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Discovering the Australia antigen


Work on lipoprotein polymorphisms
Baruch Blumberg Physician
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After my completion of my graduate work and birth of my daughter, Anne, my eldest daughter, we went back on the SS France, I think it was, across the Atlantic and on October... in... early in October, we saw Sputnik, in one of its first revolutions actually, one of its earlier revolutions, and, you know, we could see it out… out in the clear sky over the ocean, and I... I remember that well. Then we came back and I worked at the National Institutes of Health, which was a great place. It was during a period when the... it was expanding greatly. It was a time, you know, what, 10 years after the war, there were still not so many scientists but a big... but a government that was anxious to fund research and fund basic research, which it’s continued to do. And so there was always... there was plenty of money. And I remember I… I didn't really understand what a budget was; what do you mean by a budget? If you needed something, you ordered it although there was limited space and you couldn't hire, you know, there was a limitation to what you could hire and all that, but... but budgets weren't an issue.

So, I did some work on the hyaluronic acid because I’d been hired by the... the arthritis division there, and that was a big interest in arthritis. But I was much more interested in studying polymorphisms in different populations and it was kind of, there was a certain amount of bureaucratic complexity in... in getting travel funds and everything, but travel is... is fairly inexpensive, you know, I mean, of course you're not, you know, spending $200 a night for a hotel room, you know, you're usually in very modest places in that sort of fieldwork. So I was able to get funding most of the time and we did studies in the Central Pacific and Alaska. It was in contrast to the study in, in down South America and in elsewhere in the Pacific, in Asia, in Japan, and… I didn't go to Japan until later. But we kind of continued this process and... and then we introduced a… a new method. We'd mostly been using this electrophoresis method to separate the proteins by their phenotypes and we found a good deal of variation that way. But more than that, we found the distribution of the genes in different populations and we could see sort of latitudinal lines and longitudinal lines sometimes and there was some, we... we suspected some disease associations in some cases. But then we decided on a new technique. This again was when Tony Allison came to visit me in... in... at Bethesda.

So we looked at the serum of transfused patients. Now, the argument was that if there’s these polymorphic differences, then some of them may be antigenic and we knew that generally what the distribution of... of the different alleles were and for most of them if you receive five or ten transfusions, for the ones we knew about, you’d… there was a high probability that you would... you’d receive a different protein. Please, stop me from time to time I think, because I forget things, you know, pull me back to other points.

[Q] Sure.

So we didn’t… you know, we thought well maybe some of the polymorphisms that are already known might by antigenic, or there may be ones that you couldn't identify by electrophoresis, but you could by this technique. So that was the hypothesis we were testing. Well, we tested, ten, twelve, you know, I collected a lot of antiserum, and we had a panel against which we tested the transfused serum which we presumed would have the antiserum. And, so we collected a whole bunch of normal populations, people with disease, and sure enough we found an antibody, precipitant antibody, and in time we found out it reacted with the low-density lipoprotein, and it revealed a complex polymorphic system with linked alleles, there were kind of groups of alleles… groups of loci that had very complex interrelation with them and the more we did, the more complicated it got, and the more difficult it was to arrive at any conclusions. What we did find some disease associations actually, you know, along the lines of what's being done now with Snips. This was the equivalent of Snips, but at the proteomics level, in other words, we skipped the whole...  a whole period of understanding of the genes. And… and then subsequently, a colleague of mine in Norway, developed a kind of much more standardized reagent that was related to the system that we've found, we called it the Ag System and with that reagent he was able to standardize the reagents that were available and he found various associations. Now this went on to some really interesting stuff like the relation of the apolipoprotein B alleles with Alzheimer’s, one of the first, no, we didn't do that of course, but it in a way was related.

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: Pacific

Duration: 6 minutes, 15 seconds

Date story recorded: September 2007

Date story went live: 28 September 2009