The Nobel laureate and US bioterrorism consultant Joshua Lederberg once noted that man's only competition for dominion of the globe is the virus - and the outcome is not foreordained. If smallpox or other deadly microbes are ever used as pathogens-of-war, we may yet prove ourselves to be a species stupid enough to deserve extinction.
Of the various epidemics that have plagued human beings, syphilis has one of the most captivating stories. It began when the French king Charles VIII invaded the Kingdom of Naples on 22 February 1495, with thousands of French cavalry and mercenary foot soldiers as well as hundreds of camp-following prostitutes. Among the many diseases rampant in this multinational community was a new, sexually transmitted misery, one that covered the body in purulent pustules and lesions so deep that the bones were exposed. The pain was so intense that sufferers screamed day and night without respite. The Neapolitans blamed the invaders for this "French itch", while the French dubbed it the "mal de Naples". When Charles retreated a few months later, his disbanded soldiers spread the new scourge to all countries of Europe and soon to other parts of the world, where it continued to be blamed on neighbours - "the Chinese ulcer", "the Canton rash". One name stuck: the pox.
Soon after severe acute respiratory syndrome (Sars) was identified as the newest epidemic, medical teams throughout the world began to co-operate to identify and contain it. Within weeks of the first case, a spokesman for the World Health Organisation in Geneva revealed the prime suspect to be a new relative of the coronavirus family, cause of the common cold. The Canadians delivered a dazzlingly rapid gene mapping of the new-comer. At high-risk airports, travellers sporting ethereal white muzzles carried on as usual, although in reduced numbers. The daily news began to read like a fast-paced global bio-thriller by Michael Crichton.
By contrast, the cause of syphilis was not identified for more than 400 years after its first outbreak in Naples. In 1905 Fritz Schaudinn, a German parasitologist of ducks and owls, finally identified under his microscope the pale and slender creature, shaped somewhat like the ruffled edge of a lasagna noodle. He named it Treponema pallidum. This causal spirochete may be billions of years old. Its gene mapping was completed in 1998.
In the early days of syphilis, it was thought that the disease was spread by the batting of an eyelash, or even by the common American potato. The latter was suggested when it was noted that the first recorded case of the pox in Barcelona in 1493 had coincided with the return of Christopher Columbus and his sailors after the first voyage to the New World. For five centuries a debate has raged. One camp holds that syphilis was the revenge of the Americas (along with tobacco) for diseases brought by the Europeans. The other says it already existed in Europe and coincidentally mutated to a virulent venereal form at just that time. Today, studies of pre-Columbian bones on both sides of the ocean favour the American origin.
The 16th-century Italian humanist Nicolo Leoniceno observed in postmortem examinations of the Naples dead that in addition to the pustular pox, there was a less visible, though equally painful condition. This one had internal rather than external lesions. Within a decade, the malignant form gave way to a silent syphilis that could live with its host for many years without causing death.
In the 19th and early 20th centuries, medical researchers devoted themselves to understanding and treating syphilis. Containing its spread by tracking sexual partners marked the beginnings of public health departments. Treating patients with toxic substances (mercury, arsenic) without causing death in the process anticipated chemotherapy.
Physicians then estimated that 15 per cent of the population of Europe was infected with the disease. It was deemed so shameful that speaking its name was taboo: its presence was revealed at most to a few close friends, and then only on the promise of the utmost discretion. Husbands brought home chocolates laced with mercury to treat their wives on the sly without having to confess an affair. The novelist Stefan Zweig wrote that it was no mystery why many young men chose the gun when faced with the dreaded diagnosis.
Syphilis manifested itself in so many ways that the 19th-century physician Sir William Osler wrote that to know syphilis was to know medicine. Pain, pain and more pain over many years tortured sufferers. Syphilis, known as the Great Imitator of other diseases, and hence frequently misdiagnosed, caused damage to one part of the body after another.
Neurosyphilis often led to the terrifying condition known as general paralysis of the insane, or paresis. In the warning stage, before dementia set in, there were some rewards (leading to syphilis being called a Faustian bargain of sorts): extreme euphoria, electric excitement, bursts of creative energy, grandiose self-definition, and (often criminal) relaxation of inhibitions. Many physicians today, perhaps most, have never seen a case of tertiary syphilis. An exception is the medical writer Oliver Sacks, who described a 90-year-old patient who correctly self-diagnosed a late case of "Cupid's disease" - and didn't want it treated. I feel livelier, friskier, she said: "I've had impulses, I won't tell you." She hoped to live to a hundred in this rejuvenated state.
