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This is Clifton Cox representing the Teaneck Library Historic Project. I will be interviewing Dr. Miller, known to us as Jack.
(I) Jack, give us your background, your title and the work that you do and perform.
(N) OK. Well I am an MD. I am a professor of obstetrics and gynecology and also a professor of human genetics and development at the Columbia Presbyterian Medical Center. I am trained in both these fields of obstetrics and gynecology and in medical genetics and in I guess you would say that what I do most of now is genetic research. I am also involved in clinical genetics both at Columbia Presbyterian Medical School but also in my involvement in the newly founded American Board of Medical Genetics. This is a new medical specialty that was founded approximately four years ago and now has more than 900 diplomats. I am currently president of the Board of Directors of this which is a high sounding title but what it means is that I am responsible for making up the examinations for certifying the next group of physicians and other genetic counselors who are going to be involved in providing genetic care. And this Board is also involved in accrediting training programs in medical genetics.
(I) Before we get too far into this work, this very important work, give us a little something about your family. Your wife, I know, is a doctor and. .
(N) Yes, she's a Ph.D. type of doctor who was trained in biochemistry but for quite a number of years has worked in genetics and her work primarily is research. We do research together in this area. We have three children, all of whom have gone through the Teaneck school system.
(I) Your wife is . .
(N) Dorothy Miller, yes. Known as Sandy. And our three children are all I guess in a scientific mold although my son cherishes the times that he has played the guitar for money but he's really a computer scientist and, as he calls it, a generalist who likes to solve problems in many areas and
(I) They went through grade schools here in Teaneck?
(N) That's right. They were at Washington Irving and Benjamin Franklin and Teaneck High. And my older daughter, Cindy, is in graduate school right now at the University of Wisconsin, finishing up her work for a Ph. D. in molecular biology and my younger daughter, Karen, is right now applying for graduate school. She wants to study the population biology and animal behavior.
(I) Why did you select Teaneck as a place for your family to grow up in?
(N) Well, our first reason was we wanted someplace that was in reasonable proximity to our place of work and with the George Washington Bridge there, that really meant moving into Bergen County because we wanted to have a single family home rather than live in an apartment. We picked Teaneck for several reasons. One was the reputation really of having the best or one of the two best school systems in the county and we are very strong believers in public education so we liked that. We also liked the fact that Teaneck was one of the very few integrated communities and we though that we would enjoy, and we though our children should experience what it was like to grow up in an integrated community. And the other thing we liked, and I guess that dictated partly where we moved in Teaneck, was that we wanted something which was close to good public transportation, close to the schools, close to the library and we fell in love with the existence of all of these public parks. So it was the amenities along a broad range of social and cultural activities that lead us here.
(I) And of course you are from what state originally?
(N) I am from Oklahoma.
(I) Since you have been in Teaneck, what would you say about the growth of the community per se as far as developing its schools or environment?
(N) Well I think that for many of the years that we've lived here, Teaneck has clearly worked very hard to maintain high standards and to improve, if possible, what could be offered to the students. The development of all of the advance placement courses, the development of the alternative school, I think are just examples of what was going on. In the early years when our children were younger, we went it seemed to most of the school board meetings. It was a real social activity. Well, that may not be a complete answer but that. .
(I) Now, getting into your field of genetics and so forth, give us more of this very important field that is so prominent in the present day.
(N) Well, after I completed my residency in obstetrics and gynecology which was at Yale in New Haven, I asked the chairman of the department where he thought I might go. I wanted to get training in a basic science because I wanted to do academic work, have an academic career in obstetrics and gynecology, and I knew that I did not have the kind of research training that was necessary to carry out this essential function of an obstetrician/gynecologist at a university medical center. And so he said to me, well, I'll ask my next door neighbor. He knows something about this. And his next door neighbor, who turned out to be one of the deans of American genetics, Elsie Dunn who was for many years here at Columbia, recommended going to England because he felt that in the United States at that time, there really was not equivalent training to what one could obtain and I ended up in London at University College working with Lionel Penrose who
(N) That was in 1958 and I stayed there until 1960. This was at the Golfton Laboratory which initially had been called the Golfton Laboratory of Eugenics but when Penrose became the professor, he abolished that name eugenics which he did not approve of at all because it implied that we knew enough to try to improve people and he knew that we didn't know enough and may never know enough to try to create a superperson. What he was trained as was a physician and what he was concerned about was trying to understand and, if possible, prevent or treat human disease that had a genetic basis and this, I think, is the model that is now held up across the world when we talk about genetic engineering. People are afraid of this, I suspect, because they think we are trying to conjure up some superrace.
