April 5, 2024 • 41 mins
This episode of “The UMB Pulse” podcast features Allan Doctor, MD, a professor at the University of Maryland School of Medicine who was the University of Maryland, Baltimore’s (UMB) David J. Ramsay Entrepreneur of the Year in 2022. Doctor also is the co-founder and chief scientific officer at KaloCyte, a company focused on developing freeze-dried, powdered synthetic blood designed to save lives in emergency situations where traditional blood transfusions are not viable.
Doctor outlines the imperative need for an easily transportable and universally usable blood substitute for scenarios such as accidents or battlefield injuries, where immediate blood replacement can make the difference between life and death. The podcast explores the science of blood, the challenges of creating a stable and biologically compatible blood substitute, and the potential applications beyond emergency medicine. The episode also delves into Doctor’s background, the support from UMB and various grants including substantial funding from the Defense Advanced Research Projects Agency, and the future of artificial blood research at the University of Maryland BioPark.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Charles Schelle (00:00):
Dana, it's getting warmer outside.
(00:02):
You, I feel like I'm switchingover to colder drinks for my
warmer drinks.
And I got a little bit of orangeon my mind because it's opening
day today for the BaltimoreOrioles.
But you know, I, I really likedTang when I was a kid, you know,
just that powder, orangesubstance, and you just mix it
in a little bit.
Dana Rampolla (00:21):
Tang, the drink of the astronauts, right?
I think you're dating yourselftoo, Charles, I'm just going to
Charles Schelle (00:26):
say.
Well, I probably had more of thepowder form Hawaiian Punch, but
I think more people recognizelike Tang is, you know, so
universal, right?
You could bring it anywhere.
You could bring it to a picnic,you can bring it on vacation,
just, you know, anytime you needit.
Yeah.
Yeah.
Yeah.
Yeah.
Water to mix
Dana Rampolla (00:44):
it
Charles Schelle (00:44):
with.
Just that water, right?
Now, imagine.
something like Tang, notdrinkable though, unless you're
a vampire, but for use of blood.
Huh?
Dana Rampolla (00:55):
That's an interesting concept,
Charles Schelle (00:57):
right?
It is.
And so we have somebody at theUniversity of Maryland School of
Medicine who's making a freezedried powdered substance that
you just add water to to createblood that could save countless
number of lives for the peoplewho are bleeding out because of
(01:17):
a car accident or maybe theywere shot on the battlefield
serving in the military.
Dana Rampolla (01:22):
Yep.
Yep.
We have our one of our very owndoctors with us today.
He is the professor in thedepartment of pediatrics.
Dr.
Alan doctor.
We won't be able to forget thatname.
And I'm sure he's heard thatjoke before, so he is our 2022
David J.
Ramsey Entrepreneur of the Year.
He's the co founder and chiefscientific officer at KaloCyte,
(01:43):
which is working to develop, asyou said, a dried bio inspired
artificial red blood He's aprofessor in the Department of
pediatrics here at theUniversity of Maryland,
Baltimore.
He also is the director of theCenter for Blood Oxygen
Transport and Hemostasis at theUniversity of Maryland School of
Medicine.
And that's a mouthful.
It's a lot to say lots toremember.
Charles Schelle (02:06):
So he came to us from Washington University
School of Medicine in St.
Louis, and you'll hear morelater in the episode about What
made them come to UMB and theBioPark?
And it's a really encouragingstory to hear about how we
support entrepreneurs who areboth faculty researchers and,
(02:29):
and the business world ofbiotech.
Dana Rampolla (02:32):
It's a whole combo of, of things we'll be
talking about today.
I'm going to run real quick,grab myself a glass of Tang, mix
it up.
Would you like me to grab onefor you, Charles?
And we'll get started.
All right.
Jena Frick (02:47):
You're listening to the heartbeat of the University
of Maryland Baltimore, the UMBPulse.
Dana Rampolla (03:00):
Welcome, Dr.
Doctor.
We're so happy to have you here.
Allan Doctor (03:04):
Thanks.
I appreciate the invitation.
Dana Rampolla (03:07):
Let's start out today, back in my former life.
Some many, many, I won't say howmany years ago I was a biology
major.
So I do remember a little bit.
Blood is an interesting type ofsubstance.
It has very specific colors andcomponents to it.
Would you take a minute and justgive us a blood 101 lesson?
Allan Doctor (03:26):
Sure.
Blood is technically an organlike your liver and kidney.
It executes lots of importantfunctions in our body.
The one that most of us arepretty interested in is moving
oxygen from your lungs to thecells where it's consumed.
(03:47):
So everybody probably knows thatall of our cells have little
furnaces where they burn glucoseusing oxygen and the oxygen has
to get there through ourbloodstream and blood goes
through the lungs capturing theoxygen in a protein called
hemoglobin that's carried in ourred blood cells.
(04:08):
That's what makes blood red, bythe way, is the hemoglobin, and
then it gets pumped by the heartand distributed through blood
vessels so that it flows throughall of our tissues, and it then
captures carbon dioxide andother waste.
And that travels around the bodyand the wastes are excreted in
the kidney or processed in theliver and so on.
(04:30):
Blood also carries a system forclosing holes.
So if you get cut and your bloodstarts to leak out, it stops on
its own because you have aclotting system that plugs the
hole.
And that's another veryimportant function of blood.
Dana Rampolla (04:49):
Perfect.
So you've kind of laid thegroundwork for us to understand
what blood is and why we needit.
So set the scene for us.
Why are you studying aboutblood?
What problem are you trying tosolve related to blood?
And how long have scientistsbeen looking into this?
Allan Doctor (05:10):
So how long of scientists been looking into it
is a complicated question,really, in the surprisingly,
blood and its functions weren'treally understood until, really
the 1600s or 1700s when peoplefinally realized that there was
a circulatory system and thatblood was, was part of it.
(05:33):
That's a whole nother storythough.
What we study in my laboratoryis the, how blood, Distribution
is governed because we have avery efficient system for
distributing blood flow withliterally miles of routes that
our blood can take in order toget to every single cell.
(05:58):
And the important feature of oursystem is that it's scalable.
So, like, You know, you mightneed to suddenly start running
and back in the day duringevolution, you would need to run
to get food and you would needto run to get away from someone
that wanted you as food.
(06:19):
So, this was very important.
And so you had to ramp up yourengine or your oxygen
consumption.
And so blood is a big part ofthat.
Now, blood is driven through thesystem through blood pressure,
right?
It's a pressurized system.
That's what moves the blood upto your brain or through other
(06:40):
solid organs, and the pressure'sdelivered by the heart.
But like with all hydraulicsystems, they require a volume,
okay, to work, and if you startto lose that volume, like if you
bleed or you get dehydrated, thepressure falls and the system
can fail.
The system can also fail.
(07:01):
If you don't get enough redblood cells, so you start to get
anemic.
And so we study both of thosethings and how they can be
corrected by creating artificialblood.
And so we that's a large focusof the laboratory right now.
And so in order to designsynthetic blood, you have to
(07:24):
understand how blood works.
And that's, you know, also partof the program.
Charles Schelle (07:29):
You mentioned about,, bleeding and loss of
blood.
What problem you're trying tosolve as far as that need of
getting a blood supply tosomeone on site when they're
bleeding out?
Allan Doctor (07:43):
So the simple thing is first to understand
that when you're bleeding acouple of things happen that
need to be addressed prettypromptly.
So, as everybody knows, if yourheart stops.
You have to restart the heartwithin a specific amount of
time, or you start to developbrain injury, or you get organ
(08:04):
injury, or you die, and that'sminutes.
The same thing is true if youare suffocating.
You don't get oxygen into theblood, okay?
The same thing is true if yourheart is, is beating, and you're
getting oxygen into your lungs,okay?
But you lose enough blood sothat the pressure falls.
