Chapter 01: Photo-Immunology: Creating a New Field out of an Observation

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Chapter 01: Photo-Immunology: Creating a New Field out of an Observation

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Dr. Kripke begins this segment with some comments about joining MD Anderson in 1983, noting differences between the hospital environment and the research contexts she was accustomed to. She notes that professionals came to MD Anderson for many reasons, but stay because of the mission to cure cancer, a mission that "permeates the activities of the institution." She then traces how her own research on photoimmunology evolved, beginning with an observation she made in her dissertation (on immune surveillance) that "it would important to investigate the immunology of animals exposed to ultraviolet light." She had the opportunity for exactly this study from 1972" 1975, when she went to the Department of Pathology at the University of Utah's College of Medicine in Salt Lake City to look at the role of immuno-suppressive drugs in animals, including those exposed to UV light. It was "tailor-made for her interests and background." She describes the effects of UV light on the skin and the cancers induced, noting that no one else was doing similar work at the time and that her findings went against common assumptions about the progress of cancer. She presented her results at the Society for Photobiology, and "the results were so black and white, it was hard to argue with them,"and other scientists were very interested. She describes the early days of understanding that the skin is an "immunological organ."

Identifier

Kripke,M_01_20120328_S01

Publication Date

3-28-2012

Publisher

The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; Joining MD Anderson; Institutional Mission and Values; MD Anderson Culture; Professional Path; The Researcher; Overview; Inspirations to Practice Science/Medicine; Career and Accomplishments; Understanding Cancer, the History of Science, Cancer Research; Definitions, Explanations, Translations; Discovery and Success

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Tacey A. Rosolowski, Ph.D

And you joined MD Anderson in 1983 and I will want to—after we speak about this subject—go back and talk about your research area but I wanted—you talked a lot about the process that brought you to MD Anderson in 1983 from NCI-Frederick, but I wanted to get your impressions of the institution when you arrived. You said that you had heard about MD Anderson from being at conferences with colleagues, but what were your impressions when you joined the institution? What was its environment and culture like?

Margaret L. Kripke, Ph.D

Well, it was very different for me because I’d never been in a hospital environment previously. I was in academic institutions, research institutions, but never associated with a hospital, so that part was very different and was a very different experience. People were very formal, much more formal, dressed more formally because they were in an area where patients were treated. However, I was in a building that was remotely located from the hospital, and so we were relatively isolated there, and so I probably was not as sensitive to the culture of the place and what was happening to the place had I been located right on the main campus.

Tacey A. Rosolowski, Ph.D

What was the building you were located in?

Margaret L. Kripke, Ph.D

The RE Bob Smith Research Building.

Tacey A. Rosolowski, Ph.D

Did you get a sense from colleagues about what they felt about working at MD Anderson? I’m just asking because a lot of people got a sense—from other people that I’ve spoken with—they had a sense that there was a real kind of ethos of the MD Anderson professional, and I was wondering if you picked up on that at all, or if that was something that came later, if at all.

Margaret L. Kripke, Ph.D

I think that came later when I became better integrated into the institution, and it became very clear to me after I’d been here for a while that people came to MD Anderson for many reasons. A lot of it had to do with specialized training, opportunities for doing research and so on, but regardless of why they came most of them stayed. Many of them stayed, and they stayed because they fell in love with the mission of the institution, which is very visible, very palpable within the institution, and I think people really became attached to just the spirit of the place.

Tacey A. Rosolowski, Ph.D

How would you describe that mission?

Margaret L. Kripke, Ph.D

Well, the mission is to cure cancer, simple. It’s very simple, very direct, and it has a lot more verbiage attached to it, but basically the message is that the mission of the institution is to eliminate cancer in Texas, the world, the United States and the world, and it’s a mission that permeates the activities of most people in the institution. People want to work at MD Anderson because they feel like they are contributing to the mission.

Tacey A. Rosolowski, Ph.D

And that’s been a consistent—that mission has been consistent, that ethos has been consistent.

Dr. Kripke

Absolutely, yeah.

Tacey A. Rosolowski, Ph.D

That’s neat.