(I) And it is still unknown to the ordinary layman.
(N) And we look at it as simply an extension of medicine. We are trying to improve diagnosis and find ways to treat the individual who is less fortunate and that's quite a different thing.
(I) Now you've mentioned earlier that you were one of 12 people in the whole country with this particular background.
(N) That's right. Both obstetrics training and human genetic training. This is a new development, this whole idea of having medical geneticists as such. It used to be that an internist who was perhaps particularly interested in blood diseases, hematology, would learn something about sickle cell disease and fa1acemia and a series of other causes of severe anemia's and he'd have to learn some genetics but that was the end of it. You'd have other people who would learn something about genetics as it applied pediatrics or in eye diseases but now we recognize that there is a common thread in all of this and that you need to have a unified type of training to educate people up to the top level in this area and this is important both in training physicians and people, other people who are going to be working in these areas but it is also important in terms of developing people who are going to do research to try to understand more of the unknowns in this field.
(I) Do you find many young doctors leaning towards this field or this specialty?
(N) I suppose the number is still quite small in terms of the total number of young doctors who are entering training at anyone time but we are seeing more all the time. The American Board of Medical Genetics has accredited so far only 30 training programs and I think at the moment there are no more than perhaps 100 people being trained in these programs. But this is just the tip of the iceberg. We know that there are other training programs out there. It is simply that they have not yet gone through this formal kind of accreditation procedure. I suspect that within the next four years, there will be perhaps 100 training programs and perhaps at anyone time, there may be 300 to 500 people undergoing training. What this means, turning it around the other way, is that there are not highly trained medical geneticists available that you can look up in the yellow pages in every town in New Jersey. They tend to be localized in the large medical centers and there are quite a number at Columbia. I think we probably have about 8 people that have been certified by the Board to work in medical genetics.
(I) Has this put a heavy burden on this few?
(N) I don't think so because the people who have illnesses go to physicians and those physicians try to treat them or try to refer them to somebody they think may be able to help. And so it is a learning process, an education process. As we get more people trained in genetics and they demonstrate to the family doctors and pediatricians that they can help in understanding what's wrong with their patient, then there is going to be more pressure because there are going to be more referrals of patients. We've seen this in terms of prenatal diagnosis of genetic disease which started out I guess mainly being amniocentesis studies done on women over 35 years of age. Initially, very few of these women were being studied this way and as the obstetrical services at the various hospitals learned about this, they began referring more and more women over 35 for this kind of care and it isn't just in the private offices that this happens. I know at Presbyterian Hospital, the nurse in charge of the Vanderbilt Clinic for obstetrical patients automatically sends every patient who is going to be 35 at the time of birth, they send them to the genetic counselors or at least they tell them about this service and they're acquainted with the nature of the risk and why they are at increased risk over perhaps a younger sister who is only 28 and so right now I suppose there may be 50,000 women a year who are having this procedure done whereas ten years ago, it may have been 500.
(I) Does your Board set up these programs for this genetic studies or systems that are supposed to be followed?
(N) Well no. What. . the Board consists of people who are drawn from the existing training programs and the founding Board included 12 of the most experienced and eminent people working in medical genetics in the United States and the system is that a certain number of these rotate off each year and a certain number more go on. These represent in essence the major training centers and it is easy then to set up guidelines of what kind of training they see as important. What a physician really needs to know. And actually we are not talking just about physicians because there are two other groups who provide genetic services that are recognized by this Board. One is what we call the Ph.D. geneticist. They have had formal training in human genetics to the extent of doing research, doing a thesis and getting a Ph.D. They, in some respects, have the hardest job intellectually because they have to deal with mathematical formulas and work out risks and do some of the rather sophisticated manipulations to make sure that we really tell people the truth about what the risk really is. They also play an important role in the training of the young doctor who is coming into this field. To help, to make sure that they understand these principles. The other category that you wouldn't find in the usual medical specialty is the genetic counselor. These are usually individuals who get a masters degree. After college and initially many of the people who did this were women who had had their families and were now wanting to sink their teeth into something where they could accomplish something for society and so Sarah Lawrence College and a few other institutions set up two year training programs and they did this with the assistance of people who were working in medical genetics in various hospitals. For example, we always have I think two of the Sarah Lawrence trainees coming to our place for clinical training and so they have masters degrees but they play an integral part in our handling of patients with genetic disease and so the role of the Board is to ensure that standards are set for what kinds of training they should have and whether this individual has shown signs that they have mastered that training and retain enough of it that they could be effective.
(I) So before they can be accredited, they have to come by your Board?
