360 Update on Animal Gene Editing
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Kevin Folta: [00:00:00] Hi everybody. And welcome to this. Week's talking biotech podcast by collabora. And today we're speaking to an old friend, the old friend, meaning that she was one of the first. not that you're old. One of the, a friend of the podcast who was really one of the first. People we had on, I think episode number two, and then also has been on, I don't know, maybe four times you're you still wear the crown is the most talking biotech guest

So we're speaking with Dr. Alison Van Eenennaam. She's a cooperative extension specialist at the university of California Davis who works primarily in cattle and in other animal systems in the area of gene editing. Also in other areas regarding animal husbandry in California. So welcome back to the podcast, Allison.

Wow. 

Alison Van Eenennam: It's great to be here at Kevin. And to talk to you, we haven't talked to each other for ages. 

Kevin Folta: I know. I miss talking to you. I always appreciated you very much. And for those of you don't know Allison, she or should say for those of you who don't know Dr. Van Needham, I get. Too [00:01:00] familiar sometimes Dr.

Vine and him is Alison's fine. 

Alison Van Eenennam: I know with that, with that big, long name, Alison's fine. 

Kevin Folta: I, I spell it right every single time too. I, I sat down and practiced over and over again until I got it. Right. So she's a not just a scientist who works extremely well in the laboratory. But a friend of the folks who actually raise the animals and also someone who has an IMDB page, who has, does a great job in communicating with the public about biotechnology.

So someone who I always look up to a lot and someone I really appreciate is willing to take her time with the podcast. So, so there you go. There's the introduction. So, as I mentioned, we didn't speak since. I don't even know when the last time we got together here on the podcast, but, or even anywhere, but that was definitely on the other side of COVID 19.

And how did COVID 19 impact the area of gene editing in animals and the research that you were doing in your laboratory? 

Alison Van Eenennam: Yeah. well, it was a, it [00:02:00] was a pretty big disruption for everybody. I think we can all agree with that. And certainly the first few weeks you, everybody was thinking, well, this will just be, you know, couple of weeks.

Right. We'll just keep, keep on going. And obviously that's not how it turned out, but I think, you know, it's really. A difficult time to be running a wet lab. And by that, I mean a lab where you're doing work in experimental work bench work. And especially in our area where we're editing livestock. So specifically sheep and cattle is kind of, you know, large ruminants in my case.

And you wouldn't think about. All the ways that like the supply chain would disrupt things in, in a research setting. And so one of the really crucial parts of our research is having access to ovaries from cows or sheep. And typically we get those from the processing plants. And of course, during, during COVID they were you know, really Locked down basically to, to protect their workers from getting the, the virus.

And [00:03:00] so we had a really hard time accessing the. Slaughter our house basically to get ovaries so we could get O O sites so we could make embryos. So we could do transfers into cattle and sheep. And you know, just like things you wouldn't think would actually affect you and, and you probably well aware there was like pipette tip shortages and glove shortages.

And it was really a hard time for a graduate students who had just started and basically were not able to do the wet work and there. Really in the case of a molecular lab, you couldn't really pivot to do something virtually or, you know, do some sort of a bioinformatic analysis because really you needed the data to be done in the wet lab.

And so, yeah, it's been a tough time for everyone. And I, I think we're, we're happy to get back in the lab and, and we're able to start accessing the materials. We need to do our work. And so I'm hoping that 20, 22 is gonna finally pull us out. Basically a, a two year block to some extent to some of our work.

We were really lucky in that we [00:04:00] did a group of embryo transfers right before pandemic. So I think the last two weeks of February, and then those embryos took. And so the cows were just dating during the whole pandemic and gave birth to those edited calves. And so that fortunately was happened because the student who was analyzing that that's basically her entire PhD.

And if she hadn't got those embryos in the. The week she did. She wouldn't have had anything to analyze basically. And so I'm, I feel really fortunate that we got lucky with that embryo transfer, but boy you know, if you only knew what was coming, you would've planned a little differently. So yeah, it's been, been a tough time as it has for everyone.

I'm I'm not. Minimizing that, but yeah, it's been tricky, tricky to be managing a lab. 

Kevin Folta: Well, I don't know that everybody appreciates that, especially because so many labs that have resorted to so many other bioinformatic analyses like mine, you know, we, we went into consumer data and other things like that.

