My general research area is breast cancer. I define myself that way rather than as a cell or molecular biologist. What’s somewhat different about my research is that it was always my goal to do both clinical and lab research and bring them together. I think how I would characterize my research is trying to bridge basic science and clinical breast cancer research.

I originally started by defining and developing models by which we could study hormone-dependent estrogen responses in breast cancer in vitro. I developed the first system that allowed people to stimulate cells with estrogen outside the body. From that, we used those cells to study how estrogen altered the growth of cancer cells and normal mammary gland cells.

Our work has shifted some in the last few years in that we have focused predominantly on one group of growth factor receptors that interact with hormones, which we think contributes to the growth of at least 19% of breast cancers. This is the epidermal growth factor (EGF) receptor family, which includes Herceptin targets.

How did you become interested in your area of research?

In medical school I was surrounded by wonderful endocrinologists. I always thought I’d be an endocrinologist and when I trained in internal medicine I thought that I would continue to study endocrinology. Endocrinology was one of the first fields in which you could actually measure the pivotal molecules. Radioimmunoassay and radioreceptor assays transformed medicine in the 1970s. Endocrinology—being basically physiology—was the first medical discipline in which we could actually measure thyroid hormone and pituitary hormone and adrenal hormones and explain what was going on in terms of patients.

So I looked for a way to marry my scientific training in pathophysiology with my interest in cancer. Tackling the mechanics of breast cancer was a good way to do this. It’s a disease that’s 100% caused by hormones.

What are/were the greatest challenges in performing your work?

The first challenge was that the actual system didn’t exist. We had to create it from scratch.

Then the greatest challenge in my career personally came when we first published our work showing that you could stimulate breast cancer cells to grow outside the body in cell culture with estrogens and that you could study various hormones that way. The biggest challenge came when large numbers of people in the medical community couldn’t reproduce the work. So I went through about a two-year period of intense discomfort, getting up at meetings saying we just can’t do it.

The answer turned out to be that there were a variety of extremely trivial, but nonetheless important, aspects of how researchers had to play with the medium to measure an estrogen effect, if there was estrogen already there. A lot of people weren’t able to get the effect because they were using phenol red as a pH indicator. Well, phenol is a weak estrogen, so was masking the experimental effect.

It was a blessing and a curse. A curse in that it was extremely painful, and a blessing when everyone was able to reproduce the work. Then, in fact, there was a wave of forgiveness.

What would you like to convey to the general public about your work?

I think the most important generic message for the public, unequivocally, is that the kind of science, the basic understanding we now have of breast cancer has begun to pay off, and that there is an absolutely unseverable link between really good science and altering the outcomes of patients with cancer. And if they understand that excitement and how it has come about, they would be enthusiastic future supporters of the kind of research that’s going on.

If you performed your research again, or published your papers again, what, if anything, would you do differently and why?

It's so easy looking back to know how you would have done your experiments more effectively. There are a million things you would have done better. I think if anything I would have been more mature about avoiding having so many "hobbies" and would have been even more careful about staying totally focused. It's hard not be distracted by cool collaborations but I think I erred somewhat on the side of pursuing interests that in the long run may have taken more time than they were worth.

What are the implications of your work for the future of your field or neighboring fields?

I think the most interesting implication of the work we’re currently doing is that I believe it will change the way people think about the cause of cancer. Most people today think of cancer by site of origin. For example, if I told you that breast cancer is different from colon cancer is different from lung cancer you’d hardly think I was telling you something interesting. So, what I think is the most important implication of work on signaling and the EGF receptor family is that it’s not organ-specific. In the next few years, we’re going to see a complete revolution in pathology. We will no longer care whether or not the cancer arose from the bladder or the pancreas; we will simply ask, through a system of analytical tests, what are the driving molecules responsible for the cancer, and treat those. We will define pathology not by shape, but by cause.

How rapidly has the state of knowledge about your field evolved in the past decade, and what were the key discoveries that furthered the advancement of the field?

I think that, as almost anyone would say, the basic skills of molecular biology revolutionized cancer research. To me, the most remarkable thing is that we’re just about there in defining all of the gene products that are expressed in a given cell. This will transform the field.

What is your prediction for the state of knowledge about your field 10 years from now?

Revolutionary success in anticancer therapies in the next 10 years. I’m certain of that.

What lessons would you draw from your work to pass on to the next generation of researchers?

The only lesson I tell anyone any more is just do pretty work. If it doesn’t look good to you, don’t do it. You should be less concerned about where things are exactly going and more concerned with whether or not your experiments are as elegant as you can make them. If it’s clean, clear, focused, and symmetrical as an experiment, it’s beautifully designed.

Dr. Marc Lippman
University of Michigan
School of Medicine
Department of Internal Medicine
Ann Arbor, MI, USA