Medical research; Leukemia

The following program is produced by the University of Michigan broadcasting service under a grant in aid from the National Educational Television and Radio Center in cooperation with the National Association of educational broadcasters. Lukemia. A program from the series human behaviors social and medical research produced by the University of Michigan Broadcasting Service. These programs have been developed from interviews with men and women who have the too often unglamorous job of basic research. Research in medicine the physical sciences social sciences and the behavioral science vocational you will hear what may seem like a strange or an unfamiliar solve. These are the sounds of the participants of it. It's his laboratory or his clinic where the interviews were first conducted. The people you will hear today are Dr. Joseph Hill director of the widely Research Institute in Dallas Texas. And remarks by Dr. John Enders of Harvard University and Dr. John Givens Jr. of the Jefferson Medical College in Philadelphia.

And my name is Glenn Philips leukemia. Or you may have heard Lucas I think Luke anemia or Lou Cosas the mention of the word strikes fear. What is it. What are the chances of a cure. What are the present trends in research on the disease and what research approaches may prove valuable perhaps in the next half hour these questions can be at least partially answered. The late Dr. Frank Bethel of the University of Michigan defines leukemia this way. Leukemia is a fatal disease considered by many to be neo plastic. That is an abnormal growth which arises primarily in the blood forming organs and is characterized by an extensive and abnormal proliferation of the white blood cells and their precursors with infiltration into the various tissues of the body especially in the bone marrow spleen and lymph nodes. Almost invariably at some time during the disease immature white blood corpuscles appear in the circulating

blood frequently in great numbers. In most cases it is associated with anemia often of a severe degree. To illustrate the growth of abnormal cells. Picture if you will a cubic millimeter of blood. Normally in the human body. There are about seventy five hundred white blood cells in this area. Leukemia. The number increases to as high as 1 million white blood cells in the same area. I asked Dr. Joseph Hale if there are different forms of this disease. I think perhaps the two most interesting forms as far as the public is concerned are rather cute or chronic because of the diseases. Disease behaves very differently. In the chronic and some forms of may live up to 20 years or more in the acute. For if you live beyond the year and a half. However we can also divide them according to the type of cell involved. Since leukemia seems to be a type of malignant disease where there's an excessive. Proliferation of one kind of blood cell

involves only one kind of say the type that can be. The lymph or side or the grain of the site and so for us so it can be classified in two ways chronic or acute into the common blood cell types. In answer to the question are the incidences of leukemia on the increase or decrease. Dr. Hill said This question is one which is very difficult to answer because of the fact that diagnosis may be more accurate. People may be more aware of the disease. In my personal experience for example would not be a criterion because whenever you start to work in some particular way it may attract patients from farther away. Most of us however think that it is on the increase. And to me one of the most significant conversations I've had in this regard is with the pathologist from New Zealand who happened to see all of the diagnostic slides of all the leukemia is in the island for about the last 20 years. This is Dr. Staveley and he said he felt he could diagnosis accurately 20 years ago as he

could today and no reason why this shouldn't be true. And he feels that there is an increase. However this require a lot more study and careful statistical analyses in our National Institutes of Health are doing this now. Dr. Hill feels the cases of leukemia are on the increase. I asked him what he attributed this. And I have asked the tough question because immediately bring up the question of what causes leukemia and of course the ultimate answer of this is unknown but we like to think of these things rather loosely as perhaps a chemical civilization catching up with us. And not just chemical but chemical and physical. And since we know there are at least five factors that more or less certainly have something to do with the causation of malignant disease and I'm including leukemia as a special form under this. We know that our genes are hereditary Constitution our own chemistry has something to do with it because certainly. In animals there can be strains of the bread that have a high incidence

of leukemia. Secondly we know the hormones have something to do with it. This may simply be another way of saying our inheritance again because our hormonal makeup depends our horizons. Certainly chemicals have something to do with the causation of cancer this was the earliest thing that was proved. And of course everyone knows from the newspapers a little bit of radiation is going to cause cancer over us. And then finally viruses which at the moment is perhaps the most active topic in this connection. Well you can take your pick here because you can say that today. There are lots of things that bear on the problem certainly there's a question of radiation. More and more radiation. Personally I don't think this is important to some people make out because the heavy radiation that can be associated with a causational key is not the type of thing that the ordinary citizen is receiving. Certainly we get all sorts of chemicals in the air in our foods and every other way. But it's difficult to tie this in with the known chemicals that are potent. Cancer causes