But in the case of your laboratory, we talk about wet lab and that that's probably new [00:05:00] term to most people with wet markets. Oh, okay. You're working on bats now. I, I guess the other thing that I really wanted to ask you about maybe is a good idea, just to step back a second and talk about some of the innovations that have come from your efforts in gene editing strictly because since last time you were on, we've probably doubled our audience.

So can you tell me about like the pulled calves and maybe the, the ones that produce a tire tendency of males? Just to give folks a little context in terms of the innovations that have come from your program. 

Alison Van Eenennam: Sure. Yeah. So we, we work with genome editing, mostly in cattle. We have done a couple of sheep recently.

And so they're kind of cool to work with, although they're really bizarre in terms of you have to do like a little tiny kind of operation to get their embryos into their ovaries. It's quite different to cattle. You wouldn't think it would be that different, but it really is. But anyway, I digress.

So we have been working collaborating with a company rets. Produce some poll offspring, and basically poll is [00:06:00] a, a description of a trait of not growing horns and horns are very typically found in dairy cattle, genetics and there's naturally occurring genetic variations or alleles where it's a dominant trait that you don't grow horns.

And so black Angus, for example, Pulled they don't grow horns. And so you can move that allele or genetic variant from the breed of black Angus, for example, into dairy cattle, genetics, to produce dairy cattle that are genetically not gonna grow horns and horns can be dangerous to the cattle and their handlers.

And they're typically physically removed, and this is really a genetic approach to address that. And so our lab's been working on characterizing the offspring of the Polled bull. So the bull that was genome edited to not grow horns. And that's, as I mentioned, a dominant trait. And so that bull that had two copies of that dominant trait was mated with some horned Harfords here at Davis and Mendel knew what he was talking about because the dominant [00:07:00] polled allele.

Exerted its force in the, in the offspring and they all did not grow horns. And we've also since then followed up on looking at the meat and milk composition of those offsprings because these are some of the questions that have been asked around genome editing. It's a little bit of a hangover really from.

Genetic engineering where there's kind of this request for substantial equivalence in the case of plants, when you've got, for example, BT corn to show that you haven't changed any other attributes of the corn plant. And so these similar questions are now being asked from genome edited animals. And so we've been doing some, I guess I wanna, I.

Work to show that there's, there is no difference in the milk and meat of horn versus polled animals that are the offspring of genome animals, such that those types of questions are addressed and, and answered in a, in a thorough scientific experiment so that we can really focus on, in my opinion, the real risks that might be associated with these technologies rather than Kind of more [00:08:00] hypothetical risks.

So that's one project and then another project that was born actually during COVID. And, and so we we actually delivered this calf and it was right when COVID first hit and there was a real shortage of medications actually to do cesarean sections in. In cattle. So a lot of the sedatives that were used for that type of operations were in use to to intubate people.

And so we were, we were really worried. We had a calf that was overdue, that was genome edited that had been gestating. Basically for several months of COVID and we were really hoping the cow was gonna give birth with our unassisted and didn't need a cesarean section, cuz we were, we were up against the wall in terms of veterinary medications to, to do a season Cesan section.

But fortunately he came out safe and sound and his name was Cosmo. And he had been genome edited. To basically make a copy of the gene associated with sex determination in mammals. [00:09:00] And so it actually, the S R Y gene is normally located on the Y chromosome and it, when it turns on takes embryos down the male pathway.

And so that's, you would've inherited that from your dad. And I clearly didn't cuz I got an X chromosome from my dad, which doesn't carry the S R Y gene. And so. Developed down the female pathway. And so what we did was copied that gene onto an AutoZone that is a non-sex chromosome. Knocked into one of his two chromosome seventeens.

And so his offspring would be predicted to have a, a skew 75% male. So rather than 50 50 male, female we'd expect 75% male and 25% female. And. That would be useful in certain production systems, such as beef cattle production systems, where you need some replacement heifers that is fertile female XX animals, but the majority of market animals you'd prefer the male because they are more efficient at feed.

To growth conversion. And [00:10:00] so that's a, just basically moving a gene from one chromosome to another, within a species. And these are kind of some of the different edits that you could think of doing. So moving an allele from one breed to another, moving a gene from one chromosome to another or more commonly, what people are doing is just, inactivating a gene within a chromosome.

