ASH Oral History: Wayne Rundles

Rundles: Well, I'm looking over the C.V. that you have. It reminds me that my escape from the farm in Indiana came from being a Rector fellowship at DePauw University [Greencastle, IN] in 1928. This was the beginning of the Depression and any fellowship support was welcome. I was lucky in getting a good assignment at DePauw University where the people that I fell in with were predominantly premedical students. At that time I didn't know what I wanted to do other than some field of science. As time went on, Dr. [Caswell] Grave, who was professor of zoology, suggested that I might like to take a summer vacation and course at the Woods Hole Marine Biological Laboratory, which I did and enjoyed very much. This led to an appointment in the department of anatomy at Cornell University in 1933. At that juncture I was interested in the first year or two, or the first two years, of medicine which were being offered at Cornell at Ithaca. I spent four years then in doing research with Dr. James Papez, who was interested in comparative neurology. After finishing a doctorate in this area, I decided one couldn't really succeed in medical schools without having an MD degree in clinical training. It happened that the individual in charge in neuropsychiatry at Duke was visiting one summer at commencement time and told me they were developing or trying to develop a new medical school at Durham, North Carolina, and that possibly I would like to look it over. On his invitation, the next day I drove with him 600 miles from Ithaca to Durham.

Rundles: Dr. Raymond Crispell. To make a long story short, I liked what I saw and two weeks later I was enrolled as a second year medical student at Duke. Duke in those days was a young school. The reputation in the Ivy League area was probably that of more or less of a country club: they didn't know what was going to happen. But at any rate, the faculty, which had been recruited from Johns Hopkins for the most part, was young, energetic, and turned out to be a competent group of people. Dr. [Wilbert C.] Davison, the dean, had finished his medicine and training at Oxford and was somewhat of an Anglophile, so he took a broad view of medicine in this world and wanted the students here to intern elsewhere, to spend some time abroad and to invariably have a more extensive postgraduate experience than was customary. Having had graduate work before, I found Duke a congenial place for exposure to patients, doing laboratory work as one desired, and having a very flexible curriculum.

Nevertheless I thought it would be best for me to intern somewhere else and I took an internship at University Hospital, Ann Arbor, Michigan, whose chairman at that time was Dr. Cyrus Sturgis. Michigan turned out to be a good place for me. It was a different kind of medicine than I'd been used to and I had the privilege there of following up some interests that had developed actually at Duke as an undergraduate. While working the clinic here I was interested more or less in neurology to start with, having done my Ph.D. in neuroanatomy. In the clinic in those days I saw some interesting sequeli of encephalitis that developed during the World War One: a particular group of patients with diabetes seemed to have some strange physiologic and neurologic problems. As it turned out, they had some neurologic complications that were new at that time, particular to the involvement of the autonomic nervous system was not clinically recognized at that time in classic neurology, and wasn't understood by medical people dealing with diabetes. At Ann Arbor there was a very well-organized diabetic clinic, so I spent my elective time there and for a period of two years studied some of the neurologic anomalies that we were seeing. It turned out that diabetic neuropathy was of interest to many people and I was able to get together a small monograph which was published in the Quarterly Journal of Medicine. Dr. Sturgis noted that I was interested in the neurologic problems of medicine and suggested that in the blood institute, the Simpson Memorial Institute, one of the major problems was neurologic problems associated with pernicious anemia. So, after finishing that residency in medicine, I transferred as instructor of medicine over to the Simpson Memorial Institute to work with Dr. Sturgis and Dr. Frank Bethell on hematologic matters.

Rundles: No, this was all the University of Michigan. The work there was evolving rapidly with the development of anti-folic compounds and the early studies that had related to the biochemistry of the blood diseases, so my interests for a year or better there were finishing up the neurologic complications of diabetes and studying the neurologic complications of pernicious anemia. Leukemia and hemolytic anemias appear to be more challenging problems though, and from then on I stayed in the field of hematology.

Dr. Fred Hanes the first long-term professor of medicine at Duke invited me to return to Duke in 1945, the fall of that year, as an associate in medicine. This turned out to be a good move for me also, because there were many problems to deal with and there wasn't a whole lot of research being carried on at Duke at that time, partly because of the war and partly because of the youth of the institution. As time went on I was able to start a number of projects in hematology here at Duke which attracted some attention. We were studying some of the manifestations of metastatic tumors and found that what had been called metastatic disease in the past was often actually due plasma cell myeloma. We were soon having an epidemic of myeloma in our wards and this led to studies in reference to the control of plasma cell myeloma. During the first years here we were interested in a primitive chemotherapeutic agent, ethyl carbamate or urethane which produced some remissions.

Rundles: This would be in 1950. Early 1950's. This agent was very difficult to use and of course is obsolete now, but any regression in the disease activity of myeloma was welcome and some of these were quite spectacular.

Rundles: The first report of Ethyl carbamate was published in Lancet by the individuals at the Chester-Beatty Hospital in London. Dr. Alex Haddow, Dr. David Galton, Dr. George Sexton, and others were involved in the studies at that moment in London. They had looked at the field of leukemia as an abnormal type of growth and decided to investigate to all the all of the chemicals that had some antimitotic effect. Of the group that was studied were two that seemed to be outstanding: one was the carbamate compounds which are still around but not used in medicine and the sulfonic acid analogues which developed into myloran busulfan. This was my first knowledge of the work going on in London at the Chester-Beatty Institute. We extended the work and set up ways to evaluate quantitatively what happened in plasma cell myeloma, which led to studies that dealt with the plasma and urinary proteins. We were lucky here in having two individuals who were interested in that area: Dr. Joseph Beard who's in experimental surgery and Dr. Hans Neurath who later became professor of biochemistry at the University of Washington. With their facilities and collaboration we were able to study some of the proteins in myeloma and everybody was excited to see these striking anomalies reversed for the first time in the patients who responded. This actually led into the field of antitumor chemotherapy, as far as I was concerned. Along with this particular study I might mention that other problems that we had dealt with hemolytic anemia and refractory anemias which in later years became known as myelodysplastic syndrome. One of our early patients, one of the prominent textile executives here in the South developed a type of refractory anemia that was not treatable effectively at home and responded only modestly to what we did here. In looking at this type of problem it seemed to me that there might be some relationship between this type of entity and an abnormality in the synthesis of DNA and RNA which were then coming on the horizon. I thought it would be useful to meet some of the people in this field and made a trip to Tuckahoe, New York to visit with Dr. George Hitchings and Dr. Gertrude Elion at that time and was warmly received and we struck up a friendship that turned out to be useful in the long run. We weren't able to solve the problem that we started out on, but we were able to show that there were some abnormalities in nucleic acid synthesis in patients with gout. We were able to give hypoxantine, for instance, to a former mayor of Durham and produce a fulminating episode of gout which didn't do him any good perhaps, but it didn't hurt his anemia either. As time went on we began to work with more of the better established agents, particularly 6-mercaptopurine and thioguanine and derivatives with Drs. Elion and Hitchings. This project occupied about ten years of time, from the early fifties through the 1962, and we were able to show that among the great number of antipurine compounds that a few that looked very good in animals were not really effective in people. We decided that we needed to know more about the metabolism of these compounds, how they were degraded, how they were absorbed, and so forth, and undertook these studies in collaboration with the Wellcome group in Tuckahoe. To make a long story short, there were several dozen or more patients studied and specimens --urine, blood, blood cells -- transported to Tuckahoe and back. It appeared that while the mercaptopurine was presumably incorporated into DNA, that one of the ways the compound was destroyed was oxidative degradation somewhat similar to the process with which purines are degraded into uric acid. With this knowledge in hand Dr. Hitchings suggested that a compound which we knew at that time as a hydroxypyrazolopyrimidine but later allopurinol might be a useful therapeutic agent in this connection, used with the aim of reducing the destruction of the compound that we were giving. This compound was interesting in as much as Dr. Hitchings early on had studied a large number of compounds as to their effect in inhibiting an enzyme xanthine oxidase. The pyrazodolpyrimidines were suggested as chemotherapeutic agents and investigated at Columbia and NIH, it was found that the most active of these compounds produced a hemorrhagic disease and no antitumor effect. There was one that was an effective enzyme inhibitor that did not have these effects, however, and that was the hypoxanthine derivative, allopurinol. So, it was his inspiration to take an inactive compound as far as leukemia was concerned but was active in inhibiting the enzyme to see if it would improve the efficacy of mercaptopurine. This turned to out to be true and our first patient was a lady with chronic granulocytic leukemia that we studied here in May 1962. In the first study, which has been published in different areas, we were able to find out a number of things: One, it changed the metabolism of 6-mercaptopurine in a desirable way -- it protected it against being destroyed; it reduced the level of uric acid in the urine -- uric acid in the serum; and increased the amount of the precursors of uric acid that was excreted, the oxypurines. Well, in one patient we identified the changes that would take us about five years or better to nail down. As a spin off we were not able to show that the allopurinol improved the efficacy of 6-mercaptopurine anyway. It was a dose reduction economy rather than an increase in qualitative effect. The effect in monitoring uric acid seemed to be more promising. In those days we had on the ward usually one or two or more patients who had either the renal insufficiency of gout or had had acute flare-ups of gout associated with the use of moonshine or plain, ordinary, hereditary overproduction of uric acid that we were accustomed to seeing at the end stages of gouty arthritis. We explored the effect of this compound and recruited a number of patients with gout and were able to show that it was a very useful compound. Within two or three years, with many others who were recruited to study this, it was established more or less as a standard therapeutic agent in perhaps a half a million patients in the U.S. We were able to find out that there were some limitations in its use: one patient in 50 developed a sensitivity reaction. There were some other minor effects produced in nucleic acid synthesis and elimination that were potentially important but turned out not to be. On the whole this turned out to be a happy experience for this purpose.

