Doctors have talked for decades about developing a vaccine for cancer which would use the body's immune system to turn the tables on tumours; every few months we read about new trials being carried out in this field by scientists who pepper their speech with adjectives such as "promising", "exciting" and "revolutionary".
Some have even made the tantalising prediction that cancer may soon be easily treatable by a simple injection. If so, where are these much-trumpeted vaccines? Even given the lengthy trial and approval period required for new treatments, surely some should have arrived on the market by now, especially as the idea has been knocking around since the 18th century, when Dr Tachon, a French physician, discovered the cancer-fighting benefits of "laudable pus".
During the 1890s, Tachon's work was developed by William B Coley, a New York surgeon, who injected live bacteria into growing soft tissue tumours, some of which shrank after a brisk inflammatory response.
Later doctors began to notice that some skin and kidney cancers spontaneously regress, the only explanation being that they are under attack by the patient's immune system. Some melanoma (skin cancer) patients also experience vitiligo, or loss of skin pigmentation, which is an auto-immune response to the skin's own melanin-producing cells.
This may all sound encouraging, but the fact is that cancer, which comes in more than 200 forms and will affect one in three of us, is not even close to becoming a thing of the past.
Vaccines may grab headlines, but vaccine research accounts for less than £1m of the Cancer Research Campaign's £61m annual research budget, and the traumatically traditional "cut it, burn it, poison it" therapies, which have hardly changed in the past 30 years, are still the best on offer.
Even if, or when, vaccines do become a standard weapon in the oncologist's armoury, radio and chemotherapy will still be needed to shrink the tumour in the first place to improve chances of success.
Dr David Miles, joint head of the Imperial Cancer Research Fund's breast cancer biology group, is leading a vaccine trial involving 900 breast cancer patients. He says: "The idea of a vaccine is intellectually appealing, but this is an incredibly complex area, and it would be wrong to say we're on the brink of a breakthrough." He believes a vaccine is worth pursuing, however, because there is so little chance of further improvement in conventional therapies.
Various types of vaccine are being developed, most of which use either tumour cells or antigens (proteins which "mark" the surface structure of the cell).
The cells, sometimes taken from the patient's own tumour, are irradiated to kill them and then re-injected along with an agent to provoke a response from the immune system - similar to methods used by Coley more than a century ago. These cell vaccines, especially the individually tailored ones, can be complex and expensive to prepare.
Antigen vaccines, however, are cheap and easy to mass produce, and are being developed with a view to treating pancreatic cancer, for example, which is nearly always caused by a specific antigen mutation.
In Miles's trial, the vaccine, Theratope, attacks cancer cells by recognising a particular sugar which is only exposed in diseased cells. It is too early for the trial to be showing any survival benefits.
One of the problems in developing vaccines, says Miles, is that cancer cells - despite their bizarre and uncontrolled behaviour - may still be similar to surrounding tissue, and may "learn" how to switch off the signals which should alert the immune system.
Also, because there are "demonstrably effective" treatments already in use for some common cancers, such as breast cancer, it's difficult to justify testing anything new except in the most advanced cases where all else has failed. This is far from ideal, particularly as repeated chemo- therapy may have damaged the immune system to the extent where it cannot be stimulated by vaccines.
"Only patients with cancers such as melanoma, for whom conventional treatment is rarely effective, are being tested with vaccines in the early stages," he says.
David Kerr, professor of clinical oncology at Birmingham University, is three months into a vaccine trial involving nine patients suffering from hepatoma, a liver cancer - rampant in the Middle East - which is sparked by hepatitis. "Cancer vaccines were largely discredited in the 70s and 80s because at that time we didn't understand enough about the science of the immune system," he says. "But now we're in a position to plan them better. It may seem that progress has been slow, but up until now, we've really been working on finding out how to make the vaccines work.
"Surgery is always going to be the mainstay of cancer treatment, but I believe the time for rational vaccines has come. We need massive trials involving thousands of people and five years down the road we will be able to measure the vaccines' success."
