Georgetown forum; Cancer research breakthrough

Breakthroughs in cancer research topic for the eleven hundred and sixty fifth consecutive broadcast of the Georgetown University radio forum. Another in a series of educational and informative programs from Washington D.C. The Georgetown forum was founded in 1946. This is Wallace Fanning speaking to you by transcription from the Raymond Rice studio on the campus of Georgetown University historic Jesuit seat of learning in the nation's capital. Today's discussion will be breakthroughs in cancer research. Participating are Marquis Smalls and Ph.D. assistant professor of biochemistry in the Georgetown University School of Medicine and Dentistry Ernest J do Prof Ph.D. associate professor of cell biology University of Maryland School of Medicine and law Saudi law fall junior medical doctor vice president of the District of Columbia division of the American Cancer Society and assistant dean an associate professor of surgery Howard University School of Medicine medicine. Today more people are being cured of cancer than ever

before. Thirty years ago only one in five was saved. Now the figure is one out of three. And it could be one out of two if everybody heeded the seven danger signals of cancer. One of the principal reasons for this encouraging upturn is scientific research sponsored by the American Cancer Society. In hospitals and laboratories across the country 37 percent of the money that we Americans donate to the Cancer Society goes to support research. Last year that amount was 17 million dollars approximately the cost of two jet planes. Obviously it needs to be more. While progress has been made the ultimate answers to the dread disease lie ahead. Today the Georgetown forum presents two scientists are working on research projects funded by the DC division of the American Cancer Society together with the division's vice president a surgeon. No one can say whether these particular research projects will come up with solutions

but they or others like them may well pave the way for major breakthroughs in cancer research. And that's our topic today and we're going to ask Dr. Small soon to begin by telling us of his research activities. Thank you. Well since I am a biochemist and essentially a chemist we're interested essentially in the and the basic metabolism of cells. And as far as cancer orientation I believe that it's clear that the more we know about all aspects of normal and malignant cell biochemistry the more we'll be able to possibly in the near future find more and more remedies to cancer. In particular my work is concerned with nucleic acids in cancer cells. And I think it's reasonably well established now that nucleic acids.

There's two major types in the cell DNA deoxyribonucleic acid which is a long very large spiral molecule which contains all the genetic information of a cell. And the second type of nucleic acid is called RNA which is riber nucleic acid. Quite a very closely related chemically to DNA same type of molecule both the knowledge of about both these molecules as far as how they function the cell would seem to be very very important. My own project in particular is involved with the regulation of how the cell transcribes information from the DNA which is the main component of chromosomes into RNA which is actually the workhorse of a cell. It's the message of the cell. It tells the cell what types of proteins and zines etc. It should make. And we're interested in general in how this is

control or when to cell say to make an enzyme a particular enzyme. When does the cell know when not to make an enzyme. And in my particular case I'm interested in a specific control mechanism regulation so to speak. And my my interest is how do the components of proteins which are essentially small building blocks called amino acids. How do amino acids in the environment of cells control this process of making RNA from DNA. Dr. Small one thing I'd like to understand here with regard to DNA and RNA they are native to the cell are not foreign. That's true with the exception that many viruses and I'm not a viral which is so I don't really want to link by romaji with cancer although I think other speakers will be able to. Viruses are mainly nucleic acids either DNA or RNA. So it's clear

that viruses get into a cell the way they can transform a cell perhaps into a malignant cell or kill a cell is by mediating through mediation of these molecules DNA and RNA. So besides the native DNA and RNA nucleic acids to the cell there are foreign nucleic acids which can get into cells. And it's clear that it that this process is probably very much disease oriented icing. All right the doctor two prong. What about your project. Well as Dr. smallest mentioned DNA is a major compound of chromosomes and our group at the Armed Forces Institute of Bath ology has been trying to analyze the arrangements of DNA in human chromosomes a number of types of cancer. Particularly leukaemia as an Burkett's lymphoma are characterized by visible changes in the chromosomes of the patient.

