E4 EZ EE THE WASHINGTON POST.TUESDAY, OCTOBER 26 , 2021
BY CATHY FREETo dd Van Guilder knew he was
in trouble the second he flew off
his bike during a ride along the
Cuyuna Lakes Mountain Bike
Trails in central Minnesota.
He sat up to brush himself off
and saw white spots in his vision,
he said. When he closed his eyes
and reopened them, the spots
turned to a solid wall of bright
white light.
He and his friend were visiting
the 50-mile mountain biking park
in the woods on Sept. 12 for some
adventure and exercise, he said. “I
was wearing a helmet, but when I
took the fall on my bike, I landed
really hard on my stomach and
chest,” Van Guilder said. “I could
hear where my buddy [talking to
him] was, but I c ouldn’t see him. I
told him, ‘I think I have a bit of a
problem.’ ”
Van Guilder didn’t realize how
big the problem was. About 30 min-
utes later, as he lay in the woods, he
would need an emergency trache-
otomy — a surgery to make a life-
saving airway in his neck.
After his f riend called 9 11, para-
medics arrived on the scene and
saw that he was having difficulty
breathing, he said. They realized
that they needed a tank of oxygen
from the ambulance in the park-
ing lot, which was three-quarters
of a mile down the trail. They
asked aloud whether someone
would run down and retrieve it
before the situation became more
dire, Van Guilder said. A police
officer on the scene volunteered,
and jogged back down the trail.
It was lucky timing. Just then,
Jesse C oenen, a n emergency room
doctor from Hayward, Wis.,
passed the officer running down
the trail. Coenen, 38, was visitinggloves, turned them i nside out a nd
handed them to him, he said.
“Cutting somebody’s neck like
this is a rare procedure, even for a
doctor,” Coenen said. “I’d done it
before on mannequins and a pig
cadaver, and I knew by heart how
to do it. I’d just hoped I would
never have to.”
He made an incision beneath
Van Guilder’s Adam’s apple, and
after a bit got the tube in.
A paramedic quickly began to
manually deliver oxygen through
the bag valve mask.
Once Van Guilder’s o xygen levels
had risen, paramedics carefully
transported him down the trail to
the parking lot using a one-
wheeled, flat medical gurney simi-
lar to a wheelbarrow, Coenen said.
“I have to say that I wasn’t optimis-
tic he would live when they took
him a way in the helicopter,” h e said.
But at the hospital, after doc-tors gave him stitches to close up
the i ncisions in h is neck and treat-
ed him for a traumatic brain inju-
ry, Van Guilder rallied. And after
10 days he was released.
Other than a scar from the tra-
cheotomy, Van Guilder said, he
had nothing more than a scab on
his right arm and some minor
road rash on his left knee. He i s on
a soft-food diet for a while, but
once his throat is healed, he’d like
to take Coenen out to dinner, he
said.
“I talked to him on a Zoom call
and told him how grateful I am
that he happened to be there that
day at that precise moment,” Van
Guilder said. “I’m obviously ex-
tremely fortunate. What are the
odds?”
[email protected] More at washingtonpost.com/
inspired-lifethe t rails t hat Sunday afternoon t o
pedal off stress from working 13-
hour days in the ER.
When Coenen learned that the
officer was racing to fetch an oxy-
gen tank, h e and a friend offered to
help. They hurried down the trail
on their bikes, asked
the ambulance driver
for the oxygen tank,
then pedaled it back to the scene.
By this time, Van Guilder was
unconscious and the members of
the medical crew said they were
preparing to intubate him — in-
sert a tube in his throat — to make
it easier for him to breathe with a
manual resuscitator, also called a
bag valve mask, Coenen said.
Coenen said he took in the situ-
ation for about 30 seconds, then
told the E MTs that he w as a doctor.
“I quickly realized this was a
serious situation,” said Coenen,
who works at Hayward Area Me-morial Hospital.
After several attempts by Co-
enen to guide an intubation tube
down Van Guilder’s throat failed
because he was unable to see the
windpipe, t he medics tried to clear
saliva away with a portable suc-
tion device. That also
failed, Coenen said,
and h e knew t here was
only one option left to deliver air
to Van G uilder’s l ungs a nd save his
life: an emergency tracheotomy.
“His oxygen level had started to
drop, and I was getting con-
cerned,” the doctor said. “I figured
he might have anywhere between
10 and 20 minutes before he died.
That’s when I decided to enter the
windpipe through the neck.”
Coenen asked the EMTs if they
had any tools he could use. One of
them rummaged through a bag
and produced a scalpel, while an-
other removed her antisepticINSPIRED LIFEA bike rider needed lifesaving surgery. A doctor happened to be cycling by.
But he was smart — and funny.
When she was having trouble
grasping the concept of infinity,
he broke it down for her. “Imagine
you could have all the clothes that
you wanted,” Weissman said.
