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BM: Why not Hopkins? (laughs) I had spent the summer between my third and fourth year of medical school at Harvard as a clinical clerk in surgery, because I really wanted to be a surgeon. I was at Mass General Hospital, and I had a wonderful summer. I scrubbed with some of the best surgeons around. I really loved what I did, but it became quite obvious to me that I couldn't – the patients thought I was a nurse, and everybody was very uncomfortable, and there were no role models of women in surgery, so I came to grips with the fact that I probably ought to do something that was more acceptable for a woman. I decided to do pediatrics. This was recommended to me. I mean, I applied to several places – Rochester again and Boston Children's. I never thought I was going to stay in Baltimore. I just thought I was coming as – it was a good place, had a wonderful reputation. My classmates were all envious.

BM: Oh, you know, at Buffalo we were trained to be very self-sufficient clinically. We could practice medicine two hundred miles from the nearest hospital. You knew how to take your spinal fluids, do the assays on them, see whether your child had meningitis[1] or not. I mean, we were very self-sufficient. I always thought of myself as practicing medicine like my father, miles from a hospital, maybe even rurally. I don't know. I certainly felt that I could have done that.

I came to Hopkins, and this was a marvelous place at the moment that I was here, with a terrific faculty. Bob Cooke[2] who was head of Pediatrics, had just come, and he brought interesting people with him. There were good faculty here. We had conferences every noon.

One of the things I had to do from the time I started my internship was to give a research conference once a year. The first year all I did was to go through the records of the Harriet Lane Home,[3] which was the pediatric part of Hopkins, with children who had sarcoid.[4] It’s a pulmonary disease that is rather rare in children, but it did exist and I looked at that and presented the findings that were based on case records.

I think the second year, Barton Childs[5] was on the faculty at the time, and he and I went out to test heterozygotes. We went to homes of patients with pituitary pitressin-resistant diabetes[6] insipidus. The hypothesis was that it was an X-linked disease and that the mothers who were carriers might have some manifestations, and the affected males couldn't concentrate their urine. It was always a very dilute urine. So we went out to collect urine and do specific gravity determinations[7] on urine samples, and we found that they could concentrate their urine perfectly well. It was quite a recessive disorder. Having one mutant gene didn't affect the phenotype at all.

So I reported on that, and then by the third year I did a study of the flora[8] in the mouths and throats of patients who came into the outpatient department. My training in pediatrics was very heavily outpatient because Bob Cooke came in and revised things. It used to be that you spent half a year in the clinic and half a year on the floors with the patients [during] each of the two years. By the time I came along, it was one year here and one year there, and I ended up with three-fourths of my training in the clinic.

So I had a lot of outpatient experience, so I used it to test the flora of patients with the hypothesis that penicillin-resistant organisms would be more prevalent in people who had contact with the hospital, were born in the hospital, who had been in the hospital frequently, who had parents who were working in the hospital. Because you would get colonized with this hospital strain – and that's what we showed. I found myself a collaborator who could phage type[9] the organisms. We actually wrote a paper and it was published in the Bulletin of the Johns Hopkins Hospital.[10]

That's how I got started in doing research, and it was fun. It was always fun. The residents did interesting things. One of my colleagues looked at the way each of us – and it was a very independent place, very independent. You were a resident and you could do what you wanted with your patients, the patients that your interns had. We all treated bronchiolitis, which is a respiratory disease of infants. It can be very, very severe. We all had our own way of doing it. It was a viral infection, and some people didn't treat it with anything; other people treated it with this antibiotic or that. He studied the morbidity and mortality with our treatments and showed that it really didn't make much difference what we did. It would last so many days and so many would die at that point, depending –

It was very interesting and I just enjoyed it. Then it came time to try to decide what to do next. I had always been interested in endocrinology, from the time I was in medical school. We did rotations during our clinic year, and I was lucky enough to rotate with Lawson Wilkins, who was the endocrinologist here at the time. He had two fellows and the interns and residents could come [on rotation]. But one of the fellows got sick, so I was able to stay there for a month, which was a long time in my three years of training to be in a specialty clinic. And I loved it. I loved him, and I wanted to work with him. So that's what I thought I was going to do. But he had other ideas.

We're writing a book about him now, with his daughter, actually. We've been trying to do it for a while, and everybody's dying who was involved with it. (laughs) Which is unfortunate. But we're hoping to describe this fantastic man.

