June 26, 2025 • 50 mins
In this episode, Dr. Sciarretta speaks with Dr. Muhammad Mohiuddin, a surgeon who specializes in cardiac xenotransplantation (replacing failing human hearts with pig hearts). Listen to hear more about Dr. Mohiuddin's journey, the ethical and structural issues his work presents, and the moments in which his decades of revolutionary work have come to fruition.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:02):
Welcome to the Hangout Podcast.
I'm your host, david Sharetta.
Come on in and hang out.
In this episode, I wasprivileged to have a
conversation with Dr MohamedMohi Houdin.
Dr Mohi Houdin is Professor ofMedicine at the University of
(00:23):
Maryland and is also director ofthe cardiac xenotransplantation
program.
As he describes in this episode, xenotransplantation is the use
of genetically modified animalorgans in humans, and Dr Mohi
Houdin gives us an inspiringthree-decade description of his
(00:47):
career that led up to theseminal moment in which a
genetically modified pig heartwas used and transplanted into a
human who was near the end ofhis life, and what the
remarkable impact of that was.
Remarkable impact of that was.
(01:09):
Dr Mohi Houdin is a worldwideleader in this field but is
exceedingly humble.
Gives all the credit to hisfellow researchers, as well as
to the patients who haveparticipated willingly in this
collective advancement ofscience for the future good of
humanity, as we face a chronicshortage of organs to meet the
needs for organ transplantationsaround the world.
I hope you enjoy thisconversation as much as I did.
(01:32):
Welcome, dr Mohamed.
Thank you so much for joiningme today and for the generosity
of your time and your expertise.
Speaker 2 (01:49):
Thank you.
Thank you, thank you forinviting me and pleasure to be
here.
Speaker 1 (01:54):
I thought we could get started with you sharing a
little bit about your originstory, where you come from and
what led you to your currentwork from and what led you to
your current work?
Speaker 2 (02:09):
Yeah, I mean, I came to this country around in early
90s to be specific in 91,aspiring to be the best cardiac
surgeon you can be and you know,and getting all the training
here Until that time.
You know, I'm originally fromPakistan and people used to go
(02:31):
to England and get theirtraining and come back and serve
in their country.
But then US opened up and mostof my classmates started coming
to US to get their training.
My classmates started coming toUS to get their training and
that was my case also.
However, I landed at theUniversity of Pennsylvania and
(02:58):
while starting my fellowshipthere, you know I was intrigued
by the research being done there.
At that time there were some bythe research being done there.
At that time.
There were some landmark papersthat came out from that
institution, in fact thatparticular group.
So I was convinced by my mentorat that time that if I go into
(03:21):
the field of xenotransplantationI may have the potential of
helping, you know, severalhundred four more people than I
will be as just a cardiacsurgeon.
So that kind of, you know,didn't sink in at that time.
But after working there for acouple of years, and after
(03:50):
working there for a couple ofyears, you know, then I made up
my mind that this is exactlywhat I want to do, because in my
mind I believed in it.
That, although we were workingon a small animal model, putting
a hamster heart in a rat, youknow, to go from there into
human was a long journey and,you know, even my family was not
(04:11):
very committed.
That you know, is it this whatyou want to do?
I mean, do you think this isthe right path?
But, you know, for some reasonbelieved in it and and chose to
continue, uh, that that path andand that path led to it took me
(04:33):
about 33 years to do, uh, thefirst human transplant.
Speaker 1 (04:37):
So so I mean, you know, there there's lots that
happen in, yeah, thank you forthat overview and I know there's
a lot of work that went intothose three decades.
Right, as someone who, of myage, I remember the Baby Faye
case, which was kind of a popculture phenomena of, I think, a
(05:03):
newborn, an infant who received, I think, a baboon heart and
just lived for a very shortperiod of time.
What has kept you going forthree decades in a field that I
think the average person doesn'teven fully understand?
(05:24):
Right, it almost seems like asci-fi field.
Speaker 2 (05:28):
Yeah, I've been told that I've been working in a, I'm
doing some kind of a voodoowork.
I won't lie that there wereseveral periods in that journey
that when I questioned myselfthat, am I doing the right thing
(05:50):
?
Because the field at times, youknow, completely died right
indulging in this kind ofstudies.
There was a time when therewere moratorium on
genotransplantation in certaincountries like England, just
because the initial transplantswere done using non-human
(06:14):
primate organs and they laterfound out that there could be
some diseases that can betransmitted through non-human
primate, like HIV.
So that kind of killed thatfilter, just like baby faith.
There were multiple othertransplants that were done,
(06:35):
transplanting kidneys mostly,and livers, but they all failed
because they didn't have anybackground of research in it
also and you know, were done asa desperate measure to save life
.
So I mean, you know those kindof experiments did happen
(06:59):
earlier, earlier than so, andyou know I what motivated me was
whenever, you know, things got,you know, slow, or you know,
(07:22):
when I was started thinking of,you know, just going back to
cardiac surgery, you know somehope came in and that kept the
fire burning.
You know the real hope came inwhen I moved to NIH National
Institute of Health in 2005,.
In 2005, where, you know, I wasgiven complete liberty to
(07:48):
develop this program and youknow, before that you were
working for someone else, youwere following someone else's
you know mission.
But here, you know, I kind of,you know, developed my own ideas
(08:10):
and that definitely helped.
I mean there's a lot of peoplewho helped me on the way.
I couldn't have been herewithout their you know
mentorship and effort which Itried to, you know, transfer to
my mentees.
But again, like you said, itwas a very, very hard job.
(08:31):
I mean, it was like lots of upsand downs during that journey.
Speaker 1 (08:37):
Now, as I understand it as a complete layperson just
doing a little bit of research,it's fundamentally driven by the
extreme shortage of.
Let's just take in this example.
We're talking about hearts theextreme shortage of available
hearts compared to the number ofto the need.
(08:58):
Right, that's really what'sdriving that.
Talk to us about what thosenumbers look like and how that's
pushing your work forward.
Speaker 2 (09:08):
Yeah, so approximately, just in the
United States there are about150,000 people who are waiting
for an organ for transplant.
They have reached at a stage intheir organ failure where the
conventional treatments cannotprolong their life.
(09:29):
So these patients, if theydon't get a human organ, you
know they are sent to hospicewhere they spend their last days
and you know effort is made tomake that phase easy for them
and effort is made to make thatphase easy for them.
So, basically, there was nohope for these patients and,
(09:56):
however, there are othercompeting technologies that are
being developed For heart.
There are mechanical heartsavailable, left ventricular
assist device and now totalartificial heart, but they have
their own problems and they havenot reached to.
You know they have not beenable to help every single
(10:18):
patient who's on the waitinglist.
The problem with kidney is evenmore, because you know there are
larger population who have, whoare going through kidney
failure.
But at least they have a backupof dialysis for them.
But for hearts it's definitelynot.
There's no other choice if youare not eligible for a
(10:40):
mechanical device.
So all these, all thesepatients you know are in a
desperate condition, even youknow, if the organ donation is
increased several folds and youknow every single one of us
become an organ donor.
Not every single organ becomeseligible for transplant also, so
(11:02):
you know you have to match theorgans to the recipient.
You know a lot of us carrydifferent diseases, which
prevents us from being a goodorgan donor.
So all these factors kind ofyou know, prevents all the
organs that are harvested forthe purpose of transplantation
(11:25):
to get into a human.
So I mean there was an extremeneed for finding an alternate
organ and besides generating a3D printed organ, which is being
done, a 3D printed organ, whichis being done, or somehow
(11:51):
making the organ that are noteligible more eligible by, you
know, some treatment.
You know there was no otheroption.
So I mean, you know we aresuggesting, you know, non-human
organs as an alternate and withthe technique of gene
modifications, we now believethat we can alter the genes of a
(12:12):
donor organ or the donor animalto an extent that it becomes
more acceptable to humans.
Speaker 1 (12:20):
So, as you described to me when we did a previous
call previous to today, thatoftentimes the drugs that
recipients need to take toprevent the rejection of an
organ can be the thing thatactually is the most that
(12:41):
sometimes can kill the recipient, correct?
Can you talk to us about thatand about the importance of this
breakthrough of the geneticmodification of the animal heart
?
Speaker 2 (12:54):
Yeah, so I mean, you know, with the advancement of
these immunosuppressive drugs,you know we are at a stage where
, you know, the graft survivalhas extended beyond you know,
years, right, and it is allbecause of these
immunosuppressive drugs.