And you can do things like inactivate disease resistance areas where you can inactivate genes that make an animal more susceptible to a disease. So they've done that for the pers gene. It's a poor sign, a pig respiratory syndrome virus. That's very nasty and. Actually causes a lot of loss in the, in the pig industry.

And so group at Missouri was actually the first to knock that out and produce pigs that are no longer susceptible to that respiratory virus. , we're probably all pretty familiar with respiratory viruses at the moment. I'm, I'm kind after a couple years of this. So here's a genetic solution so that those pigs don't have to I guess, wear, wear pig masks.

Kevin Folta: Well, you know, all of that [00:11:00] is really nice. I, so let me go backwards to your two innovations because both of those have some very nice attributes. The hornless cattle are a huge breakthrough in that you don't have to have horns physically removed, which is great for animal welfare. And better costs for farmers, cuz that costs money to have a veterinarian come to remove those little buds out of the head of a, of a developing calf or of, of a born calf.

And then you have this other issue of feed conversion where mails are better. So it seems like you're making better use of the resources to produce more grass into more meat. So both of those things sound awesome. Where are those in terms of their deployment into the main. Chain of production either in dairy or in meat production.

Alison Van Eenennam: Well, that's an interesting question. So both of those, obviously, at least at the university here are research projects. And so I, I am not a seed, a seed developer or a, or a, a germplasm developer. [00:12:00] And so in terms of companies that are actually developing this type of technology for market as I mentioned retics was the one that was.

Associated with the making the original founder animal. That is the, the polled bull. And they have actually just recently actually got kind of an okay. To put some gene knockouts into the market. And I'll, I'll, I'll, it might get a little wonky here, but basically if you inactivate a gene and you do a targeted gene knockout, you're not introducing any novel DNA and you don't have to use quote unquote, a template to do the repair.

So you don't need to introduce any DNA sequences. And so that type of a knockout in the. Of plants, for example, in the us is, could be achieved using conventional breeding using like mutation, mutational, neurogenesis, that type of thing. And you, you would be able to introduce that without having to go through the full quote unquote GMO or transgenic kind [00:13:00] of regulatory pathway, that's different for animals.

And so the FDA is in charge of regulating. Genome edited animals or intentionally altered variations as, as they're termed in by the FDA. And they've determined that they're gonna treat all of these alterations, even knockouts as UN unapproved animal drugs and to get a drug approval. Well, as we know, as we watched the vaccines going through the drug approval process, it's quite an extensive process.

You have to show that it's safe. For the animals safe for the humans, safe for the environment it's effective all of that good stuff. And so it's quite a lengthy and expensive process. And that really was the, was the. Approach they had in place for transgenesis. And for example, AC advantage salmon went through that process and it took, you know, many years and many millions of dollars for it to finally get its approval as, as the first transgenic genetically engineered product from an animal on the market.

But [00:14:00] recently what rets did was they knocked out one particular gene it's the prolactin receptor that results in a. Mutation and slick is a term for a very sleek hair coat. And basically these animals, if you look at them, they, they just, they look kind of, Shey relative to a normal cow's coat and that enables them to dissipate heat more easily.

And so they're able to tolerate. Heat extremes. And it's a naturally occurring mutation that occurred, for example, in the Seole breed of cattle. And so recombine, duplicated effectively that knockout just using injecting CRISPR CA nine and a target guide DNA to the prolactin receptor gene, into developing embryos, and then transferred that to a surrogate cow.

And two bulls were born red Angus bulls that were. And you could see they had slick coats. And so they approached the FDA and said we would like to market these animals. And here is their phenotype, their slick and here is their knockout and here is the rest of their genome. And [00:15:00] we don't see any other unintended alterations.

There's no exogenous DNA. What do you think. And so the FDA made what they call a low risk determination, which enabled them to give or exercise enforcement discretion around these two specific bulls for this particular knockout. And what that means is those bulls on their offspring are considered low risk.

And so, although they. Quote, unquote unapproved animal drugs. The FDA is gonna exercise enforcement discretion. That is their discretion, not to exercise enforcement because it's a low risk product, but it's, it's a little bit, I, I, this is maybe not a good analogy, but you know, when you're driving in town and, and the speed limit is 35.

If you go 38. You are probably gonna be given enforcement discretion. If you go 50, you are not gonna get enforcement discretion because that's not low risk. If the speed limit is 35. And so it's, it's basically [00:16:00] saying that because this is low risk, our resources are better spent. You know, pursuing other risk or regulatory activities.

