Bruce Ponder: The gene hunter

The view from Bruce Ponder's office looks like an artist's impression. A block of impossibly green grass, the crisp angles of new buildings and a sculpture still shiny and new. When the building was being designed, he was asked to pick out the sculpture, but after a while needed some help because it all looked like "chunks of metal" to him.

The Taichi Arch - Gate of Health, a large bronze by the Chinese master Ju Ming, stands outside the entrance to the newly opened Li Ka Shing Centre, home of the Cancer Research UK Cambridge Research Institute on the Cambridge biomedical c ampus, next to Addenbrooke's Hospital. A symbol of the graceful coordination of tai chi is appropriate for the new facility, which brings together scientists and doctors from a broad spectrum of disciplines to unravel the many mysteries of how cancer kills.

Ponder, the new institute's director, is professor and head of the university's department of oncology, and co-director of two other centres on the campus - a cancer research institute and a centre for epidemiological studies of diseases. Until the new centre was ready, he moved between the different centres, at one point working from four offices. Today, he has consolidated what almost amounts to an empire. The aim is to find out how cancer works and, of course, a cure. His angle is the genetics of cancer: how we inherit a risk of developing different cancers.

Ponder's career started in medicine as a doctor, swinging from clinical work to laboratory work - unusual for the time. He had to fight for funding, as well as to be taken seriously as both a doctor and a scientist.

After general medicine and a PhD in molecular biology, he trained for a year in oncology in the US. "With cancer you have the whole spectrum of medicine," he says. "From some poor old guy with cancer of the oesophagus, who would like to die at home and how can you support him and palliate him, to cancer being the outstanding problem in biology. What cancer is, I think, is a breakdown in the way tissues are organised ... If one understood the basic biology, you might understand something about treatments."

With such broad interests, it sounds like people didn't know what box to put him in. "I didn't know what box to put myself in," he laughs. He ended up working in a bladder unit - as good a place as any to examine the way a cancer develops in a lining, he thought. One day, they were a bit busy next door in the thyroid cancer unit, so he mucked in. The move changed his life. He discovered two thick files, case notes, on families who had experienced thyroid cancer again and again through the generations.

The understanding of genetics was in its infancy and very few people were making the link between inherited genetic mutations and cancers, writing off the patterns within families as being caused by shared environment. But the link with thyroid cancer - a very rare cancer - was too strong. It was 1980, and he set out to find the gene.

"Not many of us have big discoveries," he says, but the mapping of the MEN2 gene, responsible for hereditary patterns of thyroid cancer, was his. It was the first discovery of a predisposing gene linked to a form of cancer in the UK. Six years later, they found the gene itself. "With today's technology it wouldn't take much more than six weeks," he says. His group developed the test now used in all families where thyroid cancer is identified to work out the probability of relatives being diagnosed.

The next step

It was clear that the next step would be to take the theory and apply it to a more common cancer. He chose breast cancer as several other research groups in London and Leeds were doing the same: meticulously compiling case histories of families in which hereditary patterns of the disease were emerging, and cross checking their genetic codes with other families in the hope of finding the unusual genetic variation they share. It was painstaking work, and through a mixture of "competition and collaboration" with what became an international consortium, chaired by Ponder, they were getting there.

"We were 100 yards from the finishing post when an American company saw what we'd done, raised the extra £40m needed to name the gene through hedge funds, and beat us there." It was very annoying. The company, Myriad Genetics, now owns the patent, which it is trying to enforce, to the test for the gene, BRCA1. "My group didn't find the gene ... I just led the international consortium which got us there," he says.

Today he estimates, using models based on patterns of breast cancer in the general population, that 30% of the 250,000 cases diagnosed every year have a hereditary effect. The genes discovered so far, including BRCA1, account for 20% of those or 5% of all breast cancers.

