In the New England Journal of Medicine article Osterholm and his colleagues explain, "Although the powdered carbon may have contributed to the removal of the [toxic] agent, it does not explain how the agent was introduced into the product."12 Showa Denko's own lawyer admits the filter hypothesis "is discounted by scientists at Showa
Denko." He said that "the amount of powdered carbon used for filtration had varied before ... and it was not unusual for it to dip this low."11
Strain V was considered the superman of all the previous strains used by the company. Its output was about twice that of Strain I. Osterholm argued in his paper that the newly introduced Strain V bacterium "may have produced larger quantities of the [toxic] agent than earlier strains."12 Similarly, Yanofsky points out that the higher amount of L-tryptophan in the fermentation process increased the possibility that side reactions would produce more contaminants. He says, "It's possible that one purification scheme may be quite adequate when producing low levels of tryptophan, but at higher levels, it might not be good enough."13 Thus, as Showa Denko introduced a genetically engineered strain that likely produced more contaminants, they reduced their filtration at a time when an increase may have been needed.
If genetic engineering was responsible for producing the contaminants, it provides an explanation for something else that has baffled researchers. Showa Denko's records reveal that the amount of contamination in the L-tryptophan produced from Strain V varied considerably. The lots produced in March, April, and May of 1989, for example, contained very high amounts of contamination. Levels of one contaminant dropped unexpectedly toward the end of April and all suspected contaminants had decreased considerably by the time L-tryptophan was taken off the market.14 These changes, which have baffled researchers, may have resulted from unstable gene expression caused by insertion mutation, genetic hot spots, or other unpredictable effects of genetic engineering.
Biotech companies and the FDA offer a second reason why genetic engineering was not the most likely cause of EMS: Some of the cases occurred before Strain V was introduced. According to William Crist, an investigative reporter who has spent years studying the EMS tragedy, the FDA's biotechnology coordinator, James Maryanski, told him in a July
1996 phone conversation, "We can not rule [genetic engineering] out. . . . However, we are aware of close to two dozen cases of L-tryptophan linked EMS that occurred before Showa Denko began using their engineered strain. So, there would have to be a cause other than just the mere engineering of the strains. Now, I can't say that definitively because we don't have a lot of information on these earlier cases." Maryanski asserted that "either L-tryptophan itself, or L-tryptophan in combination with something that was the result of the purification process, was probably the more likely cause."9
Crist was not convinced and decided to investigate. He discovered that the actual number of pre-epidemic cases was considerably higher than Maryanski had described. While the CDC identified nearly 100 cases that began several years prior to the May 1989 epidemic,15 the actual figure is probably between 350 and 700,9 because the agency's passive surveillance system identified only one out of every four cases— or even less.
To test Maryanski's claim that L-tryptophan by itself may have been responsible, Crist tried to find out if there were any EMS cases associated with a different company's brand. "I faxed and called about a dozen law firms who had handled [hundreds of] Showa Denko cases. None had handled or knew of even one definite case associated with another manufacturer," reported Crist. Stephen Sheller, an attorney whose firm handled over 100 EMS cases, including about ten with onset prior to the epidemic, said, "We have always been suspicious that there were EMS cases caused by other L-tryptophan. . . . However, we have never had a case that we could confirm that with. All cases that we've had [have] been traced to Showa Denko."9
In the scientific literature, Crist found three studies by CDC epidemiologists that showed that Showa Denko's product was associated with cases prior to the epidemic. Moreover, no studies anywhere implicated any brand of L-tryptophan other than Showa Denko's.
These findings contradict the FDA's claim that L-tryptophan itself may have caused the epidemic. If it had, according to CDC epidemiologist Edwin Kilbourne, "all tryptophan products of equal dose produced from different companies should have had the same [effect]."16 But Kilbourne insists there is no evidence to support this. Likewise, Gleich at the Mayo Clinic says, "Tryptophan itself clearly is not the cause of EMS in that individuals who consumed products from companies other than Showa Denko did not develop EMS. The evidence points to Showa Denko product as the culprit and to the contaminants as the cause."17
But that still leaves the question, What was responsible for the pre-epidemic cases? According to Maryanski, since EMS cases "occurred before Showa Denko began using their engineered strain... there would have to be a cause other than just the mere engineering of the strains."9 Maryanski was describing Strain V, introduced in December 1988 and subsequendy linked to the EMS epidemic of the following year. Crist, however, discovered in his investigation that previous strains of bacteria used by Showa Denko were also genetically modified. Between 1984 and 1988, the company introduced four successive GM strains, II-V.
Thus, the pre-epidemic cases of EMS also appear to be the result of L-tryptophan created from genetically engineered bacteria. This would explain why researchers found that only people who consumed Showa Denko's brand contracted EMS. And since Strains II-V were progressively modified to produce greater and greater quantities of L-tryptophan, each improved strain created more contaminants. This would explain the gradual increase of EMS cases leading up to the Strain V-related epidemic.
In the beginning, Crist wondered why the FDA didn't know about the earlier strains. They had access to the same sources of information he had, and certainly much more. But as Crist was reading a key document about the case, he happened to notice the fax imprint at the top of the page, displaying the date and sender of the document. Crist had found a smoking gun of his own. On October 2001, he wrote to Maryanski and Joseph Levitt, director of FDA's Center for Food Safety and Nutrition: "I have a copy of a September 17, 1990 fax from FDA, which appears to be a report by Showa Denko listing the parent mutant Strain I, and the genetic modifications in Strains II-V. So the agency knew that Showa Denko had used three other strains of engineered bacteria, besides the strain (V) that was linked to the epidemic cases, and did not disclose this fact to the public."
