Cindy Buckmaster  0:12  
Hello animal lovers, welcome to get real. A podcast hosted by the National Animal interest Alliance through which we'll have deeply honest conversations about animal research so we can learn together and make Compassionate Choices about our medical future together.

Welcome to Episode 15 of get real. I'm Dr. Cindy Buckmaster, your host to get real, and I have a special treat for you today. It's the story of crow nut and adorable charismatic sea lion who for me has become an ambassador for everything that is good and loving in the world, as well as a powerful reminder of how truly connected we are to one another and our changing planet. Joining us today to share Cronus story are Dr. Scott Barragan, professor and William K. Bo's, Jr. Endowed Chair in neuroscience research at the University of California, San Francisco and Dr. Clare Simeone, Marine Mammal Veterinarian, conservationist and founder of sea change health, there's a lot of love in this one, you want to share it with everyone, you know. Thank you for joining us today, Dr. Simeone. And Bear OH, man, I am thrilled to have you here to tell the story of Corona at the sea lion. Some of our listeners may have seen Cornett story in the National Geographic, and it's been all over the news outlets. And it's just an amazing story. And I really feel very honored that you can take a few minutes to speak with us personally about this whole case, which is extraordinary. And everyone will find out why in a minute. That just set me out. I think maybe we'll start with you, if you don't mind. Because you're the person who has been working with Cronin all this time, you have had a career in marine mammal medicine as a veterinarian and it would be great if you could give us a little bit of your background and how you got into this work and and how that led you to crow nut and then we can start talking about what happened with him.

Claire Simeon  2:13  
Yeah, it is. It's great to be with you, Cindy. And to tell Cronus story, I think he's really had a big impact on on me and my life and my work. And yes, so So background about me, I'm a veterinarian, and I work primarily with marine mammals. And I previously worked with the Marine Mammal Center. And that's where I initially met crow nuts. And then I've gotten a chance to work with him since he's been living at Six Flags discovery kingdom. And so you know, seeing the effects of the toxins that we'll talk about with him. And the effect that it's had on wild sea lions and just how challenging that's been to manage has been something that's really interested me over the past few years, and all of the things that came together have just been amazing to really help him and save his life. Well, and he's

Cindy Buckmaster  3:01  
so stinking cute, I can't even take it. I mean, it's just the cutest little thing. And you know, in reading the stories about I mean, he just he, he had severe seizures, they started to get very, very frequent, no moving from one or two a month to several every week tremors, confusion he couldn't eat and he dropped nearly a third of his body weight. I mean, it sounds like he went through a horrible, horrible time. And I know that our listeners may not know the story. And so this might be a great time for you to tell us sort of the general issue and what's happening to sea lions. And you know, because Corona story is the story of many, right?

Claire Simeon  3:35  
Yeah, it absolutely is. And I think it starts with looking at a toxin that's called domoic acid, that it's a toxin that is naturally produced by marine algae that live throughout the oceans. And they make up a whole bunch of the base of the food web and the specific type of algae that produces domoic acid, they look like these tiny little cigars, that kind of form chains, Sunni Chia is their name. And so naturally, they are found throughout the oceans, but they can form these large Harmful Algal Blooms. And for those of you that live along the coast, wherever that Coast may be likely are familiar with some kind of harmful algal bloom, you know, whether that's red tides and Florida or these blooms that produced a Moke acid. If you have listeners in the Bay Area, folks know that right around Christmas time is when Dungeness crab is fished, and it's this delicacy that a lot of people like to enjoy. But in past years, the Fisheries has had to shut down because there have been high levels of domoic acid in the water. And so this toxin can have really far reaching effects on health, but also economically, right, it's really impactful and biotoxins. They're becoming more frequent. These blooms are becoming more frequent and more persistent. Because we're seeing changes in our climate, we're seeing increases in sea surface temperature, you may remember back to 2015 when we had the glob on the West Coast of the United States. And it was just this massive warm water that kind of sat along the coast from Alaska all the way down to Mexico. And it correlated to one of the largest and most persistent harmful algal blooms that had ever been recorded off the coast of the United States. And that has really far reaching effects. So we'll talk about the effects on animals but then it also it's important for us as well because this toxin can cause amnesic shellfish poisoning in humans so if you were I eat the toxin, then we can be affected similarly to the way that the sea lions do. So it's it's really important for us to to understand for our own health, and then understand how it's changing in this rapidly changing world that we're living in.

