Marguerite Vogt transformed the study of all viruses

CALIFORNIA: Working from early morning
until late at night in a small, isolated basement laboratory at the California
Institute of Technology, Vogt painstakingly handled test tubes and petri dishes
under a fume hood: incubating, pipetting, centrifuging, incubating again. She
was trying to grow a dangerous pathogen: poliovirus.

It was
1952 and polio was one of the most feared diseases
in America, paralyzing more than 15,000 people, mostly children,
each year. Parents wouldn’t let their children play
outside, and quarantines were instituted in neighborhoods with polio
cases.

Scientists
were desperate for information about the virus, but many were hesitant to work
with the infectious agent. “Everybody was afraid to go to that little lab in
the basement,” says Martin Haas, professor of biology and oncology at the
University of California, San Diego, and a personal friend and collaborator of
Vogt’s for over three decades.

Vogt, a
brand-new research associate in the laboratory of Renato Dulbecco, took on the
task of attempting to grow and isolate the virus on a layer of monkey kidney
cells. The method was called a plaque assay for the distinctive round plaques
that form when a single virus particle kills all the cells around it.

Vogt
didn’t tell her parents, both acclaimed scientists in Germany, that she was
working with the virus. She later remarked that her father would have been very
angry had he known of her poliovirus work, Haas says.

After a
year of persistence, Vogt succeeded (and remained virus-free). In 1954, she and
Dulbecco published the method for
purifying and counting poliovirus particles. It was immediately used by other
scientists to study variants of poliovirus, and by microbiologist Albert Sabin
to identify and isolate strains of weakened
poliovirus to make the oral polio
vaccine used in mass vaccination campaigns around the world.

Perhaps
even more importantly, the poliovirus plaque assay enabled scientists worldwide
to analyze animal viruses at the level of individual cells, a field now known
as molecular virology. Vogt and Dulbecco’s approach remains the gold standard
for purifying and counting virus particles, including in recent studies of
SARS-CoV-2, the virus that causes COVID-19. The method, used to measure how
infectious a virus is and isolate strains of a virus for further research, is
ubiquitous in labs around the world.

Throughout a career spanning
three-quarters of a century, beginning with a publication when she was 14 years
old, Vogt contributed extensively to our knowledge of the genetics of animal development,
how viruses can cause cancer and cellular life cycles. Upon her death in 2007
at the age of 94, nearly 100 three-ring binders lined the shelves of her
office, filled with notes on decades of experiments.

Vogt was
known for her intense, inventive lab work, including what others have called
her “green thumb” for tissue culture — the process of growing cells, viruses
and tissues in a dish.

“Being a
meticulous person, she worried about every detail of the process of cell
culture,” says David Baltimore, biologist and president emeritus of Caltech who
worked for three years in a lab close to Dulbecco’s. “That’s really important,
because it is finicky. Long experience and precise handling are key to getting
good data.”

Born in
1913, Vogt grew up in Germany surrounded by science. The younger daughter of
two pioneers of brain research, Oskar and Cécile Vogt, she and her sister
Marthe were budding scientists from their youth. Marguerite Vogt’s first paper,
published in 1927, investigated the genetics of fruit fly development.

But a year after receiving her
M.D. at the Friedrich Wilhelm University in 1936, Vogt and her liberal family
were ousted from Berlin by the Nazis. Her parents lost their positions at the
Kaiser Wilhelm Institute for Brain Research (now the Max Planck Institute), and
Oskar was accused of supporting communists. The family avoided arrest or death
due to the intercession of the Krupp family, former patients of Oskar’s and
well-connected arms manufacturers who supplied the Nazi regime. With funding
from the Krupps, Oskar and Cécile set up a private brain research institute in
a remote part of Germany’s Black Forest. There, they continued their research
and offered shelter and jobs to other people fleeing Nazi persecution.

From her
parents’ institute in the Black Forest, Vogt published 39 seminal papers on how
hormones and genetics influence the development of fruit flies, work that was
later considered ahead of its time. In 1950, with the help of German-American
scientists Hermann Muller and Max Delbrück, Vogt emigrated from Germany to the
United States. Vogt rarely talked about her experiences during World War II.
She never returned to Germany and refused to speak her native tongue with
visiting German students and scientists.

After
briefly working with Delbrück on bacterial genetics, Vogt went to work for
Dulbecco on the poliovirus assay in 1952. After that success, the pair
investigated the role of viruses in cancer. Once again, Vogt developed a
technique to grow a virus — this time a small DNA-containing virus called
polyomavirus — and the pair was able to count how many cells the virus transformed into cancer cells. In subsequent
papers, the team demonstrated that certain viruses integrate their genetic
material into host cell DNA, causing uncontrolled cell growth. The discovery
changed the way scientists and doctors thought about cancer, showing that
cancer is caused by genetic changes in a cell.

In 1963,
Vogt followed Dulbecco to the Salk Institute in La Jolla, Calif. There, she
spent decades studying viruses that can cause tumors, as well as other areas
that sparked her interest, such as trying to define a cellular clock. “She was
not only very intense, she was very inventive,” says Haas. “She always knew
which way to go and what do to.”

Like the
early days studying poliovirus, Vogt worked long and hard, typically six days a
week, 10 hours per day. “She liked trying new things, so we often tried to do
techniques that she had admired in papers she had read, or we learned things
from other labs,” says Candy Haggblom, Vogt’s laboratory assistant for the last
30 years of Vogt’s career.

Vogt
never married or had children. “Science was my milk,” she told the New York Timesin 2001.
But Vogt didn’t lack for company: She was a friend and mentor to many of the
young scientists in the lab, four of whom went on to earn Nobel Prizes, and as
an accomplished pianist and cellist, Vogt hosted a chamber music group that met
at her home every Sunday morning for over 40 years, Haas says.

Bottom
of Form

In 1975,
Dulbecco was awarded the Nobel Prize in physiology
or medicine for work on how tumor viruses transform cells, a prize shared with Baltimore and virologist Howard Temin.
Vogt was not recognized, and Dulbecco did not acknowledge her in his Nobel
lecture.

During
her lifetime, Vogt did not receive a single major prize or recognition. Despite
an advanced degree and prestigious publication record, Vogt did not become a
professor or get her own lab at Salk until after Dulbecco left the institute in
1972. She was 59 years old. That rankled her, says Haas, who cared for Vogt
later in her life and thought of her like a mother. “She ran his lab while he
ran around the world giving talks,” he says. “Marguerite ran it all.”

At 80,
Vogt regularly jogged into the lab early in the morning. At 85, she published
her final paper, fittingly about how human cells slow down and lose their
ability to replicate with age.