But these immunosuppressivedrugs that are currently used in
(13:20):
human-to-human transplants,they don't discriminate between
a good and a bad cell, so theyare kind of like nuking the
entire immune system, right?
So in most cases and you aredependent on these drugs for
your lifetime, once you receivean organ, and most of the time
(13:44):
the toxicity of these drugs isthe cause of, you know, the
graft recipient's death versusthe graft itself, sometimes the
graft is still functioning verywell, but you know the person
who's the recipient, you know,kind of dies or become morbid
(14:06):
because of the toxicity of thesedrugs.
Speaker 1 (14:10):
So you mentioned very humbly that about 30, 31 years
of work went into, you know,getting to the point of the
success the first successful pigto human heart transplant.
What was that like when youfinally, you know, were in that
surgery and you know what led upto that?
(14:32):
And then what was the follow-upto it too?
My understanding is that thepatient lived for some period of
several months afterwards.
Talk us through that wholeprocess.
Speaker 2 (14:42):
So I mean, you know, honestly, throughout this period
, although I believed in it, Ithought, I think that this is a
very valid option for thesepatients who are critically ill
and have no other options.
However, you know, I neverbelieved that this would have
happened in my lifetime.
(15:03):
This would have happened in mylifetime.
So you can imagine when we putthe first big heart in a human
and it started to beat and thatperson woke up.
I cannot even describe thatfeeling right.
I mean it's like your entirelife's work coming to fruition
(15:26):
right before your eyes.
So I mean, you know that istotally.
What happened afterwards isthat you know these, the
patients who who we were allowedto give these hearts to, we're
at a stage that if we had notgiven them this heart, they
(15:47):
would have died the next day.
So, in fact, our second patient, his heart arrested twice even
before the transplant and we hadto resuscitate the heart and
keep him alive until we wereable to put this transplant in.
As I mentioned earlier, I meanthere is no alternate for those
(16:08):
patients.
There is a machine called ECMOthat you use to hook to a tubing
and that machine kind of actsas a pump to circulate the blood
, which is the main function ofthe heart.
But you cannot live on thatmachine forever.
(16:28):
It's a heavy machine, youcannot carry it.
So our first patient was onthat system for almost 40 days.
So he wasn't bedridden.
He couldn't even go to hisbathroom.
So after the transplant hismajor wish was when I'd be able
to walk to the bathroom right.
So for two months he had notbeen able to go to the bathroom
(16:51):
himself.
So some of those were the smallwins that we counted.
I mean, if you think of as alay person and say that, oh,
this, your first patient livedfor only 60 days, you know what
(17:12):
have you achieved.
I mean, you know that 60 daysis nothing for us who are
healthy, but for a person whoyou know, who doesn't know that
he will be alive tomorrow, those60 days means a lot, means a
lot.
And you know they were able toenjoy those 60 days, although
(17:33):
they were sick, but they wereable to, you know, bond better
with their families and did alot of unfinished business that
they could have done from thehospital.
Speaker 1 (17:47):
Well, I mean you, essentially you had a 60x return
on investment, so to speak.
Right, that's tremendous.
Speaker 2 (17:57):
Yeah, and you know we never promised that to the
patient because we didn't knowRight.
I mean, you know we have donehundreds, or in my case
thousands, of experiments inanimal models and we were
confident that we would not seerejection on the table.
This heart will beat and thispatient will get up.
(18:18):
But until we do that, you knowwe don't know right.
You know that will happen.
But when that happened, youknow it made even a stronger
believer out of me.
Speaker 1 (18:30):
And I know I'm sure there's definitely privacy
concerns too but was the causeof death of that patient
rejection of the heart?
Eventually and it was just youwere able to extend that much
farther than you had originallyanticipated, but eventually the
body rejected it.
Speaker 2 (18:50):
So you know, as I mentioned, these patients were
very, very sick.
So the experiments we have donebefore that led to these two
transplants were done in likehealthy animals, right.
So those animals were able totake a stronger
immunosuppression and you knowother manipulations.
(19:13):
However, these patients werealready so sick that we cannot.
So we had a dilemma whether tosave the patient or save the
graft.
So we had to create that savethe patient or save the graft.
So we had to create that a verydelicate balance between the
two.
For that we had to reduce theimmunosuppression, because that
was kind of, you know, causingthe patient to get even sicker,
(19:38):
but that made the heartvulnerable to rejection also,
and ultimately that's whathappened, right.
So we were fighting to maintainthe adequate drug levels, which
we could not because of thecondition of the heart you know,
he was getting infected and allthat and in the end, you know,
(19:59):
the rejection process took over,and in the first one we were
not clear, but in the second one, definitely this is what
happened.
But once we evaluated and weare still evaluating all the
specimens that we, these twoheroes, with whom I call heroes,
who devoted their life for thelearning of science, right.
(20:22):
I mean they themselves believethat they do not have a chance,
but they wanted to go throughthis so we could learn and help
others.
So I mean because of theircourage.
You know we are still learningto date from the specimen that
we have achieved from them.
Speaker 1 (20:41):
That's a fascinating perspective that you bring up
the courage on the part of therecipient, right?
I mean?
Oftentimes we think about thegroundbreaking efforts of the
researchers, and that'scertainly the case here, but the
ethical considerations andalmost the personal sacrifice,
(21:03):
sacrifice, familial sacrifice,of someone saying I either have
no days one day or x amount ofdays and I'm going to go through
this.
I obviously want to be around,to be with my family, but if not
, it's this sacrifice for the,for the, the future research
corpus moving forward thatperhaps can change humanity.
(21:25):
That's pretty, that's something.
Speaker 2 (21:27):
Yeah, no, that's totally.
And you know, even after thesepatients have passed, their
families have been equallysupportive and have been, you
know, spoke person for our cause, right, and because they don't
want their loved one's sacrificeto go in vain, right.
(21:50):
So they, whenever we ask themto come to our meeting and have
them write and talk to anyreporters or you know a group of
people where we are kind ofconvincing them to, you know,
consider this option.
You know they have been veryforthcoming in that help.
(22:11):
They both have written their,you know their experience and we
have published thoseexperiences from their immediate
families also.
Speaker 1 (22:20):
Now you mentioned that you never thought this
would happen in your lifetime,and so it's kind of moved faster
than you anticipated.
Is the vision that eventually,the efficacy of these procedures
will get to the point wherethey can be more routine and
used with someone for whomthere's a medical necessity, but
(22:43):
they're perhaps not at such anend stage that their survival,
no matter what happens, is inquestion?
Speaker 2 (22:51):
That's exactly the future, right?
I mean, you know that's in anideal world we would be able to.
We would have enough organs,you know, available and sitting
waiting to be transplanted thatwe don't have to wait for an end
.
Organ failure Means that youknow when the heart comes to the
(23:15):
stage where it requirestransplantation, by that time,
you know, since heart controlsthe blood flow to all the other
organs, your other organs alsostart getting damaged and you
know, in most of the cases thereis multi-organ failure.
So if we are able to prove thatthere is a heart which is from
(23:39):
a young animal, like pig, thatwill not go through rejection.
So a pig lifetime is about 20years.
So the pig that we use in theseexperiments were only one year
old.
So in an ideal world you have19 years left in that heart,
(24:02):
right.
In an ideal world, you have 19years left in that heart, right.
So if you transplant andconvince someone that, okay,
this heart you know will workfor 19 years, you have a 19-year
warranty on this heart and youmay not need a heart right now
but in five years or 10 yearsyou will need a heart.
(24:23):
So would you do you want to gothrough the suffering of those
10 years, then get another heart, or do you want to get it now,
right?
So, so this is, this is way youknow I'm talking not in my
lifetime, probably, but whoknows?
You know, and then other major,major advantages that what we
(24:47):
have not talked about is thegenetic modifications of these
organs, right?
I mean, the technology we haveavailable now was not available
like a decade ago, right, decadeago, right.
(25:07):
So with this technology, we cantake out any, any antigen that
is, you know, immunogenic tohumans, that to which we react,
and we can also add human genesto uh, to the construct and and
and make a customized pig right.
So so the future it is apossibility that you know, when
you're born, your genes aretaken out and you know, and a
(25:30):
pig is made ready for you whenyou need it, and my
understanding, too, is that theone of the benefits of the pig
is that you can grow a heartfairly quickly.
