How Innovation Works

Meanwhile Dr Eddy had another concern. With Sarah Stewart she had done a groundbreaking experiment to show that cancer could be transmitted from a tumour in a mouse to a hamster, rabbit or guinea pig, by a virus, the SE polyoma virus (the ‘S’ standing for Stewart and the ‘E’ standing for Eddy) – a momentous biomedical discovery. She knew that the monkey kidney tissue culture used to grow the Salk vaccine sometimes itself sickened with viral infections, because of monkey viruses, and she worried that these contaminating viruses might be included with the vaccine, and might cause cancer in people. In June 1959 in her own time she did experiments to show that monkey kidney cultures could indeed cause cancers in hamsters, at the site of inoculation. She was rebuked by her boss, Joe Smadel, for doing the work, because of the way it cast another doubt on the safety of polio vaccination, and when she persisted in reporting it to a scientific meeting in October 1960, she was effectively sacked from polio work and forbidden to speak about her experiments. Smadel thundered: ‘You have apparently stirred up a hornet’s nest, and there are some who are sufficiently credulous to believe that the use of monkey kidney tissue cultures in man may induce cancer in them.’ Indeed.

The contaminating virus was eventually isolated, christened SV40 and studied in detail by others. We now know that almost every single person vaccinated for polio in America between 1954 and 1963 was probably exposed to monkey viruses, of which SV40 – the fortieth to be described – was just one. That is about 100 million people. In the years that followed, the health establishment was quick to reassure the world that the risk was small, but they had little reason to be so complacent at the time. Sure enough there has been no epidemic of unusual cancer incidence among those who received contaminated vaccines, but SV40 DNA has been detected in human cancers, especially mesotheliomas and brain tumours, where it may have acted as a co-factor alongside other causes. Saying this remains unpopular to this day.

Polio eradication was targeted in 1988. Using a combination of inactivated vaccines to prevent paralysis and oral (live) polio vaccines to create full immunity, volunteers fanned out across the world to find and bring protection to adults and children everywhere. They continued throughout civil wars, crossing front lines, and even winning ceasefires to do their work, in wars in South America and central Africa. Over the next thirty years they probably prevented 16 million cases of paralysis and 1.6 million deaths. Today they have been more than 99.99 per cent successful. The last case of polio in Africa was in 2016. Only Afghanistan and Pakistan still report a very few cases: thirty-three in 2018. There, too, it will surely soon be history.

Mud huts and malaria

By the 1980s, with smallpox eradicated, and polio, typhoid and cholera in retreat, one stubborn disease remained the biggest killer, capable of ending hundreds of thousands of lives a year. And it was getting worse: malaria.

On 20 June 1983, in the hot and dusty settlement of Soumousso, in Burkina Faso, West Africa, a group of French and Vietnamese scientists began an experiment together with African colleagues. They had bought in the local market some tulle and percale cotton cloth with which to make thirty-six mosquito nets. Some were large group nets to cover more than one bed, some individual nets to cover a single bed. They now soaked half the nets in a 20 per cent solution of the insecticide permethrin and left the other nets untreated. They next did something rather odd: they tore lots of small holes in half the nets, both the treated and the untreated ones. They now had nine nets untreated and unholed, nine that were treated and unholed, nine that were treated and holed and nine that were untreated and holed. They then laid the thirty-six nets flat in the sun for ninety minutes to dry before installing them in twenty-four huts. These huts were built with the traditional mud walls and thatched roofs, but they were not meant to be used as homes. This being a research station, they were specially equipped with mosquito traps, some designed to catch the mosquitos inside the huts, and some to catch them leaving the huts.

On 27 June, volunteers began to sleep in the huts, occupying them from 8 p.m. to 6 a.m. every night for five months, one person to an individual net, three to a group net. Six days a week, three times a day, every mosquito that entered or tried to leave the huts was collected, dead or alive: at 5 a.m., 8 a.m. and 10 a.m. The live mosquitoes were kept under observation for twenty-four hours to see how many could be added to the roll call of the dead. After twenty-one weeks, 4,682 female mosquitoes had been collected, mostly of two species: Anopheles gambiae and Anopheles funestus, both malaria vectors.

