New treatments for deadly snake bites, and a fusion company that wants to get in the medical isotopes game

This episode explores innovative uses of fusion technology for medical applications and new methods for treating venomous snake bites.

1. Fusion technology is being repurposed to produce medical isotopes, offering a potential revenue stream and practical applications in healthcare.
2. The company Shine Technologies is advancing through a strategic plan to eventually achieve sustainable fusion energy production.
3. New research on snake venom treatment shows potential in using existing drugs to reduce tissue damage from bites, particularly heparins, which could revolutionize treatment accessibility and efficacy.
4. The approach of using CRISPR to screen the human genome for venom interactions could lead to broad applications in treating various venomous bites.
5. This episode highlights the intersection of advanced technology and medical research, illustrating how innovative applications can address complex health challenges.

1. Fusion Technology and Medical Isotopes

This chapter details how Shine Technologies uses fusion-generated neutrons for medical applications, sidestepping the energy production challenges of fusion. Adrian Cho: "We're not just focusing on energy; we're using the byproducts, like neutrons, for practical applications such as medical imaging."

2. Advances in Treating Snake Bites

Tian Du discusses her research on using existing drugs to mitigate the effects of snake venom, particularly focusing on the tissue damage caused by spitting cobras. Tian Du: "We've found that heparins can act as a decoy, significantly reducing tissue damage in snake bite scenarios."

1. Explore Non-Traditional Uses of Technology: Consider how existing technologies can be repurposed for new, profitable applications.
2. Leverage Existing Drugs for New Treatments: Investigate how drugs approved for other uses can address unsolved medical challenges.
3. Stay Informed on Medical Advances: Keep up with the latest research to understand potential impacts on healthcare and treatment options.
4. Support Innovative Research: Advocate for funding and support for research that bridges technology and medicine.
5. Prepare for Emergencies: Educate yourself on first aid and emerging treatments for common emergencies, like snake bites.

First up this week, Staff Writer Adrian Cho talks with host Sarah Crespi about a fusion company that isn’t aiming for net energy. Instead, it’s looking to sell off the high-energy neutrons from its fusion reactors for different purposes, such as imaging machine parts and generating medical isotopes. In the long run, the company hopes to use money from these neutron-based enterprises for bigger, more energetic reactors that may someday make fusion energy.

Next, we hear from Tian Du, a Ph.D. candidate in the Dr John and Anne Chong Lab for Functional Genomics at the University of Sydney. She talks about finding antivenom treatments by screening all the genes in the human genome. Her Science Translational Medicine paper focuses on a strong candidate for treating spitting cobra bites, but the technique may prove useful for many other venomous animal bites and stings, from jellyfish to spiders.

People

Sarah Crespi, Adrian Cho, Tian Du

Companies

Shine Technologies

Books

None

Guest Name(s):

Adrian Cho, Tian Du

Content Warnings:

None

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Sarah Crespi
This is the science podcast for July 19, 2024. I'm Sarah Crespi. First up this week, staff writer Adrian Cho talks about a fusion company that isnt aiming to sell energy, at least in the short term. Instead, theyre looking to market the high energy neutrons from its fusion reactors for x ray imaging and medical isotopes, with the hope that one day, with the money from those businesses, they could upgrade to selling energy.

Next, I speak with researcher Tian Du about finding snake antivenom treatments by screening.

Icon School of Medicine at Mount Sinai
All the genes in the human genome.

Sarah Crespi
Her paper focuses on a strong candidate for treating spitting cobra bites, but the technique may prove useful for finding treatments for many venomous animal bites and stings, from jellyfish to spiders.

Sarah Crespi
This week in science, staff writer Adrian Cho wrote about a company looking to make money from fusion, but not by creating energy.

Hi Adrian. Welcome back to the podcast.

Adrian Cho
Hi Sarah. How are you?

Sarah Crespi
Good. I'm good. So just give us a little background. How is fusion looking right now as an energy source? How's that going?

Adrian Cho
Well, it's been a dream since the 1940s that people could use fusion to generate energy. There's been a lot of progress, but there's still a long way to go. I don't think anybody realistically thinks that there will be fusion power for at least another decade or two.

Sarah Crespi
Yeah, they're fusing things, but the energy cost for fusing is so high that we're not going to be able to have extra energy after that to sell.