Speaker 1 (25:40):
Right, it's not in what a year or so.
Speaker 2 (25:44):
Yeah, so in a year the organ grows to a size of an
adult human in terms of heart.
You know, in heart it's verycritical to match the size.
But in other organs, likekidneys and livers, you don't
even have to get to the the size.
But in other organs, likekidneys and livers, you don't
even have to, you know, get tothe exact size.
(26:06):
You know, in liver you can do apartial liver.
Uh, you know.
And and if in china there was atransplant done when, when
there was a cancer in the liver,so they took the part of the
liver that had the cancer, put apig liver for a month.
During that period, you know,liver has the tremendous
(26:28):
potential of regeneration.
The liver, the original liver,grew to a size that it can
support life.
Then you can.
They took out the porcine liverand that way you know that they
bridge the transplant throughliver of a pig.
Speaker 1 (26:48):
I want to talk a little bit about both ethics,
because I'm sure that those areparts of conversations that
always come up for you, as wellas what your critics say perhaps
not your own personal critics,but critics just in general of
the field.
Right, what are some of theethical considerations that you
go through in your work?
(27:09):
And then, what do critics say,people who would like this
either this research to stop orto pause.
Talk to us about the obstaclesyou've faced in those regards.
Speaker 2 (27:24):
So one of the major reasons that we picked pig was
that you know it's been consumedfor the dietary needs
throughout the world, right?
Almost about 90,000 pigs areslaughtered each day in United
States for that purpose.
So we thought that, you know,if we are using maybe 100 pigs a
(27:47):
month for this purpose, youknow it won't be a problem.
But certainly you know therewere people who were very
critical of, you know,sacrificing a healthy animal for
that purpose, although you knowthe meat is consumed in their
(28:13):
meals.
But so that was our major issue, that you know why, you know,
sacrifice a healthy life to savea human life.
I was even asked whether youwill do the other way around.
Would you give a pig your heartto save his life?
(28:35):
Right?
So I mean, you know people goto that extent also, and I've
also been asked why is itimportant to save human life?
Right, I mean, you know, ifit's ending at a certain point,
you know why should we evenprolong it, right, you know?
So I mean you know there are alot of different opinions
(29:01):
outside.
My goal and the oath I havetaken is to save life, right?
So if, even if I save one life,I mean that is.
You know it's important for me.
So, so I kind of, you know, um,take that criticism, but, uh,
but try to convince them.
(29:21):
You know my goal is to savesomeone, you know who needs to
be saved at, you know, and thisis one of the ways I can save it
.
I mean, I'm sure you will askabout, you know the religious
restrictions right.
So you know, growing up youmust have read that.
(29:43):
You know my father used to.
You know, politely, tell me,you know, could you find
something else, could you findanother?
And still, you know I go todifferent countries where people
ask you know why pig and whycannot you do it?
Take a cow's heart?
Or you know, a camel's heart orsome other species heart, a
(30:05):
camel's heart or some otherspecies heart?
So I mean, that has always beena you know a question and still
is.
However, you know you'll besurprised to know that now the
awareness is growing.
So even in UAE, you know, thereis a verdict that because in a
(30:29):
lot of Muslim countries, youknow, the taking organs after
brain death is not allowedbecause they think that you are
mutilating the body Rightcountries there is, they are
(30:51):
thinking that you know if youcan have an organ from another
species and not mutilating thedonor, the human donor, then
maybe that is a better way to go.
And also it's also, you know,in UAE they have always issued a
fatwa, that you know, if youhave an option that you can use
(31:11):
to save a life and you're notusing it, you're making a bigger
sale, right.
So I mean, you know there aredifferent aspects, so the same
thing with.
So I'm president ofInternational Genotransplant
Association.
My effort has been to gatherall these opinions from
(31:33):
different religions.
So we have gathered, you know,all the leaders of different
religions together in one roomand ask their opinion and in the
end, the common consensus isthat to save a human life take
precedence over anything else.
Speaker 1 (31:51):
Yeah, it's interesting, you can imagine a
Buddhist as well, right, yeah,yeah, so vegetarian and do no
harm.
And it brings that ethicalquestion of by you not following
through on the Hippocratic oath, then essentially you're doing
harm.
Speaker 2 (32:09):
Yeah, yeah.
So that's, I think, the basisof you know why it's getting
popular in some of the MiddleEastern countries.
I mean, it's not done yet, butthey're interested in it.
Speaker 1 (32:25):
So, and as you were speaking and when you made this
comment that you might not seeit in your lifetime, it, almost
just as a side thought it, itreminds me of, you know, one of
these great masterpieces ofhistory.
Or we look at the SistineChapel, or we look at these
great constructions that spanmultiple lifetimes and you think
(32:48):
about architects who designedthem, or you think about master
builders or master painters whoworked on them and they knew
that they would not live longenough to see the finished
product.
But you're contributing tosomething that is greater than
yourself and greater than yourown lifetime yeah, I mean not
(33:09):
only me, I mean these patientsalso.
Speaker 2 (33:13):
I mean, you know, who do you know, I don't make a big
case of what I have done.
I kind of, you know, appreciatethe effort of these patients.
If these patients would nothave said yes to this procedure,
you know, nothing would havehappened, right?
(33:36):
So so they took the courage, soso.
So I mean, you know, they'reour two patients.
I will never forget them forthe rest of my life, right, and
I don't think history willforget those patients because of
their sacrifice, right.
So they may forget what I havedone, but those people were the
real pioneers in starting thisthing.
Speaker 1 (33:55):
Who pays for such procedures?
Are these grant funded?
Talk to us about that.
Speaker 2 (34:01):
So this is a very difficult and expensive process,
right?
So, just to give you an example, even when I do an animal
research like put a pig heart ina baboon, it costs about
$500,000, right?
So, when we did this humantransplants, they cost about
(34:23):
$1.5 million for 60 days.
So it's a very expensiveprocess at this time.
And there are several companieswho are generating these pigs
have interest in producing thesepigs in masses and and to
(34:48):
overcome this shortage of organs.
Right so they have invested alot in these experiments.
And also, our first transplantwas paid by our university and
the hospital.
The second one was paid by oursponsor who produces the pigs.
Similarly, the people who havedone kidneys they got funding
(35:13):
from their sponsors who aremaking these pigs, because these
pigs are basically considered adrug by the FDA.
We are producing this drug tosave a human life.
Speaker 1 (35:31):
And I'd imagine at some point there's also
government funding, right,Depending on, I'd imagine and
you mentioned an internationalassociation that you're the
president of.
So I'd imagine, like in thecase of China, that was probably
state funding in that case, andso is there kind of a patchwork
of state private funding forall of these efforts.
Speaker 2 (35:53):
So I do.
I do have NIH grants thatsupported, and when I was at NIH
for 13 years, it was allgovernment, federal government
funding that helped you know theprogress of this field.
However, you know, as we know,the medical system here is
totally dependent on insurance,and you'll be surprised to know
(36:17):
that our first patient had aclause in his insurance that
knows, you know, transplantationcan be done.
So these guys think way aheadof us, right?
Speaker 1 (36:40):
As you were talking about the cost, I flashed on my
own insurance and my HMO planand I'm trying to get something
approved that's out of network,something small.
That's out of network,something small.
Speaker 2 (36:54):
I thought imagine the Herculean effort to try to find
the backing for something likethis.
Yeah, so I mean, but you knowthe advantage of.
You know a lot of insurancecompanies spend a lot of money
in preventive measures, right?
So if they can spend some moneyon preventive measures so they
can avoid spending a lot ofmoney in preventive measures,
right?
So if they can spend some moneyon preventive measures so they
can avoid spending a lot if thedisease occurs or you know they
(37:18):
want you to control your bloodpressure and you know diabetes,
so that you don't get to thestage where your organs need to
be replaced, or you know othertreatments needs to be done.
Similarly, if you have a pigwhere you can take about seven
different organs from that pigand save seven different lives,
(37:45):
the cost will drastically comedown.
At least my hope is that itwill replace allotransplantation
, although initially you knoweveryone will prefer a human
organ versus a non-human organ.
But if you are able to convincethem that this non-human organ
is a better replacement than anorgan from someone who has
(38:09):
scarring diseases or, you know,is older and we don't know how
this organ will function, thatthings will change and you know
the insurance company will seeit as a you know.
So a lot of companies ask me youknow, when will you be able to
do?