Dr. Kripke

It’s very neat, and if you ride up and down the elevators in the hospital you see it. No matter who the person is on the elevator they’re seeing if they can help whoever is there, and it’s a very compassionate kind of atmosphere.

Tacey A. Rosolowski, Ph.D

When did you catch the particular fever of the mission yourself?

Margaret L. Kripke, Ph.D

Well, I think for the first 2 years I was trying to get the laboratory set up and get research going, hire people and so on, and so, again, I think that came after the first few years.

Tacey A. Rosolowski, Ph.D

I think what I’ll do is I had some questions about some leadership issues, but I think I’ll save those for a bit later when we talk about your own administrative experience, and let’s talk a bit about your own research path. I wanted to get a picture of how that all evolved from your dissertation, which as I understand was on immune surveillance and cancer, and then you had mentioned at several points that you had made key discoveries at certain points that you felt really made your career path coalesce and take direction. Would you talk a bit about where you believe the real core of your research path began?

Margaret L. Kripke, Ph.D

I was actually asked to look at a position at the University of Utah in Salt Lake City. It was in the medical school in the Department of Pathology, which had a strong immunological research component. The chair of the department and some of the faculty members there were very interested in transplantation immunology and immunological research, and they had at the time a project that was looking at the role of immune suppression in cancer, and that comes from the observation that many renal transplant patients have developed cancer at some point in their histories. And so they had a contract to study this in an animal model to look at immunosuppressive drugs and their ability to enhance cancer development in, again, in animals, and one of the carcinogens that was used was ultraviolet light. Another one—there were chemical carcinogens and so on, and so there was an opportunity to look at cancers induced by ultraviolet light, and it happens that when I did a review of the literature as a graduate student while I was doing my dissertation it was apparent that there was something unusual about the immunology of cancers in the skin induced by ultraviolet light from studies of animal models. And so—

Tacey A. Rosolowski, Ph.D

What were those unusual properties?

Margaret L. Kripke, Ph.D

Well, the dogma of the day was that the longer it took for a cancer to develop the less antigenic it would be, the less capable of being recognized by the immune system it would be, and cancers induced by ultraviolet light took a very, very long time to develop, and yet they seemed to be very highly antigenic, and so I actually wrote a sentence in my dissertation in the literature review that said it would be important to investigate the immunology of animals being exposed to ultraviolet light, some kind of an offhand comment. Well, the job in Salt Lake City clearly offered the opportunity to do that, and because my dissertation had been on immune surveillance and cancer. This was a job that was absolutely tailor-made for my interest and background.

Tacey A. Rosolowski, Ph.D

Could I interrupt you just for a second? First of all I wonder if you could just—I forgot to mention earlier that it’s going to be a fairly broad audience for these interviews, and so if you could define immune surveillance that would be really helpful. What is immune surveillance?

Margaret L. Kripke, Ph.D

It’s the ability of your body’s immune system to detect and get rid of foreign substances. Immune surveillance is what allows the body to fight off virus infections, for example.

Tacey A. Rosolowski, Ph.D

So it’s like the body is always on watch or something.

Margaret L. Kripke, Ph.D

That’s correct, and so there’s been an idea for a long time that the immune system could be used against cancer because there is some evidence that at least some cancers look like foreign substances to the immune system, and that’s called antigenic. They are antigenic, and they are therefore recognized by the immune system as not belonging.

Tacey A. Rosolowski, Ph.D

I also wanted to ask you if in addition to the unusual properties that you noticed of UV-induced cancers if there was any other reason why you chose to devote your career to the study of cancer?

Margaret L. Kripke, Ph.D

Because it turned out to be really interesting. It was a matter of following where the science led, and so in addition to the major project that I was responsible for I started working on skin cancers induced by ultraviolet light in a mouse, and the first thing that I discovered was that these skin cancers were very, very highly antigenic. They were perceived as being totally foreign by the immune system, and yet they grew and eventually killed their original host, and so that raised the question if these cancers are so antigenic that they are destroyed by the immune system of an identical twin why would they grow and persist in the original host? How did that happen? And so that was really the basis for the studies and all of what followed subsequently because it turned out that ultraviolet light exposure of the skin has the ability to modify the immune response and in a way that it changes the immune response in a systemic fashion, which was up until then unheard of because ultraviolet light doesn’t really penetrate through the skin like an x-ray does. It’s very superficial, and so no one believed initially that it could have any lasting systemic consequences.