(08:27):
In the system and that's the,they all have the same sort of
time sensitivity because thebottom line is oxygen isn't
getting to the brain and othertissues.
Now, if you bleed in a hospital,and we can control the bleeding,
so a hole opens up somewhere andyou start to bleed.
(08:48):
We can staunch the hole.
Then we can replace the lostblood with stored blood, which
is a transfusion.
And that will fix the problemevery time.
So that's a problem we can solvevery effectively, but you have
to be in a hospital.
The blood can't be deliveredoutside the hospital for
(09:10):
transfusion because it's aliving tissue and it has to be
maintained through somethingcalled a cold chain.
So it, it spoils very fast.
And really, it's only allowedoutside the refrigerators for
about four hours.
So it's just not practical tobring it out of the hospital.
The problem is that people bleedat the scene of accidents or in
(09:35):
their house, so somebody mightdevelop an ulcer and bleed in
their living room, or someonemight be in an accident, like,
let's say you were in the sceneof an accident where a bridge
collapsed you might you mighthave bleeding, or you might be
wounded on a battlefield.
(09:55):
And.
If you can't get the blood, wecan put salt water, okay, in the
bloodstream.
That's all we do now, is we givewhat are called saline
infusions, and that can improvethe blood pressure, but not if
you lose more than, say, Half ofyour blood then it's just not
(10:16):
enough and people will die.
So right now, 20,000 people ayear die before they can get to
the hospital because we can'tgive them blood.
They basically just bleed todeath.
This is quite a bit.
That's just in the US not theworld.
What we're doing is trying todevelop alternatives to natural
(10:36):
blood that are shelf stable andcould be delivered at the scene
of an accident.
So that would keep someone alivefrom the scene of an accident or
from a medical emergency outsidea hospital.
So that you could get them intoan emergency room and get
natural blood.
Charles Schelle (10:55):
I don't know if you have the statistic on the
spot, but as far as deaths dueto loss of blood What's the main
cause?
Is it a car accident?
Gunshots?
Allan Doctor (11:06):
It's, it's trauma.
So it's, it's, I couldn't tellyou, it depends on the region
whether that's more likely.
So for example, in the city ofBaltimore, you know, the car
accidents aren't going, they'reusually not fast enough to
really, you know, cause thatkind of bleeding.
You have to really be on thehighway, but that's where you
get stabbed and shot are incities.
(11:28):
Thanks.
So, for example, in Manhattan,it's all, you know, penetrating
trauma.
However, if you're in a say,where people can get going fast
enough, it's those are thedominant injury is, is a car
accident.
Dana Rampolla (11:45):
You mentioned the saline when when someone gets
that saline infusion, does, dothey still need to have a blood
transfusion when they get to ahospital or?
Allan Doctor (11:55):
Well, it depends on how much blood they lost.
So we have an incredible amountof reserve in our system.
So, for example you know, we canlose half of our red blood cells
so that if you can restore theblood pressure, you don't need
blood.
So you're Literally, we can losehalf.
We have twice as much as weneed, really almost three times
(12:17):
as much as we need, if you havea normal heart, lung, and
vascular tree.
So there's lots of redundancy inthe system, so you can
compensate for loss of red cellsby improved performance with the
heart, the lungs, and thevascular tree.
However, if you've got a weakheart Or you've got problems
(12:40):
with your lungs like emphysemaor you've got problems with your
vascular tree like if you havediabetes or kidney failure, then
you're less able to tolerateblood loss and maybe you can
only lose 20 percent of your redblood cells, but a young
healthy.
Adolescent can lose two thirdsof their red cells, and if we
(13:00):
can stabilize their bloodpressure with a salt saline
infusion, then we don't have togive them blood when they get to
the hospital.
But most of the people bleedingare not healthy 15 year olds,
unfortunately.
Charles Schelle (13:16):
Right.
So, you went into this a littlebit, but, but paint a picture,
what does artificial blood looklike from the start, and, and
how does it work to mimic realblood?
Allan Doctor (13:29):
Well, well, you have to split it into two
components.
There's the principal task ofexecuting the function of red
blood cells, which is to moveoxygen.
Okay.
And then there's the task ofhelping blood clot.
Okay.
Which is what the plasma and theplatelets do in our blood.
(13:49):
So if you need a transfusion bydefinition, you are probably
bleeding.
If you are bleeding and thatcontinues, then you can't ever
stop the problem.
So, obviously, if there's a leakin a hydraulic system, you need
to replace the fluid, but youalso have to stop the leak.
(14:10):
Or, you can't, you can'tstabilize the system.
So we have to, when we'rereplacing blood, we have to pay
attention to both things.
Now, there are differentthresholds for replacing these
two things.
And so you can get away withfirst replacing the oxygen
carrying capacity.
(14:32):
If, for example, you can use atourniquet to stop bleeding in
an extremity.
But if you have internalbleeding from an ulcer or a
fractured liver or kidney orsomething like that, or bleeding
into the chest where you can't,you know, just, it can't be
controlled easily before you getto the hospital.
(14:52):
Then we also have to givecomponents that help stop the
bleeding, which would besynthetic or artificial
platelets and plasma, the oxygencarrier.
Okay.
People have been working on thisfor almost 80 years.
And the principal problem is redblood cells can't be stored at
(15:16):
room temperature.
So What people tried was topurify the key element from red
cells, hemoglobin, and to justput that in the bloodstream,
hoping it would work.
Now, there's a reason thathumans evolved, and mammals, and
basically all animals, morecomplicated than a worm, evolved
(15:41):
with the hemoglobin encapsulatedin a membrane.
It's not free in plasma.
There's a reason for that, inthat it causes injury to blood
vessels if it's free.
And people weren't, didn't learnthis until we tried, you know,
putting Hemoglobin free into thebloodstream and people found
(16:02):
some problems that they tried toaddress with modifying it
chemically and creating complexpolymers and it looked like it
might work and they got very farwith this program, even to human
trials.
But those human trials ended upresulting in making the
recipients even sicker than theywere if they didn't get blood.
(16:27):
And so people were dying fromheart attacks and strokes who
had gotten the artificial blood.
And the FDA closed this programdown in around 2006, 2008.
And the next generation Okay, ofauction carriers all sheath the
(16:49):
hemoglobin inside a membraneinside a cell and that's a more
complicated problem.
And that's the one that we haveworked on, is that we have
designed an artificial red bloodcell where we have a membrane
that imitates the behavior ofthe membrane that encloses
hemoglobin in a red blood cell,and we strip down the contents
(17:15):
to only include the elementsthat carry oxygen.
And so we've done that, and wecan now freeze dry it, so it's a
dry powder, like instant coffee,okay, which is freeze dried, and
just like instant coffee, youreconstitute it by adding water.
(17:37):
And you can drink the coffeeright away after you add the
water, and you can transfuse theblood right away after you add
the water.
So, the way it works is that amedic would carry around the red
powder, which is freeze driedartificial red blood cells, and
you add water, and within a fewminutes, it's fully
(17:58):
reconstituted and can beadministered.
To to normalize oxygen carryingcapacity in blood.
Now, that doesn't help withblood clotting.
That's another subject.
Charles Schelle (18:11):
That's amazing.
I mean, that's, that'sabsolutely a game changer with
how nimble of a product.
It could be, as you said, freezedried, which means you can
pretty much bring it anywhere.
As, as you said, on abattlefield, potentially have
water on hand and, and savecountless lives.
Dana Rampolla (18:29):
How how are you actually testing it then?
Allan Doctor (18:34):
We've been working on this for almost 10 years.
So that's quite a bit of time.
So the initial challenge, ofcourse, was to design the shell
so that it is compatible withour body.
So biocompatible, right?
So you can mix it into the humanbloodstream.
And so we use.
(18:55):
You know, molecules they'reactually fat molecules.
