Episode Transcript
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Dr.Moira Gunn (00:11):
You know that
recent news story about the
fellow who deliberately lethimself be bitten by venomous
snakes and the scientist whoturned his blood into the most
powerful antivenom ever? Thescientist is biotech
entrepreneur, doctor JakeGlanville, and he's here today
(00:32):
to take us from his firstconversation with the gentleman
through to the creation of anunprecedented antivenom. It's a
great science story, and it's agreat biotech story. Doctor.
Glanville, Jake, welcome back tothe program.
Dr. Jake Glanville (00:48):
Moira, so
good to be back talking with
you.
Dr.Moira Gunn (00:51):
Now many of us
have heard the news that a man
had intentionally let himself bebitten over 200 times by
venomous snakes. And I must saymany of us said, what a terrible
idea. That just sounds awful onfifty fifty counts. But I know
you had a different reaction.And before we get to that
(01:12):
reaction, remind us all aboutthis man and what he did.
Dr. Jake Glanville (01:17):
Yeah. So Tim
Friedy is a man from Wisconsin
who, for seventeen years andnine months of his life, he
collected venomous snakes fromaround the world. He injected
himself with six fifty fourdoses of escalating venom from
cobras, taipans, black mambas,common kraits, western
(01:40):
diamondback rattlers, and anumber of other species, until
he had built up enough immunitythat he then would allow these
snakes, snakes that wouldnormally kill a horse, to be
able to bite him, to demonstratethat he developed universal
immunity to snake venom.
Dr.Moira Gunn (01:55):
Now while many of
us didn't hear about him till
last May, you heard about himearlier. How did you hear about
him? When was that? And whatidea came to you when you heard
the story?
Dr. Jake Glanville (02:07):
So I first
got in contact with Tim Friedy
in 02/2017. My day job isworking on universal immunity in
the area of universal vaccines.This is this emerging
appreciation that unlike ourcurrent vaccines that work
against a single strain, so forinstance, a flu shot that you
(02:30):
take, and then they change thestrains next year because the
flu mutates. And the same ideafor coronaviruses, and really
the same reason we don't have aworking HIV vaccine yet. The
idea was that these viruses havethese Achilles heels, these
conserved spots that are unableto mutate.
And if you can just teach theimmune system to target those
(02:51):
conserved spots, then you'd havea vaccine that worked against
not just one strain, but all ofthe strains, a universal
vaccine. So I was working onthis, and around that same time,
the World Health Organizationwas starting to sound the alarm
about snake envenomation as aneglected tropical disease that
affects actually a large numberof people, but there hasn't been
(03:14):
nearly enough investment in thedevelopment of antivenoms. Part
of the problem is there's a hugenumber of snakes, kind of like
there's a huge number of flustrains, and those snakes have
different venom. So I startedthinking about it, and I was
wondering, I wonder if the samebiology that makes universal
vaccines possible, I wonder ifthat might also be true of
(03:35):
venom, that they might havethese Achilles heels and we
could target them. At the time,I had worked for four years at
Pfizer doing antibodyengineering to use antibodies as
drugs, and then I had created acompany called Distributed Bio
that was also doing that.
One of the key things you learnfrom doing this kind of work is
(03:56):
that you really prefer to havehuman antibodies as the basis of
a medicine. Anti venom is notmade from human antibodies. It's
historically made from animalslike horses that are envenomed
repeatedly from snake venom, andthen their antisera, their
blood, essentially is theproduct. This was very crude
technology that's been aroundfor January, and yet if you have
(04:18):
the right antivenom for thatright snake, it can save your
life. But of course, you'drather those antibodies be
human.
And so I thought, I wonder if Icould find a person who has I
could start searching throughtheir immune system and find
some of these universalantibodies. We call them broadly
neutralizing antibodies. And soI was searching around.
(04:38):
Originally, I was trying to finda clumsy snake researcher who
may have been bit a couple timesbecause they're basically
getting vaccinated each time youget bit. And I was hoping that
would be an okay place to start.
