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TWO The Consensus Critique

Now that we have a draft of the genome, the next big challenge is understanding how genes interact with the environment.

Field Notes, NIH, 2002

As long as the health and the environment . . . environmental health, is kept as a primary focus, then it [NIEHS] has a unique role.

Testimony of Stefani Hines (US GPO 2007: 88)

Under what circumstances would environmental health scientists see molecular genetic approaches to understanding human health and illness as an opportunity, rather than a threat to the jurisdiction and standing of their field? As one environmental health scientist put it, genetic research—especially as it was being “oversold” as the key to unlocking the mysteries of all human health and illness—appeared to many “as much as a barrier as a way to take action” (Interview S50). Following the publication of the first map of the human genome and the revelation that it contains many fewer genes than initially expected, environmental health scientists argued that genomic research had produced the unintended consequence of highlighting the importance of the environment to human health (Olden & White 2005).¹ However, even in advance of this revelation, environmental health scientists had begun to advocate for the idea that gene-environment interaction was critical to understanding human health and illness. Notably, beginning in the mid-1990s, the leadership of the National Institute of Environmental Health Sciences (NIEHS) began promoting a research agenda for the field that focused on gene-environment interaction, broadly defined. To mobilize environmental health scientists to support research on gene-environment interaction, its advocates would have to convince their colleagues that molecular genetic and genomic techniques could advance the public health mission of the environmental health sciences, contribute to efforts to inform public policy, and bolster environmental health research when it is challenged in regulatory reviews and litigation. At the same time, they had to find ways of accommodating the goals and aspirations of environmental health scientists who were eager to establish a “more biomedical” approach to environmental health, which would include individual-level, clinical interventions. Reconciling these multiple and often competing visions of the field was no small feat.

This chapter examines how scientists advocating for research on gene-environment interaction made a case for this new way of thinking about environmental health research. The jumping off place for my analysis is the observation that “the basic problem for skilled social actors is to frame ‘stories’ that help induce cooperation from people in their group that appeal to their identity, while at the same time using the same stories to frame actions against various opponents” (Fligstein 2001: 113; see also Frickel & Gross 2005).² Such identities and narratives may be most powerful when they draw on the extant stock of meanings, beliefs, ideologies, practices, values, rules, and resources already at play in an arena. However, they also have to navigate those same meanings, tensions, and conflicts. For example, the dynamics of contention in the environmental health arena have meant that, to be persuasive, scientists’ framing of gene-environment interaction have to appeal to stakeholders with widely divergent, indeed opposed, substantive goals and commitments in the regulatory process.

Scientists advocating for research on gene-environment interaction developed a narrative that included both a diagnosis of the problems and challenges facing the environmental health sciences (“diagnostic framing”)³ and a set of proposed solutions to those problems (“prognostic framing”) that highlighted the potential of molecular approaches.⁴ As I will demonstrate in the following pages, the social institutions, actors, processes, and especially the politics of the environmental health arena provided “readily available scripts” (Fligstein 2001: 110) for scientists eager to promote research on gene-environment interaction. In particular, scientists mobilized long-standing critiques of the process of environmental health risk assessment and regulation.⁵

At the same time, the dynamics and concerns of the environmental health arena set an important limit on the development of narratives about gene-environment interaction and its potential contributions. That is, while identifying problems and solutions to the challenges of environmental health research, risk assessment, and regulation, advocates of research on gene-environment interaction have exercised care not to wholly undermine the legitimacy of the current risk assessment paradigm. This is not only because the current system serves as the basis for environmental health regulation, and thus public health protection, nor simply because the regulatory agencies themselves are key stakeholders in this process. Rather, as described in Chapter 5, it is because the current system provides the standards by which new, molecular risk assessment techniques are evaluated. As such, framing processes must answer the question, “If this works, why fix it?” without portraying the current system as so “broke” as to be illegitimate (Interview S41).

I call the narrative scientists crafted in response to these manifold challenges a consensus critique. A consensus critique represents an effort to bring stakeholders together around a set of shared concerns that transcend their substantive political, economic, and/or social differences. It diagnoses problems and proposes solutions in ways that are acceptable to actors who seek divergent—and often opposed—ends. Often, this is accomplished by focusing on potential improvements to a central social process, while remaining agnostic about how such improvements may change outcomes, such as the balance of power or opportunities for success among stakeholders. Related, a consensus critique might orient to core values—such as truth or fairness—that are nearly impossible for stakeholders to disavow (though, they may contest their meaning). As such, consensus critiques facilitate collective action in politically contentious arenas.

