Absolute proof or preponderance of evidence?

This article in On Earth marks the beginning of research that might have far reaching consequences in how we view disease and how our consumption is currently involved in creating health problems:

Although some diseases are inherited through a single genetic mutation — cystic fibrosis and sickle cell anemia are examples — the classic “one gene, one disease” model doesn’t adequately explain the complex interplay between an individual’s unique genetic code and his or her personal history of environmental exposures. That fragile web of interactions, when pulled out of alignment, is probably what causes many chronic diseases: cancer, obesity, asthma, heart disease, autism, and Alzheimer’s, to name just a few. To unravel the underlying biological mechanisms of these seemingly intractable ailments requires that scientists understand the precise molecular dialogue that occurs between our genes and the environment — where we live and work, what we eat, drink, breathe, and put on our skin. Herbert’s literature scan was a nod in this direction, but actually teasing out the answers in a laboratory has been well beyond her or anyone else’s reach — until now.

The earliest prototype was devised about a decade ago; since then these tiny devices, as well as other molecular investigative tools, have grown exponentially in their sophistication, pushing medical science toward a new frontier.
Gene chips are small, often no larger than your typical domino or glass laboratory slide, yet they can hold many thousands of genes at a time. Human genes are synthesized and bound to the surface of the chip such that a single copy of each gene — up to every gene in an organism’s entire genome — is affixed in a grid pattern. The DNA microarray allows scientists to take a molecular snapshot of the activity of every gene in a cell at a given moment in time.

The process works this way: Every cell in your body contains the same DNA, but DNA activity — or expression — is different in a liver cell, say, than it is in a lung, brain, or immune cell. Suppose a scientist wishes to analyze the effect of a particular pesticide on gene activity in liver cells. (This makes sense, since it is the liver that processes and purges many toxins from the body.) A researcher would first expose a liver cell culture in a test tube to a precise dose of the chemical. A gene’s activity is observed through the action of its RNA, molecules that convey the chemical messages issued by DNA. RNA is extracted from the test tube, suspended in a solution, then poured over the gene chip. Any given RNA molecule will latch on only to the specific gene that generated it. The genes on the chip with the most RNA stuck to them are the ones that were most active in the liver cells, or most “highly expressed.” The genes that don’t have any RNA stuck to them are said to be “turned off” in those cells. Scientists use the micro array to compare the exposed cells to non-exposed, control cells (see sidebar). Those genes that show activity in the exposed cells but not in the control cells, or vice versa, are the ones that may have been most affected by the pesticide exposure.

…a scientist at the Natural Resources Defense Council (NRDC), who was then a postdoctoral researcher at the University of Maryland, designed an experiment that included the use of microarrays and other molecular tools to figure out how, exactly, mercury was interfering with both our nervous and immune systems. She grew cells in test tubes — one set for mouse brain cells, another for mouse liver cells — and exposed them to various doses of mercury so that she could see which genes were being switched on and off in the presence of the toxic metal. In the brain and the liver cells, she noticed unusual activity in the gene interleukin-6, which both responds to infection and directs the development of neurons.
“We thought we had mercury figured out,” says Ellen Silbergeld, a professor of environmental health sciences at Johns Hopkins University, who collaborated with Sass on the study. Genomic tools may identify effects of other chemicals by allowing scientists to “go fishing,” as Silbergeld puts it, for things they did not know to look for.

But first, a more fundamental question: Do we even understand what today’s chronic diseases are? It is beginning to appear that what we call autism may in fact be many illnesses that we’ve lumped together because those who are afflicted seem to behave similarly. Doctors base their diagnosis on behavioral symptoms, not on what caused those symptoms. Some scientists now refer to the condition as “autisms,” acknowledging that we’ve yet to find a single, unifying biological mechanism, despite the identification, in some studies, of a handful of genes that may confer increased vulnerability. But then, genes or environmental exposures that appear to be important causal factors in one study may not show up at all in another. This leaves scientists to wonder whether the problem isn’t that the disease is so diverse in its biological origins that only a truly massive study — involving many thousands of patients — would have the statistical power to tease apart the various factors involved.

Norway has a study going with 100,000 people on the impact of environment on disease symptoms and causes using this genetic array testing. Clinton started a program in 2000 looking at large numbers of Americans and possible causes of disease symptoms, and includes a number of data sets that could be used for more general purposes. Recruiting has not started to date due to funding problems. The UK is also beginning another large, long term study.

I have included mercury levels in unborns as an example of how innovation in diagnostic procedures will allow us to measure what I have called ‘subtle toxins’ in the environment not because effects are subtle, but measurement is. Our water contains lots of medications and soluble chemicals, and there are no procedures in place to determine safety to unborns and newborns, small children (under 5).

Our ignorance is not limited to dramatic breakthroughs in technological diagnostics, however. Some procedures are simply more commonsense. The American Academy of Pediatricians found that safety levels for mercury blood levels in pregnant women was determined by drawing blood from the mother. Later, it dawned on people to test blood levels from the cortical blood of the fetus, which turned out to average 70% higher levels of mercury than the mothers, and put the fetus way over limits of safety published by EPA. Mercury is fairly common in the environment.

This sort of research costs money, and if it goes where I think it will go over the next ten years, will create concern. Does this sort of research deserve funding by government? Is the initial funding something the current private sector would ever consider? Beginning results are not expected to be ready until 2011 or later, and final results from these particular studies could carry on for several decades.

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