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Natural History
Oct, 2000

Syphilis and the Shepherd of Atlantis.(Renaissance poem about syphilis attempts to explain its origin; genetic map revealed in 1998)

Author/s: Stephen Jay Gould

The most "poetic" statement about the dreaded plague is not an early physician's hexameter but the modern map of the pathogen's genome.

We usually manage to confine our appetite for mutual recrimination to merely petty or mildly amusing taunts. Among English speakers, unannounced departures (especially with bills left unpaid) or military absences without permission go by the epithet of "taking French leave." But a Frenchman calls the same, presumably universal, human tendency filer a l'anglaise, or "taking English leave." I learned, during an undergraduate year in England, that the condoms I had bought (for no realized purpose, alas) were "French letters" to my fellow students. In France that summer, my fellow students of another nation called the same item a chapeau anglais, or "English hat."

But this form of pettiness can escalate to danger. Names and symbols inflame us, and wars have been fought over flags and soccer matches. Thus, when syphilis first began to ravage Europe in the 1480s or 1490s (the distinction, as we shall see, becomes crucial), a debate erupted about naming rights for this novel plague--that is, the right to name the disease for your enemies. The first major outbreak had occurred in Naples in the mid-1490s, so the plague became, for some, the Italian or the Neapolitan disease. According to one popular theory (still under debate, in fact), syphilis had arrived from the New World, brought back by Columbus's sailors, who had pursued the usual activities in novel places--hence "the Spanish disease." The plague had been sufficiently acute a bit northeast of Columbus's site of return--hence "the German disease." In the most popular moniker of all, for this nation maintained an impressive supply of enemies, syphilis became "the French disease" (morbus Gallicus in medical treatises, then usually published in Latin), with blame cast upon the troops of the young French king, Charles VIII, who had conquered Naples, where the disease first reached epidemic proportions, in 1495. Supporters of this theory then blamed the spread through the rest of Europe on the activities of Charles's large corps of mercenary soldiers, who, upon demobilization, fanned out to their homes all over the continent.

I first encountered this debate in a succinct summary written by Ludovico Moscardo, who described potential herbal remedies in the catalog of his museum, published in 1672: "Ne sapendo, a chi dar la colpa, li spagnuoli lo chiamorono real Francese, li Francesi male Napolitano, eli Tedeschi, real Spagnuolo" (not knowing whom to blame, the Spaniards call it the French disease, the French the Neapolitan disease, and the Germans the Spanish disease). Moscardo then added that other people attribute the origins of syphilis to bad airs generated by a conjunction of the three most distant planets--Mars, Jupiter, and Saturn--in the night sky.

How, then, did the new plague receive its modern name of syphilis, and what does "syphilis" mean, anyway? The peculiar and fascinating tale of the naming of syphilis can help us to understand two key principles of scholarship that may seem contradictory at first but that must be amalgamated into a coherent picture if we hope to appreciate both the theories of our forebears and the power of science to overcome past error: first, that the apparently foolish concepts of early scientists made sense in their times and can therefore teach us to respect their struggles, and second, that these older beliefs were truly erroneous and that science both progresses, in any meaningful sense of the term, and holds immense promise for human benefit through correction of error and discovery of genuine natural truths.

The recent work boasts none of Fracastoro's grace or charm (even in Tate's heroic couplets)--no lovely tales about mythical shepherds who displease sun gods and no intricate pattern of dactyls and spondees. In fact, I can't imagine a duller prose ending than the last sentence of the 1998 Science article, with its impersonal subject and its entirely conventional plea for forging onward to fur ther knowledge: "A more complete understanding of the biochemistry of this organism derived from genome analysis may provide a foundation for the development of a culture medium for T. pallidum, which opens up the possibility of future genetic studies." Any decent English teacher would run a big blue pencil through these words.

But consider the principal and ever so much more important difference between Fracastoro's efforts and our own. In an article written to accompany the genomic presentation, M. E. St. Louis and J. N. Wasserheit, of the Centers for Disease Control and Prevention in Atlanta, write:

   Syphilis meets all of the basic requirements for a disease susceptible to
   elimination. There is no animal reservoir; humans are the only host. The
   incubation period is usually several weeks, allowing for interruption of
   transmission with rapid prophylactic treatment of contacts, whereas
   infectiousness is limited to less than twelve months even if untreated.
   [Tertiary syphilis may be both dreadful and deadly, but the disease is not
   passed to others at this stage--S. J. G.] It can be diagnosed with
   inexpensive and widely available blood tests. In its infectious stage, it
   is treatable with a single dose of antibiotics. Antimicrobial resistance
   has not yet emerged.

