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.
So we continued, you know, doing a lot of work but again this kind of recognizing we'd started this off because of our interest in polymorphisms’ susceptibility to disease, but again recognizing that when application is possible, you should do that, and I think the fact that we were medically trained made a… made a big difference. You know, we… we… the fact that it was associated, you know, we knew all of us, Tom, Al Sutnik, Betty Jane Gerstley, myself, you know, we'd had medical experience and so we were aware of what it could be and that was very helpful in our moving forward and then I started thinking about a vaccine. Well, in an odd way the thing that precipitated it, in my recollection, is that we had a meeting with Tim Talbot once. We had a sort of staff council. There were senior and some junior scientists that would advise Tim, Tim Talbot, and he said that the government had said they were going to decrease research funding and they expected research places like universities and the Institute to find some other source of funding, implying that we ought to start getting commercially valuable products. Well, it turns out that didn't happen. You know, I mean it has happened since then but it didn't happen then, but nevertheless Tim said, ‘Well, we're going to start thinking about stuff’. So after the meeting I went back and spoke to Irvine Millman who was one of, part of our group and I said, ‘Irv, we have to make a vaccine’. Well, by that time we knew enough about the biology of the hepatitis virus to realize that, in addition to the virus, there were these huge amounts of surface antigen. We estimated once that about one percent of the serum protein in people who were carriers was made up of the surface antigen in the virus. Well, that couldn't be whole virus because anybody with that viral load would be long dead and, you know, Irv recognized that right away. He'd been, he was one, the only one of us who was trained in microbiology by the way and he had mostly worked on bacteria. So I said, ‘Irv, you know, that's got to be extra antigen in the virus, there's probably a virus in there’. And we had made observations on populations that indicated to us that we could, we knew what the protective antibody was. We had a good... we didn't know but we had a good, high probability that it was that, well, the observation was a very simple-minded one. In all the studies that we've done, we initially never, and then rarely, saw the same person who had both the antigen, i.e. something on… on the virus itself and the antibody against it at the same time. Now that is consistent with the antibody being protective and then again Kazuo Okochi, my colleague in - he was then in Tokyo, he went to Fukuoko later - Kazuo had made a… an observation in transfused people, that the ones who had antibody and evolved it were less likely to get hepatitis and again, the data weren’t overwhelming, but they were significant, so I said, ‘Irv, we can make a vaccine from the surface antigen’, so we adapted a simple method for isolating viruses from serum proteins essentially and by centrifugation column, separations, some chemical procedures, we isolated this massive amount of surface antigen from the whole virus. They… because the whole virus kind of DNA had a higher intensity and you were able to separate it pretty cleanly.
[Q] And was it that surface antigen that was represented on the diagnostic band, on your original..?
Yes, well, there probably was virus there as well but most of it would have been the surface antigen. The fact you could see it was the surface antigen, so we had some rough idea of quantities, what the ratio was. Well, then we did some simple animal experiments. We showed that if you took the whole serum and transmitted it to an experimental animal, it would become infected. If you separated what we thought was the virus with the different density from the Australia antigen, the surface antigen without the virus, it did not transmit and then we brought a patent for that in 1969.
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.