The health effects of low level radiation. My background begins in physics with a Bachelor of Science, Cal Tech, followed by working as a physicist in the navy during World War II, medicine, and MD at University of California, San Francisco, followed by five years of internal medicine residency and biophysics research at Harvard and Tufts universities, six years of radioactive tracer, metabolic clinical research at the University of California in Berkeley, and 30 years as acting director and director of the clinical laboratories and chairman of the department of nuclear medicine.

Upon retiring in 1991 as emeritus professor of laboratory medicine and radiology, I accepted an appointment as a visiting medical fellow at the U.S. nuclear regulatory commission in order to assist in revising regulation of medical uses of radioactivity. Coming to medicine through physics and biochemistry, I believe that physics together with its sister chemistry and daughter, biology, do furnish the basic knowledge of laws of nature. Our welfare really depends upon a harmonious interaction of these laws of our environments and physical body with corresponding human actions of integrity and conscience. It's important to honor your intuition and fertilize it with facts. This will create educated intuition. We must develop a learning spiral outward with balance between traditional thinking, intuitive insights and statistically significant objective observations. Good information stands the test of time, and it often takes a long time to gather reliable information.

Let's see if we can get these operative here. The interplay of intuition and observation are clearly shown in the lives of the German August [Kukule?] and the American Linus Pauling. You may recall how the chemical formula of benzine was discovered. One night, [Kukule?] had a dream in which a snake held its tail in its mouth. He awoke recognized his intuition and subsequently proposed the hexagonal formula for benzine with alternate single and double bonds. Though his formula is still used--

Though his formula is still used, two objections arose concerning a-typical properties that are not normally associated with double bonds. 66 years later, in 1931, Linus Pauling applied quantum mechanics--applying quantum mechanics, described a hybrid state which subsequent X-ray to fraction analysis supported. Linus Pauling, Nobel prize for chemistry and later, for peace, was my undergraduate chemistry professor. He remarked that before going to sleep, he always placed a pencil and note pad at bedside in order to immediately jot down any intuitive insights before they could be forgotten.

One of these intuitions was a helicle structure of DNA formed by three base strands. He discussed his insight with James Watson, one of his post graduate students. Watson then went to England to examine Rosalind Franklin's X-ray to fraction [parents?] of DNA. He took her studies to the mathematician, Francis Crick--

He took her studies to the mathematician, Francis Crick for analysis. Crick confirmed the DNA molecule was helicle, but with two strands, not three. Subsequently, Watson and Crick received the Nobel Prize for the discovery, in 1953 of the molecular structure of DNA, actually based on Pauling's imaginative concept.

We notice that there is a theoretical physicist, a Richard Feinman, and ah, he does not--he--he gives full credit to these imaginative insights, but then says that if it disagrees with experiments, it is wrong. And that simple statement is the key to science. It doesn't make any difference how beautiful your guess is, it doesn't make any difference how smart you are, who made the guess or what his name is. If it disagrees with experiment it is wrong. That is all there is to it.

When I came to the NRC, I had long accepted the biophysical assumption that because damage to DNA is proportional--(a little awkward here)--because damage to DNA is propor--OK, OK.

Because damage to DNA is proportional to the dose, that all radiation is harmful in linear proportion to the dose. This is known as the linear no-threshold hypothesis. LNT.

As I said before, the LNT hypothesis assumes that all radiation doses are harmful. It's employed to calculate the number of deaths from minute fractions of background radiation, but there's no human data to support this use. I'm speaking of low dose data which approaches to zero. Less than let's say, ah, 30 rem. 30 rem. That's ah, 300 millirem.

Then, later--a year later, in 1992, a 1989 article on breast cancer came to my attention. Though the article concluded that the risk of death from breast cancer increased linearly with radiation dose, their own statistically significant low dose data, which you will soon see, showed that low doses prevented breast cancer--were beneficial.

Now, how can this be consistent with DNA damage? Current molecular and cellular biology explain this seeming paradox. Now, many people have been informed and do believe that exposure to radiation in any dose causes cancer and genetic changes in our children. But, the recent advances in molecular biology during the past 15 years bring a new understanding of the effects of radiation on organisms. Low level radiation is actually beneficial.

Now, now this is Nobel Prize winner--I'm going from Nobel Prize winner to Nobel Prize winner. Ah, he's from the University of California at San Francisco. Mike Bishop--this was in a textbook--textbook of molecular biology, ah, 1989:

Our survival depends on our very capable damage-control biosystem, that prevents damage to DNA, repairs damage to DNA and removes damage to DNA. Almost completely.

