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PIONEERS IN SCIENCE AND TECHNOLOGY SERIES ORAL HISTORY OF DR. JOHN TOTTER Interviewed by Clarence Larson Filmed by Jane Larson February 1, 1989 Transcribed by Jordan Reed MRS. LARSON: Yeah. MR. LARSON: Start in reasonably close. Good I think we’re all set there. Just to make it safe, I’ll put these a little bit closer, a little bit more [inaudible]. DR. TOTTER: It’s kind of loose now. Yeah too many wires around aren’t there. MRS. LARSON: I thought you were going to sit on the table. MR. LARSON: No, I’ll sit on the couch. All right. Very good. MRS. LARSON: You can have this chair. DR. TOTTER: Is this one functioning now? MR. LARSON: We can test it. [Microphone feedback] MRS. LARSON: Yeah, it’s fine. MR. LARSON: Very good. Well fine, John. Of course as I mentioned over the phone, I would just like to have an informal conversation with you on some of the principles of radio exposure and the health effects and the lack of health effects and so forth. So I think we can just go at this very informally and see, cover ground, I say in about an hour, hour and a quarter. Something like that should give me a good record of some of your ideas and findings throughout this. So are you ready to go? DR. TOTTER: Yeah. MR. LARSON: Do your regular focus in close and then give a, you know, manual focus it. It is actually, right manual focus. MRS. LARSON: Every time I touch it, it gets worse. MR. LARSON: So it’s right in focus now? MRS. LARSON: Yeah. MR. LARSON: Good. Well so every time you zoom it will remain in focus. MRS. LARSON: I believe so. MR. LARSON: All right. Well we’re all set then. Very good. I’ll start right in, John, and I’ll start with something like the date today and your name and then I’ll start asking a few questions and we’ll just have a normal conversation. DR. TOTTER: Ok. MR. LARSON: All right, today is February 1, 1989, and I’m privileged to have Dr. John Totter to interview today on the subject of radiation effects. So John would you please start out by describing how you got into this particular field of study, starting with some of your background and academic work. DR. TOTTER: Well thank you, yes, I had majored in chemistry at the University of Wyoming and got interested there in biochemistry, went to Iowa on a graduate assistantship and worked for C.P. Burge to finish my Ph.D. graduate work which was done in the field of amino acid metabolism. I finished there in 1938, taught for a year at West Virginia and then for a number of years at the University of Arkansas Medical School at Little Rock. There was much interested in the development of folic acid and spending its chemistry and biochemistry. MR. LARSON: At that time, was folic acid being investigated as a possible therapeutic agent? DR. TOTTER: As a possible therapeutic agent, but at that time, we had no dream of a connection with radiation, but when Ray Edwards came to visit our school, Ray was a member of the staff at the Oak Ridge Manhattan Project in the Chemistry Division. I think he worked with [Charles] Coryell and he was the one who started talking to us about radiation and so forth and it did occur to us that since the earliest human signs of radiation exposure were lowered white cell count, which was exactly what we were working with because folic acid is required for white cell production and so we began to think of it as a possible therapeutic agent for radiation sickness of various kinds. MR. LARSON: Oh yes. DR. TOTTER: We actually did quite a bit of work on that and I came to Oak Ridge then as a participant for six months to work with C.E. Carter in the Biology Division and did study the effects of folic acid deficiency on the production of the purines and pyrimidines which are required in the nucleus of the white cell. The absence of folic acid gives a syndrome in the animals that are susceptible to whole body radiation. So this was what connected with the work here and I thought I might be able to contribute something by putting these things together. MR. LARSON: Yes, so, but folic acid, did it ever reach the stage where it was used as a possible therapeutic agent for medicine for stimulation of white blood cells or were there other agents which turned out to be better? DR. TOTTER: Well, it has been used a lot and of course for nutritional anemia it is essential. You have to use it for that, but the picture got a little confused because it seemed to help for instance with anemia patients, although their deficiency is that of vitamin B-12 and not of folic acid, but it did stimulate production of cells for instance in anemia patients but didn’t cure the other defects for instance anemia. Nowadays one is clear where one should use one and one the other. In anemias of pregnancy, folic acid is the drug of choice and anemia, such as pernicious anemia you need B-12, but both things are necessary. MR. LARSON: Oh yes. I have heard of some complications of folic acid used in pregnancy anemia. Have you ever heard of that? DR. TOTTER: No, I have not been aware of that. I haven’t followed things recently. MR. LARSON: But of course with every drug there is a certain small percentage of perhaps odd reactions that you will get in various… Well good. That’s not too vital, but going from there how did you branch out then from your interests. DR. TOTTER: Well I came to, a couple years after I had been a participant, I came back to Oak Ridge and joined the Biology Division and started then working on attempting to follow the biochemistry of changes following irradiation into its earliest stage after radiation is possible to do. Of course you know, Waldo Cohn and Charles Carter were working on separation methods for the purines and pyrimidines which are the things that are effected, seem to be affected most by irradiation. The methods available then just weren’t good enough to track down to say a few minutes. You could see if you irradiated for example an egg, when the embryo was five days or so old, you could see changes following 5,000 rads [radiation absorbed dose] of exposure but you couldn’t measure it. You couldn’t measure them objectively, but you could see the actual changes in the embryo. So to follow up on that, we had to wait a long time for development of sufficiently good methods to understand what was going on. MR. LARSON: Yes, I noticed you started using some of the units of exposure and you mentioned 5,000 rads. In so much of literature and discussion today, we speak of five, 10 millirads and so forth. So there sometimes gets to be quite a bit of confusion because you’re off by orders of magnitude and there is a slippage there in the discussions. DR. TOTTER: You put your finger on what is, what has really been the difficulty of understanding radiation because our methods required very heavy doses at that time, near lethal doses which for a chicken or a rabbit would be around five or 600 rads, which is five or six grays by modern usage and 500 rads would be 500 million millirads so our methods were simply not fine enough to pick up the changes with millirads or a few rads and they only recently have begun to get that way and that probably accounts for much of the confusion and difficulty that people have for having a proper feel for the magnitude of these doses. MR. LARSON: Yes and let’s see before we get further there is, as they say there is a matter of, you go from rads to millirads, as your talking about these. Also to add to the confusion there would be some new units brought in such as sieverts and millisieverts and so forth. Is there any simple way to get these connected together in a common translation unit? DR. TOTTER: There are ways of course, but nothing is very simple about them. The gray and the sievert are similar. The gray is named after L.H. Gray, a British scientist who was active in radiobiology. It’s a flux measure, I mean an exposure measure. The sievert is similar to it, but it’s the absorbed dose from the exposure to a certain number of grays. One gray is as an absorbed dose is one sievert and these are about 100 rads, or 100 rems [roentgen equivalent in man] to connect the old ones, but they are all connected mathematically back to the energy units that the physicists use. MR. LARSON: Oh yes. DR. TOTTER: So they are consistent with all the units now used in physics, if we used the modern units. But the old original unit was the roentgen and it was close to what we call a rad now. The absorbed doses are, a rem would be equivalent to the exposure of a rad. We called, the ratio between the exposure and the absorbed dose is called the biological effectiveness, relative biological effectiveness. These were good terms, but they’re dropping out of usage quite a bit because they are going to the modern nomenclature. I don’t know how to make this simple for the ordinary listener. MR. LARSON: Yes, of course whenever we get into discussions in the media or even in Congress these things apparently become very hopelessly entangled and there is a lot of misunderstanding I think generated when you go from grays to sieverts to rem to rad and millirad and so forth. DR. TOTTER: It’s unfortunate, but it’s confusing for scientists as well as for other people. MR. LARSON: Fine, well I think that clarifies that part of this. Well let’s go on then to your further extension of your research work as you followed through. DR. TOTTER: When I came here to Oak Ridge in 1950, Dr. [Alexander] Hollaender was chief of Biology Division and he was pushing an interest in two things. One was called the oxygen effect and this was discovered by L.H. Gray, which is very simply when you expose something biological, a live animal or tissue to radiation in the absence of oxygen you get less effect than in the presence of oxygen. The difference is about two, two and a half fold. You get, this began to be considered a direct and indirect effect. The direct effect was suppose to be the actual collision of a particle or a gamma ray with an atom to expel an electron. The indirect effect comes about because the electron in tissue is absorbed by water and water splits into a radical and an ion when it accepts a straight electron. It’s the radicals that we are interested in because they are the damaging things to tissue. They can disrupt the nucleic acid in the tissue and give rise to mutations or all sorts of other trouble. About as I say, 60 percent of the effect seems to be the indirect effect of the electron knocked loose by the absorption of the energetic ray. MR. LARSON: Now with regard to this specifically, the affects you measure by counting mutations as one thing. DR. TOTTER: That’s one way. MR. LARSON: There are other things I suppose such as life shortening or what are some of the other manifestations? DR. TOTTER: Well… MR. LARSON: Or are there histological things that you can observe, quantitatively. In other words, how do you, what are some of the quantitative ways you can assess the effect of the radiation? DR. TOTTER: On biological material? MR. LARSON: Yes, on biological material. DR. TOTTER: Well you can, the counting of the mutations is an indirect way of measuring it. A more direct way is to extract the nucleic acid and count the breaks in the, find out how many strands of the long nucleic acid assemblies are broken by the radiation because if one of those purines or pyrimidines or sugars is on the strand, except for the electron, it makes it energetic enough to break, and then we lose viscosity if were measuring, that’s one measure of it, to measure the thickness, the longer the strands are the more jelly-like the solution is that has the nucleic acid in it. So we can measure the rigidity of it, or the fluidity of the gel and get some notion of the chemical damage done. We can follow those things in a variety of ways but the way that was in common use at that time, the most effective way was simply the survival of some small organism like a bacterium, expose it to radiation and measure how many colony forming units are left out of a given number exposed. So and that led of course that the physical people understood a lot more about radiation than biologists did. Biology was a pretty, biological objects were pretty crude things to work with in radiation. The target theory arose out of that. This I think had a great effect on what people believed later about the effect of radiation. The targeting business was very analogous to Dr. [Ernest] Rutherford and his colleagues’ means of measuring the volume of the nucleus of the atom. Shoot at the target, you don’t know how big it is, but if you know how many shots you put into an area, or volume, you can tell by the survival of the target itself, which in this case would be a bacterium or a virus let’s say, by shooting enough bullets into the volume where you know it is, you can tell how frequently you will hit it and then calculate it’s actual volume from the frequency of hits. MR. LARSON: Oh yes. DR. TOTTER: So this worked very well for small viruses. You could determine the size of the virus by how sensitive it was to radiation. And radiation being the gun you shoot the bullets with. MR. LARSON: Oh yes. A very neat technique there. DR. TOTTER: So that idea dominated that there is a target that you had to hit to get some effect. And that still dominates the connection, the thought about connection between cancer and radiation. People have used it to try to figure how many steps the cancer, the cell goes through before it becomes a cancer. It so happens that the frequency of cancer again, measured against the age of an individual goes up a sixth or seventh power of age. MR. LARSON: Oh yes. DR. TOTTER: And that has been interpreted as the single cell which eventually becomes a cancer requires 67 hits. Of course it may be the progeny of the cell, not the cell itself, but I think this has mislead people very seriously about the connection between cancer and radiation because if one takes the disease like cardiovascular disease and follows its occurrence with age, it will go through about the same, about the same relationship to age, about the sixth or seventh power of the age. The frequency of cardiovascular disease in a population goes at about the sixth or seventh power of the age. It doubles every five, six or seven years in frequency. There is nothing you could think of about cardiovascular disease that would lead you to believe there is a target in the cell that you have to hit to get cardiovascular disease. MR. LARSON: Oh yes. DR. TOTTER: You think about this with cancer because you think a mutation is what causes cancer. MR. LARSON: Oh yes. DR. TOTTER: If you had not this preconception, you might not think of that as a target at all. I believe this has misled people an awful lot about cancer. MR. LARSON: Now with regard to the mechanism of course the way radiation manifests itself in the bodies of animals or humans, one of them is shortening of life, one of them cancer, cancer production, and particularly a subset leukemia production is one, and let’s see are there any other manifestations that we look at? Or… DR. TOTTER: Well, there are early… MR. LARSON: …of course other mutations? DR. TOTTER: There are early manifestations to whole body radiation. You have to distinguish between partial body and whole body radiation because they behave differently. MR. LARSON: Oh yes. DR. TOTTER: And that is a point that I would like to get to. MR. LARSON: Fine. DR. TOTTER: You’re correct. You named several of the methods. In the early days, in the ‘50’s and ‘60’s, there was still a pretty strong belief, I think this was originated by Paul Henshaw, who was a pioneer in radiation work and was here during the war at Oak Ridge, that there was life shortening, what they called non-specific life shortening, that is the life shortening going to all causes of death that they are connected with old age, but so much work has been done with high cancer strains with mice that they now believe that at least in those all of the life shortening is due to the increase in the rate of cancer, in this age-specific rate of cancer occurrence. Yet in the earlier days when the strains in mice were not so, they concentrated on using strains that had high cancer rates, people seemed to see cardiovascular effects also. This I think is a very important point which I think has been lost sight of in recent years. That comes back to the point of the difference between partial body radiation and whole body radiation. That was discovered very early by the people working at the University of Chicago. You could shield part of the body and you could change the lethal dose of radiation. So there are hormonal effects that result from the radiation and again we come back to the problem of the time in the development of sciences which you do particular kinds of work. All of the work that had to do specifically with endocrine organs exposure to cancer were done with high doses because there was no way to measure your hormonal changes easily. These were developed by Rosalyn Yalow and her colleagues much later, radioimmunoassay. So the work if one goes back into the literature and searches for effects on specific endocrine organs all the doses were very high. Nothing was done with low doses because you would expect to find anything. You didn’t have the means to find it, except for thyroid. You remember Dr. [Jacob] Furth here worked a lot with thyroid cancers... MR. LARSON: Oh yes. DR. TOTTER: …and showed numerous ways to affect the incidents of thyroid cancer [inaudible] radiation, but that work has not been followed up. It’s been largely ignored by later work. We have been more interested in the target theory approach to what happens with cancer. We have lost sight of this effect which is also one of the ways you measure. You almost, I think almost everybody is familiar with the fact that if you get a fairly good dose of radiation to your head or abdomen, you get nauseated. My thought… MR. LARSON: By a fairly good dose you mean… DR. TOTTER: Well, this is in… MR. LARSON: …like three or 400 rads. DR. TOTTER: Oh, you always get it with that. MR. LARSON: Yeah. DR. TOTTER: Even 50 rads… MR. LARSON: Oh even 50. DR. TOTTER: …it’s