The long read: After thousands of years of failure, some scientists believe a breakthrough might finally be in sight
The common cold has the twin distinction of being both the worlds most widespread infectious disease and one of the most elusive. The name is a problem, for starters. In almost every Indo-European language, one of the words for the disease relates to low temperature, yet experiments have shown that low temperature neither increases the likelihood of catching a cold, nor the severity of symptoms. Then there is the common part, which seems to imply that there is a single, indiscriminate pathogen at large. In reality, more than 200 viruses provoke cold-like illness, each one deploying its own peculiar chemical and genetic strategy to evade the bodys defences.
It is hard to think of another disease that inspires the samelevel of collective resignation. The common cold slinksthrough homes and schools, towns and cities, making people miserable for a few days without warranting much afterthought. Adults suffer an average of between two and four colds each year, and children up to 10, and we have cometo accept this as an inevitable part of life.
Public understanding remains a jumble of folklore and falseassumption. In 1984, researchers at the University of Wisconsin-Madison decided to investigate one of the best-known ways of catching a cold. They infected volunteers with a cold virus and instructed them to kiss healthy test subjects on the mouth for at least one minute. (The instruction for participants was to use whichever technique was most natural.) Sixteen healthy volunteers were kissed by people with colds. The result: just one confirmed infection.
The most common beliefs about how to treat the disease have turned out to be false. Dubious efficacy has done little todeter humankind from formulating remedies. The Ebers Papyrus, a medical document from ancient Egypt dated to 1550BC, advises a coldsufferer to recite an incantation, in association with theadministration of milk of one who has borne a male child,and fragrant gum. In 1924, US President Calvin Coolidge sat down in an airtight chlorine chamber and inhaledthe pungent, noxious gas for almost an hour on theadvice of his physicians, who were certain that his cold would be cured quickly. (It wasnt.)
Today, winter remedy sales in the UK reach 300m eachyear, though most over-the-counter products have not actually been proven to work. Some contain paracetamol, aneffective analgesic, but the dosage is often sub-optimal. Taking vitamin C in regular doses does little to ward off disease. Hot toddies, medicated tissues and immune systemboosts of echinacea or ginger are ineffective. Antibiotics do nothing for colds. Theonly failsafe means ofavoiding a cold is to live in complete isolation from the restof humanity.
Although modern science has changed the way medicine ispractised in almost every field, it has so far failed to produceany radically new treatments for colds. The difficulty is that while all colds feel much the same, from a biological perspective the only common feature of the various viruses that cause colds is that they have adapted to enter and damage the cells that line the respiratory tract. Otherwise, they belong to quite different categories of organisms, each with a distinct way of infecting our cells. This makes a catch-all treatment extremely tricky to formulate.
Scientists today identify seven virus families that cause themajority of colds: rhinovirus, coronavirus, influenza and parainfluenza virus, adenovirus, respiratory syncytial virus (RSV) and, finally, metapneumovirus, which was first isolated in 2001. Each has a branch of sub-viruses, known as serotypes, of which there are about 200. Rhinovirus, the smallest cold pathogen by size, is by far the most prevalent, causing up to three-quarters of colds in adults. To vanquish the cold we will need to tackle all of these different families of virus at some stage. But, for now, rhinovirus is the biggest player.
Scientists first attempted to make a rhinovirus vaccine in the 1950s. They used a reliable method, pioneered by French biologist Louis Pasteur in the 1880s, in which a small amount of virus is introduced to a host in order to provoke a defensive immunological reaction that then protects the body from subsequent infection. Even so, those who had been vaccinated caught colds just as easily as those who had not.
Over the next decade, as the techniques for isolating cold viruses were refined, it became clear that there were many more rhinoviruses than first predicted. Researchers realised itwould not be possible to make a vaccine in the traditional way. Producing dozens of single-serotype vaccines, each onetargeting a different strain, would be impractical. The consensus that a rhinovirus vaccine was not possible deepened. The last human clinical trial took place in 1975.
