An Interview with Alejandro Zaffaroni
Photo of Alejandro Zaffaroni

Interview by Jill Wolfson, San Jose Mercury News; and Tejinder Singh, Bellarmine College Preparatory

Interview photos by Len Lahman, San Jose Mercury News

Transcribed by Jean Ricket, Tech Museum volunteer


Tejinder Singh
Born a banker's son in Montevideo, Uruguay, Alejandro Zaffaroni studied medicine in his home country and then earned a doctorate in biochemistry at the University of Rochester, New York.

In 1951, he went to work for Syntex, which was then a small firm headquartered in Mexico City that was pioneering the production of synthetic steroid hormones. While he was at Syntex, his work with Dr. Carl Djerassi became the basis of the Pill, the oral contraceptive.

As a supervisor of both research and marketing, Zaffaroni helped transform the small firm into a large pharmaceutical house with research facilities in Palo Alto.

Singh: What one word do you think best describes the mind of an innovator, and why?
Zaffaroni: I think it is the whole issue of discovery. You look at the particular situation, a particular product, a particular event. In a very exciting process, you begin to think that there are better ways to do it. The whole aspect of discovery is thinking about bringing new concepts, new products to significantly improve something that already exists. In my case - the case of medications - it was the impact of seeing negative events in the use of medications.
Wolfson: Your innovation was to take a means of delivering medicine - a pill - that has been around since the time of the Egyptians, and making something new of it. That kind of innovation is not always met with open arms by the establishment, especially the often conservative medical establishment. Could you speak to that, and what you had to deal with ?
Zaffaroni: First of all, where did I get the idea from? I got my Ph.D. in biochemistry at the University of Rochester, New York, where I studied endocrinology, which is the working in the human body of these small glands that have a tremendously important function. They deliver very small amounts of materials that have tremendous impact in various functions: The ovarian hormone, that is required for the female physiology and, of course, the whole aspect of gestation. Testosterone, cortisone, the renal hormones, all these agents function in very, very minute amounts, highly controlled by the gland, and these are essential for the entire function and health of an individual.
It seemed to me quite evident that the way in which we administer the agents to the body are wrong, and if it is wrong for the hormones, why is it not also wrong for every compound that we throw all at once into the body?
Now, how is it possible that these very potent agents are released under highly controlled conditions, and then we bring the same agents into the body by giving a tablet at a time, or an injection at a time. It seemed to me quite evident that the way in which we administer the agents to the body are wrong, and if it is wrong for the hormones, why is it not also wrong for every compound that we throw all at once into the body?

Wolfson: Were other people thinking along the same lines?

Zaffaroni: People were saying they had no idea what I was talking about. Was this rapidly accepted by the pharmaceutical industry? That is an interesting question, because it was not. I thought the industry would look at what we were doing and say, 'Gee, it makes a good deal of sense. But they didn't.'

Wolfson: When you were met with a negative reaction to this idea, how come you didn't just give up and say 'Well, this will never be accepted.' I think a lot of young people meet problems and give up. What stopped you from giving up?
Zaffaroni: Well, first of all, the reason is that many people said 'Well, that is an interesting idea, but I don't know how it is possible to be done.' I began with the first product, which was a very thin polymeric film that could be put on the eye for glaucoma. The usual medications have to be put in several times a day, and every time you put a drop in the eye, it blurs vision and you do not see the world for an hour. So this film that we put into the eye stays there for a week, and releases the medication very, very smoothly, just at the rate necessary to maintain the control, without the side effects.

So, I think, it's OK! I found one. What now?

Was there a way that we could deliver the contraceptive into the body that would last for a year? People said 'Impossible.' Well, we did it.
The next one was a contraceptive. My prior activities at Syntex was with the development of the oral contraceptive, but you have to take a pill a day. One of the problems is that many people forget to take a pill, and so you get a pregnancy. Was there a way that we could deliver the contraceptive into the body that would last for a year? People said 'Impossible.' Well, we did it.

So people said 'Well, OK, you have a second product. What are you going to do for a third?'

For a third, we introduced the concept of transdermal, which is to put a delivery system in the form of an adhesive that will release the medication and will maintain that level of medication over time.

What this means is that when you start out with a concept, many people give up to begin with. They say, yes, very interesting concept, but what are you going to do? You have to think very hard how to create entry points that allow you to build from there. That means you have to have an incredible amount of commitment to the concept.

What is interesting now, 20 years after I started, is that there are maybe 50 to 100 companies working in the field of drug delivery and the pharmaceutical industry now has, I don't know, $10 to $15 billion sales of products based on this technology.