As you probably know the collaboration of pharmaceutical companies with universities has been sporadic. Until probably in the 1950's it was not formalized at all. I think it appeared both to the Burroughs Wellcome people and ourselves that the closer collaboration would be useful. We were delighted then in 1969 when, after surveying the whole east coast, the Burroughs Wellcome people decided to move from Tuckahoe, New York, to the Research Triangle - New York their headquarters for research and business for North America. The American research organization and their headquarters for the business were placed here. Now this has proved to be a good collaboration. They have been good citizens here. Many of our faculty have been back and forth to their research laboratories. They have been able work with many other individuals. In recent years the Burroughs Wellcome scientific interest has verged toward the control of AIDS and virology more than the uric acid problem, which was pretty well solved for practical purposes. Their interest at the moment concerns the antiviral compounds and the molecular biology at this type of agent.

My own interests went from general chemotherapy to the uric business which more or less crosses specialty lines. I tell our rheumatologists now that we helped them with uric problems they owe us one in terms in making some advance in antileukemic areas. They haven't done so yet, but we are very much of the opinion that there's an excessive amount of specialization and restriction of scientific interests these days that in the long run is going to be a great handicap both in research and in medicine. Along the way, I might mention that in the mid-fifties it appeared that there was going to be a tremendous proliferation of chemotherapeutic agents making their debuts and that we would have to study a great deal better, more scientifically and on a larger scale, the action of chemotherapeutic agents. We were able to organize, with the support of the National Cancer Institute, the Southeastern Cancer Chemotherapy Cooperative Study Group in 1956, and I was chairman of it for ten years. We thought we made good pretty good progress in those days, when the group was small and the people who were involved were all senior investigators. In this area there's been a tremendous proliferation of work, more cooperative group, larger groups, and then more recently the founding of the community cancer centers until there are over three hundred hospitals now doing this sort of work. There are some trends in this area that are noteworthy. One is that the great flood of chemotherapeutic agents that were really good, that we anticipated 30 years ago, didn't occur. We had some good ones, but in general they are more difficult to use and have a higher range of toxicity and less potentiality of cure than some of the early ones. The organization of the cooperating groups has helped, perhaps, to establish the style or protocol type of investigation, but it has also narrowed the focus of many of our colleagues; it has led to studies that had no great rationale to start with; and at the present time is somewhat controversial in terms of how much it should be expanded and how much that which some of us think is strictly experimental should be incorporated into the standard treatment. The aggressive chemotherapy has undoubtedly saved many lives or at least it has made many people better; the cure rate is not as good as we would like and the tolerance of side effects has been increased tremendously. When we started out with, say, the simple compounds, we hoped to have few or no side reactions. Now horrendous side reactions are pretty well tolerated and accepted and one of the most obvious things about chemotherapy now in the public mind is that it deforms your body; it produces a moon face, demineralizes bone, destroys the bone marrow --temporarily at least, sometimes for longer -- and loss of hair: these side reactions are better known than the good effects. So there is an uneasy balance there between doing good and doing harm, as far as the patients are concerned. This hasn't been solved and won't be solved in the foreseeable future. In my own thinking about this area, we have of course trained a lot of so-called medical oncologists who are interested only in treating disease. I think it's fair to say that the emphasis at the National Cancer Institute, particularly since the war on cancer was declared in 1971 under Nixon's administration, has been on developing better methods of treatment. This translates with Dr. Vincent DeVita's leadership into multiagent chemotherapy, larger doses, and more aggressive types of treatment. We are now coming, some of us think, to a better defined ceiling on what can be done. For instance we now know that in carcinoma of the breast that women have what looks to be stage one disease with no evidence of actual metastases at the time of surgery actually will turn out to have disseminated disease in rates of (?) one in three perhaps. Under the most favorable circumstances a cure from surgery alone or from what have we have done in the past -- more extensive localization surgery -- is limited. In the very aggressive use of chemotherapy in, say, local extensive carcinoma of the colon the results of chemotherapy are evident in, perhaps, five or six or perhaps seven percent of patients, but it's almost exactly negated by the frequencies of leukemia and the complications. So systemic therapy for established disease, at least in some of our opinions, is not very promising and in some areas it's completely useless and in others at best somewhat palliative. For that reason we are looking better now more aggressively to computers for what possibilities there are for actually preventing disease and then earlier diagnosis. In the field of prevention, we've prevented about all that's easy to prevent: we aren't using radiation at random; benzene, benzol, toluene, and these chemicals, as recognized, are not let loose on the population in general. The outstanding agent that will produce tumors these days are tobacco products and this has been the hardest thing for us to eliminate. In this part of the country there are many people who have a special interest, of course, in promoting the growth and sale of tobacco, and it's very difficult to get people to think in a logical fashion, think linearly about the health hazards of tobacco on one hand and the economic problems on the other. They should be separated because we have to recognize the bad effects as well as the good. And there are probably some good effects of it. One of the very interesting books recently has been that of Patrick Reynolds on The Gilded Leaf, which is a summary of the activities that affect Durham, Winston-Salem, the East Coast, and the ramification of great wealth in a very lucrative business arrangement. In this book, Dr. Fred Hanes, our first professor of medicine was mentioned and there are many other personal areas of interest. At the present moment we're thinking that while we have to continue with the development of chemotherapeutic agents, particularly those that are based on molecular biology and more selectivity, we have to continue on this but still we need to think in terms of prevention as well as early diagnosis. The greatest prevention opportunity, as I have mentioned, is tobacco. We are distressed to note that half of the tobacco raised in the U.S. is exported now and sold in other parts of the world to individuals who don't have the knowledge of its hazards that we have here. So we are storing up some very serious problems in Egypt, Africa, Korea, Taiwan, and Japan. We are exporting some major hazards there in a very predatory way. It should be recognized that there are things that add to the hazard of tobacco. We think tobacco in general is responsible for one-third of our cancer, and it pertains not only to carcinoma of the lung, but it increases the incidence of cancer of the mouth, throat, esophagus, pancreas, and bladder at least, and it has some ramifications in all of these other areas. The hazards of tobacco are magnified by heavy exposure to alcohol. Heavy drinkers, particularly in France and certain other areas have a greater incidence of, let's say, carcinoma of the esophagus. The hazard of tobacco is also magnified by exposure to asbestos and to such products as radioactive radon in houses. But if we eliminated tobacco we'll eliminate some of the secondary effects too.