Tacey A. Rosolowski, Ph.D

Was anyone else doing work of this kind?

Margaret L. Kripke, Ph.D

No.

Tacey A. Rosolowski, Ph.D

And how was it received when you were first—?

Margaret L. Kripke, Ph.D

People were extremely interested in it, and the model was so striking. The results were so black and white that it was hard to argue with them, and so I think people believed the data, and so the people who were really interested in the results were dermatologists who have to deal with things in the skin and ultraviolet light and all kinds of things dealing with those things and photobiologists who were very interested in what the affects of photons or light rays were on biological processes.

Tacey A. Rosolowski, Ph.D

Where was the first place that you presented these results, or was it a paper that you first published?

Margaret L. Kripke, Ph.D

I actually presented the results—it was—I don’t remember whether I published first or presented the results. It was very close together, but I first presented the results at a meeting of the American Society for Photobiology, and people walked into the room, I think, very skeptical of the presentation and walked out saying “My, isn’t this amazing?” It was a very receptive audience. That’s one of the things that I’ve always loved about that society is that it’s very receptive to new ideas, very supportive of young people, young investigators, and I was encouraged to go to that meeting by one of the collaborators on this project that I was working on in Salt Lake City.

Tacey A. Rosolowski, Ph.D

And who was that person?

Margaret L. Kripke, Ph.D

A man named John Spikes. He passed away a couple of years ago, but he was a photobiologist, and he was the photobiology consultant for this project that involved ultraviolet light.

Tacey A. Rosolowski, Ph.D

What happened next? How did you decide to take these results and further refine your experimental process to take the ideas further?

Margaret L. Kripke, Ph.D

They just really unfolded as the information came in. Since there was nothing known about this phenomenon, you have to make up hypotheses about what’s going on and then design experiments to say is it right or is it wrong? Most of the time we were wrong, as it turns out, but we discovered that ultraviolet light changes the immune system, and eventually it happens because ultraviolet light has the ability to interact with immune cells that live in the skin. That wasn’t known at the time. It wasn’t really realized how much of your immunology, how much of your immune system actually lives in the skin. There are cells that are there that are the first line of defense. There are lymphocytes, white blood cells that circulate in and out of the skin, but the whole idea of how much of skin is an immunological organ was just beginning to be brought to light, and so the work was very, very timely in showing that ultraviolet light had a dramatic effect on the immune system.

Tacey A. Rosolowski, Ph.D

How did your work in this field of immunology kind of dovetail, reflect other trends in new understandings about cancer at the time? It seems like the ‘70s was a period where a lot of new thinking was developing, and I’m wondering what else was going on that may have influenced you or that you may have influenced during that period.

Margaret L. Kripke, Ph.D

I’m not sure how to answer that. I was very focused on my own work and on the work of others that was looking at really medical problems in the skin, not necessarily cancer, so the work was not—it wasn’t only related to skin cancers. There are a lot of conditions in the skin that are triggered by ultraviolet light. For example, there are all kinds of odd skin conditions where you get allergic reactions if you go out in the sun or you have to be protected from the sun because you’re very sun sensitive, and most of the mechanisms were completely unknown at the time. There was a lot happening in dermatology, and that probably influenced me more than anything that was going on in the cancer field.

Tacey A. Rosolowski, Ph.D

What were some of the thought patterns in dermatology that influenced you?

Margaret L. Kripke, Ph.D

Well, people were looking at some strange cells in the skin and thinking that they—and the function of which was unknown and then it was discovered that the strange cells in the skin are actually part of the immune system’s antigen-presenting mechanism. These are the cells that find foreign substances that accidentally enter the skin, and they are the cells that direct the immune system to make an immune response, and so that was what was being discovered at the time, and then as a corollary to that there were other populations of immune cells that were discovered in the skin, most of which are actually affected by ultraviolet light.

Chapter 01: Photo-Immunology: Creating a New Field out of an Observation

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