And it would have had problemsbecause just like getting one
flu shot, they probably wouldjust make antibodies against
that one snake, and and that'sthe same problem that the horses
(04:59):
have. That's why antivenoms onlywork against one or a couple
species. But then I as I waslooking, I found these amazing
articles about this guy, TimFriedy, who had this astonishing
history. Not only had he had ahuge number of snakes he was
exposed to, I was looking at itas a vaccine scientist, and I
was like, Wait a second. Becausehe kept rotating between these
16 different species from everycontinent, that suggested to me
(05:22):
that if anybody anywhere hadbeating through their veins the
secret of a universal antivenom,it would be this man.
And so I knew I had to get incontact with him.
Dr.Moira Gunn (05:31):
So how did you
find him? I mean
Dr. Jake Glanville (05:33):
It was
tough. This guy was not
motivated to do this forattention, so he wasn't anywhere
on the Internet. The only thingI could find were these
articles, and there was, like, acouple YouTube videos about it.
And so I eventually got incontact with him by contacting
the the reporters. And I said,hey.
Look. I really wanna be able toto talk to this guy. And so one
of them eventually put me intouch. And and I remember the
(05:55):
first phone call, you know, Icalled him, and, and I said, you
know, this this might be anawkward question, but I would
love to get my hands on some ofyour blood.
Dr.Moira Gunn (06:05):
I want your
blood. Right out there.
Dr. Jake Glanville (06:09):
Yeah. Well,
you gotta you gotta that's what
you know, you gotta shoot yourshot. And, you don't know how
someone's gonna respond to aquestion like that. It's a
little vampiric. But the coolthing was that his answer to me
was, I've been waiting for thiscall for a long time.
And what I realized about Timwas that he had done this for
that entire period of time toprove that it was done, but his
(06:31):
goal was to then get researchbecause he felt and was
anticipating that he hadsomething special in his blood,
and if the researchers looked atit, that they could create a
universal antivenom. So he wasanticipating this problem, and
that was one of his majormotivations for doing what he
did. And so I immediately said,okay. Well, how do we start
collaborating to do this?
Dr.Moira Gunn (06:47):
So now the
science kicks in. First of all,
you have to check his story.
Dr. Jake Glanville (06:53):
Yeah. So
first, we had to spend, you
know, four months doing someboring but important stuff,
which was we needed to make surewe had an ethical study design.
What Tim does is inherentlydangerous. To state the obvious,
do not do this at home. Venom isnot safe.
And so when we were doing thestudy, we needed to make sure
(07:14):
that we didn't do anything thatimposed any additional risk to
him. And so what we settled onwas a non interventional study
design. This is the same kind ofresearch design people do when
they're looking at HIV patientsor high risk people for various
reasons. And what it was wasthat we weren't going to give
him any feedback on what venomsto take or how he had his
(07:36):
existing process, and we weren'tgoing to touch that at all other
than to send him documents thatsay, Hey, snake venom's
dangerous. You know, he waslike, Yeah, thanks.
Thanks for the tip. And then wewould just take two blood draws
twenty eight days apart, as partas he was doing his standard
maintenance self immunizations.
Dr.Moira Gunn (07:53):
Oh, he was
continuing to to get bitten and
immunize himself?
Dr. Jake Glanville (07:58):
During that
time, yeah. He had retired by
02/2018, but we drew the bloodwhen he was still doing it. And
so once we got the frameworkfigured out, that includes
setting up, an informed consentto draw the blood and requesting
an IRB. There's some things youdo. There are paperwork to make
sure you can study a humansubject.
Then we we drew two twentymilliliter blood draws. That was
(08:20):
the basis of all that research.It was shipped to my
laboratories. A coupleinteresting things you find when
you do this kind of work. One isthere are these mobile blood
drawing units that you can sendto somebody's house pretty much
anywhere in America, and theywill draw someone's blood for
you with the right paperwork,and then they'll send it to your
laboratory.