Our cell membranes are made upof fat in case people didn't
know that.
And there are five differentmolecules that we use and they
all have a surface andproperties that are very similar
(19:16):
to the ones that are in ourcells and just the right blend.
And believe it or not, we evenhave to add a little
cholesterol.
Into the membrane to make itlike a normal membrane, and it
will form like a, a littlebubble, like a balloon, and the
balloon is stuffed with thehemoglobin protein that we
(19:36):
normally have in our red bloodcells.
Only these are much smaller,they're about a fiftieth the
size of a red blood cell.
Now, the first thing was to makesure it would capture and
release oxygen, which we wereable to demonstrate.
And that it does it just like ared blood cell.
And the next thing was todemonstrate that it won't break
(19:59):
open when it's flying around thebloodstream.
So we had to work on it to makeit stable for what we call the
shearing stress of going throughcirculation.
And the next was to make surethat it didn't make the blood
too thick or thin.
That's the viscosity of theblood.
(20:20):
And then we had to make surethat it wouldn't interfere with
the way blood vessels work.
The blood vessels have to stayopen, Just the right amount so
that they create enoughresistance to create a blood
pressure, but not so small thatthey don't let blood through.
And this was a huge problem withthe, the quote, naked hemoglobin
(20:42):
that would just go straight intothe bloodstream because it
interfered with the regulationof blood flow.
blood vessel caliber so that weget they would get very small.
They would go into spasm.
Kind of like you get a cramp,you know, in your arm or leg.
And the muscles sort of clinchesup and what was happening is
(21:02):
the, our blood vessels havemuscles and they would clinch up
as if they had a cramp and thenno blood can go through.
And this was being caused by thefree hemoglobin.
So we had to make sure our cellsdon't do that.
And finally, we make sure thatthey don't activate our immune
system, because our immunesystem is designed so that it,
(21:25):
it's constantly interrogatinganything it encounters, is this
part of, of your body or not?
And if it's not, it goes afterit with a vengeance, like it
goes after a virus or a bacteriaor a fungus.
or foreign tissue.
So, it will go after foreignmaterial and that has to be what
(21:48):
we call immune silent.
And so that was all the benchtesting, okay, before we even
got into animals.
And then we started with miceand rats and now we're into
rabbits and we've been workingin for a few years.
And our next step is to moveinto primates.
(22:09):
So, and then humans and we're,what we think is about two years
away from our first trial in, inhumans.
That's
Charles Schelle (22:19):
amazing.
That's
Dana Rampolla (22:21):
incredible.
I didn't even think about theimmunity part that people,
people's cells would reject itor could reject it.
Allan Doctor (22:28):
Yes, so the, the important thing to recognize is
that because it's immune silent,there's no blood typing.
So we can give it to anybodyregardless of blood type.
And in fact, it's so immunesilent, we can give it to any
species.
So we can give the same redcells to a dog a whale you know,
(22:49):
a mouse, a zebra whatever.
So there's a veterinaryapplication for the same
product.
Dana Rampolla (22:56):
Wow, that's incredible.
Charles Schelle (22:58):
You know, I was wondering too, red blood cells
naturally have their ownlifespan.
What's the lifespan of, or doesit even matter, of an artificial
blood cell?
Allan Doctor (23:07):
Oh no, it matters.
So you want it, you want it tocirculate for just the right
amount of time.
That's right.
So red cells, by the way,circulate for about 120 days
after they're born in your bonemarrow.
It's amazing how, how, how weare constantly replacing our
(23:28):
blood.
You turn over about 1 percent ofyour red blood cells a day.
And in the course, which is, youknow, billions of red blood
cells, we have about three orfour trillion red cells, right?
Circulating right now.
It's the most abundant cell inyour body by it's about 80
(23:49):
percent of your cells are redblood cells.
And you make like, I think it'sfour or five kilograms of red
blood cells in the course ofyour lifetime.
So it's a very important cell.
So.
Ours the artificial red cellscirculate.
So about, we speak in terms ofhalf lives.
(24:10):
So that means when about half ofthem disappear.
So the half life is dependingon, on circumstances, anywhere
from 12 to 16, sorry, 10 to 16hours.
So it's suitable for bridgingtherapy from an accident to an
emergency department.
And then.
(24:30):
And then after you get to theemergency department, if you
still need blood, you would thenget natural blood so that they
don't last quite as long oranywhere near as long as a
natural blood cell does.
Dana Rampolla (24:45):
That's so interesting.
When, when you think aboutpeople with, whether they have
well this might sound like asilly question, but what if I
have like some sort ofartificial organs?
Is the blood as effective likeis there anything different if I
have something, some sort of atransplant?
Allan Doctor (25:00):
No.
In fact, there's an applicationfor transplanting that we
haven't discussed.
The primary application that weare working on right now is to
resuscitate people who arebleeding outside of hospitals.
Okay, but there are otherissues.
For example, when we do atransplant you take the organ
(25:25):
out of the donor and you put itinto the recipient and usually
the, unless it's a livingtransplant where you're, you've
got a living donor giving akidney and it's going to you
know, the recipient might be inthe next room.
Usually, you harvest the organin a certain situate place and
(25:50):
time, and you transplant it in adifferent place at a much later
time.
And the organ has to bepreserved as you go from the
donor to the recipient.
And there's a limited amount oftime that you can have an organ
out of the body.
So the time that you can have anorgan out of the body can be
(26:10):
extended if you could create anartificial circulation for that
organ.
And natural blood does not workthat well in this situation, and
so the blood substitute canextend that time.
The duration between organharvest and transplant and even
(26:32):
resuscitate organs that mightnot be working so well.
So if somebody is donatingorgans, often they're, they're
not just they're not healthy.
So they sometimes those organsare impaired and you can get
them out.
and resuscitate the organ, thenyou can salvage organs that
(26:53):
would not otherwise betransplantable.
So there's a transplantapplication for the synthetic
blood.
Also, when you go oncardiopulmonary bypass in the
hospital for heart surgery orlung surgery, sometimes you, you
have an artificial circulationand that requires blood.
(27:14):
Now, especially for babies.
Now we envision the possibilitythat you could.
When you put someone on bypass,take their own blood and take it
out of the system and store it,do the operation under
artificial blood, and thenremove that and put the natural
blood back.
(27:35):
And that would prevent somebodyfrom getting exposed to
transfusion, becausetransfusions during bypass
operations create injury.
Additionally, you've heard ofinterventional.
Radiology where they doangioplasties and open blocked
arteries.
(27:55):
So to open a blocked artery, youput a balloon in a catheter and
blow up the balloon and yourelieve a stricture or you break
open a clot.
And you do that in the brain andthe heart and the kidney, other
really vital organs.
So your ability to do that islimited by how long you can hold
(28:16):
the balloon up.
Okay, because no blood goes pastthe balloon when it's open.
If instead you can giveartificial blood through a
catheter tip that goes beyondthe balloon, then you can extend
the time that you can keep theballoon up and make those
operations, those proceduressafer.
(28:37):
So there's lots of otherapplications for this, even in
space.
So, to go to Mars there's noblood bank on possibility there,
or, and the current, believe itor not, the current plan for
space travel, if there's anaccident where there's bleeding,
is to hold pressure.
(28:58):
That's it.
So there's no possibility ofbringing a blood bank with you
because of the weightconstraints.
And the only other option wouldbe to have astronauts that have
compatible blood types, so thatif someone needed a transfusion,
you could take blood from them.
from astronaut one and give itto astronaut two.
(29:19):
Now, obviously that's not ideal.
So NASA is actually interestedin freeze dried blood because
it's light.
So there are all kinds ofapplications that are in unusual
circumstances for if we couldsuccessfully create freeze dried
blood.
Charles Schelle (29:37):
You, you brought up a good point.