(N) That's right.
(I) Now you and your wife Dorothy just recently went to England was it? Weren't you on a sabbatical somewhat?
(N) Yes. We went over for about eight months and spent the time in Scotland. We worked at different medical research counsel, research units. Hers was located at the Western General Hospital and she was working in what is or what must be the largest or second largest institute of genetics in the world and I worked about five miles away in what must be one of the very smallest research units in molecular biology and we both had a fabulous time learning new methods. The nice thing is that when you go away like this, the phone stops ringing, all of the administrative activities, all of the teaching, everything that interferes with actually going into the laboratory and carrying out all of the experiments with your own two hands. .
(I) And you could work without interruption.
(I) I'll bet that was gratifying.
(N) It was really very exciting. And the nice thing about it too is that it means that when we came back, we were, then better able to understand some of the problems that the people we work with, the younger people that we are hoping to train and turn them into better scientists, we were better able to guide them because we had done these procedures more recently and again with people who were themselves world experts. For example, I was working with a man named Southern. Now that wouldn't mean anything to the average layman or even the average physician. But anybody who's heard about genetic engineering or reads about it probably reads about Southern blots and those are named after Southern because he discovered the technique that is used there and it is a very simple one but molecular biologists have a strong sense of humor. His blots involved transfer of DNA from a gel which was used to separate DNA fragments of different sizes. It was hard to work with in that way so he worked out a method of transferring it over to a nitro-cellital filter which was more permanent and you could do things with it. Not long after that, another scientist found out a way to transfer RNA in the same way and so to show the relationship to the first technique but also to emphasize it was different, he called it Northern blots. But his name wasn't Northern. Now they've done the same thing with protein transfer and so they call that Western blots. I'm not sure what they are going to do, well we already have an Eastern Block, I suppose that's. .
(I) Fascinating. Now I understand in the near future you'll be setting up a new laboratory out in Detroit.
(N) Yes, that's right. We are moving April 1st. At least that's the date that seems to be coming into focus as a time. I am going to be director of a new program in molecular biology and genetics. Sandy is going to be a professor of pathology but her charge is really to carry out research in the program in molecular biology and genetics. It is just that for the sake of clean administrative lines and not having a husband and wife or a husband controlling his wife's salary, she has to be in a different department. And I'll also have a joint appointment in obstetrics and gynecology which is where most of the clinical genetics is carried out so in some respects, my role will be similar to what it is here. It is just that I will be playing more of an administrative role because I have to recruit young people who are going to be setting up their own research labs to work in molecular biology and what I hope to do is to keep this strongly focused on understanding human disease so that we can apply the powerful techniques of molecular biology directly then to the problems of medical diagnosis.
(I) Jack, could you explain that molecular genetics, is that it?
(I) Of course, I am an ordinary layman and of course a lot of these things you say just go right over my head.
(N) Right. Well a molecule of course is just a very small chemical which is made up of two or more elements the way water is a molecule made up of the elements hydrogen and oxygen.
(I) I remember that.
(N) And so there is a discipline which deals with atoms and molecules and so on and this is chemistry. Now the chemistry of the molecules that are found in living organisms is called organic chemistry. Why then a new name? Well, the reason for the new name is because molecular biology is really a blend. It is a mixture of biochemistry, chemistry of living and the molecules from living creatures and genetics. So when I use the term molecular biology and genetics, that's really a redundant. . because for many people, molecular biology does not mean genetics. I like to add it. What it amounts to is that the reason you use the tools of genetics as well as the tools of the biochemist to deal with what we call molecular biology is because it speeds up the understanding of unknown principles by a factor of ten or a hundred or a thousand and it's speeded up most when you deal with simple organisms that reproduce rapidly because to do genetics, you have to study inheritance and that means you have to look at several generations. Well, you know, to look at several generations in people takes a long time.
(I) Yes it does.
(N) In fruit flies, you can study another generation every two weeks and in bacteria, you can study a new generation every thirty minutes and so what it means is that bacterial genetics, while it got started very recently in relation to the early studies of the genetics of peas that Mendle started, nevertheless bacterial genetics has moved ahead phenomenonally rapidly and the genetics of bacterial viruses is similarly one of these areas in which things move very rapidly because you get so many generations in a day. And so you combine the powerful tools of genetic analysis with the powerful techniques of biochemical analysis and understanding develops much more quickly. And the particular understanding that has come out of this is learning about DNA primarily, the genetic material and RNA because DNA makes RNA and the RNA, of course, makes proteins that make up almost every substance of importance in the body. .
