http://www.thisisleicestershire.co.u...l/article.html
Private hell of Leicester scientist searching for cancer wonder drug
Saturday, February 13, 2010, 09:30
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Nine years ago, Leicester scientist Gerry Potter was making the headlines claiming to have a cure for cancer within his grasp.
It was a maverick belief and put the professor's credibility on the line. That drug is still in trials, but here is the news – another cancer wonder drug designed and built by Gerry has cleared clinical trials and been sold for a cool $1 billion
Experts say his prostate cancer killing smart-bomb – shown to shrink the most lethal tumours – could save, or prolong tens of thousands of lives a year.
His abiraterone drug has been hailed as the biggest breakthrough against prostate cancer in decades, one that may also bring new hope for breast and bowel cancer sufferers. Yet this moment of supreme vindication came at a hideous personal cost.
Gerry's relentlessly obsessive pursuit of medicine's holy grail shattered his sanity – and saw him sectioned for his own safety.
He read about his breakthrough, plastered over the front pages of the national press, while locked up in a mental health unit.
Today, we tell his remarkable story – the eureka moment that saw him imagine the blueprint for a $1 billion drug, how he built abiraterone in a fortnight, how it was so very nearly dumped, and how the desperate pleas for help from people dying of the disease pushed him over the edge...
Worth billions to the drugs companies, his discovery almost cost him his sanity
It was the day Professor Gerry Potter had waited nearly 20 years for. A triumph. Vindication. A cancer wonder drug – his drug – had finally cleared clinical trials. The newspapers were all over the story,
writes Adam Wakelin.
"Could save the lives of 10,000 a year", bellowed the front page of The Times. Potentially the biggest prostate cancer breakthrough in decades, according to The Daily Mail.
That drug, abiraterone, had just been sold for a cool $1 billion. It was projected to earn perhaps 30 or 40 times that when it went into mass production, which could be as early as next year. He was going to be rich.
And yet, how's this for irony? No-one really wanted to know.
There would be no handshakes and popping Champagne corks for Gerry.
It was joy confined. For by the time he heard the glorious news, Gerry was a patient on a mental health ward in Leicester.
Of course, mental patients like him make "discoveries" like that all the time.
Delusions don't draw gasps in the topsy turvy world of Leicester General Hospital's Brandon Unit.
Gerry could see the disbelief in their eyes as he unfolded the Daily Mail clipping sent to him by his ex-wife.
Yes, yes, Gerry. Of course you did. You came up with a cure for cancer. Now take your tablets.
Except this was no delusion. This mental patient, locked up for his own safety, really had built a magic bullet. And Gerry knew something else too. It was that obsessive pursuit of cancer's holy grail that got him sectioned.
"I was spinning all these different plates," he says. "A few went wobbly and then, all of a sudden, they all went wobbly.
"It's quite painful to talk about. I've relapsed three times in the past year. Most of it has been spent in hospital."
You might remember Gerry Potter. He first made the pages of this newspaper in 2001. The Professor and his team at De Montfort University had invented a seek-and-destroy drug that obliterated cancer cells in laboratory tests.
That smart drug was named DMU 212 – and it appeared to work on all sorts of cancers.
Was this the elusive catch-all cure for the disease, we asked. The omens looked good, said oncology experts, but it was a question that only decades of drug trials would be able to answer.
The years have been kind since our first meeting. Gerry, just out of hospital, opens the door to his Clarendon Park home, in remarkably fine fettle. The lines on the face are a little deeper and there are a few more flecks of grey around the temples, but the boyish smile remains intact.
He seems calmer, less prone to maverick pronouncements.
"That's my medication," he says, inviting the Mercury to take a seat while he puts the kettle on.
A complicated honeycomb of hexagons and lines – it looks like a drug diagram – has been scrawled in pencil on the wall by the stairs. "Me thinking out loud," he explains from the kitchen. "I try not to do that any more".
It wasn't DMU 212 that had the national press babbling about medicine's new lethal weapon against cancer in 2001. That follow-up drug, and what happened to it, very nearly destroyed Gerry's sanity.
In 2001, it was his first drug, abiraterone, that was the promising discovery trapped in drug development hell.
DMU 212 is now in a similar limbo, but, despite everything, Gerry insists that it is the bigger deal, the one that will ultimately revolutionise treatment of the disease.