So that was cool. Then we gotthe blood in our lab. His story
(08:44):
was impressive, but I'm ascientist. I wanted to check his
work. And so personally took hisblood and spun it to separate
out the cells that had the DNAfor the antibodies from the
serum, that clear liquid that'sin your blood when you remove
the cells, and that's what hasall the antibodies in it.
And I wanted to make sure thathis serum actually had
antibodies against snake venom.And so I had gone out, and it is
(09:10):
much easier than you might thinkto get ultra lethal snake venom.
There are many differentproviders that can just send it
to you. It's one of theinteresting things I've
discovered in this project. Andso I had a panel of cobras,
taipans, black mambas, westerndiamondbacks, and so forth, some
of which he had a history ofself envenoming with and and
(09:33):
some of which that he said henever had self envenomed with.
And so I took his serum, and Itook my own serum and some
control serum and tested them.And sure enough, uniquely, his
serum lit up like a Christmastree, a bunch of antibodies
binding to these snake venoms,whereas mine or other people
that don't do what Tim does,they had no reactivity. And then
(09:53):
critically, the snakes that hesaid he'd never been exposed to
lit up as well. And that got mereally excited because that
said, Oh, I think that thatmeans that he had done what I
had hoped had happened, whichwas that he had developed these
antibodies that recognized thoseAchilles' heels, which means
they didn't just recognize thesnakes that he was exposed to,
but they recognized all of theother snakes that he hadn't been
(10:13):
exposed to, and therefore helikely has the recipe for a
universal antivenom in hisblood.
Dr.Moira Gunn (10:18):
You're listening
to Tech Nation. I'm Moira Gunn,
and my guest today is JakeGlanville. Doctor. Glanville's
background includes being aprincipal scientist and
computational biologist withPfizer, a co founder and CEO of
Distributed Bio and a multiplerecipient of Gates Foundation
grants, one for the grandchallenge ending the pandemic
(10:41):
threat. You might know him fromthe Netflix docuseries,
pandemic, How to Prevent anOutbreak.
A serial bio entrepreneur,doctor Glanville is the founder,
chairman, and CEO of Scentivax.Well, Jake, now you've got all
of these antibodies, and I meana lot. You tell me you built a
(11:05):
big library of of Tim'santibodies, and by that, you
mean 2,000,000,000 antibodies.
Dr. Jake Glanville (11:14):
Yeah, so the
way the immune system works is
that your body produces atremendous number of different
antibodies. Many of these arejust lying in wait in case
they're ever useful. So when youget infected by any new virus or
bacteria or whatnot, somewherein those hundreds of millions of
antibodies, there's one thatcould be useful to you. The
(11:34):
challenge is fishing out the oneyou care about. When we got the
blood from Tim, I had separatedout the serum which we tested,
and then I had the cells, andthey contain all of the DNA that
encodes all of those differentantibodies.
We took out that DNA, and thenwe created what's called an
antibody library, which wasthose 2,000,000,000 antibodies
from TEMs, and essentially asnapshot of Tim's immune memory
(11:58):
of snake bite, but alsoeverything else that he'd been
exposed to it through in hiswhole life. Now we had it stored
in chest tubes that we couldbegin searching through over and
over again. We used a technologythat won the Nobel Prize in 2018
called phage display to do this.The good news is you've got
everything in there. The badnews is that it's the ultimate
finding a needle in a haystack.
(12:18):
And the good news is there'stechnologies to address this. So
what you do is you take thatlibrary of 2,000,000,000 things,
can bind all manner of stuff,and you want to go fish out the
one you care about. And the waywe did that is that first we
took the long neurotoxin that'sone of the key toxins in
neurotoxic snake venom, and weproduced it in our lab, and we
(12:40):
added a little tag, a tether,that we could then attach to
magnetic beads. And so that way,we have the toxin being
displayed off of magnetic beads.And we mix the library with
these beads, and then we washaway everything else that
doesn't bind.
And so only antibodies that bindto the long neurotoxin remain.
This is called panning aftergold panning. And so at that
(13:02):
point, have antibodies, and wechose to start the cobra
neurotoxin. So we have all theantibodies in his immune library
that recognize the cobraneurotoxin. But I wanted these
universal antibodies.
