P-32 Ingestion At NCI Attracts Attention; Similar Cases Seen At Labs In The Past

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Following months of press coverage, the story that began when a postdoctoral researcher at NCI received an internal dose of phosphorus-32 is continuing to attract national attention.

In the latest development, the CBS news show 60 Minutes is preparing a report on the circumstances surrounding the contamination of Maryann Wenli Ma, the researcher, who was pregnant at the time she had ingested the isotope.

Setting the stage for a public hashing out of this immensely complicated story, Ma’s lab chief John Weinstein, who is portrayed as a villain in Ma’s complaint to nuclear regulatory authorities, is also expected to appear on the program.

In a complaint to the Nuclear Regulatory Commission, Ma and husband Bill Wenling Zheng allege that Weinstein, chief of the Laboratory of Molecular Pharmacology at the NCI Division of Cancer Treatment, had been relentlessly pressuring the Chinese scientist to terminate the pregnancy. The complaint also alleges that Weinstein had interfered with the assessment of Ma’s exposure and her treatment.

“Frankly, the whole discussion is quite ridiculous,” Weinstein said to The Cancer Letter. “Given my record as a supervisor, the notion that I would be involved in such a thing to save some time on the maternity leave just doesn’t make sense.

“Anybody who has worked in my group will know that I take a mentor’s interest in the welfare, not just in research, of those involved,” Weinstein said in his first interview since the case became public.

A Series of Incidents

The incident at NIH appears to be a part of a series of similar incidents involving contamination and poisoning in US life science laboratories. Ingestion of radioactive materials and poisons has occurred in at least five other lab since 1982.

“These events occur when you take an individual who is psychologically unstable and expose him to the stress ingrained in the laboratory environment,” a victim in one of the cases said to The Cancer Letter. “The real reason for these events is that the environment of research will always be stressful, and that means these events are going to occur again.”

The radioisotope P-32 was used in four of the six cases.

So far, only one case has resulted in an arrest and two cases are under investigation. No deaths were reported in any of the incidents.

A summary of the cases follows:

  • At NIH, the source of Ma’s intake of as much as 1,000 micro-curies of P-32 remains uncertain. The researcher alleges that the contamination occurred on June 28, after she ate three-day-old leftovers from a meal at a Chinese restaurant. The leftovers were kept in the office refrigerator, Ma states in her complaint to NRC.
  • On July 14, NIH officials reported that radioactivity was detected in a water cooler near Ma’s lab. Altogether, 26 people were exposed to small doses of P-32, NIH officials said.
  • On Aug. 14, a little over six weeks after Ma’s exposure, a postdoctoral researcher at MIT ingested about 579 micro-curies of P-32 (The Cancer Letter, Oct. 27).

Though the intake was relatively small, NRC gave the case a high priority because of its apparent similarity with the NCI case.

In a press conference that concluded the on-site investigation last week, NRC officials said the exposure was not accidental, and it appeared that someone had placed P-32 in the researcher’s food or drink.

•On June 6,1994, at Rockefeller Univ., 15 people were poisoned with coffee tainted with sodium fluoride. Following the poisoning, gas jets were turned on in two laboratories, and two days later, a fire was started in a closet, police and Rockefeller officials reported at the time.

According to press reports, the New York Police Department investigation centered on a male scientist. Rockefeller, too, conducted an investigation, and, ultimately beefed up security in the laboratories. However, no arrest was made in the case.

“Neither investigation yielded enough evidence to prompt the police to make an arrest,” Rockefeller spokesman spokesmen Marion Glick said to The Cancer Letter.

•On April 20, 1988, at Duke University, a laboratory scientist ingested an estimated 3 to 9 milli-curies of P-32, said Richard Fry, deputy director of the North Carolina Division of Radiation Protection.

The circumstances of the exposure or the source of the isotope were never determined, Fry said. The researcher’s exposure was measured at 31 rem.

Investigators were unable to locate the source of contamination, and the case, which received no news coverage, remains unsolved.