The interest in it, just theconcept of substitute blood just
tips the scales and opens up allsorts of possibilities.
So with that, obviously you havethe attention of the federal
government.
So, tell us a little bit aboutsome of the funding and research
commitments that you've receivedrecently.
Allan Doctor (29:56):
So our initial seed funding came from the NIH
and the Department of Defense.
We designed this technology andcreated a company called
KaloCyte which means beautifulcell in Greek to to develop the
artificial red blood cell.
And we received about$5 millionin support from the NIH and
(30:20):
Department of Defense.
To do the initial proof ofconcept work, we've received
about another 10 to$15 millionin in grants from the NIH and
federal Government, and about$5million in private uh, equity
funding um, for the company.
(30:42):
The research program hasrecently secured a very large
grant from DARPA, which is theDefense Advanced Research
Administration.
DARPA doesn't just do biologicalresearch, you know, they
famously created the internet,Develop stealth technology and
(31:04):
other wild things.
So they do high risk, high gainprojects, and the Department of
Defense wanted to create asynthetic blood program.
So that would be both the bloodclotting and auction transport
functions.
And we competed with about 10other teams for that award,
(31:25):
which is almost 50 million todesign and generate.
synthetic blood that can befreeze dried.
Charles Schelle (31:35):
And you have an entire consortium working on
this, too, right there.
There's like a what is it a 15site consortium across the
country?
Allan Doctor (31:41):
Yes, there's multiple sites, including
several, um, large universitiesas University of Pittsburgh,
University of California, SanDiego Case Western Reserve
University Penn StateUniversity.
Are all and Ohio StateUniversity are all participating
and then several small companiesthat are generating the
(32:05):
components.
KaloCyte is generating theoxygen carrier.
There's a small company calledhemotherapeutics that is
developing the syntheticplatelet.
And there's a larger companyTeleflex that is generating the
freeze dried plasma.
And then a a research Institute.
Called Southwest ResearchInstitute that is helping with
(32:27):
production scaling and biomanufacturing.
Dana Rampolla (32:31):
It's incredible.
So you are actually here at UMB,University of Maryland,
Baltimore, working on this.
Tell us, has UMB been a supportfor this type of faculty
entrepreneurship?
Allan Doctor (32:44):
Yes, well, it's why I moved here.
So I, I was at WashingtonUniversity in St.
Louis and that's where weoriginally invented this
technology and started KaloCytein St.
Louis.
And I also led the.
You know, the critical caregroup at St.
Louis Children's Hospital andran the division of pediatric
(33:04):
critical care at Wash U Schoolof Medicine.
We were, um, working with thebiopark there which was an
incubator for small companies.
It was institutionally a littlechallenging to create an
effective and seamlesspartnership.
I think that uh, facultyentrepreneurship is an evolving
(33:26):
area in higher education andinstitutions with a major
research focus, and some havebecome more agile than others.
As our program was growing, wewere looking for an ideal
environment that would reallyfoster the opportunities for
synergy between my academic laband the, the companies that were
(33:51):
spinning out of the lab.
And so, University of Marylandyou know, we looked all over the
country and uh, was exceptionalin what they were, the
environment the proximity to NIHand Department of Defense to the
Shock Trauma Center, and theBioPark here, and the university
(34:13):
and leadership at UMB was uh,very flexible and in allowing us
to embed small companies in anew research center in
university space, which was avery innovative and frankly new
for UMB.
It is the reason we were able tocompete effectively for this
(34:37):
DARPA award.
No one else had the sameopportunity to offer the
government such synergy betweenthe small companies and the
unique capabilities that arereally only available at
research institutions.
Charles Schelle (34:52):
It's great to hear.
And we're glad that you chose usto relocate your company and
your research here.
Yeah, as you mentioned,University of Maryland Biopark
is an amazing area on ourwestern edge of our campus.
There are so many biotechcompanies there.
It's a great thrivingenvironment and it's growing.
We have the 4MLK building goingup, hopefully completed soon.
(35:16):
We'll have space for even morecompanies, more like yourself.
Allan Doctor (35:20):
You know, and, and it's not just the, the, the fact
that we came here, the, youknow, the Office of Technology
Transfer has, you know, providedincredibly robust support for
new intellectual propertygeneration.
We've created many new patentssince we've come here.
They you know, have a lot ofbusiness expertise.
(35:41):
They've supported.
Our company executive leadershipin fundraising with the local
community and Maryland itselfhas a very favorable environment
for investing in biotech.
So, it's not just the, thescience it's also been the the.
(36:02):
I guess the serviceinfrastructure that's also been
very crucial and given us a,frankly, a competitive edge that
is unmatched.
Dana Rampolla (36:12):
Tell us a little bit more about the center,
obviously it sounds like thingsare going great in this area,
but how does it fit in witheverything else that you're
doing and like how, how has itgrown in size since you've been
here significantly?
Allan Doctor (36:26):
Yeah, so the the research center is so it's
called the Center for BloodOxygen Transport and Hemostasis,
which is blood clotting.
So it's pretty obvious what wework on basically the you know,
the, if it, it has to do withblood and you know, moving
oxygen and the clottingfunctions of blood, And we work
(36:49):
on that.
We also study ways to optimizeconventional blood storage.
You know, that's basically 1950stechnology that hasn't been
meaningfully improved since thattime.
And there's a lot of room forimprovement there.
So we have a number of projectsin that area.
We've recruited two key facultymembers to join me here at the
(37:12):
center.
They each lead large researchprograms.
Each of those labs has about 10to 16 people in them.
And so they are traditional labswith graduate students and
postdoctoral fellows that studyyou know.
topics related to bloodfunction.
I also have an academic lababout that size and we study
(37:34):
acquired injury to red bloodcells.
For example, how diabetes orkidney failure or infections can
alter red blood cell functionand how to mitigate that.
We also study sickle celldisease and We're developing
therapeutics for for sicklecell.
(37:54):
So, you know, the growth hasbeen quite rapid.
Our you know, one measure of usof progress is the funding,
which has improved almost about700 percent in extramural
support since we've come here.
And that's excluding the bigDARPA grant, which is kind of an
outsized you know, addition.
Charles Schelle (38:16):
The Dean's a little bit of the same ilk of
that entrepreneurial spirit and,and supporting this with the
faculty entrepreneurship.
What have you've kind ofobserved and what can you tell
us about what Dean Gladwin kindof brings to this?
Allan Doctor (38:30):
Well, sure, I should 1st mention that, you
know, it was, you know, DeanReese that that brought me here.
And through an initiative, hecalled the STRAP program where
he basically invested sufficientresources to give a space and to
recruit an entire team.
And so he really was the seed.
(38:50):
And Dean Gladwin, as you know,has succeeded Dean Reese.
I've known Dean Gladwin foralmost 20 years.
And we work in a very similarscientific domain.
And he Also is is anentrepreneur, has started a
company called GlobinTherapeutics.
He's very supportive of our workand faculty entrepreneurship in
(39:14):
general.
We have an evolvingcollaboration, in fact.
And I couldn't be happier withhis leadership.
He's been incredibly supportiveboth he and Dr.
O'Donnell who's the vice deanfor research have been very
supportive of the center and Iexpect that others like me will
(39:36):
find this an ideal place to comeand do their science.
Charles Schelle (39:41):
Fantastic.
Well, we've really kind oftouched on the very tip of
artificial blood in our shorttime here, and hopefully your
research continues with greatsuccess, and, can't wait to have
it hit the market and saveplenty of lives,
Allan Doctor (40:00):
Well, thank you for the interest and the
opportunity to discuss it.
If anybody in the universitycommunity would like to learn
more or interact in acollaborative fashion My name's
pretty easy to remember.
And so I'd be delighted to toaddress any inquiries from the
community.
Charles Schelle (40:21):
And we'll make sure we'll put those in our show
notes too.
