US: Study Tied Pollutant to Cancer; Then Consultants Got Hold of It

During China's Cultural Revolution 40 years ago, a city doctor named Zhang JianDong was banished to the countryside of northeastern China. He arrived to a public-health emergency.

A giant smelter was spilling large amounts of chromium waste into the groundwater. Well water was turning yellow. People were developing mouth sores, nausea and diarrhea. Dr. Zhang spent the next two decades treating and studying the residents of five villages with chromium-polluted water.
In 1987, he published a study saying they were dying of cancer at higher rates than people nearby. He earned a national award in China for his research. In America, federal scientists translated it into English, and regulatory agencies began citing it as evidence that a form of the metal called chromium-6 might cause cancer if ingested.

Then in 1997, Dr. Zhang, in retirement, appeared to retract his life's work. A "clarification and further analysis" published under his name in a U.S. medical journal said there was no cancer link to chromium in the villages after all. This new conclusion, like the earlier one, soon found its way into U.S. regulatory assessments, as evidence that ingested chromium wasn't really a cancer risk.
Yet Dr. Zhang didn't write the clarification, judging by voluminous testimony and exhibits in a lawsuit in a California state court. The court papers indicate that the second study was conceived, drafted, edited and submitted to medical journals by science consultants working for the lawsuit's defendant, a utility company being sued for alleged chromium pollution. The consultants paid Dr. Zhang about $2,000 for research assistance on the second study.

That study didn't deny that the polluted area had a higher rate of cancer deaths. But it said factors other than chromium were the likely cause. This was a statement that Dr. Zhang, now dead, had explicitly disputed in a letter to the consultants. Yet he and a Chinese colleague appeared, to anyone reading the report, to be its sole authors. The litigation consultants didn't disclose their role to the journal that published it.

For years, scientists thought chromium-6 in drinking water might, at some level of exposure, pose a cancer risk. The first Zhang study, while recognized as flawed, was one reason for this view. Now many scientists think the metal doesn't pose this risk, and once again a Zhang report is a factor behind their view. How risky the metal actually is or isn't matters, because it has shown up in soil or water in parts of 37 states, according to the U.S. Agency for Toxic Substances and Disease Registry.

Regulators in California, after investigating the second Zhang report, have concluded it is dubious. They have reverted to the original dark view of chromium-6 and are moving to propose a strict limit on it in ground water. The action could ultimately require a costly cleanup, because a third of wells tested in the state exceed the envisioned limit. Costs would grow if other states followed California's lead.

The conflicting Zhang studies show what can happen when the line between advocacy and science blurs. The consultants pursued the second round of Chinese research with the clear aim of rebutting California plaintiffs' arguments, court documents show. But once that second report entered the realm of peer-reviewed science literature, it took on a life of its own in regulatory assessments of the chemical.

The consultants who worked on the second report defend it as good science. And, rejecting the notion that they ghost-wrote it, they say that Dr. Zhang was kept informed of what it said through phone calls and through an early draft that was translated into Chinese for him.

Chromium, once hailed as a miracle metal for its corrosion resistance and durability, is part of stainless steel and has been used in countless products from jewelry to fenders, under the name chrome. The legacy of this wide use is that hundreds of U.S. industrial sites are tainted with chromium-6, also called hexavalent chromium.

This variant -- so named because its atoms have six electrons available to interact with other atoms -- is widely used in alloys, paints and wood preservatives. It has long been known that breathing particles of it can raise lung-cancer risk, but the effect of ingesting it has been hotly contested. That's because digestion converts some into "trivalent" chromium, a form that not only isn't toxic but is an essential nutrient in minute amounts. The U.S. National Toxicology Program is currently conducting long-term rodent studies to try to ascertain at what level chromium-6 might be an oral carcinogen.

The China story is part of a more familiar one, that of Erin Brockovich, the feisty paralegal (played by Julia Roberts in the movie named after her) who helped a California town's residents win $333 million from a utility that had leaked chromium into their water. In 1995, arbitrators hearing the Brockovich case asked the defendant, PG&E Corp., about the original Zhang study. Lawyers for PG&E then assigned a consulting firm to look into it, telling the firm, as a former lawyer for PG&E recalls, "to follow up, to see if they could make contact and get some of the underlying data."