So then what we did next is wetook those antibodies, and then
we did the same thing but thistime with the Taipan neurotoxin.
And then we did the same thingbut with black mamba neurotoxin,
(13:24):
and finally a krait neurotoxin.Each of these is a very
different neurotoxic snake, andso by cross selecting, by
picking the antibodies not justthat bound a neurotoxin but
bound all of these four verydiverse neurotoxins, we were
trying to find these broadlyneutralizing universal
antibodies. Now, if he didn'thave them in his blood, then we
(13:44):
would have come up short. Therewould be nothing left after
doing that process.
But what we found was that therewas this very potent population
of antibodies, and one of themwas very dominant, and we named
it D9.
Dr.Moira Gunn (13:54):
D nine? Why D
nine?
Dr. Jake Glanville (13:56):
You call it
D nine because there's a you
work on these 96 well plates,and there's letters for the for
the rows and numbers for thecolumns. And so that particular
clone happened to come out ofrow d Column nine, and so we
called it D nine.
Dr.Moira Gunn (14:11):
There's no
denying it. It had to be D nine.
Okay. So now you have to go toanimals. What did you do?
Dr. Jake Glanville (14:24):
We had D9.
We knew it bound very large
panels of snake venom. We testedagainst probably 30 or 40
species at the time. And so wewanted to go say, okay. Not only
does it bind, but can it protectan animal?
And so what we did is we tookthe one toxin by itself, and we
gave it at a dose that normallywould not be survivable for a
(14:46):
mouse. In fact, we gave fourtimes the dose where that venom
toxin would normally kill themouse. But we also administered
D9. And what we found is withD9, the mice could tolerate it
perfectly well. And we reallyfound that for pretty much every
long neurotoxin that weassessed.
And so that was exciting, but D9binds to long neurotoxin, and
(15:07):
snake venom does not justcontain one toxin. It contains
multiple different toxins. Andso our next step was to ask, I
wonder if that one antibody byitself would be enough, against
whole venom from some snakesthat matter. And so there we at
some cobras, we looked at blackmamba, and the king cobra,
which, fun fact, is actually nota cobra. It's named because it
(15:29):
eats cobras.
It's a different geneticallydistinct group. And those venoms
have a lot of long neurotoxin.It just happens to be that their
particular cocktail heavilybiases towards the long
neurotoxin is the dominantreason that that snake will get
you. And in those, we were ableto give a lethal dose of the
full venom from those snakes.And that one antibody by itself
(15:50):
was able to protect the animals.
And that, that was prettyastonishing. It, it wasn't true
for many of the other snakespecies, but at least already
for six, you could show that theone broadly neutralizing
antibody was A, very broad, andb, was able to provide relevant
protection, not just against thetoxin, but in some venoms
against the whole venom and venenvenomation. And that got us
extremely excited because itsaid, we just found a broadly
(16:13):
neutralizing antibody. Thatmeans that this is no longer a
viral phenomenon. This is truefor snake venom.
And because we found one ofthese and because Tim is not
dead, that tells me that heprobably has more of these
broadly neutralizing antibodiesin his immune library. And if we
keep searching, we could buildup a universal antivenom.
Dr.Moira Gunn (16:31):
Now as can happen
in many science stories,
suddenly another scientistappears, and it did this time.
Enter doctor Peter Kwong. Who isdoctor Peter Kwong, and how does
he play into this story?
Dr. Jake Glanville (16:46):
So Peter
Kwong is an American scientific
luminary, particularly in thearea of universal vaccines and
broadly neutralizing antibodies.They say in science that you
stand on the shoulder of giantsto take the next step, and in
many respects, the work I wasdoing was based on standing on
the shoulders of Peter Kwong. Hehad broken open the story of
(17:08):
these broadly neutralizingantibodies for HIV, and it
demonstrated that they couldexist, and therefore that a
vaccine for HIV could beplausible, as well as his work
on making critical advances forenabling the RSV vaccines and
other areas. So I knew ofPeter's work, probably it was
(17:28):
the case that because of havingread his work, I was able to
wonder whether snakes could alsohave broadly neutralizing
antibodies in the first place.What happened in 2019 was that I
was awarded a Gates FoundationGrand Challenge in the Pandemic
Threat Award for my universalflu program.