Now, in the early diagnosis we don't do a very good job in teaching or in practice of recognizing, let's say, melanoma. Melanomas that come into a place of this sort [Duke], half of them are, I suppose, stage two and three in their penetration; with the prognosis as poor. We don't do a very good job in recognizing carcinoma of the breast. We teach that breast self-examination is a useful maneuver, but the facts are that we are allowing tumors to develop beyond the point of maximal control by this maneuver. The ladies who have systematic breast examinations in effect will come to medical attention earlier, but not because they have operable tumor but because they're more conscious that there is a problem. One patient in ten at this present time will develop carcinoma of the breast. The systematic use of mammography along with physical examination and recognition of risk factors and more systematic surveys that are planned ahead of time are probably the way to go in this area. One of the things that is attractive to me in this area is the rejuvenated interest of gynecologists in detecting breast carcinoma. As you probably know, some years ago there was a group of individuals in Boston who, with gynecologic training, were managing breast carcinoma. They don't do that anymore but they now have a renewed interest in early diagnosis and the use of mammography and ovular attributes.

Rundles: At Tufts, Robert is one, the internist there. And what is the gynecologist? I keep blocking on his name. I can find that for you. He's the chief of gynecology at Tufts. A very excellent person. But their position now is that gynecologists should not only look for gynecologic problems but also neoplastic problems in the pelvic area; but there's no reason they can't learn to be expert dermatologists recognizing melanomas and be connoisseurs of breast carcinoma. This would cover a great deal of early diagnostic problems.

Rundles: Yes, as I would look at it, if you take the top five -- this would be a lung, breast, uterus, prostate, and colorectal, each of these has a little different problem in terms of prevention. Lung, you prevent exposure to tobacco, asbestos, and say, radon. Breast, the problem here basically at the present stage of knowledge, is early detection; this is better recognition of risk factors, the value of physical examination and mammograms, regularly in individuals who have no symptoms. That means we ought to be working with the sixty or seventy million women who are employed, who have to do these things at their worksite. In uterus, the control of cervix has been noteworthy with Dr. Nicholas Papanicolaou test; the problem here is that we still have ten thousand women a year who develop invasive carcinoma of the cervix in this country who either don't have pap tests or gynecologic studies or the work that's done is of poor quality. We have a great problem of maintaining a good quality of medicine and that is a very difficult problem.

Rundles: Incidentally, I think the quality of medicine is something that people don't quite understand. It takes a lot of work, a lot of labor to deliver good medical service and when it was declared in 1983, or before that, that everyone was entitled to first rate medical attention, they didn't know that you're demanding immediately a tripling or quadrupling of personnel and expertise. Everybody knows that in a laboratory, if you overwork, or overload your technicians the results deteriorate. This is happening to some extent in medicine. At the present time in the pap smears, around the country half of the specimens that get to the laboratory can't be interpreted. They're technically bad. That means we haven't either taught our students or we haven't taught those in other specialties how to do this simple test and how to get it to the laboratory under the best of circumstances. In a good laboratory you ought to have 80 to 90 percent satisfactory specimens; the national average is fifty. So this is the quality of medicine. It's not only people but what you're going to do. Now in general people in this county are enamored with new tests; they're enamored with procedures. Well, medicine is not a procedure. You start off knowing the patient's age, sex, something about their family --hereditary, habits, and so forth. You have to set the stage to know what the hazards might be. You can't have people, say, subjected to Wasserman test or something like this for cancer and cholesterol for blood, cardiovascular. People want simple answers to complex problems, and they're not willing to retrench a little bit and do a good job. Quality in this country depends on a number of things: good medical education, good training. We have to train and teach people as to what they should be doing. We need to have better follow up from different sources -- the workplace, insurance, and so forth. People talk about quality but they're mainly talking about the quality of amenities, not the quality of the basic medical service. There's a need for better medical education, better understanding. I think that's in general the area. I might say that in teaching is not very good. We were talking about carcinoma of the cervix. As you probably know, there are 10,000 women a year who have invasive carcinoma of the cervix; there are also fifty thousand a year detected who don't have it. These are the cured people. This is in situ or carcinoma that would not be recognized unless there's an examination and cytology done. In many parts of the world where Dr. Papanicolaou's  cytology studies are not carried out, this ratio of 10 to 50 is closer to one to one or even reversed because women don't have the appropriate tests until they have invasive carcinoma. This applies to the orient and it applies to Latin America to a great extent.

We might just make a remark or two about prostate. Prostate is beginning to be very common as men get older. This is being diagnosed more often during transurethral resections, but there is really no progress that I am aware of in terms of prevention or earlier detection in that whole area.

That isn't the case though with colorectum. The early lesions in colon and rectal tumors are polyps. We've made progress in eliminating polyps in the rectum in the last few years and in dealing with rectal disease. But we have not really gotten into the business of using the medium range or medium reach colonoscopes that will effectively diagnose 80 percent of the left-sided colon studied in contrast to almost zero percent of early lesions, unless it's found by accident. So we have to train a lot of people to do what is a labor intensive business, somewhat expensive, but nail down or to specialize, to identify those that are high risk. Those are the people with familial polyposis or family history of colon carcinoma and so forth. So, if you want to look at what you are going to do in the cancer field, prevention is in lung; breast is early diagnosis, uterus would be better diagnosis and better understanding not only of a normal cervix but the body. Prostate is going to be bad, we can't do much with prostate. We can't do much with brain tumors, kidney tumors, many others at the moment. So there, the luck of the draw, it depends. We could probably detect eighty percent at least of the colorectal tumors which is a big entity. These all occur with an incidence upwards of 80 to 100 thousand or more a year out of a total of about a million. We could improve what we're doing now by intensifying what we can do at the moment without monoclonal antibodies or anything else if we had it organized and the resolve to really do the job right in early detection or prevention. And that to my way of thinking is what we need. Melanomas, to a certain extent, early detection is curable. You can also prevent some by not getting people sunburned and baked to death on the beaches as they've done in Australia; they've reduced the incidence. So we have to take the entities. So if you outlined the entities --let's say we have a million --

END SIDE ONE, TAPE ONE; BEGIN SIDE TWO, TAPE ONE

Rundles: I can give you a tabulation of these twenty tumors, if you like, that seem to me important: the top twenty which include ninety percent of our tumor problems. So we do kind of veer off from getting excited about some new area of development and not doing the mundane things, which just take plain work to execute, and that's the quality of medicine. I think in general the quality of medicine has improved over the few years until at least recently. I think we're trying to do too much, too fast, and too sloppy at the moment. This is what almost everybody agrees on. This leads to mistakes.