American researchers finally discovered that penicillin was an effective treatment in 1943. Gone was the fear of incurable sexually transmitted disease - until the arrival of HIV/Aids. Today, syphilis is on the rise in the UK, and although the cases still number in the hundreds (with a high percentage of those co-infected with HIV), alarmed headlines speak to the power of syphilis to frighten. Fortunately, the spirochete has not become resistant to penicillin.
Those known to have had syphilis - or thought to have had it, based on a pattern of disease outlined by the old syphilologists - include artists and writers, composers and musicians, popes and royalty, politicians and dictators, philosophers and scientists. Poignant stories of a life of suffering are often hidden in the footnotes of biographies. But how many can name more than a few well-known sufferers of the disease that Carl Jung called (in describing Nietzsche's illness) "the poison of the darkness"?
Deborah Hayden is the author of "Pox: genius, madness and the mysteries of syphilis", published this month by Basic Books (£20.99)
"Tongues of burning coal, sharp as needles"
Ludwig van Beethoven's doctor Andrea Bertolini told the biographer Alexander Wheelock Thayer that Beethoven had syphilis. Was he right? Could Beethoven's deafness have been caused by syphilitic damage to the eighth cranial nerve?
Franz Schubert wrote some of his most poignant songs after his diagnosis, when he realised that his health would never be restored. "Every night when I go to bed," he lamented, "I hope I'll never wake up, and every morning only reminds me of yesterday's grief."
Right before he threw himself into the Rhine, Robert Schumann experienced painful auditory disturbances that developed into wondrous angelic voices performing a set of five variations that he imagined to be composed by the spirit of Schubert. He was fished out and taken to an asylum.
Arthur Schopenhauer hoped to protect himself from the pox by soaking his penis in lime water. He was probably lucky, although there has been speculation to the contrary.
Gustave Flaubert described the horrors of mercury treatment: "Saturday night my tongue suddenly began to swell until I thought it was transmuting itself into that of an ox. It protruded from my mouth: I had to hold my jaws open. I suffered, I can tell you."
Guy de Maupassant jubilated: "I've got the pox! at last! the real thing! not the contemptible clap, not the ecclesiastical crystalline, not the bourgeois coxcomb or the leguminous cauliflowers - no - no, the Great Pox." In his last days in an asylum, Maupassant thought that he was the wealthy younger son of the Virgin Mary, and that his urine was full of jewels.
Abraham Lincoln told his biographer William Herndon that he had been infected in 1835-36 by a prostitute in Beardstown "during a devilish passion".
Hugo Wolf's delusions included thinking he was Jupiter controlling the weather and the head of the asylum treating Nietzsche. According to Alma Mahler, he became infected when given an evening with a prostitute as a gift.
Alphonse Daudet had the painful late condition known as tabes dorsalis, which he described vividly: "Great tracks of flame slashing and lighting up my carcass . . . tongues of burning coal, sharp as needles."
Vincent Van Gogh was treated for syphilis in Antwerp by Dr Hubertus Amadeus Cavenaille. At that time, skeletons became a theme in Van Gogh's painting.
Friedrich Nietzsche spent his last 11 years insane. Were his many maladies in previous years attributable to syphilis? Were there signs of syphilitic euphoria and grandiosity in his frenetic last works?
Oscar Wilde's friend Robert Sherard wrote that Oscar "knew himself to be syphilitic". If so, was The Picture of Dorian Gray a parable for the hidden ravages of the secret disease?
Karen Blixen (Isak Dinesen) was infected in Africa by her husband, Bror. She called syphilis "life's bitter secret" but also said: "If it didn't sound so beastly, I might say that, the world being as it is, it was worthwhile having syphilis in order to become a 'baroness'."
Randolph Churchill was one of the few whose disease was public in his lifetime. He embarrassed his colleagues in parliament with his mad look and unintelligible speech.
Al Capone's syphilis was treated with the new cure for malaria that earned the psychiatrist Julius Wagner-Jauregg the Nobel Prize. Capone's wife Mae feared it was a plot to murder him.
Adolf Hitler's friend "Putzi" Hanfstangl wrote in his memoir that Hitler was infected with syphilis in Vienna in 1908. Three decades later Hitler showed signs consistent with late syphilis of the heart. How many in Hitler's inner circle had heard the rumours and feared that the Fuhrer could go mad at any moment?