- The Washington Times - Monday, November 20, 2000

15 minutes with … Dr. William A. Haseltine

Dr. William A. Haseltine is a pioneer in genome research. And his early efforts have established the Washington area as ground zero for this fast-growing field of biotechnology.
He started Human Genome Sciences Inc., a company researching genes to discover medical treatments, in 1992 at a time when genetic research was not commonplace.
Nearly nine years later, genome companies are everywhere, but none is as close to its goal as Human Genome Sciences. The Rockville-based company is expected to become the first genomics firm to deliver a gene-based drug: Refermin, which heals wounds by making skin cells grow.
The drug is finishing research stages and is expected to be approved by the Food and Drug Administration in the next two to three years.
On the verge of success, Dr. Haseltine took some time to talk about his company and the future of medicine.
Q: What is the goal of Human Genome Sciences and why did you start it?
A: The concept is to use advances in technology … and advances in laboratory machines, which put together, dramatically increase the efficiency of biological discoveries… .
Biological knowledge, at least in our company, came in two forms: First is knowledge about what genes are, just the identification of genes. That was our first set of technologies. But that wasn't my goal that was what almost the rest of the world had been focused on with this Human Genome Project that really addresses the question of what genes are.
Our approach to that was also novel, not just ask what genes are in their stored form, in their genome form, but what genes are in the form the body actually uses them. The key departure between our approach and the Human Genome Project, which was a government-sponsored project, was to focus just on genes as they are used, not as they are stored. That was a big simplification and allowed us to move very quickly… .
The notion is that the body … makes all the substances it needs to create an adult human being. That is a marvelous thought. And all the instructions to do that are in these genes… .
What we realized is that if we could obtain copies of all those signals that the body uses, we could use those for medicine. We could use those to rebuild our body, maintain our body, repair our body and get more mileage out of our bodies as we age.
Q: The Human Genome Project announced this summer that it had completed the map of one human being's entire genetic makeup. Does that affect your work in any way?
A: The work that has been done by the Human Genome Project, which is sequencing the entire human genome which we have yet to see, by the way is not yet done. In its current form, it is very patchy and not particularly usable. So the simple answer is it has no effect whatsoever on our current activities.
Q: You said you needed new technologies to identify genes. Now that this stage is over, will technology still be as important to genetic research?
A: To give you an example, what is a typical experiment like? It used to be you take one gene, and you make its protein product, and you put it onto a cell and you observe some simple parameters: Did it grow, did it stop growing, did it die, did it move, did it change? You could measure a few changes. Well, today we take 10,000 genes we literally do this make 10,000 proteins, and put them on 10,000 individual cell types. And then we don't measure one or two changes, we measure hundreds of changes because we have new and powerful instruments… . So whereas a typical experiment in the past would generate perhaps, at most, 100 different data points, an experiment today generates 4 million data points.
So technology is becoming even more important to find out what genes do that has medical implications than it was to find the genes in the first place.
Q: What is medicine going to look like 10 years from now?
A: The individual experience with medicine will be pretty much the same as it is now. You'll go to a doctor, and the doctor will examine you, take a little sample and then say this is what's wrong with you and you should take these medications. And so your experience with medicine will be pretty much the same. What will be behind those tests will be very different. And the physician's ability to detect what's wrong with you and his ability to prescribe remedies to treat and even cure your diseases will be far more powerful… . These medications will rebuild your bones, rebuild your cartilage, rebuild your blood vessels… .
Let's take kidney disease. Today you go on dialysis and hope for a kidney transplant. Twenty years from now there will be in a hospital shelf a structure that looks like a kidney without cells. They will take a few of your cells … infuse them into this structure that looks like a kidney … and they will literary grow your own kidney right there in the hospital for you. And in a month they will re-implant that into you. They'll do that for virtually for all of your organs: A new muscle, a new bone, a kidney.
Q: So will we live forever?
A: Well, I don't know if this generation will live forever. We will certainly live longer than our parents, on average, maybe 10 to 20 years longer, and in good health.
Q: Genetic research for the purpose of making drugs was not a commercial idea when you started HGS. So what triggered the birth of genomics companies then?
A: The trigger, like with so many industries, is really a combination of factors. When I looked back and said how soon could we have created Human Genome Sciences to do rapid gene discovery, I was exclusively referring to the power of parallel computation.
Before 1991, the computer power that we needed in an affordable way just wasn't there. We would have had to use a supercomputer and a new company cannot afford a supercomputer. But fortunately … [cheaper computers] came onto the market that had the power that we needed for that early stage analysis. Now to do the type of analysis we do today it would have taken us a supercomputer in 1990-1991… .
The second is instrumentation. The instruments we needed to do rapid gene discovery simply did not exist in a functional, usable form in 1991… . The technology just wasn't there to accumulate the information we needed to store.
Q: Once medicine is so advanced that organs can be grown, what follows?
A: Well, this is what can happen, it isn't what must happen. We have to get a series of social structures right in order for this happy future [to be] obtained.
First and foremost, we must maintain a healthy system of incentives to allow the people that are putting these systems together [freedom] so they can do it again. [Genomics] companies eventually must be self-sustained. And in order to do that, there has to be the notion that there will be a market for the product, that sales will be high enough to justify a reinvestment… .
[In terms of medicine], right now we are in the very early stages of learning how to do something even more remarkable. And that is not just replacing your body with your same cells with the same age, but replacing your older cells with your cells made younger… .
Q: Getting patents on genes has become rather controversial. Where do you stand on the issue?
A: The patent issue is an issue that is misunderstood and overdramatized. It partly stems from the problem with understanding what the human gene is and isn't. Most people think of genes as their personal inheritance… . However, when you think of the gene in a different sense, that the gene is an instruction that may save part of your body, and part of your body can be a drug, the picture changes.
Let's take insulin. Everybody recognizes insulin as a useful drug. It's in a bottle and you inject it and it keeps you from dying. Most people don't think of insulin as a manufactured human part. They just think it's a drug. Well, what is it? Today insulin is made from parts of genes from one human being. Twenty years ago it was chopped out of the DNA from one human being, it was inserted into another organism, fermented in a plant, purified and manufactured and then put in a bottle. One gene, a protein manufactured, a drug that saves life.
So the notion that we can extract parts of the human body and make them useful as drugs … estrogen, testosterone, growth hormones … is deeply embedded in our legal system and the world's legal system… .
Q: Do you identify yourself more as a businessman or scientist?
A: I am both.

SELF-PORTRAIT

William A. Haseltine, president and chief executive officer of Human Genome Sciences Inc.
Age: 55
Education: Degrees from Harvard University, with a Doctorate in Biophysics.
Experience: President and CEO, Human Genome Sciences; professor, Dana-Farber Cancer Institute, Harvard Medical School. He is also former editor-in-chief of the Journal of AIDS and the founder and editor of on-line journal E-Biomed: A Journal of Regenerative Medicine.
Other initiatives: Since 1981, he has founded seven companies, each in a different area of medicine. As a scientific adviser to HealthCare Ventures, he helped establish some 20 other biotechnology companies.
My family: Married with children.
How to contact me: 301/309-8504, www.hgsi.com

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