However, even as it brings stakeholders together around set of shared concerns, a consensus critique will sideline or obfuscate issues that lie beyond its specific definition of core problems and proposed solutions. Social actors whose concerns are excluded by a consensus critique will have good cause, then, to challenge the agenda set in response to it. Consequently, the collective action facilitated by a consensus critique may give rise to the next loci of contention in an arena.

In advocacy for molecular approaches to environmental health research, the consensus critique has centered on technical challenges inherent to the current risk assessment process that a wide variety of stakeholders perceive as salient concerns. It has three main emphases. First, it highlights the challenges inherent in extrapolating from laboratory-based toxicological research— often conducted using highly standardized animal models exposed to high doses of one chemical over a short period of time—to complex interactions between human bodies and their environments in everyday settings. Second, it points to the fact that many more chemicals are in use than have been evaluated in risk assessment by the federal regulatory agencies. Third, it calls attention to questions about how to assess the risks that a substance poses to individuals who are at the sensitive end of the toxic response continuum. The success of this narrative hinges, in large part, on the fact that, although scientists, regulators, industry, and health advocates tend to disagree vehemently about the outcomes of particular risk assessments, they tend to agree nonetheless that the process itself could be improved. The consensus critique, in its firm faith in the promise of the further scientization of environmental health governance via molecular genetics, thus provides a rationale for research on gene-environment interaction, while eliding the substantive political and economic interests underlying conflict in the environmental health arena.

In addition to obviating the substantive differences of stakeholders in favor of a technical critique of risk assessment, the consensus critique offers scientists a remarkable and consequential degree of interpretive flexibility. While positioning research on gene-environment interaction as two the solution to “intractable problems” (Olden 2002: 275), it never defines exactly what gene-environment interaction is, how one should study it, or which molecular genetic technologies or applications thereof offer the greatest promise. As such, it has allowed environmental health scientists to develop research agendas focused on widely varied definitions of gene-environment interaction. Similarly, the consensus critique has opened up space for epidemiologists, toxicologists, and other researchers to develop their own subfield-specific responses to it.

This flexibility, however, has limits. Specifically, the consensus critique fails to account for the social structural issues—such as racial segregation and poverty—that shape disparities in environmental exposures in the United States. Few environmental health scientists call attention to this omission. However, as shown in Chapter 6, the limits of scientization feature prominently in EJ activists’ concerns about the ascendance of gene-environment interaction in the environmental health sciences. As such, the consensus critique is an important starting point for understanding not only how research on gene-environment interaction has emerged in the environmental health sciences, but with what biopolitical consequences.

THE CONSENSUS CRITIQUE

“The Intractable Problems”

The diagnostic component of the consensus critique centers on the limitations of the current risk assessment process. NIEHS administrators characterize these limitations as “the intractable problems” that “have long characterized the field”; they include questions about the ability of extant techniques to assess “intrinsic toxicity to humans, variation in susceptibility, crosstalk or interaction between agents in mixtures, and the type, pattern and magnitude of human exposure to chemicals” (Olden 2002: 275). Toxicologists highlight especially the challenges inherent to the two-year rodent cancer bioassay, which is the current gold standard for carcinogenicity testing:

There are major obstacles in toxicology and this has been obvious to a lot of people: extrapolation from animals to humans, all the issues about exposure, because with the rats, you’re giving a large dose over a concentrated period of time but humans are exposed to varying doses over longer periods of time and exposed to mixtures . . . and then there are issues of nutrition and genetic susceptibility (Interview S32, emphasis added).

In addition to identifying the challenges of toxicology testing, the consensus critique emphasizes the uncertainty that derives from issues surrounding the extrapolation of data derived from in vivo testing in animal model systems to establish the risks to humans. This aspect of the consensus critique is highlighted especially by regulatory scientists. For example, one regulator stated starkly, “people . . . worry about the relevance of animal studies” (Interview P03). Another regulatory scientist expressed a similar concern by stating that the two-year rodent bioassay “gives you the answers: (1) this does cause cancer in rodents; (2) this does not cause cancer in rodents; (3) this might cause cancer in rodents. Then, you have to extrapolate to humans. This entire process is difficult, slow, and expensive” (Interview P02).