Adrian Cho
To people that's correct. Right now, if you take the total amount of energy that goes into a laboratory that has a fusion reactor, the amount of energy that comes back out of the fusion is no more than a couple of percent of the total energy going in.

Sarah Crespi
No one is making net energy, but there are companies out there that are trying to sidestep their way to it, which is what you covered here.

Adrian Cho
This company, shine Technologies, is trying to make money off of fusion right here, right now. Not by selling the energy, which they can't produce in a great enough amount to make it profitable, but rather by selling what's essentially a byproduct of fusion, which is energetic neutrons. Most approaches to fusion involve getting a nucleus of deuterium. It's just a proton bound to a neutron to fuse with a nucleus of tritium, which is a proton bound to two neutrons. And when that happens, you produce something called helium four and an energetic neutron. In most approaches to fusion energy, the idea is that you will somehow capture the energy from these neutrons. And what this company has decided is that they're going to make money by selling the energetic neutrons to do various things with while they try to develop, step by step, much higher levels of fusion until they eventually get to fusion power. And the idea is to make money along the way.

Sarah Crespi
What are some of the things that they've been able to do with neutron so far?

Adrian Cho
So Schein is the brainchild of a fellow named Greg Pifer, whos a nuclear engineer who graduated from the University of Wisconsin Madison. And Greg has this vision of essentially taking four steps, both in neutron technology and economically, to get to fusion power. The first step is to use the neutrons from fusion to do the imaging of machine parts, in particular, metal machine parts like the turbine blades of jet engines.

Sarah Crespi
You can't do that with x rays. Right. You can't look inside of a metal thing with x rays.

Adrian Cho
That's right. The free flowing electrons in metal will block the x rays, but neutrons can get through. So they can actually show you defects inside a metallic solid and you can even determine the composition of the metallic solid. So shine and its precursors have been offering neutron imaging since about 2014.

In fact, GE Hitachi, which is one of the major nuclear power companies, they actually have a deal with shine to image all the fuel pins that will go into their nuclear reactors. So this is a serious thing. So they've been doing that for a decade. What they're now doing is that they've improved their neutron sources and they're now going to use them to generate medical isotopes. These are fleeting radioactive atomic nuclei, very specific ones that can be used for a variety of medical purposes. But the big two are imaging. So imaging things like your heart and fighting cancer, you can inject them into the body, and if you do it right, so that these radioactive nuclei are attached to some sort of biomolecule that will only bind to a tumor, you can send these things in and like little Trojan horses, they will burn out.

Sarah Crespi
The tumor, irradiate the stuff. Yeah.

Adrian Cho
Right.

Icon School of Medicine at Mount Sinai
The plan then is to continue to do this imaging as well as making medical isotopes.

Adrian Cho
That is the plan. And it's kind of what they're doing now. Shine has a facility in Fitchburg, Wisconsin, where they do the imaging as a service. But what they've done down I 94 in Janesville, Wisconsin, is they've built this big factory, which is not yet quite complete, but it will have eight of these new improved neutron sources that they will use to generate medical isotopes.

Icon School of Medicine at Mount Sinai
This is their next moneymaker, then this is the way they're going to fund the next step. Steps three and four, get that medical isotopes money and then on to the next stage.

Adrian Cho
Right. So the medical isotopes business is very interesting. In 2009, there were a couple of reports that pointed out that the us supply of medical isotopes is tenuous for a number of reasons. And one of them is that medical isotopes are not usually created in power reactors, but theyre created in these small research reactors and there arent that many of them. 15 years ago, most of them were running on highly enriched uranium. And thats a proliferation issue because that material could potentially be made into a bomb. And it was kind of scattershot how these different facilities would produce their isotopes. By far the most commonly used isotope is one called molybdenum 99, or Molly 99 is used in imaging for your heart, for stress tests and things like that. But it can be used in a lot of ways. In 2007, there was a sudden huge shortage of Molly 99 because this research reactor in Canada had been shut down for routine maintenance. And then that shutdown got extended because they had to do some earthquake proofing of the facility. And all of a sudden there was this big shortage of Mali 99, which is a serious thing, because every day in the US alone, there are 40,000 procedures that involve Molly 99.

Sarah Crespi
So are they actually in the market now? Are they selling off these medical isotopes at this point?