Like a thousand transplants ayear?
(38:29):
So I don't usually give themtimeline, but that's a real
possibility, right?
I mean, you know, like I said,that if you can offer a
transplant at an earlier timepoint of the disease, you can
definitely, you know, do moretransplant than even required,
more than the people who are onthe waiting list.
(38:52):
So you know, that way a lot ofthese organs will be consumed,
and the advantage is that if youhave like 20 years of life in
this organ, you can, after 20years, give exactly the same
organ again, really.
So I mean, you know that cankeep going, right.
(39:15):
So, and then you know,customizing that organ for
yourself will also help youeither reduce the immune
suppression or and my goal is tocompletely avoid the immune
suppression you, you, you modifythe genetics to an extent that
you know you don't, your, your,your organ will behave just like
(39:40):
your original organ and will,and your immune system will look
at it as its own and will notattack it.
Speaker 1 (39:48):
It's fascinating to think about how we create mental
constructs around ideas, right?
So, for example, my daughterhad jaw surgery and they placed
some essentially a cadaver boneand then eventually her body
(40:09):
absorbed it.
And the one you know school ofthought would say, oh, I don't
want to quote, unquote deadperson's bone in my jaw, but
biologically that's not even anissue, right, the body absorbs
it and it helped my daughterwith her surgery.
So we passed that, and I'm surethere's been thousands and
thousands of those surgeriesthat happen every day around the
(40:31):
country, and it's not a bigdeal.
Maybe 50 years ago people wouldhave thought that was some sort
of an abomination, and so doyou think in 100 years from now
we'll be at a place where thisis fairly commonplace?
Speaker 2 (40:45):
I hope so I mean, you know that's what we believe in,
that you know that, you know we.
You know the technique of genemodification is continuously
evolving and you know we shouldbe able to, you know, completely
change the genetics of a pigand make it more what you call
humanized and in that way avoidthe immunosuppression completely
(41:09):
or induce some kind oftolerance.
There are ways, you know, Ihave been working on and others
have been working on, to teachyour immune system to recognize
something that you're placing inyour body as not foreign and
self, so that if we are able toteach the immune system and
(41:30):
immune system is, you know, youcan teach it.
And if you are able to do that,then again you don't need all
these gene modifications.
Your immune system will learnto recognize that these foreign
antigens as their own and willnot attack them.
So that's also, you know, oneway of you know, overcoming and
(41:55):
avoiding the drugs.
You may need some drugs forinitial period of time.
Then you can slowly withdrawthem and you know, have the
patient without drugs A lot of,as you mentioned, as I mentioned
to you, that a lot oftoxicities of these drugs cause
the premature death of thepatients.
(42:17):
However, sometimes, you know,compliance is also an issue.
You know if you have to take afistful of medicine every single
day.
You know at one time you feel,and if you feel that, oh,
everything is working fine,sometimes you tend to ignore and
say that, oh, I'm fine.
(42:39):
So we have found a lot of caseswhere people have stopped
taking drugs just because theythink that they're doing fine,
whereas their organs were slowlydeteriorating.
Speaker 1 (42:53):
So they'll stop taking the drugs.
And then Rejection will happen,rejection will happen.
Yeah, wow, you mentioned thatyou have mentees.
Now, you've been doing this fora long time.
Now you've been doing this fora long time.
When you speak to the nextgeneration of physician
(43:30):
scientists perhaps even thosefrom international backgrounds,
underrepresented backgroundswhat do you tell them about
persistence and purpose anddetermination, because, I mean,
it's so humbling to think about.
You talked about this moment inwhich your entire career was
distilled down to one heartbeat.
Speaker 2 (43:44):
Yes, that's astounding.
What do you tell the nextgeneration?
No, I mean I, you know I couldhave chosen the lifestyle of a
cardiac surgeon and would havebeen, you know, very well off,
much better off.
You know, must be doing muchbetter than what I'm doing now.
(44:05):
My family would have been, youknow, my kids would have been
loan free and all that.
But, but again, you know youhave to, you have to understand
that you know there's a, therehas to be a purpose in your life
, right?
I mean, you know, if you wantto do something, that that you
are remembered afterwards also,or during your life also, you
(44:27):
know you have to find a nichewhere, where you can make a
difference.
So this is what I teach mystudent that don't be a follower
, try to find your thing.
That's a little different.
So when they come to my lab ormy program, I said I'm open to
(44:48):
your suggestions because I'm notonly here to teach you.
I'm open to your suggestionsbecause I'm not only here to
teach you, I'm here to learnfrom you.
You may come up with an ideathat I've never thought of,
right?
So, and then, when they bringthose ideas and if they convince
me that those are good ideas.
I try to encourage them topursue those ideas.
(45:11):
Some of them get exhausted andgive up.
Some of them have taken itfarther.
I mean, these days a lot ofpeople try to do get an idea,
invent something, get a patentand then sell it to a bigger
(45:32):
company.
This is a common trend now,even in medicine now.
But for science to progress,your mind needs to continuously
keep thinking.
And I also teach them to be,you know, receptive to criticism
(45:52):
.
You know because a lot.
I give you an example you know,when I first came here in this
country we had the CD drive,right.
So we and we were using the CDdrive and I thought of, and I
talked to my fellow resident, Imean it would be great if we can
(46:14):
rewrite these CD drives.
He said are you going crazy?
You don't know what goes on.
You know there's a tiny needlewho makes grooves on this CD and
they cannot be erased.
And in a few years we hadrewritable CD drives.
So I mean you know, and in afew years we had rewritable CD
drives.
So I mean you know nothing isimpossible, right?
I mean you know, and sometimesour mind cannot comprehend.
(46:34):
When I started telling peoplethat.
You know I want to put a pigheart in human.
They said you're crazy, right,but so you have to be open to
these new ideas.
So this is my.
You know what I can give back.
I mean, in particular, thereason I accepted this interview
(47:00):
was because you are focusing onour young generation, because
they are the ones who are theflag barriers, right?
We need to give them motivationto keep thinking.
Speaker 1 (47:14):
It's the power of persistence, plus creativity,
creativity, creativity right.
Speaker 2 (47:22):
I mean we have tremendous amount of creativity
among young ones, you know, Imean my kid can do things that I
could have never imagined,right.
So, but somebody have tonurture that creativity, and you
know, and push them forward andsupport them and that's the way
to progress.
Speaker 1 (47:42):
Do you use AI in your research at any?
Speaker 2 (47:46):
Not yet, but slowly, we are kind, are kind of, you
know, incorporating.
There's no, no way out, uh,from that, um, at this moment.
Uh, but, uh, but we'll, we'llsee.
I mean, you know, still it's anevolving field, um, we only are
looking at the benefits of it.
We don't know, uh, what harm itcan do, and you know so.
(48:09):
I mean, you know, in ourtransplant field it has not
caused a huge impact.
But in patient selection and,you know, identifying disease,
population and all that, youknow, ai is a huge help.
Speaker 1 (48:28):
Yeah, just even.
Yeah, analyzing large data sets, right, Right, Coming up with
patterns.
Well, you've been exceedinglygenerous with your time and I
really wanted to once againthank you and honor you for that
and for your work and yourhumility.
Is there anything that we havenot touched on today that you
were hoping we were going totalk about?
Speaker 2 (48:48):
Well, I mean all this research.
I mean this is a very criticalperiod of time because, as you
know, the funding for science isunder a big you know it's not
there.
You know it's not there, it'svery difficult to get, you know.
(49:11):
So I mean, through this, I wantto let other people know that
you know, keep investing inscience because this is the
future and you know, we canstill make good progress, still
(49:34):
make good progress and we cannotjust, you know, stop doing
science and support, you know,even if it's a smaller project
of science, just support it.
Speaker 1 (49:39):
Well, I really thank you for your time and for your
story.
It was inspired when I readabout you and your work and also
very grateful that you tookthis time and agreed to come on
my pleasure, and I willdefinitely be sharing this with
young people and with ourscience teachers, because a lot
(50:00):
of what they teach has to dowith ethics.
It's not just formulas andanalyses, but really what the
impact of that is in the realworld and in real life.
So and your work encapsulatesthat perfectly Thank you.
So.
Thank you so much for for yourtime.
(50:21):
Thanks for joining us on theHangout podcast.
You can send us an email atpodcastinfo at protonme.
Many thanks to my daughter,maya, for editing this episode.