  • In 1983, a scientist at Quidel Pharmaceuticals, a La Jolla, CA, biotechnology firm, pleaded guilty to having used a laboratory chemical to lace the office coffee pot.
  • Acrylamide, a substance used to separate proteins, lowers blood potassium levels. According to press reports, four people were hospitalized in the incidents that occurred in 1982 and 1983. The scientist was sentenced to serve a year in an honor camp, a five-year probation and a $1,000 fine, the Los Angeles Times reported at the time.
  • On Feb. 8, 1982, at Brown University, a postdoctoral researcher triggered an alarm on an area monitor after returning from a lunch break, NRC documents state. An investigation revealed radioactivity readings on the researcher and the uneaten portion of her sandwich. University officials estimated that the researcher ingested about 350 micro-curies of P-32.

“I Carry NoDoz”

No federal agency keeps track of ingestions of poisons or radioactive materials, The Cancer Letter has learned.

The NRC keeps records of the cases it had investigated, thereby leaving out the cases handled by state radiation safety agencies. Moreover, under NRC regulations, institutions are not required to report ingestions of under 600 microcuries.

Thus, the recent case at MIT was not reported to the authorities for two months until the journal Nature informed the institute that it was planning to publish a story on the incident.

Laboratory poisonings that do not involve radioactive materials are even more difficult to trace since they are generally investigated by local and state authorities.

The few researchers who are familiar with the lab poisonings expressed surprise that such events do not occur more frequently, especially at the time when the scarcity of research grants is putting additional pressure on scientists.

A victim in one of the cases said to The Cancer Letter that attempts to strengthen security at laboratories would be unlikely to stop these acts.

“The people who do this are more intelligent than average, and no matter what you do to thwart them, they will find a way to get around it,” the victim said. “The bottom line is that people have to protect themselves. I never drink coffee brewed in a public area.

“I carry NoDoz,” he said.

The existence of other cases of deliberate poisoning and radiation exposure in laboratories may cast a different light on the NCI case.

“It is disturbing that Dr. Ma, Dr. Zheng and their lawyers have rushed to judgment in this matter instead of taking a good hard look at the facts,” said Weinstein’s attorney Fred Joseph. “There are many explanations for what has taken place [at NCI], and certainly there is evidence that there have been similar situations at other labs.”

Ma’s attorney Lynne Bernabei said the existence of analogous cases can be construed as evidence of dysfunction in the environment of research laboratories.

“It’s a response to unproductive competition, where members of the same lab, instead of working cooperatively, are out for themselves to reap the benefits of any discovery,” Bernabei said.

The Mystery of Symptoms

The reports by Ma and the MIT researcher Yuqing Li that they experienced pain and discomfort following ingestion of P-32 would run counter to clinical experience with the radioactive material, several clinicians said to The Cancer Letter.

In her complaint, Ma said she experienced “sharp pains on the right side of her liver area” the night after eating the leftovers, which, according to the complaint, included fish and shrimp. MIT researcher Li reported nausea and pain in the joints, a woman who identified herself as Li’s wife confirmed to The Cancer Letter.

“I am not familiar with any side effects associated with oral P-32, even in milli-curies doses,” said Emil J Freireich, professor of hematology and oncology at M.D. Anderson Cancer Center.

“There are no symptoms at the 1,000 micro-curies level,” agreed-Louis Wasserman, a hematologist at the Mt. Sinai School of Medicine and former chairman of the Polycythemia Vera Study Group. P-32 is one of the treatments for Polycythemia Vera, a blood disorder.

Kenneth Miller, editor of the Health Physics Journal, said that even at 15-millicuries doses of P-32, patients report no pain or nausea.

“The patient experiences none of the classic symptoms you would associate with radiation overexposure,” said Miller, professor of radiology and director of the Division of Health Physics at the Hershey Medical Center at Pennsylvania State University.

If the complaint is accurate, psychosomatic pains in Ma’s case would have to be ruled out because, according to the document, the researcher experienced pains in the liver area the day before her contamination was discovered.

“I think they cannot tell you that patients who receive radiotherapy experience no pain,” Ma’s attorney Bernabei said. “I would be surprised. That would run counter to all scientific evidence that has led to setting occupational exposure limits.