I was invited to come to theGates Foundation and attend a
(17:50):
dinner. One of the otherawardees was Peter Kuang for his
program, and we were sittingnext to each other. Of course,
I'm sitting next to the guy, andso I said, Hey, Peter, would you
be interested in hearing about abroadly neutralizing antibody
story that is not involvingviruses. In fact, it's not even
involving a pathogen. It'ssnake, snakes, and snake bite.
(18:13):
And so he was immediatelyintrigued, fascinated. He's
like, okay, we gotta collaboratetogether. And so he and I began
collaborating on advancing theprogram, which had dramatically
accelerated the pace of what wewere doing.
Dr.Moira Gunn (18:25):
And at this
point, you thought, Well, we
have enough. We must publish.And you went to SELL, the highly
regarded peer reviewed journal.And what happened then?
Dr. Jake Glanville (18:35):
Yeah, so we
sent it in to Sell, and we sent
it in to an editor to just gettheir temperature on, Is this
something you'd be interestedin? And they got back to us and
said, Look, this article made myafternoon, it's super
fascinating. They said, But, youknow, I think you could do more.
The article you're describingwas a single antibody, and it
(19:00):
broadly binds to this one toxinclass, but it actually only
broadly protects against alimited number of species
because most of the other snakeshave other toxins that will
still kill you. She said, Inyour discussion, described how
this, in theory, would enableyou to add more broadly
neutralizing antibodies and makean actual broad spectrum
cocktail that could work againsta vast array of snakes.
(19:21):
She's like, I think you shoulddo that. I think that the cell
readers would see that and notjust see an idea, but actually
see the formation of a productthat could change the world. And
so Peter and I, you know, welooked at each other and we
thought about it, and on onehand, it was a risk, right?
Because it was a big lift, andwhile we were trying to go reach
for that big lift, someone elsecould come along and scoop us,
(19:42):
which means publish first, onthat one antibody or something
like it. But on the other hand,we agreed with the editor.
She was right. That was a muchmore consequential goal. It was
really what our goal was anyway.We were building towards that.
And I felt like the risk wasn'tthat bad because, again, I look
over and I'm like, Well, Tim'salive.
That means those antibodies arein there, and so I think we can
find them. We took a calculatedrisk. We said, Let's keep going,
(20:07):
and so we kept looking, and weasked, Okay, what's that next
next important toxin in therethat gets you if the long
neurotoxin doesn't? And thesecond neurotoxic snake toxin is
short neurotoxin. In fact, thoseare the two primary toxins: long
neurotoxin and short neurotoxin.
And so we fished around, andsure enough, we found a broadly
neutralizing antibody thatknocked out all short
neurotoxins as well. And when weadded those two together, then
(20:29):
suddenly there was a whole bunchof additional species that were
protected. When we were doingthis work, we decided, You know,
we want to test against a largepanel of venomous snakes. And so
we went to the World HealthOrganization and their category
one and category two list of themost medically relevant snakes
for humans. This is a long listof all the six fifty species of
(20:52):
snake.
There are almost 100 that fallinto this category. I wanted to
pick ones that weregeographically diverse, spanning
every continent that has snakes,genetically diverse. Those 19
members represented all of theremaining 300 species of
neurotoxic snakes, and I wantedthem to be the hard ones. I
didn't want to pick easy venomsthat would be easy to protect
(21:15):
against. Wanted to pick thereally tough stuff to show off
how this could be abreakthrough.
