What's Your Problem?Dalial Freitak and Annette Kleiser are the co-founders of Dalan Animal Health, a company that has brought to market the first vaccine for insects. Their problem is this: How do you turn a discovery about insect immune systems into a vaccine that can protect the bees we need to grow everything from almonds to blueberries?
Pushkin. How many times have you been stung?
Many?
Ten?
Oh yeah, yeah, one hundred. Probably each season I get a few be stunks. I mean, we do kind of a nasty things to the bee hive. We still want larvae to check the immune priming effects, and they don't like it.
Obviously, I can't blame them.
So you're telling me you had it coming.
Yes, I had it coming. I also sell it to all my students. That's okay, that's normal. Just let me know. If you develop allergies.
Does it make it harder to get students to come work with you?
No, No, not at all.
I'm Jacob Goldstein and this is What's Your Problem, the show where I talk to people who are trying to make tech logical progress. I have two guests today. One is Dhali al Freytech. That's who you just heard. The other is Anetta Claiser. Together they are the co founders of a company called Dalon Animal Health, and they have brought to market a vaccine for bees. It is the first ever vaccine for any insect, and their story is interesting and important on a number of levels, including, but not limited to, how do you even make a vaccine for an insect? Also what's going on with bees these days anyways? And if you can vaccinate bees, what other insects might you want a vaccinate. Annettaklizer is the CEO. She spent her career working in technology transfer, basically figuring out how to turn academics ideas into real world products and businesses. Later in the show, we'll have my interview with Annetta about testing the vaccine and bringing it to market and also what's happening with bees and the bee industry such as it is. But first we're going to play my conversation with dhali Al about the basic research she did that led to this idea of a vaccine for bees.
So when I started to work on insect immunity two decades ago, where was not a lot known about it, So it was a bit. It was really like I would say, in kindo shoes.
Kinder shoes like baby shoes. Yeah, baby shoes.
I think it's in English English interest. I'm sorry, but it was really like the beginnings of it. Basically, it was it was a stage where something is happening, but we don't know what it is.
At some point you get interested in this question of can be's acquire immunity. Can they become immune based on exposure to a pathogen? How does that arise? How does that question arise?
Yeah, that question actually arrived during my PhD time when I've worked with.
Moffs and not with that Okay, yeah.
It was before honeybees. So the observation what I made during the time was like, if a parental generation was growing up in the environment where a lot of bacteria present, the immunity in the second generation was changed. Now, insects do not have antibodies, and we've been looking for for decades we haven't found and they do not exist in insects as we know it today at least, And yet I observe certain transfer of knowledge of immune system activation to the second generation. And it was just like super exciting discoveries, like how is that possible? What is happening? Because they don't have antibodies, so there must be some other mechanism what is at play? And so that's what really caught me kind of fooked in that question. So how does that transfer happen? And that's there. The honeybee was really the model to study for me that kind of helped really to progress and knowledge.
And so so so so you see that there is inherited immunity, right, that offspring have have some kind of immunity that they get from their parents. And the question is how does how does that happen? What's the mechanism exactly?
And so what I actually started to think about when it's like, okay, let's take a step back and let's think how does the parental generation encounter pathogens like American fault root in honeybees? So how do we encounter it? And the answer is very simple. They eat it. Basically, It's it's a kind of like the digestive tract infection, like it would be salmonella in humans. Right, you would eat it in you would get.
Sick, food borne disease. Food. That's how these get infectious.
Disease exactly in this case in American foul broot, that's that's a food borne disease. And so my my next question what happens was what happens with bacteria in the gut And the very simple answer, they get digested, They get cut into little pieces by the enzymes, by digestive enzymes, by immune system. Now, the next question was what happens with the pieces? That was really for me this fascinating discovery where I saw that these little pieces of bacteria are transferred from a digestive system to the body cavity and I was like, okay, cool, and we know once they are there they can activate. These pieces of bacteria can activate immune system. We know that because the immune system receptors are in these parts in the body cavity, and they could trigger an immunity, which is cool. But this would be within one generation. So how would this knowledge of encountering this bacteria be transferred from one generation to a number? So that was a fascinating question.
And I know that to answer that question, you wind up looking at this at this particular protein. It's called vitellogen in right, and it's in eggs, in all kinds of eggs, in b eggs and in chicken eggs. So and you wind up looking at this protein as sort of tea to the way that immunity gets passed from the queen to her offspring. So how did you figure that out?