BM: Well, my husband [Hopkins pediatric endocrinologist Claude J. Migeon] and I and Mel Grumbach [Emeritus Professor of Pediatrics] at the University of California San Francisco, and his daughter Betsy, who is a good friend of mine, who lives in Providence and has written the historical part of the family and his background. So we're all writing about him. It's going to be a multi kind of view of this person. He was very famous and there were lots of things written about him. Rather than rely on memories, we're going to use what was written about him at the time as other contributions. How we're going to put it together, I'm not clear, but we know what we want to do.

He was very important, and he was an interesting man because he had been in practice in Baltimore as a pediatrician. Edwards Park,[11] who was the important pediatrician here, was the one who decided that we were going to have specialties in pediatrics. He told Helen Taussig[12] she was going to be a cardiologist, for instance, and she did very well in creating the field of pediatric cardiology.

He [Park] first asked Lawson Wilkins if he would do epilepsy; [Wilkins] wasn't interested, but he made him become an endocrinologist. He did it part time for a while, while he was in practice at night and – I mean, he would teach and be a part-time person here. He had a son who was eighteen years old and got killed in an accident at Christmas. When he died, it changed [Wilkins’] life and he asked himself what he really wanted to spend the rest of his life doing. He decided he wanted to be full time, so he came in here full time.

As a consequence of the son's death, we think, he really had only male fellows. They sort of were replacements for the son in some kind of way. My husband is one of his "sons." He called them his boys. When I wanted to become one of his boys, he told me I couldn't, even though he liked me a lot and we were very fond of each other. I ended up actually even living in his house with him after he had a coronary, while Claude was away for a while, to help take care of him. He was very fond of me, but he just didn't like the idea of women examining male genitalia of young boys. That's what he said, anyway.

I couldn't argue with him. I tried. I even went to Bob Cooke and said, "Please change his mind." Bob Cooke said, "Well, why don't you work with Barton Childs? He's doing something interesting. Or become a pathologist. Endocrinology's a dead field anyway." But nothing could dissuade me, and I decided to try elsewhere. Wilkins was very good. He wrote me wonderful letters of recommendation to Harvard, one of his former fellows. And he wrote letters for me to the NIH so I got my own grant. So I went to Boston Children's Hospital to do endocrinology. I couldn't do it with him, but I did it.

BM: What happened there was sort of – I had met my husband, who was an endocrinologist here, and he was working with Wilkins. We had not quite decided that we were going to get married. I decided I had to do something, so I went off to Boston. Then as soon as – I think even before I left, we realized that there was something going on with us and that we would probably end up together.

So I spent a year there, and then – I had a three-year fellowship from NIH – and then I requested permission to come back and work with Barton, with the extra two years. I expressed an interest in genetics, and the man at the NIH who was in charge of my fellowship program wrote back and said yes, he was giving me permission to transfer my grant from Boston back to Hopkins, but why didn't I tell him that I was getting married? (laughs)

At that point Claude thought it was not a good idea for me to become an endocrinologist in the same department that he was in, and he had good reasons for it, that I paid attention to. He had worked with a couple in the lab in Salt Lake City and it was a disaster when they were both together. People played one against the other. He was sure that I would never get credit for my work if I worked with him. He was running the lab at the time, which is where I would have gone after my first clinical year in Boston. I would have been doing research, because that's the way the fellowship program was set up.

Barton was anxious for me to come. I was his first fellow. He hadn't had anyone. He didn't have a lab, either, so it was quite interesting. (laughs) That's one of the reasons I hadn't decided to work with him before I left, because he had certainly offered me the possibility. I didn't know what a geneticist did, and I couldn't tell looking at him what he did. I mean, I knew vaguely that he thought about things a lot, but I really didn't – I was just in this kind of – the image of what a physician did was to have something to do with patients and study them in some kind of way. So it didn't sort of click with me at the time.

BM: I came back in 1960. I started with Barton, but then we didn't know what we were going to do. (laughs) I do remember he felt very strongly – he'd thought a lot about what a person should do, so he said, "You're going to go to Homewood [the Johns Hopkins undergraduate campus] and you're going to study genetics and biochemistry again and all of this kind of thing," which I did, which I enjoyed a lot. It was such a different experience from what I'd had all the way through medical school. I mean, I was back in college again, and it was just delightful to be taking seminars. No memory involved, just enjoying the academic questions. I took Bentley Glass's[13] courses. He just died this year, actually. And Carl Swanson, who was a marvelous cytogeneticist. And made some friends there. It was a fun thing to do.