and so on. Whether there are new forms of virus developing and this is a possibility perhaps we control the bacteria so well that maybe the viruses have a little better chance to get going. Two questions immediately suggest themselves from that answer. The first is an interesting speculation. Dr. Hill said perhaps our civilization is catching up with us. Other statements from people who said that in some of the other countries where living standards were lower. Many of the diseases baffling American scientists do not occur or occur in a much lesser extent. Dr Heal's comment was. Well actually this is an awfully interesting question. I rather think that this is hardly worth the price to be able to resist some of these diseases by reverting to the primitive ways of living and that of the some truth and that's because in very primitive societies we know that some viral diseases seem to have a very low incidence. The contrary may actually be true in that in these societies

they may have a viral disease so early in life that they develop an immunity and the bad cases die in the the population may not even be aware that the disease is common I think undoubtedly there's a good deal of truth in this. The second question I referred to was on the subject of radiation. My question to him once. Isn't it true that radiation is not in every case harmful. His answer was a little booby traps in this one. There are those who say it is that any amount of radiation is harmful and it's just a question of the more you get the more harmful it is. I don't think this has been proved however. And we know that radiation in many various ways such as taking X-ray pictures helping a diagnosis using it for therapy and so on has been a great lifesaver. And I'd hate to see the public become so fearful of radiation in various helpful forms of medicine that they would fear to have it. And the thing that I am decrying is the tendency to

be fearful of amounts of radiation for example that would be represented the difference. So you're living in a wooden house or a brick house or changing the altitude at which you live say from sea level to a thousand feet or even to move to Denver a mile up. These differences in radiation are often greater than the differences that we have been talking about. Dr. Hill also mentioned an association between leukemia and the virus. And he further commented on this possibility. This depends on what you're talking about animals or humans. There's a great deal of evidence in animals and indeed it is possible to induce leukemia and animals apparently with a virus suspension that is cell free material. It is also possible to increase the incidence of leukemia and animals that are normally resistant to it by using techniques such as Dr. Gross of New York City did where he gave the virus to the new

born mouse and in a resistant strain some months later. These mice a large percentage of these mice would develop leukemia where as they mature a mouse was quite resistant to any development of leukemia. So we have to regard experiments of this type as having a good deal of significance. We must run however that when we speak of viruses causing leukemia we're certainly not speaking in terms of the usual direct relationship of a virus to a disease because in the for example in these mice I mentioned the virus is given at birth. And yet a good fraction of the mouse's lifetime later develop the disease so there's something different here. Dr. John Enders of Harvard University and one of the world's foremost authorities on the viruses added this about the association between leukemia and the viruses and there is you definite possibility that me may be in a kid with leukemia.

It is now known that a number of different leukemia as you might cause by a viral agent. In the case of him several lightish he's been known for a long time in a variety of of the in several it indeed. Are caused by different viral agents. For example St. Louis and several like the Japanese readership will either make wine and shit for all my life. Chef a likeness of horseshoes freak however is infectious for a man. All the others are known to be caused by federal agents. Dr. Healy is intimately concerned with research on leukemia and he

enumerated his interest this way. Yes our research revolves around the patient in the sense that the problem starts here and the solutions if any are attempted solutions must end here. The same time research institute like ours operates by having a sort of a vertical type of research so to speak extending from molecules to man. This means then that we might classify approaching two types. One direct attempts on the disease itself through experimental therapy. And secondly analytical approaches that vary all the way from very careful study of the different kinds of molecules in the blood and in the cells on up to electron micrograph studies leukemia cell searching for the virus. I asked Dr. Hill if he could be given the answer to one question about leukemia. What would that one question be.

Well of course this is just a leading question I realize obviously there could be only one answer this but it would be up to much discussion that would be to find a cure for it scientifically. One would be most intrigued by the cause because you can usually get a cure but if I had one wish so to speak give me the cure because that's the thing we're trying to do is to find the cure so that we can give the public relief from this disease. However let me. Assume that you want me to go into something further along this line of my own wishes. One of the questions that intrigues me most is the question of why are tissues are so individual and why we cannot accept graphs one from another except identical twins and yet why the fetal animal can except the graft of cells from another animal such as for example a non identical twin before birth. This is one of the great mysteries if we knew all about this this might give us a

wonderful point from which to start to attempt to cure this disease. And indeed some of our recent work has been along this line as many centers in the world have tried to transplant mono from a normal well human into a sick leukemia human in whom the bone marrow has been destroyed by intensive radiation. Unfortunately we do not know of any actual cures yet of leukemia but this is potentially a real crisis based on earlier work with animals where it was discovered that it was possible to transplant tissue such as bone marrow for one mouse to another mouse not an identical twin and or the genetic equivalent of a homogeneous strain of mice. And the reason this could be done was because a sufficiently large dose of radiation was

