Thursday, January 18, 2001

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The New York Times When Gene Sequencing Becomes a Fact of Life
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"The gene-sequencing machines that unraveled the human genome were nearly the size of refrigerators and cost $300,000 apiece. Richard T. Daly's sequencers fit easily on a desk — and he is giving them away.

The reason is that Mr. Daly wants to move gene sequencing from research laboratories into daily medical practice. The company he heads, Visible Genetics, has developed a test to sequence genes of the virus that causes AIDS, providing information to help doctors choose which of the 15 or so available drugs will work best against a particular patient's infection.

"You've got a huge medicine cabinet to pick from and no good way to pick," said Mr. Daly, whose company is publicly traded and based in Toronto."

"The use of genetic information to tailor drugs to patients is usually seen as a future promise. But in the battle against AIDS, several companies say that day is here now, and they are racing to build businesses."

redux [07.06.00]
HMS Beagle Latent resistance
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"New treatments have extended the lives of AIDS patients and offered hope for a cure, but multidrug-resistant strains can still foil therapy. Researchers used analysis and computer simulations to show that resistance-related treatment failure in patients who consistently take their prescribed drugs is likely due to mutant strains present at the beginning of treatment rather than strains developing during the course of treatment as a result of residual viral replication. The finding stresses the importance of combining drugs with different resistance profiles in order to wipe out all existing drug-resistant strains of the virus early in treatment."

Reference: Ribeiro, R.M. and Bonhoeffer, S. 2000. Production of resistant HIV mutants during antiretroviral therapy. Proc. Natl. Acad. Sci. U.S.A. 97(14):7681-7686."

Proceedings of the National Academy of Sciences Production of resistant HIV mutants during antiretroviral therapy
"HIV drug therapy often fails because of the appearance of multidrug-resistant virus. There are two possible scenarios for the outgrowth of multidrug-resistant virus in response to therapy. Resistant virus may preexist at low frequencies in drug-naïve patients and is rapidly selected in the presence of drugs. Alternatively, resistant virus is absent at the start of therapy but is generated by residual viral replication during therapy. Currently available experimental methods are generally too insensitive to distinguish between these two scenarios. Here we use deterministic and stochastic models to investigate the origin of multidrug resistance. We quantify the probabilities that resistant mutants preexist, and that resistant mutants are generated during therapy. The models suggest that under a wide range of conditions, treatment failure is most likely caused by the preexistence of resistant mutants."

redux [04.05.00]
HMS Beagle Are Computers Evolving in Biology?
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"I suspect that although the new enthusiasm for computers in biology is genuine, it overlooks some basic problems in implementation. The basic difficulty, as I see it, is that although biologists use computers, they do not trust everything that comes out of them. It is one thing to use them to print up nice-looking graphs, but it is an entirely different matter to use them to think better."

"Francis Crick was once quoted as saying that no biologist had ever made a discovery using a mathematical model. I would reply that no biologist has ever made a discovery by running an electrophoretic gel. They make discoveries by using their brains. Computers, like all scientific tools, are only as good as the person who uses them. If biologists don't understand how computer models are constructed, they won't know their strengths and limitations. Without some foundation of trust, biologists will be unlikely to utilize or accept this powerful method of data analysis."