So I came back, and Barton wanted to know whether I would like to work on G6PD,[14] which is what he had done some work on. He's a klutz in the lab, so he never did lab kind of work, but he had a laboratory that one could use, and he had a technician. I said to him, "It's too biochemical." I remember that. I didn't want to do that.

At the time, it was a very exciting time in cytogenetics because chromosomes had just been discovered. I think [Joe Hin] Tjio and [Albert] Levan had looked at the first chromosomes in '56.[15] But it wasn't easy to look at them until [Paul S.] Moorehead and others made a blood method possible, where you could culture cells[16] and start looking at chromosomes for the first time.

The Moore Clinic, where Victor McKusick was working at the time,[17] had a laboratory, the first cytogenetics laboratory here, and the person who was running it was a man named Malcolm Ferguson-Smith[18]. He's actually at Cambridge now. He was from Glasgow, but he had come here just as a visiting scientist, I think, in pathology. He set up the lab, and he started working, and everybody was working with him. It was sort of an assembly line. It was quite an interesting time. We would all sit there and cut out chromosomes from photographs and label them and put them in envelopes. Then eventually you'd paste them. We were looking at all kinds of individuals for the first time, and there were lots of hypotheses about who might have an abnormal chromosome.

Especially Lawson Wilkins, he was very interested in Turner Syndrome.[19] He had suspected there was something funny with their chromosomes. You could previously look at things with Barr body determinations, sex chromatin mass[20] doing buccal [from inside the mouth] smears, and it showed that they didn't have a sex chromatin mass. When you started to look at Turner Syndrome, you found that a lot of them had forty-five chromosomes instead of forty-six, but some of them had forty-six but that one of their X's was quite abnormal. So we were learning all kinds of things. He would send over samples of blood from hermaphrodites, any people that he was seeing in the clinic.

Meanwhile, the House staff was getting very savvy, and they would send all sorts of congenital malformations over. So it was a time when everybody was discovering the chromosomal basis of disease and diseases. It was fun. I had always liked the microscope anyway, and I liked the whole thing about chromosomes.

So what happened was that Victor asked me whether I would run the lab – because Malcolm was going to leave – run the cytogenetics lab until Malcolm came back. He had some kind of feeling that Malcolm would come back. That was an interesting proposition, but Bob Cooke asked me if I would start a lab in Pediatrics and that sounded more long term. (chuckles) So I did.

I trained George Thomas, who [now] runs the cytogenetics lab [at the Kennedy Krieger Institute, established at Hopkins in 1968]. He was the first person that was put in my lab without my actually being involved in it. You could do those kind of things in those days. Someone could tell you that so-and-so was going to come to your lab to work with you. It was your boss, there was nothing you could say about it. George was a nice guy, so I didn't mind. (chuckles) In the end, he left with my technician and he set up a lab at The Kennedy. So he was the first person I really trained myself.

BM: Yep. I wasn't really doing real research in terms of experimental research. I was really looking and reporting variants. We reported the first population variants. At the time, when people started looking, they often were looking at abnormal people, so they would come up with chromosome abnormalities and attribute them to the clinical abnormality that was present.

I was looking at my own chromosomes one time as a control. I guess I was doing some experimentation. I was looking at infants who had been X rayed or extensively looking for chromosome damage and came up with some rate of breakage. I needed controls, so I used myself as a control and found, my God, I had an abnormal chromosome. It was a thirteen that looked like a pig chromosome because it didn't have a short arm; it had been truncated at the telomere.[21] So I started getting very scared because this had been reported with chronic myelogenous leukemia,[22] with mental retardation, and things of this sort.

I went to my family, to my father and mother and sisters and brothers and found that my sister carried it, and my brother carried it, and my father had it. Then I went to his eight sibs in California. So I did a study of this variant using my own family. Claude went with me to help me draw blood.

It was quite interesting because we were able to show that haptoglobin,[23] which had been mapped to this short arm of a chromosome that I didn't have, that I was heterozygous for it, so it couldn't be there. So we took a gene off the chromosome with this study. It was fun. Studied my family. Wilma Bias[24] did all kinds of blood typing of them.

I have three Rh negative children. Claude and I are both positive. Those are the kind of things you found out with – we're so different because he's French.