Adrian Cho
They are, but they are not actually selling Mali 99, which was the isotope that got them involved in this whole business because the us government wanted a way to make Moly 99 without highly enriched uranium. It turns out that their first product is an isotope called lutetium 177.

Sarah Crespi
This is the one that's targeting. That's like, you get that radiation right into the target tissue.

Adrian Cho
Right?

Sarah Crespi
And so they're making that now at shine.

Adrian Cho
They are. But this is, it's all very complicated. And so even though shine has developed this really cool, beautiful neutron generating technology, they are not, in fact, using it right now to make lutetium 177. What they are doing is leveraging their ability to make ion beams to take good old natural occurring euterbium and pull out the 13% thats euterbium 176 sticking these tiny little vials, sending it off to a research reactor in Missouri, where its exposed to neutrons. Then it comes back, and then they have proprietary methods to extract the lutetium 177. And so they're marketing lutetium 177 ironically, without using their own neutron sources.

Sarah Crespi
I just want to say that it's pretty amazing if you think about how they make drugs for use, how those plants have to be inspected and they have to meet all these guidelines. But it's still another step up to be like, we need a nuclear reactor to make this medicine.

Adrian Cho
It's a lot of, it's a very, very complicated process. And making the isotopes is only the beginning step, because exactly, as you point out, this stuff has to be purified, it has to be certified safe, medical grade.

Sarah Crespi
Right.

Adrian Cho
And so there's an enormous amount of radiochemistry, as it's called, that goes into extracting the isotopes, purifying them, packing them up and shipping them around. And all of this is extremely time sensitive because, in general, the two things that you want from a medical isotope, you want high purity and you want a short lifetime for whatever it is you're using, because you're going to inject it into the body and you want to do whatever the procedure is in a relatively short amount of time, and.

Sarah Crespi
Then no more radiation for the person.

Adrian Cho
That's why these isotopes, they're not things that decay over thousands of years.

Sarah Crespi
Well, so, okay, the medical isotope business is the next step in the four step process. If they're taking another step towards fusion for energy, whats step three?

Adrian Cho
Every step involves making this neutron source essentially more intense. And so step three would be to improve the neutron source to the point where you could use the neutrons to transmute long lived nuclear waste from reactors and make it decay much faster and make it much safer and thats potentially a much bigger market because theres all this stuff hanging around.

Sarah Crespi
Its not going away and its building up over time really hard to maintain and keep safe.

Adrian Cho
Right. And then the fourth step would be to go to fusion power and actually be able to generate power.

Sarah Crespi
Right.

Icon School of Medicine at Mount Sinai
So we're talking about now generating energy from fusion. Is Shine's approach the one that it could potentially take to make fusion energy possible?

Is that different from other stuff that I've heard about like using magnets to control plasma, things like tokamaks.

Adrian Cho
What they do is quite clever. Right. So they have this neutron source that's order of 4 meters tall. And on the tippy top there is a source that uses radio waves to generate individual deuterium nuclei, or deuterons. And then a very short electrostatic particle accelerator drives this beam of deuterons straight down and into this gas of tritium. And then they fuse in there and the neutrons come out. What Schine intends to do to make medical isotopes is to surround that target of tritium with a solution containing uranium. And the neutrons from the fusion will split some of the uranium atoms into a whole lot of isotopes. But you can then filter out of that fluid things like molybdenum 99.

In a way, they would be making these nuclei that are generally made in a reactor without the chain reaction.

Sarah Crespi
Like a fission reactor. Not a fusion reactor.

Adrian Cho
Exactly. In a standard fission reactor right. Now to make Molly 99, the state of the art is to take a slug in uranium and stick it down next to the core of a research reactor. The idea of doing the uranium in a solution makes things so much easier. You can just take the fluid out and sieve out the isotopes that you're looking for and then you just return the rest of the solution to the tank and you just keep recycling it.

Sarah Crespi
So it sounds like they're going to just keep refining this technology and making it higher energy in order to get to these later steps, either transmuting the waste or to make fusion energy.

Adrian Cho
Right. To go to a higher neutron fluxes, they'll have to do things like ionize the tritium to turn it into a plasma. And then all this stuff that you were talking about, like having a tokamak that comes into play because you can't hold a plasma in a bottle.

Sarah Crespi
You have to hold it with fields, right.

