Mark J. Rieder, Ph.D.
Dept. of Molecular Biotechnology
University of Washington
What attracted you to the study of genetics?
have an unusual background and training, but maybe not
so different from many other people doing genetics or
"genomics" research. Several of the scientists
in this field have a background in many varied academic
disciplines. For myself, I started out doing my undergraduate
studies in biomedical engineering, which had little if
anything to do with genetics. I then went to graduate
school to get my Ph.D. in Human Physiology. This is where
I began to learn much more about biology and medicine.
Near the end of my graduate time (1996) the genomics "revolution"
was starting to kick into high gear -- more emphasis and
publicity was being given to biotechnology companies,
the Human Genome project, and gene therapy, to name a
few. It was at this time that I made another jump-- from
physiology to genomics. I received an appointment at the
University of Washington in the Department of Molecular
Biotechnology--one of the premiere departments in the
country doing genomics work. During the past 3.5 years
I have been immersed in this environment and have learned
about all aspects of genomics and its relation to public
health, evolution, and society. So I haven't been always
focused on pursuing genetic research, but rather it has
evolved into something I really enjoy, and I was fortunate
to seize some opportunities when they presented themselves.
What are the practical medical uses of genetic technology?
are several standard answers to this question that most
people will draw upon. First, genetic technology promises
to provide a "DNA diagnosis" of common diseases.
Or at least the hope is to identify individuals with a
particular genetic makeup or genetic variation which may
predispose them to a specific disease. Presumably, physicians
could administer a genetic test in the office and use
that information to guide therapy or counsel the patient
about lifestyle changes that could incorporate into their
daily lives to reduce the probability that a disease would
occur. Second, and somewhat related to this is the idea
of "personalized medicine" or the prescription
of different drugs based on an individual's genetic makeup.
Some people do not respond (or respond poorly or even
die) to certain classes of drugs. Hopefully, they could
be prescreened before prescribing these drugs and avoiding
potentially harmful side effects.
How does gene therapy work?
the most basic definition gene therapy works by taking
a "normal" form of a gene (DNA) and putting
it into an individual's cells. These cells then have a
"normal" copy and the two "native"
(generally "not working") forms of a gene, both
of which were inherited from their mother and father.
The cell will "read" the "normal"
gene which was introduced and also the "native"
inherited forms. By having just one "normal"
copy of a gene the cell can then make the "normal"
protein (even though it still has 2 poorly functioning
"native" inherited forms) which will hopefully
correct the disease of interest.
Typically, how successful is gene therapy? When will gene
therapy become more commonplace?
of studies are currently underway to make gene therapy
more commonplace. The early results are not as good as
people had hoped. It turns out it is very hard to put
a "normal" gene into a cell. I think 10 years
is probably realistic.
Will gene therapy ever replace practical surgery?
is a hard question because there are so many different
reasons physicians perform surgery. Gene therapy will
probably be used in conjunction with surgery. For example,
one recent study showed that gene therapy can be used
on blood vessels to pre-treat them before they are used
for heart bypass surgery (by introducing more copies of
an anti-clotting gene into the wall of the blood vessel.).
Surgery will continue to exist but gene therapy might
reduce the need in some very specific cases.
What has your work centered on?
work has been done in conjunction with Dr. Debbie Nickerson
here at the University of Washington. We focus on trying
to define the genetic diversity or differences that exist
in the human population. So if you take DNA from two random
people and compare it, how many differences exist between
them. The general answer is about 1/1000 bp -- so we are
99.9% alike. Or, put it another way, between any two typical
human genomes about 3,000,000 differences can be found.
However some genes are very alike, they seem to have been
conserved between most people, and some genes are very
different. So there is a lot of variability on a gene
to gene basis. The real question that we, and many people,
would like to answer is -- How important are these differences
in giving an individual specific characteristics? -- like
eye color, or height, or the probability that they might
have a heart attack. Specifically, how much does our genetics
contribute to our physical characteristics and how much
is environment -- basically the age-old question of nature
(genetics) vs. nurture (environment). The answer is a
probably a big contribution from both! We just don't know
What are your career goals?
great thing about genetics is that it changes very quickly.
Questions that are interesting today might be old news
tomorrow, so you have to adapt and generate goals based
on what is interesting at the moment. Ideally, I would
like to have a laboratory where we could do good solid
work on understanding the questions I raised in the previous
How does cloning help the medical field?
is a very sensitive issue for most people in the public.
I think most scientists don't condone human cloning but
it could be used for doing animal research and getting
at the question I raised above - genetics vs. environment.
If scientists could create animals that were genetically
identical, the other differences between them would have
to be assigned to environmental effects. This is my viewpoint
as a basic research scientist.
Why are transplants more successful when the DNA of the
transplanted organ matches the DNA of the patient?
am not an immunologist -- that would be a better person
to ask -- but I can give you my basic understanding. The
body recognizes certain proteins as belonging only to
its own body. Remember I said that every person has some
slight differences between their own genes and another
person's. If a person gets a transplant and the genes
of the donor differ, they can make slightly different
proteins on the surface of the organ. The immune system
of the person receiving the transplant recognizes these
different proteins and will attack them, leading to rejection
of the organ. If one matches the specific genes (and therefore
the proteins) between two people before a transplant the
body will be less likely to reject it. This is why there
is less organ rejection from an individual in your own
family -- because related individuals share a lot of the
Mark J. Rieder, Ph.D.