So all of our listeners justcheck the description and you'll
find out how to reach out to Dr.
Allan Doctor.
So, Doctor, thank you forjoining us on the UMB Pulse.
Allan Doctor (40:34):
Thank you for the opportunity.
Jena Frick (40:41):
The UMB Pulse with Charles Chalet and Dana Rampolla
is a UMB Office ofCommunications and Public
Affairs production, edited byCharles Chalet, marketing by
Dana Rampolla.
Dana, it's getting warmer outside.
(00:02):
You, I feel like I'm switchingover to colder drinks for my
warmer drinks.
And I got a little bit of orangeon my mind because it's opening
day today for the BaltimoreOrioles.
But you know, I, I really likedTang when I was a kid, you know,
just that powder, orangesubstance, and you just mix it
in a little bit.
Dana Rampolla (00:21):
Tang, the drink of the astronauts, right?
I think you're dating yourselftoo, Charles, I'm just going to
Charles Schelle (00:26):
say.
Well, I probably had more of thepowder form Hawaiian Punch, but
I think more people recognizelike Tang is, you know, so
universal, right?
You could bring it anywhere.
You could bring it to a picnic,you can bring it on vacation,
just, you know, anytime you needit.
Yeah.
Yeah.
Yeah.
Yeah.
Water to mix
Dana Rampolla (00:44):
it
Charles Schelle (00:44):
with.
Just that water, right?
Now, imagine.
something like Tang, notdrinkable though, unless you're
a vampire, but for use of blood.
Huh?
Dana Rampolla (00:55):
That's an interesting concept,
Charles Schelle (00:57):
right?
It is.
And so we have somebody at theUniversity of Maryland School of
Medicine who's making a freezedried powdered substance that
you just add water to to createblood that could save countless
number of lives for the peoplewho are bleeding out because of
(01:17):
a car accident or maybe theywere shot on the battlefield
serving in the military.
Dana Rampolla (01:22):
Yep.
Yep.
We have our one of our very owndoctors with us today.
He is the professor in thedepartment of pediatrics.
Dr.
Alan doctor.
We won't be able to forget thatname.
And I'm sure he's heard thatjoke before, so he is our 2022
David J.
Ramsey Entrepreneur of the Year.
He's the co founder and chiefscientific officer at KaloCyte,
(01:43):
which is working to develop, asyou said, a dried bio inspired
artificial red blood He's aprofessor in the Department of
pediatrics here at theUniversity of Maryland,
Baltimore.
He also is the director of theCenter for Blood Oxygen
Transport and Hemostasis at theUniversity of Maryland School of
Medicine.
And that's a mouthful.
It's a lot to say lots toremember.
Charles Schelle (02:06):
So he came to us from Washington University
School of Medicine in St.
Louis, and you'll hear morelater in the episode about What
made them come to UMB and theBioPark?
And it's a really encouragingstory to hear about how we
support entrepreneurs who areboth faculty researchers and,
(02:29):
and the business world ofbiotech.
Dana Rampolla (02:32):
It's a whole combo of, of things we'll be
talking about today.
I'm going to run real quick,grab myself a glass of Tang, mix
it up.
Would you like me to grab onefor you, Charles?
And we'll get started.
All right.
Jena Frick (02:47):
You're listening to the heartbeat of the University
of Maryland Baltimore, the UMBPulse.
Dana Rampolla (03:00):
Welcome, Dr.
Doctor.
We're so happy to have you here.
Allan Doctor (03:04):
Thanks.
I appreciate the invitation.
Dana Rampolla (03:07):
Let's start out today, back in my former life.
Some many, many, I won't say howmany years ago I was a biology
major.
So I do remember a little bit.
Blood is an interesting type ofsubstance.
It has very specific colors andcomponents to it.
Would you take a minute and justgive us a blood 101 lesson?
Allan Doctor (03:26):
Sure.
Blood is technically an organlike your liver and kidney.
It executes lots of importantfunctions in our body.
The one that most of us arepretty interested in is moving
oxygen from your lungs to thecells where it's consumed.
(03:47):
So everybody probably knows thatall of our cells have little
furnaces where they burn glucoseusing oxygen and the oxygen has
to get there through ourbloodstream and blood goes
through the lungs capturing theoxygen in a protein called
hemoglobin that's carried in ourred blood cells.
(04:08):
That's what makes blood red, bythe way, is the hemoglobin, and
then it gets pumped by the heartand distributed through blood
vessels so that it flows throughall of our tissues, and it then
captures carbon dioxide andother waste.
And that travels around the bodyand the wastes are excreted in
the kidney or processed in theliver and so on.
(04:30):
Blood also carries a system forclosing holes.
So if you get cut and your bloodstarts to leak out, it stops on
its own because you have aclotting system that plugs the
hole.
And that's another veryimportant function of blood.
Dana Rampolla (04:49):
Perfect.
So you've kind of laid thegroundwork for us to understand
what blood is and why we needit.
So set the scene for us.
Why are you studying aboutblood?
What problem are you trying tosolve related to blood?
And how long have scientistsbeen looking into this?
Allan Doctor (05:10):
So how long of scientists been looking into it
is a complicated question,really, in the surprisingly,
blood and its functions weren'treally understood until, really
the 1600s or 1700s when peoplefinally realized that there was
a circulatory system and thatblood was, was part of it.
(05:33):
That's a whole nother storythough.
What we study in my laboratoryis the, how blood, Distribution
is governed because we have avery efficient system for
distributing blood flow withliterally miles of routes that
our blood can take in order toget to every single cell.
(05:58):
And the important feature of oursystem is that it's scalable.
So, like, You know, you mightneed to suddenly start running
and back in the day duringevolution, you would need to run
to get food and you would needto run to get away from someone
that wanted you as food.
(06:19):
So, this was very important.
And so you had to ramp up yourengine or your oxygen
consumption.
And so blood is a big part ofthat.
Now, blood is driven through thesystem through blood pressure,
right?
It's a pressurized system.
That's what moves the blood upto your brain or through other
(06:40):
solid organs, and the pressure'sdelivered by the heart.
But like with all hydraulicsystems, they require a volume,
okay, to work, and if you startto lose that volume, like if you
bleed or you get dehydrated, thepressure falls and the system
can fail.
The system can also fail.
(07:01):
If you don't get enough redblood cells, so you start to get
anemic.
And so we study both of thosethings and how they can be
corrected by creating artificialblood.
And so we that's a large focusof the laboratory right now.
And so in order to designsynthetic blood, you have to
(07:24):
understand how blood works.
And that's, you know, also partof the program.
Charles Schelle (07:29):
You mentioned about,, bleeding and loss of
blood.
What problem you're trying tosolve as far as that need of
getting a blood supply tosomeone on site when they're
bleeding out?
Allan Doctor (07:43):
So the simple thing is first to understand
that when you're bleeding acouple of things happen that
need to be addressed prettypromptly.
So, as everybody knows, if yourheart stops.
You have to restart the heartwithin a specific amount of
time, or you start to developbrain injury, or you get organ
(08:04):
injury, or you die, and that'sminutes.
The same thing is true if youare suffocating.
You don't get oxygen into theblood, okay?
The same thing is true if yourheart is, is beating, and you're
getting oxygen into your lungs,okay?
But you lose enough blood sothat the pressure falls.
(08:27):
In the system and that's the,they all have the same sort of
time sensitivity because thebottom line is oxygen isn't
getting to the brain and othertissues.
Now, if you bleed in a hospital,and we can control the bleeding,
so a hole opens up somewhere andyou start to bleed.
(08:48):
We can staunch the hole.
Then we can replace the lostblood with stored blood, which
is a transfusion.
And that will fix the problemevery time.
So that's a problem we can solvevery effectively, but you have
to be in a hospital.
