"Research is a social good we need better treatments for leukemia and arthritis but there are risks," said Dr. Ezekiel J. Emanuel, chief of bioethics at the United States National Institutes of Health. "Being a construction worker is very risky, and we pay people to do that. So why not this?"
Noting that the TGN1412 trial had been approved by two separate British regulatory bodies and that the medicine had been tested in animals, he said, "This is a terrible, tragic event but so far I don't see any clear ethical problems."
The trial subjects, who were to spend three days as hospital inpatients, were mostly immigrants, some of them students or unemployed.
"These were not people who were well off," said Martyn Day, of the London law firm Leigh Day & Company, which is representing four of the men. "They thought this was relatively risk free."
At the orientation meeting there was little time to read the 11-page consent form, Rob O. said, although they had a chance to take it home. Headaches and bruising were listed as potential side effects, as well as a severe allergy. But eating nuts or using new cosmetics could create similar reactions, the form said.
In fact, so-called monoclonal antibodies frequently produce severe generalized symptoms like aches and chills, though their use is justified by the enormous potential benefit. "At my hospital, we almost killed people the first few times we used Herceptin," said Dr. Goodyear, referring to the popular breast cancer drug, adding that he now pretreats patients with medicines to counter possible reactions.
Parexel applied to test TGN1412 in both England and Germany in December, receiving permission in England first, on Jan. 27. Many countries are streamlining review processes to attract biomedical research, a strategy that may have backfired here, Dr. Goodyear said.
It is not clear if independent immunologists reviewed the trial design, and neither Parexel nor TeGenero answered this question.
The trial began Monday, March 13, at 8 a.m., when the men began receiving TGN1412, each 10 minutes after the last. Within half an hour, the first patient had a headache and chills, said Ann Alexander, a London lawyer who is representing him. Nevertheless, doctors continued injecting new patients. About the time Rob O.'s infusion started, at 9:10 a.m., the first patient had passed out in an adjacent room, according to Ms. Alexander.
Before long, Rob O. said, he began to ache and shiver, feeling as if he had been "submerged in arctic ice." For the rest of the day, six previously healthy men moaned in uncontrollable pain, vomited and struggled for breath, Rob O. and other participants said. Though a dose of steroids temporarily blunted the symptoms, their vital signs steadily deteriorated, and they were transferred to the intensive care unit.
Two of them were placed on ventilators. Uniformed men wheeled in blood filtering machines, Rob O. recalled, to cleanse the blood of acid. Doctors told him that his immune cells were attacking his organs.
The patients' families were summoned to the hospital at 3 a.m.
In statements, Parexel and TeGenero called the reactions "unforeseen and unexpected," noting that doses hundreds of times more powerful had proved safe in animals.
The experimental application filed with British authorities released this week in response to a Freedom of Information Act request showed that the companies at least realized the possibility of a devastating immune-system reaction, and that animal studies showed some signs of immune overdrive.
Those worries were set aside when monkeys infused with TGN1412 had no problems. Although Parexel technicians continued to draw blood in the intensive care unit, the companies have not been willing to share the medical data or even meet with the participants and their lawyers, Mr. Day, the lawyer, said.
With his immune system now essentially disabled, Rob O. says he cannot work, or even take the subway, for fear of infection. His liver and kidney tests are still abnormal. Britain's National Health Service covers his doctor's bills, but he has to pay the $87 cab fare.
Under British law, Rob O. may be eligible only for $50,000 to $70,000 in compensation, said Mr. Day, unless he can demonstrate permanent harm. Anyway, tiny TeGenero took out only a $3.5 million insurance policy to cover the trial.
Lawyers for the subjects are hoping to arrange for financial compensation and full disclosure of medical information on the drug without having to go to court.
"I can't believe that nobody will pay and nobody will be punished," Rob O. said. "If I've lost 20 years of life because my liver packs in at 60 rather than 80, who will cover that?"