday, we had some friends over for dinner and they were talking about this farmer and he'd naturally selected -- naturally, what does that mean? He'd selected for his butternut squash that started very big and ended up very small and sweet. And let's just say that there was some toxin in the seed of that plant. And he concentrated it and somehow it ended up in the flesh of the seed, he ate that, and he died. Well, I'm guessing that that will be localized to him and nobody would try and repeat that mistake.
If I wanted to reproduce what he'd done then maybe I could travel across the country, find that guy, and say to him, "Hey, have you got any of those seeds that you used to produce those delicious small butternut squash?" And maybe he would be able to cough up one or two. And maybe I would be able to reproduce what he did in his garden somewhere else in the world. But for the most part, you can see that what has changed is very much localized and from the bottom up.
Whereas the genetic engineering approach, this is a top down. Like you try to engineer the genome and then you're distributing these seeds all over the world on a massive scale. It's both top down and it's globalized. Whereas the traditional artificial selection is bottom up and it's local. So, there are some, I think, fundamental differences between the two.
Leandra: If you think about modern day agriculture, I would argue from your description that modern agriculture, I guess, pretty much all agriculture taken as a whole throughout the last 10,000 years that we've been doing this, is a top down approach.
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Let's say, in the United States, even before genetic engineering was around, the first genetically engineering plant crop that popped up was, I think, in 1995 or '96. That was that BT corn or roundup resistant corn. I think it was the roundup resistant corn. These things have only been around for 20-ish years. Before that, we had basically wiped out the entire -- Let's just look at the United States. We basically wiped out the entire native ecosystem of the United States to grow four crops -- corn, cotton, soy and wheat. None of which are native to the US. And if you look pretty much any -- I can't remember the statistic but it's something like the average American eats maybe a variety of like 12 different plants.
If you go to a natural ecosystem, like say -- I live up in Seattle. If I go to the forest in the Pacific Northwest, there are dozens if not hundreds of these plant species in that forest and they're all interspersed. They're not laid out in nice rows where they're just nice species. They're interspersed and what not. To me, I have a hard time seeing the leap between going in and basically wiping out a natural ecosystem to grow four different plants and introducing one new gene to one of those plants and how that is inherently all of a sudden more ruinous potentially than -- And, I guess, ruinous to who? This is all kind of relative.
Christopher: Well, let me put it this way. So, let's define ruin as being some species becoming extinct. Wild salmon, for example. What we know today as the wild phenotype for Alaskan salmon, could they become extinct if we were to make a mistake with this genetic engineering. Is that a theoretical possibility?
Leandra: Absolutely. Absolutely. Right now, yes, so these GM salmon that grow three times faster than their native counterparts, I guess, wild type counterparts, yeah, they do, if they got out, because they have such a rapid growth advantage on their wild type, compared to the wild type salmon, they could out-compete native salmon or interbreed with them. And like what we think of as wild type salmon could completely change, absolutely.
Christopher: That's an important definition of ruin is it's forever. That species is then gone forever. As a biologist, all of these different animals on earth are very closely related in complicated ways that we don't understand. So there may be knock on effects from the loss of a single species.
Leandra: Sure, sure, absolutely. But, I think, it's kind of actually a hallmark of humanity to drive species instinct. We've been doing this for a very long time, certainly before genetic engineering was around. There's a post doc in my undergrad lab when I was at University of Arizona who did her PhD in New Zealand. She was telling me about how there used to be, in pretty recent history, something like six different species of penguin that lived in New Zealand. But they're all gone now because the Maori ate them all.
Christopher: Right. So, could you see the crucial difference though between what's happening now and what's happening before? Before, you have to kill a penguin one by one with a spear and that was the bottom up approach, like building a house brick by brick. And now we can engineer this extinction in the lab and then distribute it globally and very, very quickly, and then maybe a unique problem, a unique danger with that new top down approach.
Leandra: I think the quickness of the spread is going to depend on the generational time of the organism. Say you want to engineer some sort of fruit tree that takes forever to grow. It's not going to cross pollinate anything for maybe 30 years depending on what kind of tree it is. The widespread thing, to me, there's -- the most widespread destruction I can think of is agriculture in general. It happened very -- It's very, very universal. We've been mowing down large portions of natural ecosystems to grow things for thousands, if not the majority of modern history and, arguably, since we began agriculture.
