Interviews

Mark J. Rieder, Ph.D.
Dept. of Molecular Biotechnology
University of Washington
E-mail: mrieder@u.washington.edu

What attracted you to the study of genetics?

I 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?

There 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?

In 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?

Hundreds 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?

This 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?

My 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 how much.

What are your career goals?

The 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 answer.

How does cloning help the medical field?

Cloning 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?

I 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 same genes.

Mark J. Rieder, Ph.D.
E-mail: mrieder@u.washington.edu