Rundles: I'd say basically most of my work has been with patients and dealing with clinical research problems. And teaching. We kind of lump them all together since we can't really separate them effectively. I've been lucky, in my appointment here, that I've been able to work on the areas that seem to offer the greatest opportunities --educationally, scientifically, clinically, regardless of income and so forth. So that I've been able to select my work according to what seems to be the most important to the institution and to our own service.

Rundles: No, that's been only a part of it. The Burroughs Welcome was very important in terms of, first of all, of learning some more about the basic biological effect of the antipurines and other compounds. In meetings and all I got to know the individuals at the Chester Beatty Institute in London. From knowing a few of the other people in the American Society of Hematology and visits, I got to know the Sloan Kettering people very well and others. It's a great community of them and a community effort, I think. The free flow of information and the free discussion of problems that was at least true in our early days was I think one of the great assets that we have. Of course you have to have an institution to deal with, too. We've been lucky here to have first Dr. Gene Stead who when he began to think that one of his people could do something gave with unstinting backing; Dr. Wyngaarden followed him - same philosophy of work. Dr. Wyngaarden being a connoisseur of gout was helpful in advising ways to do things early on, particularly during some of the laboratory things that we were required to set up. From his general knowledge of what went on, he was a useful consultant on the side. So it's a happy community in that sense.

Rundles: No. One of my interests has been the evolution of American medicine: how it evolves. The American public has been extraordinarily enthusiastic about research and about developing new techniques. Of course the great era of research innovation was in the Second World War. All of the things that we now take as givens or as day-by-day tools were developed pretty much in that era. If we're going to put down one golden era of research, it would be from 1960 to the 1970's. Now the problem then became -- I don't know that this became a problem, but doctors and investigators were interested in only one thing and that is doing better and doing more. With the Great Society era -- 1965 to 1970 -- we begin to enter into an era that became expensive as far as people are concerned. Doctors weren't interested really in two things: they weren't interested in saving money and families aren't either. You have someone who's a relative and you say, "Well, it's only going to cost you a hundred thousand dollars to have your heart transplanted,'' they'll say, "Let's go for it." There's no conscience whatsoever about economy when a medical necessity arises, as you know. The doctors have not always used their resources too well. For instance, we know a lot of things we've explored that haven't been worth a hoot: freezing of stomachs, for instance, that hasn't been any good. Probably fifty percent of the chemotherapy we do now isn't doing any good, but we aren't really coming to the conclusion that we shouldn't do it yet. We're still pushing ahead.

Rundles: Because of the urge. People say, "Well, I might get better." If you've got one chance in a million, I guess most of us will take it. Although the economists will say, "That's crazy." That if you don't have a five percent chance of doing it, quit. If we were in a totalitarian society in Russia, they won't spend the time of day on studying or developing an orphan drug or something for a small population. This is our problem. We haven't really come to the moral grips of things and we haven't really given the people who are more philosophically inclined the facts on which they can see what we're dealing with. So there's a kind of fragmentation. For instance, if an agent isn't going to be useful in maybe one patient in often twenty or thirty, there's no enthusiasm for continuing it. But I think we have to have good science pursued regardless of the economy of it. But also when it comes to translating it into everyday practice we have to say, "Now, is that worthwhile or not?" I know that there are many things that we do that I wouldn't vote for having if I had the necessary ___________________.

You say, "What has changed recently?" In 1980, we began to have a change in federal philosophy. Instead of having an unlimited expansion of research and development there's been a retraction at that point in terms of funds, funding and what to do. This may be a necessity in some part, although what you're going to spend your money on depends on how valuable you think it is. For instance, at the moment, there's a great falling off of research in cancer areas in favor of AIDS. People are more afraid of AIDS than they are of cancer. So that means that the politicians and those who allocate funds are going to follow that direction. Some people think it's a ridiculous amount of support into AIDS considering the ideas that are available at the moment. It takes a certain amount of time, effort, inspiration to develop the field. You can't just throw money in it. Somebody will say it is equivalent to wanting to expand your population quickly and getting nine ladies pregnant and have a child in one month. It takes a certain amount of maturation and development.

Rundles: Well, let's take Elion and Hitchings, specifically. I used to see them about every two months. They came down here to give talks to our staff, and back and forth. We worked out ideas and we did very informally the work that has been published here. This is what I always regarded as a scientific collaboration. My knowledge of enzymology involved in the antipurine and antipyrimidine compounds was pretty skimpy and their knowledge of leukemia and these other things was equally skimpy but between us we covered the needs and had a very good relationship. As time has gone on and pharmaceutical investigation has become much more expensive, and this is part of a federal problem here, they increased the requirements, chronic toxicity, and this and this and this. It always seemed to perpetuate. At one time I suppose allopurinol probably didn't cost more than a half a million dollars to develop and for twelve or fifteen years this was the birth of the most lucrative agent. You cannot start to develop a compound now unless you're willing to put maybe fifty million or more. A great deal of this comes from federal regulations; it comes from increasing complexity. Some things that are inevitable, but a lot of it isn't inevitable, too. When you get into that money then it's a different environment. You've got to succeed in getting an agent. You've got to pay your bills, of course. But the free-for-all scientific collaboration is gone. That's just gone. An investigator now in clinical work, the first time he will hear of a new compound is when the pharmaceutical people say, "Well, I'd like to have one hundred patients with this disease treated for six months or something. Here's a handbook of what studies we need." The investigators are no longer collaborators; they're technicians. Part of this problem then results in that our better investigators don't spend much time doing that. They delegate these things to clinicians or nurse-technicians and junior people. So the quality of investigation has fallen off. Then as everybody knows there are incidents where you put a lot of pressure on people who are trying to do something and you begin to get into the area of errors and frauds and sloppy results. So I think in general, in many areas at least, there's a deterioration of quality that is hard to identify and is hard to quantitate, but it's a very real sort of thing. If you ask people who are connoisseurs of an area of medicine, they say, "There's no dearth of information. You don't know what to believe, that's the problem."  I think we need to do less but better, is what it boils down to.

Rundles: Some people have done pretty well. I don't know if they trained me or vice versa. First of all, looking down the area of people I've worked with, Doctors Bethell and Stirgis of course were very well known people in the blood field. Dr. Pauls is an ophthalmologist who's recently retired; genetics was his hobby. Dr. Hamlin is a practicing radiologist in Boston. Dr. Hodges has died. Dr. Hodges was one of the great trainers in radiology. Dr. Sebe is at Ohio State in their department of medicine. Dr. Robert Willett went into neurology and practices in Raleigh. Dr. Martin who I had collaborated with is at the University of Pennsylvania in the Wharton School of Business. Administration appealed to him more than other work. Dr. Ralph Coonrad just retired in Durham. Dr. Erends is dean of a new medical school in Venezuela. Dr. David Karnovsky is one of the better known chemotherapy experts. He died a few a years ago. He was at Sloan Kettering. Dr. Spencer Brewer is in practice in Atlanta Piedmont Hospital. This whole reference number of 51, there are a whole bunch of folks here are that are scattered around the country. Dr. Griswold was professor of public health at UNC. Dr. Warren Bell is at Jackson, Mississippi. Dr. Curly is still working at Emory. Dr. Greenberg has died and [Dr.] Hubley is the president of American Cancer Society in Atlanta. Dr. Ludlow is retired a year ago as a president of the American Cancer Society. Dr. Leone is still on the board of directors of the American Cancer Society. You know about Elion and Hitchings. One name comes up here. John Laszlo is senior vice president for research at the American Cancer Society. Dr. Takoshi Atoga is dean of the medical school in Oita, Japan. I visited him two years ago. Dr. Jack Hobson is practicing in Charlotte. These are a whole bunch of folks from different parts of the country. Dr. Hal Silberman is in charge of our emergency room here at Duke at the moment. Dr. Wyngaarden is just finishing his appointment as a director of the National Institutes of Health.