Adrian Cho
You can put the tritium gas in a can. You can't put the tritium plasma in a can because it will react with the can.

Icon School of Medicine at Mount Sinai
Maybe I'm being a little naive about where money comes from or how research is funded. But why is this company taking this approach? Why build money making into their stepwise process for getting to fusion for energy? Is this a common practice with fusion companies?

Adrian Cho
Well, so there are a number of commercial outfits that are trying different approaches to fusion energy. And sort of what distinguishes shine is this emphasis on making money right here, right now by finding something useful you can do with fusion as opposed to having this particular technological goal. So there are companies that have visions of, for instance, will make a small fusion power plant by having superconducting magnets. So they have a particular vision of what their end product is going to look like and they're trying very hard to get there. And generally, I'm just speaking very generally as businesses, I mean, they're all startups, they're all dependent on venture capital to exist. But as businesses, outfits like that tend to try to market the basic parts of their technology for different uses. So for example, they're developing magnets made out of high temperature superconducting tape. You could use those magnets for other things. And so they're trying to spin out magnets as a way to make money or power supplies because fusion depends on very high power power supplies that can react relatively quickly and things like that. So there are these sort of technological things that you could sell, but what shine is doing instead is actually trying to sell a product of the fusion process, which is neutrons. So thats the distinguishing factor here.

Sarah Crespi
Its really interesting.

Icon School of Medicine at Mount Sinai
I guess we dont really know whats going to happen if this is going to turn out. It sounds like medical isotope market is a little volatile. And yeah, theres a few more steps till we get to the fusion energy part of this.

Adrian Cho
The thing to remember is that Im a science reporter. Im not. I know, a financial reporter. Will this make money? Will they, will they get rich and.

Sarah Crespi
Lock up this market and then decide not to do anything else afterwards because they're getting rich off medical isotopes.

Adrian Cho
This is another issue. If it's not 100% clear that they will succeed because there are other people trying different approaches in medical isotopes and they're not guaranteed to succeed at this. Although they have done an enormous amount, they've raised 700 million in capital. They've got this nearly complete factory. They've got all the pieces in place. They just sort of need to get over the hump. That all looks great. But the flip side of it is that if they clean up in medical isotopes, if this becomes the way to make medical isotopes, you can imagine that that company will be under tremendous pressure to just make isotopes and money.

Icon School of Medicine at Mount Sinai
Okay, one last question, Adrienne. Do we know anything about why this is kind of an overlooked option?

Why have companies been selling the byproducts, the technology that has come along with the hunt for fusion energy, as opposed to selling the neutrons from the fusion reactions? Why has that not been considered an option before?

Adrian Cho
I don't really know. Sort of. The heyday of fusion research was in the seventies and eighties. People thought, okay, really, maybe in a decade we'll make power. That prize has been such a guide star for the field that I think that people who got into it, they got into it because they were interested in power. They didn't get into it because they were interested in doing other things with it. So that's my guess that it's just a question of emphasis.

Sarah Crespi
Thank you so much, Adrian, for coming on the show.

Adrian Cho
Thanks, Sarah. Thanks for having me. My pleasure.

Sarah Crespi
Adrian Cho is a staff writer for Science. You can find a link to the story we discussed@science.org slash podcast stay tuned.

Icon School of Medicine at Mount Sinai
For my chat with researcher TN DU.

Sarah Crespi
About finding new treatments for dangerous snake bites.

Icon School of Medicine at Mount Sinai
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Sarah Crespi
Antivenom to counteract deadly snakebites is extremely vital. More than a million people are bitten each year, and more than 100,000 die.

If they survive, a large proportion end up with long lasting injuries. Anavenom that's typically used today is based on antibodies, but it's expensive, hard to make and hard to keep. This week in science Translational Medicine, Tian Du wrote about screening the human genome for venom interacting partners and turning those partners into potential treatment targets. Hi, Tienne. Welcome to the Science Podcast.

Tian Du
Hi, Sarah. Thanks for having me on.

Sarah Crespi
Sure. You know, I've talked a lot about snakes and snake bites on this show. I'm a big snake fan, so I definitely think it's a really interesting area to research, and I just never have seen the numbers put out the way you wrote them in this paper, that the damage to human life, both from death and from injuries, is quite high. You even mentioned now that it's a high priority neglected tropical disease. According to who?