BM: Oh, by that time I had children. Within fourteen months after I was married I had my first child. Because we were not young chickens at the time, and we thought we ought to have our children while we could. I had three children in three and a half years. Barton was a little horrified. (laughs) I was on his grant at the time. The NIH came for a site visit of one of his grants -- because I was a co-investigator on his grant at this point -- and they said, "Are you contemplating having any more children?" (laughs) I felt it an inappropriate question at the moment. I had just had one, and I said, "No, not at the moment." (laughs) Two of my children had my variant and one of them didn't. I conned them into giving me blood. Bribed them. Because they were very little.

NC: Could you describe the technique? You draw blood. How do you then get the chromosomes out?

BM: You draw blood. What you want are the white cells, and these days you can separate white cells using columns or whatever. What we did at the time was just to let the blood sit for a little while until we trapped the white cells in the plasma and the red cells had settled. We'd take that and put it into a flask, closed flask, with nutrient medium. You'd have to stimulate the cells to divide because they're in the part of the cell cycle that isn't cycling, G zero cells [that is, cells in a quiescent state, not preparing to divide]. They are unless you have leukemia, the cells from the peripheral blood, so you have to take them out of G zero and use phytohaemagglutinin, a mytogen [substance which will trigger mitosis, or cell division] from plants that was used to put in with the white cells into the culture medium. You would put it in the incubator and wait three days, take them out, spin the cells down.

Then the trick was to try to get the chromosomes out of the cells, and that's what had been discovered that made it possible to use blood. That is, if you use a hypotonic solution, which had been done by accident. The first time it was used, somebody didn't make up an isotonic solution properly and it was hypotonic. What it does is to swell the cells and you can get the chromosomes. You don't want to disturb the nuclear membrane, but you do want to get the cytoplasm away from the thing so that the nucleus can swell and you can spread the chromosomes away from each other.

You put in colchicine [a plant alkaloid] – and I forgot to mention that – near the end of the seventy-two hours, and what that does is to arrest cells in metaphase, and that's when you want to look at them. So it sort of poisons the spindle so that the chromosomes can't move to the poles to go into anaphase, and you get the metaphase chromosomes because that's when they are most characteristic. So that's what we did.

Then you had to take this solution that was swollen, metaphase cells, and put them on slides. That was a trick. That is still an art. We did all kinds of things. It was fun to watch people do it. They would put the slide on the floor and drop it from great distances in order to spread better. You use water on the slide or alcohol on the slide before you put the thing on. You could dry it either quickly or not quickly. I mean, there have been all kinds of methods used, and I'm still not sure what's the best. We used fans in order to dry fast, or a flame. Flames were things that you used to dry fast, too, until when you tried to do certain banding techniques, flaming it wasn't as good as not exposing it to flame.

It was fun to see all the techniques come about, because when we started, there was no banding. You just based all your classifications on shape, and there were twelve or so chromosomes in the middle group, Group C, that you really couldn't distinguish one from the other. You just arranged them in descending order of size and tried to pair them up the best you can with where the centromere is and how long the short arm was and the long arm. Then banding[25] came around and made it much more scientific. So it was all a very exciting time.

BM: Oh, I don't remember what year. We went through certainly at least six, seven, or eight years without banding, and then it came [in 1969]. Caspersson,[26] he was from Sweden.

BM: Yeah. You'll have to check the dates because for me dates are – everything seems like yesterday, almost. So that's how we looked at chromosomes. We stained it with – aceto-orcein [extracted from lichens] was the first stain we used. It was awful. It would stain your fingers so that – especially if you were going out or something, you hated to have your fingers stained with this.

BM: Purple. (laughs) Dark purple. The aceto-orcein we used to get from London because that was better than the stuff you could get from this country. I mean, there were all kinds of fetishes about what you needed to do in order to have the best preparation.

BM: Oh, it was pretty well developed. Barton had started a pediatric genetics group, and he had gone to the Galton Laboratory in London and met Harry Harris,[27] who was a big influence in his life. And [Lionel] Penrose,[28] who was there at the time. When he came back here, he was identified with genetics. I really don't know the flavor of genetics in terms of clinical genetics is different than it was then. You saw patients. You did family studies. You had pedigrees. I mean, from a clinical point of view, it was pretty much the way we still do it.