The idea for this experiment had occurred to two of the French scientists, Frédéric Darriet and Pierre Carnevale, after noting the use of DDT-treated bed nets by the American military in the Second World War and by Chinese forces later. Why include nets with holes in them? I asked Darriet recently. Because mosquito nets rarely remain intact for long in Africa, so it is realistic to study whether a torn net is as useless as nothing or as useful as an intact net. In the case of untreated nets, a torn cloth is pretty useless, as many a restless sleeper will have experienced. But what if there is insecticide on the net to kill or repel the insects?

The Burkina Faso team’s results were truly astonishing, even to Darriet and Carnevale. They found that the presence of a permethrin-treated net, whether intact or torn, repelled mosquitoes. It reduced the number of mosquitoes entering the huts by about 70 per cent and increased the rate at which the insects left the hut from 25 per cent to 97 per cent. And it reduced the ‘engorgement rate’ – whether the mosquitoes took a blood meal – by 20 per cent for An. gambiae and 10 per cent for An. funestus. Whereas hardly any of the mosquitoes in the control huts died, 17 per cent of those in the huts with treated nets died. After five months, the nets were still highly effective as insect repellents and killers. Today the treatment of nets lasts even longer.

This beautifully simple, carefully designed, experiment, known as ‘Darriet et al. 1984’, became famous in the small world of malaria and insect control, though it has never achieved the celebrity it deserves in the popular media. It proved to be a breakthrough in the control of malaria in Africa. The impregnated bednet is the magic bullet against the disease and its vectors. The idea took a while to catch on. Impregnated bednets first started to be used on a wide scale in 2003, and that very year malaria mortality stopped increasing and began to decline. According to a recent study published in Nature, insecticide-treated mosquito nets account for 70 per cent of the six million lives saved worldwide in recent years, twice as high a percentage as anti-malarial drugs and insecticide sprays put together. By 2010, 145 million nets were being delivered each year. Over a billon have been used to date. Globally, the death rate from malaria almost halved in the first seventeen years of the current century.

Tobacco and harm reduction

The greatest killer of the modern world is no longer a germ, but a habit: smoking. It directly kills more than six million people every year prematurely, perhaps contributing indirectly to another million deaths. The innovation of smoking, brought from the Americas to the Old World in the 1500s, is one of humankind’s biggest mistakes.

Given that this is a voluntary habit, and that human beings are rational at least some of the time, it ought to be relatively easy to exterminate this killer. Just tell people it is bad for them and they will stop. Addiction being what it is, this has proved harder than that. Smoking is the source of more premature mortality than almost any other cause. Knowing that it causes cancer and heart disease made surprisingly little dent in its global popularity. The proof that smoking kills having long been established beyond all reasonable doubt has done surprisingly little to stop the habit. Advertising bans, plain packaging, bans on smoking in public spaces, deterrent messages on cigarette packages, medical advice, education – all have had some effect, especially in Western countries. But still more than a billion people in the world are addicted to lighting little bonfires of plant material between their lips.

Enter innovation. The decline of smoking in Britain has accelerated sharply in recent years, largely because of the spread of an alternative way of getting nicotine hits (which are not known to be harmful in themselves), using high technology instead of smoke: the electronic cigarette. More people vape in Britain than in any other European country. About 3.6 million Britons vape, compared with 5.9 million who smoke. The habit is even endorsed by public agencies, the government, charities and academic colleges, not because it is wholly safe, but because it is much safer than smoking. This is in sharp contrast to the United States, where vaping is officially discouraged, or Australia, where it is still – as of this writing – officially illegal.

Who was vaping’s innovator? The original inventor was a man named Hon Lik who devised the first modern electronic cigarette in order to stop himself smoking. Around the turn of the twenty-first century, he was working as a chemist at the Liaoning Provincial Institute of Traditional Chinese Medicine and smoking two packs of cigarettes a day. He wanted to quit but tried and failed several times. He tried a nicotine patch but found it a poor substitute for the hit he got from a cigarette.