"Abiraterone was first drug I ever built," he says. "The De Montfort drug is far more exciting. It's the quantum leap and it's not out there.
"People are dying," he whispers. "They want these things now and I can't give them to them. I find that very hard."
The discovery of abiraterone was not usual. There was no slow trudge to enlightenment, no complicated mosaic of minor discoveries laboriously pieced together by specialists across the globe.
This was science as we see it in films; romantic, thrilling, done at a gallop by a brilliant young man in a white lab coat.
Spool back to 1990 and Dr Gerry Potter, having just finished his PhD, was in his first week of work at the Institute of Cancer Research in London's Royal Cancer Hospital.
His colleagues on the drug discovery programme, Prof Mike Jarman and Dr Elaine Barrie, wanted to target a male hormone-producing enzyme called CYP17.
Prostate cancer tumours feed on such hormones. Medicine could stop their production through chemical castration and radiotherapy, but these approaches was often ineffective. Rogue cancer cells seemed to make their own hormones.
A laser-guided bullet to target CYP17 was needed, Mike and Elaine reasoned. Block this enzyme and you took away the cancer's exclusive food supply.
"The idea was to starve the tumour to death, not attack it directly," explains Gerry, arriving with our mugs of tea.
They asked their new scientist to design a drug which jammed the lock of CYP17 – easier said than done.
To build a jamming key you needed to know what the lock looked like.
No-one did. You couldn't see it under a microscope. "You have to work it out from the inside," he says.
"It's a bit like a glove. To know its shape, you need to understand the hand that fits it. You have a palm and fingers and thumbs. You have to work out how they all fit together."
Gerry worked on hunches and hypotheses, using his knowledge of the enzyme's basic components to scribble down different possible structures.
And then he saw it. Or rather he imagined it.
"It was a eureka moment," he says. "You instinctively know when something is right."
Now he had the lock he had to build the key to block it. That took a fortnight – a heartbeat in the time scale of hard science.
"I developed a new chemical reaction to synthesise it," he says matter-of-factly. "What I was trying was really difficult and couldn't have worked at any stage. "Yet everything fitted into place. It worked first time."
Then came the boring bit, the making of "analogues" – a hundred near replicas – so no-one could make a copycat variant and claim the idea as their own.
"None worked as well as the first," says Gerry, still slightly awed by that fact. "Everything came so easy."
Everyone involved felt the hand of history on their shoulders as abiraterone astonished in laboratory tests.
The best prostate cancer drug on the market in 1990 – ketoconazole – had a cancer inhibiting activity of 10.
"You need that number to be as low as possible," says Gerry.
Abiraterone scored 0.001 – making it 10,000 times more potent than ketoconzole.
"It was the magic bullet," says the scientist.
He "scaled up" the drug, so it could be produced in kilogram quantities – a requirement for the patent.
The patent was eventually filed in 1994 through a venture capitalist company called BTG that had funded much of the supplementary research.
It then sold on the team's hard work to Boehringer Ingelheim, a German pharmaceuticals giant with the financial muscle to support the fledgling drug through the inevitable years of clinical trials.
Abiraterone was just another roll of the dice in a game of heavily stacked odds for Boehringer.
Endless safety checkpoints have to be cleared before a drug comes to market. Get through one and more investors can be lured on board to get it through another trial.
"The drug gets more and more valuable, which is okay as long as it doesn't hit a problem," says Gerry with a weary smile.
"Only one per cent get to market. Good drugs, life-saving drugs, fall by the wayside. Any chance of failure and they get dropped like a hot potato."
Boehringer got worried when trials of abiraterone suggested it caused cortisol depletion – a hormone vital to health.
The company cashed in its chips with abiraterone, selling the drug for $40m to Cougar Biotechnology, whose name sounds like the kind of outfit that Six Million Dollar Man Steve Austin used to go behind the barbwire to investigate.
That dream looked dead, so Gerry started chasing another.
DMU 212 was the discovery that brought Professor Potter on to the front page of the Mercury in 2001.
Like abiraterone, DMU 212 targeted an enzyme, but this one seemed to be prevalent in more cancers.
It appeared to be an even smarter smart bomb than abiraterone and its laboratory results were even more remarkable.
A few granules killed 80% of cancer cells within 24 hours. Within four days the rest had all but disappeared.