administered to the mouse receiving such now a sufficiently large dose to knock out the immune mechanism and destroy the recipient's Mao. This animal then if not for the treated would die. In other words a lethal dose of radiation. Now if such an animal after the radiation is given a large number of cells from the mouth of another mouse under these conditions it will take and the mouse can sustain life on another animal cell. This causes a great deal of excitement and hope in the field the Leukemia and the hard work along this line and further attempts to do it in the human have not to date been entirely successful. It is true that in Yugoslavia when they had a big reactor reactor accident Dr. Matt parish apparently tired of these people or marrow transplantation but apparently today they have reverted back to their own cell types and therefore it was not a permanent transplant such

as you would need if you were to hope to cure leukemia by this means. And our own institute we have been interested in attempting this not using X or radiation which gives a radiation evenly all over the body perhaps a little more on the surface but rather by using radioisotopes of colloidal type injected into the vein which because of the colloidal nature that means little tiny part particles too small of the microscope see are concentrated in certain organs. The very organs where this disease is concentrated and by giving a lethal or near lethal dose of radiation in this manner and then following it with attempted falling with large doses is nearly compatible human now is possible. We had hoped that this might be a rational approach. Quite obviously certain limitations would be involved

in doing such a thing. One will have to work with terminal of key mics which is not the most favorable time to do it. We have attempted this to date without success but with some results that are promising and I am not yet convinced that this possible route has been fully explored. We have had to drop the experimental rock of the radioisotopes and attempts at transportation but have gone on to do a replant ation of the patients own marrow not only in leukemia but also in terminal cancers of various types. It works something like this if the patients mare was not involved as in a terminal cancer may not be. Or in the case of a leukemia when the first remission and the bone marrow appears to be normal. You take a large sample of this mare by several needle punctures under anesthesia from the right hip bone. This is first frozen under special conditions

so that the sailors remain alive and is preserved at the temperature of liquid nitrogen. Summers are around 200 degrees below zero. And in these conditions the bone marrow cells can be kept alive like seeds and used for replanting later. Having such mouthbreather right is something like insurance and you can then treat the patient with a degree of vigor and with larger doses than would otherwise be possible because most of the treatments that will kill the cancer cells will also kill and depress the bone marrow cells in the past has been one of the limitations of chemotherapy or radiation therapy and any malignant disease largely freed from this restriction we can now approach dosages. Of chemical agents or radiation or enter metabolize. Here's a for are considered far too dangerous to use. We are working with this technique then today and attempting to.

Two I hesitate to say curate attempting to get much longer remissions in leukemia by getting the patient into remission by a standard technique such as an the metabolites or hormones stirring them out while they're in this apparently normal state. And then instead of merely withdrawing the treatment or maintaining it and waiting for it to fail and the disease to come back we then go ahead and give many times the ordinary dosage. Whatever modality of treatment we're using. Hoping this right that we might actually either get a very much longer remissions or are just possibly cured by such a technique. You know in my case where some of the strains of leukemia may actually be weaker not exactly comparable with human leukemia some cures have been affected or many years ago by such techniques. Dr. John given Jr. explained the technique of extracting bone marrow from the human body.

In large amounts and give it its about fat and cells. If you're going to give it intravenously can be given. You can ask out of the bus by putting a needle through the outer hard played about and just strong suction getting bone marrow out this is a routine procedure to study but hardly more than a hypodermic needle. In the massive cases where we have had dollars come in and give a red you don't you can take a read out from some individual or leave the skin of the Red Berets called Perry Osteen and the rebel reform. It's not as nice to look anywhere but you don't notice it yourself you just saw the chest cage you had before. And then not red and split up and under style condition and amount taken out of it so you get a

quite a large quantity and that is given to some of these people who have had to have. Actually I do control our use of a growth of blood cells and the x ray may be so successful in controlling the overgrowth that it makes them and they make they don't produce enough white cells or something and then you give them this normal bone marrow. Going back to Dr. Hill I asked him where he felt the progress of research has brought us at the present time in the area of leukemia. His answer hold out much hope. But at the same time gives a warning to his own profession. Of course this is a question that's so important. And even those of us who are working intimately with the problem of meeting with our colleagues and sharing interesting programs. I can't answer this. It could be tomorrow or could be next century. Of course one has a right to give opinions I feel or something's bound to give in the next 10 years.