The blood can't be deliveredoutside the hospital for
(09:10):
transfusion because it's aliving tissue and it has to be
maintained through somethingcalled a cold chain.
So it, it spoils very fast.
And really, it's only allowedoutside the refrigerators for
about four hours.
So it's just not practical tobring it out of the hospital.
The problem is that people bleedat the scene of accidents or in
(09:35):
their house, so somebody mightdevelop an ulcer and bleed in
their living room, or someonemight be in an accident, like,
let's say you were in the sceneof an accident where a bridge
collapsed you might you mighthave bleeding, or you might be
wounded on a battlefield.
(09:55):
And.
If you can't get the blood, wecan put salt water, okay, in the
bloodstream.
That's all we do now, is we givewhat are called saline
infusions, and that can improvethe blood pressure, but not if
you lose more than, say, Half ofyour blood then it's just not
(10:16):
enough and people will die.
So right now, 20,000 people ayear die before they can get to
the hospital because we can'tgive them blood.
They basically just bleed todeath.
This is quite a bit.
That's just in the US not theworld.
What we're doing is trying todevelop alternatives to natural
(10:36):
blood that are shelf stable andcould be delivered at the scene
of an accident.
So that would keep someone alivefrom the scene of an accident or
from a medical emergency outsidea hospital.
So that you could get them intoan emergency room and get
natural blood.
Charles Schelle (10:55):
I don't know if you have the statistic on the
spot, but as far as deaths dueto loss of blood What's the main
cause?
Is it a car accident?
Gunshots?
Allan Doctor (11:06):
It's, it's trauma.
So it's, it's, I couldn't tellyou, it depends on the region
whether that's more likely.
So for example, in the city ofBaltimore, you know, the car
accidents aren't going, they'reusually not fast enough to
really, you know, cause thatkind of bleeding.
You have to really be on thehighway, but that's where you
get stabbed and shot are incities.
(11:28):
Thanks.
So, for example, in Manhattan,it's all, you know, penetrating
trauma.
However, if you're in a say,where people can get going fast
enough, it's those are thedominant injury is, is a car
accident.
Dana Rampolla (11:45):
You mentioned the saline when when someone gets
that saline infusion, does, dothey still need to have a blood
transfusion when they get to ahospital or?
Allan Doctor (11:55):
Well, it depends on how much blood they lost.
So we have an incredible amountof reserve in our system.
So, for example you know, we canlose half of our red blood cells
so that if you can restore theblood pressure, you don't need
blood.
So you're Literally, we can losehalf.
We have twice as much as weneed, really almost three times
(12:17):
as much as we need, if you havea normal heart, lung, and
vascular tree.
So there's lots of redundancy inthe system, so you can
compensate for loss of red cellsby improved performance with the
heart, the lungs, and thevascular tree.
However, if you've got a weakheart Or you've got problems
(12:40):
with your lungs like emphysemaor you've got problems with your
vascular tree like if you havediabetes or kidney failure, then
you're less able to tolerateblood loss and maybe you can
only lose 20 percent of your redblood cells, but a young
healthy.
Adolescent can lose two thirdsof their red cells, and if we
(13:00):
can stabilize their bloodpressure with a salt saline
infusion, then we don't have togive them blood when they get to
the hospital.
But most of the people bleedingare not healthy 15 year olds,
unfortunately.
Charles Schelle (13:16):
Right.
So, you went into this a littlebit, but, but paint a picture,
what does artificial blood looklike from the start, and, and
how does it work to mimic realblood?
Allan Doctor (13:29):
Well, well, you have to split it into two
components.
There's the principal task ofexecuting the function of red
blood cells, which is to moveoxygen.
Okay.
And then there's the task ofhelping blood clot.
Okay.
Which is what the plasma and theplatelets do in our blood.
(13:49):
So if you need a transfusion bydefinition, you are probably
bleeding.
If you are bleeding and thatcontinues, then you can't ever
stop the problem.
So, obviously, if there's a leakin a hydraulic system, you need
to replace the fluid, but youalso have to stop the leak.
(14:10):
Or, you can't, you can'tstabilize the system.
So we have to, when we'rereplacing blood, we have to pay
attention to both things.
Now, there are differentthresholds for replacing these
two things.
And so you can get away withfirst replacing the oxygen
carrying capacity.
(14:32):
If, for example, you can use atourniquet to stop bleeding in
an extremity.
But if you have internalbleeding from an ulcer or a
fractured liver or kidney orsomething like that, or bleeding
into the chest where you can't,you know, just, it can't be
controlled easily before you getto the hospital.
(14:52):
Then we also have to givecomponents that help stop the
bleeding, which would besynthetic or artificial
platelets and plasma, the oxygencarrier.
Okay.
People have been working on thisfor almost 80 years.
And the principal problem is redblood cells can't be stored at
(15:16):
room temperature.
So What people tried was topurify the key element from red
cells, hemoglobin, and to justput that in the bloodstream,
hoping it would work.
Now, there's a reason thathumans evolved, and mammals, and
basically all animals, morecomplicated than a worm, evolved
(15:41):
with the hemoglobin encapsulatedin a membrane.
It's not free in plasma.
There's a reason for that, inthat it causes injury to blood
vessels if it's free.
And people weren't, didn't learnthis until we tried, you know,
putting Hemoglobin free into thebloodstream and people found
(16:02):
some problems that they tried toaddress with modifying it
chemically and creating complexpolymers and it looked like it
might work and they got very farwith this program, even to human
trials.
But those human trials ended upresulting in making the
recipients even sicker than theywere if they didn't get blood.
(16:27):
And so people were dying fromheart attacks and strokes who
had gotten the artificial blood.
And the FDA closed this programdown in around 2006, 2008.
And the next generation Okay, ofauction carriers all sheath the
(16:49):
hemoglobin inside a membraneinside a cell and that's a more
complicated problem.
And that's the one that we haveworked on, is that we have
designed an artificial red bloodcell where we have a membrane
that imitates the behavior ofthe membrane that encloses
hemoglobin in a red blood cell,and we strip down the contents
(17:15):
to only include the elementsthat carry oxygen.
And so we've done that, and wecan now freeze dry it, so it's a
dry powder, like instant coffee,okay, which is freeze dried, and
just like instant coffee, youreconstitute it by adding water.
(17:37):
And you can drink the coffeeright away after you add the
water, and you can transfuse theblood right away after you add
the water.
So, the way it works is that amedic would carry around the red
powder, which is freeze driedartificial red blood cells, and
you add water, and within a fewminutes, it's fully
(17:58):
reconstituted and can beadministered.
To to normalize oxygen carryingcapacity in blood.
Now, that doesn't help withblood clotting.
That's another subject.
Charles Schelle (18:11):
That's amazing.
I mean, that's, that'sabsolutely a game changer with
how nimble of a product.
It could be, as you said, freezedried, which means you can
pretty much bring it anywhere.
As, as you said, on abattlefield, potentially have
water on hand and, and savecountless lives.
Dana Rampolla (18:29):
How how are you actually testing it then?
Allan Doctor (18:34):
We've been working on this for almost 10 years.
So that's quite a bit of time.
So the initial challenge, ofcourse, was to design the shell
so that it is compatible withour body.
So biocompatible, right?
So you can mix it into the humanbloodstream.
And so we use.
(18:55):
You know, molecules they'reactually fat molecules.
Our cell membranes are made upof fat in case people didn't
know that.
And there are five differentmolecules that we use and they
all have a surface andproperties that are very similar
(19:16):
to the ones that are in ourcells and just the right blend.
And believe it or not, we evenhave to add a little
cholesterol.
Into the membrane to make itlike a normal membrane, and it
will form like a, a littlebubble, like a balloon, and the
balloon is stuffed with thehemoglobin protein that we
(19:36):
normally have in our red bloodcells.
