Saul Schepartz, Ph.D., Former Deputy Director, DCTD
Mary Wolpert, Ph.D., Chief, GCOB, DTP
Joe Tomaszewski, Ph.D., Deputy Director, DCTD
Vincent DeVita, M.D., Former Director, NCI

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Saul Schepartz, Ph.D.
Former Deputy Director, DCTD

There have been many changes in cancer research since I joined the NCI in 1958. First of all, in terms of drug development, drug discovery and drug development, the pharmaceutical industry was interested only to a very limited extent in trying to pursue anti-cancer drugs, because their probability of success in terms of financial return was very small.

We knew very little about the pharmacology of drugs in those days. We know so much more now that it appears… it would seem by comparison that we were really back in the Dark Ages. However, in spite of our limited knowledge many new drugs were developed that have since proven to be very valuable in the treatment of cancer.

Mary Wolpert, Ph.D.
Chief, GCOB, DTP

1. Well, in the early days of the chemotherapy program, there was a lot of resentment on the part of many scientists who felt that the goal of NIH should be pure bench science; we should develop concepts, publish, and then leave it to the drug companies and others to follow up on good ideas.

Well, very early on in the Development Therapeutics program, we had more of a can-do attitude that you had to work with agents. You couldn't just publish on an agent that had come through somebody's laboratory, that you had to show people how to use it and you had to actually develop it until it was a drug because many drugs were not ready for prime time as we like to say.

At that time, it was unique to NIH to have that kind of a group because most of the other institutes only supported basic research. So we were really pioneers and I give NIH credit for allowing all this to happen, because I think it has flourished and I think it's now the basis for Dr. Zerhouni's Roadmap initiatives because it shows that you not only have to have the basic discoveries but you have to do something to translate these basic discoveries up to the point where they can be shown to be helpful to mankind.

2. The story I guess I remember the most was when one of the M.D.s, who will remain, his name I will not give, but he told me it was malpractice to go into clinical trial with cisplatin. And we argued about that and there was a big debate in the lab that day as to whether this was a good idea. Little by little, we started to learn how to use cisplatin, because the first patients who received it got very sick. We practically caused kidney shutdown and hearing loss in the early patients.

So this drug was almost thrown out. Then someone figured out how to use it. It took perseverance of a few individuals and little by little, we learned how to use it in combination and soon we were actually getting cures. And this was the first drug that I ever was associated with that cured patients.

And recently I saw on the cover of the magazine called Cure, the patient Zero, who was the first man who was ever cured with cisplatin for testicular cancer. And I've often thought back to that original discussion we had in the lab. If we'd listened to that M.D., it never would have happened.

Joe Tomaszewski, Ph.D.
Deputy Director, DCTD

1. The Developmental Therapeutics was created essentially 50 years ago because big pharma was not actually doing what was necessary for the treatment of cancer. There was a lot of screening that was occurring but there wasn't a program in place that would take any promising agent, do a complete evaluation of those agents in animal models.

The one thing you have to realize before you can take any new agent into man, you've got to define safety in animal models. So there was no way to do that. So there was no way to produce drug. So the predecessor of the DTP that was created 50 years ago was called a CCNSC and it was that organization that has since gone on to help develop 39 molecules that are now used today to treat cancer.

2. No program within the government can match what the Developmental Therapeutics Program in the NCI has actually achieved in relation to the numbers of new agents that have been developed with government funding and have been approved by the FDA for use in man.

So is it a successful program? It's a highly successful program. And it's one in which continued investment should actually be required because the government essentially has nothing to lose. We don't have stockholders, other than every one of us that pays taxes.

Vincent DeVita, M.D.
Former Director, NCI

1. The Clinical Center was unique. And a lot of what happened that got the cancer war going happened right here at the Clinical Center. And because the laboratories and clinics were a hallway away, my labs were on 12 North and 12 East and the floors were 12 West and I could walk 30 steps and be on the floor or I could walk around in my laboratory and be in the laboratory. It was a unique design meant to foster that kind of collaboration. And we got I think as good linking as we ever could possibly get.

The process that we followed was interesting in developing combination chemotherapy. There was a man, still alive, he's quite old and feeble, Howard Skipper, who was a mathematical modeler, and he used rodent models.

He ran parallel to Frei and Freireich, who were here doing work on leukemia, and myself and my crew who are doing work on Hodgkin Disease. And he would propose doing something in the clinic and he would do it, he would model the same experiments in mice and we learned how to put drugs together in a way that they would be more effective.

We learned how to put them together in a way to avoid accumulative toxicity to the bone marrow. We had to do what we call cell kinetic studies on the bone marrow to learn the difference between a mouse bone marrow and a human bone marrow so we could schedule a therapy that worked in the mouse, you couldn't get it on the same schedule to the human, you had to adjust it for the bone marrow.

So all this work was going on simultaneously in a ferment that was really unbelievable with people who were mathematicians, models, biostatisticians. We used to meet every Friday in the afternoon in a conference that we jokingly used to call the Society of Jabbering Idiots. And the reason for that was that no matter who stood up and started the meeting, he never ended up running it because people would run up and grab the chalk and run to the board and show their idea and so forth.

And then you'd leave that room and you had something new that you could do and test or you would feel better about what you were doing, it was really, like I said, you could feel the energy at the time.

2. When I was director of DCT, that was 1974-1980 where we had the drug development program, that was the only game in town. In 1980 we began to see a lot more involvement in the drug industry, chiefly from Bristol-Meyers Squibb. They were willing to take a chance.

I remember talking to the CEO of Bristol-Meyers Squibb, the late Richard Gelb, and suggesting to him that maybe we ought to get out of the drug development business at the Cancer Institute and let the industry take it over, and he turned white. He said, "You know, if you guys get out, there will be no industry, because it's too risky for us now." They weren't sure that there was a market for anti-cancer drugs.

Cancer is a common killer, but it's not a disease that affects 20 million people a year. So they were concerned about that. So then we also really created the biotech industry because we had a contract, the Virus Cancer Program had a contract; they grew the avian myeloblastosis virus.

That virus produced a reverse transcriptase which was the basis for recombinant DNA work in the early part of the biotech industry. All of a sudden, the industry began to produce drugs, and by the time I left the Division of Cancer Treatment, there were lots of start-up companies going into the cancer field. And now most of the biotech companies have cancer as their focus.

There is a huge difference than it was before. It turned out that there was a market if you had good drugs. I think the Developmental Therapeutics Program, because it held everything together until the industry could get going, deserves a huge amount of credit for that.