Second, and related, environmental health scientists emphasize the consequences of expensive and time-consuming nature of the two-year rodent cancer bioassays, specifically, the tremendous number of high production chemicals that have not yet been tested. In fact, scholars estimate that of the chemicals on the EPA’s high production volume list (that is, chemicals produced in high volume in industry), an estimated 93% lack basic chemical screening tests, and 43% have not been subject to basic toxicology testing (Brown, Mayer, & Linder 2002; see also Altman et al. 2008). In explaining her enthusiasm for genomics research, a toxicologist referred to the need to “break the bottleneck” in testing and “deal with the backlog of chemicals that are still waiting to be tested” (Field Notes August 2002). Another toxicologist stated:

The idea is that we’d like to be doing it better. We’d like to be doing it cheaper. We’d like to be doing it more quickly. Because you know, at eight compounds a year, and millions and millions of dollars [per compound] we’re never even going to make a dent in everything that’s out there that probably needs to be tested (Field Notes August 2002).

In reflecting on his years as director of the NIEHS and National Toxicology Program (NTP), Olden also invoked issues of efficiency in reference to his support of efforts to establish new, molecular techniques for use in risk assessment:

We were just using a few very standard assays that had been in existence for years, and there are still people who tell me we should still be doing that. But I felt that we were not providing a very good product—a quality product; and the efficiency was very poor. In other words, we were spending too much money and generating very little useful information (Olden, Oral History Interview July 2004).

Even scientists who believe that animal bioassays provide the most reliable data for risk assessment note that the current system is unable to keep pace with the demand for testing. In fact, concerns about the backlog of chemicals awaiting assessment dates back to the NCI’s Cancer Bioassay Program, the precursor of the NTP (Smith 1979). However, the volume of testing has decreased over time, as the studies conducted have become more complex and costly. As this toxicologist noted, “One change that has occurred over the years is a decrease, a significant decrease in the number of chemicals that NTP studies for carcinogenicity. Whereas in the early ’80s there were about 50 per year, in the ’90s it drifted down to somewhere around 10 per year” (Interview S96).

Third, the consensus critique positions unexamined variation in susceptibility among humans as a source of uncertainty in the risk assessment process:

We do most of our assessments based upon the typical American. We think there is going to be so many cancers averted, so many reproduction problems and so on and so forth. We do not consider the fact that individuals are different . . . granted, we do look at subpopulations . . . but [not] . . . from a genomic point of view, whereas, in fact, that’s really what we’re talking about (Interview P03).

Currently, risk assessors take the value that toxicology testing has determined to be an acceptable exposure limit for a standard human (e.g., the no observed effect level [NOEL]) and multiply it by ten (Smith 1996). Although many regulatory scientists believe that this is a conservative practice that is successful in protecting susceptible individuals, such ten-fold factors are seen as arbitrary and burdensome by regulated industries (Interview P03), and environmental health advocates question whether they are truly protective (Interview P06). This also raises the more general issue of how to protect particularly vulnerable individuals, who, with few exceptions, are not specifically protected under existing laws and regulations.

In their articulations of the consensus critique, environmental health scientists highlight the fact that such broad domains of uncertainty provide opportunities for expensive and time-consuming legal challenges to risk assessments (Michaels 2008). In the words of a toxicologist, “people who want to promote political uncertainty will use scientific uncertainty as a basis” (Field Notes, NIEHS July 2002).⁶ However, even as they acknowledge the political (and, arguably, economic) interests that motivate controversy in the environmental health arena, scientists emphasize the potential of molecular genetic and genomic techniques to address the uncertainties and limitations in current toxicological testing practices and to improve the capacity of environmental health research to contribute to risk assessment and regulation (e.g., Paules et al. 1999; Olden 2002; Simmons & Portier 2002).

The Prognostic Promise of Molecular Techniques

The prognostic component of the consensus critique positions gene-environment interaction, broadly construed, as a means of addressing these challenges. Advocates of molecular genetic and genomic approaches claim that by reducing the scientific uncertainty that has previously made environmental health research particularly vulnerable to challenges in the context of risk assessment and regulation, it will be possible to definitively and more rapidly assess a larger volume of chemicals. In general, the molecular genetic and genomic technologies and methods championed by advocates of this approach vary substantially depending on their subfields.

