Interview with Melvin Sikov

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INTERVIEW WITH MELVIN SIKOV - SYNOPSIS 1. About book plans 2. Early work on radioactive material transfer to embryo/fetus Very early work with radon - reference is in his PhD thesis Radioiodine work at Columbia His o m early interest in embryo/fetus Transplacental transfer of phosphorus 3. X-ray work at Wayne State 4. Beginning of work with plutonium - found it was embryo-toxic - would kill embryo but seldom caused malformations Effect secondary to an effect on the yolk sac Post natal effects With plutonium, if protect mother, you also protect the fetus Tumor development in newborn and young.lung5 . 6. More mobile materials - e.g. tritium 7. Have data on several actinides 8 . Uranium work - thought not important but later wished they had emphasized it more In reports but not published 9. Work with krypton Work with large animsls Freely-moving nuclides can be considered equivalent to 10. Sensitivity of fetus Problems of the young Marshallese Fetus picks up more radioiodine

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Battel le Pacific Northwest Laboratory where, and what you have seen done here and elsewhere. o r comment on the past i n some way? , This is going t o be hard t o do following an outline, without having prepared I am assuming that you don't conclude that I'm crazy t o undertake this I think this would be afun book t o read. I think it would too, ifI can do what I want t o do. I t ' s not going - I t ' s not going t o be in great depth, being this broad, i t What I want t o do i s give a perspective type of comment on how, Could you simply reminisce Let me try reminiscing,and then I ' ll just sort of take it historically. Firstly,it is my impression that the first real studies of FetalPlacental Transfer was done by Miriam Finkel during the war, and published q u i t e SIKOV: Actually she did the plutonium work with me. I t transfer because she looked afterbirth - I think i t was that I can ' t remember. I t was i n Physiological Zoology a bit later. The center for that kind of work was really here, however. wasn ' t real l y placental dogs and something else animals that were i n various stages of gestation atthe time of injection. "Transfer of Radiostrontium and Plutonium i n Laboratory Animals" have been some (Ican ' t remember the dates on that)early work with radioiodine published a little by a t Columbia. [Couldn't remember names, N.S.] It might have been Fail la. Ididn ' t know he ever dida biological experiment like that [it was

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SIKOV: Idon ' t know i f he measured actual transfer itself,butat the time I guess he described i t as " radium emanation - dissolved in water." where he got some hemorrhage i n the late fetus ' o r offspring. Ican ' t remember the exact details, IfI remember correctly,it was a study in rabbits Would you have the reference? SIKOV : Yes, i n fact, i t ' sin my thesis.At the time, I reviewed all the early STANNARD: I t would be a wonderful help i f you would be willing t o Xerox off the reference list from your thesis and let me have it.Idon ' t intend t o spend an enormous amount o f time on the period between 1900 and the beginning of the Manhattan Project, but I feel duty-bound t o say something about the background. How it all started. The fact that cyclotron-produced isotopes had already gotten a leg u p on alot of these things, etc. haven, Tom Noonan and I were talking. He was thinking in terms of doing some,work with iron and blood. 1got very fascinated by work that Wilson was 'doing ( I guess at that point he had left)but stuff that he had published on the effects on When i t came time for me t o take a thesis topic before I went t o BrookIdon ' t know why Igot fascinated because I wasn't really interested in the embryo at that point, butit just seemed awfully interesting, SOI asked him if I could work witha radionuclide - notto 90 over the same ground - at that point I couldn't distinguish between one radionuclide and another.

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The few things that had been done and all the other thinas that needed doing, I was looking for something different,and I asked if I could use radio - phosphorus and use a little bit of redeson(?). I think it was funny because he said, "Well, you ' l l be on your own" because he knew nothing about it. the summer Idid some reading, andit turned out that during the summer he had done an awful lot of reading,so he learned the area pretty well by the time Igot back. After Braokhaven (Stannard: What year was that ? ) , i t would have been ' 5 2 because Igot married i n ' 52,in the fall of '52, andI started on the thesis work by trying t o get a handle on the transplacental transfer of phosphorus and its effects.I ' v e been working on development STANNARD: Not necessarily radioactive isotopes, b u t other things too? SIKOV: Actually, a large part of my work is still radioisotopes. Itdid form the basis for working with other materials. STANNARD: During your time a t Wayne State you were i n the same area too. SIKOV: Some studies with x-ray. I learned enough t o know that everything hadn't been done earlier. We did a fair amount with x-ray, but then Idid some radiophosphorus work when I ' first went t o Wayne State then got into radioiodine during the last couple of years thatI was there. When I came out here I started with the radioiodine and then started looking into some of the other materials. Wayne State my clinical involvement - we had the definite arrangement where I would not touch the alphas (radium - radon stayed with somebody else).It didn ' t take too long here until I started getting interested in plutonium. In fact,it was funny because when I was a t In the last several years now mostly w i t h plutonium and the other transuranics. c4 STANNARD: Is i t the kind of thing you can summarize easily ? What's come out SIKOV: Well, i t was sort of a surprise to start with. sort of thing in other regards. toxic, i n the sense i t would kill embryos. We've been seeing the same One thing we found with plutonium, i t was embryoWe very rarely got malformations.