And so in this case, we've looked at your products and we are going to give you enforcement discretion. So those animals they're meat and they're, and they're GA eats or, or basically their offspring can be commercialized in the United States. And this was the same approach that was actually taken with glow fish.

If you remember, way back when those are the fluorescent aquarium fish that have jellyfish fluorescent green and orange and red, and they're really cool. I've got a couple in my house actually. And they also were considered to be trans animals, but low risk not a. Risk for most people because most people are not eating zebra fish you know, maybe a cat occasionally, but so there really was.

And also they're not a risk to the environment here because they're not actually able to thrive in the waters of the United States. It's too cold. And so they were given enforcement discretion and now they're the. Sold aquarium fish in the United States. And I think [00:17:00] that shows you that if these products can actually have an opportunity to get to market, that they can actually be a market success.

In the case of glow fish, they obviously found a market. And so that's a little bit of an advancement, but it doesn't really clear the pathway for all genetically or genome edited animals to, to. Approval cuz it's not really an approval. It's, it's, it's an, an exception if you will, for those two specific animals.

And so if, if another person makes the same mutation, they'd have to go and approach the FDA and get approval for that, that cow or fish or whatever. And so it's it, doesn't in my opinion, solve the problem so much, but at least it's a little bit of a opening for some products from companies to get to market.

Kevin Folta: Well, I think that the fact that the slick mutation, this is something that is in a number of cattle breed, that this is something that already exists. So all you're doing is emulating with the laboratory, something that has come [00:18:00] apart or come about through natural variation. So it's kind of like driving 39 or 40 miles an hour when everyone else is doing it at the same time down the highway, 

Alison Van Eenennam: it's actually no different really to the poll.

Example I used earlier where yeah. That, that mutation exists in, you know, all Angus cattle that we eat routinely. And so you know, the fact that just because that happened to use a template that that would somehow be riskier and you know, milk and meat would need to be analyzed. So in this case, the.

Excuse me, the meat of those animals was not well obviously the bulls are alive and, you know, I don't know if you know this, but you actually have to kill the animal to get the meat to do the analysis. And so that they were able to get enforcement discretion actually without providing actual meat from the animals because they use the argument that, well, we already eat slick cattle, as you mentioned.

And so there's no novel risk here. We already have consumed that. And I would make the same argument around pole and, and horn cattle and milk and meat. [00:19:00] So that's, it's, it's a step in the right direction, but it doesn't clear the path. And, you know, let's just imagine you know, I'm a fish producer and I wanna do a knockout in, in fish and I'm gonna need to knock out a gene in all of my brew stock, which.

10,000 fish a year. how would that kind of one by one you know, enforcement discretion model work on kind of the, what I think is the bigger picture here that is that we need more than one or two animals coming through. We're not like. Plant varieties where we can bulk up from a single transgenic event, we're gonna need to edit, you know, a variety of animals to maintain the genetic variation within our breed structures.

And it's not gonna be one bull. That's got the pole allele introduced. It's gonna need to be a range of bulls that have some genetic diversity to maintain our genetic diversity for future genetic improvement. And the, the system we choose has to. Kind of sync with the requirements of [00:20:00] animal breeding for the technology to be actually incorporated into animal breeding programs.

If it, if you have to take animals out of the, of the system for five years to do regulatory, you can in envision every year, our bulls get better and better because we're good breeders . And so every year they're genetically improved relative to last year. And so it really has to kind of synchronize with that.

Reality or else it won't be able to be adopted into our livestock breeding programs. 

Kevin Folta: It's all really exciting innovation. And when we come back on the other side of the break, we'll talk about some of the other current innovations that are happening and maybe step back and talk about some older innovations to kind of frame how much humans have really participated in animal genetic improvement.

This is the talking biotech podcast by collabrate and we'll be back in just a. And before we return to our interview with Dr. Van Enim, we're speaking with Jillian Hendricks. [00:21:00] She's a graduate student in the beginning of her program. Who's completing some work from previous undergraduate experience. She's at the university of British Columbia and can probably use your assistance.

Welcome to the podcast, Jillian. Hi, Kevin. Thanks so 

Jillian Hendricks: much for having. 

Kevin Folta: Yeah. So the reason I wanted to have you on is because you need a little bit of assistance. So could you tell me about the project that you're working on? 