And so, we picked this panel andwe started testing our cocktail
on the panel, and as we added inthe short neurotoxin, then
suddenly we were hitting a wholebunch of additional snake
species. Some snake specieswhere short neurotoxin was
actually the dominant toxin, andsome snake species where you had
to hit both long and shortneurotoxin, and only by knocking
(21:37):
out both of them together whichyou have protection. And then
finally, we went after thisthird toxin, which is important
for the long neurotoxins. Weused a small molecule chemical
for that, and when we added thatin, then suddenly we had
protection spanning the entireset of 19 species, with complete
protection for 13 species andpartial, which means the animals
were living longer and some ofthem were surviving, but it
(22:00):
still wasn't perfect for theremaining six. But that already
was an astonishing breakthroughin terms of the breadth of
coverage that a an antivenom hadever been able to be
demonstrated.
And so we returned that over toCell, and ultimately, was what
was published.
Dr.Moira Gunn (22:14):
So a hundred and
twenty five years ago, we got
this way of dealing withantivenom, and we've been using
it ever since. And now we haveanother way of dealing with
snake bite. What are all theadvantages now of being able to
do it this way?
Dr. Jake Glanville (22:32):
Yeah. So a
universal antivenom has a number
of advantages, particularly ahuman universal antivenom of a
limited number of components.The first and most obvious is
that right now, there are sixfifty species of snake around
the world, venomous snakes. Theycause a lot more bites than you
might think if you live in TheUnited States or Europe. The
(22:53):
world has something like fivemillion bites a year.
About one hundred and fortythousand people die, and then
there's three hundred thousandto four hundred thousand that
are losing a limb, becomingpermanently disabled. And most
of those people, they'revillagers, they're subsistence
agriculturalists, or they'rechildren. There are places where
you can't really afford to havea family member that suddenly
(23:13):
needs caring for instead of themhelping care for the family. So
it can be pretty devastating.It's also the case that most of
these bites are happening in thedeveloping world, so there's not
the same kind of economicincentives for people to go out
and make huge amounts of moneyfor these anti venoms.
Finally, the problem is that youneed a different anti venom for
(23:33):
every different snake, or maybea set of very similar snakes.
And so there's some 30 to 40products that exist out there,
different anti venoms, thattreat different local
geographies, but most of thesnakes have no antivenom. And
even for the ones where you havean antivenom, it will probably
work better in one area. If yougo into the neighboring country,
(23:53):
their snakes have evolvedenough, they're different
enough. Even if it's the samespecies, it won't work as well.
And then finally, theantivenom's made out of horse
serum. And as you could expect,when you are, injected with a
whole bunch of horse serum, yourimmune system's going to freak
out. You get an allergicreaction. One is called
anaphylaxis, and the other one'scalled serum sickness. And it's
been considered worth it becauseit's not as bad as the snake
(24:16):
venom, which will kill you, butthey have to give you a whole
bunch of medicines to helpmanage the pretty tremendous
side effects of your body beinglike, What are all these
antibodies that are not humansuddenly in my veins?
So universal human antivenomsolves all of that. So instead
of the current problem, as tobreadth, where someone gets bit,
(24:36):
imagine that you are in avillage and you got bit. Your
experience is you're going tohave to hike or be taken back to
a place where someone can giveyou an IV. And in some cases,
that could be four hours beforeyou get there. It needs to be a
place that has refrigeration,because the antivenoms have to
be administered throughintravenous infusion, IVs.
And the bigger problem is thatyou show up and they go, Oh, I'm
(24:59):
sorry you were bit. Did youhappen to have the presence of
mind while you were being bit byan ultra venomous snake to go
wrestle around the grass andfind the snake and put it in a
doggy bag for us, or at leasttake a picture so that we know
what species bit you so that wecan check if we happen to have
in stock any non expiredantivenom, even if even exists
(25:20):
for that particular class ofsnake. Obviously, that's not
always satisfied. So a lot oftimes, people don't get any
antivenom. And then if they getit, they have to treat all the
side effects.
A universal antivenom gets ridof all that. You go in. No
matter what you've been bitwith, they can give you the same
product. That actually solves aglobal macroeconomic issue as
well because it unfractures amarket where suddenly, instead
(25:42):
of 30 to 40 products, you'recreating one product to service
all snakes. And suddenly thatbecomes more economically viable
to produce that product yearafter year.