Christopher: And has that ended in disaster before, right? So, when you create a monoculture as an island for the potato farming, that was the cause of the disaster, was the fact that it was a monoculture.
Leandra: Right, yeah. There was very little genetic diversity to combat the blight, right? In that case, genetic engineering could actually be beneficial because, in that case, instead of trying to outbreed the blight, because cross-breeding takes a long time and trying to breed in resistance would take at least several generations, if you figured out--
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Say you found one potato plant that was resistant to blight, which gene or which couple of genes were responsible for that, you could then go and introduce those genes very quickly into through genetic engineering instead of trying to outbreed the blight. It's a double-edged sword. It could save something, like genetic engineering saved the papaya crop in Hawaii. It could be sort of disastrous like this use of chemical herbicides with roundup resistance.
Christopher: Yeah, but I still have a problem. I have all sorts of problems with everything. I think there's a problem with the genetically engineering your way out of a problem. I think this applies equally to the fortification of vitamins to certain vegetables too. It reminds me of the song there was an old lady who swallowed a fly. She created the problem. She swallowed the spider to eat the fly. You know the rest of the story, how it goes.
Leandra: Right, right.
Christopher: We see this in non-functional medicine or dysfunctional medicine too. A couple of weeks ago, my chief medical officer and I recorded a podcast on erectile dysfunction and for a lot of men there is a fantastic solution for that problem, that is Viagra, the drug. All you need to do is swallow this pill and you've solved the problem. But it would turn out that if you're seeing endothelial dysfunction or maybe some nerve damage from glycotoxicity in that tissue, it's probably not the only place that you're seeing a problem.
So, this could be the canary in the coal mine that's warning you of cardiovascular disease and by just swallowing the pill, sure you mask the symptoms but what's the underlying root cause? Like is the underlying root cause the monoculture or is it just the blight? Is the blight just a symptom? And so what you really need to do is look at the root cause. That's true for many things in medicine. It's just not good enough to address the symptoms. You really have to look at the underlying root cause. I think that's the problem we're trying to genetically engineering your way out of this problem. It's never going to end. That old lady is going to keep swallowing things to deal with the problem that went before.
Leandra: I think with biological systems, because they do evolve, there's always going to be a problem. Because the impending antibiotic crisis is a great example of this. We have a small arsenal of antibiotics that we've been using for the last 50 or 60 years. And now because of poor practices both in the medical realm but also in the agricultural realm, or we're just force feeding animals insane amounts -- Like 50% of the United States antibiotic supply is used in agriculture because it allows animals to be squashed into small places without getting sick but also makes them really fat. So, win-win, right, from the industrial farmers' perspective.
Because organisms evolve, it's always going to be an arms race. We have a small arsenal of antibiotics. Now, we're starting to see organisms pop up that are resistant to those antibiotics. So, do we adopt a practice that makes it easier? One of the potential solutions to the antibiotic crisis -- Bacteria, actually, have their own pathogens. They're a type of virus called bacteriophages.
Christopher: Right, right. You could buy these in supplements. Did you know that? The Russians did a lot of research in it 100 years ago and they sort of disappeared but they do still exist.
Leandra: Yeah, they absolutely still exist and they're actually the bane of the microbiologist because if your lab gets infected with phage and you work with bacteria you're in big trouble. They kill all of your organisms. And the cool thing about phage are that -- I guess, viruses in general -- is that they're specie specific. So, a bacteriophage that infects an e-coli will not typically infect and because they are -- I guess, there's some arguments as to whether or not viruses are organisms or not but they're organism-like and they have DNA and they are evolvable.
We can use engineering and directed evolution techniques to produce new phage that can attack pathogenic bacteria while leaving the beneficial bacteria intact. I think, to me, the beauty of like directed evolution techniques, which is where it's kind of like accelerated artificial selection, or genetic engineering, which is where you just -- Like evolution is an irrational design technique and genetic engineering is a rational design technique. Yeah, so direct evolution is accelerated artificial selection. Genetic engineering is where you're actually going in and making targeted changes to whatever organism's genome. To me, the beauty of this is that if you -- Ampicillin stops working, you're done. It's really hard to make changes to ampicillin that will then make it work again. Because it's a chemical.