Toxicologists have been particularly concerned to articulate how genomic technologies can reshape toxicology testing. For example, they point to four distinct, though not mutually exclusive, means by which gene expression profiling, the signal technology of toxicogenomics, could reduce uncertainty in the risk assessment process. First, they promote gene expression profiles as a means of elucidating mechanisms of toxicity and enhancing the knowledge base of toxicology. Second, they suggest that gene expression profiles may provide a basis for a new, molecular rationale for the classification (and reclassification) of toxicants (that is, grouping toxicants that share similar gene expression profiles). Third, and related, scientists are actively pursuing the potential of gene expression profiles to enable the prediction of the toxicity of unknown compounds and thereby provide a basis for their classification (that is, without undergoing the two-year rodent bioassay). Fourth, they point to the possibility that gene expression profiles could serve as new molecular biomarkers of genetic susceptibility. Together, scientists argue, these innovations could increase the speed, efficiency, predictive capacity, and specificity of toxicology testing, making risk assessment more comprehensive and more certain (Bartosiewicz et al. 2000; Bartosiewicz et al. 2001; Burchiel et al. 2001; Fielden & Zacharewski 2001; Hamadeh et al. 2002a; Hamadeh et al. 2002b; Paules et al. 1999; Pennie et al. 2000; Tennant 2001).

Some foci of the consensus critique have been taken up differently across specific subfields. The issue of human genetic variation in response to environmental exposures is the most prominent example of this; it is a central focus of initiatives in epidemiology and toxicology, as well as being the defining focus of the emerging field of environmental genomics. In the context of risk assessment, research on genetic susceptibility to environmental exposures is promoted as a means of providing more precise estimations of risk for specific humans and subpopulations thereof, replacing a one-size-fits-all approach with one that acknowledges variation among human bodies. Testifying in support of the NIEHS Institute’s Budget for 2002, then NIEHS Director Olden told the U.S. Congress that “individuals can vary by more than two-thousand fold in their capacity to repair or prevent damage following exposure to toxic agents in the environment” (Olden, Fiscal Year 2002 Budget Statement, emphasis added). This argument has been prominent also in publications by the NIEHS leadership:

At present, human genetic variation is not implicitly considered in estimating dose-response relationships, nor is it considered when setting exposure limits. Data on the prevalence and characteristics of susceptibility genes offers the potential to reduce the guesswork in risk assessment and therefore it is likely that the ability to issue fair and appropriate regulations concerning human hazards will increase markedly (Olden & Wilson 2000).

As this statement makes clear, the argument can be “extended” (Snow et al. 1986) to speak to “both sides” of regulatory battles; even though they may disagree about what “fair and appropriate regulation” would look like, industry, activists, and regulators cannot help but agree that it is a worthy goal.

At the same time, the problem of human genetic variation in response to environmental exposures is a focus of research in environmental genomics and molecular epidemiology that seeks to develop new clinical tools for identifying persons at risk, in addition to providing surveillance, early intervention, or prophylaxis to prevent disease onset. As I detail in the following chapter, NIEHS administrators frame research on genetic susceptibility as an effort to be “responsive to the needs of the American people” (Interview 27), particularly people’s need to understand “Why me?” in the context of illness: “my friend smoked the same number of cigarettes, we worked in the same industry, and why do I [have cancer]?” (Interview S37). The flexibility of the consensus critique is part of its appeal to a wide variety of stakeholders.

Negotiating Limits

In contrast to the domains of contentious politics, where such narratives are more frequently put to work to mobilize collective action, environmental health scientists who advocate for molecular genetic and genomic research face a unique challenge. Specifically, they have to make a case for a transforming the practices of environmental health science, without thoroughly undermining extant processes of environmental health research, risk assessment, and regulation. This system remains a critical part of the public health infrastructure and, as shown in Chapter 5, it also is integral to their efforts to validate new, molecular techniques. This challenge also has shaped the particular form and foci of the consensus critique.

Scientists use three primary strategies in seeking to promote molecular genetic and genomic techniques for use in testing and risk assessment without delegitimizing current practices and the regulatory policies that rely on them. First, many statements in favor of new techniques emphasize the new molecular levels of analysis made possible by molecular genetics and genomic techniques, with the goal of “moving beyond classical toxicology” (NCT 2002). The argument here is that, although current toxicology and risk assessment provide the best possible system at what environmental health scientists call the “phenomenological level,” genomics offers an innovative means of conducting toxicological research “down at the molecular level” (Field Notes, NIEHS July 2002). One hoped-for consequence of molecular-level research is that it will illuminate the pathways through which chemicals perturb biological functioning and create toxic effects, as, in the words of a regulatory scientist, “oft times . . . we have no idea in the world how some effect comes about” (Interview P02).⁷ Thus, scientists claim that that the effects observed at the phenomenological level are real, albeit poorly understood. Similarly, a molecular epidemiologist argued, “Toxicology needs to go beyond kill ’em and count ’em” (Interview S26). This framing of extant practices as both effective and limited is evident also in a paper about toxicogenomics in Science, which described toxicology as both “an imprecise science” and “a time honored way of identifying human health risks” (Lovett 2000: 536).