Interestingly, Fracastoro knew that syphilis infected only humans, but he regarded this observation as a puzzle under his theory of poisonous airborne particles that might, in principle, harm all life. He discusses this anomaly at length in part 1 of Syphilis sive morbus Gallicus:

   Sometimes th'infected air hurts
   trees alone,
   To grass and tender flowers
   pernicious known.

   When earth yields store, yet oft
   some strange disease
   Shall fall and only on poor cattle

   Since then by dear [in the British
   sense of "costly"] experiment
   we find
   Diseases various in their rise
   and kind
   Of this contagion let us take a view
   More terrible for being strange
   and new.

Thus, the very phenomenon that so puzzled Fracastoro for its anomalous nature under his concept of disease becomes an important clue under the microbial theory.

Similarly, the deciphering of a genome guarantees no automatic or rapid panacea, but what better source of information could we desire for a reservoir of factual hope? Already, several features of this base-level knowledge (base-level, that is, in both the literal and the figurative sense) indicate potentially fruitful directions of research. To cite just three items that caught my attention as I read the technical article on the decipherment of T. pallidum's genome:

1. Several genes that promote motility--and that may help us to understand why these spirochetes become so invasive in so many tissues--have been identified and found to be virtually identical to known genes in B. burgdorferi, the spirochete that causes Lyme disease.

2. The T. pallidum genome includes only a few genes coding for integral membrane proteins. This fact may help us to explain why the syphilis spirochete can be so successful in evading the human immune response. For if our antibodies can't detect T. pallidum because the invader, so to speak, presents too "smooth" an outer surface, then our natural defenses can become crippled. But if these proteins, even though few, can be identified and characterized, then we may be able to develop specific remedies or potentiators for our own immunity.

3. T. pallidum's genome includes a large family of duplicated genes for membrane proteins that act as porins and adhesins--in other words, as good attachers and invaders. Again, genes that can be located and characterized become targets for study and candidates for demobilization.

Science may have needed nearly 500 years to reach our current state of hope, but we should look on the bright side of the differences between then and now. Fracastoro wrote verse and invented shepherds because he knew effectively nothing about the causes of a frightening plague whose effects could be specified and described in moving detail well suited for poetic treatment. The thirty-three modern authors, in maximal contrast, have obtained the goods for doing good. We may judge their prose as uninspired, but the greatest "poetry" ever composed about syphilis lies not in Fracastoro's hexameter of 1530 but in the intricate and healing details of a schematic map of 1,041 genes made of 1,138,006 base pairs, forming the genome of Treponema pallidum and published with the 1998 article--the adamantine beauty of genuine and gloriously complex factuality, full of lifesaving potential. Fracastoro did his best for his time; may he be forever honored in the annals of human achievement. But the modern map embodies far more beauty, both for its factuality and utility and as Fracastoro's finest legacy in the history of increasing knowledge--a truly epic tale that we must not shy from labeling by its right and noble name of progress.

Stephen Jay Gould teaches biology, geology, and the history of science at Harvard University. He is also Frederick P. Rose Honorary Curator in Invertebrates at the American Museum of Natural History.

"Syphilis," the proper name of a fictional shepherd, entered our language in a long poem composed in 1,300 verses of elegant Latin hexameter and published in 1530 by the greatest physician of his generation (and my second favorite character of the time, after Leonardo da Vinci)--a gentleman from Verona (also the home of Romeo and Juliet), Girolamo Fracastoro (1478-1553). Fracastoro dabbled in astronomy (he became friendly with Copernicus when both studied medicine at Padua), made some crucial geological observations about the nature of fossils, wrote dense philosophical treatises and long classical poems, and held high status as the most celebrated physician of his time (in his role as papal doctor, for example, he supervised the transfer of the Council of Trent to Bologna in 1547, both to honor his holiness's political preferences and to avoid a threatened epidemic). In short, a Renaissance man of the Renaissance itself.

My inspiration for this essay flowed from the stark contrast between Fracastoro's christening of syphilis in 1530 and the style and substance of a 1998 paper on the genome of the bacterium that truly causes syphilis. Fracastoro could not resolve the origins of syphilis and didn't even recognize its venereal mode of transmission. So he wrote a poem and devised a myth, naming syphilis to honor a fictional shepherd of his own invention. In greatest contrast, the sober paper published by thirty-three coauthors in Science magazine (July 17, 1998) resolves the 1,138,006 base pairs--arranged in a sequence of 1,041 genes--in the genome of Treponema pallidum, the undoubted biological cause of syphilis.

Fracastoro's shepherd may have ended an acrimonious debate by donating his neutral name, but Fracastoro himself, as a Veronese patriot, made his own allegiances clear in the full title of his epic poem: Syphilis sive morbus Gallicus (Syphilis, or the French disease).

