SCIENCE science.org 5 NOVEMBER 2021 • VOL 374 ISSUE 6568 669In the late 2000s, for example, Platts-Mills
showed tick bites could provoke an unusual
allergic response to alpha-gal. People with
this “alpha-gal syndrome” (AGS) develop se-
vere reactions to red meat and many medical
byproducts of animal husbandry, including
the blood thinner heparin (made from pig
intestines) and implantable devices such as
bioprosthetic heart valves from cows or pigs.
(The antibodies that cause these allergic reac-
tions, elicited only by tick bites, differ from
those that attack transplanted pig organs,
which everyone carries.)
Revivicor had won regulatory approval
for its engineered pigs as a source of meat
in December 2020, and although pork chops
and sausage patties from the swine aren’t
yet commercially available, the company has
begun to send free samples to people like
Amber Shifflett of Charlotte Hall, Maryland,
who has AGS and spent months avoiding
red meat. On a Saturday in mid-October,
Shifflett, 30, cooked an allergy-safe ham
steak for breakfast. Then she had another
ham steak for dinner. “I was nervous at first,”
Shifflett says. Would her chest tighten, as it
usually did after eating meat? “I was com-
pletely fine.” Now, she says, “I just want to
savor every last bite.”
Beyond meat, Scott Commins, an allergist
at the University of North Carolina, Chapel
Hill, who treats AGS, hopes to offer his pa-
tients allergy-free pharmaceuticals. “Bacon is
nice,” Commins says, “ but I really believe that
there is a broader use of the animals medi-
cally that could arguably be more important.”
During the pandemic, for example, a safe ver-
sion of heparin would have benefited AGS
patients who developed blood clotting issues
from COVID-19.
Some medical products from alpha-
gal–free pigs could find uses beyond AGS
patients. Replacement heart valves, for in-
stance, are increasingly being made from
cow and pig tissues rather than mechanical
alternatives. But in part because of immune
attack, these bioprosthetic valves deteriorate
and must be replaced after 10 to 15 years.
To slow that attack, animal-derived valves
are stripped of cellular material and chemi-
cally treated to mask immune-stimulating
remnants. But according to pediatric heart
surgeon Joseph Turek of Duke University,
alpha-gal remains detectable at “actually
pretty astounding” levels—as he, Commins,
and others reported in The Journal of Tho-
racic and Cardiovascular Surgery in April.
An alpha-gal–free option might last twice
as long as other bioprosthetic valves, esti-
mates Turek, whose work is funded in part
by Revivicor.
The alpha-gal–free pigs could also find
use as skin donors for burn victims and as
a source of neurons to treat peripheral nerve
injuries. A company called Alexis Bio (for-
merly XenoTherapeutics) has already tested
skin from the pigs on six people with third-
degree burns. Ordinarily, doctors rely on hu-
man skin from dead people as a temporary
dressing, until patients can get a graft of
their own skin. But cadaveric skin is expen-
sive and often in short supply. Engineered
pig skin seems to function just as well to
help wounds heal for up to 9 days, the lon-
gest duration evaluated so far.
“The most striking thing [about the pig
skin] is that there is nothing striking,” says
trial investigator Jeremy Goverman, a burn
surgeon at Massachusetts General Hospital
(MGH). Because the graft only stays on the
body for a week or two, the immune system
doesn’t have time to reject it. “The use of
it is intended to be short term,” says Paul
Holzer, Alexis Bio’s CEO.
His company and another startup, Axo-
nova Medical, are also developing nerve
grafts from the same sorts of pigs. These
could supplant the current go-to approach
for nerve repair surgery: harvesting nerves
from somewhere else on a person’s body, an
option that is not always possible and can
leave people with sensory problems.
Axonova research director Kritika
Katiyar and her colleagues start with neu-
rons from Revivicor pig embryos and grow
them into nerves up to 5 centimeters long.
Having already repaired damaged leg
nerves in rats and facial nerves in pigs, the
company plans to move on to monkey stud-
ies next. Meanwhile, MGH plastic surgeon
Curtis Cetrulo, Holzer, and colleagues re-
ported in September using leg nerves from
pigs missing alpha-gal to repair damaged
arm nerves in rhesus macaques. In both
teams’ studies, over about 6 months, recipi-
ent animals’ own nerve cells replaced the
pig tissue—eliminating the risk of immune
rejection. “It looks like the host tissue has
completely taken over, and the graft has
been removed from the body naturally,”
Katiyar says.
Researchers such as University of Miami
xenotransplantation scientist Christopher
Burlak await the day when larger organ
transplants from pigs—kidneys, livers, or
hearts—help saves lives. The NYU study was
a “first step in a long road,” he says. Com-
panies are already taking the next ones,
designing pig organ donors with three or
more genes removed and up to nine added
human genes. None of those pigs’ organs
has been tested in people. “The next big ad-
vance in the field is going to be real trans-
plants,” Burlak says, “not the short-term
evaluation of xenografts in dead people.” jElie Dolgin is a science journalist based
in Somerville, Massachusetts.A
n accident in February has shut
d o w n a d i m i n u t i v e n u c l e a r r e a c t o r a t
the National Institute of Standards
and Technology (NIST)—and has
cost the United States, at least tem-
porarily, almost half of its capacity
to study materials with beams of neutrons.
In the incident, a fuel rod in the 52-year-
old reactor at the NIST Center for Neutron
Research (NCNR) in Gaithersburg, Mary-
land, overheated and partially melted, re-
leasing a small amount of radiation. The
public was never in danger, NIST says. But
the reactor won’t restart until April 2022
at the earliest, leaving thousands of users
scrambling to find beamtime elsewhere.
“We fully intend to restart the reactor,”
says Robert Dimeo, director of NCNR.
“We’re only going to do it when we’re con-
fident that it is safe to do so.”
In the meantime, the shutdown is “a
huge problem,” says Robert Birgeneau,
a condensed matter physicist at the Uni-
versity of California (UC), Berkeley, whose
team has used the neutron source to
study exotic iron-based superconductors.
Michael Hore, a polymer physicist at Case
Western Reserve University, says the shut-
down will set one of his projects back 1 or
2 years. “It’s not like we can go somewhere
else,” he says. “There are only so many in-
struments and they’re all oversubscribed
as it is.”
Liberated when atomic nuclei split,
neutrons can probe materials in ways x-
rays cannot. Whereas x-rays interact with
both the electrons and the atomic nuclei
in a sample, uncharged neutrons bounce
off only the nuclei, providing a comple-
mentary probe of a material’s atomic-scale
structure. They can also penetrate materi-
als that x-rays cannot, enabling research-
ers to image the interiors of big objectsReactor mishap
derails U.S.
studies with
neutron beams
NIST’s research reactor
suffered little damage, but
will be offline for months
MATERIALS SCIENCEBy Adrian Cho