The Times August 30 2008

Meet the man with 250 brains

David Dexter uses donated brains to unlock the secrets of Parkinson's disease

John Naish

David Dexter pulls from under his lab desk a small lidded bucket, the type that DIY stores use to sell bumper packs of filler. Inside, floating in clear fluid, is a human brain: grey, cold, murky. “This is quite a lightweight one,” he says, fishing it into his purple-gloved grasp. “When they first come in they are fresh and pink. This has been soaking in fixative for four weeks.” For squeamish laypersons like me, it feels a vaguely macabre way to tackle one of the most common diseases of ageing.

Dexter, a quiet, shaven-headed scientist, is the man with 251 brains. And he would love it if you gave him yours - once you've finished using it. He is the scientific director of the Parkinson's Disease Society Tissue Bank, at Imperial College London. The bank is at the leading edge of British efforts to discover the causes and cures for this debilitating neurological disorder.

But even highly intelligent clinicians such as Dexter can lack vital grey matter. The bank collects and dissects for study the brains of people who have died with Parkinson's. But it needs just as many “control” brains - those that belong to people who did not apparently have the disease - so that scientists have a direct counterpart of the Parkinson's brain they are studying, in terms of age, gender and time elapsed between death and preservation.

The bank is funded by the Parkinson's Disease Society at a cost of £25,000 a year. Since it opened five and a half years ago, it has collected 250 donated brains, only 17 of which are controls. “We are collecting four or five brains a month. We tend to get a peak on cold winter days and summer heat waves,” Dexter says. “The lack of control brains is our biggest problem because every time we send out tissues, we need to send out control tissues as well. His colleague Kirsten Goldring, who manages the donor programme, adds: “It's odd, but when people sign on with us as controls, they seem to live for ever.”

A race against time

The fact that brain tissue certainly does not last for ever is one of the greatest practical challenges facing the bank. As an old medical saying has it: “After death, of all the soft tissues, the brain's the first to vanish, the uterus last.” Dexter explains how news of a donor's demise sparks a race against time, geography and bureaucracy. “As soon as someone dies, his or her brain cells start dying. We need to get the preservation procedure done quickly. We need to get the brain into the lab within 24 hours. Our co-ordinator is on call 24 hours every day. We've managed to get brains to London on time from places such as Northern Ireland and Jersey.” For that to happen, all the paperwork must be in order. “It can be infuriating if we don't make it because, for example, a locum doctor only 50 miles down the road won't sign the death certificate and wants to wait until the patient's usual GP is found,” says Dexter. The process is expedited if the donor's kin know of his or her wishes. The programme has its own donor cards; standard organ-donor cards do not cover brains as they are not going to be used clinically in transplants.

Anna Lowe, 31, a management consultant living in Balham, South London, is one of the latest non-Parkinson's patients to decide to donate her brain. “My grandfather died three weeks ago at the age of 78,” she says. “I had never thought about donating, but just before he died I learnt of his plans. He had agreed to donate his brain about three years ago. The awareness of the brain bank motivated me to do it, too. He had told his wife about it, and he had all the right documents lodged. My grandfather was a retired psychiatrist and had treated people with Parkinson's. When he was diagnosed with it, he was very interested to keep up with all the latest research, and that's how he learnt about the work of the tissue bank.”

Lowe, whose grandfather's condition was diagnosed about seven years ago, believes that this decision to donate has proved a comfort to her grandmother. “It was something that he very much wanted,” she says. “He was quite prag-matic about the physical body, being a doctor, and he valued the research that his brain would help the scientists to do. It was a comfort to all of us that him donating his brain could help others.” As for her decision to donate, “I didn't have to think too much about it,” she says. “If I'm dead, I won't know about it. And I have already signed up as an organ donor for other bits and pieces. I'm quite young and it seems a long way off. It feels like something useful I could do. Dying and being a donor to help others is a wonderful thing. The most important thing is to tell your kin so they are aware of your wishes if they are asked for their consent.”

Dissecting brains is a three-person job

Over lunchtime sandwiches, Dexter explains how dissecting a donated brain quickly and efficiently is a three-person job. The most important section is the substantia nigra, a thumbnail-sized region located at the base of the brain. On a glass laboratory slide it resembles a flattened-out moth. Here the vital chemical, dopamine, is synthesised. It is responsible for creating control of our finer physical movements. Dexter shows me how, on a slide of a section of a healthy substantia nigra, there is a clear black line where the dopamine-producing cells are sited. On a slide from a Parkinson's sufferer's brain, that black line is a light grey smudge. “This is the main area affected by Parkinson's,” says Dexter, “So you've got lots of researchers wanting to look at the same small thing.”

By comparing Parkinson's brains with normal brains, scientists can tell which cell-death processes are caused by disease, and which are part of ageing. This helps scientists to understand the condition better, which enables them to develop more effective drugs and gene therapies. But brains are mysterious things. They come in very different sizes and shapes. The smallest donated adult brain was 700g.

“The largest was more than twice that size,” smiles Dexter. “We do play a guessing game about the gender, but generally female brains are smaller.” Goldring feels compelled to interject: “They are more compact and better organised.” Regardless of their gender, brains remain something of a mystery to medics while we are still alive. Even a diagnosis of Parkinson's disease is often wrong, as Dexter's team frequently discovers. “We do a detailed neurophysiological assessment of the brain to see whether they really did have Parkinson's. Only about 70 per cent of the people diagnosed as dying from the disease actually had it,” he says. “Others have conditions such as progressive supernuclear palsy. Some have Alzheimer's as well as Parkinson's: it can be a multitude of syndromes.”

Even apparently normal brains can harbour surprises, Dexter adds. “Often the control brains can give us an insight into the pre-symptomatic stages of Parkinson's. About 7 per cent of people in the general population have Parkinson's at the pre-clinical stage. But their owners frequently don't know get to know this, as many of them die of something else before they ever go on to develop Parkinsonian symptoms.”

“We just cut a flap at the back of the head”

I ask Dexter something that fascinates me - whether any people fear that by donating their brains, they might lose a part of their souls. He doesn't see this as an issue - and it's not something that will prevent him from donating his brain. But vanity can prove a potential obstacle, he says: “Some possible donors are worried that their bodies will be disfigured and they won't be able to be displayed in an open casket. But looking at the dead donor's face, you would never know. We just cut a flap at the back of the head, peel the skin over the top, cut a hole in the top of the skull, take the brain out, and then put everything back.” He mimes the procedure, then glances at my whitening face and smiles: “Oh,” he says, “You're still having your lunch.”

For more information on becoming a donor, contact the UK Parkinson's Disease Society Tissue Bank: 0207-594 9732, pdbank@imperial.ac.uk www.parkinsons.org.uk

Brains in numbers

120,000 people with Parkinson's in the UK

30,000 members of the Parkinson's Disease Society

600 number of people currently signed up to donate their brains

-80C optimum temperature for preserving a donated brain