by Dan Fagin
The expert presentations in front of Eric Green were shaping up as critical; they were perhaps the last time the attorneys would control the fate of their own case, since the case-control studies would be completed soon after. Both sides prepared intensively. Cuker pushed his experts to prepare a visual demonstration showing how contamination and cancer washed across Toms River in successive waves. He envisioned a series of maps that would serve as a sort of time-lapse movie documenting the cluster over time as well as in space. They would show how Union Carbide’s plume spread south from Reich Farm, reached the Parkway wells, and was then distributed all over town, year by year. For each cancer diagnosis, meanwhile, a dot representing the affected child’s home address would be added; by the 1996 map, there would be dozens of dots.
The maps neatly summarized the families’ powerful but circumstantial case. Toms River had an extraordinary amount of toxic pollution and a discernible cluster of childhood cancer, and the two seemed to line up, roughly, in what looked like a cause-and-effect relationship. But the families’ case was based on epidemiology, and epidemiology was a science of probability, not certainty. Its practitioners looked for correlations between exposure and disease and then tried to assess the likelihood that they were causal. Even with all the pollution and cancer in Toms River, the apparent association could never be confirmed definitively because of the unanswerable questions about long ago exposures and also because of the enigmatic nature of cancer, which struck so unpredictably and had so many possible causes. If the case ever went to trial, a jury might be persuaded by Cuker’s maps, but the lawyer would have to make an indirect argument on the families’ behalf, one that relied on surrogacy and correlation—and plenty of emotion, too.
Bruce Molholt, lawyer Mark Cuker’s volunteer toxicologist, thought that there might be a more direct way to link the children’s cancers to local pollution. His training was in molecular genetics, and he was accustomed to assessing the impact of pollutants on individual cells and genes, not on large groups of people, the traditional domain of epidemiologists. Molholt no longer did research, but he kept up with the field. He knew that by the mid-1990s, scientists all over the world were looking for—and finding—distinctive changes in genes that seemed to be associated with exposure to specific environmental pollutants. In moments of enthusiasm, the new field’s practitioners sometimes claimed that these genetic biomarkers, as they were called, were like fingerprints—unique identifiers of specific chemical exposures. They were not. Very few biomarkers were caused by only one chemical, and not everyone who was exposed to a particular compound carried the associated biomarker in his or her DNA. Lacking this one-to-one correspondence, researchers instead looked for patterns, probabilistic associations between biomarkers and exposures, which is why the new field was called molecular epidemiology.
The new discoveries were exciting, even if their meaning was unclear. New analytical tools were allowing scientists to peer into the architecture of the double helix, where they could see how certain industrial chemicals wreaked genetic havoc. Some pollutants slipped in between the tightly coiled base pairs of DNA like playing cards in a door spring; others fused with DNA and formed adducts that disrupted cell replication. No one was sure exactly what this meant for cancer causation, though it certainly seemed significant, in light of what Alfred Knudson and others had already proved about the importance of multiple “hits” on DNA in triggering cancer. If biomarkers proved to be sufficiently reliable—a big if—they might even save lives by serving as early indicators of cancer, long before tumors could be detected by conventional means, and by identifying populations that were particularly susceptible to cancer.21
What particularly excited Bruce Molholt about molecular epidemiology were its obvious implications for investigations of cancer hotspots like Toms River. So far, the research projects undertaken in the town were squarely within the twin realms of classical toxicology and epidemiology, fields that could trace their lineage back to Paracelsus. At the end of the National Toxicology Program’s two-year rat bioassay, pathologists would look for physical evidence of tumors, just as Katsusaburo Yamagiwa had done with his rabbits almost a century earlier. Similarly, Jerry Fagliano and his team were conducting a textbook epidemiological study, using exposure mapping and case-counting techniques that were much more sophisticated yet essentially similar to what John Snow had utilized during the London cholera epidemic of 1854. Fagliano identified his forty cases solely on the basis of a diagnosable tumor, not a genetic mutation or other biomarker. But tumors were only one way to document past exposure, and not a very accurate one, since most cancers had many possible causes, and most exposed people did not get cancer.
