Lewis Wolpert is professor of biology as applied to medicine at University College London. His field is genetics. A past chairman of the British Committee for the Public Understanding of Science, he has published work including two books written for a lay readership, The Unnatural Nature of Science and The Triumph of the Embryo. With his lanky figure, legs, arms and grey hair flying (and office as tidy as a 14-year-old's bedroom) he epitomises everyone's picture of the mad professor.
Four years ago that's exactly what he thought he was. Mad. Within a period of a few days his world had turned upside down. Wolpert had became convinced the medication he was taking to regulate his heart would lead to a stroke. He couldn't sleep. He couldn't work. Couldn't even get out of bed.
He was having what is generally called a nervous breakdown. He was hospitalised and treated for severe depression. It was, he says, the worst experience of his life. "More terrible even than watching my wife die of cancer. I am ashamed to admit my depression felt worse than her death, but it's true. I was in a state that bears no resemblance to anything I had experienced before. It was not just feeling very low, depressed in the commonly used sense of the word. I was seriously ill. I was totally self-involved, negative and thought about suicide most of the time."
So begins Malignant Sadness, Wolpert's investigation into depression, published this week, and the basis for a three-part BBC series, Living Hell, starting on Wednesday. The title stems from his contention that depression is not simply a continuum of sadness - which is entirely natural and beneficial - but sadness gone severely haywire. "Normal sadness is to depression," he writes, "what normal growth is to cancer." And he sees no problem in comparing the two: one in five people will experience depression in their lives and, of those, one in 10 will succeed in killing themselves. According to the World Health Organisation, depression is set to become the world's most pervasive serious illness by the year 2020, more widespread than heart diseases and cancer.
We meet at his chaotic office in the university's department of anatomy. Wolpert is on the telephone. His dismay is apparent. He has just heard the TV series, which he presents, is being screened at 11.15 p.m., when only those already interested will be watching, he points out, thus defeating the object of the exercise, which is to bring depression out of the shadows and help destigmatise society's attitude to something that, one way or another, affects the lives of nearly everyone.
It seems appropriate to confirm his view and I admit that, I too have suffered bouts of depression throughout my life. He is not surprised. He tells me he has yet to be interviewed by someone who has not either been depressed themselves or had a close relative of partner who had been. Throughout the interview that follows he continues to press for more information on my own depression. How was I treated, what was the result? Were my parents depressives? My children? Excellent as it is, Malignant Sadness offers no magic cures and Wolpert's search for answers goes on. And he is, after all, a geneticist.
"It is incredibly pervasive," he says. "Yet there's a collusion between patients and GPs of not admitting it. I think we're just ashamed at not being in control in the way we think. In a way if you're incontinent you may be embarrassed, but it's not your fault."
The guilt, the notion that depression is somehow one's own fault, must have been particularly abhorrent to Wolpert, who describes himself as "a hardline materialist reductionist" - in other words, someone who believes the seeds of any disorder are traceable to its biological roots. At the outset he convinced himself his own depression was a side-effect of a new drug he had been taking for his heart condition. It was only at the proof stage of the book that he realised that, in doing so, he was reinforcing the stigma of depression. "Even I, with all this openness was saying: `No, no, mine was totally biological. Nothing to do with me or my brain.' He acknowledges now that the truth is far more complex.
Wolpert had several motives for writing the book, not least because he wanted to understand what had happened to him. "I mean, we've all been low and miserable but everybody I speak to agrees that when you're severely depressed it bears no relationship to anything else. It's something quite out of the general experience." Although accounts of the misery of depression do exist (he cites William Styron's Darkness Visible and Kay Redfield Jamieson's Touched With Fire), they are personal and highly subjective. He could find no easily accessible information on the current state of knowledge, psychological and neurological, in order to educate himself.
In the end it was his wife, the writer Jill Neville, who persuaded him to write Malignant Sadness. "My wife couldn't cope with my depression. She couldn't accept it. We were happily married, I had a good job. `What do you mean you want to kill yourself?' She found it enormously difficult. She never told anyone I was depressed; she kept it from everybody. She was embarrassed and she also thought it would ruin my career."
