Genetics and occupational safety and health.

In occupational health much has been made of the potential impact of the “genetic revolution” on worker health.1 Schulte2 and OEM are right to ask the direct question—what hath this wrought? In the accompanying editorial Schulte acknowledges that although genetics has not yet had a major impact upon occupational health and safety, with continued research critical questions raised by this type of information will need to be addressed and answered.2 Has what we posited 20 years ago to be a relatively straightforward march toward understanding genetics and integrating these data into exposure‐related disease susceptibility become so very complex? Just how important is this issue and how far away are we from genetics having any palpable effect on worker health? The general approach to the hazardous environment can be characterised by (1) problem recognition, (2) evaluation of the environment, and (3) application of controls (including prevention and hazard elimination). This simple guiding paradigm has stood the test of time. We apply it today, intuitively and explicitly including the rapid changes in science and technology. Does the genetic revolution affect our paradigm? Indeed, it is probable that knowledge of genetic susceptibility to a toxicant or infectious agent could affect our recognition of potential harm as well as our parallel evaluation of the hazardous environment. In fact, it also might suggest novel control strategies or approaches to hazard elimination. Hence, keeping a watchful eye on the progress of this “revolution” is indicated. Where are we to look for the signposts? As Schulte suggests, genetic variation in individual response to exposure to beryllium stands as a prominent example. Here the science is sound and there is active discussion of the appropriateness of worker genetic testing and screening.3 The practice of occupational medicine in this one area has incorporated the genetic data, although as yet there is no consensus on its potential utility. Although the science addressing genetic susceptibility to workplace toxicants is not similarly established for any other case, it is conceivable that this may occur. In the case of infectious agents, we have the example of the CCR5 polymorphism and its association with resistance to HIV.4 Here the science is sound, but this has had less prominent effects upon worker health. It is similarly likely that there will be genetic variation described that will have a significant impact on individual susceptibility to other important infectious agents, such as tuberculosis.5 This will resonate in the healthcare workplace, as well as in other workplaces where this disease is endemic. Interestingly, what these cases have in common is that they are single agent exposures with a pathologic process involving pathways that are either known or under very close scrutiny. Thus, one is tempted to assert that it is far too early to look for scientifically useful biomarkers of susceptibility to complex mixtures and complex environments. As this really represents the majority of workplaces, it is completely possible that the genetic revolution will affect worker health only very moderately in the foreseeable future. That is not to say that genetics may not have profound influence; rather, the simple has become complex, and the utility of this technology must await a scientific consensus that is likely to remain elusive. So, what of the contributions in the meantime? Where will this research have an impact? Assessing this landscape, it is likely that the study of genetics and genomics applied to exposure‐related disease will point us in new directions and thereby reap enormous rewards in defining disease mechanism. One profound example actually arises from the recognition of disease associations that are not genetic. Rather, our research is now pointing us to the companion study of epigenetics. This can be defined as the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence.6 Epigenetic changes are almost certainly responsible for heritable adverse consequences of DES, and recent research points to likely epigenetic roles for the induction of the toxic consequences of herbicide exposure,7,8 and asthma and respiratory disease (which are obviously exposure‐associated).9 Hence, perhaps one of the great contributions of genetics and genomics to occupational health is not in the elucidation of gene‐environment interactions and disease associations. Rather, one of the real values of this research is its failure to become a part of practice and, thereby, has opened other complementary paths of research. So it is—the simple becomes complex. As we move ahead we can be assured that new paradigms will emerge to supplant the old ones, pushing us further towards having the tools we require to more completely understand occupational disease. Genetics is a piece of the puzzle, but only a piece. We have begun to realise this and, importantly, we may soon be ready to incorporate what we have learned and move forward once again to new frontiers. The practice of occupational medicine is ready to incorporate novel approaches and information, but only when it is rigorously tested, medically reliable and ultimately adaptable into our time‐tested framework for protecting worker health.