Jillian Hendricks: For sure. So I'm working with the university of British Columbia on a project where we're looking to interview people who are working in genetics, specifically within the ag sector.

Who are actively having to, you know, discuss or communicate gene editing with others. And basically the goal is to, you know, understand how people talk about gene editing. And you know, this could be somebody who's in industry or more in the scientific or academic 

Kevin Folta: field. And when you're saying someone in the ag sector, are you talking about animals or strictly plants?

It could be either. Okay. So were anybody who is interested or [00:22:00] working in, so you're saying specifically working in gene editing. And are you looking for people who are actively communicating with the public or just kind of people who are doing that and maybe planning to communicate with the public?

Jillian Hendricks: Yeah, well it not even as limited to the public, you know, it could be farmers or customers as well, but. You know, it's really somebody who is currently, you know, talking to different stakeholders, whether it is the public or farmers about gene editing. 

Kevin Folta: Very good. And so this is going for research that you're doing for for, for class or for towards publication.

Yes. 

Jillian Hendricks: It's for publication. 

Kevin Folta: And how many people do you need? 

Jillian Hendricks: I'm looking for about 15 or so participants to interview. 

Kevin Folta: So if you're someone who's involved in gene editing and you could kindly contact Jillian and help her by filling out a survey, it's, it's a short survey, right? 

Jillian Hendricks: Yeah, it's just an interview about an hour long, a bit less, 

Kevin Folta: maybe.

Okay. So if you could, if you could take the time to do the interview with her, it would really help her project. And it's really [00:23:00] important that we help to understand the landscape of how we communicate gene editing. So this is something that'll have dividends for all of us. So if someone wanted to contact you, where would they reach out?

Jillian Hendricks: So you could contact me by email and my email address to spell it out is J H E N D R I C. At mail.ubc.ca. 

Kevin Folta: Very good. And I'll include that in the show notes. So anybody who needs to find it can do it that way too. Jillian Hendrix, good luck in your work. You know, there's so many people who really wanna support research for students because you are the next ones who get to do this.

And we really appreciate you taking the time to join us and good luck with what you're doing. Thanks so much, Kevin. And now we're back on the talking biotech podcast by collabrate. And we're speaking with Dr. Allison van Enim. She's a cooperative extension agent extraordinaire out in Davis, California, and an old friend of the show.

And she works [00:24:00] mostly with cattle and other ruminants in the area of gene editing and genetic engineering. It's exciting cuz on Twitter, I always see that you're speaking at meetings and animal biology all over the globe and. When you're at these meetings, what are some of the innovations that you're seeing that look particularly exciting?

Alison Van Eenennam: Well, there's, there's, I mean, there's different, simple genome editing applications that I think are, are pretty exciting. So there's a couple of disease resistant applications pers that the porcine reproductive. Respiratory syndrome virus, which is actually the first product that's being taken through the FDA approval process for full approval as, as a genome edited knockout product.

And so that's, that's pretty exciting, but there's also just, it's almost breathtaking the developments in stem cell technology, and that's, there's been some recent papers out where basically they've been able to grow. Embryo bodies from stem cells. Basically produced mice. These are that from, from.

From [00:25:00] stem cells, which is kind of, it just opens up a whole bunch of different opportunities to use those for not only research and, and human medicine type of applications, but what, what are the opportunities to use something like that to produce an embryo that you could transplant into a.

Recipient livestock animal and produce offspring that way. And then maybe do the edits in stem cells or something like that. Is it just, I think that area is, is obviously very hot from a human therapeutic perspective and of course that's where most of the money goes. And so we kind of follow in the DRS of, of the human researchers in terms of developments that they introduce into mice and then human therapeutic trials.

Then carted over into the livestock industries. And so I think those are some of the things I've seen recently that are pretty exciting. And I just more generally, I think, you know, what, what editing really does to me is it, it offers an opportunity to introduce a targeted Trait into our [00:26:00] breeding populations.

And that's breeders. That's what breeders are always trying to do, but usually we have to deal with mating animals and having kind of uncontrolled segregation of alleles. And we don't always get the. The alleles we want, or all of the different genetic combinations together in the one animal.

