An Interview with Bruce Montgomery, Former Chairman, WBBA
Seattle, WA, May, 2005
Q: What if you were eighteen years old today, but knowing what you know. What
course of study and what kind of career do you think you would pursue?
A: When I was eighteen I was planning an undergraduate
degree in chemistry, which I thought would be a really good scientific background,
and then planned to go to medical school. I didn’t have highly refined
long-range plans. The biotech industry didn’t exist. The pharmaceutical
industry was basically a New Jersey phenomenon, very classically based mostly
natural microbe or plant based drugs. The most exciting field was biochemistry.
Biological degrees were mostly not molecular biology, but were focused on the
study of flora and fauna.
What I learned at the UW was how to be a scientist and how to
do interesting things. My advice would be, instead of having a plan, I’d
say what interests you? And be flexible. I’d seek the best education I
could get with as much practical experience as possible. For instance, when
I was an undergraduate I did a lot of research with Alvin Kwiram, which was
equivalent to a graduate student’s lab for a year and a half. It was incredibly
valuable, and 30 years later we’re still good friends.
So I would say go for a quality type of experience. I wouldn’t
pick a field. Even if you’re an M.D./Ph.D. candidate, you do your Ph.D.
and then spend 4 to 6 years doing your MD and then your residency. The half-life
of knowledge of a Ph.D. now is about 3 to 4 years. So even if you got a Ph.D.
and then an M.D., the Ph.D. would be somewhat obsolete. It’s the skills
you learn of discovery, analysis and leadership; those are timeless. I would
encourage someone not to pick a field, but to do something that gives them those
skills
With what I know now, I’d make exactly the same choices.
I can’t say that about other things in my life.
Q: As you look back from here on what you’ve been
involved with, what one accomplishment stands out as particularly fulfilling?
A: In 1983 I left Seattle to go to San Francisco
to do a fellowship in pulmonary medicine. Prior, I had spent a year in clinical
research at Harborview that led to great publication. I showed up with more
advanced skills than they anticipated. I was at ground zero of the AIDS epidemic
at San Francisco General Hospital. At the time the survival of AIDS patients
was 6 weeks. There were two competing theories back in 1983 and one was we should
provide hospice treatment and there was a second which was we should do research.
The amount of federal investment in AIDS research - it wasn’t called HIV
AIDS; the virus wasn’t known - was zero. I decided that I would join the
faction conducting research. We focused on treating and preventing PCP, a form
of pneumonia very common in AIDS patients. We did the first animal studies,
human studies, and by 1989 we got FDA approval of the second AIDS drug. I started
that work in 1984/85; I was barely 36 years old and had my first drug approved.
Within months, tens of thousands if not a hundred thousand people were on aerosolized
pentamidine, which substantially prevented pneumocystis carinii pneumonia. This
kept many people alive until the development of the antiviral drug cocktails.
More importantly, we established by trial design much of the methodology for
later AIDS trials and we also showed that this was a market. Before 1984-85,
pharmaceutical companies weren’t interested in AIDS because they thought
the people were going to die in six weeks and there were only 2000 people diagnosed.
By 1990 Big Pharma was involved full scale in research.
Q: Could you please tell a bit more about how the methodology
of trials affected subsequent research?
A: One of the problems was what are the end points
in an HIV trial. Is it death, progression to disease, pneumonia? What are the
rates of progression? If you knew all this events, one could easily design a
trial. The second trial is a lot easier to do because you can determine what
the sample size needs to be.
When we decided to do a Phase III we had $25,000. Phase III programs
can cost a hundred million. So how did we do it? We put together a consortium
of hospitals. We did a dose response study and enrolled over 500 patients. It
was a simple large study with the end points being death or progression to disease.
This was published in the New England Journal of Medicine. The typical protocol
in my company now is 64 pages. This protocol was only four pages but it was
a very elegant design that clearly proved the higher dose worked better than
a lower dose. Ergo the drug must work. With that we understood the incidence
of events -time to progression and the end points, which allowed other future
studies to be based on these models. The biostatistician, David Fiegel who worked
with me later became head of the anti-viral division of the FDA. He led the
efforts to speed up approvals of AIDS drugs.
After this, I left academic medicine, which puts very little value
on developing therapies. They want scientific discoveries and NIH grants, not
a drug that actually works. It became pretty obvious to me that I was an industry
person, not an academic person because what I was trying to do wasn’t
aligned with the reward system in academia. It’s not good or bad; it’s
just different.
Q: Of the people you have known and worked with, who stands out as particularly
deserving of your admiration?
A: I’d say two people. Alvin Kwiram. He
was a tough professor, one of the toughest one could face. He did a phenomenal
job as chair of chemistry, building the department, then as research provost,
and is just a great person. The other is Len Hudson, Professor of Pulmonary
Clinical Care at the UW. In a very competitive area he managed to always find
interest in what other people were doing and always used his influence to help
people build their careers. He was never a 'me-me' type. He made the University
highly competitive but never brought out competition among the people he worked
with. That’s a leadership style which is in the long term very successful.
Q: Let’s talk more about the kind of leadership
that’s necessary to succeed in your field.
