Chapter 09: New Lines of Research and Building a New Program at UCSD
Files
Identifier
MendelsohnJ_01_20050103_C09
Publication Date
1-3-2005
City
Houston, Texas
Interview Session
John Mendelsohn, MD, Oral History Interview, January 03, 2005
Topics Covered
The Interview Subject's Story - The Researcher; The Researcher; Professional Path; Overview; Definitions, Explanations, Translations; Discovery, Creativity and Innovation; Discovery and Success; Professional Practice; The Professional at Work; Multi-disciplinary Approaches; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Technology and R&D; Patients; Patients, Treatment, Survivors
Creative Commons 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
James Olson:
: Now jump back in time. I’ve been doing some reading and a little writing interesting on the Tenth International Cancer Congress here in 1970. Do you remember hearing about reverse transcriptase and Temin and Baltimore? Because there’s been a lot of hype about (inaudible) and perhaps there would be some announcements about the viral origins of the human cancer at this conference. And nothing happened except the last paper was Temin’s and Baltimore’s about reverse transcriptase after almost everybody had left. Some of the wire services kind of picked it up. Do you remember hearing about the science of it and being surprised.
John Mendelsohn, MD:
: I didn’t remember it occurring at this conference, but I remember hearing about it. It was – well first of all, I come out of Watson’s lab, so DNA to RNA to protein – so the idea of, wait, RNA to DNA – that was a revolution. I remember that very well because I was doing research in my lab that depended on my being up to date on this knowledge. The idea that viruses cause cancer, that was the prevalent model that the NCI – when I was there in my training, the NHI, I was in Dr. Salzman’s laboratory, not the NCI. It was the Institute of Allergies and Infectious Diseases was where he was located. But there was a lot of cancer research – a lot of cancer-related research going on in that lab. Most of the mouse models of cancer depended on viruses. And I was in a lab that had done a lot of work on that and he was in a lab that had done a lot of work on that and a man named [Habel], Carl Habel, had pioneered this area and we all thought that the most common cause of cancer was going to turn out to be a virus and it was Bishop and Varmis that showed the virus was already carrying the animal’s DNA in it, in this case the mouse’s DNA, and the oncogenes were really part of the host and not part of the virus. So I remember that.
James Olson:
: Can you tell us about you know the epidermal growth factor idea and the – I’m – is there a moment you remember when a light turned on or is more evolutionary the thinking on it?
John Mendelsohn, MD:
: Both, but I was studying lymphocytes and what stimulated their proliferation and I went on a sabbatical and I didn’t do that much studying of epidermal growth factor, but sabbaticals clear your mind. When I came back from my sabbatical, the coincidence was really just beneficial. We were building the UCSD Cancer Center and there were two PhDs at UCSD who were iconoclastic and a little different in their approach. One was Nathan [Kaplan] in the chemistry department, and the other was Gordon [Sotto], who was in the biology department, and they were really interested in translational research, what we call translational – that term was not used then. And the Cancer Center, I really was put in charge of building the UCSD Cancer Center in 1977. We had written the core grant, and we had raised money for a building, and then I went off on sabbatical and came back. Now it was time for me to build the scientific program. There was an old building on the campus, and they had allowed Dr. Sotto and Dr. Kaplan to develop a nude mouse colony there. This was before you could buy them. We met a few times and talked a lot about cancer, and we talked about the need for building up research that took models like the nude mouse model into consideration, and they agreed to join the cancer center. I recruited them into the cancer center. These were two outstanding scientists. One was a member of the academy and the other joined the National Academy right after he left UCSD, I think. We took this old building called the Mouse Colony House, and the university renovated some labs, and they moved their labs into this building. I started going into that building – I had my own laboratory studying lymphocytes and we were talking about solid tumors, which are 85 to 90 percent of all cancers. Right around that time, a lot of work was coming out about the epidermal growth factor, and here I am using (inaudible) in the study of lymphocytes and it turns out that a much better defined system was