50 THE SCIENTIST | the-scientist.com
PROFILEdecided to abandon a career as a doctor and head back to the
lab. “I just did not like it,” he says. Not only was the medical
internship an imperfect fit, a family illness made this a
particularly trying time in his life.
Witte decided to return to Stanford, but Weissman
suggested that before he packed his bags and crossed the
country again, he reach out to David Baltimore, who was
then a professor of microbiology at MIT. “I kind of laughed
because David Baltimore had won the Nobel Prize about two
years prior, and I was sure that the lineup of people trying to
get into his lab was quite long,” Witte recalls.Fortunately for Witte, Weissman knew Baltimore and
called to put in a recommendation for his former mentee. “Irv
said such wonderful things about him that I thought I would be
missing out on a terrific person if I didn’t take him,” Baltimore
recalls. “And of course, it worked out terrifically well.”
At the time, a focus of Baltimore’s lab was the Abelson
murine leukemia virus, a retrovirus that causes cancer in
mice. As a postdoc, Witte worked diligently to characterize a
protein encoded within the virus’s genome, which eventually
led to the discovery that it was a tyrosine kinase. “My graduate
work and my postdoc were the most enjoyable times during my
[scientific career], because all I had to do was be in the lab and
do the work that I love,” Witte says.EXPLORING NEW FRONTIERS
Witte left Boston in 1980 and headed west again to set up
his own lab at the University of California, Los Angeles. Within
the first few days of arriving, Witte met Jami McLaughlin, a
research assistant in the department. The two started dating
shortly after and got married in May 1984. A few months
later, McLaughlin joined Witte’s lab, where, alongside Witte’s
graduate students, she helped clone and sequence BCR-ABL,
an oncogene that causes human leukemias. “It’s really been
a partnership over many years, with her doing some of the
really critical experiments that led to these important results,”
Witte says.
His team later identified Bruton’s tyrosine kinase
(BTK), a protein produced by a mutated gene in X-linked
agammaglobulinemia, a human immune deficiency marked
by a loss of B cells (Science, 261:358–61, 1993). Further
investigations of BTK’s expression and kinase activity
eventually led to the develop of ibrutinib (Imbruvica), a drug
used to treat B cell–associated leukemias and lymphomas.For almost three decades, Witte’s research centered on
leukemias and lymphomas. Then, in the mid-1990s, he started
hearing from relatives who had been diagnosed with prostate
cancer. “They would call me asking, ‘What should we do?’” he
recalls. After digging through the literature, Witte discovered
that there had been little change in the treatment of prostate
cancer for several decades. The paucity of advances in this
field led him to a radical decision: to shift his focus from
blood cancers to prostate cancer. “That wasn’t easy at that
stage of my career,” Witte says. “I had a very well-established
reputation in one area, and no reputation whatsoever in this
new area.”
But just as he had persevered with his groundbreaking
experiments in the 1970s, he pushed himself to work through
any roadblocks that popped up as he started down a new
research path. This work has led to, among other things,
pinpointing the population of stem cells that gives rise
to human prostate cancers (Science, 329:568–71, 2010).
Another realm where Witte’s perseverance paid off was in
his participation in industry, particularly with companies
developing cancer drugs. “One of the important things
about Owen was that he has been unafraid to get involved
in companies,” Baltimore says. “Many researchers are
comfortable working both with industry and as academics,
but that was not true 20 years ago when Owen was first doing
that.” It allowed him to have an even greater scientific impact,
Baltimore explains.
Witte has also had an impact on his students with his
scientific curiosity and warmth. Witte was incredibly
knowledgeable and was an insightful mentor with high
expectations for his students, says Charles Sawyers, now
a physician-scientist at Memorial Sloan Kettering Cancer
Center. “I found [his lab] to b e the most intellectually
stimulating community of people,” he says. “I was like a
sponge, soaking up everything, because I was so new to the
area.”
Prostate cancer researcher John Lee of Fred Hutchinson
Cancer Research Center recalls Witte’s softer side. During
his graduate work in Witte’s lab, Lee’s mother was diagnosed
with metastatic bladder cancer and passed away a year after
starting treatment. “Owen was very supportive during that
period,” Lee says. “But the other really important thing that
he told me was that [when it comes to cancer research],
there’s a lot of work yet to be done.”
Witte’s lab continues to contribute important discoveries
to cancer research. One of the most recent was demonstrating
that epithelial cancers starting in different organs, such as
the prostate and lung, develop into highly aggressive, lethal
late-stage tumors by a nearly identical mechanism (Science,
362:91–95, 2018). The discovery suggests that targeting a set
of “master” gene regulators could potentially help treat a wide
range of cancers, Witte says. “I’m 70 years old and I’m still
really jazzed up about this new finding.” gI’m 70 years old and I’m still really jazzed up
about this new finding.
— Owen Witte, UCLA