quite frequent. If you look at the statistics of the thing, it’s somewhere between one and 40 or 50 rads, it would be almost sure to give you nausea, maybe as low as one rad. MR. LARSON: Is that right? DR. TOTTER: This certainly has to be a hormonal effect. My thought is that it affects the appetite and satiety centers in the [inaudible] and the lower part of the brain. It tells you, this is a hypothesis that I have been developing, tells you that you have eaten too much. MR. LARSON: Oh yes. DR. TOTTER: When you get a dose of radiation and you get nauseated, you don’t want to eat. That’s the main thing, the result of it because the body has been fooled into believing that it’s had an overdose of food. MR. LARSON: Oh yes. DR. TOTTER: I can’t prove that of course, but I think it’s correct because there was an experiment done by a physicist working at the University of Chicago. Around 1950, Leon Jacobson who later became dean of the medical school at Chicago and some of the other colleagues in which they exposed mice to gamma radiation from radium. They found to their very great surprise that the ones that received a tenth of a rad a day of whole body radiation from gamma rays lived longer than the controls. MR. LARSON: Let’s see. A tenth of a rad. That’s a hundred… DR. TOTTER: That’s a hundred millirads a day. A hundred and ten actually they received. Those that received 1,100, ten times that dose, didn’t have a shorter life. Some had a little bit longer life and some had a little bit shorter life, but their median age at death was about the same. Those that received higher doses, say 220, 2,200 a day did live a shorter life. They had a life shortened just as you mentioned a while ago and there were extra cancers. The cancer rate was higher, but not much was said about the other things except they did some chemical work on the carcasses of the animals after they were dead and found that the fat was low, fat content was low in the carcasses, the radiated animals. MR. LARSON: Now this was actually amounts of say only 2000 millirads? DR. TOTTER: Yes. MR. LARSON: That’s good. I can remember in the work of [Arthur] Upton, when he performed his experiments on genetic effects of life shortening and cancer production and so forth, he was using much higher doses, something like 50 to 500 rads, which is way out of this range. DR. TOTTER: Most of them were like that. These were single exposures though and remember that the Chicago experiment I’m talking about was a continuous exposure. It was so that the animals absorbed as much or were exposed to as much as several hundred rads before they died. MR. LARSON: Oh yes. DR. TOTTER: Of course it was partly on that basis that the Upton experiment was set up. We, the people who were concerned with the planning of the Upton experiment were quite a large number of people involved, calculated the number of animals they would have to have for single exposure to just a few rads and decided that there was either not the money or the facilities to handle that large number of animals. So that’s why the doses were higher. There was one set with 10 rad exposure and it’s a very interesting thing about those. They lived on the average the same as those who received no radiation. This is 10,000 millirads at a single exposure, but the lives of the few were shortened a little and the lives of the few were lengthened a little so that the average turned out exactly the same as the controls. Now I think this kind of confirms the experiment done by [Egon] Lorenz and his collaborators at Chicago in a way, but a curious thing about the Chicago experiment is that because they exposed the animals in a room that had radium in it they could never leave the controls in that same room. The controls had to go in a different room. A lot of people have said then that this was no experiment. You have no controls. So we will throw that experiment away, it’s no good because a few other investigators have been unable to duplicate that experiment… MR. LARSON: I see. DR. TOTTER: …and there are others who have been able to duplicate it and what has happened, very unfortunate I think from the stand point of the development of radio-biology is that people chose to discredit the experiment rather than to try to find out why there was a discrepancy between the laboratories. This was a terrible mistake in the long run because it will cost us enormously in misunderstanding of the cancer problem and the radiation problem, both. MR. LARSON: Well let’s see now. How would you summarize then the effect of the Lorenz experiment and its meaning? DR. TOTTER: I can give you my explanation of it, but you must understand that many people don’t agree with it. MR. LARSON: Yes. DR. TOTTER: My interpretation is that the low doses of whole body radiation and the effect on the endocrine glands was larger than any effect that cancer induced. What happened was that these animals were discouraged from eating because their satiety and appetite centers were affected by the radiation. MR. LARSON: By the low dose how do we define that? Ten rads? What do we call the low dose there? DR. TOTTER: The low dose is the 110 millirads to 1,100 millirads per day would be the low dose. MR. LARSON: Yeah. DR. TOTTER: Those, I say the endocrine effect was larger than any deleterious effect of the radiation and it reduced the food intake of the animals and because of that they lived longer. MR. LARSON: Right. DR. TOTTER: Now, it may have… MR. LARSON: But they’re given daily doses… DR. TOTTER: That’s right. MR. LARSON: …so that the accumulated dose… DR. TOTTER: Was very large. MR. LARSON: …was very large. If you gave one rad or 1000 millirads over a period of one month would be 30,000 millirads. So I’m sorry I interrupted there, but now what, I come back to the effect on the result of that and what your interpretation is. DR. TOTTER: Yes, well, I think when you go high enough in the exposure and by this you probably began with a single dose exposure of over 10 rads, 10,000 millirads, somewhere above that, then the deleterious effect on cancer and perhaps on cardiovascular disease exceed any effect that can be induced by a change in appetite. MR. LARSON: Oh yes. DR. TOTTER: So that’s what you see. You don’t see the other effects. When you go to these lower doses and the point to be made about that is that we could estimate the internal dose which would be to, equivalent to, now let me back up a moment. What I want to say is that the food produces the same kinds of radicals that radiation produces. That’s why the body mistakes the radiation effect for a food effect. MR. LARSON: Oh yes. DR. TOTTER: So we can tell then by the type of experiment that was done by Lorenz how much of those radicals are produced by food daily, ordinarily, without any exposure to radiation. It looks as if in the mouse it’s almost equivalent to one rad per day, 1000 millirads a day. That is the effect of food because those animals you see had not had their lifespan changed. The median lifespan was the same. You could expose them to that much rad a day continuously and it wouldn’t affect them. So that, well I shouldn’t say it’s equal to the internal dose that means the dose from one rad a day is so much less than the dose you get from food that it has no effect. MR. LARSON: Oh yes. DR. TOTTER: You could think back, make a comparison to almost everybody that has worked in radiobiology has started out believing that the only kinds of radicals the body sees are those produced by external radiation and internal radiation that we call background. And that’s something like 100, 200 millirads a year. MR. LARSON: Oh yes. DR. TOTTER: But actually we see a far, far higher number of those radicals from the food we eat. If you impose a dose of radiation on top of what we normally get from ourselves, not radiation, but the radicals that are produced by radiation, if we impose an external dose, then it’s the fraction of the total dose that’s represented by those that cause the increment of damage. It is a little damage piled on a lot that we are already handling. It is not equivalent to the background radiation. Its equivalent to hundreds of times the background radiation. So, I think it’s silly of people to look only at background radiation as the background which we normally suffer. That’s only a minute part of it. But the reason that people don’t accept that and don’t pay much attention to this possibility is that there is no way to measure that flux in the body, the flux of real radicals because there is no method that is sensitive enough to pick it up. You could not measure chemically the effects of 10 or 100 rads of exposure by looking at the tissues of the body. So we can’t see that. The nearest we have to a method is electron spin resonance and that you know is limited by the fact that water boils it. So in the presence of water you can’t measure that very sensitively, but there are people working now trying to measure indirectly. You can measure it indirectly in several ways and the flux is that, the flux of radicals produced from just metabolism of food is large, large enough to be equivalent to some matter of rads a day, external exposure. MR. LARSON: Well then, so, as I say, experimentally this is a very difficult field then to investigate. Now with regard to this then, the, when we come to examine differences naturally occurring say between sea level and say Denver and so forth, we get 100 MR difference in annual exposure and so forth, this doesn’t lie within probably the realm of being able to see whether it has a beneficial effect or a deleterious effect. It’s so small it’s blocked by internal things. So you would need much greater things. Therefore this brings up the, you know, the alarming response that people get to the minute traces that fell out from Chernobyl say in the arctic where the reindeer are now getting five or 10 more millirems than they would normally get and they feel that this will increase up the food chain up to double or triple that. But still it’s so small compared to… DR. TOTTER: You could miss a meal and handle all of that stuff. Just by missing one meal. MR. LARSON: Missing a meal would wash out the whole effect on this. So and actually studies of that type are likely to be at best misleading and even perhaps worthless. DR. TOTTER: It’s a terrible thing, Clarence, that we spend so much money on that kind of thing because that’s diverting money from other very worthy causes that have no, no difficulty like that with them. This is a matter of great concern to me and I hope becomes to other people that we can get back on the track to really understand this. There is almost no work supported now that relates radiation to endocrine function. You cannot get it through the study sections at the National Institute of Health. Now there was one person who was interested in that and this story is interesting because it amplifies my worry about the narrowness of each individual’s concentration in science on some specific problem. We’ve lost a lot of the generalness in science by concentrating so heavily and of course concentrating heavily on a narrow area does produce fantastic results, but somebody has to be back there to put all the narrow fields together somewhere along the way and we lack that pretty badly. Tom Dougherty you remember was in charge of the Utah project. MR. LARSON: Oh yes. DR. TOTTER: Tom Dougherty was an endocrinologist. He was an endocrine biochemist really. MR. LARSON: Oh yes. DR. TOTTER: And he knows also, or was interested in the white cell reduction following whole body radiation because he had studied stress and one of the signs of stress was a reduction in the white cells. That’s perfectly well know that a little bit of cortisone or something like that will reduce the white cells, stimulate the adrenals and the white cells go down. He told me many years ago that he thought that the small dose of whole body radiation would adjust the stress on the body which affected the adrenals and caused the reduction in white cells. White cells are sensitive to radiation and most people believe that they are killed and that’s why they go down. They don’t believe in the endocrine effect there. Now he’s the only one I know of who used relatively low doses of radiation and tried to study their effect. No one else, all of the other endocrine work with radiation that I know of starts at around 500 rad level… MR. LARSON: Oh yes. Five hundred. DR. TOTTER: …completely out of the range where one should work, and if you ask a radiobiologist now, he’ll say oh well those experiments were tried and they didn’t find anything. The reason was they were not working with sensitive enough methods and they were using far too much radiation. Most things, all need to be done again because the methods for depicting endocrine changes are now very much more sensitive than they ever were before. Dougherty was convinced that we were overlooking something like that, but he was not in the position apparently to carry on the work out there. They had a mission which was quite different from that. It was to study the effect of fission products, as you recall. MR. LARSON: Yeah. DR. TOTTER: He died a number of years ago. So far as I know he’s the only radiobiologist who really believed that we should look at the endocrine effects of whole body radiation. MR. LARSON: Now when it comes to these various levels of exposures we had a wonderful opportunity to study this in the Hiroshima, Nagasaki studies and in newspaper accounts and general accounts there is a good deal of, oh, misinformation, or lack or information or taking little pieces of that data and so there is, there seems to be a lot of confusion in the interpretation of these things and I have looked over some of these studies. The latest one I had access to was I think a 1977 tabulation and there were several things that if you examined it very carefully it stood out. If you take the cohorts which had lower levels, you know like below 100 rad, or below 200 rad or something, or below 50 rad and so forth, and examined the number of deaths from cancer in these various things, you get a very confusing picture. Depending on what cohort it was very evident, like, I don’t know, one of them let’s call it zero to 50 or the zero to 100 something like that, that showed, seemed to be a protection against cancer. Then when you got over the 200 of course the damage, there was an increase in there. Then if you take out the population as a whole and then just examined death and non-death, there seemed to be fewer people dying who have been exposed, just taking the population as a whole as compared to the controls. So there is an awful lot of confusion and you can almost pick out different cohorts and prove different things. I was wondering if you had any general feeling, has there been real sense made of this and what are the conclusions? DR. TOTTER: I think you describe the situation as most people see it pretty well. Those who believe that the low doses, the effects are under, what should I say, that we underestimate the effects of low doses, have a scenario as to explaining why. They don’t see the death so they create them with a pencil and paper and they do it in the following fashion. They say there is a five year gap between the real systematic set up of the Atomic Bomb Casualty Commission and the atomic bomb. They say that the people that were traumatized by the bomb, the survivors, the weaker ones died because of their exposure to various other things besides radiation and so yet only the stronger ones are present and that’s why you don’t see much effect in low doses because the population is not represented, the original population. My interpretation would be exactly the opposite of that. So I can create, I can save these people with pencil and paper just as the way they kill them with pencil and paper. If my idea is correct about the endocrine effect, one of those effects if your body believes you’ve had too much food, you have a short life. You know when you restrict the food, the life is lengthened. So it’s reasonable to say if you get too much food it’s shortened. Or if you get as much food as you would like to eat its shortened, but really the susceptibility to cancer and the susceptibility of cardiovascular disease are genetic things. Genetic things interact with the environment and one of the things that happens when you have plenty of food is that you have a short life and die from cardiovascular disease and you die early from cardiovascular disease. That reduces the next generation because these people have not time enough to reproduce fully. They died too young. That’s what happens, the ones that were exposed to small doses of radiation, the body interpreted this as extra food and they died of cardiovascular disease so that we have left a cohort which is richer than those that are going to die of cancer. This is just the opposite of what they say. So I can argue that the effect we are seeing is less than we should, or is more than we should see. That there should be a greater protective effect of those instead of having a curve which is high at low doses, we have one that should be even lower. There are no, is no way that we can decided objectively between these two things. So they both should be thrown out. MR. LARSON: Oh yes. DR. TOTTER: So what we see is exactly about right. We see no effect below 50 rads a dose, and above that we begin to see the extra cancers which you would expect. MR. LARSON: But right along with that there seems to be a lower mortality overall. As I remember the numbers at one point in ’77 there were say, you would expect say 22,000 deaths in this particular 35 year period, or whatever it is, and there were only 2,000 deaths. DR. TOTTER: That’s consistent with my interpretation. These people got extra food, I mean were fooled into believing that they had extra food so they didn’t need as much later and they should live longer. The rate should be a little lower. MR. LARSON: Primarily because there, they eat less and therefore their diet was optimum to their long range survival. DR. TOTTER: There is a terrible narrowness about people who