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Atthe same time something we have not been able t o take the time t o follow upon, and we definitely want to,it does seem t o synergise with other materials that are carci nogeni c . STANNARD: Non radioactive materials? not due to an effect on the embryo itself,but secondary to an effect on the only i n the rodent. sac. A t the same time the cells in the gonads and the original progenitor cells of the system are formed i n the yolk sac,and there is a transient yolk sac i n other species, including man. work we were doing with the rat was completely unrelated t o everything else, and i t did turn out that the distribution in the baboon was the same,and it didn ' t take up i n the yolk sac. i n the human. However, the potential effects on the gonad or the hematopoietic system does have a potential, and this i s something we are working now. We have put a lot of emphasis looking a t the post natal effects,.and we haven't restricted things t o the embryo, but we have been trying t o get a view relative to stage of development looking a t various embryonic stages, but also looking a t newborns, juveniles, weanlings, and comparing those with the adult. Yes. Right now i t looks like most o f the embryo toxic action itself is I t was kind of interesting because the yolks ac is of prime importance Itis the only group that has a residual, or persistent yolk -- ledid one experiment with baboons t o see whether the So i n terms of the embryonic death, one wouldn't see i t With various materials YOU find qualitative differences, which have t o be factored in,but also quantitative differences. I f any o f these do relate to particular systems that are developed, o r developing, a t the time o f administration, re-distribution of and i t ' s probably correct,that the fetus.is much more sensitive than the mother. Particularly with pre-natal exposure, i t ' s dogma, i t ' s accepted, kl So,if.you are looking a t risk,you set the risk relative to the fetus. When you w get t o radioactive materials and other forms of energy a n d chemical substances .as well, you might produce an effect in the embryo. If you look a t long term effect, or relative risk, you have t o look a t what that particular dose level i s going t o mean i n terms of the mother. From everything we've seen sofar

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with plutonium, i t looks like if one protects the mother, one has protected STANNARD: This is because o f the poor transfer ? has a transient availability exposures, you never worry about acute effect. you might get a given amount intoa fetus o r even a new-born. dose basis, the new-born might be more sensitive - i n - facy,it might be quite a bit more sensitive.If you take a new-born, any animal,and incorporate a given amount of material into it (say there is no excretion). Poor transfer and the fact - - - i f you look a t something that only and a single exposure ora limited number of I f you look at it in perspective, which is going to weigh 8 grams, by the time itis weaned itis going t o increase i t ' s body weight eightfold, roughly, so i f there is no loss you still have a eightfold dilution o f concentration. factor of six o r eight you've gotten further dilution, so even ifit ' s more By the time i t grows by another sensitive (and here you have to factor everything in because you may be doing something by virtue of that dose which is going to be persistentL you still have this tremendous dilution which is going to affect all your dosimetric started out looking a t inhalation of plutonium dioxide, comparing the newborn with the adult. (of the aerosol) which we didn ' t get. hoped for, which may have been just as well because we found here that We've gotten i n some things recently, on the other hand. We We were aiming for real narrow size distribution They were a little broader than we had the total amount of activity per gram i n the newborn lung is less than i n the adult. What happens is, judged from lung auto-radiographs and from the counts i n the nose - o r the nasal area i n block, the newborn nose have gone off on some experiments now using chromium labeled microspheres trying toget this defined and then go back t o some effects and upper respiratory passages are a very good Only the small particles are getting down into the lung. We

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studies with the plutonium. But here, for the given amount o f material - even though the animal is growing - i f you are dealing with a particulate, the cells at risk will probably stay the same - o r the groups of cells at risk may stay the same. of the lung that has taken place inthe neonatal period. speculated that bronchialization does have a predisposed tumor development, so the newborn lung is quite immature, soif you have a particle sitting there (particularly if you are dealing with small particles) as these things are developing,you may end up with a lot of cells a t risk. The ones that are exposed i n the bronchi develop out,and you get new cells at risk. These cells are more sensitive .... The response may be greatly exacerbated because of the growth So that is one sidelight we have gotten into. The newborn is an entirely different problem, i n some regards, than i s the fetus. STANNARD: This is, giving the dose tothe newborn? How old? STANNARD: Oh, how do you do i t ? SIKOV: Actually the little tubes that the disposable syringes come in,with a little modification (cutting off the tip and putting i n the animal, we can geta good nose only exposure). STANNARD: How about things like tritium, very mobile materials? With plutonium i f you protect the mother,you protect the fetus because so little of i t gets across. From the inhalation experiments we're going t o the day following birth. What of things like tritium? SIKOV: Witha mobile material you wouldn't expect this. I t depends on how much - what kind of concentrations - and what your exposure regimen might be. Certainly with radiophosphorus i t was not the case because we could go a t a fraction of the LD-50 and get very massive malformations. tritium have seen this sort of effect. we are going t o be able t o draw some generalizations. t o do, and I ' v e been hoping t o do for the last couple of years, and Ijust never. ' People working with I think we are getting toa point where This is one thing I want

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can the month to do it,but we have data witha number o f the transuranics looking a t the fraction going into the fetus. deposition i n the placenta and i n the yolk sac. atit, looking atit in terms o f valance, etc. No pattern has yet evolved. Some of it relates to the maternal affinities for the materials, but we now have some uranium data,and we are going t o have t o get some more for We are also looking a t the I t ' s going t o take alot of sitting down. ---other members o f the fuel cycle. The uranium is kind of important. When we didit,it didn ' t look like it would be real interesting, and i t wasn't real important a t the time, so we figured well, l e t ' s concentrate on something else,but I think we are going t o have t o go back toit anyway. We have uranium, neptunium, americium, plutonium, curium, comparable data with all of …