While he was ill (the depression was fairly short, lasting about three months) Wolpert went along with the family line but admits to having felt uneasy about it. Once he recovered, however, he accepted a commission from the Guardian to write about it. "It had a greater response than anything else I have done. I claim I can go almost anywhere in the world and someone will say, `you're the chap who wrote that article about depression'."
It was as if, he says, he had been a homosexual who had "come out". The torrent of letters, full of praise and pleas for more information, came both from depressives and relatives of depressives who, like his wife, were finding it impossible to cope.
Wolpert is an expert communicator, and the book takes the reader seamlessly from the history of melancholy (from Aristotle to Burton) to the latest advances in neurology. His chapter on the chemistry of the brain - we need to know how it works to understand why drugs that act on the levels of serotonin and noradrenaline are effective - is remarkably easy to follow, given the complexity of the brain itself. (To demonstrate the vastness of the problem facing neurologists, he points out that if each brain cell were the size of a human being, the brain would cover an area of ground equivalent to Manhattan and stretch 10 kilometres up into the sky.) Until the advent of anti-depressant drugs, psychotherapy had been the only way of treating depression. And, says Wolpert, in spite of the advances made with drug treatment over recent years, psychotherapy still has a part to play. Not, he insists, psychoanalysis, which he has little time for ("extremely damaging; it only makes you worse") but cognitive therapy, in which the patient's perception of his or her situation is challenged.
"You alter the way the person thinks. Your immediate panic response. When one is severely depressed, one is negative about everything and cognitive therapy is about reality-testing." The half-full, half-empty thing. WHETHER depression is triggered by emotional trauma or some biological lack or imbalance, no one knows, but Wolpert now believes both are involved. "My image of depression is as follows. You've got the biology and the cognition. So something chemical makes you negative, the negative feeds the biology so you're in your vicious circle. You can either break it with therapy, by showing that your thoughts are distorted, or by dealing with the chemistry." However, just relying on a drug, Wolpert believes, is a mistake.
"I think that if you just deal with the chemistry it may be just a little too easy when things begin to go wrong again to not control the cognition. Because cognitive therapy does as well as drugs, except for very severe depression."
Because, for all the advances made in drug treatment over the past 10 years, Wolpert has discovered that whatever the course of action followed - drugs, psychotherapy or even placebo - the success rate remains the same - at roughly a third. Depression is ultimately self-limiting. Even if you do nothing, you will eventually get better. The problem is that before that point arrives, 10 per cent of depressives are dead because so few seek help. It's back to the stigma again.
However, the rational scientist in him still believes the long-term hope of a cure lies in chemistry although, he says, predicting the future is very, very hard. "I can't imagine what new psycho-dynamic things they could come up with. But there has been a remarkable new finding. Most of the drugs that have been used for depression either worked on noradrenaline or serotonin. There's a new one that will soon come on to the market that blocks the receptor for Substance P." Substance P is so named because it is involved with pain. "It is a completely different pathway," he says.
Statistics show that once you've had one depression there's a 50-50 chance you'll have another. When his wife died 18 months ago he was very worried the depression would reoccur. "But although mourning is the closest thing to depression, it is really a totally different experience. I did not feel suicidal when Jill died. I was coping with her illness." He thought about contacting his cognitive therapist but didn't; somehow he got through - helped, he says, by physical exercise, jogging, cycling and playing tennis. He ends the book with the advice offered in the 17th century by Robert Burton in his Anatomy of Melancholy: "Be Not Idle".
"By that I don't mean you to run around - although there is good evidence that it raises endorphin levels - but you have to take control of your own life. Go and see a doctor, go and read up about depression. That's what I mean by `Be Not Idle'. No one else is going to do it for you."
Malignant Sadness by Lewis Wolpert is published this week by Faber & Faber, price £9.99 in UK. A Living Hell is on BBC2 at 11.15 p.m. on Wednesday