Second, advocates of molecular genetic and genomic techniques argue that they will provide a means of doing toxicological risk assessment that is quicker and less expensive and that satisfies the demands of the animal rights movement for reductions in animal testing. This comment implies that, although current testing regimens provide accurate data, they are inadequate for testing “everything that’s out there” (Interview S27). For example, scientists suggest that genomic techniques could be used to set priorities for toxicology testing at the NTP, thereby increasing its efficacy, given limitations in available time and money for testing:

The Program has always been interested in looking at alternative methods, other short-term tests that might provide indications of risk. These are extremely valuable in screening and prioritizing chemicals. So, for example, if you had 50 chemicals and you could only study 10, which ones would you choose? (Interview S96).

Framing the potential contribution of new techniques in this way emphasizes the fiscal and social costs of contemporary toxicological techniques, while leaving their scientific validity unscathed.

Thirdly, scientists emphasize the possibility that molecular genetic and genomic techniques will expand the range of applications of environmental health research. For example, while acknowledging the traditional relationship between environmental health science and environmental regulation, some environmental health scientists frame gene-environment interaction as a means of also developing a range of behavioral and clinical interventions that could improve public health. Advocacy for “a more biomedical environmental health” (Interview S20), which integrates “lifestyle prescriptions” to minimize the risks of exposure or new pharmaceutical interventions to prevent harmful consequences of exposure (Olden, Guthrie, & Newton 2001), does not impugn the current regulatory regime. Rather, it points to a different approach entirely.

Only rarely, and always “off the record,” would an environmental health scientist offer an unequivocal critique of risk assessment. For example, this scientist stated: “Risk assessment to me is a black box nightmare. They’re making very important decisions based on very limited information. They have a legal obligation to make decisions. But the data is just terrible. So, there is real temptation to use new approaches, because anything is better than nothing, which is what they have now” (Field Notes 2002). Another scientist commented: “Risk assessment is where magic happens, and you have to be careful when you go there . . . . The fact that somebody does some science doesn’t make risk assessment less magic” (Field Notes 2001).

More often, using limited frames, proponents of molecular genetics and genomics have been able to promote molecular genetic and genomic technologies as a means of improving toxicology and risk assessment, without discrediting current techniques and standards. This has been critical both to maintaining the legitimacy of the NIEHS, the NTP, and the regulatory system that their research supports and, related, to bringing to the table a wide variety of stakeholders in risk assessment and regulation.

THE MULTIPLE MEANINGS OF GENE-ENVIRONMENT INTERACTION

The interpretive flexibility of the consensus critique has also played an important role in these processes. The consensus critique states that there are limitations to current methods within the environmental health sciences and proposes that molecular genetic techniques offer a way of improving the reliability and validity of environmental health research. However, it never specifies techniques, nor does it offer a precise operational definition of gene-environment interaction. Because gene-environment interaction therefore can encompass a wide range of research foci and techniques, its advocates have been able to garner the support of scientists with disparate research agendas and commitments.

Gene-environment interaction has multiple meanings, which have been shaped by the specific organizational contexts and intellectual lineages of environmental health scientists.⁸ To begin, some scientists define gene-environment interaction as the study of the inherited individual and subpopulation genetic susceptibilities that make some people more vulnerable than others to being harmed by environmental exposures. For example, speaking at a meeting of environmental health and justice activists in New York City in 2002, Samuel Wilson, then the Deputy Director of the NIEHS, explained:

Genes controlling responses to environmental factors have variations in their DNA sequences. That’s just a fact that we’ve begun to appreciate. We see that there are variations. There are many examples where a combination of an exposure and a gene variant are required for an adverse health effect. This is the gene-environment interaction concept (Field Notes 2002).

The identification of individuals and subpopulations that are genetically susceptible to the effects of environmental exposures is a relatively new goal for the environmental health sciences. Toxicologists often explained this new focus to me in terms of their increasing interest in the two outlier populations on a dose-response curve, depicted in Figure 1⁹:

Figure 1.Dose-response curve.