Then, in January last year, an editorial appeared in the Expert Review of Vaccines that once again raised the prospect of a vaccine. The article was co-authored by a group of the worlds leading respiratory disease specialists based at Imperial College London. It was worded cautiously, yet the claim it made was striking. Perhaps the quest for an RV [rhinovirus] vaccine has been dismissed as too difficult or even impossible, it said, but new developments suggest that it may be feasible to generate a significant breadth of immune protection. The scientists were claiming to be on the way to solving a riddle that has stumped virologists for decades. Onevirologist told me it was as if a door that had been closedfor many, many years had been re-opened.
Part of the Imperial scientists motivation was the notion that since we now have vaccines for many of the most dangerous viruses(measles, polio, yellow fever, cholera, influenza, andso on), it is time to tackle the disease that afflicts us mostoften. Rhinovirus is by far the most common cause ofillness, says Sebastian Johnston, a professor at Imperial and oneof the authors of the editorial. Look at what people spend on ineffective over-the-counter medications. Ifyou hada safe and effective treatment, youd take it.
I asked Johnston if he was optimistic. He pointed out that because their studies so far have only been in mice, they are not sure that the vaccine will work in humans. The data is limited, he says. But its encouraging. It was not the resounding triumphalism that I was expecting, but then cold scientists learned long ago to be careful about making grand proclamations. Theirs is an undertaking that, more than anything, has been defined by consistent disappointment.
The first scientist to try and fail to make a rhinovirus vaccine was also the first scientist to distinguish it from the jumble of other cold viruses. In 1953, an epidemiologist called Winston Price was working at Johns Hopkins University in Baltimore when a group of nurses in his department came down with a mild fever, a cough, sore throat and runny nose symptoms that suggested the flu. Price took nasal washings from the nurses and grew their virus in a cell culture. What he found was too small to be influenza virus. In a 1957 paper, The isolation of a new virus associated with respiratory clinical disease in humans, Price initially named his discovery JHvirus, after his employer.
Price decided to try to develop a vaccine using a bit of deadrhinovirus. When the immune system encounters an invading virus even a dead or weakened virus it sets out to expel it. One defence is the production of antibodies, small proteins that hang around in the blood system long after the virus is gone. If the virus is encountered a second time, the antibodies will swiftly recognise it and raise the alarm, giving the immune system the upper hand.
At first, Price was encouraged. In a trial that involved several hundred people, those vaccinated with JH virus had eight times fewer colds than the unvaccinated. Newspapers across the US wanted to know: had the common cold been cured? The telephone by my bed kept ringing until 3 oclock in the morning, Price told the New York Times in November 1957. The celebration would be short-lived. Though Prices vaccine was effective against his particular JH rhinovirus strain, in subsequent experiments it did nothing. This indicated that more than one rhinovirus was out there.
By the late 1960s, dozens of rhinoviruses had been discovered. Even in the alien menagerie of respiratory disease,this level of variation in one species was unusual; there are just three or four influenza viruses circulating at any one time. Scientists at the University of Virginia decided to try a different tactic. Instead of inoculating patients with a single strain of rhinovirus, they combined 10 different serotypes in one injection. But after this, too, failed to shield participants from infection, they were out of ideas.
As hope for a vaccine receded, scientists began investigating other ways to combat colds. From 1946 until it closed in 1990, most research into respiratory viruses in the UK was undertaken at the Common Cold Unit (CCU), a facility backed by the Medical Research Council that occupied a former wartime military hospital in the countryside near Salisbury. In its four decades of operation, some 20,000 volunteers passed through the doors of the CCU, many to be willingly infected with cold virus in the name of scientific progress.
An early experiment at the CCU involved a group of volunteers being made to take a bath and then to stand dripping wet and shivering in a corridor for 30 minutes. Afterthey were allowed to get dressed, they had to wear wet socks for several hours. Despite a drop in body temperature, the group did not get any more colds than a control group of volunteers who had been kept cosy.