A biomarker study of the Toms River children, Molholt thought, held out the hope of uncovering clearer evidence of exposure—not quite a fingerprint, but something more convincing than the correlative evidence of Mark Cuker’s maps. It would also be a way of expanding the focus of the investigation beyond SAN trimer, which Molholt worried was getting too much attention compared to other compounds in the town’s air and water. He thought that many of the chemicals dumped in Toms River—especially benzidine and anthraquinone dyes—were good candidates for a biomarker study. The dyes, he thought, were probably intercalators, which meant that they could damage genes by slipping between two base pairs of DNA. Several carcinogenic pollutants had already been shown to intercalate, including benzo(a)pyrene, the coal tar ingredient that Ernest Kennaway in 1932 had confirmed as the first known synthetic carcinogen. Benzidine and anthraquinone were excellent clothing dyes because they were highly reactive, binding tightly to fibers, and because they did not dissolve in water. Those same qualities, Molholt thought, probably made them DNA intercalators. They would be attracted to the hydrophobic environment of the inner surface of the double helix, binding there and, perhaps, triggering cancer-promoting mutations.
If he could convince a molecular epidemiologist to look for biomarkers in Toms River children, Molholt thought, new evidence strengthening the families’ case might surface, maybe even in time to give them extra leverage in the looming settlement negotiations. He already had someone in mind for the job.
CHAPTER TWENTY-TWO
Blood Work
The call from Bruce Molholt surprised Barry Finette. Although he studied how synthetic chemicals damage DNA—a potentially litigious topic if there ever was one—Finette was not called often about legal cases. Many scientists involved in the Toms River investigations were veteran expert witnesses in environmental lawsuits, specializing in one side or the other. Molholt and Richard Clapp almost always testified on behalf of alleged victims of pollution, while Philip Cole and Elizabeth Delzell of the University of Alabama usually worked for manufacturers. But Finette was not a professional witness. He did not particularly like lawyers, and he worked at the University of Vermont, well off the beaten path for big-time biomedical research.
Back in 1998, two years before Bruce Molholt called him, Finette had caused a stir in the world of environmental cancer research by discovering that children of pregnant women exposed to secondhand cigarette smoke carried rare genetic mutations associated with leukemia and lymphoma.1 It was a novel finding, but it did not make Finette a well-known figure in the field. He did not mind in the least. Finette was a pediatrician as well as a molecular geneticist, and he made a point of spending almost as much time seeing children as he did analyzing DNA in his lab. Even if he had given up seeing patients to focus on research, the monomaniacal lifestyle of a high-profile investigator would have been incompatible with his family choices. Finette and his pathologist wife shared an old farmhouse south of Burlington with their blended household of six children, three adopted from difficult homes. He was the legal guardian of a seventh child. In Vermont, a state suffused with altruists and unconventional families, the Finettes fit right in.
Bruce Molholt’s unexpected proposition resonated with Finette in every way he cared about. In his lab and at the Vermont Cancer Center
, where he saw young patients, Finette puzzled over the enduring riddles of childhood cancer. If some common chemicals are mutagenic and carcinogenic, why are malignancies so rare in children? If cancer is closely linked to aging (the average age at diagnosis is sixty-seven), why is there any childhood cancer at all? Scientifically, what Molholt was proposing sounded awfully interesting—and feasible, too. Molholt had access to a population of children with two attributes that were almost never this well documented: They had been exposed to toxic chemicals via the local water supply, and they were much more likely than expected to have developed cancer at a young age. Finette’s work on secondhand smoke led him to believe that genetic changes could be important clues for understanding the causes of childhood cancer. He envisioned setting up a comparative study of exposed and unexposed children, another case-control design. But while Jerry Fagliano’s case-control was aimed at finding out whether cancer risk was affected by the proximity of a child’s home to air or water pollution, Finette’s study would look for evidence of exposure directly in the bodies of the children, in the DNA of their white blood cells. Based on his earlier work, Finette thought there was a decent chance he might find something interesting.