available to study cell proliferation because the EGF receptor was really chemically defined in the late 1970s. The EGF molecule, which was stimulating that receptor, had been discovered in the 60s, and Stanley Cohen was involved in both of those. He won the Nobel Prize in the 1980s for that combined discovery, and there were data coming out that cancer cells had high (inaudible) of EGF receptors. Then this curious new chemical property of an enzyme called the (inaudible) was being discovered. The first (inaudible) that was discovered was Sarc, which was an oncogene, and then Stanley Cohen published in 1980 that low and behold, the EGF receptor was a (inaudible). So working with Dr. Sotto, who was an expert in growth factors, and I had been looking at stimulating cell proliferation, in this case, using (inaudible) with lymphocytes. Just sitting down one day --and I don’t know who said it first. We just agreed that we ought to try to block the binding of EGF to its receptor and see if that could stop cells from proliferating. We thought that this was relative to cancer because there were only three (inaudible) known at that time, and one was the EGF receptor and the other was an oncogene, Sarc. We didn’t know – it turns out that the EGF receptor is an oncogene, a cellular oncogene. We didn’t know that then, though. We decided to try to raise molecule antibody. We didn’t know how to – we weren’t chemists. We didn’t know how to make a molecule like ARISA work in the cell. But I knew a lot about immunology because I had been studying lymphocytes, so we decided to make a molecule antibody and then we decided to use our nude mouse colony to try to see if we could block the growth of tumor cells. We made a molecule antibody, and the way I describe it is like putting a piece of chewing gum in the lock – the EGF receptor is the lock and the EGF is the key. You’re putting a piece of chewing gum in the lock so the key can’t get in. It was that clear-cut a plan. The work mainly was done by two post-docs in the laboratory, and we had to screen – there was already one antibody available that had been used to purify the receptor. There had already been a study that didn’t block any activities. It bound to the receptor but it was used to purify the receptor but we were screening for an antibody that not only bound to the receptor but prevented activation of that receptor and that was a very tough assignment for these two post-docs to work on. It took a couple of years. I wrote a grant to the NIH and it was turned down because it was thought it couldn’t be done. But once we had the preliminary data, we rewrote the grant and I captured a grant. Eventually when I came here, I had four grants. The NCI was very supportive of my research once I showed them the initial concepts of my work. They invested tens of millions of dollars in RO1 grants, and program projects, and National Cooperative Drug Discovery Group grants, and the NCI also paid for taking the antibody we had made and converting it into a human chimera, which is less allergenic. But anyway, was there a moment? I think there was probably a weekend. We had a lot of lab meetings together, usually at Dr. Sotto’s house.
James Olson:
: Now, when you say a lab meeting, these were with the post docs? [27:10
John Mendelsohn, MD:
: These were post docs in his lab. They were interested in growth factors and receptors, and a few of my people would come who were interested in stimulating lymphocytes. But his was the larger lab, and we concocted this idea of making an antibody and trying to make an antibody that would block the receptor. The first few papers we published, the first publications started coming out in 83 and 83 was – 83, 84, 85 while I was at UCSD, we were co-authors on those papers. But Dr. Sotto’s interests changed and he is – he began studying ways of solving the world’s food problem by growing algae in saltwater as a source of protein. He was doing research out in the desert out next to the Salton Sea in California, and on the roof of our cancer center, he was growing algae and adding salt and getting it to grow in salt water. Because his dream was to take the ocean --and he’s doing this in Eritrea in Ethiopia now. He’s got a big project, funded mostly by philanthropy I think. He’s using sea water and using bulldozers to open channels in the desert, and then close them and trap the seawater, and grow algae there, and solve the world’s food problem. I moved on to Sloan-Kettering and took this project with me and carried it forward from there.
Recommended Citation
Mendelsohn, John MD, "Chapter 09: New Lines of Research and Building a New Program at UCSD" (2005). Interview Chapters. 1451.
https://openworks.mdanderson.org/mchv_interviewchapters/1451
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