are concerned working with cancer and those who are concerned working with something else. The narrowness I was talking about a while ago. I have a book in there produced by the U.S. Public Health Service that is so big, weighs 15 pounds and it is about cancer and nowhere in that book can find, can you find a word about the rate of cardiovascular deaths in those populations that are being studied. Familiar instances as talking about Utah which has the lowest cancer rate of any state in the continental United States. Nowhere does anyone say they also have the lowest cardiovascular death rate. Nowhere can you find that, but it’s true. It’s lower in proportion to the total death rate in exactly the same proportion that cancer is lower. I say this is an inherited factor and when one is low the other is low. What people should be looking at when they follow the atomic bomb casualties is both causes of death. One should look at cancer in relation to cardiovascular death. What you were saying a moment ago, they don’t die as often, they are lower on cardiovascular death because that is the main thing that fixes the lifespan. So we make terrible mistakes at not looking at the boundaries of, extending the boundaries of what we look at. I believe people would have a totally different conception of cancer if they always linked it to the cardiovascular rates that occurred in the same population. MR. LARSON: Yes, you know, of course, this is a little bit aside from our discussion, but of course in our civilization you know, the horror of a child or a person having to go without a meal is just something, how could any civilization be so cruel as to inflict that on them. In my interviews of people in particular who grew up in the Depression years, including myself, money was so scarce one common way of saving money was to eat two meals a day and you would be surprised that at least four Nobel Prize winners during that particular period saved money by eating two meals a day. They are now all in their 80’s, but there are all kinds of these factors which enter into the lifespan. So it gets so confusing. DR. TOTTER: That’s a good, a particularly good one you mentioned because I’ve looked for information on our average food intake during the Depression and the best I can find, one survey was made and it was about 10 percent lower on the average than on either side of the Depression. So the people who were born in the decade from 1930 to 1940 are just now beginning to die at a fairly good rate and in the next two decades we’ll find out if they on the average lived longer than the people before. I think they will. MR. LARSON: Yes, well that’s rather interesting because that was very common, all of the schools, graduate students and college students, they all had that same problem of trying to live on 30 and 40 dollars a month during those days and as they say there were very famous people here who… DR. TOTTER: People talk about the Baby Boom, actually this lack of food during the Depression is part of the reason for the reduction in birth rate. The Baby Boom is a return to the birthrate that they had before the Depression. One can find other populations that were starved like the Netherlands population I think in ’44. The birthrate dropped to zero while they were in that famine and then it returned promptly after the famine was over. MR. LARSON: Oh yes. DR. TOTTER: So I think they should talk about the birthrate depression rather than the Baby Boom. MR. LARSON: Yes. That’s a very good point. Now with regard to other investigations that you were in at the time, oh, I wanted to get a little discussion on the subject of hormesis, is that the way to pronounce it? DR. TOTTER: Hormesis, yes. MR. LARSON: Number one would you define the term. At least in one dictionary I didn’t even find it, but what is the definition of the term? DR. TOTTER: The definition of hormesis is the effect that a toxic agent has at low doses that seem to stimulate something. Arsenic is a very good example of it. Low doses of arsenic are quite stimulating to people and horses. Many a horse trainer made his money by feeding his horses arsenic just before he traded him. Their coat gets sleeker, they look healthier and they’re more active. Of course if you give more, it kills them. That low dose effect of toxins can improve things, to seem to improve things is called hormesis. MR. LARSON: Oh, all right, fine. DR. TOTTER: We’ve already discussed it to some extent because experiments of Lorenz were the first example in animals of a hermetic effect of radiation. Lengthening of the life is regarded as a hermetic effect. MR. LARSON: Yes, I believe there are quite a number in nutrition. Cobalt I believe among the sheep in Australia or something. I think they found that there were certain areas that were low in cobalt and it was very deleterious and when they added cobalt to the feed there was a… DR. TOTTER: There is a very interesting story about that. I don’t know if you remember Harry Stout. MR. LARSON: Oh yes. DR. TOTTER: He was the one who showed them how to cure that cobalt deficiency. MR. LARSON: Oh, is that right? That I did not know. DR. TOTTER: He told them to use the neural nuts that you have on crescent wrenches you know. MR. LARSON: Yes. DR. TOTTER: That’s a cobalt containing steel. MR. LARSON: Yes. DR. TOTTER: Those wrenches are made of that and that little nut they poked it down the throat of the sheep and it stays in the forestomach and it doesn’t get lost. It doesn’t get out of there and slowly erodes and frees the cobalt at about the rate sheep needed. MR. LARSON: So you don’t have to keep adding it. DR. TOTTER: No. MR. LARSON: That’s fantastic. I believe that at least there is a fad now that adding selenium is good for… I don’t know whether that’s considered a fad now or not. DR. TOTTER: It is a fad because the fad people have picked it up. It’s a nutritional fad. I worked with selenium when I was an undergraduate. I was at Wyoming where selenium toxicity was very bad. MR. LARSON: Of course, the toxicity is very bad. DR. TOTTER: Yeah. MR. LARSON: But is there a small amount which is… DR. TOTTER: A small amount because it is required for, it’s very interesting how that fits into the discussion. It’s required for oxidase which oxidase is, which oxidizes glutathione with hydrogen peroxide. It’s a requirement for that enzyme and that enzyme is what reduces the last traces of radicals in places where they are not wanted because the radicals will affect the glutathione. So, selenium actually reduces the free radicals that I think are the cause, the root cause of cancer in… MR. LARSON: Oh yes. Well that, of course things like vitamin D, overdoses of vitamin D can kill you, kill children, but we need certain amounts. DR. TOTTER: That’s right. MR. LARSON: There are a lot but the hormesis effect of radiation is, there seems to be some evidence, but there is not enough work really to really define it. I might ask a question of you. For instance, if you had your choice of living in an entirely free, it would be impossible, but an entirely free radiation from birth, or one which had normal radiation, which would you chose? DR. TOTTER: I think there is nothing to choose between… that brings an important point about the definition of hormesis that I didn’t touch on. The person who is promoting hormesis mostly in this country believes that it is required. Radiation is required for the body, that is, it is a nutritive to the body. What I am claiming is a little different. It is that radiation fools the body into believing it has received nutrition. MR. LARSON: I see. Your mechanism is different from that. DR. TOTTER: It’s a little different. I think that the bad repute that it has comes from the idea that it is nutritive and so I try to combat that idea and say, “No, it just fools the body into believing it has had some food.” MR. LARSON: Oh yes. DR. TOTTER: I believe people would accept that easier than they would accept that radiation was good for them. MR. LARSON: That radiation was good for people. So in other words you don’t think that if a person had a choice between living in an absolutely free radiation atmosphere for his life, he wouldn’t necessarily suffer from it. DR. TOTTER: I don’t think he would, but there is a school of thought that quite possibly the random radiation effects have something to do with the biological clocks, setting the biological clock. And I have no particular strong opinion about that, but I doubt it. It was one of the first things that was suggested for effective radiation and it was shown to be wrong in that particular instance. There is still a possibility that it has something to do with setting clocks. MR. LARSON: Yes, well a natural radioactivity of potassium was thought at once to have some role in the heart. DR. TOTTER: Yes, that’s the one I was speaking... MR. LARSON: Was that one you were speaking of? Fine. Okay. Well, let’s see. How would you summarize the, we can start in now with your present writings and investigations and so forth. What are your present main interests? DR. TOTTER: Well, I am trying to learn enough about demographic techniques to show by some methods, which people haven’t thought of or haven’t tried, that there is really no real change in incidents of cancer over the years. I guess that’s a little bit the wrong way to say it. What I am trying to show is that cancer is a normal cause of death and it is inherited in the same fashion as other causes of death in old age like cardiovascular disease. That is we have a certain amount of energy which we get from our food and a certain rate that we can use the energy. It’s used for what purposes: It keeps us warm, it enables us to find more food, exercise, to work, enables us to reproduce, and part of it is used for maintenance of our bodies so that these functions will go on. We, by natural selection, always tend to decrease deficiency because we compete with other creatures or each other for the use of the available food. There is currently a pretty strong belief that the reason we die, we age and die is because it’s more efficient in the long run for that to happen then to try to use so much energy for maintenance that we live forever. You can very easily show thermodynamically that that is true. It’s better to make new people than it is to try to keep the old ones going. So I believe that the whole thing is very rationally worked out. And that we will find that cancer is just another part of that system. What I want to be able to show is that you cannot interpret cancer as an accidental cause of death, the vast majority of it, a small amount perhaps, but it would be very small. MR. LARSON: Perhaps less than one percent or something. DR. TOTTER: Yeah, something like that. In special cases, maybe four or five percent, but normally one percent or less. I cannot find incontrovertible proof of that, but that’s what I’m shooting for. MR. LARSON: Oh yes. DR. TOTTER: Now, the, when I try to talk to people who are interested in cancer about natural selection, they think I’m crazy. It’s almost impossible to get them to think of this in terms because they believe that the bell shaped curve which represents our rate of dying, frequency of dying is not a normal curve in most cases. It’s a distorted normal curve and I’m saying that if we were living in a neutral environment it would be normal. The fact that it’s distorted shows that we are being selected very rapidly for a different longevity. That’s why the curve is not normal, but if it is a normal curve, or suppose to be a normal curve in a neutral environment, there are two ways to look at it. One is that the variance is due entirely to the environment. We all inherit a specific lifetime and the varying environment produces the bell shape of the curve and I believe that the common, it’s commonly accepted among cancer researchers that that’s the case. It’s all in the environment. You inherit a specific lifetime and everybody inherits the same one. That seems silly to me. Most of the variance in that curve is variable I think and it’s over this point of whether our lifespan is largely inheritable or largely environmental is the crux of the argument. Now I think it’s very easy to show that much of it must be inheritable and to talk to population biologists I think you’d get no argument, but they’ve never talked to the cancer people and the cancer people never talked to them. That’s the difficulty. MR. LARSON: Yes. Well now the cancer people are overwhelmed by the environmental factor of smoking of course which is, that’s such a big and unusual thing. Probably it is disputed how big the factor is, but undoubtedly it is a big perturbation in there. But otherwise, are there other, what are some other environmental factors which supposedly increase cancer rate, or affect cancer rate that are environmental? DR. TOTTER: Well, its’ perfectly clear that environment affects specific cancers. Now there is no question that we have dropped in our number of stomach cancers and I’m not even sure that smoking has done part of that, but that rate is, if you suggest that rate it immediately raises a howl of protest because smoking affects the motility of the stomach and it reduces tension and tension may be cause of acid production which may be the cause of stomach cancer. You can make out a possible scenario for that, but irrespective of that while the lung cancer goes up the stomach cancer goes down until it’s nearly disappeared. People will not connect those two things. They absolutely refuse to because they think that the environment produces accidental cancers one way or another. And any one that goes down, you’re just lucky because you changed the environment in some way you don’t know about. If cancer susceptibility is inherited then if one cancer goes up another has to go down, or some others have to go down because you’re inheriting, you have 20 percent of the people can get a cancer, can die of cancer, let’s say. Well if you get a lot of lung cancer then the other cancers must be less than that to make the 20 percent, but if we’re dependent on an oncogene scattered somewhere in our tissues and we can’t have a cancer unless there is an oncogene there. All right, it’s changing environment is not going to affect the people that don’t have the oncogene. Some of them, it’s like blood groups. Some of them inherit the oncogene for colon cancer and some don’t. I don’t know what causes the stimulation, or gets those to change to become active and it may be like something people think. I’m inclined to doubt the target theory even for that, but, simply because it’s misleading us in other respects, but if there is such a thing as cancer in one spot withdrawing general resistance to cancer in some fashion, not just local, but general, then having one cancer effects the rates of other cancers. So, I’m trying to think of that. What I am mostly trying to do is not settle on any hypothesis that will channel my thinking as I believe others have channeled theirs so they can’t get out of a hypothesis that’s no good. MR. LARSON: Your microphone just dropped down to your pocket. Now come back to, just press it on. Come back to that theme. There of course has been a lot of pressure in recent years about the synthetic things that are put into our atmosphere, the food chain, the insecticides, some things that are put into soil and so there are all kinds of new sources of carcinogenic compounds in particular insecticides and herbicides and so forth and so now large stores advertise the organic grown. Bruce Ames has pointed out that the natural, in order for a plant to survive through evolution it has had to synthesis its own insecticides in order to survive against insects and in many cases those insecticides are just as carcinogenic as synthetic ones, more so because you can sometimes tailor them to avoid these. I was wondering if you had any general feeling about these things that we add to the environment to avoid carcinogens. How would you classify the various things and their dangers? DR. TOTTER: Well I’m quite sure we are overly concerned for the short term but we should be concerned for the long term. We have to know what these things do and how fast they leave and so forth and we don’t do that well enough. I went through that experience myself on our farm when I was a boy. I use to help spray for the cotton bollworm and the first thing we could get ahold of was the lead arsenic. That killed the worms all right if you got it there fast enough. MR. LARSON: Oh yes. DR. TOTTER: But years later when we tried to grow cantaloupe there was too much arsenic in the soil. MR. LARSON: Yeah. Of course arsenic, copper arsenic was very commonly used. DR. TOTTER: Very commonly used in the old days. MR. LARSON: Paris Green. DR. TOTTER: Yeah, Paris Green. MR. LARSON: The green was due to the copper. DR. TOTTER: We kept a pound or two of that around all the time when I was a boy and I was warned against how poisonous it was. MR. LARSON: So of course these modern ones usually don’t have metals… DR. TOTTER: Don’t have permanent elements. MR. LARSON: …toxic metals in them and are synthesized in such a way, actually I believe there are certain carcinogens in, what is it? Oh, mushrooms, and in peanuts, and so forth. DR. TOTTER: Oh yeah. There are numerous… They are everywhere. MR. LARSON: They are natural. DR. TOTTER: Bruce’s point is that we probably owe most of our cancers to those, but I think he’s coming more around to my point of view that it’s internal and not from external agents that we get them. MR. LARSON: Oh yes. DR. TOTTER: I think that we owe the fact that we have to have cancer to the economy of nature. We could avoid that cancer but we would lose something else that we have to have if we did. So it’s cheaper to have the cancer than it is to build a wall against other things. The thing, it’s a very simple proposition and any thermodynamicist would tell you that something like this has to be correct. If you had to produce the protein enzymes to combat all of these things that Bruce Ames was talking about, it would be more expensive than having a few cancers. So you allow enough of those