The Scientist - USA (2020-04)

48 THE SCIENTIST | the-scientist.com

PROFILE

REED HUTCHINSON/UCLA

S

itting at a lab bench at MIT in the late 1970s, Owen Witte

finally had to admit he was stuck. He had identified a

cancer-causing protein encoded in the genome of the

Abelson murine leukemia virus, which infects mice. Prior work

had led Witte to hypothesize that this protein should be a kinase,

an enzyme that attaches phosphoryl groups to amino acids. But

after double- and triple-checking his methods and repeating the

experiments several times, he failed to find evidence that this

was the case.

Witte’s idea that the Abelson murine leukemia virus

(A-MuLV) protein should be a protein kinase stemmed primarily

from work by molecular biologist Raymond Erikson, then at the

University of Colorado, and his colleagues. They had shown that

the oncogenic viral gene src was associated with protein kinases,

and Witte expected to find something similar with A-MuLV. He

followed the standard protocol for characterizing protein kinases

by identifying their phosphorylated amino acid products, which

involved adding the A-MuLV protein to an acidic solution, heating

it, then waiting 24 hours for the enzyme to complete its action.

But in the end, Witte could see only free phosphates—compounds

that are transferred during a kinase reaction.

Exasperated, he tried something different. He analyzed his

solutions at several time points during the reaction rather than

only at the end. The new protocol worked. Finally, after several

months of trying, he’d identified the elusive amino acid, which

appeared within a few hours (Nature, 283:826–31, 1980). To

Witte’s surprise, the amino acid was neither phosphoserine nor

phosphothreonine, which, at the time, were thought to be the

primary phosphorylated amino acids produced by protein kinases

in mammals. Instead, it turned out to be phosphotyrosine, which

had never before been observed as the product of a protein kinase

reaction. The A-MuLV protein was a newly discovered type of

enzyme: a tyrosine kinase.

Another team, led by To n y Hunter at the Salk Institute in

California, nearly simultaneously reported tyrosine kinase activity

associated with another virus that causes cancer in chickens.

Witte, after setting up his own lab, demonstrated that a homolog

of the A-MuLV tyrosine kinase, ABL1, was highly active in human

leukemias—a discovery that contributed to the development of

a lifesaving leukemia therapy called Gleevec (imatinib). The

discovery of tyrosine kinases also revealed an entire class of

enzymes that could be medical targets. It is “probably the single

greatest discovery that I could ever imagine being associated

with,” Witte says.

FROM SUBURBIA TO STANFORD

Born in Brooklyn in May 1949, Witte started his life as a city

boy, then spent much of his childhood and adolescence in

Levittowns along the East Coast of the US. Levittowns were

large housing developments that sprang up after World War II

to house veterans and their families. Abraham Levitt and his two

sons, William and Alfred, founded the company that constructed

these developments, which became the prototypical American

suburbs—sprawling neighborhoods with rows upon rows of

nearly identical homes, situated on rectangular land plots with

driveways and neatly trimmed lawns.

When Witte was in third grade, Levitt & Sons hired his

father, and the family moved to one of the cookie-cutter suburbs

in Pennsylvania. Witte credits his early interest in science to a

fifth-grade teacher in the Pennsylvania Levittown. “She taught

science not by reciting facts from a textbook, but with hands-on

experiments,” Witte says, noting that one such experiment

involved learning about the circulatory system by dissecting a

cow’s heart. “That allowed us to learn what real science is about.”

Witte continued to do hands-on science as he got older,

working at the Department of Health conducting bacterial

counts in lakes, swimming pools, and restaurants. But at the

time, he wasn’t dead set on a career in science. In high school

he was drawn to the culinary arts, and later, in 1967, he went

off to study at Cornell University in Ithaca, New York, with an

undecided major. While he was there, he considered a career in

hotel management, but was drawn back to science after taking

classes in the university’s College of Agriculture, where he was

exposed to various scientific disciplines, including food science

and microbiology.

Witte developed an interest in research while working

in the lab of Lawrence Slobin, a professor in the department

of microbiology, studying how antibodies stop viruses from

replicating within a host. It was 1971, right in the middle of the

Vietnam War, when Witte was finishing up his final undergraduate

Through his studies on oncogenic viruses, University of California, Los Angeles, professor

Owen Witte has helped develop lifesaving treatments.

BY DIANA KWON

Cracking Down on Cancer

That’s the great beauty of science.... Doing

work because the question is interesting and

not necessarily being able to anticipate when

it might actually be useful down the road.

— Owen Witte, UCLA