The consulting firm was ChemRisk. It was founded 18 years ago by a prominent toxicologist, Dennis Paustenbach, who has consulted for dozens of companies and serves as a Bush appointee on a board of scientific advisers to the U.S. Centers for Disease Control and Prevention. According to a tally in a textbook he edited, he helped save industry hundreds of millions of dollars in cleanup costs for chromium pollution in New Jersey. His firm was paid more than $7 million for this help, Dr. Paustenbach has testified.

ChemRisk assigned an affiliate in Shanghai to track down Dr. Zhang, and it found him at his home in JinZhou in northeast China. ChemRisk then hired Dr. Zhang at $250 a month to consult.

His 1987 study focused on five villages downstream of the JinZhou Ferroalloy Co. smelter. Village wells were polluted with chromium. His study said the contaminated area had a higher death rate from all cancers, but especially stomach and lung, than the surrounding region.

ChemRisk scientists didn't dispute that. But they sought to determine whether individual villages' levels of chromium exposure correlated with their death rates. The idea was that if chromium was really the culprit, then the death rate ought to be highest in the villages with the most exposure to chromium.

Unfortunately, Dr. Zhang's data weren't good enough to determine individual villages' exposures to chromium. So as a surrogate, ChemRisk looked at villages' distances from the pollution source -- on the theory that the shorter this distance was, the more chromium exposure the village probably got.

They concluded that cancer death rates weren't always higher the closer the village was to the pollution source. That finding led them to doubt that chromium was to blame for the five-village area's overall higher cancer death rate.

Trial Exhibits

A ChemRisk biostatistician wrote in a 1995 internal memo that he foresaw two "products" for PG&E from ChemRisk's work with Dr. Zhang. One was a report that could be the basis for trial exhibits showing "the absence of the association between cancer and groundwater exposure to hexavalent chromium," said the memo. Like many others, it is on file in state court in Los Angeles County, where PG&E -- the defendant in the Erin Brockovich case -- is again facing litigation by residents alleging chromium pollution.

The other product, wrote the ChemRisk scientist, William Butler, would be a report to be submitted to a peer-reviewed journal, with Dr. Zhang as the lead author. Dr. Butler requested a budget of $25,000, which he said would cover 60 hours of his own time to, among other tasks, "interpret data" and "write reports." He budgeted Dr. Zhang's contribution as "research assistance."
Dr. Butler added: "It is at times difficult to convince Dr. Zhang of the importance to us of the specific details of his studies so that we can execute our own analyses."

Three weeks later, ChemRisk faxed Dr. Zhang a draft of a new study of the five villages, translated into Chinese. While reiterating the overall higher cancer death rate, it offered ChemRisk's new analysis saying village distances from the smelter didn't always correlate with death rates. Dr. Zhang wrote back that "I totally agree with what you wrote: 'There is no positive correlation between cancer mortality and the distance of the village to the pollution source or the level of contamination.' "

However, Dr. Zhang had previously told ChemRisk he never tried to assert such a link. And after reading the draft, he told the firm he didn't accept its conclusion that "lifestyle of the residents and other environmental factors unrelated to chromium contamination" might explain the overall higher death rate for the contaminated area.

"This is only an inference; it is inappropriate to consider it as a cause," he wrote to ChemRisk, in a letter filed in California state court. Dr. Zhang instructed the consulting firm to replace that assertion with a vaguer one mentioning several possible variables, as well as the need for more research.

Yet the report, as later published, even more strongly linked the higher cancer mortality to lifestyle and other non-chromium factors. Instead of saying these might be the cause, the published report called them the "likely" cause.
The published report then went further and stated flatly that the higher rate of cancer death in the five villages was "not a result of the contaminated water." Neither stomach-cancer nor lung-cancer deaths "indicated a positive association with hexavalent chromium concentration in well water," the published article said. Neither of those statements was in the draft that was translated into Chinese for Dr. Zhang to read.