Rundles: He's been invited to come back here. He's been on an adjunct business. I don't know whether --He's got two or three things that have been offered him. Dr. Earl Metz is professor of medicine at Ohio State. Dr. Robinson is chancellor for medical affairs at Vanderbilt. Dr. James Vogler is at Emory, still working away. Jordan Gutterman is rather well-known in the interferon field at M.D. Anderson Hospital. Jerry Logue is chairman of hematology at university of Buffalo. I guess you know there's been another venture into writing the hematology book with Bill Williams and his group.

Rundles: Well, let's see. The first edition of this came [out in] '72 perhaps. Should be reference 90 here. About 1970. With the advances in hematology that were occurring it seemed to many of us that the existing textbooks weren't quite adequate. Dr. Max Wintrobe's book was a classic for years and years. Edition number five of his book got to be a little bit bulky and a little bit of a composite business. Then as he told us later, his edition six that we all called "The Blue Max" was kind of hopeless. It got to be a hodgepodge. So several of us thought we ought to get a more authoritative business put together. So several of us with talked someone not on here. We finally settled on Bill Williams as the editor. He was making a change in assignment from Pennsylvania to Syracuse and the four of us -- Beutler's from California, Erslev from Pennsylvania, and myself -- spent a good deal of time for about five years writing this hematology book. McGraw Hill thought that it might sell luckily 5,000 or so copies. Of the first edition, they ran out three times and ended up by selling 25,000 or 30,000. Then it's taken off and has been one of the more evolved, or accepted books since then. I haven't collaborated in the last edition. But for the first two or three it kept on going and getting bigger, and I think it was well received by those who are investigative inclined. So that was another successful venture as far as we were concerned. Another success I guess from the general standpoint here has been the awarding of the Nobel Prize last December to George Hitchings and Trudy Elion for their concepts in drug development which had been noteworthy. I wouldn't have classified it just that way, but at they were given recognition a little late in their careers for contributing many things. First of all the antimetabolites were mentioned; the uric acid control; again the first effective compound in the anti-viral compound acyclovir; acyclovir and then more recently in the AIDS business. So their contribution is very extensive. These have all been successful ventures. We could have done better probably. We've gone over this area from the time when you begin to do research as kind of an adjunct to a career in say teaching academic medicine to the era in which we have people who are not teaching any more, who aren't having anything to do with patients, and they're spending all of their time in research, so that kinds of fragments it in that sense. When I started out in hematology I knew Dr. William Dameshek very well. Took many trips there. He and Henry Stratton thought that the time had come when we needed to have a specialty like hematology. Over the criticism of people like Carl Moore and Dr. Wintrobe, and others. They thought that when you begin to fragment medicine you lost its flavor completely. That argument has long been lost, now, and all at once instead of having internists interested in academic medicine as the dominant people, you begin to have cardiologists and infectious disease and ten others. I think there are now thirty certificates or boards of some type or another that identify different individuals. You can do a better job in one area, for sure. But you also don't know a lot that you should know. So it's a mixed bag. I don't think we have that solved at the moment at all. At one time the people in our division here were all individuals who were conversant with general hematology/oncology. We now have people who couldn't care less about hematology; it's all oncology. And in the hematology field you have people who are interested in platelets and nothing else. Coagulation and nothing else. I don't know the degree to which some people are interested in bone marrow cultures. Some people are interested in bone marrow transplantation and nothing else. So I think it's kind of a loser in some ways that our core teaching needs to be kept strong, and we need to keep broad view as to what's going on in different fields or else you get caught napping.

Rundles: Well the personalities are, of course, important, in medicine particularly. Doctors in general don't do well in taking care of patients unless they like people -- unless they're interested in people. If you take someone who is only interested in writing papers or something of that sort they don't do very well in that area. We have them all from individuals who are interested only in personalities down to people who are interested in nothing bigger than a microsome or something. It varies all over the place. It's fortunate because a variety of talents are required in medicine and if you are aware of your students and their long suits and their short suits you can help guide them into areas where they'll be more successful. The most successful person I think in that whole field is Dr. [Eugene] Stead in this department who spent a lot of time, always made rounds when he was here and he was always here for the twenty years he was chairman. Most successful in building up people, meaning making careers for them. It's very difficult to do.

Rundles: Eugene Stead. He's a Brigham trained person and one of the revered people in internal medicine. Personalities have a lot to do with it. We have people in our group now who don't like to take care of patients. They're impatient and they're not going to spend the time which is fatal in that regard. A successful doctor has to know a range of things. The successful specialist has to know one thing. And we have more one-objective people than we used to have. They don't do well in teaching. They don't do well in patient care. These are the variations that you'd expect. There's no one generic doctrine; they all vary. To get the people doing the right things and to make the best of their abilities is about the best you can do in an
institution.

Your other question had to do with what?

Rundles: Well I guess I've forgotten but there's a nice history, I think, that Jim Tullis has written a history of the early days. The important societies in the early days were the American Society for Clinical Investigation and the Association of American Physicians, the Atlantic City group. Anybody who was anything always went to those meetings. I guess my first contact with Dr Dameshek is from 1945 or '46. It was 1945 I gave my first paper there; that was on diabetic problems. Got to know Dr. Dameshek the next year or so and always enjoyed his outlook. He began to talk along with Henry Stratton about the need for a society of hematology to focus in that area and have a journal. We had one or two meetings. I think we had a meeting in Boston and a meeting in Atlantic City in a room not much bigger than this actually, at least bedroom size. And talking about the need for it. One or two of the people who came along, Dr. Wintrobe voted against it: he didn't think it needed it; you need a general internist and you needed an investigatively minded internist and that was it. But Dr. Dameshek prevailed, and they began to develop the society and the journal. Bill Dameshek wrote around to ask if any of us wanted to contribute to volume one. I think one of my contributions in volume one was something on prognosis of the neurologic problems in pernicious anemia. But as that took off, it kept on increasing and it was popular, and we a blood club then that met with a society in Atlantic City and grew up in a kind of organizational framework. I think for the time that Bill Dameshek was alive, he was probably the dominant force in the whole thing. It kept growing. The need was obvious, and then after a while those who thought the need hadn't been obvious recognized that it was. It just went on in that direction. The Society, I think, has been successful, and I think it was the year that I was president -- when ever that was.