Cindy Buckmaster  5:44  
Wow, yeah. So what happened during the blob? Did you see a lot of sick marine mammals then as a consequence of all the domoic acid?

Claire Simeon  5:53  
Yeah, well, it was kind of a one two punch, there were the effects of the domoic acid. And there were also the effects were sea lion moms had to travel farther off shore dive deeper just to find food for their offspring, because this hot water was causing the fish to shift and then they had to go and so they were basically abandoning their pups. So you would see starving sea lion pups along the beaches, and then also really sick and seizing animals, when you have an active bloom of pseudo nature, certain species of fish will eat the algae, they'll ingest it, and then they'll, they'll have a whole bunch of this toxin in their bodies. And then larger animals, like sea lions will eat the fish, and then they'll have large amounts of toxin in their bodies. And so if you have animals during a harmful algal bloom that are eating a bunch of fish in this area, they'll strand or they will beach themselves, they'll come on to shore, and there'll be very sick, they'll be seizing, some of them might be comatose, and it can certainly be a fatal disease. So a lot of the time responders that are part of the Marine Mammal Stranding Network will try to rescue these animals to bring them into rehabilitation to try to do everything that we can to try to flush the toxin out of the body to hopefully avoid any permanent brain damage. A lot of animals unfortunately, do die from this, even with treatment, what can happen is that they basically can develop seizures that don't stop, and at that point, we can make the decision that it's more humane to euthanize them if their seizures just don't stop or if we suspect for another reason that that they're not going to survive. Unfortunately, we don't have a specific antidote to the toxin, but it is water soluble. So if we can flush it out of the system with with a lot of fluids, and then control the seizures with anti seizure medication, then hopefully, you can help the animals that are the least affected. But unfortunately, that's not all of them.

Cindy Buckmaster  7:47  
Right. So Crona was one of these sea lions who is stranded on the beach. And you've known krona, since the first stranding, is that right?

Claire Simeon  7:55  
I wasn't involved in his initial care, but I was working with colleagues who were treating him and so he was on my radar then back in in 2017. And he stranded in San Luis Obispo, kind of central California. And he was a juvenile animal and he was lethargic, he was kind of thin. But other than that there wasn't a whole lot specific that was wrong with him. And veterinarians didn't see any seizures at that point. So he was released about a month or a couple of weeks after, and then he stranded again, and he seemed disoriented. He was also approaching people. And that's one of the things that is really challenging with some of the behavioral changes that come with being exposed to domoic acid is that it can change the behavior of animals. And while it may seem cute or interesting, the animals are not afraid of us. Unfortunately, that's a really bad sign for a wild animal. You know, we want wild animals to be wary of humans, we want them to be living their life and not interfering with ours. So when he lost that fear, and he was approaching people, everything that was when veterinarians slot, you know, there may be something happening with exposure to domoic acid. And so he was released a second time, actually far out on the feral on islands, to try to give them a chance to just be with other sea lions and not around people. Then he came back again, onto the beach. You know, at that point, he was actually coming up to people at a public restroom on the beach, and he had lost weight. You know, it was clear that even though he had been out there in the wild that he wasn't adequately able to care for himself and his body condition was getting worse and so he was deemed unable to survive on his own in the wild. And so at that point, National Marine Fisheries Service is the government agency that's responsible for animals that are along the coastline or that are rehabilitation. They help to find a place where animals that are non releasable can get the care that they need for the rest of their lives. And so at that point, he was placed at Six Flags in Vallejo, California, and he did start to have seizures. So it was a little bit clearer from then on what was likely happening.

Cindy Buckmaster  10:02  
So when he got to Six Flags, he obviously had a team of caregivers. And I mean, he's just such a sweet little guy. I imagine that they took right to him, you know, can you describe the relationship between Corona and his caregivers?