“That’s infinity.”
Laura Friedman, a classmate
who shared an apartment with
Weissman during senior year, said
an image from graduation is
seared in her mind: Weissman
arriving on a moped, clad in cap
and gown, but different from the
rest. Weissman had also received
his master’s degree in biochemis-
try in the same time his class-
mates took to get their undergrad-
uate diploma.
“We were all hard-working.
And Drew worked a level harder
than all of us,” Friedman said.
He decided to pursue a joint
medical and scientific graduate
degree at Boston University
School of Medicine. He worked
hard, but efficiently. When other
students were studying the night
before a big test, he and Mary
Ellen would play tennis.
He seemed to be going through
life with a firm sense of who he
was and what he wanted to do,
although he didn’t talk much
about it. His family jokes that he
has a daily word quota. Mary
Ellen recalls her husband turning
to interrupt her once and saying,
without malice, “We’ve already
talked today.”
What was always clear was that
science was central. He was curi-
ous. He trained to be a doctor
because he wanted to be a better
scientist, said Mary Ellen, a child
psychologist. He dreamed his
work could lead to a vaccine or
therapy that could benefit people.
“He just wants to do his thing,
think about things, make his
brain happy and move on,”
Mary Ellen said.A chance encounter
In 1991, Weissman went to
work i n the laboratory of Anthony
S. Fauci, director of the National
Institute of Allergy and Infectious
Diseases. Working in Fauci’s lab
introduced him to new connec-
tions b etween the l ab and people’s
health. Before Google, w hen t here
was a diagnostic question any-
where in the world, people would
call Fauci’s lab to figure it out.
“If you put a person in a situa-
tion like that, the learning is im-
mense,” Mary Ellen said.
He became fascinated by a re-
cently discovered immune cell
that branched like a tree under
the microscope, with limbs that
extended and retracted. These dy-namic dendritic cells were key to
how the immune system learned
to defeat pathogens — and Weiss-
man thought they would be the
best target for vaccines.
“They travel around the body
looking for foreign things,” Weiss-
man said.
When he started his own labo-
ratory, he wanted to work on tar-
geting these cells.
Two things mattered in looking
for a spot for Weissman and his
family to land, Mary Ellen re-
called: an institution with the po-
tential for fruitful collaborations
and a place with access to good
schools for their daughters, Ra-
chel and Allison.
Harvey Friedman recruited
Weissman to the medical school
at the University of Pennsylvania,
where he was chief of the infec-
tious-diseases division.Weissman was an unconven-
tional hire — he wasn’t trained as
an infectious-diseases doctor, so
Friedman had to battle his depart-
ment chair to bring him in.
Not long after the move t o Penn
in 1997, Weissman ran into an
intense Hungarian s cientist at t he
photocopier, Kariko. Before sci-
ence journals were online, scien-
tists laboriously copied articles to
keep apprised of the latest devel-
opments. Kariko and Weissman
worked in different departments,
but they were always competing
for time at the same copier.
Kariko told Weissman about
mRNA and her intention to turn it
into a powerful medicine, certain
it could b ecome a method o f deliv-
ering therapeutic proteins to cure
disease. Weissman wondered if it
could also be a way of delivering a
foreign viral protein to the den-
dritic cells that he wanted to tar-
get for vaccine development. He
asked Kariko if she could synthe-
size some mRNA for him to try in
an experiment.
Weissman had been successful
securing grants and had start-up
funds left over from the univer-
sity. He initially u sed those to help
underwrite his scientific work on
mRNA, a side project for a labprimarily focused on HIV. Weiss-
man brought his expertise as an
immunologist and his interest in
vaccine development. Kariko
brought exhaustive knowledge of
RNA, a biochemistry background
and unbounded enthusiasm for
the work.
“He understood that [Kariko]
had something a lot of people
didn’t u nderstand,” said Mark Dy-
bul, a longtime colleague of Weiss-
man’s who trained with him in
Fauci’s laboratory.‘We didn’t give up’
The first obstacle was scientif-
ic. The RNA triggered a harmful
inflammatory response.
This was a major setback for
Kariko, who had been hoping to
use mRNA as a therapeutic in the
brain. If they could not find a way
to quell the inflammation, it could
be a dead end for RNA as a thera-
py. Weissman remained intrigued
that the molecule might make a
good vaccine.
This was the kind of scientific
frustration they were both used
to, and for seven years they
worked on mRNA, trying to un-
derstand how to turn it from a
biological process into a medical
technology.
Messenger RNA is a code writ-
ten with a four-letter alphabet —
C, G, A and U. Kariko and Weiss-
man discovered that if they made
a tiny chemical modification to
the U, it had a profound effect —
the mRNA no longer triggered
inflammation and made much
more protein.
