3 June 2005
Inherited Disease Findings Stir Evolutionary Debate
by Kate Melville

A disease you are suffering from could be the result of your great-grandmother being exposed to a toxin. Washington State University researchers reached this controversial conclusion after finding that environmental toxins can alter the activity of an animal's genes in a way that is transmitted through at least four generations after the exposure. Their discovery suggests that toxins may play a role in heritable diseases that were previously thought to be caused solely by genetic mutations. The findings, reported in Science, are controversial because they raise the possibility that environmental factors may play a much more significant role in evolution than has previously been believed. Michael K. Skinner, of Washington State University (WSU), said the findings represented a new way to think about disease. "We believe this phenomenon will be widespread and be a major factor in understanding how disease develops." Skinner and a team of WSU researchers exposed pregnant rats to environmental toxins during the period that the sex of their offspring was being determined. The chemicals the rats were exposed to - vinclozolin (a fungicide commonly used in vineyards) and methoxychlor (a pesticide that replaced DDT) - are known as endocrine disruptors, chemicals that interfere with the normal functioning of reproductive hormones. The researchers used higher levels of the toxins than are normally present in the environment, but their study raises concerns about the long-term impacts of such toxins on human health.

Pregnant rats that were exposed to the endocrine disruptors produced male offspring with low sperm counts and low fertility. Those males were still able to produce offspring but their male offspring had the same problems. The effect persisted through all generations tested, with more than 90 percent of the male offspring in each generation affected. While the impact on the first generation was not a surprise, the trans-generational impact was unexpected. While scientists have long understood that genetic changes persist through generations, usually declining in frequency as the mutated form of a gene gets passed to some but not all of an animal's offspring. Skinner said the current study showed the potential impact of what is known as epigenetic inheritance. This means the transmission from parent to offspring of biological information that is not encoded in the DNA sequence. Instead, the information stems from small chemicals, such as methyl groups, that become attached to the DNA. In epigenetic transmission, the DNA sequences - the genes - remain the same, but the chemical modifications change the way the genes work. Whilst epigenetic changes have been observed before, they have not been seen to pass to later generations.

Skinner said that epigenetic changes might play a role in diseases such as breast cancer and prostate disease, whose frequency is increasing faster than would be expected if they were the result of genetic mutations alone. The finding that an environmental toxin can permanently reprogram a heritable trait also may alter our concept of evolutionary biology. Traditional evolutionary theory maintains that the environment is primarily a backdrop on which selection takes place, and that differences between individuals arise from random mutations in the DNA. The work by Skinner and his group raises the possibility that environmental factors may play a much larger role in evolution than has been previously realized.