radicals to escape destruction so that you can use them to destroy these strange compounds that come in and that’s exactly the way it is. The peroxidase as you see all produce those radicals and the advantage of a radical is nonspecific. It will attack anything organic and you don’t have to have a specific enzyme for it. A peroxidase is a very nonspecific enzyme but a trypsin or a chymotrypsin is a very, very specific enzyme it will only work on a certain kind of bond. So you see, the balance of nature makes you produce both kinds of these things because it’s energetically more economical to do it that way. So if the people who are seeking complete prevention of cancer are probably going to kill us all... MR. LARSON: Oh yes. DR. TOTTER: …if they ever find something then. I think that we do not take into consideration enough what the real economy of nature is. MR. LARSON: Yes, well of course, actually, I don’t know what the exact figures are but you hear these figures bandied about in the last 50 years. We have probably increased the lifespan of people 15 to 20 years. It’s throwing our social security plans all out of whack and everything else and of course that is gradually going to reach a plateau of course. DR. TOTTER: A plateau at some point. MR. LARSON: But there is no doubt about it being a fantastic increase in the lifespan in the last 40 or 50 years. So, it isn’t exactly that the appearance of chemicals and radiation are killing our people off at a great rate. The numbers just don’t bear that out. DR. TOTTER: This brings up another point that I might make with you. You talk about increasing the lifespan. We get this from the life expectancy tables and it’s perfectly true, but if you look at what the maximum lifespan is, well, let me back up a moment. The cancer institute people will tell you that, the people that are working with the demographic figures, that cancer in men has increased. I should say the age adjusted rate in men has increased. For women it has gone down slightly. If you look at the real data, the fact is the fraction of people dying is the same in both sexes. MR. LARSON: Oh, is that right? DR. TOTTER: Yeah. Nobody ever tells you about this. MR. LARSON: I’ll be darned. DR. TOTTER: And the reason, the odd reason that the men are going up and the age adjusted in women are going down is because women have actually increased their lifespan and men have not. So the cancer spread is over a larger number of years and the rate is down. So the fraction stays the same. MR. LARSON: The fraction stays the same. DR. TOTTER: These are the kinds of crazy things… MR. LARSON: You really have to examine the figures carefully in order to come to a logical conclusion about these things. DR. TOTTER: That’s right. That’s right. MR. LARSON: That’s very important. Incidentally, just happened to think, how do your views on radiation coincide with our mutual friend Merril Eisenbud? Merril’s been working on this field of radiation for a long time. DR. TOTTER: Merril is a pretty sound scientist, but I don’t, I haven’t talked to him for a long time. I am sure he’s much less concerned about the cancer than other people are in radiation. Is that correct? MR. LARSON: Oh yes. That’s right. DR. TOTTER: So, they probably do coincide. MR. LARSON: In fact, he’s very concerned about the, you know, the irrational fear of the cancer and these extremes that are being used to clean up these minute traces of radioactive materials, spilled uranium and so forth and so on which is entirely nonproductive use of money. DR. TOTTER: That’s the biggest problem that faces us for the next few decades. I often wonder whether the people who are doing these things have a real hidden agenda. Everyone knows that the problem comes because there are so many people and we also know, I think realists don’t believe that you can change that. MR. LARSON: That’s right. DR. TOTTER: But the others, some of them may be trying these things just to bring us to the edge of some kind of a catastrophe that will reduce population. I wonder how many of them know that they are doing this and how many are doing this because they have a single track mind; only think of one thing at a time. MR. LARSON: Well, that gets to be very discouraging. I see some of these things. The clean ups you know, these are going to cost $22 billion to do this and so forth. At the most it might possibly save one life, although there would probably be 20 lives killed by bulldozers and so forth in doing this. DR. TOTTER: The clean-up will surely kill more. MR. LARSON: So, and it’s sort of an insanity that is going on in these extreme things. We’re right in the middle of it and it apparently has great momentum. There is also a selfish stand point. You know when The Great Society proposed the poverty programs the human cry of all the sociologists coming to Washington, “There’s money in poverty,” was the great cry of the times. Today, there is money in scaring people to death. That money is getting into the billions and billions all the time. That undoubtedly affects the people on this. So we’re faced with trying to get some rationality into hazards of all types, radiation, chemicals, and insecticides and so forth and so on. But there is no very simple problem. DR. TOTTER: It’s like we’re fighting a losing battle too because what you’re saying basically is to get people to think more quantitatively and half the spending for arithmetic has gone down in the schools, and we’re not improving. MR. LARSON: That’s right. Then of course the arithmetic, very little arithmetic incorporates the statistics and probabilities into them these days, which are the two basic things that we use all our life in order to evaluate the meaning of numbers, but that’s left out. Incidentally who is in the Washington area, who are some of the more sensible people involved in status statistics or biometry and so forth and so on these days. Do you know any? DR. TOTTER: The best statistician that I know of in the National Cancer Institute are Nathan Mantel, and if he’s still active, and an epidemiologist, they have a good epidemiologist there, but I’m not sure if he’s still active. I can’t think of his name now, but these are not the people who determine what is said, now there is an ex-member who I think is way off and that was Marvin Schneiderman. He believes in as John Bailer, believes in the age adjusted values for cancer which are really misleading and should be abolished. MR. LARSON: Oh yes. DR. TOTTER: So, Marvin Schneiderman is still active, but he is no longer with the National Cancer Institute. MR. LARSON: Oh yes. DR. TOTTER: He’s a good statistician but an awful poor biologist. MR. LARSON: Oh yes. DR. TOTTER: I think that’s the problem. MR. LARSON: You have to tie those together in order to get some very good sound opinions. DR. TOTTER: I don’t know the real answer to that question, but almost nothing that comes out of the American Cancer Society or the National Cancer Institute for the public’s consumption or even out of the National Academy of Science, their nutrition book on cancer is pretty bad. MR. LARSON: That brings me to the final subject that I wanted to ask you about and that is this book by, that was put out by the National Academy on radon. Did you see? It’s a fairly thick book, maybe 300 pages or something like that. It’s not very easy reading because it’s got a collection of different things. It’s awfully hard to read, but apparently out of that book came this statement, you know, where we have 2,000 deaths per year from radon. DR. TOTTER: That’s crazy. MR. LARSON: That is such a crazy statement. So I went into the book and tried to find the rationale. The book doesn’t have the data or the facts in there. And I was wondering if, have you come into any discussions as to what they arrived at, what the data is and so forth. DR. TOTTER: I know a little bit about the original background, but I don’t know much about anything recent. Again I like to call on Perry Stout for pointing out, what’s the matter with that problem. He says he looked very carefully at the lifespans and so forth, or what he could find out about them on burrowing animals who live in a much higher radon concentration than we do. He never found any lung cancers in any of these burrowing animals. MR. LARSON: That’s an interesting point. DR. TOTTER: Burrowing animals you know that live in those tailing deposits where the radon concentration must be awful high and they maintain a population without any trouble at all. I think this is biological knowledge enough to be skeptical about anything said about radon and lung cancer and ordinary population. MR. LARSON: Of course, you know one of the things that really bothers you, they sell these kits you know, millions of dollars for these kits. Everybody was buying a kit; put them in a corner of the basement. So they put them there right where it would be a stagnant area in the corner of the basement… DR. TOTTER: Where nothing moves. MR. LARSON: …where nothing moves… DR. TOTTER: Nobody gets to it. MR. LARSON: …and nobody ever gets to, and then they take the readings there. You know the readings should be taken in the average living space. I would bet that for every hundred positive readings that you would get by the basement, you would get only one in the living space. DR. TOTTER: It would be something like that. That’s about right. MR. LARSON: So, I would say just as a start of that, if there is any effect whatsoever as, it’s probably 100 to one off. DR. TOTTER: I tell you what you might do just for your amusement sometime along that line, the fellow who really is behind all the present scurry about radon, that fellow [Victor] Archer who had charge, Archer and [F.E.] Lundin I think were the original pair that had charge of the original USPHS’s [U.S. Public Health Service] radon studies. Archer has written a paper somewhere about ’82 or ’83 in the Nuclear Safety Journal, Journal of Nuclear Safety. I think you’re familiar with it. It’s published here. MR. LARSON: Oh yeah. DR. TOTTER: Bill Cottrell used to edit it. It’s right next to one of mine in there and I don’t think everyone sees that Journal outside the very specific people involved in nuclear reactor safety which you’d do well to read because it tells you kind of what makes Archer tick. MR. LARSON: Oh yeah. DR. TOTTER: Just a statistical study on background in various diseases. It’s absolutely weird, a weird story. If you look at that it will give you an idea of how to judge the architect of the whole radon problem. MR. LARSON: Oh yes. DR. TOTTER: I don’t know if this should go on there or not, but there was a lot of politics involved in that before you came to Washington. It inundated me quite a bit. MR. LARSON: This is edited. This tape is edited. DR. TOTTER: If you don’t like it, take it off. MR. LARSON: It’s whatever. DR. TOTTER: Okay and it really started, the real trouble started in ’59. That’s when the industrialist from California was trying to, was chairman of the AEC [Atomic Energy Commission], what was his name? MR. LARSON: That was before [Glenn] Seaborg. DR. TOTTER: Just before Seaborg. He was only there for a year or so. MR. LARSON: Yeah. DR. TOTTER: It doesn’t matter. I don’t think he was at fault, but it happened under him I think because the production people and the reactor people felt that the biologists were cutting in on their promotions because they made everything look unsafe. So they decided to get the biology out of the AEC and they, he found out rather quickly that there had to be an internal safety operation. So they flipped the biology division into operational safety and biology research, and then they said that biology research would go to USPHS. They were far along on their bickering. The Bureau of Rad[iological] Health was created out of a cadre of unemployed or nearly unemployed uniform personal from USPHS. They expected to inherit $80 million or so, but all of a sudden the Joint Committee stepped in and said you can’t do this, they don’t have any competence. You better keep that in the AEC. That’s what saved the research program when Seaborg came, but then the Congress told us we had to get together with this Bureau of Rad Health, had to do things jointly, but all they were interested in was taking the good part of our program and letting the part they didn’t want go. It was a political thing from then on. They wanted our money. MR. LARSON: Oh yes. DR. TOTTER: The way they tried to get it was to back sub rosa I think largely, the claims of everybody who was anti-AEC. Now I know that happened because when [John] Gofman went off, fired his rocket, I talked to the deputy director who was a neighbor of ours at the Bureau of Rad Health and I talked at some length about I thought, frankly thought that Gofman was off his rocker. He’d blown a gasket and within 24 hours Gofman knew everything I had said. MR. LARSON: I’ll be darned. DR. TOTTER: That came to me through I think one of the deans of Minnesota who heard Gofman’s talk shortly thereafter that in which he quoted a number of things that I had said to this member of the Bureau of Rad Health and he sent me a transcript. They had tape recorded the talk and I recognized these things that I had said across my back fence. MR. LARSON: I’ll be darned. DR. TOTTER: So I sent a copy of the transcript to that guy. He wrote a long letter of apology and a letter to Gofman saying, “Old Totter didn’t really mean these things.” But that’s what has happened all along. There has really only been one or two people in there who refused to attack everything that the AEC did because they were sounder scientists than the others. They were not politicians and Billy Mills was one of those. He had taken his training with [inaudible] Goldmeier and he never joined in that, but most of them were dead set on undermining the AEC in any way they possibly could. That still goes on. It’s inherited. Those people are all gone now. They are no longer there, but some of that bitterness over the loss of that $80 million is probably what is going to carry this fight on. MR. LARSON: Oh yes, and it actually still permeates into that report at the National Academy Foundry, that insane recommendation that several thousand deaths are due to radon coming into basements, which is so ridiculous. Well that certainly adds a lot to the background of this whole thing. Well fine. Are there any other points that you think are worth mentioning here? We have covered a lot of ground here and a lot of background and a lot of valuable information. DR. TOTTER: I see there is a meeting going to be held shortly on the peer review system. MR. LARSON: Oh I hadn’t heard about that. DR. TOTTER: I just saw something about it. They were going to talk about who the peers are and how the reviewers, editors and reviewers, how the editors get their reviewers and so forth. It’s an important meeting, but I don’t know whether the right people will attend. MR. LARSON: I didn’t, that somehow went by, I think there was a little squib in Science about it, but I didn’t really read the article. So, of course one of the, a lot of these peer review systems get to be old boy networks. You know, they are repeated, and repeated, and repeated. The peer review system is a perfectly logical thing, it’s only the makeup and how it’s administered. DR. TOTTER: There needs to be some way of clearing it up every once in a while. I don’t know anything better, but it is in that shape and I would say the epidemiology business is the worst of the lot. Only the ones who have an established name can, are allowed to publish anything. MR. LARSON: And particularly anyone who tries to get in different points of view there are just immediate, in fact I have heard some awful stories, this is off the record. There have been definitely in some of the agencies including the DOE [Department of Energy] and even before that ERDA, somebody will want to make a study, you know, of certain things, good scientists and essentially the message comes through loud and clear, “Well, fine, make this study, but make sure the conclusions are this.” They don’t say it exactly in that way, but it will raise the eyebrow and a few other things. That message gets through loud and clear. So you get, there is an awful lot of studies that come through in this particular… DR. TOTTER: I got told in a letter from a fellow who I actually asked to review my paper said, “Why would you take away the hope for these people?” MR. LARSON: This is the sort of thing… Well, but these are all the tough problems. DR. TOTTER: Yeah. MR. LARSON: But as I say, I always say as long as there is all this money scaring people to death, we are going to have business. DR. TOTTER: We sure are. MR. LARSON: Well thank you very much, John. I sure appreciate this. DR. TOTTER: You’re welcome. MR. LARSON: You’ve really been a great help in giving this very valuable background. DR. TOTTER: I hope you get something worth keeping. MR. LARSON: Well this, I go back… [End of Interview]
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Title | Pioneers in Science and Technology Series: John Totter |
Description | Oral History of Dr. John Totter, Interviewed by Clarence Larson, February 1, 1989 |
Video Link | http://coroh.oakridgetn.gov/corohfiles/videojs/CL_Totter.htm |
Transcript Link | http://coroh.oakridgetn.gov/corohfiles/Transcripts_and_photos/GMU-Clarence_Larson_Interviews/Totter_Final.doc |
Collection Name | Clarence Larson Collection |
Related Collections | COROH |
Interviewee | Totter, John |
Interviewer | Larson, Clarence |
Type | video |
Language | English |
Subject | Atomic Bomb; Cancer; Manhattan Project, 1942-1945; Radiation; |
Organizations/Programs | Oak Ridge National Laboratory (ORNL); |
Date of Original | 1989 |
Format | flv, doc |
File Size | 363 MB |
Source | George Mason University, Fairfax, VA |
Citation | Clarence E. Larson Science and Technology Oral History collection, Collection #C0079, Special Collections & Archives, George Mason University Libraries. |
Location of Original | Oak Ridge Public Library |