Crist continued, "It appears that FDA has tried to defuse and downplay the issue of genetic engineering by shifting the blame to tryptophan itself, using pre-epidemic EMS . . . cases as justification."9 The FDA did not respond to his letter.
Continuing to pore over data, Crist discovered that earlier strains of Showa Denko's GM bacteria also produced contaminated product. In fact, a German firm had rejected shipments of Showa Denko's L-tryptophan in 1988, prior to Strain V, due to the presence of an impurity. He wrote, "According to internal Showa Denko documents, when Showa Denko was questioned about the . . . impurity, they admitted that they couldn't determine a lack of toxicity of the impurity because they couldn't figure out what the impurity was."9
After the outbreak, a study that tracked one of the EMS-related contaminants (Peak E/EBT) identified it in pills manufactured as early as August 19, 1986. Thus, both Strains III and IV produced this impurity. And one person who contracted a severe case of EMS in November 1987 was taking L-tryptophan produced from Strain III. His pills were tested and identified as Showa Denko's with their characteristic pattern of impurities.9
Showa Denko also tested their products, but some of their most important test results are no longer available. According to John Baker, an attorney who represented several EMS victims and served as a member of the National Steering Committee for litigation against Showa Denko, "after reviewing the company documents and the depositions of company employees, expert scientists retained by Plaintiffs in the EMS litigation in the United States have opined that Showa Denko appears to have destroyed some of the serial chromatograms that showed contaminants in their L-tryptophan product in 1988."9
In what appears to be a tacit acceptance of responsibility, however, Showa Denko did extend out-of-court settlements to pre-epidemic cases of EMS—those who had taken L-tryptophan created from its earlier GM strains of bacteria. In total, the company paid a total of over $2 billion to more than 2,000 victims.
The number of victims who got EMS from L-tryptophan produced by earlier strains of Showa Denko's GM bacteria may be much higher than originally thought, because identification of the disease can take years. An article in the June 2001 National EMS Network Newsletter states, "While many believe there were pre-epidemic cases of EMS that were either given another diagnosis or no diagnosis at all because the term 'eosinophilia-myalgia syndrome' was not a part of the medical lexicon, some people are only now discovering that they have EMS." The way that a pre-epidemic EMS case is determined is "first by establishing that a person in fact consumed L-tryptophan produced by Showa Denko (SDK)."18 Studies show that many patients diagnosed with eosinophilic fasciitis (EF), fibromyalgia, and scleroderma had taken L-tryptophan and therefore may have had EMS but were misdiagnosed.
Don Hudson of Louisiana is one such patient. He says, "My first EMS symptoms began in November 1987. By February 1988, I was extremely ill and had been hospitalized. My treating physician was totally baffled. He ran every test conceivable, including a muscle biopsy. I was on the edge of death and slipping fast. For whatever reason, I stopped taking L-tryptophan, and within a month my condition had improved past the critical stage. My doctor diagnosed the problem as fibromyalgia, but he told us that my illness was one of those things that medicine just couldn't explain."
When Hudson attended a fibromyalgia support group, he quickly became aware that his situation was quite different from the others. "None of the other members had life threatening symptoms. Practically all gave me a blank look when I asked how high their eosinophils had gotten. I had an eosinophils count of 25,000 to 58,000, whereas zero to 400 is normal."9 Hudson's count remains high and, like many other EMS victims, he continues to face symptoms every day. Hudson battles temporary blindness, irritable bowel, unbearable muscle pain, fatigue, tremors, and breathing trouble, among other problems.
When Strain V was first implicated, FDA investigators should naturally have obtained the bacterium to verify that it produced the contaminated L-tryptophan. But Maryanski told Crist in an interview that the FDA never obtained samples of the bacterial strain. An article in Science claims that Showa Denko destroyed all of their bacteria when the toxicity problems first emerged.11 But when Crist contacted Showa Denko's attorney Don Morgan in March 2001, he heard quite a different story. According to Crist, Morgan revealed "that Showa Denko offered to give FDA the cultures, but they did not want to mail them, as apparently FDA had requested." When exposed to the environment, the bacteria can mutate and produce additional impurities. Morgan told Crist "that FDA never followed through on Showa Denko's offer to turn over the bacteria, in such a way that they could show FDA the proper way to handle them, etc. [Morgan said] the company finally destroyed the bacteria in 1996."9
Crist wrote to Sam Page, then a scientific director at the FDA, asking him to respond to Morgan's claim. His questions remained unanswered. Crist submitted several Freedom of Information (FOI) requests to the FDA and CDC in 1998 and again in 2001. Crist said, "In 1998, responses were received from FDA and CDC, but none of the specific documents and/or information requested were supplied. In 2001, FDA FOI staff said that the information requested either 'was lost' or 'could not be found,' and that the people who were involved at that time (1989-90) had all left FDA." Crist told the FDA representative that several of the scientists and officials to whom his requests were directed, including Sam Page, Rossanne Philen, Henry Falk, and Edwin Kilbourne are all still at the FDA or CDC, but the FDA FOI staff person repeated that the people involved had left. Crist says, "Their failure to respond suggests that the questions may, in fact, be on target. . . . Now, it appears that they both may have known all along that the GE strains did play a crucial role in EMS and that they concealed this information to protect the U.S. biotech industry."9
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