Did Dr. Zhang change his mind and sign on to these conclusions? Documents and testimony by former ChemRisk scientists show that ChemRisk drafted the text and graphics of the final report in English, on ChemRisk computers, three months after translating the earlier draft into Chinese. Dr. Zhang, who died in his late 60s in 1999, couldn't speak English, the ChemRisk scientists testified.

In depositions, former ChemRisk scientists acknowledged they might not have translated the final article into Chinese. But they maintained, and continue to assert, that Dr. Zhang was aware of its contents from phone conversations and from the early draft he did read. Tony Ye, a former ChemRisk scientist who speaks Chinese and served as the liaison with Dr. Zhang, testified that he kept Dr. Zhang "informed" of everything ChemRisk concluded for the article and that it was published with Dr. Zhang's "agreement."

Dr. Zhang's son, Zhang Hongzheng, bristles at the idea that his father would wittingly have retracted his award-winning 1987 findings. Dr. Zhang was "sure of the relations" between cancer and chromium-6, says the son, who says he helped his late father in the research. "My father's 1987 article won an award. It's impossible that he would have overthrown what he said. That's like saying his previous painstaking effort was a total waste," the son said in an interview.

Submitting the Study

In December 1995, ChemRisk submitted the new study of the villages to the Journal of Occupational and Environmental Medicine. ChemRisk's Mr. Ye signed the cover letter and gave his own home address and phone number as contact information, as he did in subsequent correspondence with the medical journal. His letters to the publication were written on plain white paper and made no reference to either ChemRisk or PG&E.

Asked why not, a former ChemRisk official said it was because the study was "not a work product, per se," of the consulting firm. The official, Brent Kerger, was manager of litigation services for ChemRisk, which at the time was a unit of an engineering firm called McLaren/Hart Inc. He and ChemRisk's founder, Dr. Paustenbach, both testified that ChemRisk had wanted to have credit on the paper but that Dr. Zhang told Mr. Ye he didn't want to let the consulting firm share in his authorship.

Mr. Ye, in an interview, said he didn't recall Dr. Zhang ever telling him that.
PG&E says its role should have been acknowledged when the article was published. "The lesson in this case is that it's in everyone's interest to have full transparency," said a spokesman for the utility. He added that "nothing published in the scientific literature since [1997] challenges Dr. Zhang's research and conclusions." PG&E paid ChemRisk about $1.5 million in all for litigation support, according to Dr. Paustenbach's testimony. Other court documents said that included about $20,000 for the China research.

The medical journal that published the study required acknowledgment of research support, both then and now, said its editor, Prof. Paul Brandt-Rauf of Columbia University. "It sounds like there were some things that, had I known, I might not have approved of, including not telling us who their funders were," he said.

One person who did appear on the article -- but seems to have played a minimal role in it at best -- was Li ShuKun. The article listed her as co-author. According to Dr. Zhang's son, she was his father's girlfriend and did no research. Dr. Li, a physician at a health and anti-epidemic station, wouldn't discuss her relationship with Dr. Zhang but said he asked her to write the report from his data because he was busy, and she did so, in Chinese. She said she never saw it again. Former ChemRisk scientists said they never received a Chinese draft. They testified in California court that they had no contact with Dr. Li. They said they added her as a co-author at the request of Dr. Zhang.

Broader Impact

The 1997 article began to influence scientific views. In 2000, the U.S. Agency for Toxic Substances and Disease Registry updated its chromium profile, adding a paragraph about the 1997 study. The passage concluded with the concept Dr. Zhang had pointedly rejected in his memo to ChemRisk. The entry said the 1997 study's authors "commented that these more recent analyses of the data probably reflect lifestyle or environmental factors, rather than exposure to chromium(VI)."
Soon other bodies, such as the Environmental Protection Agency and the California Department of Health Services, also cited the second study to that effect. A 2001 report by a special panel of scientists for the state of California discussed the 1997 paper and concluded there was no need to tighten chromium-6 standards.