Rights | Copy Right by the City of Oak Ridge, Oak Ridge, TN 37830 Disclaimer: "This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that process, or service by trade name, trademark, manufacturer, or otherwise do not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof." The materials in this collection are in the public domain and may be reproduced without the written permission of either the Center for Oak Ridge Oral History or the Oak Ridge Public Library. However, anyone using the materials assumes all responsibility for claims arising from use of the materials. Materials may not be used to show by implication or otherwise that the City of Oak Ridge, the Oak Ridge Public Library, or the Center for Oak Ridge Oral History endorses any product or project. When materials are to be used commercially or online, the credit line shall read: “Courtesy of the Center for Oak Ridge Oral History and the Oak Ridge Public Library.” |
Contact Information | For more information or if you are interested in providing an oral history, contact: The Center for Oak Ridge Oral History, Oak Ridge Public Library, 1401 Oak Ridge Turnpike, 865-425-3455. |
Identifier | TJCL |
Creator | Center for Oak Ridge Oral History |
Contributors | McNeilly, Kathy; Stooksbury, Susie; Reed, Jordan; |
Searchable Text | PIONEERS IN SCIENCE AND TECHNOLOGY SERIES ORAL HISTORY OF DR. JOHN TOTTER Interviewed by Clarence Larson Filmed by Jane Larson February 1, 1989 Transcribed by Jordan Reed MRS. LARSON: Yeah. MR. LARSON: Start in reasonably close. Good I think we’re all set there. Just to make it safe, I’ll put these a little bit closer, a little bit more [inaudible]. DR. TOTTER: It’s kind of loose now. Yeah too many wires around aren’t there. MRS. LARSON: I thought you were going to sit on the table. MR. LARSON: No, I’ll sit on the couch. All right. Very good. MRS. LARSON: You can have this chair. DR. TOTTER: Is this one functioning now? MR. LARSON: We can test it. [Microphone feedback] MRS. LARSON: Yeah, it’s fine. MR. LARSON: Very good. Well fine, John. Of course as I mentioned over the phone, I would just like to have an informal conversation with you on some of the principles of radio exposure and the health effects and the lack of health effects and so forth. So I think we can just go at this very informally and see, cover ground, I say in about an hour, hour and a quarter. Something like that should give me a good record of some of your ideas and findings throughout this. So are you ready to go? DR. TOTTER: Yeah. MR. LARSON: Do your regular focus in close and then give a, you know, manual focus it. It is actually, right manual focus. MRS. LARSON: Every time I touch it, it gets worse. MR. LARSON: So it’s right in focus now? MRS. LARSON: Yeah. MR. LARSON: Good. Well so every time you zoom it will remain in focus. MRS. LARSON: I believe so. MR. LARSON: All right. Well we’re all set then. Very good. I’ll start right in, John, and I’ll start with something like the date today and your name and then I’ll start asking a few questions and we’ll just have a normal conversation. DR. TOTTER: Ok. MR. LARSON: All right, today is February 1, 1989, and I’m privileged to have Dr. John Totter to interview today on the subject of radiation effects. So John would you please start out by describing how you got into this particular field of study, starting with some of your background and academic work. DR. TOTTER: Well thank you, yes, I had majored in chemistry at the University of Wyoming and got interested there in biochemistry, went to Iowa on a graduate assistantship and worked for C.P. Burge to finish my Ph.D. graduate work which was done in the field of amino acid metabolism. I finished there in 1938, taught for a year at West Virginia and then for a number of years at the University of Arkansas Medical School at Little Rock. There was much interested in the development of folic acid and spending its chemistry and biochemistry. MR. LARSON: At that time, was folic acid being investigated as a possible therapeutic agent? DR. TOTTER: As a possible therapeutic agent, but at that time, we had no dream of a connection with radiation, but when Ray Edwards came to visit our school, Ray was a member of the staff at the Oak Ridge Manhattan Project in the Chemistry Division. I think he worked with [Charles] Coryell and he was the one who started talking to us about radiation and so forth and it did occur to us that since the earliest human signs of radiation exposure were lowered white cell count, which was exactly what we were working with because folic acid is required for white cell production and so we began to think of it as a possible therapeutic agent for radiation sickness of various kinds. MR. LARSON: Oh yes. DR. TOTTER: We actually did quite a bit of work on that and I came to Oak Ridge then as a participant for six months to work with C.E. Carter in the Biology Division and did study the effects of folic acid deficiency on the production of the purines and pyrimidines which are required in the nucleus of the white cell. The absence of folic acid gives a syndrome in the animals that are susceptible to whole body radiation. So this was what connected with the work here and I thought I might be able to contribute something by putting these things together. MR. LARSON: Yes, so, but folic acid, did it ever reach the stage where it was used as a possible therapeutic agent for medicine for stimulation of white blood cells or were there other agents which turned out to be better? DR. TOTTER: Well, it has been used a lot and of course for nutritional anemia it is essential. You have to use it for that, but the picture got a little confused because it seemed to help for instance with anemia patients, although their deficiency is that of vitamin B-12 and not of folic acid, but it did stimulate production of cells for instance in anemia patients but didn’t cure the other defects for instance anemia. Nowadays one is clear where one should use one and one the other. In anemias of pregnancy, folic acid is the drug of choice and anemia, such as pernicious anemia you need B-12, but both things are necessary. MR. LARSON: Oh yes. I have heard of some complications of folic acid used in pregnancy anemia. Have you ever heard of that? DR. TOTTER: No, I have not been aware of that. I haven’t followed things recently. MR. LARSON: But of course with every drug there is a certain small percentage of perhaps odd reactions that you will get in various… Well good. That’s not too vital, but going from there how did you branch out then from your interests. DR. TOTTER: Well I came to, a couple years after I had been a participant, I came back to Oak Ridge and joined the Biology Division and started then working on attempting to follow the biochemistry of changes following irradiation into its earliest stage after radiation is possible to do. Of course you know, Waldo Cohn and Charles Carter were working on separation methods for the purines and pyrimidines which are the things that are effected, seem to be affected most by irradiation. The methods available then just weren’t good enough to track down to say a few minutes. You could see if you irradiated for example an egg, when the embryo was five days or so old, you could see changes following 5,000 rads [radiation absorbed dose] of exposure but you couldn’t measure it. You couldn’t measure them objectively, but you could see the actual changes in the embryo. So to follow up on that, we had to wait a long time for development of sufficiently good methods to understand what was going on. MR. LARSON: Yes, I noticed you started using some of the units of exposure and you mentioned 5,000 rads. In so much of literature and discussion today, we speak of five, 10 millirads and so forth. So there sometimes gets to be quite a bit of confusion because you’re off by orders of magnitude and there is a slippage there in the discussions. DR. TOTTER: You put your finger on what is, what has really been the difficulty of understanding radiation because our methods required very heavy doses at that time, near lethal doses which for a chicken or a rabbit would be around five or 600 rads, which is five or six grays by modern usage and 500 rads would be 500 million millirads so our methods were simply not fine enough to pick up the changes with millirads or a few rads and they only recently have begun to get that way and that probably accounts for much of the confusion and difficulty that people have for having a proper feel for the magnitude of these doses. MR. LARSON: Yes and let’s see before we get further there is, as they say there is a matter of, you go from rads to millirads, as your talking about these. Also to add to the confusion there would be some new units brought in such as sieverts and millisieverts and so forth. Is there any simple way to get these connected together in a common translation unit? DR. TOTTER: There are ways of course, but nothing is very simple about them. The gray and the sievert are similar. The gray is named after L.H. Gray, a British scientist who was active in radiobiology. It’s a flux measure, I mean an exposure measure. The sievert is similar to it, but it’s the absorbed dose from the exposure to a certain number of grays. One gray is as an absorbed dose is one sievert and these are about 100 rads, or 100 rems [roentgen equivalent in man] to connect the old ones, but they are all connected mathematically back to the energy units that the physicists use. MR. LARSON: Oh yes. DR. TOTTER: So they are consistent with all the units now used in physics, if we used the modern units. But the old original unit was the roentgen and it was close to what we call a rad now. The absorbed doses are, a rem would be equivalent to the exposure of a rad. We called, the ratio between the exposure and the absorbed dose is called the biological effectiveness, relative biological effectiveness. These were good terms, but they’re dropping out of usage quite a bit because they are going to the modern nomenclature. I don’t know how to make this simple for the ordinary listener. MR. LARSON: Yes, of course whenever we get into discussions in the media or even in Congress these things apparently become very hopelessly entangled and there is a lot of misunderstanding I think generated when you go from grays to sieverts to rem to rad and millirad and so forth. DR. TOTTER: It’s unfortunate, but it’s confusing for scientists as well as for other people. MR. LARSON: Fine, well I think that clarifies that part of this. Well let’s go on then to your further extension of your research work as you followed through. DR. TOTTER: When I came here to Oak Ridge in 1950, Dr. [Alexander] Hollaender was chief of Biology Division and he was pushing an interest in two things. One was called the oxygen effect and this was discovered by L.H. Gray, which is very simply when you expose something biological, a live animal or tissue to radiation in the absence of oxygen you get less effect than in the presence of oxygen. The difference is about two, two and a half fold. You get, this began to be considered a direct and indirect effect. The direct effect was suppose to be the actual collision of a particle or a gamma ray with an atom to expel an electron. The indirect effect comes about because the electron in tissue is absorbed by water and water splits into a radical and an ion when it accepts a straight electron. It’s the radicals that we are interested in because they are the damaging things to tissue. They can disrupt the nucleic acid in the tissue and give rise to mutations or all sorts of other trouble. About as I say, 60 percent of the effect seems to be the indirect effect of the electron knocked loose by the absorption of the energetic ray. MR. LARSON: Now with regard to this specifically, the affects you measure by counting mutations as one thing. DR. TOTTER: That’s one way. MR. LARSON: There are other things I suppose such as life shortening or what are some of the other manifestations? DR. TOTTER: Well… MR. LARSON: Or are there histological things that you can observe, quantitatively. In other words, how do you, what are some of the quantitative ways you can assess the effect of the radiation? DR. TOTTER: On biological material? MR. LARSON: Yes, on biological material. DR. TOTTER: Well you can, the counting of the mutations is an indirect way of measuring it. A more direct way is to extract the nucleic acid and count the breaks in the, find out how many strands of the long nucleic acid assemblies are broken by the radiation because if one of those purines or pyrimidines or sugars is on the strand, except for the electron, it makes it energetic enough to break, and then we lose viscosity if were measuring, that’s one measure of it, to measure the thickness, the longer the strands are the more jelly-like the solution is that has the nucleic acid in it. So we can measure the rigidity of it, or the fluidity of the gel and get some notion of the chemical damage done. We can follow those things in a variety of ways but the way that was in common use at that time, the most effective way was simply the survival of some small organism like a bacterium, expose it to radiation and measure how many colony forming units are left out of a given number exposed. So and that led of course that the physical people understood a lot more about radiation than biologists did. Biology was a pretty, biological objects were pretty crude things to work with in radiation. The target theory arose out of that. This I think had a great effect on what people believed later about the effect of radiation. The targeting business was very analogous to Dr. [Ernest] Rutherford and his colleagues’ means of measuring the volume of the nucleus of the atom. Shoot at the target, you don’t know how big it is, but if you know how many shots you put into an area, or volume, you can tell by the survival of the target itself, which in this case would be a bacterium or a virus let’s say, by shooting enough bullets into the volume where you know it is, you can tell how frequently you will hit it and then calculate it’s actual volume from the frequency of hits. MR. LARSON: Oh yes. DR. TOTTER: So this worked very well for small viruses. You could determine the size of the virus by how sensitive it was to radiation. And radiation being the gun you shoot the bullets with. MR. LARSON: Oh yes. A very neat technique there. DR. TOTTER: So that idea dominated that there is a target that you had to hit to get some effect. And that still dominates the connection, the thought about connection between cancer and radiation. People have used it to try to figure how many steps the cancer, the cell goes through before it becomes a cancer. It so happens that the frequency of cancer again, measured against the age of an individual goes up a sixth or seventh power of age. MR. LARSON: Oh yes. DR. TOTTER: And that has been interpreted as the single cell which eventually becomes a cancer requires 67 hits. Of course it may be the progeny of the cell, not the cell itself, but I think this has mislead people very seriously about the connection between cancer and radiation because if one takes the disease like cardiovascular disease and follows its occurrence with age, it will go through about the same, about the same relationship to age, about the sixth or seventh power of the age. The frequency of cardiovascular disease in a population goes at about the sixth or seventh power of the age. It doubles every five, six or seven years in frequency. There is nothing you could think of about cardiovascular disease that would lead you to believe there is a target in the cell that you have to hit to get cardiovascular disease. MR. LARSON: Oh yes. DR. TOTTER: You think about this with cancer because you think a mutation is what causes cancer. MR. LARSON: Oh yes. DR. TOTTER: If you had not this preconception, you might not think of that as a target at all. I believe this has misled people an awful lot about cancer. MR. LARSON: Now with regard to the mechanism of course the way radiation manifests itself in the bodies of animals or humans, one of them is shortening of life, one of them cancer, cancer production, and particularly a subset leukemia production is one, and let’s see are there any other manifestations that we look at? Or… DR. TOTTER: Well, there are early… MR. LARSON: …of course other mutations? DR. TOTTER: There are early manifestations to whole body radiation. You have to distinguish between partial body and whole body radiation because they behave differently. MR. LARSON: Oh yes. DR. TOTTER: And that is a point that I would like to get to. MR. LARSON: Fine. DR. TOTTER: You’re correct. You named several of the methods. In the early days, in the ‘50’s and ‘60’s, there was still a pretty strong belief, I think this was originated by Paul Henshaw, who was a pioneer in radiation work and was here during the war at Oak Ridge, that there was life shortening, what they called non-specific life shortening, that is the life shortening going to all causes of death that they are connected with old age, but so much work has been done with high cancer strains with mice that they now believe that at least in those all of the life shortening is due to the increase in the rate of cancer, in this age-specific rate of cancer occurrence. Yet in the earlier days when the strains in mice were not so, they concentrated on using strains that had high cancer rates, people seemed to see cardiovascular effects also. This I think is a very important point which I think has been lost sight of in recent years. That comes back to the point of the difference between partial body radiation and whole body radiation. That was discovered very early by the people working at the University of Chicago. You could shield part of the body and you could change the lethal dose of radiation. So there are hormonal effects that result from the radiation and again we come back to the problem of the time in the development of sciences which you do particular kinds of work. All of the work that had to do specifically with endocrine organs exposure to cancer were done with high doses because there was no way to measure your hormonal changes easily. These were developed by Rosalyn Yalow and her colleagues much