Look, this is never going to bethe same value as a blockbuster
cancer drug that first worldpeople will pay huge amounts of
money for. But it's a very largenumber of people, and you can
make it profitable, and thatmeans it can be sustainable and
solve some of the problems ofpharmaceutical companies
(26:04):
divesting and working onantivenom. So the second thing,
in addition to it working on allsnakes, is that because it's
human antibodies and just acouple of them, that gives you
certain types of advantages forthe product profile, so how this
can actually be deployed.Current antivenom is made from
horse or other similar animalsera, and there could be 10,000
(26:27):
or more antibodies in there. Andeach antibody has a different
preference for how it likes tobe, freeze dried or
concentrated.
And unfortunately, that meansit's really hard to go freeze
dry or concentrate this serafrom horses because a lot of the
antibodies are going to fallapart when you try to resuspend
them. And that means that youcan't do that, and so people use
intravenous infusion, IV bags,and that means you need to have
(26:48):
them at a hospital that hasrefrigeration and has a doctor
who can give an IV things thatwe take for granted in The
United States but typically nottrue in many of the areas where
people are actually needingtreatment for snake bite. And
that means you have to travelfor four hours to get to the
hospital. When you suddenly onlyhave a couple human antibodies,
then you can find a set ofconditions that you can freeze
(27:10):
dry these things it's calledlyophilization where they can
all be freeze dried and thenthey can be resuspended. That
opens up a new powerful productthat's kind of like an EpiPen
for antivenom, which is you havethe freeze dried product that no
longer requires refrigeration.
You have the excipient, which isthe saline plus maybe some
sugars, and that could exist ina dual chambered syringe. So
(27:31):
that means that could bedeployed out in the villages, it
could be deployed in a backpackof a warfighter, and when
there's a problem, you justtwist, the liquid resuspends,
and then it can be injectedintramuscular. And then the last
obvious advantage is that theseare human antibodies. Body is
while it's not been evolved totolerate a whole bunch of horse
antibodies loaded in at once,it's perfectly happy having very
(27:52):
high doses of human antibodies.They are actually the biologics
class of the most popular andwell established drugs precisely
because your body's evolved totolerate a large amount of human
antibody, which means you coulddose it safely closer to where
the person was bit withouthaving to have all these
accessory support functions at ahospital to deal with the
anaphylaxis and the serumsickness.
(28:13):
And so pretty much across everyaxis, it creates a superior
product that can be deployedcloser to the time of bite,
which matters, because thelonger you wait after a bite,
the more irreversible damageyou're going to suffer and the
more likely you are to die. Itallows you to just have the same
product for every snake, and itallows that product to be
administered quickly withoutknowing what type of snake bit
(28:34):
you, which means more people aregonna get antivenom and that
more people are gonna gettreated. And so these were all
major advantages and part of whywe've been pushing on this.
Dr.Moira Gunn (28:41):
Okay. What about
Tim? What's happened to Tim?
Dr. Jake Glanville (28:45):
So one of
the things that I felt was
really important here Inbioscience, sometimes you find
amazing molecules or an amazingbiospecimen from a human. And
that's cool. Sam's not thefirst. There are others where
this has been the case. But ingeneral, biotechnology has
(29:07):
struggled with powerfulspecimens drawn from a human,
and that human deriving nobenefit of their use.
Other people receive a benefit.The classic example was
Henrietta Lacks in the HeLacells that are used now in
laboratories all over the world,and she and her family were
frustrated that she didn'treceive any benefit for it. I
(29:29):
was wanting to make sure thatnot just that we had a good
ethical design for the studies,but that we recognized in an
ethical manner the appropriateamount of time that Tim spent on
this, which was really, this ishis life's work, eighteen years.
And so, Tim, been hired by us asthe director of herpetology. He
has equity in the company, andthen he and I have a special
(29:51):
agreement that if there's anyparticular bonuses or benefits
that come out of the anti venomprogram, whatever they are, he
and I are sort of locked step toreceive equal.