"Most of that effect is not when you have a very rare genetic mutation like BRCA1 or 2. It's not a strong effect. It's a genetic predisposition of a combination of a lot of weak effects," he explains. "It's the same genetic variation that determines the shape of your face; there's a familial resemblance but it's not exactly the same. It's due to the whole hand of cards you've been dealt and this is probably the genetic pattern that underlies most illnesses, from high blood pressure to asthma to diabetes."

What he hopes to find, in years to come, is a way of assessing an individual's overall risk of developing a particular cancer. Such advances would open up a whole can of worms, he admits, including, he says, the prospect of genetic testing before birth. People would need to develop a whole new understanding of the risk they face, as written in their genes. "They need to understand that things are not deterministic, genetics is not deterministic. It's not 100% you're going to get this, or 0%. There is a quantitative way of thinking about this.

"Increasingly, we're going to be moving towards personalised medicine, tailoring medical intervention to individuals, but in almost all areas it will be a matter of probability. The danger is that you will give people information about their risk which they will misinterpret and become needlessly anxious about."

Holy grail

The holy grail of finding early ways of diagnosing cancer could also leave people helplessly living with cancer for longer. A new generation of genetic tests, but also screening programmes and special scanners, will increasingly pick up on very small, latent and benign cancers. This could cause people intense worry and even prompt unnecessary treatments, loading pressure on the already stretched NHS.

"There are post-mortem studies of people they have scraped off the road after car accidents, sliced them up and found out that most of us have something that a pathologist would call cancer. They could have lived to 120 and we'd never have known.

"One of the things that may happen is that in our quest to develop better and better tests for early diagnosis of cancer we will end up detecting quite a lot of cancers that were never going to do anything in the lifetime of the individuals. We also need to find better ways to find out which cancers mean business and which cancers don't."

He talks about the problem of prostate cancer, which is not screened for in the UK on the NHS but is in the US and privately here. Men are "undoubtedly" having their prostates removed at the first sign of abnormal cells, with all the side-effects that brings, when they could have lived healthily for many years. He stops and thinks. "You do have to be careful not to do more harm than good."

Is it a personal responsibility he feels for what happens to his science? "What I worry about is the science being presented in an uncritical and overly enthusiastic way. People need to understand the caveats and limitations."

Genetic diagnosis is a key theme of the new institute. The institute's building is paid for by a private benefactor, Sir Ka-Shing Li (it's hard to believe, here on the Cambridge biomedical campus, that there's any funding crisis in higher education), who is also funding the £2m chair of which Ponder is the first holder. It's all based around his personal approach of combining clinical work with the basics back in the laboratory. Everything he ever wanted, really. "I've been heading in this direction for 30 years," he says.

He has four grown-up children: a concert pianist, a journalist, a patent lawyer and a daughter who has a PhD in biology and now looks after three children, part of the expanding brood of grandchildren for Ponder and his wife.

His wife has been central to his career: a trained nurse, she got involved in the collecting of the case histories of families when he first started his genetics work. She went round the country researching families who had turned up at Addenbrooke's, tracing family trees, taking blood samples. Today she is chair of the Genetic Interest Group, an umbrella group for medical charities for rare genetic diseases. "She understands not only the theory but how it impacts the families," he says. It's clear she has influenced his work intensely.

Ponder is a scientist who is intensely motivated by the people he met in his consulting room when he diagnosed them with cancer. The scientist in him is "very competitive" he admits, but cancer research has got to be based on collaboration, he says. "I want this place to be very good but I don't think it's appropriate to try to be better than the other cancer centres. That's not what about we're trying to do. We all want the same thing."

Curriculum vitae 

Age: 62

Job: Head of the department of oncology, University of Cambridge; Li Ka Shing professor and director of the Cancer Research UK Cambridge Research Institute; co-director of the Strangeways Research Laboratory for Genetic Epidemiology; co-director of the Hutchison/MRC Research Centre

Likes: photography, gardening, golf, travel, wine, ducks

Dislikes: cigarette smoke, canned music, things that prevent you getting on with things

Married: with four children