later, radioimmunoassay. So the work if one goes back into the literature and searches for effects on specific endocrine organs all the doses were very high. Nothing was done with low doses because you would expect to find anything. You didn’t have the means to find it, except for thyroid. You remember Dr. [Jacob] Furth here worked a lot with thyroid cancers... MR. LARSON: Oh yes. DR. TOTTER: …and showed numerous ways to affect the incidents of thyroid cancer [inaudible] radiation, but that work has not been followed up. It’s been largely ignored by later work. We have been more interested in the target theory approach to what happens with cancer. We have lost sight of this effect which is also one of the ways you measure. You almost, I think almost everybody is familiar with the fact that if you get a fairly good dose of radiation to your head or abdomen, you get nauseated. My thought… MR. LARSON: By a fairly good dose you mean… DR. TOTTER: Well, this is in… MR. LARSON: …like three or 400 rads. DR. TOTTER: Oh, you always get it with that. MR. LARSON: Yeah. DR. TOTTER: Even 50 rads… MR. LARSON: Oh even 50. DR. TOTTER: …it’s quite frequent. If you look at the statistics of the thing, it’s somewhere between one and 40 or 50 rads, it would be almost sure to give you nausea, maybe as low as one rad. MR. LARSON: Is that right? DR. TOTTER: This certainly has to be a hormonal effect. My thought is that it affects the appetite and satiety centers in the [inaudible] and the lower part of the brain. It tells you, this is a hypothesis that I have been developing, tells you that you have eaten too much. MR. LARSON: Oh yes. DR. TOTTER: When you get a dose of radiation and you get nauseated, you don’t want to eat. That’s the main thing, the result of it because the body has been fooled into believing that it’s had an overdose of food. MR. LARSON: Oh yes. DR. TOTTER: I can’t prove that of course, but I think it’s correct because there was an experiment done by a physicist working at the University of Chicago. Around 1950, Leon Jacobson who later became dean of the medical school at Chicago and some of the other colleagues in which they exposed mice to gamma radiation from radium. They found to their very great surprise that the ones that received a tenth of a rad a day of whole body radiation from gamma rays lived longer than the controls. MR. LARSON: Let’s see. A tenth of a rad. That’s a hundred… DR. TOTTER: That’s a hundred millirads a day. A hundred and ten actually they received. Those that received 1,100, ten times that dose, didn’t have a shorter life. Some had a little bit longer life and some had a little bit shorter life, but their median age at death was about the same. Those that received higher doses, say 220, 2,200 a day did live a shorter life. They had a life shortened just as you mentioned a while ago and there were extra cancers. The cancer rate was higher, but not much was said about the other things except they did some chemical work on the carcasses of the animals after they were dead and found that the fat was low, fat content was low in the carcasses, the radiated animals. MR. LARSON: Now this was actually amounts of say only 2000 millirads? DR. TOTTER: Yes. MR. LARSON: That’s good. I can remember in the work of [Arthur] Upton, when he performed his experiments on genetic effects of life shortening and cancer production and so forth, he was using much higher doses, something like 50 to 500 rads, which is way out of this range. DR. TOTTER: Most of them were like that. These were single exposures though and remember that the Chicago experiment I’m talking about was a continuous exposure. It was so that the animals absorbed as much or were exposed to as much as several hundred rads before they died. MR. LARSON: Oh yes. DR. TOTTER: Of course it was partly on that basis that the Upton experiment was set up. We, the people who were concerned with the planning of the Upton experiment were quite a large number of people involved, calculated the number of animals they would have to have for single exposure to just a few rads and decided that there was either not the money or the facilities to handle that large number of animals. So that’s why the doses were higher. There was one set with 10 rad exposure and it’s a very interesting thing about those. They lived on the average the same as those who received no radiation. This is 10,000 millirads at a single exposure, but the lives of the few were shortened a little and the lives of the few were lengthened a little so that the average turned out exactly the same as the controls. Now I think this kind of confirms the experiment done by [Egon] Lorenz and his collaborators at Chicago in a way, but a curious thing about the Chicago experiment is that because they exposed the animals in a room that had radium in it they could never leave the controls in that same room. The controls had to go in a different room. A lot of people have said then that this was no experiment. You have no controls. So we will throw that experiment away, it’s no good because a few other investigators have been unable to duplicate that experiment… MR. LARSON: I see. DR. TOTTER: …and there are others who have been able to duplicate it and what has happened, very unfortunate I think from the stand point of the development of radio-biology is that people chose to discredit the experiment rather than to try to find out why there was a discrepancy between the laboratories. This was a terrible mistake in the long run because it will cost us enormously in misunderstanding of the cancer problem and the radiation problem, both. MR. LARSON: Well let’s see now. How would you summarize then the effect of the Lorenz experiment and its meaning? DR. TOTTER: I can give you my explanation of it, but you must understand that many people don’t agree with it. MR. LARSON: Yes. DR. TOTTER: My interpretation is that the low doses of whole body radiation and the effect on the endocrine glands was larger than any effect that cancer induced. What happened was that these animals were discouraged from eating because their satiety and appetite centers were affected by the radiation. MR. LARSON: By the low dose how do we define that? Ten rads? What do we call the low dose there? DR. TOTTER: The low dose is the 110 millirads to 1,100 millirads per day would be the low dose. MR. LARSON: Yeah. DR. TOTTER: Those, I say the endocrine effect was larger than any deleterious effect of the radiation and it reduced the food intake of the animals and because of that they lived longer. MR. LARSON: Right. DR. TOTTER: Now, it may have… MR. LARSON: But they’re given daily doses… DR. TOTTER: That’s right. MR. LARSON: …so that the accumulated dose… DR. TOTTER: Was very large. MR. LARSON: …was very large. If you gave one rad or 1000 millirads over a period of one month would be 30,000 millirads. So I’m sorry I interrupted there, but now what, I come back to the effect on the result of that and what your interpretation is. DR. TOTTER: Yes, well, I think when you go high enough in the exposure and by this you probably began with a single dose exposure of over 10 rads, 10,000 millirads, somewhere above that, then the deleterious effect on cancer and perhaps on cardiovascular disease exceed any effect that can be induced by a change in appetite. MR. LARSON: Oh yes. DR. TOTTER: So that’s what you see. You don’t see the other effects. When you go to these lower doses and the point to be made about that is that we could estimate the internal dose which would be to, equivalent to, now let me back up a moment. What I want to say is that the food produces the same kinds of radicals that radiation produces. That’s why the body mistakes the radiation effect for a food effect. MR. LARSON: Oh yes. DR. TOTTER: So we can tell then by the type of experiment that was done by Lorenz how much of those radicals are produced by food daily, ordinarily, without any exposure to radiation. It looks as if in the mouse it’s almost equivalent to one rad per day, 1000 millirads a day. That is the effect of food because those animals you see had not had their lifespan changed. The median lifespan was the same. You could expose them to that much rad a day continuously and it wouldn’t affect them. So that, well I shouldn’t say it’s equal to the internal dose that means the dose from one rad a day is so much less than the dose you get from food that it has no effect. MR. LARSON: Oh yes. DR. TOTTER: You could think back, make a comparison to almost everybody that has worked in radiobiology has started out believing that the only kinds of radicals the body sees are those produced by external radiation and internal radiation that we call background. And that’s something like 100, 200 millirads a year. MR. LARSON: Oh yes. DR. TOTTER: But actually we see a far, far higher number of those radicals from the food we eat. If you impose a dose of radiation on top of what we normally get from ourselves, not radiation, but the radicals that are produced by radiation, if we impose an external dose, then it’s the fraction of the total dose that’s represented by those that cause the increment of damage. It is a little damage piled on a lot that we are already handling. It is not equivalent to the background radiation. Its equivalent to hundreds of times the background radiation. So, I think it’s silly of people to look only at background radiation as the background which we normally suffer. That’s only a minute part of it. But the reason that people don’t accept that and don’t pay much attention to this possibility is that there is no way to measure that flux in the body, the flux of real radicals because there is no method that is sensitive enough to pick it up. You could not measure chemically the effects of 10 or 100 rads of exposure by looking at the tissues of the body. So we can’t see that. The nearest we have to a method is electron spin resonance and that you know is limited by the fact that water boils it. So in the presence of water you can’t measure that very sensitively, but there are people working now trying to measure indirectly. You can measure it indirectly in several ways and the flux is that, the flux of radicals produced from just metabolism of food is large, large enough to be equivalent to some matter of rads a day, external exposure. MR. LARSON: Well then, so, as I say, experimentally this is a very difficult field then to investigate. Now with regard to this then, the, when we come to examine differences naturally occurring say between sea level and say Denver and so forth, we get 100 MR difference in annual exposure and so forth, this doesn’t lie within probably the realm of being able to see whether it has a beneficial effect or a deleterious effect. It’s so small it’s blocked by internal things. So you would need much greater things. Therefore this brings up the, you know, the alarming response that people get to the minute traces that fell out from Chernobyl say in the arctic where the reindeer are now getting five or 10 more millirems than they would normally get and they feel that this will increase up the food chain up to double or triple that. But still it’s so small compared to… DR. TOTTER: You could miss a meal and handle all of that stuff. Just by missing one meal. MR. LARSON: Missing a meal would wash out the whole effect on this. So and actually studies of that type are likely to be at best misleading and even perhaps worthless. DR. TOTTER: It’s a terrible thing, Clarence, that we spend so much money on that kind of thing because that’s diverting money from other very worthy causes that have no, no difficulty like that with them. This is a matter of great concern to me and I hope becomes to other people that we can get back on the track to really understand this. There is almost no work supported now that relates radiation to endocrine function. You cannot get it through the study sections at the National Institute of Health. Now there was one person who was interested in that and this story is interesting because it amplifies my worry about the narrowness of each individual’s concentration in science on some specific problem. We’ve lost a lot of the generalness in science by concentrating so heavily and of course concentrating heavily on a narrow area does produce fantastic results, but somebody has to be back there to put all the narrow fields together somewhere along the way and we lack that pretty badly. Tom Dougherty you remember was in charge of the Utah project. MR. LARSON: Oh yes. DR. TOTTER: Tom Dougherty was an endocrinologist. He was an endocrine biochemist really. MR. LARSON: Oh yes. DR. TOTTER: And he knows also, or was interested in the white cell reduction following whole body radiation because he had studied stress and one of the signs of stress was a reduction in the white cells. That’s perfectly well know that a little bit of cortisone or something like that will reduce the white cells, stimulate the adrenals and the white cells go down. He told me many years ago that he thought that the small dose of whole body radiation would adjust the stress on the body which affected the adrenals and caused the reduction in white cells. White cells are sensitive to radiation and most people believe that they are killed and that’s why they go down. They don’t believe in the endocrine effect there. Now he’s the only one I know of who used relatively low doses of radiation and tried to study their effect. No one else, all of the other endocrine work with radiation that I know of starts at around 500 rad level… MR. LARSON: Oh yes. Five hundred. DR. TOTTER: …completely out of the range where one should work, and if you ask a radiobiologist now, he’ll say oh well those experiments were tried and they didn’t find anything. The reason was they were not working with sensitive enough methods and they were using far too much radiation. Most things, all need to be done again because the methods for depicting endocrine changes are now very much more sensitive than they ever were before. Dougherty was convinced that we were overlooking something like that, but he was not in the position apparently to carry on the work out there. They had a mission which was quite different from that. It was to study the effect of fission products, as you recall. MR. LARSON: Yeah. DR. TOTTER: He died a number of years ago. So far as I know he’s the only radiobiologist who really believed that we should look at the endocrine effects of whole body radiation. MR. LARSON: Now when it comes to these various levels of exposures we had a wonderful opportunity to study this in the Hiroshima, Nagasaki studies and in newspaper accounts and general accounts there is a good deal of, oh, misinformation, or lack or information or taking little pieces of that data and so there is, there seems to be a lot of confusion in the interpretation of these things and I have looked over some of these studies. The latest one I had access to was I think a 1977 tabulation and there were several things that if you examined it very carefully it stood out. If you take the cohorts which had lower levels, you know like below 100 rad, or below 200 rad or something, or below 50 rad and so forth, and examined the number of deaths from cancer in these various things, you get a very confusing picture. Depending on what cohort it was very evident, like, I don’t know, one of them let’s call it zero to 50 or the zero to 100 something like that, that showed, seemed to be a protection against cancer. Then when you got over the 200 of course the damage, there was an increase in there. Then if you take out the population as a whole and then just examined death and non-death, there seemed to be fewer people dying who have been exposed, just taking the population as a whole as compared to the controls. So there is an awful lot of confusion and you can almost pick out different cohorts and prove different things. I was wondering if you had any general feeling, has there been real sense made of this and what are the conclusions? DR. TOTTER: I think you describe the situation as most people see it pretty well. Those who believe that the low doses, the effects are under, what should I say, that we underestimate the effects of low doses, have a scenario as to explaining why. They don’t see the death so they create them with a pencil and paper and they do it in the following fashion. They say there is a five year gap between the real systematic set up of the Atomic Bomb Casualty Commission and the atomic bomb. They say that the people that were traumatized by the bomb, the survivors, the weaker ones died because of their exposure to various other things besides radiation and so yet only the stronger ones are present and that’s why you don’t see much effect in low doses because the population is not represented, the original population. My interpretation would be exactly the opposite of that. So I can create, I can save these people with pencil and paper just as the way they kill them with pencil and paper. If my idea is correct about the endocrine effect, one of those effects if your body believes you’ve had too much food, you have a short life. You know when you restrict the food, the life is lengthened. So it’s reasonable to say if you get too much food it’s shortened. Or if you get as much food as you would like to eat its shortened, but really the susceptibility to cancer and the susceptibility of cardiovascular disease are genetic things. Genetic things interact with the environment and one of the things that happens when you have plenty of food is that you have a short life and die from cardiovascular disease and you die early from cardiovascular disease. That reduces the next generation because these people have not time enough to reproduce fully. They died too young. That’s what happens, the ones that were exposed to small doses of radiation, the body interpreted this as extra food and they died of cardiovascular disease so that we have left a cohort which is richer than those that are going to die of cancer. This is just the opposite of what they say. So I can argue that the effect we are seeing is less than we should, or is more than we should see. That