George Thomas had started the cytogenetics laboratory there. He was a biochemist, not a real cytogeneticist, so that was never his first love. He was doing a lot of screening at the time for protein variance and for enzyme deficiencies and for – I mean, they were doing the same kind of things that we do now. It would be interesting maybe to talk to him about how the laboratory has changed through the years.

As far as I can see, there were newer and newer more refined techniques being used, but the approaches were not different. Now you can screen for everything at the same time, and it wasn't quite that efficient, so I don't see that there were too many differences.

Barton started our Genetics Journal Club with me as a fellow, and we would meet in his home. He had a group of people who came under his influence who were not fellows. There was Mike Kaback,[29] who was working on Tay-Sachs disease,[30] Jerry Winkelstein,[31] who was a hematologist, and Jerry O'Dell, who was interested in bilirubin.[32] I mean, there was a whole group of faculty in our department who were working on real genetic problems, even though they weren't geneticists.

That was Barton's idea. He always thought that genetics should be an outgoing kind of thing. You don't bring patients in. So he never had a big clinic. There was a genetics clinic, but it wasn't a big encompassing one. He always felt that we should go out and help people in their clinics rather than bring everybody in to a genetics clinic. Because genetics was bigger than that. You understand what I mean.

BM: Yes. Victor was a clinic builder. It was interesting. I feel fortunate to have grown up with being influenced by the two of them. I used to go to the Moore Clinic conferences as well when I was working over there in cytogenetics. It sometimes disturbed me. He [McKusick] would bring patients in to be sort of studied, but he wasn't taking care of them perhaps. He had endocrine patients coming in with goiters and things. The endocrinologists would get very upset because their patients would be called in to a clinic, and they would ask the endocrinologist, "Why am I going here?" But, you know, people go where someone summons them. He was collecting these people but not really taking care of them. I thought that was not good. That reinforced the idea that you really want to leave people where they are, and with people who can take care of them. And give those people the advice about how to study the individuals, if they need to do that, or collaborate with them, or do something like that, rather than the other.

He did bring in a lot of interesting patients, and you always had interesting people to see. I could see it from Victor's point of view, and I could certainly see it from Barton's point of view, and I could see it from the endocrinologists' point of view. They were tugging for patients, which still goes on, as you know. (laughs) People don't want their patients to be put into someone else's study without being a part of it.

JC: And Barton Childs was in Pediatrics. How do these departments fit together in the medical school?

BM: How do medicine and pediatrics fit together? Well, it wasn't any different than it was anywhere else I'd ever been. I'd been at Mass General and I'd been in Buffalo. That's my experience. They were pretty much separate departments. There wasn't a terrible amount of interaction between them, and there still isn't an enormous amount of interaction between them. Mike Weisfeld [chair of Medicine at Hopkins] runs his show, but I don't know how much interaction there is between what George Dover [chair of Pediatrics] does and what he does.

My husband is actually going out to San Diego for the endocrine meetings and he's giving a talk about congenital adrenal hyperplasia,[33] which is a steroid disorder, an inborn error of steroid metabolism. He's being asked when do you give up your patients to medicine? Because pediatricians often see these patients, and then when do you turn them over to an adult physician? He would say, for this disease, it's usually bad when you do because the philosophies are so different in medicine and pediatrics. Certain disorders, it makes no difference. People tend to want to get rid of diabetics as fast as they can because they're very painful to take care of.

Pediatricians care whether you comply. When they give you an appointment, they call you up a week beforehand to remind you of that appointment, and if you don't make it, they call you to bug you about it. But if you go to an internist, as you and I all do, they don't care whether you make an appointment or don't make an appointment, and nobody's going to call you up and ask you why you didn't show up. It's an entire different philosophy.

So if you have something where it's pretty critical, for example, not allowing a female to masculinize too much, then you might want to keep her under control yourself because you know you can do it better than to send her on. I think there's different philosophies. There's even trouble about when you part with patients, even if they're – he's got some patients that are forty years old and they're still being seen in pediatrics.

[1] Meningitis is an inflammation of the protective membranes covering the brain and spinal cord.

[2] Dr. Robert E. Cooke (1920-2014) was head of Pediatrics at Johns Hopkins from 1956-1973. A friend and advisor to Eunice Kennedy Shriver and President Lyndon Johnson, he worked to overcome barriers for developmentally disabled children and was a founder of the Head Start program.