Rachel Weissman, Drew’s older
daughter, was in middle school
when her dad told her he was
excited because he had discovered
something in the lab.
Her first question was whether
he had named it after t heir family.
It was something called mRNA,
he told her.
“You did name it after us!” she
said. Her mom is Mary Ellen, she
was Rachel, ’n Allison was her
younger sister.
But top scientific journals were
not interested.
Weissman recalled that even at
the solid but specialized journal
Immunity, it was a long back and
forth to publish. The work was so
far ahead of its time that few
people recognized its signifi-
cance.
Over the years, Kariko and
Weissman tried everything to
push their ideas forward. They
sought grants. They founded a
company to turn their technology
from a novel finding into some-
thing that could save people’sthis moment.
For more than two decades,
Weissman and Kariko worked
shoulder-to-shoulder at the lab
bench to turn m essenger RNA, t he
genetic instruction books that tell
cells how to build proteins, into
medicine. If DNA is the blueprint
of life, mRNA is the work order
that makes it happen. They were
convinced this natural process
could be harnessed to revolution-
ize how vaccines are made and
transform how diseases are treat-
ed.
But the typical gatekeepers in
science — journal editors, grant
reviewers, investors — weren’t
convinced. Messenger RNA was
unstable, prone to fall apart.
When it was injected into ani-
mals, it triggered an inflammato-
ry response, making them sick,
not better.
In 2005, Weissman and Kariko
found a way to vastly increase
mRNA’s therapeutic potential — a
simple chemical tweak to one let-
ter of its genetic code. This
changed everything, they
thought. Then, nothing hap-
pened.
“Our phones never rang. No-
body cared,” Weissman said. “But
we knew the potential and never
stopped working on it.”
Interest in the field had begun
to heat up in the specialized world
of biotechnology in recent years,
but it was the pandemic that
abruptly propelled the technol-
ogy onto t he biggest s tage imagin-
able. The first-of-their-kind Pfiz-
er-BioNTech and Moderna vac-
cines use mRNA to teach the body
how to recognize and block the
coronavirus. Their technology has
become mainstream, overnight.
But the pandemic is the be-
ginning, not the end of the sci-
entific story.
Weissman wants to use mRNA
vaccines to defeat influenza, stop
the next coronavirus pandemic,
prevent herpes, end HIV. He sees
even broader opportunities on
the horizon: a cure for sickle cell
anemia that could be scaled up
and deployed in Africa, unlike
current treatments, and pave the
way for other therapies.
In contrast to their reserved
boss, the scientists who work in
Weissman’s rapidly growing lab
are ebullient. They share apho-
risms from the places they grew
up to describe their pursuit.
“Somebody else peels the or-
ange, and the other people drink
the juice,” said Xiomara Mercado-
López, a senior investigator work-
ing on vaccines for influenza and
a therapy for herpes, invoking a
saying from Puerto Rico, where
she grew up.
“Somebody takes the walnuts
from the fire, but you enjoy them
all,” said Elena Atochina-Vasser-
man, an adjunct assistant profes-
sor originally from Russia, who is
working on a vaccine against the
stomach b ug norovirus. S he keeps
a sleeping bag stowed at her desk
so she can work more efficiently.
“Somebody else planted the
tree, but we have the shade,” said
Qin Li, a senior research investi-
gator focused on a universal influ-
enza vaccine.
He ‘was born 40’
Growing up in Lexington,
Mass., Weissman was noticeably
more disciplined, self-possessed
and capable than other kids, his
younger sister, Stephanie Weiss-
man, recalled. When they went
sailing with cousins, Drew would
sail and everyone else would be
crew — which meant he did every-
thing.
“He is one of those people who
was born 40,” Stephanie said.
At Brandeis University, he met
his future wife, Mary Ellen Weiss-
man. A friend introduced them
when Mary E llen was having trou-
ble with calculus. It was hard to
get to know him at first, and they
wouldn’t start dating right away.
WEISSMAN FROM E1
lives.
Haitao Hu, a scientist who
joined t he l ab to p ursue his gradu-
ate degree shortly around the
time of their breakthrough in
2005, said Weissman’s lab was a
remarkable place to learn how to
be a scientist.
A paradox of science is that as
investigators grow more success-
ful, they often end up with huge
labs, doing so much traveling,
giving talks and writing grants
that they drift farther from the lab
bench.
Weissman was curious, not am-
bitious, following the ideas where
they led and more focused on
mentoring scientists in his lab
than traveling.
“He enjoys science. He loves
basic research,” Hu said.
When Weissman ran into a
problem in the lab, he would often
start a project at home. Build a
deck. Do some plumbing. Put an
addition onto the house.
Often, while he labored on
something completely different,
he would find a way to solve the
problem he was ramming into at
work.