there should be a greater protective effect of those instead of having a curve which is high at low doses, we have one that should be even lower. There are no, is no way that we can decided objectively between these two things. So they both should be thrown out. MR. LARSON: Oh yes. DR. TOTTER: So what we see is exactly about right. We see no effect below 50 rads a dose, and above that we begin to see the extra cancers which you would expect. MR. LARSON: But right along with that there seems to be a lower mortality overall. As I remember the numbers at one point in ’77 there were say, you would expect say 22,000 deaths in this particular 35 year period, or whatever it is, and there were only 2,000 deaths. DR. TOTTER: That’s consistent with my interpretation. These people got extra food, I mean were fooled into believing that they had extra food so they didn’t need as much later and they should live longer. The rate should be a little lower. MR. LARSON: Primarily because there, they eat less and therefore their diet was optimum to their long range survival. DR. TOTTER: There is a terrible narrowness about people who are concerned working with cancer and those who are concerned working with something else. The narrowness I was talking about a while ago. I have a book in there produced by the U.S. Public Health Service that is so big, weighs 15 pounds and it is about cancer and nowhere in that book can find, can you find a word about the rate of cardiovascular deaths in those populations that are being studied. Familiar instances as talking about Utah which has the lowest cancer rate of any state in the continental United States. Nowhere does anyone say they also have the lowest cardiovascular death rate. Nowhere can you find that, but it’s true. It’s lower in proportion to the total death rate in exactly the same proportion that cancer is lower. I say this is an inherited factor and when one is low the other is low. What people should be looking at when they follow the atomic bomb casualties is both causes of death. One should look at cancer in relation to cardiovascular death. What you were saying a moment ago, they don’t die as often, they are lower on cardiovascular death because that is the main thing that fixes the lifespan. So we make terrible mistakes at not looking at the boundaries of, extending the boundaries of what we look at. I believe people would have a totally different conception of cancer if they always linked it to the cardiovascular rates that occurred in the same population. MR. LARSON: Yes, you know, of course, this is a little bit aside from our discussion, but of course in our civilization you know, the horror of a child or a person having to go without a meal is just something, how could any civilization be so cruel as to inflict that on them. In my interviews of people in particular who grew up in the Depression years, including myself, money was so scarce one common way of saving money was to eat two meals a day and you would be surprised that at least four Nobel Prize winners during that particular period saved money by eating two meals a day. They are now all in their 80’s, but there are all kinds of these factors which enter into the lifespan. So it gets so confusing. DR. TOTTER: That’s a good, a particularly good one you mentioned because I’ve looked for information on our average food intake during the Depression and the best I can find, one survey was made and it was about 10 percent lower on the average than on either side of the Depression. So the people who were born in the decade from 1930 to 1940 are just now beginning to die at a fairly good rate and in the next two decades we’ll find out if they on the average lived longer than the people before. I think they will. MR. LARSON: Yes, well that’s rather interesting because that was very common, all of the schools, graduate students and college students, they all had that same problem of trying to live on 30 and 40 dollars a month during those days and as they say there were very famous people here who… DR. TOTTER: People talk about the Baby Boom, actually this lack of food during the Depression is part of the reason for the reduction in birth rate. The Baby Boom is a return to the birthrate that they had before the Depression. One can find other populations that were starved like the Netherlands population I think in ’44. The birthrate dropped to zero while they were in that famine and then it returned promptly after the famine was over. MR. LARSON: Oh yes. DR. TOTTER: So I think they should talk about the birthrate depression rather than the Baby Boom. MR. LARSON: Yes. That’s a very good point. Now with regard to other investigations that you were in at the time, oh, I wanted to get a little discussion on the subject of hormesis, is that the way to pronounce it? DR. TOTTER: Hormesis, yes. MR. LARSON: Number one would you define the term. At least in one dictionary I didn’t even find it, but what is the definition of the term? DR. TOTTER: The definition of hormesis is the effect that a toxic agent has at low doses that seem to stimulate something. Arsenic is a very good example of it. Low doses of arsenic are quite stimulating to people and horses. Many a horse trainer made his money by feeding his horses arsenic just before he traded him. Their coat gets sleeker, they look healthier and they’re more active. Of course if you give more, it kills them. That low dose effect of toxins can improve things, to seem to improve things is called hormesis. MR. LARSON: Oh, all right, fine. DR. TOTTER: We’ve already discussed it to some extent because experiments of Lorenz were the first example in animals of a hermetic effect of radiation. Lengthening of the life is regarded as a hermetic effect. MR. LARSON: Yes, I believe there are quite a number in nutrition. Cobalt I believe among the sheep in Australia or something. I think they found that there were certain areas that were low in cobalt and it was very deleterious and when they added cobalt to the feed there was a… DR. TOTTER: There is a very interesting story about that. I don’t know if you remember Harry Stout. MR. LARSON: Oh yes. DR. TOTTER: He was the one who showed them how to cure that cobalt deficiency. MR. LARSON: Oh, is that right? That I did not know. DR. TOTTER: He told them to use the neural nuts that you have on crescent wrenches you know. MR. LARSON: Yes. DR. TOTTER: That’s a cobalt containing steel. MR. LARSON: Yes. DR. TOTTER: Those wrenches are made of that and that little nut they poked it down the throat of the sheep and it stays in the forestomach and it doesn’t get lost. It doesn’t get out of there and slowly erodes and frees the cobalt at about the rate sheep needed. MR. LARSON: So you don’t have to keep adding it. DR. TOTTER: No. MR. LARSON: That’s fantastic. I believe that at least there is a fad now that adding selenium is good for… I don’t know whether that’s considered a fad now or not. DR. TOTTER: It is a fad because the fad people have picked it up. It’s a nutritional fad. I worked with selenium when I was an undergraduate. I was at Wyoming where selenium toxicity was very bad. MR. LARSON: Of course, the toxicity is very bad. DR. TOTTER: Yeah. MR. LARSON: But is there a small amount which is… DR. TOTTER: A small amount because it is required for, it’s very interesting how that fits into the discussion. It’s required for oxidase which oxidase is, which oxidizes glutathione with hydrogen peroxide. It’s a requirement for that enzyme and that enzyme is what reduces the last traces of radicals in places where they are not wanted because the radicals will affect the glutathione. So, selenium actually reduces the free radicals that I think are the cause, the root cause of cancer in… MR. LARSON: Oh yes. Well that, of course things like vitamin D, overdoses of vitamin D can kill you, kill children, but we need certain amounts. DR. TOTTER: That’s right. MR. LARSON: There are a lot but the hormesis effect of radiation is, there seems to be some evidence, but there is not enough work really to really define it. I might ask a question of you. For instance, if you had your choice of living in an entirely free, it would be impossible, but an entirely free radiation from birth, or one which had normal radiation, which would you chose? DR. TOTTER: I think there is nothing to choose between… that brings an important point about the definition of hormesis that I didn’t touch on. The person who is promoting hormesis mostly in this country believes that it is required. Radiation is required for the body, that is, it is a nutritive to the body. What I am claiming is a little different. It is that radiation fools the body into believing it has received nutrition. MR. LARSON: I see. Your mechanism is different from that. DR. TOTTER: It’s a little different. I think that the bad repute that it has comes from the idea that it is nutritive and so I try to combat that idea and say, “No, it just fools the body into believing it has had some food.” MR. LARSON: Oh yes. DR. TOTTER: I believe people would accept that easier than they would accept that radiation was good for them. MR. LARSON: That radiation was good for people. So in other words you don’t think that if a person had a choice between living in an absolutely free radiation atmosphere for his life, he wouldn’t necessarily suffer from it. DR. TOTTER: I don’t think he would, but there is a school of thought that quite possibly the random radiation effects have something to do with the biological clocks, setting the biological clock. And I have no particular strong opinion about that, but I doubt it. It was one of the first things that was suggested for effective radiation and it was shown to be wrong in that particular instance. There is still a possibility that it has something to do with setting clocks. MR. LARSON: Yes, well a natural radioactivity of potassium was thought at once to have some role in the heart. DR. TOTTER: Yes, that’s the one I was speaking... MR. LARSON: Was that one you were speaking of? Fine. Okay. Well, let’s see. How would you summarize the, we can start in now with your present writings and investigations and so forth. What are your present main interests? DR. TOTTER: Well, I am trying to learn enough about demographic techniques to show by some methods, which people haven’t thought of or haven’t tried, that there is really no real change in incidents of cancer over the years. I guess that’s a little bit the wrong way to say it. What I am trying to show is that cancer is a normal cause of death and it is inherited in the same fashion as other causes of death in old age like cardiovascular disease. That is we have a certain amount of energy which we get from our food and a certain rate that we can use the energy. It’s used for what purposes: It keeps us warm, it enables us to find more food, exercise, to work, enables us to reproduce, and part of it is used for maintenance of our bodies so that these functions will go on. We, by natural selection, always tend to decrease deficiency because we compete with other creatures or each other for the use of the available food. There is currently a pretty strong belief that the reason we die, we age and die is because it’s more efficient in the long run for that to happen then to try to use so much energy for maintenance that we live forever. You can very easily show thermodynamically that that is true. It’s better to make new people than it is to try to keep the old ones going. So I believe that the whole thing is very rationally worked out. And that we will find that cancer is just another part of that system. What I want to be able to show is that you cannot interpret cancer as an accidental cause of death, the vast majority of it, a small amount perhaps, but it would be very small. MR. LARSON: Perhaps less than one percent or something. DR. TOTTER: Yeah, something like that. In special cases, maybe four or five percent, but normally one percent or less. I cannot find incontrovertible proof of that, but that’s what I’m shooting for. MR. LARSON: Oh yes. DR. TOTTER: Now, the, when I try to talk to people who are interested in cancer about natural selection, they think I’m crazy. It’s almost impossible to get them to think of this in terms because they believe that the bell shaped curve which represents our rate of dying, frequency of dying is not a normal curve in most cases. It’s a distorted normal curve and I’m saying that if we were living in a neutral environment it would be normal. The fact that it’s distorted shows that we are being selected very rapidly for a different longevity. That’s why the curve is not normal, but if it is a normal curve, or suppose to be a normal curve in a neutral environment, there are two ways to look at it. One is that the variance is due entirely to the environment. We all inherit a specific lifetime and the varying environment produces the bell shape of the curve and I believe that the common, it’s commonly accepted among cancer researchers that that’s the case. It’s all in the environment. You inherit a specific lifetime and everybody inherits the same one. That seems silly to me. Most of the variance in that curve is variable I think and it’s over this point of whether our lifespan is largely inheritable or largely environmental is the crux of the argument. Now I think it’s very easy to show that much of it must be inheritable and to talk to population biologists I think you’d get no argument, but they’ve never talked to the cancer people and the cancer people never talked to them. That’s the difficulty. MR. LARSON: Yes. Well now the cancer people are overwhelmed by the environmental factor of smoking of course which is, that’s such a big and unusual thing. Probably it is disputed how big the factor is, but undoubtedly it is a big perturbation in there. But otherwise, are there other, what are some other environmental factors which supposedly increase cancer rate, or affect cancer rate that are environmental? DR. TOTTER: Well, its’ perfectly clear that environment affects specific cancers. Now there is no question that we have dropped in our number of stomach cancers and I’m not even sure that smoking has done part of that, but that rate is, if you suggest that rate it immediately raises a howl of protest because smoking affects the motility of the stomach and it reduces tension and tension may be cause of acid production which may be the cause of stomach cancer. You can make out a possible scenario for that, but irrespective of that while the lung cancer goes up the stomach cancer goes down until it’s nearly disappeared. People will not connect those two things. They absolutely refuse to because they think that the environment produces accidental cancers one way or another. And any one that goes down, you’re just lucky because you changed the environment in some way you don’t know about. If cancer susceptibility is inherited then if one cancer goes up another has to go down, or some others have to go down because you’re inheriting, you have 20 percent of the people can get a cancer, can die of cancer, let’s say. Well if you get a lot of lung cancer then the other cancers must be less than that to make the 20 percent, but if we’re dependent on an oncogene scattered somewhere in our tissues and we can’t have a cancer unless there is an oncogene there. All right, it’s changing environment is not going to affect the people that don’t have the oncogene. Some of them, it’s like blood groups. Some of them inherit the oncogene for colon cancer and some don’t. I don’t know what causes the stimulation, or gets those to change to become active and it may be like something people think. I’m inclined to doubt the target theory even for that, but, simply because it’s misleading us in other respects, but if there is such a thing as cancer in one spot withdrawing general resistance to cancer in some fashion, not just local, but general, then having one cancer effects the rates of other cancers. So, I’m trying to think of that. What I am mostly trying to do is not settle on any hypothesis that will channel my thinking as I believe others have channeled theirs so they can’t get out of a hypothesis that’s no good. MR. LARSON: Your microphone just dropped down to your pocket. Now come back to, just press it on. Come back to that theme. There of course has been a lot of pressure in recent years about the synthetic things that are put into our atmosphere, the food chain, the insecticides, some things that are put into soil and so there are all kinds of new sources of carcinogenic compounds in particular insecticides and herbicides and so forth and so now large stores advertise the organic grown. Bruce Ames has pointed out that the natural, in order for a plant to survive through evolution it has had to synthesis its own insecticides in order to survive against insects and in many cases those insecticides are just as carcinogenic as synthetic ones, more so because you can sometimes tailor them to avoid these. I was wondering if you had any general feeling about these things that we add to the environment to avoid carcinogens. How would you classify the various things and their dangers? DR. TOTTER: Well I’m quite sure we are overly concerned for the short term but we should be concerned for the long term. We have to know what these things do and how fast they leave and so forth and we don’t do that well enough. I went through that experience myself on our farm when I was a boy. I use to help spray for the cotton bollworm and the first thing we could get ahold of was the lead arsenic. That killed the worms all right if you got it there fast enough. MR. LARSON: Oh yes. DR. TOTTER: But years later when we tried to grow cantaloupe there was too much arsenic in the soil. MR. LARSON: Yeah. Of course arsenic, copper arsenic was very commonly used. DR. TOTTER: Very commonly used in the old days. MR. LARSON: Paris Green. DR. TOTTER: Yeah, Paris Green. MR. LARSON: The green was due to the copper. DR. TOTTER: We kept a pound or two of that around all the time when I was a boy and I was warned against how poisonous it was. MR. LARSON: So of course these modern ones usually don’t have