And of course both diagnostically and from the point of view of treatment it would be very desirable to know exactly what the change as seen in the light microscope involves and the alteration of the DNA molecules in the chromosome. Now we approach that by using the electron microscope to look at chromosomes both from cancer cells and from normal human tissue culture cells and particularly Dr. Lampert our collaborator at the Armed Forces Institute has recently found evidence for changes quantitative changes in the. The way that DNA molecules are packed into chromosomes altered chromosomes associated with Burkett's lymphoma cancer

condition picking up a little bit on another Dr. Small sense ideas the involvement of viruses in these diseases. I think that at present the idea is current and very exciting one that Burkett's tumor may actually be one of the forms of cancer that is induced by viruses. Viruses have been seen in the nuclei near the chromosomes of this type of cancer cell. And we hope eventually to be able to visualize exactly what the relationship is between those viruses and the altered chromosomes associated with the disease. Thus far you have discussed cancer cells and viruses and sort of an unrelated way and I wonder if Dr. Laforet could bring it down to the to the clinical application

of the cancer. I think it's important for us to realize that for those. Of us who are actually in the practice of taking care of patients who have cancer that we so in need the services of the scientists who are actually trying to find out what makes a normal cell become abnormal. What makes it become a cancerous cell and thus can spread and invade different tissues of the body. You must also realize that all the work that is done in the laboratory in the end is really an attempt to benefit the patient because this is the person we are really trying to reach. Now how can you benefit a patient the patient doesn't know what he or she has. We say rebel the two symptoms of make patients come to the doctors anyway one is pain and the other is blood pain because it hurts in blood because it frightens the patient. And many times cancer presents in the absence of these two symptoms for that reason the American Cancer Society has. Made a list of seven warning signals we used to call them

seven danger signals but now we change that to seven warning signals and recently Mr. Millet tells me that their public relations department has come up with a little acronym the word caution and attempt to help patients Remember what are the seven danger signals. And I think I like to just repeat those because it will let people know what they are used to the sea change and bowel bladder habits. A sore that does not heal you. Unusual bleeding or discharge thickening. I love and the breast are elsewhere. I ended gesture not difficult in swallowing the obvious change and a wart mole. And then there's a nagging cough hoarseness and when one thinks about that even if he happened to forget what some of them happened to be he could think go back and find out what the seven warning signals were and we say if they persist for longer than two weeks then he should

have an investigation of the samples by his physician. And there's really nothing magical about a two week period but it just so happens that if it's not a malignant lesion it's likely that it will dissipate within that two week period and to be sure that the patient gets early care. We want them to heed the 7 warning signals you cannot treat a patient unless you know what the patient has and knowing. But he has a malignant tumor somewhere in his body. It can be cheated adequately in many cases. And if and if he has any suspicion about anything at all and he's not in a position to he doesn't have a family doctor if you will at what what can he do Doctor. Well I think that the best thing if a patient does not know what it is to call his local division of the American Cancer Society then he can be directed to one of several clinics particularly in the metropolitan Washington area where he can get the proper treatment and diagnosis. And that's the proper treatment

by the symptoms and the disease that he has and this is the best thing for him to do. Darkest most and getting back to the research aspect. Both you and Dr. Drew probably again you have discussed your show yeller research. I I don't personally know it I suspect there must be a difference between the cells of the human liver for example as opposed to a lymph node. What how do you or your DNA and RNA factors are present in all types of tissue. Well it's very interesting really that. All the DNA of all the cells in a human body or a particular species whether it be liver cells or pancreas or blood cells or epithelial cells skin cells the

DNA the chromosomes are the same there's the same genetic information and all the cells of the body. People have done experiments in various systems where one can take a cell which is a one type of cell and by culture make it differentiate into a different type of cell. So potentially all the information of this of the body is in every cell. The interesting thing and although it might seem esoteric It really is an interesting thing as well. How do Cells differentiate during during embryology palaces. Why is it that certain cells become liver cells and certain cells become blood cells even though they all have the same genetic information. People are actively working in this aspect of research now basic research people working with in tissue differentiation. And again as I said I don't think it is esoteric or unrelated to cancer as it would seem because cancer cells in fact are derived from normal cells. And we're interested when we know we understand the the normal situation how do

normal cells differentiate into different types of cells even though they have the same genetic information. I think we'll get closer to understanding how cancer cells also differentiate into malignant cells from normal cells. Apparently again since I'm interested in regulation and control mechanisms I think it is involved involved here. And since i'm a chemist I'm interested at this control at a molecular level. Perhaps Dr. Toprol can also talk about this but it's clear that the DNA in the cell in the chromosome is probably covered by other molecules proteins perhaps and the way that certain cells become expressed in certain ways other cells are different types of cells is perhaps which area of the genetic information is covered up by certain areas certain other molecules so it can't be expressed. The other hand other cells this area might not be covered up. So this information can be read by the cell. As I said it's read by making RNA and RNA is again the workhorse of the