Claire Simeon  10:15  
Yeah, there is a really tight team of caregivers and actually a large team, you know, so Randy, Ashley, Stephanie, Talad, Caitlin, Aaron, Marissa Clayton, Kate, Alex, Brooke, Kaylee, Eric, and Diane, all of these people so committed to Corona from the minute that he got there as they are for all of the animals that they have, you know, he's maybe one of a dozen animals that this team might focus on. And it's clear that they become bonded to him, right as all animal caregivers to and it's funny to see, you know, Corona, he definitely would have favorite humans. And so, you know, so like Clayton is currently his favorite human. But you know, before that, it was Stephanie and Ashley, and Randy, and I'm sure it must hurt to like fall out of favor with Corona, right. But he would be very focused on one of them in particular. And as a team, they were so meticulous in the records that they kept, and the observations that they made, you know, and that that was such a really key piece of tracking his disease and the progression of everything, you know, Randy had such good attention to detail. So she started to notice small things like he seemed to slowly shift his preference for eating towards the afternoon, something that you were, I might not notice, you know, but instead of like ravenously, eating right at 7am, he'd sort of show a little bit of interest, and then kick in around eight, and it would get a little bit later and later, and those minor changes actually ended up signaling that one of his episodes was coming on when he'd stopped eating for a few days. So they, they had such great attention to detail for all of the small behavioral changes, and they kept in such close contact with us, you know, like Ashley kept really meticulous records. Like she would contact me at the beginning of every month and say, you know, okay, Cronus records for the month already, you know, how has he been doing? Like, let's talk through it. And of course, everything is very professional and how they're communicating with me. You know, Tom would always like, tell me that Corona ate really well that day. But then, you know, I hear him calling him by his various nicknames like chrome at the donut or karo or so. So it was really clear, just like, just like, they do have human animal bonds, but any of the animals that they work with over long term for these non releasable animals, it's really clear how much they care about them. Yeah, so

Cindy Buckmaster  12:35  
it sounds like they got really attached to him. And he stayed relatively symptom free from these major seizure issues. He was having right for quite a while, I mean, so like, so how long was he there, that they were all just kind of hanging out, you know, them in Corona and donut and, and having fun, right? How long before he started to show some serious signs of illness,

Claire Simeon  12:54  
for about the first year to year and a half, he really remained pretty seizure free and just had a very occasional seizure, and then, you know, went on his phenobarbital. But after about a year and a half, the seizure started to become more frequent. And his behavioral changes started to become more dramatic as well. So he would go through these extended periods of time, at some point in the like, in the summer of 2021, where he was going up to 16 days a month, you know, more than half the month, not eating anything at all. And so there was a period of time where things were well controlled. And then as can happen with patients with epilepsy, they can progress and we lose control.

Cindy Buckmaster  13:32  
So presumably, the acid is gone from his system at this point, but there's sort of this latent period, I imagined, and then and then later on, the seizure disorder can kick in.

Claire Simeon  13:42  
Yes. And that's been found in in other sea lions and other species as well, where you can have the initial insult, and then there can be this latent period where everything seems fine. And then you can see epilepsy develop and brain damage. And that's what happened for Corona, and then it, it just continued to kind of snowball on itself.

Cindy Buckmaster  14:02  
And so these people who were so in love with this animal, then and now they start to see him have some real serious issues. I mean, what did it look like for his caretakers when he would have these seizures? And I mean, what was their response to this?

Claire Simeon  14:15  
Well, you know, seizures and sea lions looks similar to you know, seizures in dogs, or even in us and humans, and it depends on the type but with Corona, he would lose consciousness. So so he would pass out and he would usually, you know, be on his side, and then have the convulsions, his entire body, so, you know, his flippers would be flapping and if any of your listeners have been around or had loved ones that have had seizures, you know, it's very scary to witness. And there was one time when Corona had a seizure when he was floating in the water, and they literally had to scoop them out. And I remember that Diane cried that day, you know, it was it was a dark day because we didn't know if he was going to survive,

Cindy Buckmaster  14:56  
like goodness. So how long did this go on?