Dr. Paustenbach, the ChemRisk founder, served on this panel. He resigned before its report was issued because of a public flap over a perceived conflict of interest, since his firm was a consultant to chromium defendant PG&E.
When the panel's report came out, Dr. Paustenbach emailed it to his former colleague Dr. Kerger, with a note: "Buy a good bottle of wine, pull up a chair...and then read this. Then, say to yourself 'Yep, I really finally did something good for society.' "

California's Office of Environmental Health Hazard Assessment had also begun looking into the 1997 study, however, and assigned an epidemiologist to review it. He found several "limitations and oddities," he later wrote. For instance, the study called for "further follow-up of this cohort," implying that it was, itself, a follow-up of a cohort of villagers, which would make it a particularly rigorous kind of study. In reality, there was no follow-up of individuals.

The state epidemiologist, Jay Beaumont, described in internal memos what he suspected were improprieties in the 1997 study. He listed them under the heading "The Case for Scientific Publication Fraud," including: "ChemRisk did virtually all the work and didn't mention themselves. Zhang maybe did no new work, yet is first author"; and, "Acknowledgement of funding not made."

Risk Calculations

Redoing Dr. Zhang's 1987 analysis in greater detail, Dr. Beaumont calculated that in the overall area with chromium-tainted well water, the odds of dying from stomach cancer were 81% higher than in adjacent nonpolluted areas and 69% higher than for the province as a whole.

Dr. Butler, the former ChemRisk biostatistician, says such a comparison isn't appropriate because the surrounding area includes an industrial town whose population isn't comparable to that of the five polluted villages, where farmers live. Minus that town, Dr. Butler said in a written reply to questions, "I see no...patterns of cancer rates that challenge the conclusions" of the 1997 study. Dr. Butler acknowledged four "minor errors" in the 1997 study that he said didn't change its conclusions.

California's Dr. Beaumont found insufficient evidence to assume that contamination was higher closer to the smelter, as the 1997 analysis did.
But ChemRisk's Dr. Kerger maintained that distance was "a reasonable surrogate for chromium-6 exposure." Using that surrogate, the 1997 report said villages where people presumably got the most chromium exposure didn't always also have the highest rates of cancer death.

In scientific terms, there was no "dose response." And this, Dr. Kerger said in his own written response, is "a critical consideration in determining the validity of a claimed association between chemical exposures and cancer."

Dr. Kerger maintained that the article didn't represent itself as a follow-up of a "cohort" of villagers. He said he would agree that use of the term "cohort" once in the study "was not an ideal choice of terms."

He added: "The bottom line is that all of the text, table and figures in the final manuscript were considered to be appropriately detailed and complete by Dr. Zhang and by the peer reviewers."

California's Dr. Beaumont has submitted his own analysis to a science journal, where peer reviewers have given him comments, according to a spokesman for his agency. California regulators have set aside the 2001 report by a special panel of scientists, partly because of Dr. Beaumont's analysis. Based on many studies besides those in China, they are expected soon to propose a "public health goal," or safe limit, for chromium-6 in drinking water.

Setting Limits

This would be the nation's first such limit focused just on the most toxic form of chromium. Currently, water standards exist only for total chromium. The EPA's is 100 parts per billion, and California's is 50 ppb. For chromium-6, California is likely to propose a safe limit of only about three ppb to six ppb, early drafts suggest.

A standard that strict could compel widespread cleanup. The metal has already been found above three ppb in more than 1,200 water sources in California. If other states or the EPA followed California's lead, treatment and litigation costs could soar nationwide.

Meanwhile, the second Zhang study is still having an influence.
Ore-processing plants in northern New Jersey once produced millions of tons of chromium waste that was used as landfill throughout Hudson and Essex counties near New York City. Chromium-6 has turned up in Jersey City Little League diamonds and, this fall, near the Weehawken-Manhattan ferry terminal.

ChemRisk's Dr. Paustenbach has been instrumental over the years in persuading New Jersey regulators to ease cleanup standards for the metal. An article he co-wrote was cited in a recent New Jersey report that concluded it still wasn't known whether chromium-6 is carcinogenic when ingested. One plank of the Paustenbach argument: that Dr. Zhang's "follow-up study" didn't find a cancer link.

New Jersey's chief risk analyst, Alan Stern, says he's aware Dr. Zhang published an earlier study tying chromium in water to cancer deaths -- the study that California regulators now believe is accurate. But, he says, "we haven't read it because it's in Chinese."

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