And I, I always use the example of, of I, if you've got kids, they, if you're with the same partner for those kids, they all had the same opportunity to, to have your genetics sampled from you and your partner. But they all came out very differently. Right? so typically the first one comes out and you know, There's always that first born wanting to Excel and you're think, wow, you know, what a, what a great kid and, you know, I'm such a good parent.

And then the next one gets a really different selection of alleles. And maybe they're the really sporty one. And they're really different personality. And then, you know, number three comes along and they're the comedian that's their. Niche in the, in the, his, in the family. And they've all got an, a random selection of oils.

And so what editing really enables you to do is take the very [00:27:00] excellent improved genetics that we have in our livestock. So the ideal dairy cam cattle germplasm for, for being a dairy cow and introduce in a very targeted way, an alteration like maybe slick or not growing horns, or a resistance to a part.

Virus without diluting all of that excellence that we've taken generations of just conventional breeding to improve. And that that's, to me, it's, it's I use the analogy of kind of a cherry on top of an ice cream Sunday. So the ice cream sundae is our breeding programs, which involves a lot of record keeping and breed associations and pheno typing and genomic selection and embryo transfer and artificial insemination.

all of that, which makes great progress. And then. The cherry on top of your Sunday is that you can now introduce a useful variation in a very targeted way to compliment and, and complete your ice cream sundae. 

Kevin Folta: That's a really nice analogy because I, in a traditional breeding [00:28:00] sense, you would be taking that ice cream sundae and maybe putting it in a blender with a piece of pizza.

you know what I mean? You, you you're, you're completely mixing the genetic deck and these. Genetics that we have already are already quite elite. And this is a time of tiny little adjustments that we can do genetically with with a very surgical approach rather than wide genetic crosses that, you know, you mentioned you get a few offspring out of, out of cattle, but also the question of time.

I mean, if you're in a, a cattle breeder, you can spend a lifetime. Just in the process of maybe getting one good innovation, but if you can do it with genetic engineering, you might be able to compress that timeframe into a few years. And so how much of a, a advantage is this and, and where are they using it now in terms of other cattle?

Are there livestock? 

Alison Van Eenennam: Well, so I mean, I, I guess the big advantage is the big, the advantage gets bigger as your generation [00:29:00] interval gets longer. In other words, it's gonna be much more of advantage in cattle breeding than it is in mouse breeding . But having said that the mice people are still pretty happy to do it too.

So I think the longer your generation interval, the longer it's going to take for you to introduce. Traits using conventional breeding. And so that's where the, the big advantage is. You asked specifically where it's being used in cattle or other livestock. And I think I'm correct in saying that as of today, there's actually.

No approved livestock products. That's been gene edited on, on the market, but I actually, when I think about that, I'm wrong. I think Japan has used it in a fish species. And they, they approved the, the tomato, right? The high GABA tomato, I think they've also approved a fish. Fish and eating fish there.

So I guess I'll, I'll correct myself. There's been a couple of limited approvals and that, that, and I, the ones I'm aware of are in Japan. But there's a lot of useful things you could do. And [00:30:00] it's, it's really, I think the regulatory around the world is trying to get its get its It's it's arms around it.

I'm actually on my way to an, an international conference on genome regulation, editing and animals in Brazil. In a couple of weeks where regulators from all over the globe are gonna be coming together to talk about, you know, what's a sensible approach to regulating these products. Because I think we don't wanna repeat the.

Over regulatory or the regulatory expense and burden that was associated with genetic engineering. Just because that really precluded everybody except large multinational companies from being able to afford that regulatory cost. And I, I hope we don't repeat that again, cuz it really stopped animal breeders from having access to genetic engineering.

Because who, who has the funds to, to pay your multimillion dollar or the investors that are willing. You know, 20 years for an approval. And so I think for the sake of this technology, and, and I would argue more generally for the ability to introduce useful traits into our breeding [00:31:00] programs, with the knock on sustainability benefits that I alluded to associated with conventional breeding, we need to have nimble regulations that allow safe products to get to market and are appropriately harsh on products that.

High risk. But the worst thing you can do is have very, very high regulatory bar for very low risk products. That's like, there's, that's a no win. So you spend a lot of money and you don't get much return on in terms of public health or safety, because it wasn't a, it wasn't a unsafe product to begin with.

And, and I hope we don't go and repeat that again. 

Kevin Folta: Could we talk a little bit about the gal safe pig and, and where that is, and if that somehow got around regulation in a different way. Yeah. 