Claire Simeon  15:00  
Well, because his health fluctuated so much, you know, he would have these long bouts, and then he would kind of come out of it and have a period of time where he gained a lot of his weight back, he would be seizure free for a couple of months. And so I think that was also really challenging, because it's one thing to have a pretty continuous decline where things are just not getting better. But there were really periods of time where he would rally. And of course, you know, I sign up for the hard stuff, the emergencies and the disease, and that's my job. But you know, I can't imagine that that's what Aaron signed up for when she was sitting alone in the dark in the middle of the night watching and waiting to see if Corona who she cared about so much was going to have another seizure, and then to see that and then, like a week later, him, you know, seemingly bouncing back to normal. That is, that's just so so hard to, to live through.

Cindy Buckmaster  15:52  
At what point did you all finally realize, you know, what, he's, he's really got an issue, now we're going to have to do something,

Claire Simeon  15:59  
when he really lost, like a quarter of his body weight, you know, he lost 80 pounds at one point, and we were then you know, having discussions about how much more is really something that we want to put him through? Because if this is just going to continue to happen, and cycle, and you know, to her credit, Diane, whatever Crona needed she she made happen, you know, anytime you had a setback, she asked me, What can we do better, you know, what can we offer him what's best for him. And so looking for other options, what was always in our mind, but then it was kind of always tempered with this reality of things slowly getting worse. And for me, having seen so many wild sea lions with the same disease and just see them seizing become comatose, dying from it, it was very hard for me to kind of see that path as the most likely path of what was going to happen. And so I felt helpless as well. And I didn't want him to I didn't want him to suffer. And so I really wished that there were more options available than what we had.

Cindy Buckmaster  17:07  
And so you had these conversations about, you know, his quality of life. And I imagine based on the sound of things that euthanasia was probably going to happen quickly.

Claire Simeon  17:16  
Yeah, we were having conversations about at what point would reconsider euthanasia and wanted to have a plan in place, because that involves talking to government agencies that involves talking to the entire team and being really clear about what would happen and when we would get to that point if we needed to. And so we were having those discussions.

Cindy Buckmaster  17:37  
And then along comes this wonderful scientist named Dr. Scott Barragan from UCSF, who's a lifelong career neurobiologist, and somehow you and he knew one another, tell us the story about how that evolved and how you pulled him into the story of Corona.

Claire Simeon  17:53  
So Dr. Bear ban had given a lecture given a presentation about his work at the Marine Mammal Center, and he was already collaborating with my colleagues and had been having conversations with them. And so my husband, who's also a veterinarian, had been working at the center and working with Scott said, Oh, my gosh, you have to call Scott. He's gonna save the day. And he said, you know, you're you guys are out of options, but talk to Scott and see where he is because he knew that Scott had been working on this really groundbreaking research. And so he said, You know, I'm not sure exactly where he is with it right now. But reach out to him, see if there might be a chance for this to help Chroma.

Cindy Buckmaster  18:35  
So Dr. Barragan, what was it exactly that you are giving lectures on in the Marine Mammal Center,

Scott Barragan  18:41  
I had approach Dr. Francis Golan a couple years earlier to the corona story, because we had been developing a interferon based cell therapy for treating intractable epilepsies that are focused in the hippocampus, normally, and we had been planning to scale that up to larger animals before eventually, you know, maybe going to humans. So the project was developed in rodents. And basically, the simple explanation is we take cells from embryos that are destined to become a certain type of an inhibitory cell. And we're able to transplant those embryonic cells into the brain of another animal. And we found that over the years that they integrate, and they increase inhibition, which is important in epilepsy, where there's usually a decrease in inhibition. And so that approach had scaled up to the point where we had already treated several runner models, mostly in mice with these cell transplants, and they were very effective. They basically cured the animals if we put the cells in after they had developed epilepsy. And so to get that to a larger species, we've been planning and using pig embryos as a donor instead of mouse cells. And I had known for a very long time because of work of my colleague, Paul Buckmaster, down at Stanford that these domoic acid poisoned sea lions developed a form of epilepsy that was hippocampal specific and resemble temporal lobe epilepsy. So basically, it mimicked the types of rodent models we had and so as the pig project advanced, I approached the Marine Mammal Center to talk to Dr. Cohen Arne who is running it and say, hey, you know, this is what we've been doing. I showed her the papers and talked about it said, I think we can maybe do this for the sea lions. And so we worked with her. We talked with her a couple of times, then I think she asked me, if I remember correctly to come down one morning and present to the group. And I think that's the seminar was really just an informal meeting, where I presented what my lab did, and kind of my hope that we can maybe scale this up for sea lions. So I'm guessing that's the meeting where Sean was in the room. And so that's probably that chance interaction of presenting that story before we'd actually done anything to the staff at the Marine Mammal Center.