And that was to recognize his 18of research and development in
his bloodstream to create thesemolecules. We're lucky to have
him. He has an astonishingautodidact knowledge of all
(30:12):
things snake, all things snakebite, all things venom, and so
he participates with us inelecting the additional toxins
to go after, looking atveterinary and clinical networks
to be able to proceed against.And then he's communicated with
pretty much everyone in the antivirulent world. He's also our
major networker.
Those are the various things hedoes with us at the company. I'm
very fortunate to work withsomeone like Tim.
Dr.Moira Gunn (30:33):
Well, it's two
decades of his life. And when
you think what he did and he wasout there pretty much alone
doing this. It has to be hard ona life.
Dr. Jake Glanville (30:45):
Yeah. And it
was. Not just the pain. He made
this his life's focus. When Ifirst talked to him, he told me
about all these bites and soforth.
To give you a sense of howobsessed and dedicated he was to
this, he told me he had notes.And I said, Okay. I wasn't sure
(31:06):
what to expect. And when hesends them to me, I was
completely blown away. It wasthis meticulous record that
spanned seventeen years and ninemonths, where every single time
he self envenomed, he recordedthe species, the microgram, and
slowly escalated up tomilligrams of of dry weight, the
site of immunization.
He took a diameter of swelling,so he monitored the amount of
(31:29):
swelling. He had a self reportedpain score and some pretty rowdy
notes. And he did this theentire time. That's how I know
he had six fifty four bites and200 two zero two bites and six
fifty four self immunizations.It's how I was able to monitor
his process.
Even in that data, you couldread at what you could tell at
what point he had developedimmunity because the swelling
started dropping, even if thedoses increased. And so that
(31:52):
gave me a little snapshot intohow much this had become an all
consuming obsession for him. Andthat obviously had consequences
in his life. The man had boxesupon boxes of snakes in his
basement. It had been convertedto a vivarium.
He was spending all his time onthis, and, you know, eventually,
(32:12):
his his wife had had left him.They got divorced, and his child
had become estranged, he hadn'tseen him in a while. It was
honestly the nobody expected theamount of press that we got out
of the publication of the Sellarticle. It was gratifying, but
I think my favorite part aboutall of it was that Tim called me
(32:32):
one day, and he said his son,who had been estranged, had
called him and said, Dad, Ifinally understand what you were
doing all that time. I'm proudof you.
And I just felt like thatredemption arc meant made the
whole thing worth it.
Dr.Moira Gunn (32:45):
Wow. Big story on
many levels. Jake, of course, I
wanna thank you so much forcoming in. I also wanna thank
you because as I went throughthe other media coverage, I got
to see pictures of sentivacresearch scientists, including
my former students, Joel Andre,Hannah Hero, and Mark Bellin. My
(33:09):
students are the best as youknow.
And they are. There they are inin the coverage. And I wanna
thank you for just showing ushow science gets made, how
exciting how exciting it is, andhow you gotta take risks and a
tremendous human story allaround.
Dr. Jake Glanville (33:25):
Well, just
wanna, first off, thank you for
having me on. Second, I wannathank you for what you've done
with the USF program. You know,Mark is my co author on the
paper. Joel and Hannah have beentremendous. Like, we we are able
to do these kinds of projectsbecause of the remarkable
training that the folks get atthe University of San Francisco
(33:46):
Biotechnology program, and,we're lucky to have them.
So thank you for all that you'vedone there. And and, again,
thank thank you for, taking thetime to share this story. I'm
I'm, excited on where we'regoing next. We have the half of
the cocktail. We're working tofinish the other half for the
vipers.
And I I think we're gonna havesomething that could have
lasting value for the nextcentury to come, and and that
(34:07):
that that's gratifying.
Dr.Moira Gunn (34:08):
My guest today is
doctor Jacob Glanville, the
founder, chairman, and CEO ofCentivax. More information is
available on the web atcentivax.com. That's centivax.
Centivax.com.