More immediately promising is another type of vaccine - the only true vaccine, in the prophylactic sense. It attacks viruses, which have in recent years been implicated in up to 20% of all cancers and may be responsible for more. These include the human papilloma, or wart, virus, which causes 99% of cervical cancers, the human T-cell leukaemia virus, and the Epstein-Barr virus, which can cause glandular fever and is also associated with lymphoma and naso-pharyngeal cancer.
The hepatitis B and C viruses can cause liver cancer - the commonest cancer worldwide. There is already a vaccine for hepatitis B, which in trials seems to protect the woodchuck - a burrowing rodent native to North America, also known as the groundhog - from liver cancer, and which may be responsible for falling cancer rates in Taiwan. There could also be a viral link to some breast cancers, while Kaposi's sarcoma, found in Aids patients, is caused by the cytomegalo virus and a herpes virus.
Another much-vaunted trial area is genetic vaccines. These use disabled retroviruses from mice to introduce cancer-fighting genes into the immune system. Work is still at a very early stage, and has raised fears that the viruses could "infect" more than one type of cell with the genetic material, potentially causing other cancers, or permanently affecting future generations by ending up in egg or sperm cells. They could even be transmitted to other people or the environment.
Miles, however, is "cautiously optimistic". "It's hard enough to make a vaccine against a virus - and that's an obvious foreign agent," he says. "If we can't even vaccinate against the common cold, it gives you some idea of how long it will be before we can routinely vaccinate for cancer."
The idea has strong appeal for patients, however. "They feel they can use their own immune systems to fight the disease, enabling them to take control in some way rather than being the recipient of an unpleasant treatment from doctors."
Dee Merry, 54, who was diagnosed with breast cancer in 1995 and secondary liver cancer last year, is taking part in Miles's trial. "Secondary cancer is treatable, but not curable," she says. "So this certainly can't do me any harm. I believe very strongly in positive thinking and if vaccines are ever going to work, someone has to be involved in the trials. It's great to be involved in something that's going to help people in the future too."
Dee, a former prison officer, says the vaccine injections in her thighs are like "100 bee stings" and cause extreme discomfort for a day or two. "But it's worth it even if the cancer flares up again. At least it might build up my immune system to the point where I can put up the best possible fight."
Miles says the most important weapon against cancer will continue to be improving understanding of the disease. "Even though we may not be seeing anything spectacular just yet, there are incremental improvements," he says. "With a disease as common as cancer, those improvements are important, and this is an area in which we cannot justify stopping work."
Vaccines: the state of play
Genetic vaccines:
US and French scientists have found a way of enabling the immune system to recognise an abnormal genetic structure called a telomere, which is switched on in 85% of cancer cells and allows them to grow and divide endlessly. A prototype genetic vaccine uses programmed white blood cells to attack cells with this abnormality and kill them before they grow into a tumour.
Breast cancer:
Herceptin, an engineered antibody, recognises a surface abnormality in up to 30% of breast cancer cells and can induce remission. It is already licensed for use in the US and may soon be available in the UK. Scientists in New Orleans have isolated a virus associated with breast cancer. It is not contagious, but is in the genetic make-up of up to 30% of the population and almost identical to one identified as a cause of breast cancer in mice in 1942. Lead scientist Robert Garry says the virus was found in 85% of 30 breast cancer samples.
Cervical cancer:
US scientists, with $3million in government funding, are using genetically modified tobacco to make a vaccine to protect against human papilloma virus. Cynics say the government is just trying to appease politically powerful, yet hard-pressed tobacco farmers in an election year. Other HPV vaccines are being tested in Europe and have been used successfully in the US on animals. Beagle breeders have used one in kennels for years to prevent the spread of a highly contagious wart, caused by a virtually identical strain of the virus.
Lung cancer:
The US firm Introgen has developed a device similar to an asthma inhaler to introduce a lung cancer vaccine into the body. They say using it between cigarettes could repair the damage caused to cells by the toxins in the smoke. It would infect cells with a harmless virus modified to carry a human gene, p53, that normally repairs damaged DNA, or causes cells to die if the damage is too great. The body's regular supply of p53 is often made ineffective in smokers by the chemicals in the smoke.
Kidney cancer:
Seventeen sufferers were treated with a vaccine at the University of Göttingen in Germany. Four achieved total regression, three more partial regression, and two saw their cancer stabilise for over a year.