Only these are much smaller,they're about a fiftieth the
size of a red blood cell.
Now, the first thing was to makesure it would capture and
release oxygen, which we wereable to demonstrate.
And that it does it just like ared blood cell.
And the next thing was todemonstrate that it won't break
(19:59):
open when it's flying around thebloodstream.
So we had to work on it to makeit stable for what we call the
shearing stress of going throughcirculation.
And the next was to make surethat it didn't make the blood
too thick or thin.
That's the viscosity of theblood.
(20:20):
And then we had to make surethat it wouldn't interfere with
the way blood vessels work.
The blood vessels have to stayopen, Just the right amount so
that they create enoughresistance to create a blood
pressure, but not so small thatthey don't let blood through.
And this was a huge problem withthe, the quote, naked hemoglobin
(20:42):
that would just go straight intothe bloodstream because it
interfered with the regulationof blood flow.
blood vessel caliber so that weget they would get very small.
They would go into spasm.
Kind of like you get a cramp,you know, in your arm or leg.
And the muscles sort of clinchesup and what was happening is
(21:02):
the, our blood vessels havemuscles and they would clinch up
as if they had a cramp and thenno blood can go through.
And this was being caused by thefree hemoglobin.
So we had to make sure our cellsdon't do that.
And finally, we make sure thatthey don't activate our immune
system, because our immunesystem is designed so that it,
(21:25):
it's constantly interrogatinganything it encounters, is this
part of, of your body or not?
And if it's not, it goes afterit with a vengeance, like it
goes after a virus or a bacteriaor a fungus.
or foreign tissue.
So, it will go after foreignmaterial and that has to be what
(21:48):
we call immune silent.
And so that was all the benchtesting, okay, before we even
got into animals.
And then we started with miceand rats and now we're into
rabbits and we've been workingin for a few years.
And our next step is to moveinto primates.
(22:09):
So, and then humans and we're,what we think is about two years
away from our first trial in, inhumans.
That's
Charles Schelle (22:19):
amazing.
That's
Dana Rampolla (22:21):
incredible.
I didn't even think about theimmunity part that people,
people's cells would reject itor could reject it.
Allan Doctor (22:28):
Yes, so the, the important thing to recognize is
that because it's immune silent,there's no blood typing.
So we can give it to anybodyregardless of blood type.
And in fact, it's so immunesilent, we can give it to any
species.
So we can give the same redcells to a dog a whale you know,
(22:49):
a mouse, a zebra whatever.
So there's a veterinaryapplication for the same
product.
Dana Rampolla (22:56):
Wow, that's incredible.
Charles Schelle (22:58):
You know, I was wondering too, red blood cells
naturally have their ownlifespan.
What's the lifespan of, or doesit even matter, of an artificial
blood cell?
Allan Doctor (23:07):
Oh no, it matters.
So you want it, you want it tocirculate for just the right
amount of time.
That's right.
So red cells, by the way,circulate for about 120 days
after they're born in your bonemarrow.
It's amazing how, how, how weare constantly replacing our
(23:28):
blood.
You turn over about 1 percent ofyour red blood cells a day.
And in the course, which is, youknow, billions of red blood
cells, we have about three orfour trillion red cells, right?
Circulating right now.
It's the most abundant cell inyour body by it's about 80
(23:49):
percent of your cells are redblood cells.
And you make like, I think it'sfour or five kilograms of red
blood cells in the course ofyour lifetime.
So it's a very important cell.
So.
Ours the artificial red cellscirculate.
So about, we speak in terms ofhalf lives.
(24:10):
So that means when about half ofthem disappear.
So the half life is dependingon, on circumstances, anywhere
from 12 to 16, sorry, 10 to 16hours.
So it's suitable for bridgingtherapy from an accident to an
emergency department.
And then.
(24:30):
And then after you get to theemergency department, if you
still need blood, you would thenget natural blood so that they
don't last quite as long oranywhere near as long as a
natural blood cell does.
Dana Rampolla (24:45):
That's so interesting.
When, when you think aboutpeople with, whether they have
well this might sound like asilly question, but what if I
have like some sort ofartificial organs?
Is the blood as effective likeis there anything different if I
have something, some sort of atransplant?
Allan Doctor (25:00):
No.
In fact, there's an applicationfor transplanting that we
haven't discussed.
The primary application that weare working on right now is to
resuscitate people who arebleeding outside of hospitals.
Okay, but there are otherissues.
For example, when we do atransplant you take the organ
(25:25):
out of the donor and you put itinto the recipient and usually
the, unless it's a livingtransplant where you're, you've
got a living donor giving akidney and it's going to you
know, the recipient might be inthe next room.
Usually, you harvest the organin a certain situate place and
(25:50):
time, and you transplant it in adifferent place at a much later
time.
And the organ has to bepreserved as you go from the
donor to the recipient.
And there's a limited amount oftime that you can have an organ
out of the body.
So the time that you can have anorgan out of the body can be
(26:10):
extended if you could create anartificial circulation for that
organ.
And natural blood does not workthat well in this situation, and
so the blood substitute canextend that time.
The duration between organharvest and transplant and even
(26:32):
resuscitate organs that mightnot be working so well.
So if somebody is donatingorgans, often they're, they're
not just they're not healthy.
So they sometimes those organsare impaired and you can get
them out.
and resuscitate the organ, thenyou can salvage organs that
(26:53):
would not otherwise betransplantable.
So there's a transplantapplication for the synthetic
blood.
Also, when you go oncardiopulmonary bypass in the
hospital for heart surgery orlung surgery, sometimes you, you
have an artificial circulationand that requires blood.
(27:14):
Now, especially for babies.
Now we envision the possibilitythat you could.
When you put someone on bypass,take their own blood and take it
out of the system and store it,do the operation under
artificial blood, and thenremove that and put the natural
blood back.
(27:35):
And that would prevent somebodyfrom getting exposed to
transfusion, becausetransfusions during bypass
operations create injury.
Additionally, you've heard ofinterventional.
Radiology where they doangioplasties and open blocked
arteries.
(27:55):
So to open a blocked artery, youput a balloon in a catheter and
blow up the balloon and yourelieve a stricture or you break
open a clot.
And you do that in the brain andthe heart and the kidney, other
really vital organs.
So your ability to do that islimited by how long you can hold
(28:16):
the balloon up.
Okay, because no blood goes pastthe balloon when it's open.
If instead you can giveartificial blood through a
catheter tip that goes beyondthe balloon, then you can extend
the time that you can keep theballoon up and make those
operations, those proceduressafer.
(28:37):
So there's lots of otherapplications for this, even in
space.
So, to go to Mars there's noblood bank on possibility there,
or, and the current, believe itor not, the current plan for
space travel, if there's anaccident where there's bleeding,
is to hold pressure.
(28:58):
That's it.
So there's no possibility ofbringing a blood bank with you
because of the weightconstraints.
And the only other option wouldbe to have astronauts that have
compatible blood types, so thatif someone needed a transfusion,
you could take blood from them.
from astronaut one and give itto astronaut two.
(29:19):
Now, obviously that's not ideal.
So NASA is actually interestedin freeze dried blood because
it's light.
So there are all kinds ofapplications that are in unusual
circumstances for if we couldsuccessfully create freeze dried
blood.
Charles Schelle (29:37):
You, you brought up a good point.
The interest in it, just theconcept of substitute blood just
tips the scales and opens up allsorts of possibilities.
So with that, obviously you havethe attention of the federal
government.
So, tell us a little bit aboutsome of the funding and research
commitments that you've receivedrecently.
Allan Doctor (29:56):
So our initial seed funding came from the NIH
and the Department of Defense.
We designed this technology andcreated a company called
KaloCyte which means beautifulcell in Greek to to develop the
artificial red blood cell.