cell. Talk about I might pick up on that again. The fact is of course that all types of cells in the human body have the same amounts of DNA in their chromosomes. But in our group we suspected that the other materials proteins and to some extent RNA that are associated with the DNA in the chromosome might vary in a mound. And of course if they did this would mean that the chromosomes would differ in their total weights. Now as it happened Dr. Gunther barre at the Armed Forces Institute had developed a technique for weighing very small objects like chromosomes with the electron microscope. And so in our group we have been weighing single human chromosomes with Dr. Barres technique

including both normal ones and the equivalent ones from. Cells of cancerous origin. What we have found is that indeed the weights of corresponding chromosomes are different and different normal tissues for example in leather or in blood cells and that they are different again and cells of cancerous origin. Now we would not mean to imply that differences of that kind are causative necessarily as opposed to simply associated symptoms of the disease. That's something that can't be told immediately by just from the detection of the difference. But nevertheless we feel that either diagnostically or as a key to the mechanism of the disease and that we're on a very exciting track in this

work and weighing human chromosomes. But I was interested if you think that this extra weight might be possibly involved with integration of other foreign DNA like viral DNA in the chromosome. Well that thought has occurred to us as we are at present not. Thinking and terms of extra DNA in the chromosome so much as the development of a higher percentage of protein you see even in normal human chromosomes the DNA is only about 15 percent of the total weight of the chromosomes and the range of differences from tissue to tissue is at least 100 percent from one tissue to another. Now we think that if there should be a difference in the amounts of DNA in the cells of cancerous origin because of the integration of say a viral

DNA that that difference of itself would probably be masked by the greater differences in proteins. But it's definitely a possibility that we're thinking about and hope to design experiments to detect. Dr. Yunus going at the beginning of this broadcast you mentioned the. I'm out of money at the Cancer Society spending on research some 17 18 million dollars last year in the federal government is spending even more. And I think we should point out here that this money that is being spent in research is money that is very well spent. And I would just like to point out a few examples of of some things that have been gained that we have been able to apply in a clinical sense as a direct result of the type of our share of the result of the diversity that we've been hearing about how it actually helps the patient. This is a thing I think we must keep uppermost in our minds. All of this that we're doing is to help the patient no matter all the work be in the laboratory to work the things that you try on the wards. All of this is done in an attempt to help the patient who has the disease

cancer several years ago. Most children who developed leukemia had they went right ahead and died without having in a remission a toll. Now we still don't have a cure for leukemia but some 85 90 percent of children now get remissions from the various types of drugs that are available to treat them. And I sense this is true we are certain that one day we will have drugs that will cure leukemia. And this brings to mind have a malignant form of cancer of the uterus of the womb. At one time this tumor called choreo carcinoma was almost 100 percent fatal. When a woman had this cancer you knew she was going to die. Now on the basis of work that was done primarily at NIH using a chemotherapeutic agent a drug called methotrexate. Many of these women can be salvaged and can be cured. So I think that it's well for us to point these out. Not all of these answers leukemia the cancer of the uterus but patients who have cancers of the head and neck

area for example the refined techniques and X-ray treatment many of these patients can be benefited and cured. And I think we should also emphasize something that really I have to emphasize sometimes to my colleagues and that is that cancer can be cured cancer can be cured. And granted that and some cases when it's advanced very little can be done but when the diagnosis is made early for example in cancer the uterus when it's made as early stage almost 100 percent of these patients can be cured of that illness. You know I think one of the most confusing and at the same time difficult things to understand on the part of the layman about this whole matter. It is the broad range of diseases which are classified as cancer we hear about lymphomas of which there are several types. If I understand correctly we hear about skin cancers we hear about uterine cancer as we hear about well just almost any kind you can think of and in an effort to help us

understand we laymen. I wonder if you could tell me what what is the single if there is a single factor of that they are that they have in common. How is it that that you can group or or define these individual things into a group as big as being cancer. Well we define cancer as an abnormal growth and spread of cells and when we have but if you talk about the whole spectrum of cancer then that would be all forms of malignant tumors within the body. But then if we're talking about the different types like the lymphoma as well that would be those that and involved those to stamp it with just cells in the blood Yes that's that's Kansai facking cells in the blood and lymphoma cancer affecting tissues that have. Lymphatic are going to have left tissue within them. I guess the only thing that we know that's common to all of them is that if there is a malignant tumor each has undergone some change that made that cell abnormal and in the majority of