After several conference calls with Jan Schlichtmann and the families’ other lawyers, Finette said yes. Like many professionals who had gotten involved, he was already developing an attachment to the families, even though he would never meet most of them. Molholt, Schlichtmann, Linda Gillick, and Bruce Anderson were just voices on the telephone, but Toms River was turning into more than just another research project. “I felt if I could help answer any of these questions then it would be worth it,” Finette recalled. “This was potentially a unique opportunity, but potentially a minefield as well.”
One of the biggest landmines was the difficulty of getting enough human subjects to participate to yield a statistically significant result. If Barry Finette wanted to find out whether there really was something different about the DNA of the children who drank Toms River water, he would need to test as many children as possible. But getting blood samples from the kids would not be easy. The Toms River children were already all too familiar with the agony of needles, and many of the families whose children were now in remission were trying to forget that they had ever been touched by cancer. They would not be eager to participate in a research project that would bring back such painful memories.
The chemotherapy and radiation therapies the children had already endured posed another difficult complication. Those excruciating treatments had severely damaged the children’s DNA, making it impossible to determine which mutations might have been caused by environmental exposures that predated treatment. Finette’s solution was to draw blood also from their healthy brothers and sisters, who presumably had drunk the same tainted water as their sick siblings and were genetically similar to them. Since he was using a case-control model, Finette would also need samples from a control group: children who were not from Toms River and had not drunk the water but who matched the ages and sexes of the exposed children. Later, he would also include another matched control group: out-of-town children with cancer. Finette made this last addition so that if he found a pattern of genetic anomalies in the exposed Toms River children, he could be reasonably confident that it was caused by local pollution and not by the disease itself.
Finding enough willing children in all those categories would have been difficult even if Finette were blessed with a huge budget for recruitment, which he was not. The lawyers had budgeted just $30,000 for the entire project. Finette could afford to hire a local phlebotomist to draw the blood samples, but everything else in Toms River—including recruiting participants—would have to be handled by volunteers.
In the fall of 2000, Linda Gillick began contacting the TEACH families and urging them to give blood for Finette’s research. Within weeks, the phlebotomist had specimens from thirty-two Toms River children who had been diagnosed with cancer, forty-nine of their healthy siblings, and forty-three healthy children from out of town (matched to the siblings by age and sex). The totals were lower than Finette had hoped, but they would have to do. Bruce Anderson took charge of shipping the vials to Vermont. For the first shipment, he made the mistake of writing “Fragile: Blood Samples” in large letters on the box. Late that night, he got a call from a supervisor at United Parcel Service informing him that UPS would not ship such dangerous material. “After that,” Anderson recalled, “I learned to take all the labels off the outside of the box.”
By November, the cryogenic freezer in Finette’s lab was full of small plastic tubes, each containing a New Jersey child’s blood, processed into dried pellets and frozen at exactly 80 degrees below zero Fahrenheit. Two young researchers at the lab were already busy thawing out some of the samples and beginning the painstaking search for telltale biomarkers, one chromosome at a time.
At the same time that Barry Finette’s team was analyzing the first blood samples from Toms River, the lawyers were gathering in downtown Newark, not far from Nick Fernicola’s old stomping grounds, for the first of the expert presentations that would determine whether Jan Schlichtmann’s dream of a negotiated settlement was a hopeless fantasy or a realistic possibility. Loosely presiding over this informal “science court” was Eric Green, one of the country’s most famous mediators and a founder, in the early 1970s, of what became known as the alternative dispute resolution movement. In Toms River, Green was not technically serving as a mediator; he had no legal power and no authorization to try to broker a settlement. For now, Green saw his role as pushing both sides to make their most persuasive case, without holding anything back.
