MRC National Institute for Medical Research, London

Some people think the risks of vaccination exceed the risks from the diseases we want to suppress.

Although this topic was the most popular and the subject of our winning entry, most entrants sounded rather unconvinced about the merits of vaccination. They knew about the success with smallpox but didn't really convey the immensity of that victory or of the victories over polio and diphtheria. Surprisingly, no-one mentioned the recent success of the meningitis B vaccine in preventing the disease in Britain. Just a few years ago, the arrival of students at university for the autumn term was marked by several deaths from this disease. There was also no mention of measles which used to be a fairly serious disease in Britain and still kills two million children each year. The crux of the subject is that once an entire population is vaccinated, the potential for further infection is markedly reduced - so called "herd immunity". There are a number of examples from recent times where vaccination campaigns became ineffective and a disease returned. Some entrants mentioned the resurgence of diphtheria in Russia, and others the resurgence of measles in Ireland and other places after concerns about the safety of the MMR vaccine.

To write about the risks of adverse effects is a very challenging exercise. The important thing to know is that vast international organisations are involved in clinical trials of vaccines, and they could not countenance the use of a vaccine if the chance of serious adverse effects was more than "remote". The best entries gave the right weight to the MMR vaccine affair (ie the association with autism was unproven).

An anti-inflammatory drug known for a hundred years has merits only discovered recently.

An interesting way of tackling this essay would have been to present Aspirin as the first instance of a "folk medicine" being made into a standardised drug that was subjected to recognisably modern controlled trials on animals. None of the entrants quite got this perspective although the best entries showed that the ancient interest in willow bark as an analgesic was understandable once salicylic acid was known as a pure substance. When the acetyl ester was marketed in 1889 by the German company Bayer, it was the very first remedy for headaches, arthritic pains and fevers that was effective, safe and cheap.

The next challenge for our entrants was to convey the importance of the extraordinary discovery, made by John Vane more than fifty years later, of how the drug works. Aspirin relieves the symptoms of inflammation that result from damage to the body (ie wounding, bruising or microbial infection), by interfering with the synthesis of substances called prostaglandins. Later on, clinicians discovered that a low dose of aspirin reduces the risk of heart attacks, colonic cancer and Alzheimer's disease; almost certainly by preventing the inflammation that contributes to these diseases. The drug has obviously been hugely successful in terms of sales and usefulness but companies don't brag about it because it is so cheap, is not covered by patents, and it makes very little money for their shareholders.

Vitamin D is made in our skin in sunlight but too much sun can cause cancer.

All the entries on this title showed a good appreciation of the relevant facts but the essays would have been enhanced if the stories were told in a historical context. The impulse that led scientists to discover vitamin D was the deficiency disease called rickets - bandy leggedness resulting from soft bones - that was extremely widespread in children living in European cities in the nineteenth and early twentieth century. In the 1920s, two ways of correcting this deficiency were discovered; cod-liver oil and sunshine. Sunlight stimulates synthesis of vitamin D from ergosterol in the skin and the vitamin is stored in the liver. The reason rickets was so common formerly, was that city skies were dark with smoke (from coal) and many children worked in gloomy factories throughout daylight hours before the start of compulsory schooling.

How much sunshine we need is not easily measured but everyone knew that it was not very long, although it wasn't clear if they knew this might be hard to get in a British winter! The importance of vitamin D in mobilising calcium was understood by all entrants, and one even discovered that current research suggests vitamin D is actually a growth factor for some classes of lymphocytes and may be important in strengthening immunity to infection. Every one knew that people with pigmented skin need more exposure but none of the essays mentioned the incidence of vitamin D deficiency in some British Asian women. It is quite difficult to obtain sufficient vitamin D solely from food, although some is present in fish, liver, milk and eggs. One entrant noted that new born babies need sunlight because breast-feeding does not provide enough vitamin D. All entries showed that severe sunburn makes people vulnerable to skin cancer through damage to DNA by ultraviolet light. However, surveys have also shown that people who are habitually exposed to a lot of sunshine have higher levels of vitamin D in their blood and a lower risk of contracting most types of cancer (except melanoma).