A: The problem with leadership is we work in
a society that values its leaders but finds them wanting. People want a leader
who can take input, separate the wheat from the chaff, take the organization
where it needs to go and is relatively nurturing and supporting rather than
screaming and shouting. The problem is very few people in our industry, myself
included, have all the requirements for the perfect CEO. The perfect CEO knows
bench research, understands clinical trial design, has FDA relationships, knows
marketing, knows how to do an IPO, can handle interpersonal conflicts among
a staff, is successful with investors. The list of what they want from a CEO
is impossible. No one can fulfill the list and the job is very difficult, so
what you have to do is you’ve just got to do your best. Most importantly,
you can’t play for yourself in this business, because if you do you’ll
lose your partners - your colleagues, employees, investigators, the FDA, and
more importantly, your patients, which is who we’re trying to help. But
if you take care of everyone else, things will work out ok for you. If you start
putting yourself as number one, you’re going to get yourself into a lot
of trouble.
Q: What’s the right leadership style to succeed
in an arena which requires very substantial interdisciplinary collaboration?
A: In order to get a drug approved, you need
many disciplines. Big Pharma has done this by having a huge organization with
someone on top. The problem is when organizations get so large the top people
aren’t making decisions, they’re making policies and procedures
on how decisions should be made. You have your smartest people trying to write
down rules. In a small organization, you can have your brightest people making
the decisions. At Big Pharma you’ve got the smartest people in the world
but the organization is so big they can’t help people down in the organization
where their help would be important. You need a critical mass from start to
finish in drug development which is probably 100 to 200 people. If you’ve
got 40,000 people, how do you manage them effectively? What you’re doing
is you’re just laying processes out, you’re not effectively managing.
And since a lot of this is gut call based on early data, making decisions, pushing
programs forward, that takes a diverse skill base. There’s probably hundreds
of good ideas at Big Pharma that probably aren’t getting to the top because
of the noise that’s blocking them out.
Q: Imagine you have become Secretary of the Department
of Health and Human Services. What one adjustment to national policy would be
the top of your list?
A: We haven’t dealt with the issue of whether
medicine is a right or an option. We have a society in which a quarter to a
third of the people don’t have any health insurance, but they really do,
because they can show up and get it for free when they’re sick. That strategy
of not sharing the risk is basically bankrupting the system. If people can get
a free ride or think they can dodge the bullet often they’d rather invest
in a new pickup truck. We don’t mandate that people pay into a health
care system yet society is not going to allow people to go without any health
care.
We need a national debate about what we really want. Is it a single
payer system that everybody’s a member of and then you can option some
enhancements? There are so many vested interests it’s difficult to even
start the debate without goring people’s oxes.
The FDA does a fabulous job, they have great employees but the
most important thing I’d do is build a campus where they can come together,
interact and learn from each other and not repeat each other’s mistakes.
We should build a a pentagon-type complex where everyone could be together.
The other problem is that the FDA is woefully under funded in terms of IT and
tools that would allow them to pick up drug interactions. Other essential things
are being ignored. We’re not investing in drug safety. Many drugs that
are unsafe are off patent; they’re generic; they’re made by bulk
manufacturers who have no incentive to insure drug safety.
We’re the only advanced country in the world without a national
healthcare system. Things could be done that would simplify the system. You
could mandate one form for all insurance claims - this would save hundreds of
millions of dollars, just by having one form for all insurance claims. There
are a lot of economies in the system that we could capture, but we’re
not chasing them out. We spend far more on administration than Canada does.
Also, there are huge pay disparities historically between different medical
specialties. People who do procedures get paid more than general care specialties.
This discourages people from going into primary care. We’ve got to decide
whether every heart surgeon deserves to be paid three times the President of
the United States when 70% of the money comes from the government. The problem
is physicians work for the government but they don’t know it.
Q: What scientific advancement in the past five years
have you found personally most exciting?
A: Since I’m a development guy, I like
to see the late stage. You can see years and years of molecular biology research
and understanding different enzymes and how things work, how cells work and
so forth, then someone puts it all together and takes a compound that affects
one particular enzyme and says, "aha, I’ve applied it." The
example in the past five years for me would be Gleevec, the drug that came out
of Novartis, which is a treatment for chronic myeloid leukemia. They actually
figured out the cause, tyrosine kinese enzyme gone astray. They developed a
specific inhibitor, and many patients are cured. That’s impressive. This
took 25 to 40 years of understanding leukemia, synthesizing all that information
to come down to a pill that works. And it shows that with more understanding
in the future, one can expect more drugs with results like this. It’s
the same thing as Fleming’s discovery of penicillin. Wahoo! Salk’s
vaccine. Wahoo! Gelvac is the latest wahoo moment. But was Salk given the Nobel
prize? No, because it was derivative research, based on people who figured out
the cell cultures. All that work that allowed the development of a vaccine.
So I’m impressed with the late stage findings. But they are standing on
the shoulders of giants.
Q: When did you first detect within yourself the impulse
toward science?
A: Like every other chemist, I built rockets
in my garage and blew things up and thought this was scientific experimentation.
You gravitate to the things you’re good at, and I was good at it in school.
I saw a lot of fun in it. My father was a rocket scientist, so that was a hot
place to be but by the 70’s that seemed to be petering out. I was drawn
to an area where there was a lot of excitement.
Q: Which comes back to the first part of the interview,
about how to prepare for a career in the life sciences.
A: The quote I have on my computer is one from
Louis Pasteur. “Chance favors the prepared mind.” You just have
to have a prepared mind.
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