Can you tell us a little bit about what happens when you get bitten? You know, what are the effects? Like, I think specifically we can talk about spitting cobras because that's what you focus on in the paper.

Tian Du
Yeah. So, like you said, snakebite really affects millions of people worldwide, and there are obviously lots of different species of snake. What we wanted to focus on was the spitting cobras, because lots of venoms can attack your heart or your nervous system, and those are like the deadly venoms, but there are these venoms that contain more sort of tissue damaging toxins around the bite site, the damage of skin and muscle, and that's what's in these spitting cobras. And we wanted to look at that just because, like you said, these survivors are left with these permanent disabilities from.

Sarah Crespi
The snake bites and antivenoms don't work necessarily very well at the site of a wound. They're more just like overall systemic approach.

Tian Du
Yeah, exactly. So our current treatments for snakebite are only antivenoms, and we don't have any antivenoms that can actually counteract that tissue damage. And we think that that's likely because those antibodies are just too large and because they have to be administered intravenously, they don't go out to the periphery like a legend or an arm, which.

Sarah Crespi
Is probably where you got bit, right?

Tian Du
Yeah, exactly.

Sarah Crespi
The other issue here is the mechanism. Venoms are this complex mixture, and we don't know much about their specific targets on the cell or in the cell that they actually need to interact with to kill the cell. What's important for that process really hasn't fully been explained or understood. And you in this paper, took a very, I'd say, nonjudgmental approach. Like, you didn't make a lot of assumptions when you went to find the important molecules in the human body. You basically looked at every single gene. Can you describe that process for us a little bit.

Tian Du
Yeah. So we wanted to look at it, as you said, non biased approach. And we use this technique a lot in our lab called CRISPR, whole genome CRISPR screening. Essentially, we use CRISPR, the gene editing technology.

If you do that in one cell, you can target a gene, turn it off and then compare. How does that gene work against. Compared to a normal cell, how does it work against a venom? But we basically take a whole pool of cells and we turn off a different gene in each cell that covers the whole genome. Then we add our venoms onto that, and we can really quickly cover the whole genome and see what genes are helping the cells to survive and which genes are actually making it worse for the cells.

Sarah Crespi
Which did you find were more important things that were helping the cells survive or things that were making it worse for the cells? Because in some ways, if you take those away, maybe the venom won't be able to interact with the cell or something.

Tian Du
Yeah. So we use this really just to find the processes, and we look at both sides of those that help the cell and those that detract. But what we found was really interesting was that by looking at two different species of Africans being cobras, a lot of the genes, when we took it out of the cell, that helped. That means it's a little bit backwards. It means that in a normal cell, that's what the venom is latching onto.

Were these long sugar chains on a cell surface.

Sarah Crespi
So these are outside of the cell, but they are basically helping the toxins attach to the cells and do their dirty work.

Tian Du
Yeah. So I guess we can kind of think of it as a doorknob into the cell. So the toxins are kind of latching onto that. And we found this really interesting. And intuitively, it kind of makes sense as well, because these sugar molecules. So heparin or heparin sulfates, they're ubiquitous across our cells and animal cells. So there's possibly, like an evolutionary thing here where the snake is hijacking something common across evolution.

Sarah Crespi
Yeah. It wants its venom to work, whether it's a mongoose or a humanity.

Tian Du
Exactly. Yeah. So either to catch prey or also to use as defense against things that are wanting to attack it.

Sarah Crespi
Yeah. So you mentioned heparin or heparinoids. So that's. Some people might be familiar with this. This is, you know, a drug that people use right now to prevent blood clotting. And, you know, if you ever take a sample and put it in a test tube, you know, sample of blood, it's probably got a little heparin in there to prevent it from clotting. So that, for me, was just like, wow, this is already touching on something that we already have medical knowledge of how people and heparin work together. Was that something that you were surprised by?

Tian Du
I think I was surprised. It's kind of really lucky for us because what we really wanted to do was find a mechanism and then be able to repurpose something to block that mechanism. And to have a drug that's already there, it's already used across the world was really exciting. So we could just take that immediately and test it, which was really great.

Sarah Crespi
Right. So you test it in mice, testing it in cells. And what happens when you added these already available drugs to those setups?