[3] After losing two young sons to rheumatic fever, Baltimore banker Henry Johnston and his wife Harriet Lane bequeathed their joint estate to Johns Hopkins to establish a curative home for ill children and advance the study of pediatric disease. The Harriet Lane Home for Invalid Children opened in 1912 and evolved to become today's Hopkins Children's Center.

[4] Sarcoid is a disease in which abnormal collections of inflammatory cells, or granulomas, form nodules in the lungs and associated lymph glands. Most cases resolve naturally, but a few are life-threatening.

[5] Barton Childs (1916-2010) was Professor of Pediatrics at Johns Hopkins from 1949 until his retirement in 1981 and Professor Emeritus until his death. Among his scientific contributions was the demonstration of random inactivation of X-chromosomes in mammalian female somatic cells. Childs wrote extensively on genetic screening and behavioral genetics and stated in 1999 that health and disease would be understood in the future as based on genetic-environmental interactions. An interview with Dr. Childs is included in this collection.

[6] This congenital form of diabetes is characterized by massive bladder enlargement and bilateral hydroureter and hydronephrosis. Pitressin is an antidiuretic hormone.

[7] The specific gravity of a urine sample indicates the concentration and dilution capabilities of the kidneys.

[8] Bacteria, with a few eucaryotic fungi and protists, are the most numerous and obvious microbial components of the normal mouth and throat flora.

[9] Phage typing detects single strains of bacteria.

[10] BR Migeon, BS Minchew. Some observations on the staphyloccus in a pediatric out-patient population. Bulletin of the Johns Hopkins Hospital 1960 Nov;107: 262-270.

[11] Edwards A. Park (1877-1969), the third chief of Pediatrics at Hopkins, 1927-1946, pioneered a holistic approach to pediatric medicine and created divisions of pediatric cardiology, endocrinology, neurology, and psychiatry.

[12] Helen Brooke Taussig (1898-1986) was director of the Harriet Lane Home from 1930 to 1963. She is credited with the conceptual development of the surgical shunt procedure (the Blalock-Taussig-Thomas shunt) used to correct tetralogy of Fallot (the congenital heart defect that is the most common cause of "blue babies.")

[13] H. Bentley Glass (1906-2005) was a pioneering American geneticist. His controversial and eloquent scientific writing influenced other geneticists even after he had retired. He became Academic Vice-President and Professor of Biological Sciences at the new State University of New York Stony Brook in 1965. His papers are at the American Philosophical Society in Philadelphia. See: http://www.amphilsoc.org/mole .

[14] Glucose-6-phosphate dehydrogenase.

[15] Tijo and Levan established the correct number of human chromosomes (46) in 1955 at the University of Lund in Sweden. See: Tjio JH, Levan A. The chromosome number of man. Hereditas 1956; 42: 1-6.

[16] Paul Moorehead, Peter Nowell, et al published their peripheral leukocyte culture methodology in 1960. See: Moorehead PS, Nowell PC, Mellman WJ, Battips DM and Hungerford DA. Chromosome preparations of leukocytes cultured from human peripheral blood. Experimental Cell Research 1960; 20: 613-616.

[17] Victor McKusick (1921-2008), often considered the founding father of medical genetics, was the University Professor of Medical Genetics at Johns Hopkins until his death, having founded the Division in 1957. He also founded the database of genes and genetic disorders, Mendelian Inheritance in Man in 1966 and continued as its chief editor in its print and online forms until his death. An interview with McKusick is available in this collection.

[18] Malcolm A. Ferguson-Smith (1931- ) established the first human chromosome diagnostic laboratory in the USA during a fellowship at Hopkins 1959-61. He established the Cambridge Resource Centre for Comparative Genetics in 2002.

[19] Turner Syndrome is a genetic condition in females in which one X chromosome is missing or abnormal. It was first described by endocrinologist Henry Turner in 1938. Girls with Turner syndrome are commonly short, have dysfunctional ovaries and may suffer from a variety of physical disorders (including congenital heart disease and hypothyroidism) and/or cognitive deficits.

[20] Chromatin is the complex of DNA and proteins that forms the chromosomes in the nucleus.

[21] A telomere is the region of repetitive nucleotide sequences at each end of a chromatid [single of a paired chromosome], which protects the ends of the chromosome from deterioration or from fusion with neighboring chromosomes.