(I) Does this mean that in the future or even now that you will be able to correct a defective genetic problems as say a person who has muscular dystrophy or something. Will you be able to say correct that where if they had an offspring, they would not pass this on?
(N) Well, I think that is going to be quite far away. People hold that up as a goal and they say well if we could inject a normal copy of that gene that is defective and interferes with muscle function, we could turn this person into a healthy person. I am not sure that we are going to be successful very quickly in that kind of genetic therapy. There are areas in which you can hope to do this by replacing cells that have a defective gene by cells in which the gene has been corrected. That, too, is pretty far down the road. I think those are the goals but what we have in the meantime is that these tools, these techniques of molecular biology, are really ways to understand the system that we are looking at. Right now, for example, we would all (END OF SIDE I - BEGIN SIDE 2) There are people who are working very hard with children or adults who have these different kinds of diseases, some of which have genetic causes. Some we don't know. The molecular biologist frequently looks at this in a broader perspective and says, what we don't understand is what makes a nerve cell different from a muscle cell. We have to have basic understanding of nerve cells. The way to get that most quickly is to turn to a very simple organism that does have nerve cells and these nerve cells make connections into what you might call a minute brain or a ganglion, something like this, so that you can have a reflex, you can have behavior.
And right now there are people who are using very simple organisms that reproduce a new generation every two weeks in order to study the development of the nerve cells and how they interact in those organisms. One of the organisms that is used for this now is, the fruit fly, and they are getting very exciting results which I expect in a few years may turn out to be directly applicable to understanding how nerve cells in the human work. And there are other very simple organisms like that. One of them is a tiny worm whose behavior is no more complicated than just sort of wiggling one way or the other but by watching it, you can see that occasionally a worm appears which has abnormal turning behavior and in the ten years that this organism has been studied, a group of scientists, most of them at Cambridge in England, have actually discovered enough genetic disorders that influence this behavior that they've been able to discover how many chromosomes this organism has and to map the genes along it.
They know more genes that influence behavior in this little organism than is known about any other organism except in the human being and I think this kind of basic research seems very esoteric. You wonder well why should we spend any money doing that and I think the answer is that it speeds up the whole pace of research. That we'll know sooner what goes wrong, what can go wrong with the nerve cell and I don't know whether this is the approach we will have to use to look at aging but it is just kind of a fascinating approach and I am interested in it in part, I think, because my early training was in medicine and my long term goals are to see the solution to medical problems that have been dogging us all these years and we still see it with children dying of terrible diseases that we still don't understand. So anything we can do that will speed up the day that we can do something about this I think is . .
(I) Well this research, besides improving the human health, it will also make it possible for you to improve our food supplies.
(N) Yes. There is a lot more impetus now on this. The genetic engineering possibilities there are very great. The problem of producing a super wheat, they are quite different from producing a super person.
(I) I imagine it would be, yeah.
(N) In that when we are planting wheat, usually we are only looking for one or two things. We may want bigger kernels or we may want a kernel that has more protein in it or with some plants, you want something that has less saturated fat or you are trying to influence one characteristic just as with cattle for many years.
(I) Cut down the cholesterol possibility and increase your protein.
(N) That's right. You do this with cattle. You try to increase the milk yield and there was a time when they were trying to increase the production of butter fat and now though it is probably more the protein they want than the butter fat. Well you can make changes that will influence one character like this. Not that it is easy but it can be done and that's the goal of genetic engineering. Now one of the problems that comes up is that sometimes when you create one of these varieties of wheat say, it may be so superior that everybody wants to plant it and you find that you get tens of millions of acres of it and suddenly a new type of rust or a new bug or something that likes wheat finds this and then you discover that this strain which is so good for producing what you want has almost no resistance to this agent that is killing it. And you have something like the potato famine in Ireland I guess which was produced by a smut that grew on the potatoes and rotted them. So that's another area is to try to find techniques that will increase disease resistance and to keep what they call the genetic pool, to maintain a lot of varieties of natural wheat, natural ryes and so on so that we don't run into serious long term problems because of the fact that there are lots of little plants and animals out there that are looking after themselves and doing it at our expense.
(I) Yes. I know they ask cities and farmers and so forth to cut down on what do they call it, DDT?
(I) And of course the bugs increased so I guess now they'll have to do something to possibly counteract that in some way I suppose.
