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Emily Oster's work on gender ratio and hepatitis B infection


Researching the effect of genetic factors on the hepatitis B virus
Baruch Blumberg Physician
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I think that was when I was spending a fair amount of time doing that... trying to encourage people to start a vaccination program and to look into the cancer prevention vaccine and so I... but there were other aspects of… of hepatitis virus that... that we were interested in... in and again going back to this concept of the polymorphisms, what we had found was that the susceptibility to becoming a chronic carrier of hepatitis B virus, there was a measure, it was an influence and it was a genetic influence, I wouldn't say control, but a genetic factor in the... in the way individuals responded and since our…  and the... the first research I did on… on Australian antigen was on its genetics, first studies we did were family studies and we showed a... a genetic relation to them. It was like a polymorphism. Nothing has happened to change my mind. It is a polymorphism, the ability to be carried. And since then, there've been ten loci, probably now that you have SNPs and everything, it will be 30, 40 loci that are related to susceptibility to hepatitis B. Okay, now we have a polymorphic trait. There're advantages and disadvantages. As I said before, and we talked about this a little bit in the beginning, you know, a third of the world's population's been affected. That's overwhelming. There are other viruses, that's true as well. It's got to have an impact and why… why did it last this long? How can you bare the... the killing factor? Which, by the way, hits people after the child-bearing age so presumably it would have little effect on the number of offspring. But as a consequence, I got very interested in the other aspects of hepatitis B, and probably the most interesting one we found was the relation to gender.

Right from the start we'd been looking, because we did a lot of family studies, we'd look at mothers and fathers and their offspring and we had a lot of family data. Well, we did a study, I wanted... we wanted to do a... a family population study in Greece, in… in a… in a highly endemic country, and we… there were some very good hepatitis scientists in… in Greece. There… there's quite a lot of it there, and they were, you know, very well-trained, outstanding people and I think we had a mutual decision that we'd do a study of a population there, but we wanted to find a kind of community, a... a community, a whole community where the prevalence was quite high and we... where the people would agree to participate in the study. And we... what had happened is that they had done a study of blood donors from different parts of the country and... and then also tested school children, national... nationwide and the highest prevalence they found was in the province of Imathia which is up in near Macedonia, you know, and... and one town had the highest prevalence in that place. It was a small community, a few, a couple of thousand people called Plati, so the... the capital of that province is Saloniki, so, you know, it's up in the north and there was a community that had been settled by refugees from Turkey. You know, you probably recall that after the Second World War, the... the Turks had… had these pogroms I think you have to call them or sort of attacks — although they deny it, by the way — there was a big political controversy, against Armenians and also against the Greek population. You know, on the basis of the treaty of Lausanne there was a huge exchange of populations, a very large number of... of Greeks who lived mostly in Cappadocia and... and I think in Anatolia too, went on down to the coast. One of the biggest at the time, it was the largest exchange of people anywhere and… and a large number of Turks but not so many, so that was like a third of the population of Greece and they had this campaign to build new towns and they built them up in this… in the… in that province in the north. It was… it was Macedonia province and Imathia district and the… which was quite diseased. It hadn't been settled, you know, because it wasn't very healthy. And so this community where people migrated from Turkey or had been required to migrate and their descendents, so 80,85 percent of them, their origins were in Cappadocia, a very interesting population, caused me to read a lot about them history of that sad time. They had an incredibly high prevalence. So we did a family, I had some of my anthropology students and my Greek colleagues stay, you know, stayed there. They were there for weeks, months and we got essentially a 90%, 80% of the entire population we tested and… and looked at the distribution in families. And one of the things that was looked at was the number of offspring and the gender of the offspring, and when you sorted them out that way and then looked at the response that the parents had had to infection with the hepatitis B virus. So the two polar responses you can have, if one would be chronically infected, then you have the surface antigen. The other has developed antibody against the surface, which gives you protection so that, when you… when you get infected, if one of those happens, if you become a carrier, you're at high risk of chronic liver disease, cancer. The other happens, you're protected. Big change in your fate depending on what happens to them. If the parents were carriers of the hepatitis B virus, there was a higher ratio of boys to girls among their offspring than if the parents had developed antibody. It was a little more complicated than that but broadly it’s that, and if the parents had not been infected or had no serological evidence, they were in between. That's an amazing finding. What do you do next when you find, when you do it again? So Tom London and others, we eventually did a study in... in the Philippines; Papua, New Guinea; place called Karkar, Greenland and then subsequently there were studies, another study done in France and another study… and another study done in Greece. They were all in the same direction. Now, there might have been a lot of studies that people did that didn't show but they weren't published, you know, that's the problem, you know, you get negative results, people don't publish them. But in any case I was convinced, I mean you do it five times. Well… well, there… there wasn't much more we could do, you know, we would have liked to have looked into the… the biochemistry of it or the immunology, you know, whatever, but we were really pretty much onto the vaccine and… and the phyllanthus by that time so it didn't do that and it... nobody noticed it, you know, and the effect by the way was very large. As far as I can make out, it was the biggest biological effect on gender.

American research physician Baruch Blumberg (1925-2011) was co-recipient of the Nobel Prize in Physiology or Medicine in 1976 along with D Carleton Gajdusek for their work on the origins and spread of infectious viral diseases that led to the discovery of the hepatitis B virus. Blumberg’s work covered many areas including clinical research, epidemiology, virology, genetics and anthropology.

Listeners: Rebecca Blanchard

Dr Rebecca Blanchard is Director of Clinical Pharmacology at Merck & Co., Inc. in Upper Gwynedd, Pennsylvania. Her education includes a BSc in Pharmacy from Albany College of Pharmacy and a PhD in Pharmaceutical Chemistry from the University of Utah in Salt Lake City. While at Utah, she studied in the laboratories of Dr Raymond Galinsky and Dr Michael Franklin with an emphasis on drug metabolism pathways. After receiving her PhD, Dr Blanchard completed postdoctoral studies with Dr Richard Weinshilboum at the Mayo Clinic with a focus on human pharmacogenetics. While at Mayo, she cloned the human sulfotransferase gene SULT1A1 and identified and functionally characterized common genetic polymorphisms in the SULT1A1 gene. From 1998 to 2004 Dr Blanchard was an Assistant Professor at Fox Chase Cancer Center in Philadelphia. In 2005 she joined the Clinical Pharmacology Department at Merck & Co., Inc. where her work today continues in the early and late development of several novel drugs. At Merck, she has contributed as Clinical Pharmacology Representative on CGRP, Renin, Losartan, Lurasidone and TRPV1 programs and serves as chair of the TRPV1 development team. Dr Blanchard is also Co-chair of the Neurology Pharmacogenomics Working Group at Merck. Nationally, she has served the American Society of Clinical Pharmacology and Therapeutics on the Strategic Task Force and the Board of Directors. Dr Blanchard has also served on NIH study sections, and several Foundation Scientific Advisory Boards.

Tags: Greece, Turkey, Cappadocia

Duration: 7 minutes, 59 seconds

Date story recorded: September 2007

Date story went live: 28 September 2009