[22] Chronic myelogenous leukemia is a cancer of the white blood cells, characterized by increased and unregulated proliferation of the granulocytic cell line in the bone marrow. It is today highly treatable with tyrosine kinase inhibitors.

[23] Haptoglobin is the protein that binds free hemoglobin, thus preventing kidney damage and loss of iron.

[24] Wilma B. Bias (1928-1913) became a Professor of Medical Genetics at Hopkins and founded the Immunogenetics and Transplantation Laboratory there in 1967.

[25] Banding is the staining of bands, or chromosome segments, to allow the precise identification of individual chromosomes or parts of chromosomes.

[26] Torbjorn Oscar Caspersson (1910-1997) was the head of the medical cell research and genetics department of the Karolinska in Stockholm until his retirement in 1977. As a doctoral student there in 1963, he was the first to use an ultraviolet microscope to determine the nucleic acid content of the cell nucleus. In 1969, Caspersson and Lore Zech used a quinacrine mustard stain that revealed light and dark lateral bands along the length of chromosomes. This banding method permitted the accurate identification of all 22 autosomes and the X and Y chromosomes and the highlighting of structural abnormalities and extra chromosomes. See Caspersson T, Zech L, Johansson C and Modest EJ. Identification of human chromosomes by DNA-binding fluorescent agents. Chromosoma 1970; 30 (2): 215-227.

[27] Harry Harris [1920-1994] was a pioneering British geneticist. He was one of the first to link variations in protein to variations in DNA and both to medical disorders and abnormalities. Harris spent much of his career at the Galton Laboratory but moved to the University of Pennsylvania as Harnwell University Professor of Medical Genetics in 1976.

[28] Lionel Penrose [1898-1972] was a British psychiatrist, medical geneticist, mathematician and chess theorist who carried out pioneering work on the genetics of mental retardation. He held the Francis Galton Chair at University College London from 1945 to 1965 and influenced many British and American geneticists.

[29] Michael M. Kaback later developed an enzyme assay for prenatal Tay-Sachs screening (see note 36) that enabled prevention and virtual elimination of the disease in susceptible populations. He is currently Professor of Pediatrics and Medical Genetics at the University of California San Diego.

[30] Tay-Sachs disease, first identified in the 1880s, is a rare autosomal recessive genetic disorder, in its most common (infantile) form, causes a progressive deterioration of nerve cells and of mental and physical abilities beginning around six months of age and usually resulting in death by the age of four. The disease is caused by a mutation in the HEXA gene on chromosome 15, resulting in an insufficiency of hexosaminidase A, a vital enzyme that helps break down glycolipids in nervous tissue. Tay-Sachs carriers are found predominantly in Ashkenazi Jewish, French-Canadian and Cajun populations.

[31] Jerry Winkelstein was Division Chief of Pediatrics at Johns Hopkins until his retirement. His major research interest was in the molecular biology of immune deficiency diseases.

[32] Bilirubin is the yellow breakdown product of normal hemoglobin catabolism, excreted in bile and urine. Elevated levels of bilirubin may be indicative of hepatitis or other disorders.

[33] Congenital adrenal hyperplasia refers to a group of autosomal recessive disorders, resulting from genetic mutations that affect the production of cortisol from cholesterol by the adrenal glands.

[1] Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence.

[2] Carol Greider is the Daniel Nathans Professor of Molecular Biology and Genetics. She discovered the enzyme telomerase as a graduate student in 1984 and shared the Nobel Prize in 2009 for her research on this enzyme. She and historian Nathaniel Comfort were married in 1993.

[3] Howard Hughes Medical Institute, originally founded in 1953 by the billionaire aircraft designer Howard Hughes, has been run by a group of trustees since 1984. Genetics was chosen as one of the original four research areas at that time. The Institute both conducts its own research at its home campus (Janelia Farm in Virginia) and funds other investigators through grants.

[4] Philip E. Hartman (1927-2003) was professor of biology at Hopkins from 1965. He was a pioneering researcher in microbial genetics.

[5] Now at NIH, with the Genetics of Health and Disease Study Section.

[6] Now Professor of Pediatrics and Genetics at Harvard.

[7] NIH Career Development "K" awards provide early career support for senior postdoctoral fellows or faculty-level candidates.

[8] Cardiologist Richard S. Ross served as Dean of the Johns Hopkins Medical School from 1975 to 1990.

[9] Now Professor and Head of Anatomy and Cell Biology at the University of Iowa.