(N) Yes. I don't know what they'll do but they will. There's another area in which there's a lot of concern and that's the use of antibiotics in the feed of chickens and hogs and maybe other farm animals because this had an unexpectedly good effect in speeding up the growth rate and improving the health of these animals. The problem is that whenever you give very low doses of antibiotics, bacteria that are around, you tend to select bacteria that are resistant to those antibiotics and so one of the problems we have in the hospital is that many of the bacteria that are there are resistant to everything that we use. The worst thing that you can do is pick up an infection in the hospital. But what we are afraid of is that some people may be picking up their infections from farm animals that are harboring bacteria that are resistant to penicillin and streptomycin and cloromycetin and auriamycin and so on so there's just one more example of the way in which nature very quickly evolves to overcome changes in the environment that we produce and. .
(I) Do you set a time on your research projects or . .
(N) Well we estimate how long it will take to carry out research. We are always wrong but most research in this country at least is funded by either the National Institutes of Health or the National Science Foundation or some other government agency such as the Office of Naval Research or they're supported by private foundations like the March of Dimes Birth Defects Foundation or the Cystic Fibrosis Foundation or the Foundation for this or that disease and so on. And in order to get research funds from these sources, the scientist has to submit a very detailed proposal of what he wants to do, why he wants to do it, the scientific rationale, the budget, how many people it is going to take and how much of their time and so it is all spelled out in great detail. The reason we are always wrong is because we are dealing with the unknown.
(I) That's right. I was going to say it seems like it would be almost difficult to determine the time element of completing a project. As you say, you are dealing with an unknown factor.
(N) Well, we know how long it takes to do a lot of the procedures. What we don't know is whether the prediction we made, that is the hypothesis we are testing, is right or wrong and very frequently we do the experiment and we get an interesting result. It isn't the one we predicted but it gives us new information. And what they say, they call this serendipity. If you have the intelligence or luck perhaps to recognize that what you've found is an interesting result that you should follow up and well I guess the discovery of penicillin itself was an example of this. The person didn't set out to discover penicillin. He just happened to recognize that his experiments were ruined because something had gotten in and killed the bacteria he was trying to study.
(I) And it turned out to be a very positive result. That is just marvelous.
(N) So you have to keep an open mind because the result you get that is interesting may not be interesting in terms of the question you were phrasing but it may be extremely important in terms of a different and slightly related question and so you can't be too narrowly focused. Otherwise you'll just throw everything away that isn't right, dead on the path that you've set for yourself.
(I) Jack, what gave you your desire and motivation to become a doctor and then of course you went right from gynecology into genetics, and etc. What keyed that interest?
(N) Well I think this was held up to my brother and me from a very early age. I know when we were I suppose five to eight years old, we had a cousin who became a pharmacist but at that time, he was in his training and he was staying with us because his home was 150 miles away and he was very much interested in medicine and held it up as a goal although it was not a goal that he could achieve. We had an aunt who also held up medicine. So I think in a sense it was a family goal. We knew that in the distant past there had been a cousin who was an M.D. back in Ohio and I knew, I suppose, by the time I was in high school that I had a cousin who was a radiologist in Houston. I didn't know him and I knew almost nothing about medicine because I remember when I was being interviewed for medical school and they asked whether I had any relatives who were doctors and I said oh yes, I had a cousin who was an X-ray technician. I didn't know the difference between a radiologist and a technician. So it was just a long cherished goal and I know that by the time I was probably 15 that I wanted to do medical research. I didn't understand anything about it except that I knew that there were lots of unsolved questions there and I suppose I didn't realize then that I wasn't really going to be good at it so I held it up and sort of worked for that. .
(I) What would be some of the key ingredients you would like to tell a young person that would some day be interested in becoming a doctor of genetics or gynecology or whatever that they really need to pursue this endeavor?
(N) Well that's a hard question. It's got four parts to it perhaps. I think one of the things that I would try to show them is that it is a very exciting life and I think if you can motivate people, young people, that they'll work a lot harder towards achieving a goal. It is easy to hold up medicine and medical research because they are clearly providing a much needed service for people in distress and I suppose there are other motivations that people have, social prestige may be important for some people, money may be important for some people. If it is money they want, then they'd probably head for a career in medical practice and not in medical research since the salaries that are paid by universities are far lower than physicians can earn in practice. But I think what motivates an individual is so variable that you can catch people and get them into medicine by a dozen different ways. I don't know if that really answers your questions but I'd do it again if I . .
(I) Well I feel quite honored to know you, a prominent person like yourself in this field and when I'm reading about the research accomplishments in genetics, I'll probably say, well I know Dr. Orlando Miller probably had something to do with it.
(N) You'd probably say Jack did. I thank you for those kind remarks.
(I) And I am sure this will be a very important tape for the Teaneck Historical Project. It is very wonderful. Thank you very much.
(N) You are certainly welcome.
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