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Observations on beneficial effects of hepatitis B antibodies


Researching disease susceptibility
Baruch Blumberg Physician
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We started the… the story talking about the… our interest in polymorphisms and how they relate to disease susceptibility, and that was the initiation of the research and it's kind of characterized the research, our research, on hepatitis and I think those of others as well, and there's… there's a lot of… a kind of message from… from this approach that I think is very important now at… at a time when so much is… progress is being made in genomics and proteomics. A consequence of this view of things is that, you know, a gene, in a sense, never operates, or nearly never operates, on its own. There are some genes that are highly deterministic and although there's… if you have the gene, the probability of getting an associated phenomena, an associated disease is… is extremely high. But those… there are many of those but they tend to be rare, and the total sum they contribute to the disease load of humans is relatively small compared to things like heart disease, stroke, you know, diabetes, infections; they're a small part of the load. Now, the genetics that's involved with these really big diseases that kill a lot of people and the ones that most people are concerned about, they tend to be these sort of susceptibility genes which means they're not highly deterministic and that their interactions with other genes in the same environment, with environmental factors and with behavior, is extremely important and you have to understand the whole complex. So the bottom line is biology isn't destiny and you can change the effects of your genes and that's what doctors do all the time; you know, if you have diabetes and your insulin's not being processed properly, or you're not producing enough of it, they give you insulin. That's interfering with the effects of the genes. If you're… if you have genes that make you susceptible… susceptible to hepatitis B virus and we've identified, we and others, have identified multiple loci, well, you get the vaccine and you don't get hepatitis. So the effect of the genes is… is inconsequential there.

Now, the other interesting thing is that the very same genes that make you susceptible to hepatitis B virus also make you susceptible to specific other organisms and we developed a… a approach to that, in which we developed a classification of infectious agents based on the fact that each of the agents in this particular category, this… the classification, are related to the same susceptibility gene. Now, in some… in some cases, a allele that makes you susceptible to one of those agents will make you resistant to another, so you can't talk about good genes and bad genes. You have to talk about a good in what way, or bad in what way, and… and as a consequence, by the way, this notion of gene substitution therapy, the idea you get a bad gene, you get it out and put… or… or change its impact, and then put a big gene in, another gene, quotation marks, ‘good gene’, I think it's not… it's not going to work and it hasn't worked, you know, there's no substitutional gene therapy, because it goes ahead on the notion that the main function of the gene, which is usually the first one that's found, is the only function. Well, it's patent… you know, genes have multiple functions. Now, part of the reasons that they have multiple functions is that nature doesn't throw genes away. Nature tends to conserve them, and, you know,  that's very… that can be studied quantitatively by looking at the conservation parts of the gene or different genes and they come to us from… from species, you know, that are earlier on the evolutionary scale than humans, and I think one of the most amazing biological findings of the past century was that mammals share a third of their genes with archaea. Now, archaea are… are, it's thought, the… one of the organisms, a group of organisms, bacteria-like organisms that differ in their gene sequences and a variety of other ways from bacteria, that they are… they're very early in the scale of living matter and they may conceivably have been the first living things. And then there, by the way, there are viruses in archaea and I'll get to that later when we talk about space. So we share genes. Well, those genes still have… still contain the potential of the organisms from which they came, and in a way we… it's very hard to know what those are because they were expressed in very different environmental situations. Well, nobody knows… can foretell the future; we're actually… we are foretelling the future now we're considering climate change and it's going to, you know, which independent… well, climate change with human cause attached to it. Well how are we going to respond to that new environment? And one of my current interests, or a major current interest, is how earth-bound organisms respond to being in space. And as I said, I'll get to that later, but I… but I did want to make this point that we continue… we never gave up our interest in this inherited susceptibility to disease and… and the work on hepatitis really — subsequent work — really made that patently clear.

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: polymorphism, hepatitis B, genes, disease susceptibility, archaea

Duration: 6 minutes, 47 seconds

Date story recorded: September 2007

Date story went live: 28 September 2009