“He’d use that as an outlet
when he was frustrated, and often
that meant there was something
broken or halfway done,” Rachel
recalled recently.
There were still more hurdles
before mRNA could become use-
ful for medicine: its fundamental
instability. Norbert Pardi, a scien-
tist who trained with Weissman
and Kariko, spent three years try-
ing to find a safe and efficient way
to deliver it intact. After a long
string of failures, he made what
felt like a last-ditch effort to see if
a lipid nanoparticle — a submi-
croscopic bubble of fat — devel-
oped by the Canadian company
Acuitas Therapeutics could be
used to protect the molecule and
deliver it to cells in living animals.
For the test experiment, he cre-
ated mRNA encoding an enzyme
called firefly luciferase. As the
name suggests, if cells made the
enzyme, then they would light up
once he injected another protein.
Pardi injected it into a mouse
and saw light. To this day, Pardi,
who now runs his own lab at Penn,
remembers the date — Aug. 20,
2014.
When he talked about it with
Weissman the next day, they both
knew what it meant. This was
going to work.
Weissman recently received an
honorary degree from Drexel Uni-
versity’s College of Medicine, and
at commencement, he wished an
audience of young physicians alifetime of frustration.
“The person who achieves his
goal is the one that has faced
frustration and dealt with it, un-
derstood it and used it to their
advantage,” Weissman said. “We
repeatedly fell, were knocked
down, ignored. And we kept get-
ting up, and we didn’t give up.”Prepared for battle
When outbreaks of the Zika
virus occurred in 2015 and 2016,
Weissman began working on a
vaccine. His family thought this
might be his breakthrough mo-
ment.
Rachel, more than anyone in
the family, could talk science with
her dad. She followed in many of
his footsteps, taking many of the
science classes he did at B randeis.
She spent a summer working in
his lab. Her senior year, she weld-
ed a sculpture of the molecule
that made mRNA work, pseudou-
ridine.
But even Rachel, conversant in
science, realized her dad wasn’t
keeping them in the loop and so
set up a Google alert with his
name.
The Zika vaccine was success-
ful in protecting monkeys, but it
went back on the shelf as the
threat receded. It turned out to be
a dry run.
When the coronavirus pan-
demic hit, Rachel called him.
“You’re on this, right?” she
asked.
“Yeah, yeah,” he told her.
Mary Ellen and daughter Alli-
son volunteered for a vaccine tri-
al. Weissman felt he couldn’t, be-
cause he didn’t want to have the
appearance of bias. His lab has
received funding from BioNTech,
and he consulted with the compa-
ny, but his and Kariko’s inventions
are crucial to both the Moderna
and Pfizer-BioNTech vaccines.
Weissman found out the Pfizer-
BioNTech vaccine was remark-
ably effective when Mary Ellen
interrupted his work early one
morning in November. She had
heard it on the news.
Weissman let the moment sink
in and then told his wife he need-
ed to get back to work. He did call
his parents, who are in their 80s,
to let them know.
When the Pfizer-BioNTech vac-
cine was given an overwhelming
thumbs up by an expert federal
advisory panel, all but ensuring it
would get a regulatory green light,
Rachel FaceTimed him.
“Dad, your vaccine,” she said.
“It can go into people.”
His face, she recalled, was char-
acteristically blank. He had been
in meetings all day.
Scientists will debate how
much the chemical modifications
Kariko and Weissman discovered
contribute to the vaccines’ suc-
cess. A n mRNA vaccine that did
not incorporate those changes
flopped.
Weissman thinks he knows
why.
More than a year before the
pandemic, he and colleagues
showed that modified RNA is key
to a robust immune response. It
triggers key immune cells called T
follicular helper cells. Those T
cells then drive the immune cells
that produce virus-fighting anti-
bodies. Unmodified mRNA, on
the other hand, triggers mol-
ecules that block those T cells.
When Friedman, the Brandeis
classmate, got her shot, she called
Weissman minutes afterward.
“I cry when I think about Drew
in so many different ways. I called
him after both my vaccines, say-
ing, ‘Thank you for saving my life
and for saving the world, and also
— as a friend,’ ” Friedman said.
“You’re welcome,” she thinks he
replied
Then, ever the consummate
physician and friend, he remind-
ed her: She should really stay
there for the full 15 minutes after
her shot in case of any adverse
reaction.
[email protected]‘We knew the potential and never stopped working on it’
“I called him after
both my vaccines,
saying, ‘Thank you
for saving my life.’ ”
Laura Friedman, a former
Brandeis classmateRACHEL WISNIEWSKI FOR THE WASHINGTON POST
Drew Weissman’s Lewis S. Rosenstiel Award, which was also given to Katalin Kariko for their work on messenger RNA vaccines
against the coronavirus, sits on a s helf in Weissman’s office at the University of Pennsylvania.