Yes, so there was absolutely And I do remember this moment. It's it was we had a lab meeting in hell Sinking and then this new post talk in our group. She presented her work on the honeybee Betelo Jenny, and she mentioned in her talk, oh and in fish it's shown that vitellogenny can buy into bacteria. That was like this one sentence and for me it was like, oh my god, this must be my shuttle bus for the pieces of bacteria. So after the lab meeting was over, I asked, can I talk to you for a moment. So I said, hey, I believe that your protein takes my signal to next generation. Do you have some of it in a lab and can we do experiment to prove it. She was like, yeah, well it's a bit expensive, but yeah, I think it's a cool idea that's cue to try. So it was literally us two post dogs. So we ordered a bunch of honey queens and we carried out the experiment and it was it was very exciting. It literally have to say, I mean I could not sleep the night before and then we carried out the experiments and it was exactly as we predicted, so intelligent in verse exactly a protein what takes the pieces of bacteris the next generation. I mean, I think that has been one of the most happiest moments of my life. I mean, I could not sleep entire night. I was keeping the smile on my face. Oh my god, Yes, we did it. We did it.
We did it. We did it.
So from there, how do you get to the idea of making a vaccine?
Good question? I think first we've really focused only on the science and basic research and fundamental results of it, what it means for a science, and it's a preak crough understanding how immunity works in invertebrates and in insects.
And.
And somebody kind of told us, hey, you know, could you use it also in industrial level? So it's kind of like a vaccine, right, And we said, yeah, it's kind of like a vaccine. And when somebody laughed, oh, you should, you know, take it, take it further, and we were like, oh, yeah, we should take it further. And we got in contact with Innovation Services in Helsing University and we pitched our idea to them. And their first question, of course results, is it already published? Can we patent it? And we said no, no, no, it's not published yet. We are preparing publication and we never even thought about patenting it at that moment. And they said, okay, we should patent it, and we would like to take this project further and see if we can make a real world product and the company out of it. And I think from that moment on, I was totally set in it and I was thinking, yes, I want to make it a real world product.
What kind of responses were you getting when you were pitching your ideas.
I think people looked at with a mixture of all, that's really cool idea and like, huh. I still have everywhere and I know it's gonna be a podcast. But whereas this queen cage, I always have it with me. I still have it obvious with me as we're.
Literally holding it up when you just carry it around.
With you, Yes, I do, and have it on my table and my work office, in my home office, in all my bags then I travel, so I would say, no, it's not injection, it's oral vaccine. You see, this is where Queen Bee's held, and this is where vaccine will be.
And just to be clear, you're holding up a little sort of transparent plastic case, maybe a little bigger than a pack of gum, about the size of a pack of gums, say, with little airholes presumably, so you put the Queen Bee in there and the holes are so the queen can breathe exactly.
That's what I've been pitching for past uh a few years, and Annette was one of the people I pitched it to and I convinced her.
Annette is Annetta Claiser, the person who wound up being Dhaliel's co founder at Dalon Animal Health. In fact, Dalan is for dahali Al and Annetta dal On. We'll be back in a minute to talk with Annetta about how she and dhali all turned Dhaliel's basic research into a vaccine that has now been used on millions of beats.
My name is Aneticizer and I'm the CEO of DNA Animal Health.
How did you get into the bee vaccine business?
By complete accident? It was a complete accident. I was at the University of Helsinki in twenty eighteen to visit DA Frighttack happened to be in the office while I was visiting, and the director called her in and said, you have to meet these folks and tell them about your b vaccine. And so she presented to us. She came into the room and I was just amazed. I was just say, we all know bees are dying we all know they're essential for our survival around the world. It's a big issue, and we all throw our hands up and here is somebody that has an idea, yet very early stage, but still you know it was it was an idea that that we had to take. And so we got together and we talked, and a few months later we decided to start a company and give it a try.
So you had been working in technology transfer for years at this point, right, and sort of essentially helping universities turn scientific ideas into companies. You had never jumped ship before. You had never seen an idea that made you say, holy cow, I'm gonna quit my job and go all in on this one idea. Why this one?
Because it was so different and so urgent and so important. It was not an incremental improvement over existing technologies. This was fundamental. This was a game change. I mean, we all talk about game changes in innovation, but here there was a true game change. And yeah, you're right. I've been doing this job of looking at innovations for fifteen or twenty years and people often said, well, one day you're going to see this one thing, you know, And I love my job. I get to see different things all the time, and it's fantastic, all this innovation, all these amazing ideas, and I get to be part of all of them. But this couldn't wait, and it's it just grabbed me. It grabbed me, and it was clear from the moment I saw that I had to do it.