Rundles: Sixty-seven was the last meeting in which people could talk to each other. We had at that time a plenary session and two concurrent sessions at most. That was in Toronto. Everybody kind of knew what everybody else was doing at that time. You were conversant. From then on, the other opinion, that I wasn't entirely happy with, directed that there was going to be an unlimited number of special sessions. So instead of having two sessions that you can alternate -- cover everybody's interest -- you had 20 sessions in which you spent a good deal of your time trying to get to one or another. And that's been the problem here at the moment. You get more and more activities and then you split off from that. Some very good teaching sessions aren't very good. But it's gotten to be, again, a little bit too large to be comfortable with and to serve the original purpose of communication. I was impressed last year with another thing that I would not have approved, and that is that there were seminars and symposia given by pharmaceutical companies who chose the speakers and who attracted an audience by giving a free drink and a buffet dinner in order to come to their symposia and listen to the latest pitch on whatever they were pitching. I think that kind of kills a society after a while. After a while you think you are going to a trade fair rather than to a scientific society. How far that's going to go, I don't know, and I don't know for sure how much protest there was to that. I thought it was a -- one-time if you had a sponsorship of one or two publishing houses you had a cocktail party or small meeting, that didn't hurt too much. But when everything was sponsored by 20 or 30 people, and they're putting big bucks in it, you're treading the wrong direction in science.

Rundles: Oh, it's a drift. Most things drift. No one plans it that way. Someone will say, "Well, I'd like to give you some money to this or that." And they say, "Ok." It kind of drifts.

Rundles: Well, one's legacy dribbles down to not much, you know? [laughter] What we've tried to do is to promote good medicine, a good service to patients who have sickness. Approaching these things on a scientific basis insofar as you can and to take groups of patients who have significant problems, investigating them systematically and seeing if you can't make some inroads. In general, science, you know -- good science, hopefully -- you kind of increase your knowledge base and you go along for a while and you increase a little bit more. It's a cumulative thing. If we got to the point where you couldn't trust the data, when you couldn't trust the honesty of people who were recording things, you being to deteriorate into kind of a political anarchy type of thing. I'm not sure which way we are heading at the moment. The pendulum certainly swings and there are people who want to be very rigorous in quality, and I agree with that myself. It's a quality operation and the development of people to do the right thing and whatever legacy there is pretty much a very transient sort of thing. You get deleted out very fast in this business because of increasing number of people, increasing information, and every once in a while we have someone who looks up a problem and says, ''My goodness. You knew about that 15 years ago." That's always pleasant to hear that. At the moment I'm spending most of my time in trying to consolidate some of these areas in which I mentioned there's a big tumor problem. As the population's grown older and diseases have become more complicated, it's going to be harder to render good service. The whole field of cancer control, that whole area, is rather chaotic in my view. I would like to kind of clarify that business by what we're putting together this fall to at least have another landmark on which you can base group progress from then on, identify the important problems, stress that there is no one approach that's going to solve all these 20 problems. You've got identify them, and you ought to have a program that is maximally effective in all of them if you can or least identify the areas where there's an opportunity. Right at the moment I don't see any opportunity for either preventing or treating better brain tumors or pancreatic tumors, kidney tumors, and so on. So do the things you can do practically. But then identify solid research, basic research. Encourage and promote it far as you can which in the long run will solve problems we don't recognize at the moment.

Rundles: That's about it.

July 11, 1989

Rundles: Very well, thank you. A little warm.

[tape stopped]

Rundles: I forgot to give you this morning a program that I've been spending time on, which encompasses a meeting of the American Cancer Society, the North Carolina Division, in collaboration with the Comprehensive Cancer Center of Duke University. On the first page -- there's one insert that will be in the final program -- the plan of the program is as you see outlined. The ACS has been celebrating its75th year now as a voluntary science-based organization, which represents the public interest in cancer control. I've been interested to note that the public continues to be enamored by research and the development of new agents and procedures. By using the means now available to prevent cancer and improve the results of treatment by making diagnoses earlier are much more likely in my opinion to produce the dividends they're looking for. A variety of cancer centers are supported in this state by private, state, and federal funds out of recognition that cancer control is a do-it-yourself proposition to a large extent and that high quality medical care requires continuous monitoring and scientific refreshment. This is theme of this Fall's symposium. We're trying to pinpoint those areas which we should pay more attention to and for practical purposes make them active programs of the American Cancer society, both in North Carolina as an example, and nationally where they need such an example to follow. The symposium here is known as the Audrey Meyers symposium because Dr. Meyers is one of the outstanding leaders in the ACS for years and was a very dedicated volunteer in Virginia and had some special interest in North Carolina. We're going to emphasize in this particular symposium this fall the rational use of mammography, which means that we are using this as a tool in conjunction with physical diagnosis, the recognition of risk factors and so forth as part of the program that's designed for making diagnoses of breast carcinoma earlier. Since this is one of our major problems in the cancer field we think that should be given priority. The second area which is neglected pretty thoroughly throughout the country is the use of medium reach colonoscopic examinations and intelligent use of genetic factors, family histories, and so forth, to recognize the presence of polyps in the colon, which are the precursors of colorectal carcinoma. Polyps are curable; fifty percent of rectal neoplasia are, providing they have not extended into the bowel wall, but if the colon has been breached or local metastases have occurred the mortality rate is very high. The early recognition of malignant melanoma is hot climates such as this is important because it's something out in front; it doesn't cost anything to look and if you know what to look for, we can begin to recognize earlier stages which are curable. We also need to recognize that there are limits to what you can do with chemotherapy and other treatment in lung cancer, in melanoma, and emphasize to the public that you do not wait until there are symptoms that are flagrant or the traditional seven warning signals which three out of seven at least represent advanced disease, which is somewhat of a misleading type of sign to emphasize. To make things practical in this whole field we think that we have to teach lay people and physicians the science base of, say, breast disease recognition. We have to teach people to do the procedures that they are not now doing and then we have to not ignore that fact that these things cost money and time. In this particular area of the country we have many research organizations particularly in the Research Triangle where now we have 43 organizations that are primarily concerned with research and development in their particular areas. We have pharmaceutical companies -- Burroughs-Wellcome, Glaxol, Becton Dickensm, and others -- and we have larger installations such as IBM, who now have 11,000 employees there. To do anything really practical in the cancer control field we have not only to use our standard physician and clinic relationships but also to develop better designed programs in industry. At the moment there are 117 million people on someone's payroll -- two-thirds of these are probably women -- and the treatment and diagnosis of early disease must be done, I think, where they're working because otherwise they're going to have to get substitutes for their job as well as babysitters at home and all other problems that are attendant. So, one of the things we're emphasizing in this particular program is the industry-sponsored health programs around the country which by and large will pay a lot of attention to low back pain, major coronary disease but don't particularly pretend to do anything with the cancer prevention other than to say, "Don't smoke." We think there's a misemphasis in education and a good opportunity here for preventative medicine that we are just not exploiting. We want to emphasize the things that the people who attend this conference can take home to their local communities to use there and not rely on cancer centers or on major medical centers to execute. Actually only ten percent or less of all cancer is taken care of at cancer centers and these are not necessarily efficient organizations. They're big and complicated. So, this is the idea. It is outlined here in terms of those who are coming in from outside to talk. Dr.Richard Love from Wisconsin. Dr. Charles Smart who is now at NCI, Dr. Bailey who has some ideas for how do you train endoscopists these days with using computer simulated set-ups, which I think is a wave of the future. We've talked about industry sponsored health programs and then the Blue Cross Blue Shield organization is now changing their policy and we hope to have a satisfactory accounting made of that by Susan Gleason. Any program of education has to be supported and made palatable by some fun, so we have an outstanding Gilbert and Sullivan here who are going to perform one night I think, to grace the program. The action and practicality of some of the issues we've mentioned are going to be outlined one morning and we hope that will be successful and perhaps perpetuate it from here on. I might mention that in this university we have a comprehensive cancer center. In 1971, when Richard Nixon signed the second Cancer Act, it provided funds for building and organizing and maintaining 20 comprehensive cancer centers. Before that time there were only four: National Cancer Institutes, Sloan Kettering, Dana Farber, or Roswell Park, I guess at that time, and M.D. Anderson at Houston. The number quickly became 20, and over the years the competition for this type of funds has increased to the extent that there are now 60 in various stages of repair. Some are more successful than others. Some are more comprehensive than others. We were regarded as being very comprehensive at one time, although in the research area I'm sure that others exceeded what we were doing in almost every dimension. At any rate, we have a general cancer center. We specialize in giving good cancer treatment and we have some quite respectable cancer programs in dealing with melanoma, breast carcinoma, all of the medical oncology things and so forth. We've had for many years a trophoblastic center and for the gynecologic malignancies it's been very successful. There four people who probably had a little more than others to do with this being designated as a comprehensive cancer center: one was our own medical oncology group; two, Dr. William Shingleton in surgery had been a well-known experimentalist in therapy; Dr. Joseph Beard at that time was one of the leading, world-wide experts in leukemia viruses and immunology; Dr. Biggner, Dr. Woodhall, and other were interested in brain tumors. We had a focus of people to build around. This wing of the building here that we built to take out of the general hospital those services that had some serious interest in cancer and get them together to working together. We had also Mr. Evan Jones, basic science, our experimental investigative cancer building across the campus here. It's been very successful. Then we have an animal isolation facility in which we can work with dangerous viruses. These are the main things out of the comprehensive cancer center. I might say that there has been a very solid apprehension from the very start of these centers and others that they might be so concerned with research that they neglected what could or should be done for patients. It is a translation of the basic science in oncology into clinical practice that we kind of earmark as cancer control. As you would imagine when you try to influence medical practice you always run into trouble. Doctors are jealous of from whom they get their advice, and they want to make sure it's right when they adopt it. So there are some pull and tugs on that. Dr. [Knowles one time said, "If you don't think there's any system in medicine just try to change something." We have of course encountered some changes and been successful sometimes and sometimes not. At the moment we're going to emphasize the cancer control activities here. First, because we believe it should be done; two, it's practical to do. We may have some financial, business problems because teaching and research that deals with clinical matters has been difficult to support. I think it's conceded that some of our granting agencies are a little skewed in what they are supporting. At any rate we hope we can finance it. A third reason is that none of the cancer centers are going to be called comprehensive unless they have cancer control operations working in some detail. So these are our chief things here. You've asked me to contrast the American Society of Hematology with the Leukemia Society. The American Society of Hematology has from the start been a group that was primarily internists. Later, pediatricians as they developed an interest in oncology and leukemia came into the fold, but with the emphasis of Dr. Hale Hamm this has been a kind of premorphic type of society in which everyone was welcome to come whether they were biochemists, experimental tumorologists, or whatnot. It's premorphic society, and for that reason it's become very large. The last meetings have had 3,000 or 4,000 people, and it's become so large that those who have have, say, an interest in myeloma have a hard time finding any of their own clone. It's difficult. It's become perhaps too large and while it's successful in some way, there are some problems with it. There are problems of bigness as well as being too small. The Leukemia Society of America has a been a successful one. They have focused on leukemia, particularly on acute leukemias in children -- to some extent in adults. They've focused their interests and have had a simpler life for that reason. When I was on their board of trustees at one time, I was impressed with the quality of the people who worked with them, their administrative staff and their insight into the plan. I would think that the outstanding success has been the Leukemia Scholars. This is reasonably will paid, was a prestigious award and over the years these have been outstanding individuals. I think that's perhaps their outstanding success. The American Society of Hematology has been successful in supporting Blood as a journal; they have had good symposium; there's been a good teaching program with the national meeting; and in general it's been a good solid society collaborating with the international society and having joint meetings every four years.

