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Biotech / Medical : XOMA. Bull or Bear? -- Ignore unavailable to you. Want to Upgrade?

To: aknahow who wrote (7530)	10/25/1998 4:10:00 PM
From: Robert K.	Read Replies (1) \| Respond to of 17367

George, I just read the discover articles. Very well written and thought provoking. Xoma was a small portion, but excellent PR. I found very interesting the toothpaste, & cleanser bit, and also the constant good bacteria vs bad bacteria battles. All right on the money IMO. I do plan on using this info to alter my lifestyle a bit and also to assist individuals to maintain their good bacteria. For all that havent read it, its a must read. Again excellent and well written articles. Jackie> when you read it, let us know your opinion.

To: aknahow who wrote (7530)	11/5/1998 12:44:00 AM
From: jackie	Read Replies (1) \| Respond to of 17367

George, Your question here really registered with me and I've been stitching together some thoughts that seem to have collided recently. I hope you don't object to my stepping in on your question. To address your question directly, if BPI pans out, I'm sure there will have to be a strong case for awarding the Nobel to the discoverer(s). After all, the proposed role of BPI in the theories being tested are fundamental to our understanding of the sepsis cascade, endotoxins, etc. This year's winners of course won because they happened on a unifying principle explaining the efficacy of nitroglycerin and Viagra. To carry the discussion forward a little, consider how much light this discovery involving nitric oxide (not nitrous oxide, laughing gas. This is no laughing matter.) casts on the Xoma conversations. There has been a running discussion on this thread, an appropriate one, on what BPI and related molecules are doing in the immune response. What is interesting, is to see one does not need a large and complex molecule for decisive roles in the human body. Consider, a fairly simple molecule like nitric oxide has been involved in an least the following three biotech stories: 1) Nitroglycerine. I always wondered how on earth an explosive could be so effective at controlling angina. Now we know. 2) Viagra. Enough said else where about the impact of this drug. 3) Somatogen's recombinant hemoglobin product. George, you remember this one don't you? The last stumbling block SMTG ran into, perhaps the straw that broke the camel's back, was the product's tendency to scavenge nitric oxide. This was completely unexpected and coming at the time it did, forced SMTG to sell out as they simply did not have the money to solve the problem. They certainly seemed to have several new reengineered products without this problem, but not the time to implement them. On reflection, it is obvious why such a characteristic would be most undesirable in a blood substitute. Removing the nitric oxide would have the effect of tightening the arteries. If the patient had a heart condition, and at the time they were pursuing a setting of heart surgery, this could be fatal. On the one hand, you want to get more oxygen to the heart, after all that's why you're giving the product in the first place. Yet, at the same time, the product is interfering with the distribution of the oxygen by narrowing the coronary arteries. Not a good strategy. By the way, the SMTG story may be finished, but not the artificial hemoglobin. Baxter recently dropped their salvaged hemoglobin product to concentrate solely on the recombinant hemoglobin. I think they'll pull it off. I do wonder, as an aside, if Northfield Labs' Poly-Heme doesn't suffer from the consequences of nitric oxide scavenging? My point is, and there is a point to all of this, if even a simple molecule like nitric oxide can carry completely unanticipated biologic activities, where does that leave something as complicated as BPI? How many activities will it eventually be associated with? So with those thoughts in mind, we can watch the BPI debates with a new perspective. We need to appreciate how weird the pathways can get in this business of biotech. Hence the need for extensive testing, even after approval. Because of this previously unknown behavior of nitric oxide, one company pursuing the goal of artificial blood lost it's independence, another made a fortune on a cure for penile erectile dysfunction, the pharmacokinetics of a drug whose efficacy was well established was finally elucidated, and a couple of guys get the Nobel prize in medicine. Of course, simplicity does not rule out a significant biologic role for a molecule. The most important molecule of all in biology is water. I learned to appreciate the basic role of water and the hydrogen bond from James Watson's "Molecular Biology of the Gene." There is also a good discussion of the importance of taking water's presence into account when building computer models of molecular biology. This discussion can be found in the November issue of Scientific American. By the way, without the hydrogen bond, water would sink when frozen, ending all life in short order wherever the temperature drops below freezing. In addition, without the hydrogen bond in water, it would boil at minus 100 degrees C. Regards, Jack Simmons