Alison Van Eenennam: So the gal safe pig is a really interesting example. So the gal safe pig is a genetically engineered pig. And there was a lot of kind of confusion when that was approved a couple of years ago.

It was approved [00:32:00] after editing had come on the scene. And so editing of course is touted as a really useful way to do a knockout, but the girl, the girl safe pig was done the old fashioned way. And what I mean by that is a transgenic construct with an antibiotic. Resistance marker was used to do a knock in to that gene.

And then and that basically inactivated the gene and then the cells that had the knock in were selected with a antibiotic. And then that cell line was cloned to produce the pig that had the knockout. That's how we used to have to do knockouts. That's why, you know, gene editing is so. Better than that approach, but that experiment was done 20, 20 years ago, I think.

And those pigs were designed to be for biotherapeutic or medical applications. They weren't really designed to be a food animal, but whilst they were at it and they were getting the regulatory approval for using those pigs for things like heart valves or what have you, they thought, well, we may [00:33:00] as well ask for food use approval because there's.

Population of people who are allergic to a particular sugar that makes them not able to eat red meat. And that allergy is often spread by the, the lone star tick. And so basically by knocking out this particular gene, the sugar is no longer present in the meat. And so people that were allergic to this red meat that had this food allergy would technically be able to eat the meat from the gal safe pig.

And so that was given a limited food approval for one. Herd of pigs or. Is it herd? I'm not sure herd's the right paper. I 

Kevin Folta: think, I think 

Alison Van Eenennam: it's flock. That's, 

Kevin Folta: can't be right. Either watch, I dunno, 

Alison Van Eenennam: pocketful of pigs. And that's the one farm that's, that's basically growing them for biomedical applications, but there's no reason that their meat shouldn't be consumed.

Because. There's a, it's just a gene knockout. And those pigs were that was the dual use approval that was got a lot of press, but often the, the nuance of the fact [00:34:00] that actually this is not a gene edited animal. It's actually a genetically engineered animal. It was produced 20 years ago that didn't get so much press because.

That's a little bit less of a, of a, a rapid response story than than it is for the genome edited. So at the moment to my knowledge, the only two us animals that have, have had are able to go to market are those two Red Angus that have the enforcement discretion that I alluded to at the earlier on in the podcast.

And there are no other animals that have but there's no animals that have had approvals that are gene edited to date. 

Kevin Folta: Okay. But we're talking about those are approvals. But, you know, you go to a lot of meetings, you're all over the globe, you know, and, and when you look at the posters and you see what people are doing and, and I do too, and I get to see examples of how these things are, are going down, what are some of the really outstanding innovations that you think really could help people or the planet or animal husbandry that are coming from biotechnology and animals?

Is there something that really [00:35:00] stands out? Well, I, 

Alison Van Eenennam: I. There's one really cool application. There's a fish company that down in San Diego and they've they've inactivated a gene in fish that's required for gait production. So basically produce sterile fish, which actually has its own uses. So there are groups that are producing sterile salmon.

To prevent the inter crossing of Atlantic salmon in, in net pens, like in off Scotland and, and up in Norway from being reproductive capable to interbreed with wild salmon populations. So trying to prevent that you know, Brew stock that's been selected for increased growth from inter breeding with those wild salmon populations.

And so that's, that's one use in and of itself. So that's that's sterility, but in this case, what they're doing is they're doing a thing where they're complimenting the germ line with genetically superior. Cells. And so basically what you do is it's kind of like artificial insemination. So you'd like to use the best sire, but you, you have to, you know, [00:36:00] go through and, and put straws into into receptive females.

What if you could put. The same germ line that it improved germ line into the mail fish that are gonna be used as your BR as your seed stock for the next generation of fish, and basically increase your intensity of selection on the mail side by having them have a germ line that is comprised of.

Of basically semen that's come from the best animal. And so that's, and that, that could be done in a couple of different, well, fish are really cool in that regard. So they, their germ line will take pretty much any species . And you can also do things like sex reversing fish, where you could produce fish that produce all one sex.

And so there's some really interest. Locations there there's, there are people working to make all female chickens so that you only have the hens getting born. So there's not a lot of use for males in, in a egg laying facility. And again, right, right there, you've basically doubled the [00:37:00] efficiency or, or half the number of animals you need, whichever way you wanna look at it.

