What do a pig, a tick borne meat allergy, and a pinch of cocaine have in common? The three
of them hold a key for a revolutionary heart transplant. Stay with me and I’ll tell you how.
On January 7th, a group of scientists and doctors at the University of Maryland Medical Center
transplanted a genetically modified pig heart into the body of a 57 year old man
with a terminal heart disease. The patient is being monitored but, as I’m recording this video,
in mid-February, the procedure is looking like a complete success.
We have several cardiologists trying to find any fault in it
but they have not been able to do it. The heart is contracting rigorously, as it should,
and all those parameters are coming back as if this heart is as good as new.
This is Muhammad Mohiuddin, the Director of the Cardiac Xenotransplantation Program
at the University of Maryland Medical Center and a member of the team that performed this
surgery. He has spent years researching these kinds of transplants to make this possible.
Believe it or not, pig organs have long been key to research on xenotransplantation. And
that’s for a number of reasons. They can be bred quickly, they're domesticated,
and their organs are similar, or physiologically similar,
to the ones of human and non-human primates.
In the US alone, over 100.000 people are waiting for a transplant, and on average,
17 people die every day waiting for an organ, according to data from the American Transplant
Foundation. These transplants could potentially save thousands of lives of people who die waiting
for a compatible organ, but they come with significant risks. The most obvious one is
triggering a dangerous immune response, basically having the body reject this foreign organ.
That’s where the genetic modifications, together with drug therapies, come into play.
One of the most important contributors to this rejection, in the case of pig organs,
is a sugar molecule called alpha-gal. Most mammals have it. People don’t, but they may
develop antibodies against it during their lives, mostly through the bite of a tick. So, if you get
a pig heart, you may end up rejecting it because your body is seeing this sugar for the first time,
or you can have a very strong immediate reaction because your body was already
predisposed to react to it, maybe from a tick bite that you don’t even remember.
And an interesting fact: that tick bite, and that same sugar, are also behind an allergy to meat
that some people develop, the so-called alpha-gal syndrome.
In 2020, the FDA approved a genomic alteration in pigs to eliminate this
sugar, which opened the door for pork that people with this allergy could eat safely,
but also for potential xenotransplants like the one we have just seen.
Going back to this particular case, scientists performed ten different gene modifications
in the pig. Three genes responsible for the rejection were deactivated.
Six human genes were inserted to facilitate the acceptance of the heart.
And another additional gene was deactivated to prevent an excessive growth of the pig
heart tissue, because pig hearts are normally bigger than human hearts.
The genetically modified pig was provided by a company called Revivicor. On the morning of the
transplant surgery, the surgical team removed the pig’s heart and placed it in a Heart Box,
a machine that keeps the heart preserved until surgery. And another interesting fact:
this was done with the help of a solution that contains cocaine, a tiny amount,
among other less attention-grabbing ingredients such as insulin, adrenaline and cortisol.
This surgery was an experimental procedure, but it was also the only chance for David Bennett,
who had been deemed ineligible for a conventional transplant and had already
spent months in the hospital. That’s why the Food and Drug Administration granted
emergency authorization for the surgery through what is called the "compassionate use provision".
This is a path that can be used when a new treatment that has still not been approved
is the only option available for a patient with a life-threatening condition.
Bartley P. Griffith is the Director of the Cardiac Transplant Program at the
University of Maryland Medical Center and the surgeon who led the transplant.
I've been asked how we would define success and I think we've surpassed
in many measures what we would have expected.
We have a heart that's,
you know, out five weeks and performing normally, requiring no assistance...
Our immunosuppressive protocol that Dr. Mohiuddin has basically invented and trialed
is working flawlessly.
Don't know what next week, or tomorrow, is going to look like,
but we're taking one foot in front of the other,
and I'm optimistic.
Scientists have been researching xenotransplantation for a very long time,
including blood transfusions as early as the 17th century.
More recently, in the XX century, several doctors tried to transplant kidneys and hearts from
baboons and chimpanzees into human patients. One of the most famous procedures took place in 1984,
when doctors transplanted a baboon heart into a baby girl with a rare and congenital heart defect.
She survived for 20 days but her body ended up rejecting the heart.
...she had already outlived any of the recipients of similar operations...
However, pig heart valves have been used successfully in humans for over 30 years.
In 2016, Dr. Mohiuddin and a team of scientists had already managed to keep a pig heart alive
in the body of a baboon. In that case, the pig heart was not replacing the monkey heart,
but it was still attached to the circulatory system. Call it "bonus hearts". Two years later,
a team of researchers at the University of Munich managed to perform full transplants
from genetically modified pigs into four baboons. They survived for months before being euthanized,
and the researchers told the media back then that they were enjoying life, including watching TV.
Genomic alterations open the door to solving many of the problems that come with these therapies in
humans. Last October, surgeons attached an altered pig kidney to a braindead patient, and it worked,
although they only followed the results for a couple of days.
There are still a lot of questions around the
feasibility of xenotransplants. But the potential is huge.
It is a game changer, because if this works and, you know, and I hope it'll work,
we will have these organs available. We can, you know, we have the technique of genetically
modifying. So if they're more tweaking required for, for modifying the genes, we
will be able to do that. And can customize the heart, or the organ, for the patient.
Dr. Mohiuddin has already said they’re planning to publish the results of the
procedure and share them with the scientific and medical community.
Again, this case was an experiment, but if other teams are able to replicate it,
the field will move closer to a future where nobody dies waiting for a compatible organ.