A new drug was found to decrease Hepatitis B virus. The drug is an analogue of one of the nucleic acid bases of DNA and probably works by being incorporated into the virus and disrupting viral genes during viral DNA replication. However, patients in a clinical trial of the drug began to experience drastic overproduction of lactic acid and liver failure leading to death. The most likely explanation for the problem:

The overproduction of lactic acid is evidence that fermentation is occuring on a large scale. Knowing that the drug can interfere with DNA replication, it makes sense to conclude that it has interefered with mitochondrial DNA and affected normal ATP production.

If the mitochondria's ability to produce ATP were disrupted, the ATP would have to be produced outside the mitochondria, by fermentation taking place in the cytosol. Though it is normal for the body to use fermentation, especially by muscle cells during hard excercise, fermentation is a temporary response that cannot be sustained in humans.

In the case of patients in this clinical trial, ongoing exposure to the drug would disrupt mitochondrial DNA as use continued, rendering more mitochondria unable to produce ATP. Lactic acid production as a by-product of fermentation would continue, and eventually overwhelm the liver.

The Biology Project
University of Arizona
Tuesday, August 20, 1996
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