The lifelong shadow hanging over the Elephant Man drug trial victims

By Kathryn Knight

On a hospital ward, patients were writhing and screaming in agony. Their organs were failing, their heads swollen and many were projectile vomiting as their immune systems began to completely shut down.

It looked like a scene from a horror film, yet this was the appalling reality for six young men who had been in perfect health until they signed up to take part in a drugs trial a decade ago.

It was, they believed, a chance to make some easy money and do their bit for medical science at the same time.

But what should have been a routine trial in a private clinic at Northwick Park Hospital, North-West London, soon spiralled into one of the most infamous medical emergencies, and became known as the "Elephant Man" drug trial because of its shocking side-effects. Now a BBC documentary is to revisit the dramatic events that resulted in the young men, including a Kiwi, fighting for their lives, Daily Mail reports.

Featuring extraordinary personal testimony from those who took part in the trial, the doctors who treated them and the investigators tasked with discovering what went wrong, it tells the story of what happened and how it changed the way drug trials are conducted.

One of the men, Ryan Wilson, then just 21, spent four months in hospital and had his fingers and sections of his feet amputated following the trial. Shockingly, he, along with the other five, will never truly know the extent of the long-term damage caused to their bodies.

Of course, none of the eight volunteers had any idea what lay ahead when they gathered in March 2006 at a private unit at Northwick Park run by Parexel, an American company that helps pharmaceutical and biomedical companies develop and launch their products.

The group, aged between 19 and 34, had signed up to take part in the Phase 1 trial, meaning they were the first humans to test the drug known only as TGN1412. It was designed to manipulate the immune system with the hope being that it would eventually revolutionise cancer treatment.

Having been successfully tested on monkeys, expectations were high.

They were split into two groups of four, with one in each receiving a placebo - although no-one, including the clinicians, knew who.

The atmosphere was relaxed and light-hearted, as Rob Oldfield, then 31 and recently returned from an acting course in LA, recalls.

"A friend of mine had done trials and he said I should sign up. They were offering £2,000 ($3452) and I thought that was 'ok', he says. "I was interested in the scientific contribution I could be making. It was a medicine being tested in a laboratory approved by the Government. What could go wrong?"

For Raste Khan, then a 23-year-old recent graduate, the motivation was even simpler.

Raste Khan, a 23-year-old recent graduate, said: "Medical trials were like a get-rich-quick-scheme. A no brainer". Photo / BBC
Raste Khan, a 23-year-old recent graduate, said: "Medical trials were like a get-rich-quick-scheme. A no brainer". Photo / BBC

"Medical trials were like a get-rich-quick-scheme," he says. "A no brainer."

All knew there was risk involved, and filled in an 11-page consent form which detailed the hazards of taking part - to an extent.

"We all knew there was a tiny amount of risk but the side-effects were 'you might get hives, you could get anaphylactic shock' - which you can get from a bee sting," recalls Rob.

Dispatched to their beds on their ward, the drug was administered intravenously with each man receiving their dose ten minutes apart.

Patient 001, and the first to receive the drug, was David Oakley, originally from Christchurch, New Zealand. Newly engaged to fiancee Katrina, he was in the midst of planning their wedding when he signed up.

"I had lots to look forward to," he recalls.

But within minutes of receiving the drug David contracted a headache which rapidly got worse.

"I told the nurse that I was having a major headache," he says.

"She arranged a cold compress on my forehead, but didn't give me anything for it as they didn't want to taint the effects of the drugs they were testing."

Excruciating back pain followed.

"I had severe pain in my lower back - it was way worse than the migraine," David recalls. "I was trying my hardest to twist and turn to find a position where I could feel less pain. I couldn't understand. It was horrible."

Raste, meanwhile, could only look on in horror at David's plight. Unaware he had been given the placebo, he believed he was shortly to undergo the same horror. "I was assuming that my body was maybe a bit slower and it was going to kick in shortly. It was daunting, extremely scary," he says.

As subject number seven, Rob received the drug almost an hour later than David - who by then was already experiencing his adverse reactions - and recalls feeling almost immediately as though he had been "dipped into ice".

"My whole body went freezing cold and I started shaking," he says. "This wasn't something you could stop, it was so extreme. It was horrendous."

New Zealander David Oakley was part of the Elephant Man drug trial. Photo / BBC
New Zealander David Oakley was part of the Elephant Man drug trial. Photo / BBC

Events accelerated. Four hours into the trial, the patients were screaming in agony while the bewildered clinical team descended into panic.

"It was all manic, everything was happening all at once," Raste says. :They were vomiting, they were screaming in pain, people were fainting, they couldn't control their bowels . . . it was like a horror movie."

"I remember the doctors not knowing what to do," adds David. "They probably hoped it would only last a short time. They weren't expecting it to carry on and get worse."

But it did get worse as, one by one, the men "tumbled like dominoes".

Daniel Bradford, the doctor in charge of the trial, ran down two flights of stairs into the hospital's intensive care unit to grab "the first two doctors he could see". In a recent newspaper interview, he confessed he felt "completely out of control".

As well he might. His patients' bodies were shutting down, some more rapidly than others.

On his ward Rob remembers Ryan - whom he had chatted to at the start of the day about how he was taking part to fund driving lessons - being wheeled away connected to beeping machines.