I'd also like to underline thatthis podcast is entirely
separate from my day job and, assuch, all opinions expressed
(50:42):
herein are mine and mine alone.
Thanks for coming on in andhanging out.
Welcome to the Hangout Podcast.
I'm your host, david Sharetta.
Come on in and hang out.
In this episode, I wasprivileged to have a
conversation with Dr MohamedMohi Houdin.
Dr Mohi Houdin is Professor ofMedicine at the University of
(00:23):
Maryland and is also director ofthe cardiac xenotransplantation
program.
As he describes in this episode, xenotransplantation is the use
of genetically modified animalorgans in humans, and Dr Mohi
Houdin gives us an inspiringthree-decade description of his
(00:47):
career that led up to theseminal moment in which a
genetically modified pig heartwas used and transplanted into a
human who was near the end ofhis life, and what the
remarkable impact of that was.
Remarkable impact of that was.
(01:09):
Dr Mohi Houdin is a worldwideleader in this field but is
exceedingly humble.
Gives all the credit to hisfellow researchers, as well as
to the patients who haveparticipated willingly in this
collective advancement ofscience for the future good of
humanity, as we face a chronicshortage of organs to meet the
needs for organ transplantationsaround the world.
I hope you enjoy thisconversation as much as I did.
(01:32):
Welcome, dr Mohamed.
Thank you so much for joiningme today and for the generosity
of your time and your expertise.
Speaker 2 (01:49):
Thank you.
Thank you, thank you forinviting me and pleasure to be
here.
Speaker 1 (01:54):
I thought we could get started with you sharing a
little bit about your originstory, where you come from and
what led you to your currentwork from and what led you to
your current work?
Speaker 2 (02:09):
Yeah, I mean, I came to this country around in early
90s to be specific in 91,aspiring to be the best cardiac
surgeon you can be and you know,and getting all the training
here Until that time.
You know, I'm originally fromPakistan and people used to go
(02:31):
to England and get theirtraining and come back and serve
in their country.
But then US opened up and mostof my classmates started coming
to US to get their training.
My classmates started coming toUS to get their training and
that was my case also.
However, I landed at theUniversity of Pennsylvania and
(02:58):
while starting my fellowshipthere, you know I was intrigued
by the research being done there.
At that time there were some bythe research being done there.
At that time.
There were some landmark papersthat came out from that
institution, in fact thatparticular group.
So I was convinced by my mentorat that time that if I go into
(03:21):
the field of xenotransplantationI may have the potential of
helping, you know, severalhundred four more people than I
will be as just a cardiacsurgeon.
So that kind of, you know,didn't sink in at that time.
But after working there for acouple of years, and after
(03:50):
working there for a couple ofyears, you know, then I made up
my mind that this is exactlywhat I want to do, because in my
mind I believed in it.
That, although we were workingon a small animal model, putting
a hamster heart in a rat, youknow, to go from there into
human was a long journey and,you know, even my family was not
(04:11):
very committed.
That you know, is it this whatyou want to do?
I mean, do you think this isthe right path?
But, you know, for some reasonbelieved in it and and chose to
continue, uh, that that path andand that path led to it took me
(04:33):
about 33 years to do, uh, thefirst human transplant.
Speaker 1 (04:37):
So so I mean, you know, there there's lots that
happen in, yeah, thank you forthat overview and I know there's
a lot of work that went intothose three decades.
Right, as someone who, of myage, I remember the Baby Faye
case, which was kind of a popculture phenomena of, I think, a
(05:03):
newborn, an infant who received, I think, a baboon heart and
just lived for a very shortperiod of time.
What has kept you going forthree decades in a field that I
think the average person doesn'teven fully understand?
(05:24):
Right, it almost seems like asci-fi field.
Speaker 2 (05:28):
Yeah, I've been told that I've been working in a, I'm
doing some kind of a voodoowork.
I won't lie that there wereseveral periods in that journey
that when I questioned myselfthat, am I doing the right thing
(05:50):
?
Because the field at times, youknow, completely died right
indulging in this kind ofstudies.
There was a time when therewere moratorium on
genotransplantation in certaincountries like England, just
because the initial transplantswere done using non-human
(06:14):
primate organs and they laterfound out that there could be
some diseases that can betransmitted through non-human
primate, like HIV.
So that kind of killed thatfilter, just like baby faith.
There were multiple othertransplants that were done,
(06:35):
transplanting kidneys mostly,and livers, but they all failed
because they didn't have anybackground of research in it
also and you know, were done asa desperate measure to save life
.
So I mean, you know those kindof experiments did happen
(06:59):
earlier, earlier than so, andyou know I what motivated me was
whenever, you know, things got,you know, slow, or you know,
(07:22):
when I was started thinking of,you know, just going back to
cardiac surgery, you know somehope came in and that kept the
fire burning.
You know the real hope came inwhen I moved to NIH National
Institute of Health in 2005,.
In 2005, where, you know, I wasgiven complete liberty to
(07:48):
develop this program and youknow, before that you were
working for someone else, youwere following someone else's
you know mission.
But here, you know, I kind of,you know, developed my own ideas
(08:10):
and that definitely helped.
I mean there's a lot of peoplewho helped me on the way.
I couldn't have been herewithout their you know
mentorship and effort which Itried to, you know, transfer to
my mentees.
But again, like you said, itwas a very, very hard job.
(08:31):
I mean, it was like lots of upsand downs during that journey.
Speaker 1 (08:37):
Now, as I understand it as a complete layperson just
doing a little bit of research,it's fundamentally driven by the
extreme shortage of.
Let's just take in this example.
We're talking about hearts theextreme shortage of available
hearts compared to the number ofto the need.
(08:58):
Right, that's really what'sdriving that.
Talk to us about what thosenumbers look like and how that's
pushing your work forward.
Speaker 2 (09:08):
Yeah, so approximately, just in the
United States there are about150,000 people who are waiting
for an organ for transplant.
They have reached at a stage intheir organ failure where the
conventional treatments cannotprolong their life.
(09:29):
So these patients, if theydon't get a human organ, you
know they are sent to hospicewhere they spend their last days
and you know effort is made tomake that phase easy for them
and effort is made to make thatphase easy for them.
So, basically, there was nohope for these patients and,
(09:56):
however, there are othercompeting technologies that are
being developed For heart.
There are mechanical heartsavailable, left ventricular
assist device and now totalartificial heart, but they have
their own problems and they havenot reached to.
You know they have not beenable to help every single
(10:18):
patient who's on the waitinglist.
The problem with kidney is evenmore, because you know there are
larger population who have, whoare going through kidney
failure.
But at least they have a backupof dialysis for them.
But for hearts it's definitelynot.
There's no other choice if youare not eligible for a
(10:40):
mechanical device.
So all these, all thesepatients you know are in a
desperate condition, even youknow, if the organ donation is
increased several folds and youknow every single one of us
become an organ donor.
Not every single organ becomeseligible for transplant also, so
(11:02):
you know you have to match theorgans to the recipient.
You know a lot of us carrydifferent diseases, which
prevents us from being a goodorgan donor.
So all these factors kind ofyou know, prevents all the
organs that are harvested forthe purpose of transplantation
(11:25):
to get into a human.
So I mean there was an extremeneed for finding an alternate
organ and besides generating a3D printed organ, which is being
done, a 3D printed organ, whichis being done, or somehow
(11:51):
making the organ that are noteligible more eligible by, you
know, some treatment.
You know there was no otheroption.
So I mean, you know we aresuggesting, you know, non-human
organs as an alternate and withthe technique of gene
modifications, we now believethat we can alter the genes of a
(12:12):
donor organ or the donor animalto an extent that it becomes
more acceptable to humans.
Speaker 1 (12:20):
So, as you described to me when we did a previous
call previous to today, thatoftentimes the drugs that
recipients need to take toprevent the rejection of an
organ can be the thing thatactually is the most that
(12:41):
sometimes can kill the recipient, correct?
Can you talk to us about thatand about the importance of this
breakthrough of the geneticmodification of the animal heart
?
Speaker 2 (12:54):
Yeah, so I mean, you know, with the advancement of
these immunosuppressive drugs,you know we are at a stage where
, you know, the graft survivalhas extended beyond you know,
years, right, and it is allbecause of these
immunosuppressive drugs.
But these immunosuppressivedrugs that are currently used in
(13:20):
human-to-human transplants,they don't discriminate between
a good and a bad cell, so theyare kind of like nuking the
entire immune system, right?
