For three decades, to about 1950, there was one reliable treatment for people with late-stage syphilis. You could infect them with malaria. The little thread-like corkscrew organism of syphilis that worked its way into the central nervous system and then the brain, causing blindness, paralysis and insanity, had one weakness. It could not withstand heat. It was killed when incubated above the normal body temperature of 37 degrees Centigrade for a few hours.
There were no microwave ovens into which the pox-ridden could be popped. But a neurologist at the University of Vienna in 1917 hit upon a bright alternative: he inoculated the syphilitics with blood from patients with malaria. He let them go through three or four attacks of fever, and then gave them quinine.
The result was a sensation: the syphilitics got no better but at least they got no worse. Tens of thousands were saved from an agonising death, says Robert Desowitz, a US microbiologist, in his 1992 memoir The Malaria Capers. The Viennese neurologist got the Nobel prize and the technique spread over the world.
It was about the only occasion on which anybody had a good word to say for the malaria parasite. Now almost half the world's population is at risk, the existing drugs are losing their impact and the number of deaths is growing. If global warming continues, the disease could move north - and be roaming its old haunts in Europe. The word itself is Roman, from mal' aria, bad air, after the miasma or fine mist supposed to be the cause of it.
The trouble with malaria was that for the first 5,000 years or so of recorded history, nobody knew what it was, except that it was swift, often lethal, and left its survivors helpless for weeks. When the Assyrians invaded the Jordan Valley they were smote by the Angel of Death, aka malaria, according to parasitologists.
It was more than 20 centuries before people realised that the Angel of Death might be a creature rather than a miasma, and not until 1880 that Charles-Louis-Alphonse Laveran, a French military physician serving in Algeria, spotted the plasmodium parasite in the blood of a sick artilleryman.
But the hero of the hour - celebrated at a recent conference in Hyderabad in India - was Capt Ronald Ross, a military medical man stationed in India. On August 20th, 1897, in Secunderabad, Ross extracted a cyst from a dissected mosquito and realised he was about to complete the connection between an insect, a parasite, a human and a terrible disease that, even now, kills someone every 12 seconds.
There are many kinds of mosquito. The one that matters is the group called Anopheles. There are about 380 species of Anopheles but only 50 or so matter as malaria transmitters. Of these, only the females count. The males are vegetarians, dining off sap and dew. Only the females drink blood. But mosquitos are only carriers, or vectors, of the disease. They have to be infected with a parasite called Plasmodium.
There are more than a million deaths a year from malaria in Africa - most of the victims tiny children. They die because their brief lives are spent where the mean winter temperature is higher than 15 degree Celsius, and where there are pools of still water. It helps if the humidity is high. The female anopheline mosquito bites and sucks blood, meanwhile injecting her saliva into the human bloodstream. The saliva contains an anticoagulant to stop the blood clotting while she drinks it. It also contains thousands of tiny threadlike parasites called sporozoites.
These find their way through the bloodstream to the human liver, where they form spores in the cells and multiply. Two weeks later, the liver cells burst and release huge numbers of spores, now called merozoites, into the bloodstream. This is the point at which the sufferer begins to feel feverish, and very ill. Each merozoite finds a red blood cell and invades it. It eats the haemoglobin and grows until it is half the size of the cell. Then, suddenly the invader divides into up to 24 bits, bursting the red blood cell: each of these 24 particles becomes a merozoite and attacks a new blood cell.
And so it goes until the sufferer develops some sort of immunity, or is cured by drug treatment. In both cases, the infection remains: it can return, unpredictably, at intervals. Alternatively, the patient may die.
Even in this century, communities still clung to the explanation that fevers blew in with the air from the swamps. But malaria could be beaten. And the story of this begins with the bark of what is now called the cinchona tree which cured the wife of the Spanish viceroy in Lima in 1638. The bark later helped contain fever on a swampy estate south of Madrid. Quinine had arrived.
Nobody understands why a tree high in the Andes should hold the therapy for a disease which occurs only in lowlands, 5,000 miles away. But quinine became - in the words of Henry Hobhouse, in his 1985 book Seeds Of Change - one of the "plants that changed the world".
Malaria is a debilitating disease. If you have it, all you can do is sit around miserably. When you get better, you are weak and inclined to despair. With quinine, people could get on with things. The British got on with colonising Africa and India.
Once people understood how malaria spread they could think of ways to tackle it. Note that the mosquito has to catch the parasite from a human, so beware of strangers. As the female mosquito breeds in stagnant water, one should drain the marshes or pour kerosene over the top of pools to choke the larvae. The female mosquito feeds only at night, so use mosquito nets. The insect's range is only two miles, so move away from the river. The parasite cycle accelerates in hot weather, so send the wife and kids to the cool hills.
The draining of the marshlands hit the disease one way. The arrival of the all-purpose, long-lasting pesticide DDT hit it in another. People became stronger and more prosperous: the southern Mediterranean turned from a depressed area into a tourist playground. But then DDT, which killed everything, was banned. By 1960, a confident World Health Organisation had anti-malarial policies at work in 100 nations. It was confident that the disease could be all but abolished: four million affected, perhaps, by 1980.
It didn't work out like that. When the time came, 400 million were still badly affected by malaria. Now things are worse. Estimates vary: conservatively 1-1.5 million die every year because of malaria, but it could be 2.5 or even 3 million if you count the disease as a "contributing factor". Every year 500 million people fall ill. Every minute of every day, four babies die because of malaria.
All this is for several reasons. One is that when things go well, humans become complacent, or forget: expensive public health programmes are allowed to falter or lapse. Another is that the parasite's lifecycle is swift but air travel is even more swift. A fresh strain is always on the wing. A third is that nature always fights back: throw a prophylactic drug at a microbe and it mutates to accommodate it. But humans don't mutate, so throw an even more powerful drug and the side-effects become even more alarming. And a reliable vaccine seems as far away as ever.
A fourth reason is that when society breaks down, or war breaks out, medical programmes collapse. Once India had 75 million cases a year. The number went down to 10,000. Now malaria is back with four major epidemics in the last three years.
Global warming adds a new hazard: the disease never quite left southern Europe, and it could be back in northern Europe in a decade.
But that's a safe bet anyway: air travel means 20 million Western tourists are at risk every year. The WHO forecasts a 16 per cent growth rate in the disease over the next three years. That means that by the year 2000 there will be another 80 million cases.
And malaria is not the only old plague to find a new life in a changing world. Two other great killers, diphtheria and tuberculosis, are both on the march again in eastern Europe and Asia. In the Russian Federation, another old friend is back: syphilis has increased 30-fold. And that, too, is likely to be heading this way.