By basically using genetics to produce the animals you want. And to. Produce animals that, that you don't want. And those are the, some of the things that excite me because it offers the opportunity to really alter our breeding program design and, and further reduce the inputs needed to produce a, a unit of food.

And I think that's a really important thing. And, and more generally, I think there's some different applications that, that make sense in extensive livestock production systems. Things like AI are really difficult in countries that don't have access for, to, you know, liquid nitrogen, for example, or AI technicians.

And so if you can put the best genetics into natural service mails of whatever, a species, then you have the opportunity to distribute that genetics. And that's always been a bit of a bottleneck, especially in the developing countries. Just due to the resources that are kind of required to, to [00:38:00] get animals bred using artificial insemination and.

Even that simple old technology has the opportunity to, to be more widely distributed using some of these modern genetic tools. 

Kevin Folta: Yeah. I really like that idea of creating males that can deliver, as you say, natural services because what it does is it takes out that whole artificial insemination problem where you have to have liquid nitrogen and straws of semen that you're moving around the globe.

And so it allows folks in the developing world to have access to superior genetics. And that's, that's great stuff. As far as I'm concerned, you know, the Thing you mentioned and just I'll put a little underline under it. You know, we hatched a lot of chickens here at my place and, you know, we, we end up with half of 'em being roosters and you only need one per flock, you know, of certain number of females.

And so we end up having a lot of males that you have to feed to get the size, and then, you know, then we end up beating them. But [00:39:00] in large, Layer production, which for egg production, the males are sacrificed immediately. Like as soon as they detect that it's a male. It, it it's it's euthanized. So this idea of having strictly female production, isn't just a question of efficiency, but it's also a really nice thing in terms of the uglier sides of animal husbandry.

Yeah. And, and what about other innovations in your program? Like what are you working 

Alison Van Eenennam: on next? So actually collaborating with a doctor in San Francisco at U C S F to develop a sheep model for a, a human disease condition. And so sheer often Quite useful bio biomedical models for diseases that humans get that aren't very well replicated in mouse models.

And so for example, you can mimic a genetic mutation that results in a disease in humans, in sheep, and then because sheer the size they are you can test therapeutics or maybe different you know devices [00:40:00] to help human patients, you can kind of model them in sheep and see if they help that sheep to cope with that disease condition.

And so that's kind of a biomedical application. My real focus is agriculture. And so we've got some knockout sheep that we're meant to grow. 60 to have higher rates of post weaning gain based on mouse experiments. And so with genome editing, we can test that hypothesis in our actual livestock populations.

And see if that observation in a model species carries over into the, the The production animals. And so that's one project we're working on one where we're doing a knockout for a particular viral disease in cattle to see if we can produce cattle that are not susceptible to viruses. And we are doing some work in stem cells too.

and so yeah, lots of, just lots of it's a really exciting time to be involved in this area, cuz there's so many cool developments happening in the basic research. In human and, and mouse genetics that, you [00:41:00] know, it's like, well, how I wonder how that might work in cattle. And so that's, that's kind of the fun of it.

And it doesn't always what happens, what works in a mouse. Doesn't always work in a cow. In fact, I would say more generally what works in a mouse almost never works in a cow . And so it's not that trivial to translate some of this stuff to our livestock species and, but it's important because that's.

That's where the food's at. And so we need to, to have that research done in the livestock species. 

Kevin Folta: So Dr. Alison Vaneen and I thank you very much for your time and for visiting us again and talking about the cutting edge of animal innovation. A lot of these things seem to be no brainers to me, and I'm really excited.

You're doing this work and really representing for the animal industries that are using genetic engineering and gene editing to really bring us to next generation of improved animals for livestock. So thank you very much 

Alison Van Eenennam: for joining me. Well, thanks, Kevin. It's great. Speak with you again. And I hope we meet in the real world in, in the future.

Kevin Folta: yeah, I hope so. I mean, we used to see run into each other, like every few weeks it seems, and, [00:42:00] you know, post pandemic, you know, it's been a little different, but let's, you know, we'll work on. And as always, thank you for listening to the talking biotech podcast by collab. Remember to share with a friend, talk to people who are skeptical, share the innovations that show the improvements for people in a planet and for the livestock that we use, it's really important that people get excited about the next frontiers, because they really are exciting innovations.

It ultimately better for us, better for animals and better for our planet. This is a talking biotech podcast, and we'll talk to you again next week.