Some people think all genetically engineered products are unsafe. Is this likely?

Most entrants gave a good account of the advantages of genetically engineered insulin. They argued it should be identical to human insulin, free of contaminating viruses and prions, immunologically unreactive, and therefore must be better than the animal forms that were used between 1922 and the 1980s. None of the entrants picked up the idea that this technology allowed manufacturers to make fast and slow acting forms by an appropriate modification of the protein sequence and that this could be used to manage diabetes better than the old system.

The problem with most entries was that they were strongly influenced by unbalanced sources (usually websites) that were in some cases extremely critical of genetically engineered insulin. Families of a few diabetics are (or have been) convinced their relatives died or suffered very serious side effects (such as comas) when the genetically engineered form was introduced. This has been thoroughly investigated by statisticians who found no evidence of an increased death rate amongst diabetics when genetically engineered insulin was introduced. An important clue to understanding the controversy is that complaints were confined to certain countries, such as the UK, where there was vigorous debate in the press. In countries without this discussion there were few adverse reports of the safety of genetically engineered insulin. It seems some diabetics did report that genetically engineered insulin felt different from the old forms and indeed the manufacturers do warn that they may not perceive the warning signs of low glucose levels so early. One entrant was convinced no proper clinical trial was done but in fact every new version of a drug has to be submitted for approval to licensing authorities in most countries.

Smallpox in the wild has been eradicated but people still worry about its use by terrorists.

Most entrants had a strong appreciation of what a devastating disease smallpox was, both in respect of its symptoms and its infectiousness. However an illustration of the harm the disease has done in the past would have given these essays greater breadth. One notorious example was after the arrival of Columbus, resulting in the deaths of about 95% of the original inhabitants of the New World. Some estimates suggest 10% of the death rate in 18th century Europe was due to smallpox and the deaths of many European monarchs indicate it was not just a disease of poverty. However, the aim of this essay is to establish if the disease is still a danger.

On one hand we know that the WHO thinks the disease is eradicated, on the other, there is widespread suspicion that terrorists have access to stocks of the virus or perhaps an equivalent. All the entrants knew about the eradication campaign but were a bit vague about how potential terrorists might have access to smallpox. President Yeltsin did admit Russia continued making weapons after the Convention on Biological Warfare in 1972 but there is no unequivocal evidence that these weapons exist now. Most entrants realised that if an epidemic was deliberately created now, we would have very low immunity and the consequences would be extremely serious. Understandably, no one was very convinced about the official plan for tackling an outbreak.

In clinical trials of new medicines some patients report feeling better when they have had the placebo (a dummy pill with no active ingredient). Is this a problem for drug trials?

There was only one entry on this topic, a strong and well-informed essay that, with a bit more substance could have been a contender for a prize. This entry showed how Louis Lasagna was the first person to demonstrate objectively that a placebo made people feel better and reduced their perception of pain because of a perception that they should feel better, once given medication.

Well-conducted clinical trials of a new drug always include a placebo in a double blind trial (where neither the patient nor the researcher knows whether the drug being administered is a real drug or a placebo). This ensures patients and doctors do not unconsciously influence the outcome of the trial and the pharmaceutical benefit of the drug is established if the patient responds better than with a placebo.

Studies with magnetic resonance imaging indicate certain areas of the brain (the prefrontal cortex) respond when the body is expecting relief (whether the expectation is realistic or imagined) and these trigger a reduction of activity in pain-sensing areas of the brain. The prefrontal cortex may trigger release of pain-relieving substances in the midbrain. Drugs that interfere with opiates seem to prevent the placebo effect, which suggests biochemicals called endorphins might be involved. This is not the only explanation; it may be that the prefrontal cortex directs attention away from pain.