Let's talk about let's talk about the b industry for a moment. Let's just do that. I know almonds are a big deal, but I want to even start zoomed out a little bit more. So. There was this moment some years ago when everybody was talking about colony collapse and there was a certainly alarming, I don't know whether it was alarmist kind of discourse about oh my god, bees are gonna go away, and then we're gonna be screwed because we won't be able to grow food anymore. Plainly, that didn't happen, right, Like what First of all, what was the deal with that? And what happened?
So we lose about on average forty to sixty percent of hives every year, and.
It's it's has proved sustainable just because people are able to create new colonies constantly.
However, it gets more and more expensive Okay, the labor costs, the restoring the colonies just it's it's pushing, it's really putting a strain on beekeepers.
Okay, the worst case scenario did not come to pass, but we're still losing lots of colonies every year, far more than the historical more. That's the state of play now. On the sort of be pollination industry side, on the demand, like, what is the market for honeybees? Who is who is paying beekeepers to bring their hives to the fields every year? What's that market look like in the in the US, in North America.
Well, eighty percent of the world almonds come from California. So in almonds are just a whether it's through almond milk or in Massaban.
From my point of view, kind of a niche youth but go crazy, yes.
But apparently almonds, you know, used around the world, and they don't grow without Without honeypots, there would not be a single almond. So California brings in on large semi trucks several million hives every year from across the country to pollinate for six weeks. They're put into the almond orchards and do their thing, and so you have it is like it's like a big you know, airport, like where many you know, bees mingle and mix and they you know, they spread diseases and they and they spread diseases, you know, not among themselves, but also to other insects. After the islands, they then go to Washington's for the apples, then to the pumpkins, and over to Maine for the blueberries. They go off and on the semi trucks and are shipped across during the pollination season until they end up in the center of the country or in the you know, like the Midwest, where they then start honey production. Interesting, so once the pollination season is over, the honey production starts, and that's the food industry.
And so it's the same colony like traveling around the country, presumably multiple generations of bees the same colony. And as it's sort of an endless loop, it's like a traveling it's like being on the road like rock stars or a circus.
Or something that's exactly right. So it gets kicked off. The season gets kicked off in February in California with the almonds, and then they just travel around and it ends in October when they're ready for their winter hibernation and get this stay either go into cold storage where it's big warehouses, and then all starts over again.
Go back back to California for the almonds. Okay, so that is the context as far as bees go or bees in the United States's let's go back to you and dhali all starting the company. You meet her, You guys decide to turn this basic research she's done into a company into a real thing. Like what's the state of play? What are things like when you start the company?
So yeah, so her lab was closed out. She was on her way to accept a position or had accepted a position in Austria at the university, so there was no lap. There was a pending patent application that the university had filed, and that was it. And I had her brain, and.
You had her brain and a pending patent. That was the.
Company exactly right. And so we petitioned the university to give us to licensees the technology so that we could find found a company around it and also start raising money to finance this endeavor. And then we had to develop a regulatory path for getting something like this approved. Now, if this was a chicken vaccine or a human vaccine or a dog vaccine. We would know what the regulatory path would be, we'd know how many animals we'd need, we'd know how to manufacture it. We know everything has been done before one.
Hundred and fifty years, right, like Pasteur made a chicken vaccine and a dog vaccine before he made a human vaccine.
Yeah, so he and none of this existed. There was no regulatory framework.
Nobody ever made a vaccine for an insect.
Before it had ever done this before.
So tell me about the disease that you want to vaccinate against.
It's called American fowl root.
An fowl brood.
Our root, and contrary to its name, it actually exists in every country around the world, and it is very contagious. It's like anthrax for bees. So a few spores in a hive are sufficient to wipe out your colony. Highly contagious, and if you do contract the disease, you have to pour gasoline over the colony and burn the hive, the colony, all your equipment, everything that came in touch with it, and buried under the ground.
So it's like biblical that's like a biblical injunction, or is what all of the bees die.