Cindy Buckmaster  20:31  
And this is before Corona was even there. So our plan

Unknown Speaker  20:34  
initially was, you know, because we knew these sea lines were getting stranded and collected up by the Marine Mammal centers in the rehab centers that we would basically initially just kind of work on developing the surgical approach and transplanting the cells on animals already designated for euthanasia, and then kind of optimizing that approach. And if it looked promising, then maybe we would try, you know, alive sea lion. We didn't know at the time. And we found out later that OSHA, I guess, or the animal care, people, were not going to let us release a sea lion that we had transplanted with pig cells and its brain. And so we were kind of stuck in this mode of, well, maybe we do some acute treatments and watch animals for a few months. But then that was the best we could do. At that time. I didn't know that sea lions in captivity who had to make acid poisoning.

Cindy Buckmaster  21:15  
So let's get back to Corona. I mean, it's the same with the others. Right. So the domoic acid poisoning causes an issue in the animal's brain in the hippocampus. And maybe for our listeners, you can describe exactly what was going on in Corona, its brain that was causing this horrific seizure disorder that he had what was going on in his brain? And how would what you had been working out in mice help him and why,

Unknown Speaker  21:39  
in general, when you have epilepsy, whether it's in people or in animals, it's kind of like an electrical storm. So you're going around normally, and then all of a sudden, you have this huge wave of electrical activity, that synchronized all at once. And that generates seizure event, depending what part of the brain it's in, you know, convulsive seizure event. Normally, in many types of epilepsies that are called acquired temporal lobe epilepsy, the damage is specific to one region called the hippocampus, the hippocampus is one on each side of our brains controls a lot of memory functions and cognitive functions. And it's also kind of this relay point for where seizures usually originate. And so we know for many, many years that in patients at least they get damaged, this part of the brain is very specific for certain cell types and basically lose these inhibitory neurons that are putting a brake on this electrical activity. And so you can imagine when you have your brakes don't work as well, you're more likely to speed through and have a crash. And that's kind of what happens with patients with epilepsy. As this damage increases. It's a normally there's only two treatments. One is to give a drug that maybe will boost this inhibitory system, pharmacologically. And those are benzodiazepines, usually diazepam, things like that are commonly used. And sometimes in patients where the damage is only one of their Hippocampus on one side, neurosurgeon can go in to remove that hippocampus and hopefully get some measure of seizure control. So our approaches is a little bit different was to say, hey, we're gonna leave this damaged hippocampus in place, but we're going to put back these inhibitory cells that have been lost. And so that was basically the project we've been developing here at UCSF for about 1516 years before the corona story. And the simple premise is that these inhibitory cells, if you could add more of them back. And if they can integrate in the circuit, where you put them, they're going to increase inhibition in a natural fashion. And that will then you know, restore the brakes on the system and prevent you from having these seizures. And so that's what we're hoping to do with Kodak because there have worked very well in lower animals that can mice,

Cindy Buckmaster  23:23  
amazing. So you develop some stem cells.

Unknown Speaker  23:26  
So stem cells involve taking pluripotent cell at an early stage, either from human or whatever, and then deriving it in culture into the type of neuron you want. This is more of a cell transplant. This is, you know, transplant, we're taking actually embryonic or fetal tissue from area of the brain where the cells are born. It's very specific. It's called the medial ganglionic eminence, and the types of inhibitory cells we want are born there. And then they migrate into our brain and various regions. So we basically harvest these cells freshly, and then we just transplant them into an animal and they become what they're supposed to become. So this is not a stem cell approach. It's a cell transplant approach, but it uses fetal tissue. It's most similar to work done in the 1980s in Parkinson's disease, where Kurt Fried's group had taken fetal dopaminergic tissue and put it into patients with Parkinson's disease. And he found some modest success with that. And most importantly, those cells actually didn't do anything damaging to those patients. And they've survived for, I think, up to 21 years in those patients. So it mimics that more than what are called Stem Cell Technologies, which try to derive the cells.

