A Genetics Pioneer Sees a Bright Future, Cautiously
Among scientists, 84-year-old Arno Motulsky is known as the “father of pharmacogenomics.” In 1957, Dr. Motulsky, a medical doctor and researcher at the University of Washington, published an article reporting that two drugs had negative interactions with enzymes produced by certain human genes. Might this be true of other pharmaceuticals, Dr. Motulsky wondered? His question set off a revolution in research. Dr. Motulsky, who grew up Jewish in Nazi Germany, barely made his way out of wartime Europe and to safety in America.
“What we know about the genome today is not enough for all the miracles many expect from this field.”
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Q. IN 1939 YOU BOARDED AN OCEAN LINER FROM HAMBURG TO CUBA WITH YOUR MOTHER, BROTHER AND SISTER. DID YOU EVER GET THERE?
A. We got as far as Havana harbor. Our ship was the S. S. St. Louis. The Cuban government had canceled the transit permits of most of the passengers — nearly a thousand refugees. We could not disembark.
Q. YOU MUST HAVE BEEN TERRIFIED.
A. I was 15. At that age, one tends to be optimistic. Many of the older men, they’d been in concentration camps and they had a better sense of what could happen. For days, appeals went out to the U.S. government to take us in. Then the Cubans ordered the St. Louis out of Havana harbor. The captain — who was a decent sort — sailed the ship up the Florida coast, hoping something would change. You could see Miami. Eventually, the St. Louis turned around for Europe. Our family was given asylum by Belgium. After a year in Brussels, we got our visas for America, but before we could leave, the country was overrun by the German Army.
Q. WERE YOU THEN INTERNED?
intern (PUNISH)
Hide phoneticsverb [T often passive]
to put someone in prison for political or military reasons, especially during a war:
Many foreigners were interned for the duration of the war.
A. Yes, I was sent to a succession of camps in France. Though conditions were bad — hunger, typhoid — I always tried to know what was going on. I always tried to get a hold of newspapers, which was very difficult.
After many months, the Vichy French moved those internees with the possibility to emigrate to a special camp near Marseilles. We were allowed to visit consulates in the city. I spent much time at the American consulate, pleading for a renewal of my now-expired visa.
That came through right before my 18th birthday. So 10 days before I turned 18, I crossed into Spain. From there I went to Lisbon and eventually Chicago, where my father was. If my visa had taken any longer, I wouldn’t be here today because Franco had barred males over 18 from transiting through Spain; I would have ended up in Auschwitz, like most of the people I left behind.
Q. WHAT BECAME OF YOUR MOTHER AND SIBLINGS?
A. For two years, there was no news. In Brussels, they’d gotten orders to be “resettled in the East.” With the help of Belgian friends, they illegally crossed into Switzerland. We didn’t see them until 1946.
Q. HOW DID YOU BECOME A DOCTOR? THAT COULDN’T HAVE BEEN EASY FOR A PENNILESS REFUGEE KID.
A. I had a great piece of luck. When I was 20, I was drafted! The Army needed doctors for the war. They put me into a special program, where they sent me to Yale and later to medical school.
Q. HOW DID GENETICS BECOME YOUR SPECIALTY?
A. While at Michael Reese Hospital in Chicago, I met the hematologist Dr. Karl Singer, and he had all these modern ways of studying blood. That interested me. Because there are hereditary blood diseases, I soon became interested the genetic aspect of hematology.
Q. YOUR OBSERVATION IN 1957 ABOUT THE INTERACTIONS BETWEEN THE ENZYMES PRODUCED BY GENES AND SOME DRUGS — DOES IT PLEASE YOU TO SEE HOW IMPORTANT IT HAS BECOME?
A. Yes, because at first the idea was not well accepted. I remember going to an important pharmaceutical executive and I said, “I found a new way to find out about drug reactions.” And he kissed me off: “Drug reactions?”
Things also moved slowly for a long time because it was hard to test for this. But now, with the new DNA testing, you can do many things faster and better. And with the modern computerized genomics, you can even test for reactions to many different enzymes, all at the same time.
On the other hand, I think the promise of pharmacogenetics is sometimes overhyped. There are people who think we’ll be able to solve almost everything with an individualized prescription. We need more research, which will be expensive.
Q. WILL HEALTH INSURANCE PAY FOR DNA TESTING AND CUSTOM PHARMACEUTICALS?
A. That’s a problem. On the hopeful side, people say it may soon be possible to sequence a person’s genome for $1,000. Once they figure out low-cost ways to sequence the genome, the price of personalized medicine will come down.
Still, one shouldn’t be misled. What we know about the genome today is not enough for all the miracles many expect from this field. There’s a lot about what regulates the genes and how they interact that we still need to understand. We won’t have the answers by tomorrow.
Q. AT 84, YOU’RE STILL WORKING. WHAT ARE YOU TACKLING IN YOUR LABORATORY?
A. One project I’m very excited about relates to human color vision. About 8 percent of males have inherited red-green color blindness. This is caused by hereditary abnormalities in color sensitive pigments of the retinal cones in the back of the eyes, which are actually part of the brain. Our laboratory found that one-half of males with normal color vision had the amino acid alanine in their red pigment, while the other half all carried the amino acid serine, at the same site. This finding means that the same exact red color is perceived as a different type of red, depending on a person’s genetic makeup.
Q. WHAT’S THE POINT OF KNOWING THIS?
A. It’s exciting to learn that because of heredity, different people can see the same thing differently. I think this may prove useful in studying more complex brain functions. If this were 20 years ago, I’d focus on neurogenetics. What’s going on in the brain, that’s the last frontier.
Q. DO THE EXPERIENCES OF YOUR CHILDHOOD HAVE AN IMPACT ON YOUR LIFE AND WORK TODAY?
A. I often think about it. Whenever something good happens, I say to myself, “Look, you almost didn’t live to experience this.” When I see pictures from Africa, I think: “That could be me. I was once a refugee.”
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