[10] Director of the Institute of Medical Genetics and Professor of Pediatrics, Ophthalmology, Molecular Biology and Genetics, and Institute of Genetic Medicine at Johns Hopkins.

[11] Professor and Director of Pediatric Urology at Johns Hopkins.

[12] Cystic fibrosis is an autosomal recessive genetic disorder in which thick, sticky mucus builds up in the lungs, digestive tract, and other areas of the body, including the pancreas and liver. CF results from a mutation of the gene that expresses the CFTR protein, which regulates the composition of sweat, mucus and digestive fluids. The most common symptoms are difficulty breathing and frequent lung infections; life expectancy is about 40 years in the US.

[13] Muscular dystrophy refers to a group of inherited muscular diseases characterized by progressive weakness of skeletal muscles, difficulty in locomotion, atrophy and death of muscular cells and tissues, and defects in muscle proteins. There are several different forms and genetic etiologies; life expectancy varies. There are no cures at this time.

[14] Carlo Croce (1944 - ) is an Italian-born physician and oncologist whose research focuses on the genetic mechanisms of cancer. He has worked in the US since 1970 and since 2004 has been Director of Human Cancer Genetics and Chairman of Molecular Virology, Immunology and Medical Genetics at the Ohio State University Comprehensive Cancer Center in Columbus. Previously, he had been Director of the Kimmel Cancer Center at Thomas Jefferson Medical College in Philadelphia, where he discovered the role of microRNAs in cancer pathogenesis and growth.

[15] Scott Gilbert is now Howard A. Schneiderman Professor of Biology at Swarthmore College.

[16] Frank Ruddle (1929-2013) was an American geneticist and pioneer in human gene mapping and in chromosome transfer technologies. He joined the Department of Biology at Yale University in 1960 and remained there throughout his career, taking on a joint appointment in Human Genetics when that Department was formed. In 1974, Ruddle organized the first Human Gene Mapping workshop, and in 1980, his lab at Yale created the first transgenic mouse. An interview with Ruddle is available in this collection.

[17] Now Director of the Manton Center for Orphan Disease Research at Boston Children's Hospital.

[18] Daniel Nathans (1928-1999) shared the Nobel Prize in 1976 for his discovery of restriction enzymes that cut DNA segments at specific points, making recombinant DNA technology possible. He was a faculty member in the Johns Hopkins Department of Microbiology from 1962 until his death. His papers and a detailed profile are available at http://profiles.nlm.nih.gov/ps/retrieve/Collection/CID/PD .

[19] Donald D. Brown has worked at the Department of Embryology at the Carnegie Institution of Washington since 1962, serving as Department Director from 1976 to 1994. He has made major contributions to the understanding of gene expression and hormonal control of expression during embryonic development.

[20] Robert M. Blizzard (1936-2005) moved to the University of Virginia in 1973 and worked there until his retirement in 1994. He is noted for his role in elucidating the critical role of growth hormone in child development.

[21] See note 16.

[22] (Under her maiden name Barbara L. Ruben) Rubin MI, Calcagno PL, Ruben BL. Renal excretion of hydrogen ions: A defense against acidosis in premature infants. Journal of Pediatrics 1961 Dec; 59: 848-860.

[23] John W. Littlefield (1925 - ) was Chair of Pediatrics at Hopkins from 1974 to 1985 and then Chair of Physiology from 1985 until his retirement in 1992. Among his scientific contributions were the discovery of the role of ribosomes in protein synthesis and the development of a method to isolate hybrid cells, which was used by others to localize genes to specific chromosomes and to produce monoclonal antibodies. His papers are in the Hopkins Medical Archives; see: http://www.medicalarchives.jhmi.edu/papers/littlefield.html .

[24] Howard M. Dintzis is now Professor Emeritus of Biophysics and Biophysical Chemistry at Hopkins. His wife Renee Z. Dintzis is Associate Professor of Cell Biology. He carried out a classic experiment in 1961 that determined the linear directionality of protein synthesis (from the amino to the carboxy terminus). See: Dintzis HM. Proceedings of the National Academy of Sciences of the USA 1961; 47: 247-261.

MIGEON, BARBARA

INTERVIEW
JUNE 2 AND 3, 2015

MIGEON, BARBARA

INTERVIEW JUNE 2 AND 3, 2015

INTERVIEW
JUNE 2 AND 3, 2015