Tian Du
Yeah. So in the cells, you can add the heparin. So we kind of use it as a decoy for the venom, and it completely obliterates that cell death that the venom causes. And when we inject the different heparins into the mice. So we first inject snake to mimic a snake bite and then inject the heparin afterwards, and it dramatically reduces that tissue damage.

Sarah Crespi
That's pretty amazing. So what does this mean about how close it might be to the clinic to use this mechanism that you discovered and this relationship with heparins? You know, how close to the clinic could we be then for treating snake bites with this?

Tian Du
Yeah, I think we're quite optimistic about this because it's already essential medicine, and some of the heparins are FDA approved for self administration.

That really cuts down that lengthy process of getting it to market with some of the antivenoms. There's like an inaccessibility issue with those. Like, you have to.

Sarah Crespi
Oh, yeah, yeah.

Tian Du
You have to go to a hospital or you have to travel to get to these places because the heparin is stable at room temperature and you can self administer it. Hopefully, this can be distributed to those remote regions faster.

Sarah Crespi
And now, is it likely that some other snakes that have a similar effect on tissue might also be using a similar mechanism for attacking cells and that heparins could help with those bites?

Tian Du
Yeah, so we actually looked at the venom. We separated the venom into its major components, and we found that the heparin was binding really strongly to these, what is called cytotoxic three finger toxins. I guess it's kind of in the name of the toxin, but that is what's causing a lot of that tissue damage.

We looked at asian snakes that also had a large component of the venom. Were these three finger toxins, and it could block those as well in cells. So there is hope that this can treat a lot of snake venoms that are rich in those toxins.

Sarah Crespi
Could you see this approach that you did here? You're focusing on how they're entering cells, how they're killing cells, the cytotoxic effect of the venomous. But what about those more systemic effects that you talked about attacking the nervous system or attacking the circulatory system, the heart? Could this approach be used to also look for places to intervene in those mechanisms?

Tian Du
Yeah, for sure. So one of the limitations, I guess, with using the crispus screen setup we have at the moment is that the readout for that is cell death.

Icon School of Medicine at Mount Sinai
Right.

Sarah Crespi
Binary. Does it kill the cell? Does it not kill the cell?

Tian Du
Yeah, exactly. But we do have new screening systems that we're kind of looking at in the lab to look at the, say, calcium influx into a cell. So that will really target those neurotoxic substances. And we are looking across lots of different venoms into those kinds of things as well.

Sarah Crespi
That's wonderful. What about other venoms that might be affecting people out there?

Tian Du
I guess I just want to also highlight the technology that we used. As we were mentioning, you can take a venom that we don't know very much about and then find all of these mechanisms and then lead to a drug. So we're screening lots of different venoms, not just snakes. We're looking a little bit closer to home in Australia.

Sarah Crespi
Platypus. Right.

Tian Du
There's platypus venoms. Yeah. Spiders, blue bottles, and australian snakes as well. So I think we sort of want to use this technology more broadly to sort of, there's like, a lofty goal of finding broad acting venom treatments.

Sarah Crespi
That's amazing. And it's perfect for where you live.

Tian Du
Yeah, exactly.

Sarah Crespi
Is it the fact that you're in Australia that made you want to work on venoms, on snakebites, or what attracted you to this area of research?

Tian Du
That's a great question. I think I changed my answer a lot. But I think growing up in Australia, having grown up watching Steve Irwin, really has ingrained that passion in me. I've always loved creepy crawlies as a kid. I'm also a Scorpio, but I guess that doesn't matter at all.

Sarah Crespi
They do have venom. Yep.

Tian Du
Yeah. There's a love of animals, definitely. And being able to combine that with finding things that can really help people is a great thing as well.

Sarah Crespi
Fantastic. All right, thank you so much, Tian.

Tian Du
Thank you.

Sarah Crespi
Tian. Du is a PhD candidate in the John and Ann Chong lab for functional genomics at the University of Sydney. You can find a link to the science translational medicine paper we discussed@science.org.

Sarah Crespi
Podcast and that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us@sciencepodcast.org to find us on a podcasting app, search for Science magazine, or you can listen on our website, science.org podcast. This show was edited by me, Sarah Crespi, and Kevin McLean. We also had production help from Megan Tuck at Potage.

Our music is by Jeffrey Cook and Wen Koi Wen on behalf of Science and its publisher, Aaa's. Thanks for joining us.