One day in the laboratory at work he acquired some liquid nicotine and began experimenting with ways of vaporizing it. The first commercial electronic cigarette had been marketed in the 1980s, without success, and prototypes date back to the 1960s, with patents on the use of nicotine vapour even in the 1930s. Now with the miniaturization of electronics, however, Mr Hon had better luck. His first machine was big and cumbersome, but by 2003 he had filed a patent on a smaller device using a more practical mechanism. Further miniaturization followed and he submitted the product for testing at the Pharmaceutical Authority in Liaoning and by the Chinese military’s medical institute. It went on sale in 2006. But, remember, the inventor is not necessarily the innovator. Vaping has not succeeded in catching on as much in China as in Britain. Why?

In 2010 Rory Sutherland, an advertising executive stopped by an office in Admiralty Arch in central London to see an old friend, David Halpern, who had just begun working as head of David Cameron’s new Behavioural Insights Team, otherwise known as the ‘nudge unit’. During the course of the conversation, Sutherland pulled out an electronic cigarette he had bought online and inhaled.

By then electronic cigarettes had been banned in Australia, Brazil and Saudi Arabia among other countries, at the urging of either the tobacco farmers or public-health pressure groups worried that this was in effect a new form of smoking. It was surely only a matter of time before Britain also outlawed the technology.

Halpern had not seen an electronic cigarette. He asked Sutherland to explain and was intrigued by the thought that the risks of vaping might be the lesser of two evils – like vaccinating to prevent smallpox or chlorinating to prevent typhoid. Or like distributing clean needles to heroin addicts to prevent HIV infection, a controversial policy adopted by Britain in the 1980s which had proved remarkably effective in keeping the HIV infection rate among drug addicts far lower than in other countries. ‘We looked hard at the evidence and made a call,’ wrote Halpern later. ‘We minuted the PM and urged that the UK should move against banning e-cigs. Indeed, we went further. We argued we should deliberately seek to make e-cigs widely available, and to use regulation not to ban them but to improve their quality and reliability.’

That is why this innovation caught on more in Britain than elsewhere, despite furious opposition from much of the medical profession, the media, the World Health Organization and the European Commission. Strong evidence from well-controlled studies now exists that vaping’s risks, though not zero, are far lower than smoking: it contains fewer dangerous chemicals and it causes fewer clinical symptoms. One 2016 study found that after just five days of vaping, the toxicants in the blood of smokers had dropped to the same levels as those of people who quit altogether. A 2018 study of 209 smokers who switched to e-cigarettes and were followed for two years found no evidence of any safety concerns or serious health complications.

But vaping ran up against the same sort of entrenched opposition from vested interests as greeted Lady Mary Wortley Montagu’s inoculation. Tobacco interests got it banned in many countries; pharmaceutical companies lobbied to have it restricted in others, the better to protect their prescribed gums and patches; public-health lobbies argued against it, the better to protect their stop-smoking practices. In 2014, at the height of an ebola epidemic, which ought to have been a priority, the director-general of the World Health Organization, Margaret Chan, made it clear that she considered opposing vaping a high priority. The European Commission also tried to kill the industry in 2013 by demanding e-cigarettes be regulated as medicinal products.

That proposal was dropped, but Europe’s Tobacco Products Directive, which came into force in 2017, brought a ban on high-strength e-liquids and on the advertising of e-cigarettes. This compromise partly helped the industry by introducing standards and subjecting products to strict product-safety regulations, including toxicological testing of the ingredients, as well as rules to ensure tamper-proof and leak-proof packaging. In the United States, by contrast, there was little regulation, but there were lots of attempts to ban vaping products, and sure enough people soon began to die, almost all of them as a result of buying black-market vaping products containing not nicotine, but THC oil, an ingredient of cannabis, contaminated with a thickening agent called vitamin E acetate. In effect, in an echo of the Prohibition era, while the British government encourages vaping but strictly regulates the products, the American government discourages it then does little to ensure its safety.

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