So in most cases and you aredependent on these drugs for
your lifetime, once you receivean organ, and most of the time
(13:44):
the toxicity of these drugs isthe cause of, you know, the
graft recipient's death versusthe graft itself, sometimes the
graft is still functioning verywell, but you know the person
who's the recipient, you know,kind of dies or become morbid
(14:06):
because of the toxicity of thesedrugs.
Speaker 1 (14:10):
So you mentioned very humbly that about 30, 31 years
of work went into, you know,getting to the point of the
success the first successful pigto human heart transplant.
What was that like when youfinally, you know, were in that
surgery and you know what led upto that?
(14:32):
And then what was the follow-upto it too?
My understanding is that thepatient lived for some period of
several months afterwards.
Talk us through that wholeprocess.
Speaker 2 (14:42):
So I mean, you know, honestly, throughout this period
, although I believed in it, Ithought, I think that this is a
very valid option for thesepatients who are critically ill
and have no other options.
However, you know, I neverbelieved that this would have
happened in my lifetime.
(15:03):
This would have happened in mylifetime.
So you can imagine when we putthe first big heart in a human
and it started to beat and thatperson woke up.
I cannot even describe thatfeeling right.
I mean it's like your entirelife's work coming to fruition
(15:26):
right before your eyes.
So I mean, you know that istotally.
What happened afterwards isthat you know these, the
patients who who we were allowedto give these hearts to, we're
at a stage that if we had notgiven them this heart, they
(15:47):
would have died the next day.
So, in fact, our second patient, his heart arrested twice even
before the transplant and we hadto resuscitate the heart and
keep him alive until we wereable to put this transplant in.
As I mentioned earlier, I meanthere is no alternate for those
(16:08):
patients.
There is a machine called ECMOthat you use to hook to a tubing
and that machine kind of actsas a pump to circulate the blood
, which is the main function ofthe heart.
But you cannot live on thatmachine forever.
(16:28):
It's a heavy machine, youcannot carry it.
So our first patient was onthat system for almost 40 days.
So he wasn't bedridden.
He couldn't even go to hisbathroom.
So after the transplant hismajor wish was when I'd be able
to walk to the bathroom right.
So for two months he had notbeen able to go to the bathroom
(16:51):
himself.
So some of those were the smallwins that we counted.
I mean, if you think of as alay person and say that, oh,
this, your first patient livedfor only 60 days, you know what
(17:12):
have you achieved.
I mean, you know that 60 daysis nothing for us who are
healthy, but for a person whoyou know, who doesn't know that
he will be alive tomorrow, those60 days means a lot, means a
lot.
And you know they were able toenjoy those 60 days, although
(17:33):
they were sick, but they wereable to, you know, bond better
with their families and did alot of unfinished business that
they could have done from thehospital.
Speaker 1 (17:47):
Well, I mean you, essentially you had a 60x return
on investment, so to speak.
Right, that's tremendous.
Speaker 2 (17:57):
Yeah, and you know we never promised that to the
patient because we didn't knowRight.
I mean, you know we have donehundreds, or in my case
thousands, of experiments inanimal models and we were
confident that we would not seerejection on the table.
This heart will beat and thispatient will get up.
(18:18):
But until we do that, you knowwe don't know right.
You know that will happen.
But when that happened, youknow it made even a stronger
believer out of me.
Speaker 1 (18:30):
And I know I'm sure there's definitely privacy
concerns too but was the causeof death of that patient
rejection of the heart?
Eventually and it was just youwere able to extend that much
farther than you had originallyanticipated, but eventually the
body rejected it.
Speaker 2 (18:50):
So you know, as I mentioned, these patients were
very, very sick.
So the experiments we have donebefore that led to these two
transplants were done in likehealthy animals, right.
So those animals were able totake a stronger
immunosuppression and you knowother manipulations.
(19:13):
However, these patients werealready so sick that we cannot.
So we had a dilemma whether tosave the patient or save the
graft.
So we had to create that savethe patient or save the graft.
So we had to create that a verydelicate balance between the
two.
For that we had to reduce theimmunosuppression, because that
was kind of, you know, causingthe patient to get even sicker,
(19:38):
but that made the heartvulnerable to rejection also,
and ultimately that's whathappened, right.
So we were fighting to maintainthe adequate drug levels, which
we could not because of thecondition of the heart you know,
he was getting infected and allthat and in the end, you know,
(19:59):
the rejection process took over,and in the first one we were
not clear, but in the second one, definitely this is what
happened.
But once we evaluated and weare still evaluating all the
specimens that we, these twoheroes, with whom I call heroes,
who devoted their life for thelearning of science, right.
(20:22):
I mean they themselves believethat they do not have a chance,
but they wanted to go throughthis so we could learn and help
others.
So I mean because of theircourage.
You know we are still learningto date from the specimen that
we have achieved from them.
Speaker 1 (20:41):
That's a fascinating perspective that you bring up
the courage on the part of therecipient, right?
I mean?
Oftentimes we think about thegroundbreaking efforts of the
researchers, and that'scertainly the case here, but the
ethical considerations andalmost the personal sacrifice,
(21:03):
sacrifice, familial sacrifice,of someone saying I either have
no days one day or x amount ofdays and I'm going to go through
this.
I obviously want to be around,to be with my family, but if not
, it's this sacrifice for the,for the, the future research
corpus moving forward thatperhaps can change humanity.
(21:25):
That's pretty, that's something.
Speaker 2 (21:27):
Yeah, no, that's totally.
And you know, even after thesepatients have passed, their
families have been equallysupportive and have been, you
know, spoke person for our cause, right, and because they don't
want their loved one's sacrificeto go in vain, right.
(21:50):
So they, whenever we ask themto come to our meeting and have
them write and talk to anyreporters or you know a group of
people where we are kind ofconvincing them to, you know,
consider this option.
You know they have been veryforthcoming in that help.
(22:11):
They both have written their,you know their experience and we
have published thoseexperiences from their immediate
families also.
Speaker 1 (22:20):
Now you mentioned that you never thought this
would happen in your lifetime,and so it's kind of moved faster
than you anticipated.
Is the vision that eventually,the efficacy of these procedures
will get to the point wherethey can be more routine and
used with someone for whomthere's a medical necessity, but
(22:43):
they're perhaps not at such anend stage that their survival,
no matter what happens, is inquestion?
Speaker 2 (22:51):
That's exactly the future, right?
I mean, you know that's in anideal world we would be able to.
We would have enough organs,you know, available and sitting
waiting to be transplanted thatwe don't have to wait for an end
.
Organ failure Means that youknow when the heart comes to the
(23:15):
stage where it requirestransplantation, by that time,
you know, since heart controlsthe blood flow to all the other
organs, your other organs alsostart getting damaged and you
know, in most of the cases thereis multi-organ failure.
So if we are able to prove thatthere is a heart which is from
(23:39):
a young animal, like pig, thatwill not go through rejection.
So a pig lifetime is about 20years.
So the pig that we use in theseexperiments were only one year
old.
So in an ideal world you have19 years left in that heart,
(24:02):
right.
In an ideal world, you have 19years left in that heart, right.
So if you transplant andconvince someone that, okay,
this heart you know will workfor 19 years, you have a 19-year
warranty on this heart and youmay not need a heart right now
but in five years or 10 yearsyou will need a heart.
(24:23):
So would you do you want to gothrough the suffering of those
10 years, then get another heart, or do you want to get it now,
right?
So, so this is, this is way youknow I'm talking not in my
lifetime, probably, but whoknows?
You know, and then other major,major advantages that what we
(24:47):
have not talked about is thegenetic modifications of these
organs, right?
I mean, the technology we haveavailable now was not available
like a decade ago, right, decadeago, right.
(25:07):
So with this technology, we cantake out any, any antigen that
is, you know, immunogenic tohumans, that to which we react,
and we can also add human genesto uh, to the construct and and
and make a customized pig right.
So so the future it is apossibility that you know, when
you're born, your genes aretaken out and you know, and a
(25:30):
pig is made ready for you whenyou need it, and my
understanding, too, is that theone of the benefits of the pig
is that you can grow a heartfairly quickly.
Speaker 1 (25:40):
Right, it's not in what a year or so.
Speaker 2 (25:44):
Yeah, so in a year the organ grows to a size of an
adult human in terms of heart.