Basically everything dies and you e suit your equipment because everything that came in touch with this contaminated hive is now can pass on the disease to another hive. So it's and then and in some countries all the hives that were in a two mile radius have to be quarantined, so moving restrictions. You can't you know, you can't do anything with them anymore. So it affects your neighbor. It's also very costly. You know, the flowers don't wait if you need to make honey, if you need to pollinate, and the disease hits your neighbor and all of a sudden, you can't put your hives into the almonds or the pumpkins. You lose half of your annual income. And so it's just a really devastating disease. And DAYA had convincing data on it, so we said, okay, let's go after American fower root and see if we can tackle this as our first trial vaccine. And so we generated new data. We had our elite candidate for the vaccine, and we set up a meeting with the USDA to make our case, which was the first step that this is a vaccine and not something else, and that what we're doing is actually giving in a controlled way this dead pathogen and it activates the immune system and the animals are protected.
Presumably when you're going to the USDA, the number of people who knows how to do is be vaccine trial is zero. Nobody's ever done it, always ever thought about it before as far as I know. So, like, you've got to actually make the vaccine right, So what is that?
So you take your pathogen, okay, and you grow it up because it's a bacteria, it grows.
In case this is the terrible American foul brood. You're growing American foul brood in the lab, no.
Lamb, and then you you inactivate it. Okay, you kill it so it's dead, dead, and you make sure it's absolutely there's nothing in there that survived.
Now you have the vaccine and you need to test it, right. You need to essentially do a clinical trial. But it's a clinical trial of bees to see if the vaccine works on them. And my understanding is you have to start by vaccinating the queen bee. And I'm curious just how that happens.
How do you do that their queen produces queen breeders that make a queen, and then they the queen mates flies around in her amazing flight. Then they catch her and put her into little claps plastic cages. They're called queen cages, and with a few nurse bees. These are young bees they have just hatched, and those bees feed royal jelly to the queen.
They're called nurse bes.
And these nurse bees are in the cage with her, and in the cages of sugar paste, which is made of powdered sugar and corn syrup or powdered sugar and water, so different, but it's a it's a sugar paste. And we put our vaccine, which is a liquid formulation, into this sugar paste, and the nurse bees will eat it make royal jelly out of and the royal jelly now has pieces of the vaccine, and that's what they feed, Okay, because the queen doesn't like to eat herself.
She needs to be fun, amazing like like a true queen. So so you give the vaccine plus sugar paste to those nurse bees. They eat it. They make royal jelly with vaccine in it for the queen. Then the queen eats that royal jelly, and then what happens.
So we have like fifty queens sitting there. Some of them get vaccinated, others get not vaccinated. Research it doesn't know which.
One randomize a good randomized blinded trial.
We put them now out into real hives.
Okay, out in the world. Out they're going to work.
They go out into the world, and then we wait and the queen will emerge out of this little cage and the hive. If the hive accepts her, she will start laying eggs. And after a few weeks we will go into the hive and take frames where the queen has laid the eggs and bring them back to the lab and will take one day old larby the researchers always tell me, you know when they're one day all when you barely can see them or not all. Okay, tiny tiny larvae, And these brood diseases like American firebroot, they only hit the larbe in the first three days once you make it, like infant diseases, so you can only get sink when you're a little child, but not later. And that's the same here. So we need to get these one day old larvae. They put them in a little pittri diish, feed them with larval food, and bombard them with disease.
So what do you find. So you have your control group and you have your vaccinated group. They're getting bombarded with foul brood. What happens?
And we had between thirty to fifty percent higher survival in the lab. And so based on that, and based on all the aspect of vaccine development, of purity and safety and all of this, the regulator said, okay, we're going to give you the market approval and the uscilization to sell on a conditional basis. So we started selling. We shipped the first vaccine in May of last year to.
May of twenty three and how's it going. How's it going now?
It's going well, it's going well. It's It was interesting because we didn't do any advertising, We didn't do any promotion around it because we felt it was such a new tool and we were such a small company that we wanted to really work on the ground WI speekeepers to introduce this new product to see how does it integrate into their operations.
Like where are you now? How many how much vaccine are you selling? How many bees are getting vaccinated?
I think they are probably twenty to twenty five thousand hives colonies vaccinated.
Out and you sell in the US and Canada, Is that right?
Yes? In Canada.
So you you found in the lab in these sort of very harsh, intense lab conditions that the vaccine reduced infection by thirty to fifty percent. Do you have an estimate of its efficacy in the field.
Well, so far none of the colonies out there have tested or tested positive or have shown American fibers.
And you have tens of thousands of colonies have been vaccinated and the number that have been found to have American fabrit is zero, So that seems good.