“Even in external exposures, P-32 has been reported to produce very serious side effects,” Bernabei said. Ma was not available for comment. The scientist’s agreement with 60 Minutes precludes her from speaking to other news organizations, Bernabei said.

Revoke the NIH Licence?

One possible explanation for the symptoms was suggested by Anthony Fainberg, an expert in safety of nuclear materials.

“It does not take a rocket scientist to see that anyone who eats three-day-old shrimp may be susceptible to gastric distress, particularly in the second trimester of pregnancy,” Fainberg said to The Cancer Letter.

Ma was in the 17th week of pregnancy at the time of her contamination, the complaint states.

In the complaint, Ma’s attorneys argue that NIH has systematically failed to control and secure radioactive materials.

To support the claim, the complaint presents an overview of problems NRC has found during inspections on the NIH campus. These included a contamination of a sink with Iodine-125, external contaminations of researchers with P-32, as well as citations for the lack of “constant surveillance of radioactive materials in the nuclear pharmacy” and “failure to refrain from drinking and eating in a restricted area.”

“At the very least, I see a materials handling problem at NIH,” said Fainberg, a physicist who until recently was a science policy analyst at the congressional Office of Technology Assessment. “At worst, I see a security problem, which could be particularly serious, especially if there is a lunatic running loose.”

Fainberg, who reviewed the Ma complaint at the request of The Cancer Letter, said the majority of violations cited in the complaint were minor.

“When NRC goes to a facility and looks, they always find violations,” said Fainberg. “That’s why hey do it.”

It would be outrageous to use any of the problems and violations cited in the complaint as a pretext to shut down DNA research at one of the world’s premier AIDS and cancer research facilities,” Fainberg said.

Weinstein’s Version

In his first detailed response to the allegations in Ma’s complaint, Weinstein said he had never pressured Ma to terminate her pregnancy. “The subject of the termination of pregnancy did come up, but it’s interesting to note that it was Dr. Zheng who brought up that subject,” Weinstein said to The Cancer Letter.

Weinstein said that after learning about Ma’s pregnancy he encouraged her to fill out the forms required by the NIH Radiation Safety Branch, he said.

“I was the one who got the declaration of pregnancy form [and] I explained it to them,” Weinstein said.

Moreover, Weinstein said that, contrary to allegations, he had never insisted that Ma continue her work with radioactive isotopes. “I leave it to an individual investigator to decide on the kind of work they are doing,” he said.

In the interview Weinstein offered his version of a crucial event in the controversy: a meeting with Ma and Zheng, followed by dinner at a Chinese restaurant. It was the leftover food from that dinner that may have been contaminated with P-32, the complaint states.

Contrary to the complaint, which characterized the meeting as “unpleasant,” Weinstein said the meeting was amicable and productive.

“Their experiments had been failing [and] they were frustrated,” Weinstein said. “I thought we had made good progress in pinpointing possible reasons for why their experiments were failing and what to do about it.”

After the meeting, Weinstein reluctantly accepted the invitation to have a late lunch with Ma and Zheng, he said.

“I was scheduled to go out at 6:30 that evening, so it wouldn’t have been my choice to go out to lunch starting at 2:30, but I felt that this was a gesture on their part, and so I had to take it up,” he said.

Weinstein also disputed the allegations that after learning of Ma’s contamination, he had objected to informing the NIH Radiation Safety Branch, delayed Ma’s transportation to a hospital and, later, advised a hospital physician to “discontinue his efforts to collect [Ma’s] urine over a 24-hour period.”

“My reaction throughout was one of concern for Dr. Ma, concern for Dr. Zheng, and an attempt to help provide the best possible care, reassurance and information for diagnosing the amount of contamination,” Weinstein said.

Weinstein said that after ascertaining that contamination had in fact taken place he called Radiation Safety Branch. Weinstein said he had never advised hospital physicians to stop collecting Ma’s urine. “That’s ridiculous,” he said.

The complaint quotes Weinstein telling Ma that “the baby should be worried,” an apparent reference to possible health effects of the exposure on the fetus. In an interview, Weinstein said he could never have made that statement.

“I don’t know what those words mean,” he said. “It’s certainly not the way I would speak.”

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