Leonard — who counts Multiplicity and
Gattaca among her favorite movies —
walks the walk: she and her husband gave
each other the gift of genome sequencing
for Christmas.
“A lot of people say, ‘Aren’t you scared
what the genome will tell you? There’s
so many things in there we don’t know
what to do with,’” says Leonard. “Well,
yeah. But there’s a lot we do know what
to do with now, and we’ll learn more
about the stuff that we don’t know.” But
she acknowledges that clinical genome
sequencing carries a social responsibility
and raises ethical questions. To that end,
73 UVM staff and faculty members
underwent genome sequencing earlier
this year to raise awareness about plans
for clinical genome sequencing at UVM.
A post-sequence survey looked at the
experience overall, and Leonard and her
team will follow up with the ten who
signed up to participate but dropped out
before sequencing to better understand
their concerns.
Though genomic sequencing is
not new to the College of Medicine, its
clinical application is, a fact that has
been acknowledged well beyond the
state’s borders.
“Debra is bringing genome
sequencing into clinical medicine in ways
that should make UVM a model system
for others to emulate,” says Geoffrey
Ginsburg, M.D., Ph.D., co-chair of
the National Academies of Science,
Engineering and Medicine (NASEM)
Roundtable on Genomics and Precision
Medicine, of which Leonard is a member
representing the College of American
Pathologists. Adam Berger, Ph.D., a former
NASEM Roundtable staffer who is now
a senior fellow in the U.S. Department of
Health and Human Services, says, “At the
Roundtable, we were really looking at how
you build a genomic medicine program
— how to integrate genetics and genomics
into clinical practice. Debra is out there
actually doing it. It’s a great effort to be
initiated and she’s the perfect leader.”
It’s safe to say it wouldn’t be happening
for a long time at the College of Medicine
— if ever — if Leonard had listened to
her undergraduate advisor, who told her
she was not cut out for medical school,
although she’d planned on being a doctor
from the age of 14. Like so many who
choose medicine, she says she always
wanted “to help people,” without grasping
what that might look like: “I didn’t really
understand what ’help people’ would
mean over the long term of my career
because I thought it was help sick people.”
Lacking the mentoring she now recognizes
she needed, Leonard revised her plan to
be a doctor, and after college graduation
took a job as a technician at the Eaton-
Peabody Laboratory at Massachusetts
Eye and Ear Infirmary, assisting
researchers from Harvard, MIT, and
Massachusetts General Hospital.
With her college advisor’s comment
echoing in her head, Leonard then went
to New York to start Columbia’s two-year
BSN program with an eye to becoming a
nurse practitioner. Newly married to an
NYU graduate student, she also needed
to find a job, which she did by knocking
repeatedly on the door of an auditory
physiology research lab at Columbia where
Shyam Khanna, Ph.D., was working. She
helped conduct research that would be
published, but perhaps more importantly,
Khanna told her right out of the gate that
she belonged in medical school. It was a
message she had trained herself to ignore,
but when another colleague asked if she’d
ever considered an M.D./PhD program
she reconsidered. She was accepted into the
NYU Medical Scientist Training Program
and earned a Ph.D. in molecular biology in
addition to her M.D. Even then, she says,
she stuck her fingers in her ears every time
the head of the program said pathology
was the only place for dual-doctoral
degrees, continuing to believe she wanted
to be Marcus Welby, the quintessential
family practice physician. But her next
evolution, to mother — she had one son
in the middle of her Ph.D. program and
another in the first year of her residency
— forced her to acknowledge that the 100-
hour or more work weeks (there were no
work hour limits for residents at that time)
that would be part of an internal medicine
residency and fellowship, coupled with the
demands of parenthood, were more of a
juggle than she was prepared to undertake.
Another take-away from that period
that Leonard brings to her role as chief is
the importance of a life beyond medicine:
“We’re a family-friendly department
because there’s no good time to have kids.
Whenever someone decides to have kids,
it’s fine with me — my only rule is I have
to hold the baby.”
As Leonard was looking for her first
faculty position, it was an exciting time
in pathology: polymerase chain reaction
had just been discovered and molecular
pathology and diagnostics were being
developed. Leonard accepted a position at
Case Western Reserve, where she was the
lone molecular pathologist and tasked with
the responsibility of establishing a clinical
molecular laboratory, before moving on to
the University of Pennsylvania, where she
took over a larger clinical laboratory. After
almost a decade there, Leonard went to
Weill Cornell Medical College, where she
served as vice chair of laboratory medicine
and oversaw the creation of a molecular
pathology laboratory while also serving
as chief diversity officer for the medical
college. All the while, on the heels of the
Human Genome Project, next-generation
sequencing that would make possible
the sequencing of a patient’s genome was
beginning to look like a clinical reality.
“We weren’t sure at that point whether
you would even want to ever do a genome
sequence on a patient,” says Leonard, “but
there were a lot of diseases where doing
large segments of the genome would be
much more cost effective than testing one
gene at a time as separate tests.” Nextgen
sequencing was being put into play
in clinical laboratories, but only at large
universities. Leonard, who had been part
of a national discussion about ACOs and
the future of healthcare reform, saw an
opportunity for genomics to play a role
in patient care in Vermont, which was
then tackling single-payer healthcare. Yet
for the UVM Medical Center, with its
relatively small catchment of less than a
million patients, classic molecular testing
that looked at a mutation in a single gene
wasn’t feasible. Fortunately, gene panels
using next-gen sequencing offered an
alternative, and today, with a 29-gene
solid cancer panel now in use, Leonard
and her colleagues will next develop
multi-gene panel tests for blood cancers
and inherited cancer risk, followed by
pharmacogenomics. The final step will be
entire genomes.
The new laboratory, at 5,000 square
feet, will encompass three individually
pressurized laboratory rooms. Niki
Sidiropoulos, M.D. leads the genomic
medicine laboratory, working with Leonard
and two other molecular pathologists,
technical specialists, medical technologists,
genetic counselors, and a pre-authorization
staff member.
“We’re not only developing the tests,
but working with the healthcare team
to integrate our genomic tests into care
pathways,” says Sidiropoulos. “Everyone
on this team is dedicated to building the
best possible service. We view ourselves
as offering a quality service, and not just
testing” — though it’s worth noting the
team has been commended by outside
sequencing companies for the quality
of its data — attributing much of that
to Leonard’s leadership. “To be a young
faculty member and have that kind
of inspiration in your chair — she’s a
colleague — is just truly remarkable,”
especially in a relatively new field, she says.
Mentoring has long been important
to Leonard. She especially watches out
for those who aren’t familiar with the
mechanics of higher education.
“I learned about academia on my
own. I don’t think it should have to
be that hard for people who want an
academic medical career with a goal of
helping others,” she says. She directed
the residency training program at Weill
Cornell, and maintains a philosophy
that “once you’re my mentee, you’re my
mentee for life."