Ryan Wilson, who nearly died, has been left with fingers and toes like stone and that are now gradually falling off. Photo / BBC
Ryan Wilson, who nearly died, has been left with fingers and toes like stone and that are now gradually falling off. Photo / BBC

Ryan was rushed to Northwick Park's intensive care unit, where off-duty consultant Dr Ganesh Suntharalingam had been called in by panicked colleagues.

"He was really as unwell as anyone I'd ever seen," he recalls of his first patient. "It was clear this was a very serious situation. We also knew there were five more people up there who had received the same drug. The clock was ticking, the rate at which they were deteriorating was very rapid."

As the intensive care beds filled up one by one with the critically ill human guinea pigs, outside police vans were criss-crossing London carrying extra equipment to help in the escalating crisis.

The consultants, meanwhile, were desperately trying to understand what had happened - and how to treat it.

For while the men's symptoms - organ failure and unstable blood pressure - looked like an extreme immune reaction known as a cytokine storm they could also have been occurring as the result of infection. The two required different treatment - and if the medics made the wrong call the results could be fatal.

"There was really no margin for error," Dr Suntharalingam admits today. "It was a big decision to take but it was one we had to get on with. We made the decision we would treat them as cytokine storms."

That meant administering a "significant" dose of steroids. After that, all anyone could do was wait - and pray.

Meanwhile, the patients' families had to be informed. At 2am the following morning, medical staff called Rob's mother and told her to come to the hospital. 'The doctors were saying this is your goodbye perhaps,' he recalls.

David's fiancée Katrina's telephone call came at 3.30am after which, heart pounding, she too raced to the hospital to see her critically ill partner.

"I don't think anything could prepare you for what you saw when you first went in,' she says now.

"His cheeks were very swollen, so much so that his eyes looked more like slits. His face was just round like a ball and his stomach was huge. It was pretty scary to see somebody you love so disfigured."

While police investigators declared the unit where the trials had taken place a crime scene, the six men continued to fight for their lives.

"David was in and out of consciousness. He would have enough strength to squeeze my hand, but that was about it before he would drop off," recalls Katrina. Then, 48 hours after they had been admitted to intensive care, Dr Suntharalingam recalls there was a sea-change.

"Suddenly, on Wednesday morning, we were doing a ward round and I thought 'Something's happened'. The four patients who were awake told us within about an hour of each other that they suddenly felt much better."

The group, aged between 19 and 34, had signed up to take part in the Phase 1 trial, meaning they were the first humans to test the drug known only as TGN1412. Photo / BBC
The group, aged between 19 and 34, had signed up to take part in the Phase 1 trial, meaning they were the first humans to test the drug known only as TGN1412. Photo / BBC

Yet, while their vital signs had improved, they were far from out of the woods. It would be another five days before Rob and David were moved out of intensive care on to a regular NHS ward and another two weeks before they left hospital. Even then, they were shockingly weak, their immune systems depleted.

"My organs were back working, but I was like an 80-year-old, my muscles were wasted away," David recalls. "We had no immune system at all, we were given instructions not to go on the Tube, trains or buses in case someone was to cough near us."

Then came the bombshell realisation that their future health was likely to be affected. It was a question that appeared all the more urgent when further tests revealed an anomaly in David's blood which sometimes appears prior to cancerous lymphoma.

It has since been shown to be unrelated to TGN1412, but for many months the discovery cast a long shadow. 'I got married roughly three months after the drug trial and normally you'd think about having children afterwards,' says David. 'That was something I was worried about. Could the drug flow into a child's system? I was very down.'

Both men were, at least, in a better state than Ryan Wilson, who remained in hospital for four months fighting the symptoms of pneumonia, septicaemia and dry gangrene which meant his fingertips fell off and part of his foot and toes had to be amputated.

"I remember him showing his hands like 'Hey, what about my hands'," Rob recalls. "I saw that his fingers had blackened and there was no hope for saving them. I realised he'd come out of this in a bad way and someone was the reason for that."

Now, as then, his feeling was that all the men were "just cogs in the machine".

A subsequent investigation by the Medicines & Healthcare Products Regulatory Agency (MHRA) served to underline that sentiment. In a report two months later, it declared that not only was there no formal system in place to provide 24-hour medical cover, but clinicians had not properly considered the safe dosage of the drug for humans.

The drug was administered ten times more quickly into the men's bloodstream than it had been in monkeys. The report added that an inspection of the Parexel unit did not find anything which they believed had contributed to the effects suffered.

The MHRA's report paved the way for a further independent report which made 22 recommendations to improve the safety of first-in-man (Phase 1) trials - among them that volunteers cannot be dosed all in the same day. They now apply throughout Europe.

It means, according to David Webb, professor of Clinical Pharmacology at the University of Edinburgh, that clinical trials are "safer than they have ever been". It comes as some consolation to Rob and David, who in 2009 received undisclosed compensation from Parexel in an out-of-court settlement.

"I'm glad to have been part of something that has reformed the whole industry," says Rob, who today is still pursuing a career as an actor.

It's a sentiment echoed by David who is now a father of three despite his fears that he would never be a parent. He remains convinced that medical trials are at the forefront of science.

"It's not until you have a loved one that is really sick and could be dying and they're saved by a drug which obviously went through this sort of drug trial initially that you fully appreciate how important those things are," he says.

- Daily Mail

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