The news went global. It would be years, probably decades, before the drug was available at bedsides, we warned.
That didn't stop the begging letters, desperate pleas from the dying franked with postmarks from all over the world.
They came in a flood. All asking for a few of Gerry's magic pills. The scientist answered as many as he could, agonising over every reply.
How do you tell the mother of a dying seven-year-old girl you can't help her? How do you snuff out that last faint hope when you believe you have the biggest breakthrough since penicillin?
He never forgot those letters. They drove him on and they made him lose his mind.
We step outside for a cigarette break. Seeing Gerry spark up is a surprise. He never used to smoke.
"I started in the hospital," he says, puffing on an expertly made roll-up. "The only time you got to leave was when they escorted you outside for a smoke.
"The health risks don't bother me. I've got a cure for cancer, haven't I?" He laughs, but it's a hollow laugh.
De Montfort University set up a company called Spear Therapeutics, bankrolled by Cancer Research UK and others, to take DMU 212 forward.
American venture capital firm Advent International committed $8.5m to further develop the drug. It was a huge investment, but it came with strings.
All further work on DMU 212 would be done in the US.
"I lost control of my drug," says Gerry.
He tries to be philosophical. Gargantuan amounts of money are needed to bring a drug to market.
"You need the right partner or the drug doesn't fly," he says. "I found that hard to accept at the time. The deal left us powerless."
DMU 212 is going through pre-clinical development, inching along the same torturous path as abiraterone.
"They'll be trying to add to the package," he explains. "Every time you get a good result you go back to the market for more money."
Gerry had his first breakdown in 2006. The crippling weight of all that expectation got too much. He worked himself into the ground, doing 12-hour days in his lab before spending another eight in his office writing up research.
"I wouldn't get home until 5am and I'd be back at the university by 9am," he says. "Eventually, I just went ga-ga."
Diagnosed with manic depression, he had three relapses last year. Most of it was spent in the Brandon unit.
"Hell," he whispers. "Like being in a nightmare. "I met lots of interesting people and the staff were good, but not a nice place.
"They injected me with drugs to calm me down. I was a walking zombie."
His long-time girlfriend, Sarah, moved to France.
"We're on good terms. She wants me to go out to see her," says Gerry. "When you're up with manic depression you feel invincible. You're gripped by this mania. I can't have been easy to live with."
He took three books with him into hospital, setting himself the challenge of decoding DNA. For Gerry, it was like a crossword puzzle.
"Like a crossword puzzle, but in a whole new language," he laughs. "You have to learn the language before you can solve it.
"I still had to have a challenge. Even in there, as bad as I was, I couldn't just stop."
Ihaven't got cancer. Cancer's got me. And it's going to have to bloody deal with me. That was singer Ian Dury's brilliantly belligerent response when he was diagnosed with the disease.
It is a sentiment that perfectly sums up Gerry Potter's remorseless battle with the Big C.
Trials of abiraterone have shown that it can shrink tumours in 80% of the most aggressive forms of prostate cancers. The second biggest killer of men in Britain may become a manageable disease.
That's why pharmaceutical giant Johnson & Johnson bought Cougar Biotechnology for $1bn.
Abiraterone has been proven to help patients whose cancers have spread to their bones, livers, even their lungs.
Survival rates will be boosted by many years just by taking four pills a day. There seem few side-effects.
Dr Johann de Bono, who steered the drug through clinical trials, has suggested that it could eventually make chemotherapy obsolete.
A study of 1,200 patients worldwide is now in progress and the drug could be licensed and available in the UK as early as next year.
Cancer has taken Gerry to the brink. The disease might not be beaten but, regardless of what happens to DMU 212, he's given it a hell of a bloody nose.
Abiraterone earned him £9,000 last year. When it goes worldwide the royalties may make him a millionaire.
"I suppose they will, yeah," he says, as if we're talking pennies. "It doesn't really matter because I'll put it all back into my research anyway."
He plans to be back at work in a few weeks, ignoring my advice to rest on his laurels for a few months. Sort your garden out Gerry, I tell him, get properly better, go on holiday, then go back to work – and take it easy.
"I will," he promises. Then he starts to smile a familiar smile. "There's such a lot to do. I've got to get my research up and running again.
"I feel good. Ready to tackle new challenges."
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