And this is the system that Mike Bishop--and this is the system ah, that Mike Bishop, the discoverer of the [onco-gene?] referred to. We see the, ah, hundred million free radicals surrounding DNA, but they are largely removed by anti-oxidants and ah, enzymes that scavenge these free radicals so that only one percent get through to actually react and alter the DNA. That still is a million alterations in every cell's DNA every day. But, we have an enzymatic repair system that repairs most of this. So that only one in 10,000 of these, ah, alterations persist. So now we've ah--only have a hundred persistent alterations in every cell, every day, but we then have a final ah, clean-up process of removal of these persistent alterations--one is, ah, by apotosis that's known as cell suicide--the Japanese call it ah, altruistic suicide. Ah, the ah, necrosis--sometimes the cell is damaged so badly it just dies. It doesn't get programmed to death. Or the cell differentiates. Once the cell differentiates, even though the ah, alteration of DNA is there, that cell can no longer replicate so it will never become a mutation that has any genetic influence on other cells. And finally, when--when all else fails, and we actually have a--a growth, ah, and the--and the immune system hasn't nipped it in the bud, even a well-established ah, tumor--malignancy, as we will see, can be removed by the immune system.

So that in order for us to be healthy and live to a ripe old age and avoid cancer, what we need to do is to keep this system strong. It turns out that it's not the ah, damage to DNA, not the persistent alterations that are produced by radiation ah, that ah, determine the effect of radiation. They're too small. If you notice those little small numbers under "persistent DNA alterations"--that--the background radiation--low LET--the radon just affects the lung--the whole body, the low LET radiation ah, produced one ten millionth of the persistent alterations that our own metabolism produces. So, it's not the ah, amount of mutations that radiation produces, but its effect on this system that's important. High doses harm this entire anti-mutagenic DNA damage control biosystem, low doses, as we will see, stimulate it. And this is well documented in [un-scare?] 1994. Low doses stimulate every aspect of this. The anti-oxidant and--and enzymatic scavenging, the repair enzymes ah, are stimulated, and the removal process ah, and immune system ah, are all stimulated by low dose radiation.

Now if you'll --if you'll notice on that previous, ah, view graph, there was about one mutation a day that accumulates in every cell--maybe--maybe as many as two, but of that order of magnitude--one or two mutations oc--will accumulate in every cell every day. Now a--of course, as I said before, cells that don't replicate--ah, let's not actual call it mutation--it would be a persistent alteration, but in the stem cells--in the germ cells that do replicate, every day one of them accumulates a mutation, and these alternations which are not eliminated by our ah, biosystem are residual mutations and a very small fraction of these eventually become the cancers that are the cause of death in approximately 25% of the population in old age. In other words, when these mutations have accumulated to the point where they damage the c--damage--when they damage the damage-control system, then, ah, when you begin to see, ah, cancers appear.

Now the rate--the rate of DNA mutations produced by background radiation is negligible. Ten million times lower than the natural normal rate of oxidative damage, even when double strand breaks are considered. Many chemicals, other factors, have a far greater effect than radiation on cell damage.

Well, what is this background radiation that we're talking about? I think you've already seen, ah, this before. I just want to emphasize that ah, the 200 millirem per year derived from radon is a, actually a calculated value, based on what the effective whole-body dose would be if it did radiate the whole body, but it only radiates the lung and the--actually, the--the lung gets 2,000 millirem per year. That's from the natural radon that is--comes out of the rocks i--i--in the--in the earth--the radon that we all have in our homes.

Cosmic radiation, 27 millirems, terrestrial, 28, internal 39, medical--medical is the one are where you can control a significant amount of radiation simply by avoiding all, ah, diagnostic procedures. Consumer products--and then we see that the nuclear power and fallout are less than 3 millirem and that includes ah, things such as ah, air travel--crossing the country is 4 millirem, of course not everybody crosses the country every year, but ah, going to the next meeting on the West Coast, ah, everybody who flies across will get 4 millirem.

Again, this is just to emphasize how little DNA damage is performed by this background radiation that we've just looked at. In 100,000 cells every day we have 10 million persistent DNA alterations caused by these reactive oxygen species--free radicals of oxygen, and only one persistent alteration due to radiation--10 million to one.

But even though it's a very, very small fraction of the damage that it does to DNA, radiation nonetheless is extremely important. Because high doses of radiation decrease the activity of this anti-mutagenic DNA damage control system, allowing this enormous amount of damage to pour through. Low doses, however, stimulate this anti-mutagenic biosystem so that there are fewer mutations, less mutations accumulate, you live longer.

And this, ah, shows the response of the ah, metabolic and radiation DNA damage control system--the anti-mutagenic system we've been talking about--to low LET radiation. Now, that--the low LET radiation goes up almost linearly. It doesn't look linear because it's on a log scale, but it is almost linear. And so, in truth, the damage produced is ah, virtually linear, but its damage to DNA is very small, but its effect in stimulating the damage control system is large. We seen ah, at 10 milliceverts per year or one rem per year--we're talking about--background radiation--one would have a 20% ah, increase--and this is a very conservative estimate (experts have gone over this)--20% increase in the response of the system, which would correspon--that's the green line--which would correspondingly reduce the ah, mutations ah, 20%, you see, going from one a day to 8/10ths a day, which is what we say--which--we had one a day before, and now, this is the situation--(five minutes?)

