Searching for the magic bullet

More than 25 years before, another photograph had also struck a chord with women across Britain. It showed a man standing in a white coat outside Oxford Street underground station rattling a tin to raise money for his own cancer research project.

An amazed passer-by alerted the national press that the cancer expert Dr Anthony Leathem (pictured above, photo: Ed Nicks, Oxford Times) had taken to the streets to raise money and alert the world to his work. Reporters and television crews were soon descending on the Leathems' Oxfordshire home in Long Wittenham to learn more about Dr Leathem and his wife, Patricia, and their vision of a future free of breast cancer.

Years before, working as a pathologist at Middlesex Hospital (later University College London) Dr Leathem had become increasingly disturbed by the number of post-mortem examinations he was having to carry out on young women with breast cancer. So he had taken the decision to devote his life to improving breast cancer survival, with Mrs Leathem setting aside a room in their Oxfordshire home to produce all the fundraising material.

Sitting in the Abingdon headquarters of Against Breast Cancer, the charity he formed with his wife in 1993, Dr Leathem chuckles as he recalls various stunts, such as once balancing on his head a giant African snail that a photographer spotted in his lab, to keep the funds coming in for the pioneering research.

Results of Dr Leathem's research published in The Lancet, where he identified a chemical difference between aggressive and non-aggressive breast cancer cells, helped raise his national profile, but the couple had still to dip into their joint salaries to get the charity up and running.

Leathem House was opened in Abingdon Science Park, following the charity's move from Harwell last autumn, with Simon Cowell's mother, Julie Cowell, the president of Against Breast Cancer, cutting the ribbon. Since then, things have certainly moved on and exciting news from the United States suggests that they are about to move on again.

For Dr Leathem is anxious to talk about reports that American scientists have developed a vaccine to protect against breast cancer that is expected to be tested on women within the next two years.

Dr Vincent Tuohy, the American immunologist who made the discovery, said the effects could be "monumental", with the potential to prevent up to 70 per cent of all breast cancers.

But Dr Leathem, in his usual ebullient style, is bent on sharing his sense of excitement, along with a plea for caution, with readers of The Oxford Times. For when it comes to breast cancer vaccines, you would be hard pressed to find many researchers in Europe able to offer more insight into the quest for this holy grail of immunology.

The main goal of Against Breast Cancer is to develop its own breast cancer vaccine, following an ongoing investigation into the levels of natural immunity in breast cancer patients and how the immunity of women can be stimulated to fight the spread of the disease.

A glance at the headlines generated across the world in recent weeks may suggest that the Americans are now far ahead. But the complexity of breast cancer means that this is no 'race to the pole'. The Against Breast Cancer vaccine research takes a totally different approach to the Americans and Dr Leathem believes the vaccines would help women with different forms of the disease.

"The American vaccine, if it works in humans, would be most effective against the less aggressive cancers that are most likely to respond to surgery," said Dr Leathem. "It is a really exciting direction for finding a vaccine to prevent breast cancer."

Crucially, the Americans appear to have confirmed that women's immunity systems can be used to combat breast cancer, something researchers have been engaged in trying to establish for more than a century.

"This lays the foundations for stimulating immunity to other tissue-specific targets to prevent cancers."

Whenever a news story like this breaks, breast cancer helplines are invariably inundated with calls from women -- hardly surprising when you realise that one in nine women will develop the disease in their lifetime, with the figure projected to rise to one in seven by 2024.

Newspapers reported that "the simple jab could help save the lives of 12,000 women who lose their battle against breast cancer in Britain every year, as well as reduce the 46,000 patients annually diagnosed with the disease in this country".

Yet the American trials carried out at Cleveland Clinic's Lerner Research Institute in Ohio, with the findings published in the journal Nature Medicine, have so far have only been conducted on mice and it could be some time before the vaccine is available.

Six mice were, in fact, injected with a vaccine that targets the protein alpha-lactalbumin, with six given a dummy vaccine. After ten months, the mice that received the dummy had developed serious breast tumours but none of the ones vaccinated against the protein. What is exciting for Dr Leathem is that this is the protein found in the majority of breast cancer patients, but not in healthy women, except while mothers are breastfeeding.

"This group had the idea of stimulating immunity against a protein present in breast cancer. It is beautifully simple and in a way so obvious; chemicals in milk might stimulate the immunity system. And if you can stimulate immunity against this protein in milk, you can also stimulate immunity against the protein found in breast cancer.

"More work is needed but optimistically, we might apply this to humans, preventing breast cancers, with the side effect that women vaccinated would lose the ability to produce milk."

More worryingly, Dr Leathem, an honorary senior lecturer in surgery at University College, London, adds: "It would not be effective against the most aggressive cancers," he warned.

"The immunity would be less likely to work on them. The model is based on a protein of mature, organised cells and is therefore present in the more mature, organised cancer cells such as low-grade, less aggressive cancers."

The Against Breast Cancer team research continues to be focussed on 'markers' of very aggressive cancers, with an aim to find a vaccine that targets lethal forms of the disease. And whereas the Americans have been targetting proteins, Against Breast Cancer's efforts are focused on glycans.

The ABC research team believes some patients have a natural immunity that eliminates cells dividing out of control, stopping tumour formation. Such faulty cells are identified by the immune system because they bear glycans, sugars coating the outer surface of cells, which differ from normal cells.

Although useful blood or urine chemical markers have been isolated for a handful of cancers such as prostate and some forms of leukaemia, none has yet been found for breast cancers.

Once the biochemists have identified these markers, it will be possible develop antibody therapies to target specific cancer glycans. "What we want is a magic bullet," said Dr Leathem. "That is what we are looking for."

But what sounds so simple is proving hugely expensive. Gordon Vallance, the charity director, said the organisation expected to hand over £700,000 to progress the research this year, and hoped to give £1.5m next year. A research team of nine scientists and researchers is based at UCL's Institute of Women's Health, where Dr Leathem is a senior lecturer. Their salaries, equipment and lab space are entirely funded by the charity's supporters.

It is a sobering thought that it took 200 years to eradicate smallpox and to fully understand how to stimulate the immune system to combat it. But Dr Leathem is hopeful that next year the charity will be publishing an important paper on cancer glycans and the immunity of patients, and he remains hopeful of a vaccine being produced within ten years.

The team is also looking into why cancer cells travel to other parts of the body and huge effort is being put into studying diet and lifestyle.

This study, which has been going on for five years, has involved 3,000 cancer patients, with a significant number having been treated at the Churchill Hospital, Oxford.

When the trial is completed, the charity will publish all its findings -- positive, negative and non-proven -- on the link between diet and lifestyle and improved breast cancer survival.

In the meantime, the blood and urine samples collected at the start of the study are a crucial resource for biochemists seeking to develop a vaccine.

Julie Cowell has been a passionate supporter of the charity after being introduced to Dr Leathem by her oncologist Margaret Spittle. The mother of the X-Factor judge, who is a patron of the charity, was diagnosed with breast cancer at the age of 73, 12 years ago.

The Leathems' nephew, the GMTV presenter Ben Shepherd, is another celebrity patron.

Some new developments in treatment are already available and the importance of breast awareness cannot be diminished.

But Mrs Cowell and Dr Leathem, like millions of others, continue to look ahead to the day when their granddaughters go off to have their vaccination.

The target is clear and that magic bullet will be found, it is just a question of when.