20 THENEWYORKER,FEBRUARY28, 2022
ANNALS OFMEDICINE
CHANGE OF HEART
The first successful transplantation from pig to human may solve a donor shortage.
BY RIVKAGALCHEN
ILLUSTRATION BY CARNOVSKY
I
n the early hours of January 7th, the
cardiothoracic surgeon Bartley Grif-
fith, unable to sleep, went to his kitchen
to make coffee. It was about 2 a.m. His
usual mug is tall, and he had to remove
the stand from his Krups machine in
order to fit it. “Next thing I realized, I
had coffee all over the floor. I had for-
gotten to put the cup under,” Griffith
told me. “You get a bit wiggly, a bit su-
perstitious.” He asked himself, “Do you
know what you’re about to do?” Griffith
has forty years of surgical experience. But
later that morning he was scheduled to
perform a surgery that would be unusual
even for him: the world’s first transplan-
tation of a pig’s heart into a human.
Griffith’s team, at the University of
Maryland Medical Center, had received
confirmation from the Food and Drug
Administration only seven days earlier,
on the evening of December 31st, that
the experimental surgery was approved.
“It was just two lines or so,” Griffith
said. “It read, ‘Good luck with the sur-
gery!’” But Griffith and his colleague
Muhammad M. Mohiuddin, who jointly
run the school of medicine’s Cardiac
Xenotransplantation Program, had been
working together toward this goal for
five years. “So then, there we were in
the hospital on January 1st, thinking
how to make this actually work.” The
medical center had to decide that it was
willing to pay for the procedure—in-
surance tends not to cover xenotrans-
plantation. The patient, David Bennett,
Sr., a fifty-seven-year-old man with se-
vere heart failure, had to undergo four
psychiatric evaluations, to make sure he
could give consent. All the staff who
might work on the experiment had to
be given permission to opt out. “So many
people are involved with the care of a
patient,” Griffith said. “We have a binder
of four hundred or so consents—peo-
ple wanted to participate.”
Mohiuddin, who led the lab work
that studied the transplantation of the
pig heart, lives an hour from the hospi-
tal. There was a snowstorm on Janu-
ary 6th, so he spent the night on the
sofa in his office. “My wife has given up
on me for a while—she knows what I
am going through,” he told me. “I spent
thirty years just driving for this.” On the
morning of January 7th, he headed the
surgery that extracted the heart from a
year-old genetically modified pig, which
had been raised at a facility in Virginia
run by the company Revivicor. (Reviv-
icor is a spinoff of PPL Therapeutics,
known for making Dolly the sheep, the
first mammal cloned from an adult cell.)
Pigs have about thirty thousand genes.
Ten of those genes in the donor pig had
been altered, through a time-consum-
ing gene-editing process. (CRISPR tech-
nology has recently sped up similar pro-
cesses.) Three genes largely responsible
for making sugars that a human body
would consider foreign were “knocked
out”; a gene that controls how large and
how fast the heart grows was also de-
leted; and six genes that help regulate
antibody function, inflammation, and
coagulation cycles in humans were
“knocked in.” The pig heart was now,
in theory, more likely to be taken on by
the patient’s body as “self ” rather than
as “foreign.”
After Mohiuddin’s team extracted
the pig heart, they placed it in a box re-
sembling a high-end automatic bread-
maker; the box keeps a transplant heart
cold and metabolically active. It pumps
a fluid through the heart that is made
up of saline, cocaine, and a few other
components. The box and the solution
were developed by researchers in Swe-
den. “Every time we import one of these
boxes, I have to fill out special forms
More than three thousand people are typically waiting for a new heart in the U.S. from the D.E.A.,” Mohiuddin said.