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However, with something like bacteriophage, they're evolvable. So, if your organism, the pathogenic orgasm evolves, which it's going to do, because whenever you give an organism a selective pressure, especially a negative selector pressure, they're going to evolve away. They're going to evolve like some sort of resistant technique. So, you're now, I guess, competing on the same field. Now, you have a technology that is also evolvable because it too is also an organism rather than trying to stick to just chemicals or just the 12 crops that are typically grown in the US, for example, if that makes sense.
Christopher: It does. I still don't think we've gotten away from this top down versus bottom up thing. It's interesting to me that this is a time when engineering and computer science are looking towards evolution and natural selection to try and guide the way they engineer things because the top down approach hasn't worked very well and all the biologists are trying to go back to what the computer scientist and engineers have already done and seem not to work.
Leandra: Yeah. If you take a gene from, say, a fish and you put in a tomato, that is, to me, that's still along the analogy of the brick because that gene in fish was still experiencing selection as was the tomato and now you've just mixed them together. However, it's such a small change that you're still 99.99% tomato and now you just have this little bit that benefits from some perspective, actually. I should say like a lot of these genetic engineering applications don't actually benefit the plant that much.
So, for example, roundup resistance. Unless that plant is in the presence of roundup, expressing a protein that makes you resistant to roundup is just an energetic cost, right? So, from my perspective, if that gene were to make it out into the wild, unless it's in an environment that is being sprayed with roundup, the gene is probably going to degrade. And actually, this is a big aspect of my research in synthetic biology, is because, yeah, it's like you want these organisms to perform some computational behavior that really has absolutely no benefit to the organism from the organism's perspective.
Like this is just big and clunky and it takes me a lot of energy to make it and if I break it I can reproduce faster and then all of a sudden -- Yeah, these things are very genetically unstable from a functional perspective. I don't know. For me, it really depends on what that--
Christopher: I'd like to talk about glyphosate. I've looked at this with Tommy with a very open mind. And we've really struggled to find really much evidence that it's particularly toxic. Are we wrong about that? Where would you -- Tell me what you know about it.
Leandra: In the reviews that I've read, it seems like, yeah, like glyphosate doesn't necessarily look to be too terribly toxic by itself. But if you mix it with all the adjuvants that are in roundup then there does appear to be some potential like physiological problems. I've seen theories from people in MIT who think that this stuff can accumulate aluminum and then transfer it across the gut barrier.
Christopher: But no experimental evidence?
Leandra: I don't think so. I don't think they did any experiments.
Christopher: But have you seen anything -- So, it's been suggested to me there might be some disruption of the gut microbiome. Again, I've only seen experimental data from poultry where they showed that there was a decrease in lactobacillus and bifidobacteria, which, I think, people are universally decided on being quite good.
Leandra: Yeah, yeah.
Christopher: Have you seen anything else or know anything about the gut microbiome and glyphosate or roundup, I should say?
Leandra: My guess would be is if it's affecting lactobacillus and bifido and in poultry, I don't see why it wouldn't affect lactobacillus and bifido in humans. Those are the same taxo of bacteria. I've also seen some reviews showing that if you treat human tissue cultures with roundup it causes necrosis whether or not that is applicable to the human organism for our digestive systems, effectively break it down to the point where it's no longer problematic, hard to say.
Christopher: So, who's going to do these experiments? Do you think that data will emerge at some point showing safety? Do you not think that this type of thing, the emphasis should really be on whoever is introducing these chemicals into the environment to show that they're safe?
Leandra: Yeah. I should say that, yeah, my knowledge of the safety the practices that have been around roundup are pretty limited. Based on the research that I've seen, I'm pretty skeptical whether or not this stuff is safe for human consumption. Whether it affects the microbiome or if it contributes to the degradation of the gut barrier, I have no idea if Monsanto has adequately--
[0:40:19]
Christopher: Safety tested?
Leandra: Or even just shown the burden of proof that would be necessary, I guess, to so ubiquitously introduce something like this to the environment. There were some German -- I can't remember if it was the German or the Italian scientist recently, I think within the last two years, who compiled something like 1800 papers. And this was like looking at the safety of all GMOs available on the market. But presumably, some of the roundup testing is in there. Something like 1800 papers and the vast majority of the research was showing these things to be safe both from a health perspective and from an environmental perspective. I guess, that goes back to like what the definition of safe.
Christopher: You're right. There's so many problems. It's really, really difficult. And then I would argue that just because -- Let's say that I put on a blindfold and some ear muffs and I try to cross the busiest road I could find in Santa Cruz and, by chance, I didn't get by a car and I survived the day. Would you conclude from that that it's safe to cross the road with a blindfold and ear muffs from that point forward?