Each--sorry, let's just skip this--we're running out of time.

Each, ah, step in this process preventions ah, st--we arbitrarily say there's a 7% stimulation of that--7% stimulation of enzymatic repair and 7% stimulation, all of which come up to a 20% overall ah, response of the system, bringing the mutations down to 8/10ths in a day.

Now, I have a number of epidemiologic studies which, ah, I don't have time to present, but ah, I do have them shown in some handouts that I left on the table in the hall. I do have these figures, that I'm not going to show now in some handouts that are in the hall, so that if you want to see the epidemiologic evidence which corresponds to this ah, improved, ah, longevity and the decreased cancer occurs with exposure to low dose radiation, ah, please pick it up, take a look at it.

I just do want to show one--the last one here, because I said you would see it later, so I'll just show it now. This is actually the data that--an-and this was plotted up by--not by my self, but a physicist at the Massachusetts General because the authors of the article did not publish the graph. They just published the tabular data. You see it's significant at 15 rem, ah, more than two standard deviations below the ah, controls. We have a 34% decrease in br--breast mortality. This is that prevention. In other words, a third of these women who otherwise--now [those are?] controls who received little or no radiation--a third of them that died would not have died if they had received this 15 r. Now th--these are small doses. This is about the size of a mammogram--2/10ths of a --2 ah, 2 millirem--I'm sorry, 200 millirem--2 milliceverts, ah, and ah, in each fluoroscopic examination. And they were at a tuberculosis hospital and had many examinations.

This shows the response of the lymphatic immu--im--immune system to ah, low dose radiation. At about 35 rem, or .35 [grey?] you see there's a peak response of the immune system--this is in mice ah, in the intact, ah, mouse on the right, a 40% increase.

Now, this has been studied for quite a while by Professor Sakomoto, ah, and his group in Japan. He also was, ah, in charge of the radiotherapy unit. He found that when he, ah, injected malignant cells into the groi--into the groin of the mouse, that in about, ah, a month, they would metastasize to the lung, and then about a--ah, two, three weeks later, he would, ah, look at that. And you see here the--you see here the, ah, at 15 rem the metastases fell--at 15 rem, the metastases fell to 40%, but as the radiation increased to 50 rem, the immune system was harmed and actually the mice had more metastases to their lung than they, ah, had without any radiation.

So, Professor Sakomoto, being very ah, concerned and interested in this, had a patient who was very far advanced--terminal ah, with ovarian cancer--huge mass in the abdomen, metastases all over the peritoneum, all the organs were covered, and metastases in the lymph nodes as well. The ah, gynecologist said that she was terminal, she could not survive more than six months, but in order to ah, make ah, those remaining months more comfortable and allow her to eat, this huge mass which was pressing on her ah, colon, ah, had to be, ah, irradiated with high doses. Professor Sakomoto felt, well, in this case, what he'd also do while he's doing that is give low dose, ah, whole body--low dose whole body, ah, radiation to stimulate the immune system, and this was the ah, plan.

HE, ah, later ah, irradiated patients either whole body, from head to toe, or half body for just the chest, ah, from the ah, top of the thorax, that is the bottom of the neck down to the bottom of the rib cage. And he would do ten ah, rem, three times a week or 15 rem twice a week--that is 30 rem altogether each week for five weeks for a cumulative dose of 150 rem.

Well, this patient responded amazingly well to this. Ah, sh--at six months she felt fine, and ah, felt that ah--that they had cured her. However, at 18 months, she began to lose weight, go down hill and ah, had to ah--and finally expired at two years. She did not have a malignant cell in her body when they did post mortem, ah, examination. She was free--wha--what killed her was the blockage of her colon by the high dose radiation. The scarring had completely shut down her colon and that was the [ah/end?].

Now, so after that and similar cases, ah, Professor Sakomoto did a series of--of non-Hodgekins Lymphoma patients. And here is a patient who had half-body radiation--half body radiation and we see that this tumor which was at the base of the brain and the top of the nose--remember the half body radiation doesn't extend beyond the supersternal notch here. Just seven weeks later--disappeared.

And these are the results that he obtained with his non-Hodgekins Lymphoma patients. Three of them, as you see, ah, expired within the first three and a half years. But after that, they all survived--that is, the other twenty all survived out to nine years is when--when he ah, turned in his report, whereas the--the patients who did not receive low dose, ah, radio-immunotherapy--they cons--ah, continued to die off and by nine years we only had 50% survival as against, ah, 84.

So, in conclusion, the experience and the facts that ah, Richard Feinman talked about demonstrate that we cannot assume that all ah, low doses of radiation are harmful. It has never been validated. There's no data to support that. And it provides the current basis for public fear for nuclear technology and enormous expenditures to protect the public from all applications of nuclear technology--applications that are very beneficial for humanity, and for the environment.