Survivor guilt for beating drug bullet
Jonathan Este, London
March 18, 2006
THEY dosed the men at two-minute intervals. But five minutes after the human guinea pigs had been given the TGN1412, the drug trial started to go dramatically wrong.
The man who had been injected first suddenly started to complain about being hot. He took off his shirt but then he started to shake violently.
Minutes later the third of the six men trialling the anti-inflammatory drug started to vomit. Shortly after that No4 said he could not control himself and needed the toilet. He collapsed before he could make it.
Within minutes, six of the eight men who were trialling the drug were showing dramatic and disastrous reactions, a situation that none of the doctors at the London clinic were prepared for.
Two days later, four of the men are reported to be "improving" while two others remain in a critical condition.
One of those two, Ryan Wilson, a 21-year-old apprentice plumber from north London, reportedly begged doctors to "put him to sleep" as the pain became too intense to bear. His relatives were already grieving last night after they were told he had suffered heart, lung and kidney failure.
"They say they cannot give us any hope," Mr Wilson's sister-in-law, Jo Brown, said. "They have no idea how to treat him because they know nothing about the drug he's been given. It doesn't look good."
Myfanwy Marshall, from Adelaide, whose 28-year-old boyfriend is also fighting for his life, said she barely recognised her partner who she described as looking like "the Elephant Man".
"He is largely lifeless," she told journalists. "I can't even get an eyelid movement or a squeeze from his hand. He is a shell of who he is. He is completely puffed up, his face, his body; he is like the Elephant Man.
"When I walked in there, I expected to see his small face and curly black hair but he looks like a monster. He has tubes up his nose, in his heart, liver, lungs, neck and hands. They told me he could be like this for six months to a year.
"They tried to pump the drug out of his system but all his internal organs are infected. They said he could die at any moment. He needs a miracle."
Ms Marshall has retained a lawyer who said the drug companies could be held responsible for the injuries suffered by the volunteers.
"It's commonplace for drug companies to pay people who are involved in clinical trials small amounts of money such as this," solicitor Anne Alexander said.
"The fact this has gone so disastrously wrong and will result in a very detailed investigation does not enable the drug companies to avoid any obligations they've got."
The eight men had been offered pound stg. 2000 ($5000) each to test TGN1412 - a drug designed to treat leukemia, rheumatism and multiple sclerosis - which is made by pharmaceutical company TeGenero AG, based in Wurzburg, Germany, and was being tested at the London clinic by US research firm Parexel.
Raste Khan, who was the second to be administered with a drug, which turned out to be a placebo, described the scenes in the clinic's ward as "a living hell" that became a "vomiting bath" as one by one the men who had been given the actual TGN1412 started to show violent side effects.
"People were fainting and coming back to consciousness. The gentleman on my left was screaming, saying his back was hurting. It was horrible. It was terrifying because I kept expecting it to happen to me at any moment. But I felt fine and didn't know why. An Asian guy next to me started screaming and his breathing went haywire as though he was having a terrible panic attack.
"They put an oxygen mask on him but he kept tearing it off, shouting 'Doctor, doctor, please help me!' He started convulsing, shouting that he was getting shooting pains in his back.
"I feel guilty that I had the placebo. It was like Russian roulette. I was doing it for the money.
"But pound stg. 2000 is not worth your life."
Ms Brown said she could not recognise her young brother-in-law, Mr Wilson. "His head had swollen to nearly three times its normal size," she said. "His neck was the same. It was wider than his head and his skin had turned a dark purple. At first none of us recognised him. He looked nothing like the Ryan we know and love. His nose was spread across his face like it had been squashed.
"Ryan had tubes in his nose and mouth and was hooked up to a machine helping him breathe and to a kidney dialysis machine. His eyes had been Sellotaped up and he had been sedated. The doctors told us Ryan begged them to put him to sleep because he was in so much pain. He was in agony. Our fear is that he may never wake up." An inquiry is under way on the manner in which the drug was administered and whether the trial should have gone ahead at all. TeGenero had reportedly never tested its products on humans before - and it emerged that the American testing company, Paraxel, had initially been refused permission to test the TGN1412 because of safety fears.
TeGenero's chief scientific officer, Thomas Hanke, who said the company was "devastated" by the tragedy, said the new drug had shown no side effects when tested on animals. However, lawyers acting for one of the victims at Northwick Park hospital, northwest London, raised doubts about the animal experiments that TeGenero claimed to have carried out.
The Sun reported that a dog had died after being administered with the drug, but neither the testing firm nor the drug's manufacturer confirmed this.
The clinic has called for help from international experts in immunology and toxicity in an attempt to understand the dramatic and life-threatening symptoms.
Ganesh Suntharalingam, the clinic's director of intensive care, said that some symptoms were recognisable, but the overall reaction was not.
It was too early to say whether the men would make a full recovery.
"There is an inflammatory process going on that seems to have been triggered by something - that process started to affect other parts of the body so we have two jobs to do," he said.
"One is to try to treat the inflammation and the other is to deal with the consequences of it."
The investigation will focus on the manner in which the drug was administered.
John Henry, a clinical toxicologist at St Mary's Hospital, London, told reporters: "The dose they were using is the whole key here. What was their target dose and what did they start with?
"They should have started with a minuscule dose and given it to the first two volunteers to see if there was any reaction. Then they should have moved on to the next two volunteers and multiplied the dose. You can't, in all conscience, give six people the same dose and hope they will all react perfectly.
"It is just common sense."
The head of a testing company, who asked not to be identified, said the drug-testing industry was "praying" that the incident had been the result of a human error.
"If it is not due to human error then it means that you can take a new molecule through discovery and laboratory testing, through all the animal studies and see nothing untoward until you take it into man at a minuscule dose and you see a catastrophic event.
"That would undermine the testing and development of all new medicines."