Cindy Buckmaster  24:22  
Yeah, thank you. That is an important clarification. And I'm not sure that came through in the in the media.

Unknown Speaker  24:27  
And to be honest, it's a bit of a problem because they get lumped together. And there's a lot of commercial interest in trying to generate certain cell types, including these inhibitory cells. But the reality is that even though a lot of people have claimed this and companies have claimed this, there is no equivalent human stem cell line that makes the same types of inhibitory cells that these harvesters mg cells make.

Cindy Buckmaster  24:46  
Well, that is a very interesting point because we keep hearing from you know, groups who are opposed to research with animals that you know, the answer to everything is stem cells. And here you're saying very, very clearly that even though we have advanced in stem cell technologies, we haven't even advanced to the point where We could actually create cells from stem cells to do what it is we need them to do in the hippocampus and stop seizure activity. The only way to do that is to get fetal tissue that's already destined to do that, put it in there, let it integrate and do its thing. Is that right?

Unknown Speaker  25:14  
That's absolutely correct. And a very important distinction in that inhibitory cells, which we're talking about these cells make GABA, which is an inhibitory transmitter are very diverse. And so the problem with the Stem Cell Technologies is how to make them into these very specific types of cells, cells we use, or maybe 30%, of the types of inhibitory cells, 30, and 50%. And there are other types as well. And some of those actually would integrate and create the opposite condition, because those are cells that inhibit other inhibitory cells. It's a very fine distinction. And the stem cell technologies are fantastic. And they've come a long way. But they're not to the point where they can make these very specified cell types that we need, in this case for epilepsy and maybe other related disorders. And the second part is they also have to have an ability to migrate and integrate. And stem cells don't normally do that. But these progenitor cells, these cells, we harvest, they maintain that ability. So those are two important distinctions. You have to have the right type of inhibitory cells, and they have to be able to migrate and integrate in the host brain after you transplant them. In this case, we used pig embryos. So we worked with the veterinarians at UC Davis as part of this collaboration to obtain pig embryos at the correct age where the cells are born. And they're available and worked by Mariana Casella, who is a very talented postdoc in my laboratory who drove this project. During these years, she would go out to UC Davis and get these fresh pig embryos that were harvested from a cow that was destined for euthanasia at the correct age. And we had been characterizing them for several years before we approached the sea lion people to make sure they were making the types of cells we needed. And so Mariana had done work in rodents, to transplant these cells into rats to see if they look the same to look at them in culture and in a variety of different techniques we have available to show that these cells are identical to the mouse cells, we've been working with our therapeutic.

Cindy Buckmaster  26:53  
Right, I think that's an interesting thing to talk about. Just briefly, right? I mean, because I like to remind people that treatments like this don't just come from thin air, right? You said that you spent 15 years, just doing basic science in this part of the brain trying to figure out you know, how things worked in there and what was going wrong and and maybe how they could be fixed. And you came up with this idea of using these cultured progenitor cells. Maybe you can talk a little bit about the basic research involved in what motivated you what even made you think about this, what inspired you to start working on this puzzle, and that eventually, then led you to Corona?

Unknown Speaker  27:26  
I guess since the late 1990s, when I was a postdoctoral fellow and then my early Professor years, I'd always been interested in studying the role of these inhibitory cells in the hippocampus and cortex and the role in epilepsy. So I had a long kind of background of knowing these cells were important both for controlling seizures and when they were defective for producing seizures. In early 2000s. I was approached by two colleagues here at UCSF, Arturo Alvarez Boulia and Jon Rubinstein. And they had actually had two fascinating discoveries Jon Rubinstein had discovered were in the embryo that these specific interneuron subtypes are born later other groups add to this, but John was one of the earliest groups during this and he had found this medial ganglionic eminence region as the source of the types of inhibitory neurons that populated the hippocampus, the areas that were studied in the cortex. Arturo had separately found that if you harvest these progenitor cells, and then you transplant them, that they would migrate in the host animal. And so they arrived in my office, I think, sometime around 2001, or 2002, and sat down and showed me these pictures of cells they had transplanted that became inhibitory neurons. And I was pretty fascinated, and of course, interested because like I said, I've been studying the role of these inhibitory neurons in epilepsy in the first place. And I said, Yeah, I would love to find out if these cells can integrate, and functionally, you know, prove inhibition. And if that's possible, which was the first couple years of looking at the project, I said, Hey, I think we could actually develop this as a treatment for epilepsies. Because putting these cells in would actually stop potentially a patient from having epilepsy. And so we've been thinking about and working on that in the early 2000s, through about 2008 or nine when we started to test the first animal models, and it was very effective right off the bat when we transplant these animal models of epilepsy. And so we started to progress to look at various models, different models representing different types of human epilepsies. And then, I think when Maryann joined the lab, which was right after Bobby hunt, who's now a professor at UC Irvine, had showed in his seminal study that we can cure mice that had temporal lobe epilepsy, she joined to take it to the next level, which was to see if we could progress this into larger animals and took on the project of first looking at these pig energy cells. And then later, of course, she was integral to the corona story as well.