Previously, susceptible populations and resistant populations were identified primarily so that they could be excluded from analysis (i.e., to avoid misestimating the effects on the “normal” population) (Hattis 1996). However, as detailed in the following chapter, environmental health scientists interested in human genetic variation in response to environmental chemicals define susceptibility (and, less often, resistance) as a primary focus of their research.

In a second definition of gene-environment interaction, environmental health scientists contend that in order to understand—and intervene in—the effects of environmental exposures on human health, one must identify their effects on genes and gene expression. For example, a molecular epidemiologist explained that her research on gene-environment interaction focused on:

. . . actually proving that people had these compounds, these carcinogenic compounds, inside them . . . [and] had damaged DNA because of these carcinogens. See, before that, all we had was the industrial hygiene people [who] would tell us, “yes, these people have inhaled carcinogens or PAHs, or benzene or something.” And maybe there were some assays, some urine-type assays, showing that people were excreting them. But the molecular [biomarkers], the adduct assays were the first to show that these compounds actually interacted with, and permanently bound to things like DNA (Interview S12, emphasis added).

This definition encompasses research on environmental mutagenesis, DNA repair mechanisms (and their impairment), and epigenetics; it is also a defining focus of molecular epidemiology.

This second definition of gene-environment interaction—with its focus on how environmental chemicals affect genes and their functioning—was already built into the infrastructure of the NIEHS and NTP. From its inception, genetic damage was “identified as a component of environmental hazards” of interest at the NIEHS (Barrett, Oral History Interview February 2004). During the 1970s, NIEHS scientists (many of whom had transferred from the Biology Division of the Oak Ridge National Laboratory) established the field of genetic toxicology (Frickel 2004), which focused originally on “the potential of chemicals to induce heritable changes in germ cells that lead to genetic disorders in subsequent generations” (Shelby, Oral History Interview April 2004).¹⁰ Many of these researchers shared an interest in developing short-term tests to “study the mechanisms of chemically induced DNA damage and to assess the potential genetic hazard of chemicals to humans” (Tennant et al. 1987). In the early 1970s, the work of Bruce Ames and his colleagues made a strong connection between DNA damage and cancer and provided a relatively easy mutagenesis bioassay—the Salmonella test—to identify carcinogens (Ames et al. 1973).¹¹ Soon thereafter, following the advocacy of prominent environmental health scientists, short-term tests for mutagenesis were “enshrined in regulatory requirements and in biomedical research more generally as carcinogenicity screens” (Frickel 2004). As such, there was significant genetic toxicological infrastructure and expertise at the NIEHS and NTP.

Research on the molecular mechanisms of carcinogenesis has been another site for the development of research on gene-environment interaction at NIEHS. As Carl Barrett, formerly the Scientific Director of NIEHS, recalled, “There was not much of an emphasis in the early days, the first decade of the NIEHS, on cancer because there was a cancer institute. So there was . . . an intentional focus away from cancer to distinguish NIEHS from NCI [National Cancer Institute].” However, beginning in the late 1970s, “there was a growing interest and involvement in cancer [research] within the institute” (Barrett, Oral History Interview February 2004). In 1987, the NIEHS founded the Laboratory of Molecular Carcinogenesis (LMC) and charged it to “elucidate the genes involved in the [cancer] process and use that information to understand how the environment impacts it” (Barrett, Oral History Interview February 2004). By focusing on the role of environmental chemicals in cancer causation, the LMC added complexity to then ascendant scientific explanations of genes as the primary basis of cancer causation (Fujimura 1996): “While we were doing the molecular analysis, we were also studying how a number of environmental chemicals worked . . . [and] we developed a paradigm for thinking about how environmental health worked—that health and disease [are] a consequence of the interaction between ones genes and environment over time” (Barrett, Oral History Interview February 2004).

In addition to the flexibility of this paradigm across varied scientific disciplines (with their different definitions of gene-environment interaction and ways of studying it) and stakeholders in the environmental health arena (with their different investments in the process of risk assessment and regulation), it has been importantly flexible over time.

[All the major genomics initiatives at NIEHS] were part of a greater strategy of trying to bring new technologies and new concepts to bear in terms of environmental health sciences, and they really are extensions of the concept of gene-environment over time (Barrett, Oral History Interview February 2004).