There is a contrast between the National Cancer Institute and the American Cancer Society that some are concerned about. As you probably know, cancer became recognized as a disease of increasing importance in the early 1900's. In 1914 a society was organized by some practitioners and pathologists and an insurance executive in New York City. In 1914 the organization was called the American Society for the Control of Cancer. After 75 years we're now coming back to cancer control, perhaps. But they were gathering statistics; they were emphasizing the value of early diagnosis, which is about all they could do, and also histology and the classification and so forth. The American Cancer Society didn't grow very much during the first 40 years. Actually it wasn't until the Women's Field Army was organized that it became apparent the women were going to be motive power in making volunteers, and they did a good job.

The real organization though as we know it now was created in 1944, 1945 by Albert and Mary Lasker. Mr. Lasker had made a good deal of money in advertising, and Mary had been concerned with health problems for many years. Together they thought a lot of improvement could be made. There were some innovations that were very good: one is that they thought that without a research arm this society, the American Cancer Society would never go anywhere. They'd never supported research before 1944, 1945. Secondly, doctors tend to talk to doctors in their own jargon and don't communicate very well. The Laskers thought that if you could have a council or a board of people who represented the public as well as the scientists it would be a stronger board. To a lot of apprehension, they did organize it so that half of the board of directors was lay people and half were scientists of one variety or another -- mostly doctors. This turned out to be a great success and one of the charms of this body is that doctors and others who go there have learned banking from bankers and advertising from advertisers and law from lawyers and so on. It makes a delightful learning experience when they're all together. I went on this board after being on their scientific panels for some 15 to 20 years, in 1971 I guess it was, and was always delighted with the other people that I met there. I learned a lot from them in things that I wouldn't ordinarily come in contact with. Unfortunately in recent years the American Cancer Society like all others has become bigger and has bigger obligations and is now getting more diffuse. So that aspect is now dropping out.

The other thing about the American Cancer Society that should be recognized is that as it has become larger and raising more money it's spending more money. It has been possible to keep a good research organization and good panels together and their research budget, which is now about 75 to 80 million a year is respectable and on the whole managed extremely well. On the publicity side, advertising side, crusade side, these individuals don't always know what the science is. So we are now in the midst of making a big campaign of emphasizing the importance of diet in the control of cancer. No scientist I know of thinks you're going to control brain tumors, breast carcinoma, or 10 others by eliminating broccoli or putting in broccoli or something into your food. There's no science involved in this, and some of us think that's verging on the fraudulent. Like the big campaign now to keep everybody's cholesterol low. That is 10 percent true, probably. The rest of it is dubious. But anyhow, the American Cancer Society is a good society. It has two and a half million volunteers and these individuals represent the Society in communities and they can do some service work; they can do education work; and they can support such things as mammography clinics if we get these organized well. So this is our problem at the moment is to get valid, scientific programs going in communities; being sure they're supported both by money and activities, efforts-in-kind to make them useful educationally. I think it will work out.

In Massachusetts for instance you have an excellent society. Has done very well for a long time. They support their own research programs as they do in Florida, Illinois, and California. This always brings into a little bit of the question should you have a national research effort or should it be more disseminated. At the moment the sentiment is to have a national research program insofar as possible and only on an exceptional basis would you support a statewide program. We have no state ACS program here and don't want one really because we would rather have our investigators send in their proposals to the national offices and we participate there and we can thereby support things that have some countrywide merit rather than local interest. But these are problems that kind of come and go.