Of course, you wouldn't. And we see this in the financial markets all the time. Just because you know what the S&P 500 did yesterday, doesn't really mean anything about what it's going to do tomorrow. And, of course, if people didn't know that then there will be no financial markets. I'm not very compelled with that sort of data but I will look at it though. Can you maybe send me a link afterwards so I can link that in the show notes?
Leandra: Yeah, sure. It's interesting too that it's coming from these European scientists where the view of GMOs is pretty ubiquitously negative. The EU, I think, has pretty profusely banned the sale and, if not, also the growing of GMOs, I think. Yeah. So, I think a lot of this comes down to sort of like a philosophical and a semantics argument. It's like what is your definition of GMO? What is your definition of safe? What is your definition of negative effects on human health?
Like okay, if it doesn't cause massive necrosis of the gut endothelial cells within 90 days, is it safe? Or did you find out 20 years later that the stuff has been maybe slowly eroding the gut barrier contributing to chronic inflammation, which then can cause a host of other problems? With the current scientific techniques that we have, can we nail that down to just being caused by roundup or glyphosate or any of these technologies? It's a really complicated field.
Like I try to have skeptical but also open mind about pretty much all technology because I feel like -- The microbiome is an excellent example of this. For decades, if you made any claim that the microbiome did anything besides help digest your--
Christopher: You're a quack.
Leandra: Yeah, you're crazy. But then all of a sudden, within the last five years, we're like, "No, guys, it's really important." That's kind of the perspective that I try to take because somebody -- It comes out in five years that, yes, is genetic engineering, is this uniquely dangerous technology and here's all of the problems it has caused? Absolutely, I will change my mind.
Christopher: To some extent, what I'm doing here is really not fair because much of my thinking for this interview has been shaped by Nassim Nicholas Taleb.
Leandra: Yeah. Actually, I just read his paper.
Christopher: The Precautionary Principles. I will, of course, link to that. And for people that don't know Taleb he's a distinguished scientific adviser and a professor of engineering at the New York University School of Engineering. So, Taleb describes what he calls the carpenter fallacy which is when you're dealing with a game of chance, what you really need is a probablist not the carpenter that built the roulette wheel. I'm talking at the moment to a genetic engineer that understands the carpentry of the roulette wheel but what we really need is someone that understands risks.
And I'm not trying to suggest that I understand risk but I'm pretty sure that Taleb does. So, maybe I should link to his precautionary principle paper and have people read that and make up their own mind. Okay. I think we better wrap it up here but I'm sure that people listening to this have got some questions and maybe ideas for other people that I should interview or maybe you've got some questions for Leandra and maybe if I collect those up and organize it nicely she might be able to answer some of those for us. I'm kind of asking you a question at the same time as maybe a statement. Would you do that for us?
Leandra: Yeah, sure. Or field you to someone who's, I think, yeah. I should say that I am by no means an expert in plant engineering. I just happen to do genetic engineering.
[0:45:09]
My incentive to propose a presentation for AHS was just I wanted to present an alternate viewpoint from someone who might be a little bit more educated on these topics than any average person being someone who actually works in genetic engineering. I guess, you can take that with a grain of salt or not but I can't claim to be an expert on how this is done in plants but I can also point people to resources that I found very--
Christopher: Excellent. Please do that and I'll link to those in the show notes. Well, thank you very much for your time, Leandra. I really, really appreciate you. And I hope I wasn't too mean or aggressive.
Leandra: No, absolutely not.
Christopher: Like that guy who was invading your -- It's very difficult to invade someone's personal space over Skype but I hope I didn't come close.
Leandra: No, no, no. I am perfectly willing to listen to someone's opposition. I would prefer if they would speak in a tone that isn't aggressive. Basically, I'm willing to listen to what you say but I would prefer if you didn't shout at me.
Christopher: Okay. I'll try my best.
Leandra: I think it's always healthy to sort of have a skeptical mind about everything including GMOs. I think you should be skeptical on both sides. Should be skeptical of the people who are saying that they're going to destroy the world but also be skeptical of the people who say they're going to save the world. It's probably somewhere in the middle.
Christopher: Well, thank you very much for your time. I really appreciate you. Thank you.
Leandra: Yeah, of course.
[0:46:38] End of Audio
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