In Her Words
Virginia Minnich – Oral History Transcription (Cont.)
Brodman: When they have this hemoglobin E, what is the result?
Minnich: If it is just a E heterozygous, you would never know it. If it is E-homozygous, it is much like hemoglobin C-homozygous, there is not much connected with it, not much anemia. But if you combine it with thalassemia, then it is a disease and not just a genetic marker. They not only have lots of beta thalassemia but they have lots of alpha thalassemia, meaning that the alpha chain is not being synthesized.
Brodman: When that happens, what is the effect?
Minnich: Then the genes just do not work, so you’re not making that globin chain and you have anemia.
Brodman: I noticed that when you did the hemoglobin E carriers in the entire population you used electrophoresis and found that 13.6% of the Thais (you examined over 1,000 Thais) had the hemoglobin E. But in 213 Chinese you didn’t find any at all.
Minnich: The ones that have E, are the ones in Southeast Asia, the Cambodians, the Vietnamese, the Malayans.
Brodman: Are they all one race?
Minnich: I am not sure they are all one race, but they are in some way intermixed.
Brodman: They have lived in the same area for so long it would be hard not to have intermarriage. In 10 members of a family in Thailand that you examined you couldn’t differentiate thalassemia homozygous hemoglobin E from the heterozygous hemoglobin E disease. How did you explain this?
Minnich: This has been pretty well worked out since I started working on it. If you have thalassemia with E, it just means that your chains are not like your alpha chain. Beta chain is not working, just not structurally there, they are just not being made. So if you put E with alphathalassemia, for instance, with a homozygote then you probably have only one gene that is making anything and this one gene is making E.
Brodman: Is there anything that can be done for these people?
Minnich: Nothing except for genetic counseling and that is it. That is a hard thing to do, especially if you are not from that culture.
Brodman: You also examined the hemoglobin in newborns, you studied the instances of abnormal hemoglobin in cord blood.
Minnich: They sent me the cord blood and it had Bart’s hemoglobin. Now Bart’s was first described by Lehman in England at Bart’s Hospital, so that is why it is named Bart’s. It is seen only in cord blood in alpha chain abnormalities.
Brodman: And you thought it might be due to the slow synthesis of the alpha chain?
Minnich: Actually, now it is pretty well settled that it is due to a gene that just is not there. It is not even synthesizing any hemoglobin.
Brodman: Mostly it is in the Negroes, or blacks, as they call themselves.
Minnich: Yes, it is more in the blacks than in the white population.
Brodman: Is there any relationship to their sickle-cell anemia?
Minnich: No, I figure there are just more genetic abnormalities in the blacks than the Caucasians in the United States.
Brodman: You continued to work overseas in Turkey. You worked on pica. What did you find?
Minnich: We found that the women were eating clay. The clay in Turkey is used for washing clothes and every household buys it at the grocery store and the women just take a pocketful of clay and eat it. [It is] just a habit much like smoking cigarettes, and when they feel like it, they eat some. The clay itself in Turkey combines with iron. I think, though, the pica comes first. They are eating clay because they’re iron deficient and it just makes it worse. That is really what I think. They don’t get the iron deficiency from eating the clay; they eat the clay as a result of the iron deficiency.
Brodman: Is that true here in the United States?
Minnich: That is true here in the United States, too. People who have pica here in the United States are iron deficient to start with.
Brodman: Can they be helped to stop eating the clay?
Minnich: As soon as they get enough iron, they stop.
Brodman: They stop on their own?
Minnich: They stop on their own. Children will do it too. As soon as the child’s hemoglobin starts coming up he stops eating it.
Brodman: If they don’t, what happens to them if they continue to eat the clay?
Minnich: They continue to be anemic.
Brodman: Is the clay the same in the United States as in Turkey?
Minnich: No, I have tested a good many clays and they are not the same. Our clay is much less alkaline than the clay in Turkey. The clays I tried here did not decrease the absorption. There, it is much like celation. The iron is exchanged for the calcium in the clay.
Brodman: I suspect these women who are iron deficient also may be calcium deficient, too.
Minnich: Well, they get plenty of calcium from the clay. They might be, but I don’t think so.
Brodman: Usually you think of women with many pregnancies as being calcium deficient.
Minnich: Well, in some of them there is a big calcium deficiency I am sure. I was only working on iron.
Brodman: You did most of your work on anemia and iron, sickle cell anemia and sickle cell traits, thalassemia and hypochromic anemia?
Minnich: That is iron deficiency.
Brodman: What do you think were your major findings over the years?
Minnich: I think probably the best thing I did was to set up laboratories – get laboratories going. I did that in Havana and I did it in Thailand and I did it in Turkey. I think that is one thing that I can do is to set up a lab and get it started and working. I think the other was the hemoglobinopathies. I did a big study in newborns, here, and followed them until they were over a year old.
Brodman: What did you find?
Minnich: At that time, the theory was that you were born with all the alpha chains that you were going to make. They were there when you were born. The work I did confirmed this with laboratory tests and showed this was really what happened. All alpha chains are there when you are born, or just about all of them. So the alpha chains – if you had a child with an alpha chain deficiency as in G Philadelphia – were the same at birth as when it was a year or two old. That is one thing I found. Also, we noted that the alpha chains could go with the gamma chains of hemoglobin F so that you had a new hemoglobin. They called that hemoglobin F St. Louis. I never called it that because all it was, was hemoglobin G Philadelphia with gamma chains which are the chains that make fetal hemoglobin – alpha and gamma.
Brodman: You followed these children until they were about a year old? Later on they did not change either?
Minnich: No change. Well, I haven’t pestered any of them after five years, but usually in a hemoglobin G Philadelphia heterozygote the hemoglobin is not low. It has no effect on the amount of hemoglobin that you have and circulate. It was at that level. It was the same all through.
I think these things are really what I have done. My contribution is setting up laboratories, and getting others to work.
Brodman: Also knowing what is needed as well as all the things you have found out. I also noticed you did some work on mutagenesis.
Minnich: That was my last program. After I stopped on hemoglobin, I worked on audiovisual aids for two years. Then I worked on glutathione synthetase and worked out the method for glutathione synthetase with Dr. Majerus’ help. I did all the tests but it was he who suggested I do glutathione, so I did it.
Brodman: What did that test show?
Minnich: It shows that it takes enzymes to put the glutathione molecule together. We found the first synthetase to put the first two amino acids together and there is a second one that puts the third one on the end. It is three amino acids.
Brodman: It sounds like biochemistry.
Minnich: I have done some very sophisticated biochemistry in my lifetime.
Brodman: Yes, and I wonder how many people realize how good you are.
Minnich: Because I found one hemoglobin, did most of the work on it, separating it, doing the analysis of it, doing the fingerprinting for the amino acid analysis, and so . . .
Brodman: They also said you did away with electrophoretic methods in favor of a much simpler method of identifying hemoglobins. You have really done quite a lot. It is very unusual for somebody to spend 40 years in one institution. Did you ever think of going elsewhere?
Minnich: Well I think these trips elsewhere are the ones [when] I came back satisfied.
Brodman: Well that is a very good feeling indeed. How come you never stopped long enough to get your Ph.D.?
Minnich: I thought about getting a Ph.D., but Dr. Moore said, “Why do you want a Ph.D.? You don’t need one.” That is really why I don’t have one.
Brodman: You agreed that you didn’t need one?
Minnich: I don’t think I need a Ph.D., but I would have loved to have an M.D. He also didn’t see why I should be a M.D.
Continued
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