One of the things that we have learned perhaps in the last 25 years has been that cancer is not a single disease; it isn't due to one etiology, one etiological factor; it can't be treated uniformly and can't be diagnosed uniformly. It was interesting to me that when the National Cancer Act was talked about that there was sentiment within the National Cancer Institute to have a group of centers around the country where you'd send in specimens or something of this sort and you'd get your diagnosis by parcel post. The problem with that is it doesn't work. It isn't like venereal disease that they were looking at in those days. It's quite a different problem entirely. We haven't really overcome that. People think about cancer as cancer. They don't in their thinking or in their operations don't really nail it down as they should either from the standpoint of diagnosis or the treatment or prevention or research. All of these things should go together.

In this list, which I'm publishing here in the near future for my symposium this fall, you'll see that about one million ten thousand patients will be found to have cancer in the U.S. this year. A hundred and fifty-five thousand will have lung cancer and unless we find lung cancer very early, which we do in not more than10 percent of the patients, the jig is up: the mortality is about 92 percent at the moment. In addition to this being a self-induced disease in which the cause is known and could be remedied the side effects of nicotine and the products in tobacco, cigarettes in particular, produce a good deal of lung tissue damage and cardiovascular disease. It's estimated 350,000 patients a year die of tobacco induced medical problems. That obviously, in these days, is the big problem. It's difficult because people, as we mentioned this morning, do not separate the health consequences of tobacco from the economic. We probably would make money if we just bought out the tobacco farmers, tobacco companies and prohibited export because we are  losing more than we're making on this economically. We're losing a lot on this in this one thing and of course contributing to the national problem. Colo-rectal carcinoma is a 151,000 a year new diagnoses. The mortality for this is over 50 percent. The problem here is that the diagnostic tests that have been used in the past have not been very effective. You don't wait for symptoms to develop. Only a few people have blood in the stools. Analyzing stools for blood as we have has not been very effective and has been a poor method. There's no substitute that we know of except for identifying families in which this disease, particularly tumors and polyps, occur. Examining them and relatives for polyps and using the appropriate instrumentation which is the fiber optic medium range colonoscopes. It's not practical to use a barium enema, it's not practical to use a full range colonoscope. It's too expensive and too uncomfortable. But there's a lot that could be done here by identifying the populations at risk and then making systematic examinations. Actually, when it comes down to it, individuals who've been previously well should have a medium range reach colonoscopy examination when they're 50, at 55, and 60, and if they don't have any by then you can forget them as being at increased risk. So it's not all that difficult if you had your sights fixed on the rights things and set up the instrumentation and the people who can learn this technique, which is not very difficult. We talked this morning about breast disease. All women when they are approaching 40 need to be introduced into a program of surveillance for asymptomatic disease. Sometimes we miseducate people. For instance, we miseducate people who might have colo- rectal carcinoma by saying, "If you don't have blood, why you don't have it." Or if you do a sigmoidoscopy and look at the lower twelve centimeters of the colon and forget the other hundred, you miseducate people. Rigid colonoscopes are uncomfortable. Much more uncomfortable than the flexible instruments and so they are inducing resistance for further diagnostic study. So, we aren't doing the right things, in other words. We've talked about breast self examination. Actually the only organization that advocates breast self-examination in this day and time is the American Cancer Society. We are educating people to look for lumps. We ought to educate people to find them before the lumps by routine planned studies. You can add this up: there are three hundred, four hundred and fifty thousand -- Almost half of the cancer problem could be solved by edict if you could do the right things at the right time. In prostate, as I mentioned this morning, this is an involutional problem very often associated with benign prostatic hypertrophy [BPH]. The problem here is that no way has been found to predict who was going to get this disease, diagnosis it early, or to induce effective therapy. This is an unknown and the future will depend on the development of agents that will perhaps suppress the development of BPH or carcinoma as an involutional problem. This morning we talked about uterus. There are invasive carcinomas. Thirteen thousand now. Endometrium we don't we do quite right either. The prevailing recommendation is to do a endometrial biopsy at the time of menopause and if it's alright, forget it. Actually if you plot out the time in life when the different diseases arise, endometrial carcinoma begins to become prevalent in the fifties and sixties. So you've got another20 years that surveillance would be advisable and there are some very good ideas as to prevention, or treatment here. I might say that the treatment of breast carcinoma -- First of all you have to diagnose it. But there are easier ways to treat it now than there were some years ago. Surgery is becoming less radical and in the elderly individuals who are 70 or over who develop breast carcinoma, the use of hormone treatment at a primary therapy rather than secondary is as effective apparently as surgery. Since the only thing you lose with, say, tamoxifin --which is a hormone you'd use -- the only things you lose is that the tablets are a little bit expensive, not too expensive. But it has no side reaction as is easy and practical. So, it's education along the lines we need. In bladder carcinoma, it's interesting here that a great deal has been eliminated in the last few years by the eliminations of dyes and chemicals in industry, particularly. But the incidence of bladder carcinoma in men is still twice what it is in women. So there are habits or industrial or other things that are important. We can't prevent lymphomas. Sometimes you can cure them but early diagnosis is useful. In oral carcinoma, it is diet. Particularly the avoidance of chewing tobacco, beetle nut, the heavy alcohol, cigarettes. These are the things that are important. Melanoma is in part associated with sun damage to the skin, but still, early diagnosis is the right thing to push. Pancreas is like prostate: we can't find it early and when we do find it we can't do much about it. So the usual dictum is that you don't screen for something you can't do anything about. It's like asking questions you don't want to know the answer. Kidney, urinary tract that same way. Stomach is disappearing. Ovary is increasing a little bit. Brain we're not doing very much. On down the line. This list of 20 entities offers opportunities for prevention as well as early detection and better treatment. It's in those areas, I think, that the American Cancer Society has to bite the bullet and say, ''These are the things we advise. It may or may not cost. If it's feasible, we will insure it so you spread the risk. But we will set up the system in industry and elsewhere so that you have a systematized business." Everyone will have to get into the act. I think that you cannot delegate a problem of this magnitude to any specialty. There's no oncology group will ever take this up. The people who should be interested in, say, melanoma it would be pediatricians; that's about their only contribution that's possible. In cervix, in women after the age of 18 or 20 have to be looked at for an infectious disease is what this amounts to. Endometrium is like prostate: this is an involutional hormone problem. Melanoma means that you have to educate a lot of people to know what to look for. And on down the line. We could identify each one of these and this will be the subject, I think, of the push from here on, as far as education is concerned. It's an interesting program. It will be tantalizing. I think one thing I would like to emphasize is that you cannot do two things: You cannot make a new specialty and put all oncology problems into their lap. Pediatricians have to know that kids develop melanomas, that nevi (?) sometimes need to be removed. In all instances they should avoid damage to the skin from sunburn, particularly. Gynecologists are great, and they're showing the right interest because they are going to be looking for pelvic tumors and they're going to be a great deal more interest in breast tumors. And that's great because that's economy and practical and they have the patients. General internists and general surgeons and possibly the well-trained family practitioners may take up the slack. But I look for a greater contribution to come from business and industry when they get good medical departments and know what to look for. That means we have to give bare bones, good solid advice and not kind of shilly-shally and say we're not going to look for everything. The legal people have a good term: de minimus. The law does not concern itself with trifles. We have to concern ourselves with the big issues. And we're going to have one, two, five percent swept through the cracks; that's inevitable but it's better to have one, two, five percent swept through than 95 percent. So it's a challenge to us and I think you see some very interesting things in this area.

Rundles: I think this is about what I am concerned with at the moment.

©2008 Columbia University

back to Dr. Rundles's profile