I like to feel that we get it in our time. Certainly the amount of time and effort and money being expended in this area is greater than ever before. My only fear is that too many of us may be working in the same area. Lead becomes popular chemotherapy for example is the thing that most of the money is being spent on today and I think this is necessary because it to date has been the best way of treating the Kenyans. And yet screening 40 or 50000 Amaar compounds a year. We haven't come up with anything that is curative yet. And this program has been going on a long time. I think it must continue the answer may still lie in this direction. But I do hope that we don't just go down the same road together but that people try to turn out new ideas new concepts and rough and crude as it may sound. The immunological approach and this transplantation approach I feel has not yet been fully exhausted. And the other hand the virus theory is of a great deal of

interest today and those of us who are working with electron microscopes are seeing little bodies in the cells of leukemia tissues that look like viruses that the size of viruses or the shape of viruses. But of course we can't prove that individual little sphere is a virus. This Rouse is of interest and if we can succeed in freeing such viruses or particles and then by chemical type-A techniques concentrating them. And proving their viruses and getting a test system in animals this is the type of thing we need but this is just the type of thing that isn't worked out yet. We're just on the verge of many of these techniques. Raji had made very rapid advances and I hope that this time we can prove or disprove definitely whether they play a role in human leukemia. There is no question that research in technological areas has taken giant strides toward solving mysteries of our world. Almost every day we can hear or see on

radio and television all read in the newspapers of some concrete example as man heads into the uncharted realm of space. This is not true in medical and social research. Why we might ask. It is possible only to speculate on an answer. One speculation is that the public themselves will support research if there is something material and tangible to see immediately whether as some have said they can see it ascend skyward to success or meet temporary failure before leaving the launching pad. The payoffs in medical research are not so material. Here the great achievement yield dividends in lives saved and happier and healthier lives. In normal healthy growing children. I ask Dr. Hill whether he agreed with the theory that a lack of public support was produced by materialism. He said Oh yes I think it is. Let me say that I think it's up to us to try to show the concrete results. For example our last meeting of our board of trustees when I was attempting to challenge them to get out and help more with the

supports. And we showed them a little child. Who has had acute leukemia now almost four years and has been perfectly well during this time has grown norms of the school and so on. On previous occasion I showed them two boys in the teams would run athletic trophies although they have acute leukemia. I think these type of concrete results that we can use. To show people that something is being done. Actually previously prior to the era of chemotherapy in modern therapy these children all have been dead probably in less than a year. The surest and most direct means of reaching the public is through the medium of communication. I asked Dr. Hill but the communication media could do to help. Support is of vital importance. For those doing research in this area. By support I'm thinking particularly local support local farms. And local enthusiasm and help in various ways. For example our institution the relatives of

friends the parents of leukemia children without our requesting them and banded together to help. Through an association to carry education and appeals for funds in this type of thing for our institution. The really great advances sometimes in research are achieved by. By investing funds in long shots by reaching out into the unknown. It's true there are lots of funds available for research and I think our federal government is doing a wonderful job in in making funds available in this manner for research projects. But let the institutions need funds of their own local farms that can be used as sort of the cement to keep the structure together. Because. Research grants are on specific projects and to obtain one must outline the project have a very very rational idea rather concrete ideas on how to carry out the

experiments and so on. There are however better fronts of progress that we must make setting up whole new departments and so on. One must have funds for and so this type of support I think is the most important thing the communication medium can and list for the various institutions in the country. Once reaching the public however appeals are useless if they fall on deaf ears Dr. Hill voiced his opinions about the apathy of American people. Well of course as I was a tens if think it can't happen to me. On the other hand I can give you some concrete examples of the public reaction has been most heartwarming. The first example I happen to think of doesn't relate directly to leukemia but our chemists have been searching for a molecule in the blood that has to do with one phase of the clotting mechanism of course is important to look him in because hemorrhage is one of the symptoms of this disease and one of the cause of death. But in order to carry on this rug it was necessary to have a very large quantity of human blood. And one of the suburbs of Dallas I'm being made aware of this problem.

Volunteered one hundred four pints and gave one hundred four pints of human blood to be used for another purpose and research I think this is a remarkable tribute to the public's ability to understand and act in leukemia research. There may be hope in the not too distant future if Dr. Healy is correct. He said he looked for some breakthrough perhaps within the next decade but continued public support and patients are needed. Next week you will hear Dr. Francis Forester of the University of Wisconsin Dr. Hans Reese also the University of Wisconsin's Medical School professor Roger Williams of the University of Texas and Dr. J Morrison Brady the medical director of the Muscular Dystrophy Association of America Incorporated as they discuss neurological and muscular diseases. On the next program from the series human behavior social and medical research Glen Phillips speaking asking that you join us next week and thanking you for being with us at this time.

This program has been produced by the University of Michigan broadcasting service under a grant in aid from the National Educational Television and Radio Center in cooperation with the National Association of educational broadcasters. This is the NEA E.B. Radio Network.