metals… DR. TOTTER: Don’t have permanent elements. MR. LARSON: …toxic metals in them and are synthesized in such a way, actually I believe there are certain carcinogens in, what is it? Oh, mushrooms, and in peanuts, and so forth. DR. TOTTER: Oh yeah. There are numerous… They are everywhere. MR. LARSON: They are natural. DR. TOTTER: Bruce’s point is that we probably owe most of our cancers to those, but I think he’s coming more around to my point of view that it’s internal and not from external agents that we get them. MR. LARSON: Oh yes. DR. TOTTER: I think that we owe the fact that we have to have cancer to the economy of nature. We could avoid that cancer but we would lose something else that we have to have if we did. So it’s cheaper to have the cancer than it is to build a wall against other things. The thing, it’s a very simple proposition and any thermodynamicist would tell you that something like this has to be correct. If you had to produce the protein enzymes to combat all of these things that Bruce Ames was talking about, it would be more expensive than having a few cancers. So you allow enough of those radicals to escape destruction so that you can use them to destroy these strange compounds that come in and that’s exactly the way it is. The peroxidase as you see all produce those radicals and the advantage of a radical is nonspecific. It will attack anything organic and you don’t have to have a specific enzyme for it. A peroxidase is a very nonspecific enzyme but a trypsin or a chymotrypsin is a very, very specific enzyme it will only work on a certain kind of bond. So you see, the balance of nature makes you produce both kinds of these things because it’s energetically more economical to do it that way. So if the people who are seeking complete prevention of cancer are probably going to kill us all... MR. LARSON: Oh yes. DR. TOTTER: …if they ever find something then. I think that we do not take into consideration enough what the real economy of nature is. MR. LARSON: Yes, well of course, actually, I don’t know what the exact figures are but you hear these figures bandied about in the last 50 years. We have probably increased the lifespan of people 15 to 20 years. It’s throwing our social security plans all out of whack and everything else and of course that is gradually going to reach a plateau of course. DR. TOTTER: A plateau at some point. MR. LARSON: But there is no doubt about it being a fantastic increase in the lifespan in the last 40 or 50 years. So, it isn’t exactly that the appearance of chemicals and radiation are killing our people off at a great rate. The numbers just don’t bear that out. DR. TOTTER: This brings up another point that I might make with you. You talk about increasing the lifespan. We get this from the life expectancy tables and it’s perfectly true, but if you look at what the maximum lifespan is, well, let me back up a moment. The cancer institute people will tell you that, the people that are working with the demographic figures, that cancer in men has increased. I should say the age adjusted rate in men has increased. For women it has gone down slightly. If you look at the real data, the fact is the fraction of people dying is the same in both sexes. MR. LARSON: Oh, is that right? DR. TOTTER: Yeah. Nobody ever tells you about this. MR. LARSON: I’ll be darned. DR. TOTTER: And the reason, the odd reason that the men are going up and the age adjusted in women are going down is because women have actually increased their lifespan and men have not. So the cancer spread is over a larger number of years and the rate is down. So the fraction stays the same. MR. LARSON: The fraction stays the same. DR. TOTTER: These are the kinds of crazy things… MR. LARSON: You really have to examine the figures carefully in order to come to a logical conclusion about these things. DR. TOTTER: That’s right. That’s right. MR. LARSON: That’s very important. Incidentally, just happened to think, how do your views on radiation coincide with our mutual friend Merril Eisenbud? Merril’s been working on this field of radiation for a long time. DR. TOTTER: Merril is a pretty sound scientist, but I don’t, I haven’t talked to him for a long time. I am sure he’s much less concerned about the cancer than other people are in radiation. Is that correct? MR. LARSON: Oh yes. That’s right. DR. TOTTER: So, they probably do coincide. MR. LARSON: In fact, he’s very concerned about the, you know, the irrational fear of the cancer and these extremes that are being used to clean up these minute traces of radioactive materials, spilled uranium and so forth and so on which is entirely nonproductive use of money. DR. TOTTER: That’s the biggest problem that faces us for the next few decades. I often wonder whether the people who are doing these things have a real hidden agenda. Everyone knows that the problem comes because there are so many people and we also know, I think realists don’t believe that you can change that. MR. LARSON: That’s right. DR. TOTTER: But the others, some of them may be trying these things just to bring us to the edge of some kind of a catastrophe that will reduce population. I wonder how many of them know that they are doing this and how many are doing this because they have a single track mind; only think of one thing at a time. MR. LARSON: Well, that gets to be very discouraging. I see some of these things. The clean ups you know, these are going to cost $22 billion to do this and so forth. At the most it might possibly save one life, although there would probably be 20 lives killed by bulldozers and so forth in doing this. DR. TOTTER: The clean-up will surely kill more. MR. LARSON: So, and it’s sort of an insanity that is going on in these extreme things. We’re right in the middle of it and it apparently has great momentum. There is also a selfish stand point. You know when The Great Society proposed the poverty programs the human cry of all the sociologists coming to Washington, “There’s money in poverty,” was the great cry of the times. Today, there is money in scaring people to death. That money is getting into the billions and billions all the time. That undoubtedly affects the people on this. So we’re faced with trying to get some rationality into hazards of all types, radiation, chemicals, and insecticides and so forth and so on. But there is no very simple problem. DR. TOTTER: It’s like we’re fighting a losing battle too because what you’re saying basically is to get people to think more quantitatively and half the spending for arithmetic has gone down in the schools, and we’re not improving. MR. LARSON: That’s right. Then of course the arithmetic, very little arithmetic incorporates the statistics and probabilities into them these days, which are the two basic things that we use all our life in order to evaluate the meaning of numbers, but that’s left out. Incidentally who is in the Washington area, who are some of the more sensible people involved in status statistics or biometry and so forth and so on these days. Do you know any? DR. TOTTER: The best statistician that I know of in the National Cancer Institute are Nathan Mantel, and if he’s still active, and an epidemiologist, they have a good epidemiologist there, but I’m not sure if he’s still active. I can’t think of his name now, but these are not the people who determine what is said, now there is an ex-member who I think is way off and that was Marvin Schneiderman. He believes in as John Bailer, believes in the age adjusted values for cancer which are really misleading and should be abolished. MR. LARSON: Oh yes. DR. TOTTER: So, Marvin Schneiderman is still active, but he is no longer with the National Cancer Institute. MR. LARSON: Oh yes. DR. TOTTER: He’s a good statistician but an awful poor biologist. MR. LARSON: Oh yes. DR. TOTTER: I think that’s the problem. MR. LARSON: You have to tie those together in order to get some very good sound opinions. DR. TOTTER: I don’t know the real answer to that question, but almost nothing that comes out of the American Cancer Society or the National Cancer Institute for the public’s consumption or even out of the National Academy of Science, their nutrition book on cancer is pretty bad. MR. LARSON: That brings me to the final subject that I wanted to ask you about and that is this book by, that was put out by the National Academy on radon. Did you see? It’s a fairly thick book, maybe 300 pages or something like that. It’s not very easy reading because it’s got a collection of different things. It’s awfully hard to read, but apparently out of that book came this statement, you know, where we have 2,000 deaths per year from radon. DR. TOTTER: That’s crazy. MR. LARSON: That is such a crazy statement. So I went into the book and tried to find the rationale. The book doesn’t have the data or the facts in there. And I was wondering if, have you come into any discussions as to what they arrived at, what the data is and so forth. DR. TOTTER: I know a little bit about the original background, but I don’t know much about anything recent. Again I like to call on Perry Stout for pointing out, what’s the matter with that problem. He says he looked very carefully at the lifespans and so forth, or what he could find out about them on burrowing animals who live in a much higher radon concentration than we do. He never found any lung cancers in any of these burrowing animals. MR. LARSON: That’s an interesting point. DR. TOTTER: Burrowing animals you know that live in those tailing deposits where the radon concentration must be awful high and they maintain a population without any trouble at all. I think this is biological knowledge enough to be skeptical about anything said about radon and lung cancer and ordinary population. MR. LARSON: Of course, you know one of the things that really bothers you, they sell these kits you know, millions of dollars for these kits. Everybody was buying a kit; put them in a corner of the basement. So they put them there right where it would be a stagnant area in the corner of the basement… DR. TOTTER: Where nothing moves. MR. LARSON: …where nothing moves… DR. TOTTER: Nobody gets to it. MR. LARSON: …and nobody ever gets to, and then they take the readings there. You know the readings should be taken in the average living space. I would bet that for every hundred positive readings that you would get by the basement, you would get only one in the living space. DR. TOTTER: It would be something like that. That’s about right. MR. LARSON: So, I would say just as a start of that, if there is any effect whatsoever as, it’s probably 100 to one off. DR. TOTTER: I tell you what you might do just for your amusement sometime along that line, the fellow who really is behind all the present scurry about radon, that fellow [Victor] Archer who had charge, Archer and [F.E.] Lundin I think were the original pair that had charge of the original USPHS’s [U.S. Public Health Service] radon studies. Archer has written a paper somewhere about ’82 or ’83 in the Nuclear Safety Journal, Journal of Nuclear Safety. I think you’re familiar with it. It’s published here. MR. LARSON: Oh yeah. DR. TOTTER: Bill Cottrell used to edit it. It’s right next to one of mine in there and I don’t think everyone sees that Journal outside the very specific people involved in nuclear reactor safety which you’d do well to read because it tells you kind of what makes Archer tick. MR. LARSON: Oh yeah. DR. TOTTER: Just a statistical study on background in various diseases. It’s absolutely weird, a weird story. If you look at that it will give you an idea of how to judge the architect of the whole radon problem. MR. LARSON: Oh yes. DR. TOTTER: I don’t know if this should go on there or not, but there was a lot of politics involved in that before you came to Washington. It inundated me quite a bit. MR. LARSON: This is edited. This tape is edited. DR. TOTTER: If you don’t like it, take it off. MR. LARSON: It’s whatever. DR. TOTTER: Okay and it really started, the real trouble started in ’59. That’s when the industrialist from California was trying to, was chairman of the AEC [Atomic Energy Commission], what was his name? MR. LARSON: That was before [Glenn] Seaborg. DR. TOTTER: Just before Seaborg. He was only there for a year or so. MR. LARSON: Yeah. DR. TOTTER: It doesn’t matter. I don’t think he was at fault, but it happened under him I think because the production people and the reactor people felt that the biologists were cutting in on their promotions because they made everything look unsafe. So they decided to get the biology out of the AEC and they, he found out rather quickly that there had to be an internal safety operation. So they flipped the biology division into operational safety and biology research, and then they said that biology research would go to USPHS. They were far along on their bickering. The Bureau of Rad[iological] Health was created out of a cadre of unemployed or nearly unemployed uniform personal from USPHS. They expected to inherit $80 million or so, but all of a sudden the Joint Committee stepped in and said you can’t do this, they don’t have any competence. You better keep that in the AEC. That’s what saved the research program when Seaborg came, but then the Congress told us we had to get together with this Bureau of Rad Health, had to do things jointly, but all they were interested in was taking the good part of our program and letting the part they didn’t want go. It was a political thing from then on. They wanted our money. MR. LARSON: Oh yes. DR. TOTTER: The way they tried to get it was to back sub rosa I think largely, the claims of everybody who was anti-AEC. Now I know that happened because when [John] Gofman went off, fired his rocket, I talked to the deputy director who was a neighbor of ours at the Bureau of Rad Health and I talked at some length about I thought, frankly thought that Gofman was off his rocker. He’d blown a gasket and within 24 hours Gofman knew everything I had said. MR. LARSON: I’ll be darned. DR. TOTTER: That came to me through I think one of the deans of Minnesota who heard Gofman’s talk shortly thereafter that in which he quoted a number of things that I had said to this member of the Bureau of Rad Health and he sent me a transcript. They had tape recorded the talk and I recognized these things that I had said across my back fence. MR. LARSON: I’ll be darned. DR. TOTTER: So I sent a copy of the transcript to that guy. He wrote a long letter of apology and a letter to Gofman saying, “Old Totter didn’t really mean these things.” But that’s what has happened all along. There has really only been one or two people in there who refused to attack everything that the AEC did because they were sounder scientists than the others. They were not politicians and Billy Mills was one of those. He had taken his training with [inaudible] Goldmeier and he never joined in that, but most of them were dead set on undermining the AEC in any way they possibly could. That still goes on. It’s inherited. Those people are all gone now. They are no longer there, but some of that bitterness over the loss of that $80 million is probably what is going to carry this fight on. MR. LARSON: Oh yes, and it actually still permeates into that report at the National Academy Foundry, that insane recommendation that several thousand deaths are due to radon coming into basements, which is so ridiculous. Well that certainly adds a lot to the background of this whole thing. Well fine. Are there any other points that you think are worth mentioning here? We have covered a lot of ground here and a lot of background and a lot of valuable information. DR. TOTTER: I see there is a meeting going to be held shortly on the peer review system. MR. LARSON: Oh I hadn’t heard about that. DR. TOTTER: I just saw something about it. They were going to talk about who the peers are and how the reviewers, editors and reviewers, how the editors get their reviewers and so forth. It’s an important meeting, but I don’t know whether the right people will attend. MR. LARSON: I didn’t, that somehow went by, I think there was a little squib in Science about it, but I didn’t really read the article. So, of course one of the, a lot of these peer review systems get to be old boy networks. You know, they are repeated, and repeated, and repeated. The peer review system is a perfectly logical thing, it’s only the makeup and how it’s administered. DR. TOTTER: There needs to be some way of clearing it up every once in a while. I don’t know anything better, but it is in that shape and I would say the epidemiology business is the worst of the lot. Only the ones who have an established name can, are allowed to publish anything. MR. LARSON: And particularly anyone who tries to get in different points of view there are just immediate, in fact I have heard some awful stories, this is off the record. There have been definitely in some of the agencies including the DOE [Department of Energy] and even before that ERDA, somebody will want to make a study, you know, of certain things, good scientists and essentially the message comes through loud and clear, “Well, fine, make this study, but make sure the conclusions are this.” They don’t say it exactly in that way, but it will raise the eyebrow and a few other things. That message gets through loud and clear. So you get, there is an awful lot of studies that come through in this particular… DR. TOTTER: I got told in a letter from a fellow who I actually asked to review my paper said, “Why would you take away the hope for these people?” MR. LARSON: This is the sort of thing… Well, but these are all the tough problems. DR. TOTTER: Yeah. MR. LARSON: But as I say, I always say as long as there is all this money scaring people to death, we are going to have business. DR. TOTTER: We sure are. MR. LARSON: Well thank you very much, John. I sure appreciate this. DR. TOTTER: You’re welcome. MR. LARSON: You’ve really been a great help in giving this very valuable background. DR. TOTTER: I hope you get something worth keeping. MR. LARSON: Well this, I go back… [End of Interview] |
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