And we received about$5 millionin support from the NIH and
(30:20):
Department of Defense.
To do the initial proof ofconcept work, we've received
about another 10 to$15 millionin in grants from the NIH and
federal Government, and about$5million in private uh, equity
funding um, for the company.
(30:42):
The research program hasrecently secured a very large
grant from DARPA, which is theDefense Advanced Research
Administration.
DARPA doesn't just do biologicalresearch, you know, they
famously created the internet,Develop stealth technology and
(31:04):
other wild things.
So they do high risk, high gainprojects, and the Department of
Defense wanted to create asynthetic blood program.
So that would be both the bloodclotting and auction transport
functions.
And we competed with about 10other teams for that award,
(31:25):
which is almost 50 million todesign and generate.
synthetic blood that can befreeze dried.
Charles Schelle (31:35):
And you have an entire consortium working on
this, too, right there.
There's like a what is it a 15site consortium across the
country?
Allan Doctor (31:41):
Yes, there's multiple sites, including
several, um, large universitiesas University of Pittsburgh,
University of California, SanDiego Case Western Reserve
University Penn StateUniversity.
Are all and Ohio StateUniversity are all participating
and then several small companiesthat are generating the
(32:05):
components.
KaloCyte is generating theoxygen carrier.
There's a small company calledhemotherapeutics that is
developing the syntheticplatelet.
And there's a larger companyTeleflex that is generating the
freeze dried plasma.
And then a a research Institute.
Called Southwest ResearchInstitute that is helping with
(32:27):
production scaling and biomanufacturing.
Dana Rampolla (32:31):
It's incredible.
So you are actually here at UMB,University of Maryland,
Baltimore, working on this.
Tell us, has UMB been a supportfor this type of faculty
entrepreneurship?
Allan Doctor (32:44):
Yes, well, it's why I moved here.
So I, I was at WashingtonUniversity in St.
Louis and that's where weoriginally invented this
technology and started KaloCytein St.
Louis.
And I also led the.
You know, the critical caregroup at St.
Louis Children's Hospital andran the division of pediatric
(33:04):
critical care at Wash U Schoolof Medicine.
We were, um, working with thebiopark there which was an
incubator for small companies.
It was institutionally a littlechallenging to create an
effective and seamlesspartnership.
I think that uh, facultyentrepreneurship is an evolving
(33:26):
area in higher education andinstitutions with a major
research focus, and some havebecome more agile than others.
As our program was growing, wewere looking for an ideal
environment that would reallyfoster the opportunities for
synergy between my academic laband the, the companies that were
(33:51):
spinning out of the lab.
And so, University of Marylandyou know, we looked all over the
country and uh, was exceptionalin what they were, the
environment the proximity to NIHand Department of Defense to the
Shock Trauma Center, and theBioPark here, and the university
(34:13):
and leadership at UMB was uh,very flexible and in allowing us
to embed small companies in anew research center in
university space, which was avery innovative and frankly new
for UMB.
It is the reason we were able tocompete effectively for this
(34:37):
DARPA award.
No one else had the sameopportunity to offer the
government such synergy betweenthe small companies and the
unique capabilities that arereally only available at
research institutions.
Charles Schelle (34:52):
It's great to hear.
And we're glad that you chose usto relocate your company and
your research here.
Yeah, as you mentioned,University of Maryland Biopark
is an amazing area on ourwestern edge of our campus.
There are so many biotechcompanies there.
It's a great thrivingenvironment and it's growing.
We have the 4MLK building goingup, hopefully completed soon.
(35:16):
We'll have space for even morecompanies, more like yourself.
Allan Doctor (35:20):
You know, and, and it's not just the, the, the fact
that we came here, the, youknow, the Office of Technology
Transfer has, you know, providedincredibly robust support for
new intellectual propertygeneration.
We've created many new patentssince we've come here.
They you know, have a lot ofbusiness expertise.
(35:41):
They've supported.
Our company executive leadershipin fundraising with the local
community and Maryland itselfhas a very favorable environment
for investing in biotech.
So, it's not just the, thescience it's also been the the.
(36:02):
I guess the serviceinfrastructure that's also been
very crucial and given us a,frankly, a competitive edge that
is unmatched.
Dana Rampolla (36:12):
Tell us a little bit more about the center,
obviously it sounds like thingsare going great in this area,
but how does it fit in witheverything else that you're
doing and like how, how has itgrown in size since you've been
here significantly?
Allan Doctor (36:26):
Yeah, so the the research center is so it's
called the Center for BloodOxygen Transport and Hemostasis,
which is blood clotting.
So it's pretty obvious what wework on basically the you know,
the, if it, it has to do withblood and you know, moving
oxygen and the clottingfunctions of blood, And we work
(36:49):
on that.
We also study ways to optimizeconventional blood storage.
You know, that's basically 1950stechnology that hasn't been
meaningfully improved since thattime.
And there's a lot of room forimprovement there.
So we have a number of projectsin that area.
We've recruited two key facultymembers to join me here at the
(37:12):
center.
They each lead large researchprograms.
Each of those labs has about 10to 16 people in them.
And so they are traditional labswith graduate students and
postdoctoral fellows that studyyou know.
topics related to bloodfunction.
I also have an academic lababout that size and we study
(37:34):
acquired injury to red bloodcells.
For example, how diabetes orkidney failure or infections can
alter red blood cell functionand how to mitigate that.
We also study sickle celldisease and We're developing
therapeutics for for sicklecell.
(37:54):
So, you know, the growth hasbeen quite rapid.
Our you know, one measure of usof progress is the funding,
which has improved almost about700 percent in extramural
support since we've come here.
And that's excluding the bigDARPA grant, which is kind of an
outsized you know, addition.
Charles Schelle (38:16):
The Dean's a little bit of the same ilk of
that entrepreneurial spirit and,and supporting this with the
faculty entrepreneurship.
What have you've kind ofobserved and what can you tell
us about what Dean Gladwin kindof brings to this?
Allan Doctor (38:30):
Well, sure, I should 1st mention that, you
know, it was, you know, DeanReese that that brought me here.
And through an initiative, hecalled the STRAP program where
he basically invested sufficientresources to give a space and to
recruit an entire team.
And so he really was the seed.
(38:50):
And Dean Gladwin, as you know,has succeeded Dean Reese.
I've known Dean Gladwin foralmost 20 years.
And we work in a very similarscientific domain.
And he Also is is anentrepreneur, has started a
company called GlobinTherapeutics.
He's very supportive of our workand faculty entrepreneurship in
(39:14):
general.
We have an evolvingcollaboration, in fact.
And I couldn't be happier withhis leadership.
He's been incredibly supportiveboth he and Dr.
O'Donnell who's the vice deanfor research have been very
supportive of the center and Iexpect that others like me will
(39:36):
find this an ideal place to comeand do their science.
Charles Schelle (39:41):
Fantastic.
Well, we've really kind oftouched on the very tip of
artificial blood in our shorttime here, and hopefully your
research continues with greatsuccess, and, can't wait to have
it hit the market and saveplenty of lives,
Allan Doctor (40:00):
Well, thank you for the interest and the
opportunity to discuss it.
If anybody in the universitycommunity would like to learn
more or interact in acollaborative fashion My name's
pretty easy to remember.
And so I'd be delighted to toaddress any inquiries from the
community.
Charles Schelle (40:21):
And we'll make sure we'll put those in our show
notes too.
So all of our listeners justcheck the description and you'll
find out how to reach out to Dr.
Allan Doctor.
So, Doctor, thank you forjoining us on the UMB Pulse.
Allan Doctor (40:34):
Thank you for the opportunity.
Jena Frick (40:41):
The UMB Pulse with Charles Chalet and Dana Rampolla
is a UMB Office ofCommunications and Public
Affairs production, edited byCharles Chalet, marketing by
Dana Rampolla.
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