You know, in heart it's verycritical to match the size.
But in other organs, likekidneys and livers, you don't
even have to get to the the size.
But in other organs, likekidneys and livers, you don't
even have to, you know, get tothe exact size.
(26:06):
You know, in liver you can do apartial liver.
Uh, you know.
And and if in china there was atransplant done when, when
there was a cancer in the liver,so they took the part of the
liver that had the cancer, put apig liver for a month.
During that period, you know,liver has the tremendous
(26:28):
potential of regeneration.
The liver, the original liver,grew to a size that it can
support life.
Then you can.
They took out the porcine liverand that way you know that they
bridge the transplant throughliver of a pig.
Speaker 1 (26:48):
I want to talk a little bit about both ethics,
because I'm sure that those areparts of conversations that
always come up for you, as wellas what your critics say perhaps
not your own personal critics,but critics just in general of
the field.
Right, what are some of theethical considerations that you
go through in your work?
(27:09):
And then, what do critics say,people who would like this
either this research to stop orto pause.
Talk to us about the obstaclesyou've faced in those regards.
Speaker 2 (27:24):
So one of the major reasons that we picked pig was
that you know it's been consumedfor the dietary needs
throughout the world, right?
Almost about 90,000 pigs areslaughtered each day in United
States for that purpose.
So we thought that, you know,if we are using maybe 100 pigs a
(27:47):
month for this purpose, youknow it won't be a problem.
But certainly you know therewere people who were very
critical of, you know,sacrificing a healthy animal for
that purpose, although you knowthe meat is consumed in their
(28:13):
meals.
But so that was our major issue, that you know why, you know,
sacrifice a healthy life to savea human life.
I was even asked whether youwill do the other way around.
Would you give a pig your heartto save his life?
(28:35):
Right?
So I mean, you know people goto that extent also, and I've
also been asked why is itimportant to save human life?
Right, I mean, you know, ifit's ending at a certain point,
you know why should we evenprolong it, right, you know?
So I mean you know there are alot of different opinions
(29:01):
outside.
My goal and the oath I havetaken is to save life, right?
So if, even if I save one life,I mean that is.
You know it's important for me.
So, so I kind of, you know, um,take that criticism, but, uh,
but try to convince them.
(29:21):
You know my goal is to savesomeone, you know who needs to
be saved at, you know, and thisis one of the ways I can save it
.
I mean, I'm sure you will askabout, you know the religious
restrictions right.
So you know, growing up youmust have read that.
(29:43):
You know my father used to.
You know, politely, tell me,you know, could you find
something else, could you findanother?
And still, you know I go todifferent countries where people
ask you know why pig and whycannot you do it?
Take a cow's heart?
Or you know, a camel's heart orsome other species heart, a
(30:05):
camel's heart or some otherspecies heart?
So I mean, that has always beena you know a question and still
is.
However, you know you'll besurprised to know that now the
awareness is growing.
So even in UAE, you know, thereis a verdict that because in a
(30:29):
lot of Muslim countries, youknow, the taking organs after
brain death is not allowedbecause they think that you are
mutilating the body Rightcountries there is, they are
(30:51):
thinking that you know if youcan have an organ from another
species and not mutilating thedonor, the human donor, then
maybe that is a better way to go.
And also it's also, you know,in UAE they have always issued a
fatwa, that you know, if youhave an option that you can use
(31:11):
to save a life and you're notusing it, you're making a bigger
sale, right.
So I mean, you know there aredifferent aspects, so the same
thing with.
So I'm president ofInternational Genotransplant
Association.
My effort has been to gatherall these opinions from
(31:33):
different religions.
So we have gathered, you know,all the leaders of different
religions together in one roomand ask their opinion and in the
end, the common consensus isthat to save a human life take
precedence over anything else.
Speaker 1 (31:51):
Yeah, it's interesting, you can imagine a
Buddhist as well, right, yeah,yeah, so vegetarian and do no
harm.
And it brings that ethicalquestion of by you not following
through on the Hippocratic oath, then essentially you're doing
harm.
Speaker 2 (32:09):
Yeah, yeah.
So that's, I think, the basisof you know why it's getting
popular in some of the MiddleEastern countries.
I mean, it's not done yet, butthey're interested in it.
Speaker 1 (32:25):
So, and as you were speaking and when you made this
comment that you might not seeit in your lifetime, it, almost
just as a side thought it, itreminds me of, you know, one of
these great masterpieces ofhistory.
Or we look at the SistineChapel, or we look at these
great constructions that spanmultiple lifetimes and you think
(32:48):
about architects who designedthem, or you think about master
builders or master painters whoworked on them and they knew
that they would not live longenough to see the finished
product.
But you're contributing tosomething that is greater than
yourself and greater than yourown lifetime yeah, I mean not
(33:09):
only me, I mean these patientsalso.
Speaker 2 (33:13):
I mean, you know, who do you know, I don't make a big
case of what I have done.
I kind of, you know, appreciatethe effort of these patients.
If these patients would nothave said yes to this procedure,
you know, nothing would havehappened, right?
(33:36):
So so they took the courage, soso.
So I mean, you know, they'reour two patients.
I will never forget them forthe rest of my life, right, and
I don't think history willforget those patients because of
their sacrifice, right.
So they may forget what I havedone, but those people were the
real pioneers in starting thisthing.
Speaker 1 (33:55):
Who pays for such procedures?
Are these grant funded?
Talk to us about that.
Speaker 2 (34:01):
So this is a very difficult and expensive process,
right?
So, just to give you an example, even when I do an animal
research like put a pig heart ina baboon, it costs about
$500,000, right?
So, when we did this humantransplants, they cost about
(34:23):
$1.5 million for 60 days.
So it's a very expensiveprocess at this time.
And there are several companieswho are generating these pigs
have interest in producing thesepigs in masses and and to
(34:48):
overcome this shortage of organs.
Right so they have invested alot in these experiments.
And also, our first transplantwas paid by our university and
the hospital.
The second one was paid by oursponsor who produces the pigs.
Similarly, the people who havedone kidneys they got funding
(35:13):
from their sponsors who aremaking these pigs, because these
pigs are basically considered adrug by the FDA.
We are producing this drug tosave a human life.
Speaker 1 (35:31):
And I'd imagine at some point there's also
government funding, right,Depending on, I'd imagine and
you mentioned an internationalassociation that you're the
president of.
So I'd imagine, like in thecase of China, that was probably
state funding in that case, andso is there kind of a patchwork
of state private funding forall of these efforts.
Speaker 2 (35:53):
So I do.
I do have NIH grants thatsupported, and when I was at NIH
for 13 years, it was allgovernment, federal government
funding that helped you know theprogress of this field.
However, you know, as we know,the medical system here is
totally dependent on insurance,and you'll be surprised to know
(36:17):
that our first patient had aclause in his insurance that
knows, you know, transplantationcan be done.
So these guys think way aheadof us, right?
Speaker 1 (36:40):
As you were talking about the cost, I flashed on my
own insurance and my HMO planand I'm trying to get something
approved that's out of network,something small.
That's out of network,something small.
Speaker 2 (36:54):
I thought imagine the Herculean effort to try to find
the backing for something likethis.
Yeah, so I mean, but you knowthe advantage of.
You know a lot of insurancecompanies spend a lot of money
in preventive measures, right?
So if they can spend some moneyon preventive measures so they
can avoid spending a lot ofmoney in preventive measures,
right?
So if they can spend some moneyon preventive measures so they
can avoid spending a lot if thedisease occurs or you know they
(37:18):
want you to control your bloodpressure and you know diabetes,
so that you don't get to thestage where your organs need to
be replaced, or you know othertreatments needs to be done.
Similarly, if you have a pigwhere you can take about seven
different organs from that pigand save seven different lives,
(37:45):
the cost will drastically comedown.
At least my hope is that itwill replace allotransplantation
, although initially you knoweveryone will prefer a human
organ versus a non-human organ.
But if you are able to convincethem that this non-human organ
is a better replacement than anorgan from someone who has
(38:09):
scarring diseases or, you know,is older and we don't know how
this organ will function, thatthings will change and you know
the insurance company will seeit as a you know.
So a lot of companies ask me youknow, when will you be able to
do?
Like a thousand transplants ayear?
(38:29):
So I don't usually give themtimeline, but that's a real
possibility, right?