cases by far the majority of these malignant tumors can spread elsewhere. I think this points up to some of the basic work that Dr Smalls and Dr do prod doing trying to find out what is it that makes that normal cell. What is this thing that makes that cell become abnormal so I think once that door is unlocked then week I can answer your question much more intelligently. Yes and I think most of us are pretty well convinced that the answer to that question is not a single one at all but that different forms of cancer will will be found to have different types of origin and different mechanisms perhaps caused by viruses. Others induced by types of chemicals for instance those present in cigarette cars and still other mechanisms that we don't know about. What about what about the materials that are introduced to preserve food and to sweeten drinks and things of that nature are they

possible as this would fall into the chemical category would it. Well I don't know of any case where a preservative of that sort has been shown to be a cancer agent perhaps one of the other mistake in Iceland for example cancer of the stomach is fairly common and it is it has been related to the fact that these people eat a lot of smoked fish Bence pirating which is an agent that can cause cancer in the experimental animal is found in this but no one can say that this is the reason they developed cancer of this of the stomach. I would like to just make one point about the cigarette cause the best way to cure something is to prevent it and I think there's no question even though it has not been proved definitely 100 percent that smoking causes cancer of the lung. This is the most common form of cancer that occurs in males. And there's certainly a great relationship between heavy smoking and development of cancer. So if we stop smoking those of us who smoke we can certainly think stop the increasing numbers of patients who are developing the most

common cancer in males and that is cancer of the line. I would like to ask Dr. Smith and doctor to probe they have told us pretty much how in their particular specific fields of research out how they've come to where they are now and I wonder if they could project just a little bit for us and give us an idea of what we might expect doctors Mawson what what would be the ideal thing for your research to culminate in. Well as far as as far as cancer aspects of my research and my own particular work I'm looking at a control mechanism how this hello malignant cells control are in a sense this is I'm looking at a specific type how to amino acids which are outside the cell. How do they affect RNA synthesis. One thinks of cancer cells as being a perhaps a non-regulated cell a cell that's lost its sense of being this keeps multiplying. So I guess the ultimate in my type of research as far as cancer application would be to find

differences in this particular little thing that I'm looking at between different types of cancer cells and certainly between cancer cells and normal cells normal cells B cells that are well regulated cancer cells being perhaps cells that are not well metabolic be regulated. And how might this be translated into a possible cure. Well thanks. The following mentioned initially of part of his talk that leukemia has been treated by various drugs. I'll just very quickly one drug which has been used and seemingly somewhat successful is an enzyme called disparage an ace. This is a natural enzyme is a protein as I was talking about made from RNA. It's made in cells. This is an enzyme which breaks down what an amino acid disparaging presumably leukemia cells need more of this particular Mino acid and other cells so but the basic understanding about disparaging ace How can you how can you how can you make

cells make a lot of us you can use a lot of it. How can you learn about mechanism of action of disparaging ace this is very practical and this goes back. It's both BASIC BASIC and it also relates very highly to the clinical work. Dr. De Prof. We have just one minute. Yes well I might just mention the problem detection of cancer which has come up here before and there is a form of leukemia that develops in adults generally called chronic granule acidic leukaemia. It was found at the Institute for Cancer Research in Philadelphia a few years ago that a very unusual type of chromosome is associated with that form of leukemia. What we hope to do is to be able to characterize that chromosome with the electron microscope and to develop ways to detect. The incipient condition I had in advance much sooner than it could be done by conventional methods. Doctors of all of this is what American Cancer Society Research is

doing. Yes it is and what I would like to see is for the American Cancer Society be able one day to cease to exist because it has stated in its charter that once this disease is read from our nation completely in the world it will no longer exist. Breakthroughs in cancer research participating in our discussion Markey small assistant professor of biochemistry in the Georgetown University School of Medicine and Dentistry Ernest J. Do associate professor of cell biology University of Maryland School of Medicine and law Saudi law fall junior vice president of the District of Columbia division of the American Cancer Society and assistant dean and associate professor of surgery Howard University School of Medicine. You have attended the weekly discussion program the Georgetown University radio forum broadcaster which was transcribed in the Raymond Rice studio on the campus of historic Georgetown University in Washington D.C. next week you will hear discussed

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