The ability of the concept of gene-environment interaction to be extended over time has meant, in practice, that new technologies and research agendas can be subsumed under its aegis. For example, in 1997, the major genomics initiative at NIEHS centered on sequencing genes that conferred susceptibility to environmental exposures (i.e., environmental genomics); by 2001, NIEHS had also launched a major effort to use microarrays to study the effects of environmental chemicals on gene expression (i.e., toxicogenomics). More recently, researchers have promoted the promise of epigenetics by referring to gene-environment interaction (Olden et al. 2011). Research on gene-environment interaction has been undertaken with a staggering array of techniques, including high-throughput gene sequencers, molecular biomarkers, cDNA and protein microarrays, genome-wide association studies, and quantitative PCR, to name just a few. Thus, the concept of gene-environment interaction has engaged environmental health scientists even as the substantive foci, technologies, and concepts at the center of research shift and change.

CRITIQUING THE CONSENSUS CRITIQUE

Despite its rhetorical strengths and successes, not all environmental health scientists have been persuaded by the consensus critique. NIEHS administrators freely admitted that scientists whom they referred to as “traditional toxicologists” were “not happy” with changes underway at the NIEHS and NTP and referred me to their colleagues for “dissenting” opinions (Field Notes, NIEHS 2002).

However, given the scope of the proposed and ongoing changes to their field, it was surprisingly difficult to find scientists who were critical of research on gene-environment interaction or, related, the development of molecular genetic and genomic techniques for risk assessment. In the one overt exception, a scientist referred to toxicogenomics as “crapola” and contested the relevance of research on molecular mechanisms to the NTP’s public health mission:

. . . everybody coming out of school in the last 15 years are all molecular, DNA is the answer, which [it] may be and which is fine. But [at NTP] we need some people with practicality. We need some people with [skills in] toxicology . . . empirical descriptive toxicology. [If] you find out something causes cancer, then let somebody else mess around with the mechanism. . . . I don’t want to know how it does it . . . I want to know, “Is this safe?” (Interview S97).

Further, a few scientists took issue with the promise of individual techniques of studying gene-environment interaction, noting, for example their “skepticism” regarding research being done in specific transgenic mouse models (even while endorsing research being done with other transgenic mouse models) (Interview S96). However, on the whole, those scientists identified by their peers as dissenters commented on the successes of their field, built on traditional approaches to assessing risks and preventing exposures, rather than offering a critique of emerging molecular approaches to environmental health research. For example, a toxicologist—who in the course of our interview told a colleague who dropped by that I was there to talk with her as “one of those who isn’t in the ‘genes will save us’ camp”—commented: “My interest is in, what can we change to make people healthier? We can change exposures. . . . You can’t change your gene pool” (Interview S28).

As with the consensus critique, the counternarratives offered by dissenting scientists were based on key aspects of the field’s identity, including its relationship to public health and its unique contributions to regulatory decision making and public policy. For example, when I asked a toxicologist about his perspective on the potential of molecular genetic techniques to improve toxicology testing and risk assessment, he responded by highlighting the successes of the NTP in preventing environmentally associated diseases:

I think the NTP does probably more than any other program on issues related to disease prevention. . . . How many lives were saved by reducing human exposure? That’s hard to determine with accuracy. But we know that there are carcinogenic agents in our environment and workplace, risks are elevated, and it is our goal to provide scientific information that can be used to reduce human risk from environmental agents. . . . That is, as far as I’m concerned, the major mission of NTP . . . Our role is to provide the science so that decisions are made that are protective of public health (Interview S96).

Similarly, a scientist contended that the rodent cancer bioassay program—despite its limitations—has succeeded in providing “EPA with the ammunition that they may need.” (Field notes, NIEHS June 2002). Even scientists who, on the whole, supported the adoption of molecular genetic and genomic techniques pointed to the historic successes of current methods of toxicology testing. For example, a molecular epidemiologist acknowledged that “The other side . . . is that this way has served the public well. If you screen out the things that kill rats, you will protect a lot of people” (Interview S26). A toxicologist pointed out that repeated efforts to replace animal bioassays have come to naught: “ . . . other thoughtful people have attempted to replace the bioassay with something, as we say—faster, more accurate, cheaper and less animals—and that’s our goal. But in the 25 years I’ve been in this [field] there’s been a thousand substitutes, none of which have worked” (Interview S97).