It was Green’s idea to schedule thirteen all-day sessions, scattered over four months. Each side would bring in experts to address every disputed fact in a case that had hundreds of them. What were the causes of childhood leukemia? How fast can SAN trimer move through sandy soil? Exactly what did the Toms River Chemical Company dump into the river in the 1960s and 1970s? How can you tell whether a cancer cluster is real or a random fluke? Green wanted the lawyers to hear each other’s best arguments and most persuasive expert witnesses on all of those questions and many others.
None of the attorneys involved had ever been through anything quite like it; nor had most of the experts they flew in from as far away as California and England. “That was the scariest room I’ve ever been in. It seemed like there were five hundred lawyers in there,” remembered epidemiologist Richard Clapp. Actually, there were only about twenty lawyers and consultants present most of the time, but the room was so cramped that it felt like more. The host, a water company lawyer named Steve Picco, quickly learned that no matter how many bagels he ordered, they would be devoured in less than five minutes. By mutual agreement, the proceedings were confidential and completely off the record, which meant that the lawyers had to take their own notes. There would be no official record.
What they witnessed was an extraordinary series of clashes over scientific issues that seemed hopelessly arcane when considered individually but that collectively would determine whether the Gillicks, the Andersons, the Pascarellas, and all of the other Toms River families would get the satisfaction—and compensation—they had sought for so many years. Schlichtmann kept reminding everyone that the process was supposed to be a cooperative search for answers, not an adversarial slugfest, but he often seemed to be trying to convince himself as much as everyone else. By now, the lawyers around the table knew that if there was going to be a negotiated settlement, its terms would almost certainly be determined by how impressed each side was with the other’s arguments—and by how impressed Eric Green was. Green could not force a settlement, but he would be listening to every word and giving his assessment, privately, to each side.
At one of the presentations, Mark Cuker finally got to show off the color-coded maps that encapsulated the families’ case. The maps purported to show how pollution and then cancer spread (or “metastasized,” in Schlichtmann’s words) acro
ss Toms River. Emma Ansara, a twenty-four-year-old assistant to Clapp, had created the maps. She was terrified to be showing them to a roomful of hostile attorneys. “I felt very much out of my league, and very underdressed,” Ansara remembered. The maps, covering a period of about fifteen years, were simple: Colored lines superimposed on a street map of Toms River represented the pipes carrying tainted Parkway well water; colored dots marked the addresses of newly diagnosed children. Clapp thought the pattern was obvious: A colored line would extend into a section of town and then, on the next few maps of the sequence (representing the next few years), dots would begin to accumulate in the same area. “It was just sort of jaw dropping how well they lined up,” he recalled. Schlichtmann was even more excited: “When I saw Dick Clapp’s maps, I knew this was going to be another Woburn. I knew we had it; this was compelling,” he remembered. But the pattern, if there really was one, was far from perfect. There were cases in uncontaminated neighborhoods, and no cases in some areas where the water had been tainted. And even if there really was a discernible pattern, the maps were merely a visual representation of the same indirect, correlative evidence that had frustrated environmental epidemiologists for almost a century. The apparent, if partial, alignment between pollution and cancer could be merely coincidental.
Were the maps convincing enough to sway a jury? More to the point, was the other side now worried enough to consider a settlement that would keep the case out of court? Certainly, the lawyers for the families thought they were making progress. So did Clapp, after what he heard his counterpart on the other side of the case say in an unguarded moment. Jack Mandel was an epidemiologist at Exponent, a huge firm that often supplied expert witnesses to the chemical industry. Inside the conference room, Mandel had argued that the cluster was coincidental. But out in the hallway during a break, as the two men chatted, Clapp was surprised to hear Mandel agree with his observation that the case was looking a lot like Woburn. As Clapp remembers it (but Mandel does not), Mandel then said something even more surprising: “I think they should settle, don’t you?”2