I mean, you know, like I said,that if you can offer a
transplant at an earlier timepoint of the disease, you can
definitely, you know, do moretransplant than even required,
more than the people who are onthe waiting list.
(38:52):
So you know, that way a lot ofthese organs will be consumed,
and the advantage is that if youhave like 20 years of life in
this organ, you can, after 20years, give exactly the same
organ again, really.
So I mean, you know that cankeep going, right.
(39:15):
So, and then you know,customizing that organ for
yourself will also help youeither reduce the immune
suppression or and my goal is tocompletely avoid the immune
suppression you, you, you modifythe genetics to an extent that
you know you don't, your, your,your organ will behave just like
(39:40):
your original organ and will,and your immune system will look
at it as its own and will notattack it.
Speaker 1 (39:48):
It's fascinating to think about how we create mental
constructs around ideas, right?
So, for example, my daughterhad jaw surgery and they placed
some essentially a cadaver boneand then eventually her body
(40:09):
absorbed it.
And the one you know school ofthought would say, oh, I don't
want to quote, unquote deadperson's bone in my jaw, but
biologically that's not even anissue, right, the body absorbs
it and it helped my daughterwith her surgery.
So we passed that, and I'm surethere's been thousands and
thousands of those surgeriesthat happen every day around the
(40:31):
country, and it's not a bigdeal.
Maybe 50 years ago people wouldhave thought that was some sort
of an abomination, and so doyou think in 100 years from now
we'll be at a place where thisis fairly commonplace?
Speaker 2 (40:45):
I hope so I mean, you know that's what we believe in,
that you know that, you know we.
You know the technique of genemodification is continuously
evolving and you know we shouldbe able to, you know, completely
change the genetics of a pigand make it more what you call
humanized and in that way avoidthe immunosuppression completely
(41:09):
or induce some kind oftolerance.
There are ways, you know, Ihave been working on and others
have been working on, to teachyour immune system to recognize
something that you're placing inyour body as not foreign and
self, so that if we are able toteach the immune system and
(41:30):
immune system is, you know, youcan teach it.
And if you are able to do that,then again you don't need all
these gene modifications.
Your immune system will learnto recognize that these foreign
antigens as their own and willnot attack them.
So that's also, you know, oneway of you know, overcoming and
(41:55):
avoiding the drugs.
You may need some drugs forinitial period of time.
Then you can slowly withdrawthem and you know, have the
patient without drugs A lot of,as you mentioned, as I mentioned
to you, that a lot oftoxicities of these drugs cause
the premature death of thepatients.
(42:17):
However, sometimes, you know,compliance is also an issue.
You know if you have to take afistful of medicine every single
day.
You know at one time you feel,and if you feel that, oh,
everything is working fine,sometimes you tend to ignore and
say that, oh, I'm fine.
(42:39):
So we have found a lot of caseswhere people have stopped
taking drugs just because theythink that they're doing fine,
whereas their organs were slowlydeteriorating.
Speaker 1 (42:53):
So they'll stop taking the drugs.
And then Rejection will happen,rejection will happen.
Yeah, wow, you mentioned thatyou have mentees.
Now, you've been doing this fora long time.
Now you've been doing this fora long time.
When you speak to the nextgeneration of physician
(43:30):
scientists perhaps even thosefrom international backgrounds,
underrepresented backgroundswhat do you tell them about
persistence and purpose anddetermination, because, I mean,
it's so humbling to think about.
You talked about this moment inwhich your entire career was
distilled down to one heartbeat.
Speaker 2 (43:44):
Yes, that's astounding.
What do you tell the nextgeneration?
No, I mean I, you know I couldhave chosen the lifestyle of a
cardiac surgeon and would havebeen, you know, very well off,
much better off.
You know, must be doing muchbetter than what I'm doing now.
(44:05):
My family would have been, youknow, my kids would have been
loan free and all that.
But, but again, you know youhave to, you have to understand
that you know there's a, therehas to be a purpose in your life
, right?
I mean, you know, if you wantto do something, that that you
are remembered afterwards also,or during your life also, you
(44:27):
know you have to find a nichewhere, where you can make a
difference.
So this is what I teach mystudent that don't be a follower
, try to find your thing.
That's a little different.
So when they come to my lab ormy program, I said I'm open to
(44:48):
your suggestions because I'm notonly here to teach you.
I'm open to your suggestionsbecause I'm not only here to
teach you, I'm here to learnfrom you.
You may come up with an ideathat I've never thought of,
right?
So, and then, when they bringthose ideas and if they convince
me that those are good ideas.
I try to encourage them topursue those ideas.
(45:11):
Some of them get exhausted andgive up.
Some of them have taken itfarther.
I mean, these days a lot ofpeople try to do get an idea,
invent something, get a patentand then sell it to a bigger
(45:32):
company.
This is a common trend now,even in medicine now.
But for science to progress,your mind needs to continuously
keep thinking.
And I also teach them to be,you know, receptive to criticism
(45:52):
.
You know because a lot.
I give you an example you know,when I first came here in this
country we had the CD drive,right.
So we and we were using the CDdrive and I thought of, and I
talked to my fellow resident, Imean it would be great if we can
(46:14):
rewrite these CD drives.
He said are you going crazy?
You don't know what goes on.
You know there's a tiny needlewho makes grooves on this CD and
they cannot be erased.
And in a few years we hadrewritable CD drives.
So I mean you know, and in afew years we had rewritable CD
drives.
So I mean you know nothing isimpossible, right?
I mean you know, and sometimesour mind cannot comprehend.
(46:34):
When I started telling peoplethat.
You know I want to put a pigheart in human.
They said you're crazy, right,but so you have to be open to
these new ideas.
So this is my.
You know what I can give back.
I mean, in particular, thereason I accepted this interview
(47:00):
was because you are focusing onour young generation, because
they are the ones who are theflag barriers, right?
We need to give them motivationto keep thinking.
Speaker 1 (47:14):
It's the power of persistence, plus creativity,
creativity, creativity right.
Speaker 2 (47:22):
I mean we have tremendous amount of creativity
among young ones, you know, Imean my kid can do things that I
could have never imagined,right.
So, but somebody have tonurture that creativity, and you
know, and push them forward andsupport them and that's the way
to progress.
Speaker 1 (47:42):
Do you use AI in your research at any?
Speaker 2 (47:46):
Not yet, but slowly, we are kind, are kind of, you
know, incorporating.
There's no, no way out, uh,from that, um, at this moment.
Uh, but, uh, but we'll, we'llsee.
I mean, you know, still it's anevolving field, um, we only are
looking at the benefits of it.
We don't know, uh, what harm itcan do, and you know so.
(48:09):
I mean, you know, in ourtransplant field it has not
caused a huge impact.
But in patient selection and,you know, identifying disease,
population and all that, youknow, ai is a huge help.
Speaker 1 (48:28):
Yeah, just even.
Yeah, analyzing large data sets, right, Right, Coming up with
patterns.
Well, you've been exceedinglygenerous with your time and I
really wanted to once againthank you and honor you for that
and for your work and yourhumility.
Is there anything that we havenot touched on today that you
were hoping we were going totalk about?
Speaker 2 (48:48):
Well, I mean all this research.
I mean this is a very criticalperiod of time because, as you
know, the funding for science isunder a big you know it's not
there.
You know it's not there, it'svery difficult to get, you know.
(49:11):
So I mean, through this, I wantto let other people know that
you know, keep investing inscience because this is the
future and you know, we canstill make good progress, still
(49:34):
make good progress and we cannotjust, you know, stop doing
science and support, you know,even if it's a smaller project
of science, just support it.
Speaker 1 (49:39):
Well, I really thank you for your time and for your
story.
It was inspired when I readabout you and your work and also
very grateful that you tookthis time and agreed to come on
my pleasure, and I willdefinitely be sharing this with
young people and with ourscience teachers, because a lot
(50:00):
of what they teach has to dowith ethics.
It's not just formulas andanalyses, but really what the
impact of that is in the realworld and in real life.
So and your work encapsulatesthat perfectly Thank you.
So.
Thank you so much for for yourtime.
(50:21):
Thanks for joining us on theHangout podcast.
You can send us an email atpodcastinfo at protonme.
Many thanks to my daughter,maya, for editing this episode.
I'd also like to underline thatthis podcast is entirely
separate from my day job and, assuch, all opinions expressed
(50:42):
herein are mine and mine alone.
Thanks for coming on in andhanging out.
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