Cindy Buckmaster  29:26  
Yeah. So now so we're at the corona, that story. So now we have this poor animal, the vet and the caregivers, the team they've been talking about, you know, maybe the only thing humane to do for Corona now is to euthanize him. So now tell us what happened. So tell us how you found out about Corona take us down that whole path that part of the journey for Corona? What happened? What were your expectations?

Unknown Speaker  29:47  
There was late in September I received an email from Claire and Shawn saying they had this sea lion this rescued sea lion at Six Flags that was having severe epilepsy domoic acid sea lion, and that maybe I should see if I can come out and maybe develop it transplant technique for him, see if our procedure could work and tested on it. So I got up one morning, I drove out to meet everybody. And they brought out Coronas to show me. Of course, I'm not a veterinarian, and I'm not a sea lion expert by any means. And so it's kind of fascinating to give a consult about an epileptic sea lion is really the first time I'd probably seen one in person. And I explained that, you know, yeah, we had this approach, we're pretty confident that the pink cells, you know, that we've been studying were good that there were the types of cells we would need for therapy, that they were safe. And we weren't quite sure about some of the logistics of the surgery necessary, because we hadn't tested that out yet. But we had an idea how we'd want to do it. And I basically, I think, I told the group, I said, Hey, you know, I don't know if I could save Corona, I can promise you worst case scenario, we'll put the cells in and nothing will happen, you know, we're not going to cause a tumor, we're not gonna make his condition worse, I was pretty confident that I said, you know, it might or might not work. And if it does work, then it'll be pretty effective. Because when we've done this successfully, rodents, all the animals became basically seizure free and improve their behavior. So I said is potentially could be life changing for them. At the same time, there's also possibility that it just doesn't work at all. So after the visit, I started, I guess, a series of separate email chains with different groups. There are three kinds of logistical issues. One was my group, specifically getting together to make sure we had pig's cells available, and then getting the procedures and the techniques and the instruments that we would need on site. So we'd have to go on the road with my lab. So that was our side of it. A second group, fortuitously, was this collaborator. It had been Inglis, who was at UC Berkeley, and he had been doing MRI imaging on domoic acid poisoned sea lions, so we've been talking to him for a while. And he actually had a scan of Crona from a couple years earlier. So we started to talk to the imaging team about what kind of MRI guided surgery approach we would need. Laura across the vet who was here helps my department on the clinical side, the neurosurgery side from a company called Brain lab, they kind of convenient to see what type of images we would need to do this on site. A third group is I approached the neurosurgeons, my chair, Eddie Chang, and two of the residents in our program, John Andrews, and Ryan Ryan, and asked them, you know, if they're available, we had a technique and approach, we just hadn't tried it first. And so they kind of had a workout, adapting what we did in rodents to a larger animal and getting the frame and all the things necessary to deliver the cells. The fourth team, which was Claire, and company was finding a site to do this, because this was during COVID, we had no mechanism to bring the animal to UCSF or to Berkeley. And so we had to find a remote site where we can get an MRI scan live, get all the people to that site, have all these teams, get our lab to the site themselves, and then be available or equipment wise with the vets necessary to anesthetize them and do all this other stuff to do this on site. And so that ended up being something Claire's group figured out at a clinic in Redwood City that agreed to let us do this on site.

Transcribed by https://otter.ai