More rarely, scientists would suggest that by absorbing scarce resources and introducing new forms of uncertainty into toxicology testing, new molecular techniques would impede and delay the regulatory process. In part, this concern is about the distribution of resources within the environmental health sciences and the possibility that investing in new techniques will divert support from current toxicity testing programs:

. . . people who want the environment protected are concerned that, by siphoning resources away from the chronic studies that are already readily accepted by the agencies, into something that may not be as accepted by them, is to make either a longer time to regulatory intervention, or preclude it, actually preclude it (Interview S41).

Even more to the point, a university-based environmental health researcher commented: “when NIEHS spends so much of their money on the genetic revolution, I wonder how much of that they can really devote to . . . more environmental issues” (Interview S50).

A related set of issues centers on the possibility that the chemical industry could use the uncertainties attendant to new molecular approaches as a rationale for delaying regulatory review of their products. In fact, some scientists suggested that the chemical industry’s interest in genomic approaches to risk assessment was motivated precisely by the potential of new and complex techniques to complicate and delay regulatory processes:

[They] see it as a tool, a delaying action . . . [They say] “I’m going to do this study first to guide me and it will take me two years.” And the regulatory agency says, “okay go ahead.” So, that means two more years that industry can use the product without any regulatory [oversight] . . . it’s a great delaying tactic. Any new technology, it’s always a good delaying tactic for environmental health risk assessments (Interview S41).

Officially, the chemical industry favors the development of new “-omics” technologies that can be used in risk assessment (Henry et al. 2002). However, scientists disagree as to whether, to what extent, and for what reasons, the chemical industry supports the development of genomic techniques. Although some scientists claimed that industry supports these technologies for their ability to delay regulatory reviews, others suggested that “Officially, they’re very supportive, but really they’re not interested at all . . . in the development of better ways of finding out that their products are toxic” (Field Notes, NIEHS 2002). Others noted that establishing a consensus about the applications of new technologies was likely to require significant effort,¹² because even having “more . . . confidence in the models that you use . . . doesn’t mean they won’t still be controversial and there won’t be the arguments from industry and public interest groups, what’s safe and what isn’t” (Interview S81). Such comments were the only overt acknowledgement that the various parties interested in the development of molecular genetic research and technologies in the environmental health sciences hold very different substantive goals vis-à-vis risk assessment.

In fact, the broader politics of environmental health and especially environmental justice remain almost completely absent from the consensus critique and appear only rarely in the counternarratives of dissenting scientists. Neither diagnostic nor prognostic framing of research on gene-environment interaction tends to draw on the issues of racism and environmental justice raised by environmental justice activists.¹³ In their talks to meetings of activists and, more rarely in publications, environmental health scientists claim that research on gene-environment interaction will help us to understand and ameliorate health disparities in the U.S. (e.g., Olden and White 2005). However, many of the solutions proposed in such articles center not on remediating environmental injustices, but rather on identifying genetically susceptible populations¹⁴ and using genomics to better target pharmaceuticals according to “race specific drug response” (Olden and White 2005).

On the rare occasion that scientists raised issues of inequity, it was most often as a counternarrative vis-à-vis the consensus critique. For example, a scientist renowned for his research on lead poisoning in children—a condition marked by dramatic disparities by socioeconomic status (SES) and racial background—commented:

It’s just that to the extent that we think we can understand the genetic contributions to different diseases and solve the world’s problems without addressing environmental pollutants or inequity in our systems, I think we’re really fooling ourselves . . . I think scientists have to confront poverty just as much as they confront genetics (Interview S50, emphasis added).

As we will see in Chapter 6, the omission from the consensus critique of broader social factors, such as poverty and racism, associated with environmental exposure and its focus rather on technical aspects of research and risk assessment have shaped the responses of environmental health and justice activists to research on gene-environment interaction.

FROM PROGNOSTICS TO PRACTICE

The dynamics of contention in the arena of environmental health shape the practices and meanings of environmental health science in the United States. In particular, the dynamics of contention surrounding risk assessment provide readily available scripts for scientists advocating for research focused on gene-environment interaction. These scientists frame the limitations and uncertainties inherent to toxicology testing, in general, and the two-year rodent cancer bioassay, in particular, as the “intractable problems” that undermine their science, jeopardize the standing of their research and institutions, and impede their ability to contribute fully to public health efforts. The consensus critique, then, points to the possibility that, by addressing the technical challenges of toxicology testing, risk assessment, and regulation, molecular genetics and genomics will solve the ongoing dilemmas of environmental health research and governance. As I detail in Chapter 5, the consensus critique has been taken up by myriad stakeholders in the environmental health arena, including, importantly, the regulatory agencies.