Why Toxics and Genes Go Together

By Marc Lappé

Sooner or later, many of the readers of the Genetics/Toxics Stopwatch will be perplexed over the juxtaposition of two apparently distant fields of science in one heading. Just what is the relationship between genetics and toxicology - and why put them together as if they were a single theme? The answer is both practical and, we think, persuasive. For one, the work we do at CETOS frequently bridges these two gaps. We are as interested in the impacts of the new genetics as we are in those of toxicology. More arguably, the two sciences impinge on each other in often under appreciated ways.

Our work on pesticides and sensitive ecosystems is a case in point. When we do an ecological analysis of the impact of chemicals on endangered species, as we did in the Smith River Flood Plain described in this issue, we consider the chronic impact of pesticides on species survival - and their genetics. The obligation to perform a mutagenicity test to look for genetic damage is one of the parameters of the EPA's requirements for evaluating chemical use in the environment. But more critically, if we are concerned about endangered species, we are concerned about their genetic integrity.

It is no accident that critics of genetic engineering have been appalled at the laissez faire attitude to the cross-contamination of food crops with genetically modified pollen. So are we. This contamination has now been confirmed in indigenous corn species in Mexico, near the center of genetic diversity of corn, near soybean fields in England and adjacent to canola-growing farms in Canada. These genetic excursions threaten to contaminate native germ plasm with foreign, human-selected genes - and to persist in the newly gene-contaminated crops as they in turn replicate. A similar problem is occurring with the contamination of wild species of salmon with farmed salmon genes that increase the activity of growth hormone. In both instances, the changes can be perpetuated indefinitely. But a greater, less graphic risk is occurring in the natural world even as this is written: the impact of gene-damaging chemicals on endangered and slow-reproducing species.

Toxics come into play with species survival when chemicals alter reproduction significantly as occurred with the endocrine disrupting chemical, DDT and resulting loss of egg shell integrity in birds. Toxics also can damage a species reproductive ability by impairing sperm or egg production, or sperm mobility. Each of these factors is potentially reversible, if the chemical in question is taken out of circulation. The dramatic recovery of the American bald eagle is a case in point: since DDT was banned in the late 1960s, eagles have recovered from a low of as few as 40 nesting pairs to 6,000 breeding pairs in the continental United States.

The greatest impact of toxic chemicals and allied physical agents like radiation is the most invisible. Many chemicals that are in our biosphere are selectively damaging to genes. The "genotoxicity" of some 3,000 chemicals has been charted by the EPA's Gene-Tox program. The most common category for such chemicals is in the pesticide class, particularly among fungicides and nematocides like those used extensively in the flower industry. The types of genetic damage produced by such chemicals can affect cells in the body, and predispose them to becoming cancerous for instance. Or, they can affect the so-called "germ cells" of the testis or ovary, giving rise to damage of sex cells that can pass their abnormality to future generations.

From an ethical point of view, anticipating or preventing harm is more important than reversing harm or producing benefits. This theme is captured in the famous Hippocratic maxim "Do not harm" to which every physician swears allegiance. Preventing genetic harms is presently an all but invisible assignment to our national agencies charged with protecting the genetic integrity of endangered species, as well as human health. Many of the chemicals and radiation of greatest concern for producing inheritable mutations are commonplace: at one time, we were all exposed to background radiation that is exacerbated by radioactive fallout. We are now planning to transport tons of nuclear waste to Yucca Flat and other repositories. We are also facing a serious terrorist threat from "dirty" bombs that could spread radiation anew.

Follow-up testing in Nagasaki and Hiroshima showed that radiation there greatly increased the number of lethal mutations passed on to offspring - infant mortality directly after the bomb ranged from 8-9 per 100 births. A silent percentage of non-lethal mutations has been passed on to another generation. Less well known is the genetic damage produced by Saddam Hussein's gassing of the village of Halabja in the early 1990s. In this atrocity, thousands of villagers were allegedly gassed with mustard gas, a potent gene-damaging chemical developed in World War I. Hundreds of children have apparently developed cancer and birth defects as visible indicators of the degree of genetic damage.

Some of the pesticides in use in the flower industry may be comparably capable of producing genetic damage, including benomyl, metam sodium and 1,2 dichloropropane. Rather than single these and related genotoxic chemicals out for special attention, the EPA lumps genetic toxicity in with the roster of chemical tests needed to assure safety. The fact that a chemical has potent mutagenicity, for instance, does not disqualify it from widespread application. Since genetic damage can be irreversible, this omission has serious consequences.

Of the 3,000 or more mutagenic chemicals in commerce, none are excluded from use because of a positive genetic toxicity test. This means we are constantly being exposed to potential gene-damaging chemicals even as we are launching a program of new awareness about the limited number of genes in the human genome. While some genetic damage, notably that from ultraviolet light, is repairable other damage is not. More critically, some of the chemicals hone in on sensitive sites in the human genome that control the complex repair system for correcting genetic damage. When a specific gene that controls genetic repair is damaged, such as those for breast and ovarian cancer called "BRCA1" and "BRCA2" the consequence is an enhanced vulnerability for target tissues to become cancerous. And when the mutation occurs in a gene that normally keeps tumor growth under control (so-called "suppressor" genes, notably one known as p-53), the damage can lead directly to the outgrowth of a tumor.

All of this speaks to a common need to monitor our genetic health, and to ensure that fewer contacts are made between people and potentially gene-damaging chemicals. We at CETOS are dedicated to this proposition, and have recently written a book called Cutting DNA (Common Courage Press, in press) that highlights our arguments. Because so much of human exposure to mutagens occurs through food and its pesticide residues, it is all the more incumbent on the government to tighten its regulations on the use of gene damaging chemicals among pesticides. We believe the presently under-regulated area of non-edible floral and related products is a key source of unrecognized toxicants - and among them, gene damaging chemicals.