Yes.
Do you have a next animal that you want to try and vaccinate after bees?
Shrimp?
Shrimp? Is that because shrimp are farmed for food? Is that the setting where you would vaccinate shrimp?
Yes, it's food security.
Yeah. And so is there a particular shrimp pathogen that you're working on.
It's it's white spots syndrome, it's a virus and rabiosis, which is a bacteria.
Like more or less. When do you think you'll apply for approval for shrimp?
Probably in if we're lucky, in if we're lucky in two US three years. So because we have shown that we can vaccinate and protect a wild animal from viruses, from deadly viruses. We've shown that we can protect a honeybee from bacterial diseases and from fungal diseases. So we can show that this is possible in insects by activating the innate immune system. We believe and we know that this immune system is conserved across invertebrates. We believe we can use that same approach for shrimp, for mosquitoes, for our kind of animals that currently have that we rely on shrimp and bees that are extremely important for our food security and have no non chemical sustainable ways to protect them. And then beyond that, take it into areas that for these infectious vector based infectious diseases that have a huge impact on human health. But we also don't have anything. So it's really estalin. We want to open up this entire space and really harnessing the power of this immune system that is completely neglected.
Are you talking about mosquitos, because the notion is you could vaccinate mosquitoes against the pathogen that causes malaria. Is that the idea there that's the idea any mosquito transmitted disease, if you could vaccinate the mosquitos, they wouldn't transmit the disease. So are you working on that one?
That would be my next one. We're not working on it yet.
We'll be back in a minute with the lightning ground. Okay, let's do the lightning round. What was the best idea you ever saw before you met Dahlia?
It was a refrigerator, a freezer where you could freeze fruit without becoming a mushy.
Whatever happened to that idea?
I have no idea, so as.
I understand it. You grew up in a wine growing region in Germany and you're into wine, and so what I always want to know is what's a good cheap bottle of wine that I can buy?
Ooh, I mean, I'm I'm partial to actually Spanish wines.
Like a rioja, Like what should I buy?
Or they are just amazing, amazing wines.
What's one surprising thing you've learned about bees since you started the company?
Seeing well, the TransGeneration immune priming is pretty.
Well, that's the big one. That's the big one obviously, But are there any other just like weird be facts that you know now that you didn't know before.
I think understanding or looking at the super organism how it works together.
Superorganism is this idea that the colony, the entire colony, is sort of like an animal.
Like one animal. Yeah, the individual cannot survive on its own. It needs everybody in the society of these to make it, to share information, to keep each other warm, to feed each other, all of that, And that's just amazing to see every single every single day.
Another cliser is the CEO of Dolla and Animal Health. I also did a lightning round with her co founder, the company's chief scientific officer, Dali al fright tag. Here's that part of the interview. Now to close the show, what's your second favorite insect?
And different ants? I cannot pinpoint one species of ant, but yeah, why why ants?
What's fascinating about them?
They have so many different adaptations, you name it, they have it. They can wage wars at each other. They can count the size of the opposite army. Literally, they know if the opposite side is too beak, they need to run away. If it's smaller, and they they will engage in the battle. They build structures, they build houses, they have farming. They are fascinating, absolutely fascinating organism group.
What should I do to reduce the risk of getting stung by bee?
Don't go close to beehives?
Fair enough?
Well, Also, the other thing, what I would recommend if you have a bee close to you, do not panic, do not start waving around. So keep your calm and bees appreciated.
What's one thing most people get wrong about bees?
I think a lot of people believe that the honeybee queen is the one who rules the colony. I kind of strongly disagree with that. I think it's the workers who are ruling the high because as soon as queen is not performing balling off anymore, she's gonna be removed and the new queen will be raised. So it's really all for a hive, all for the common good, and it's not so much about her, it's about the hive.
So is a b colony a socialist paradise?
Yeah, I guess you could say that. It's definitely. I would not say it's a monarchy. Ooh, it sounds like that. I don't think.
So the queen is working for the workers, yep.
I mean she gets to leave a high once in her life, rest of the time she spends inside and needs to produce offspring. As soon as she fails, she will be replaced.
Yeah, she's got one job.
She's got one job.
Today's show was produced by Gabriel Hunter Chang. It was edited by Lyddy Jean Kott and engineered by Sarah Bruguier. You can email us at problem at Pushkin dot FM. I'm Jacob Goldstein and we'll be back next week with another episode of What's Your Problem.