To epitomize some horrendous complexities of local politics: Verona had long been controlled by the more powerful neighboring city of Venice. Italy did not yet exist as a nation, and the separate kingdom of Naples maintained no formal ties to Venice. But commonalities of language and interest led the citizens of Verona to side with Naples against the invading French forces of Charles VIII, while general French designs on Italian territory prompted nearly a half century of war and strong Italian enmity, especially following Charles's temporary occupation of Naples.

Meanwhile, Maximilian I, the Hapsburg Holy Roman Emperor (who ruled an Austrian-dominated confederation in western and central Europe, despite the name), added Spain to his extensive holdings by marrying both a son and a daughter to Spanish rulers. He also allied himself with the Pope, Venice, and Spain to drive Charles VIII out of Italy. A decade later, given the shifting alliances of realpolitik, Maximilian had made peace with France and even sought its aid to wage war on Venice. His successful campaign split Venetian holdings, and Maximilian occupied Fracastoro's city of Verona from 1509 until 1517, when control reverted to Venice by treaty.

Fracastoro had fled the territory to escape Maximilian's war with Venice. But he returned in 1509 and began to prosper both immediately and mightily, so I assume that his allegiances lay with Maximilian. But to shorten the tale and come to the relevant point, Maximilian (at least most of the time) controlled Spain and regarded France as his major enemy. Fracastoro, as a Veronese patriot and supporter of Maximilian, also despised the French presence and pretensions. Fracastoro's interest therefore lay with absolving Spain for the European spread of syphilis by denying the popular theory that Columbus's men had inadvertently imported "the Spanish disease" with their other spoils from the New World. Hence, for Fracastoro, his newly christened syphilis would be called morbus Gallicus.

I can't boast nearly enough Latin to appreciate Fracastoro's literary nuances, but experts then and now have heaped praise upon his Virgilian style. Joseph Scaliger, perhaps the greatest scholar of the generation after Fracastoro's, lauded the work as "a divine poem," and Geoffrey Etough, the major translator of our time, writes that "even Fracastoro's rivals acclaimed him second only to Virgil." In this essay, I will use Nahum Tate's English version of 1686, the first complete translation ever made into any other language and a highly influential work in its own right (despite the clunkiness of Tate's heroic couplets in utterly unrelieved iambic pentameter). This version remained a standard source for English readers for more than two centuries. Tate, one of England's least celebrated poets laureate (or is it poet laureates, or even poets laureates?), wrote the libretto for Henry Purcell's short operatic jewel Dido and Aeneas. A few devout choristers may also know his texts for "While Shepherds Watched" or "As Pants the Hart." We shall pass by his once-popular adaptation of King Lear, with its happy ending in Cordelia's marriage to Edgar.

Syphilis sive morbus Gallicus includes three parts, each with its own form and purpose. Part 1 discusses origins and causes, while parts 2 and 3 narrate myths in closely parallel structure, devised to illustrate the two most popular (though, in retrospect, not particularly effective) cures. Fracastoro begins by defending his choice of morbus Gallicus as a name for the disease:

   To Naples first it came
   From France, and justly took
   from France his name
   Companion from the war....

He then considers the theory of New World transmission on Spanish ships and admits the tragic irony, if true:

   If then by Traffick thence this
   plague was brought
   How dearly dearly was that
   Traffick bought!

But Spanish shipping cannot be blamed, Fracastoro holds, because the disease appeared too quickly and in too many places, including areas that never received products from the New World, to validate a single point of origin:

   To whom all Indian Traffick
   is unknown
   Nor could th'infection from the
   Western Clime
   Seize distant nations at the
   self same time.

Spain must therefore be absolved:

   Nor can th'infection first be
   charged on Spain
   That sought new worlds beyond
   the Western main.
   Since from Pyrene's foot, to Italy
   It shed its bane on France,
   while Spain was free.

   From whence 'tis plain this Pest
   must be assignd
   To some more pow'rful cause and
   hard to find.

The remainder of part 1 presents Fracastoro's general view of nature as complex and puzzling but intelligible--thereby exemplifying Renaissance humanism, an attitude that tried to break through the strictures of Scholastic logical analysis to recover the presumed wisdom of classical times ("renaissance" means "rebirth") but that did not yet include the belief in the primacy of empirical documentation that would characterize the rise of modern science more than a century later. Fracastoro tells us that we must not view syphilis as divine retribution for human malfeasance (a popular theory at the time)--a plague that must be corrected but cannot, as a departure from nature's usual course, be comprehended.

Rather, syphilis originated by natural causes that can, in principle, be understood. But nature is far more complex and unattuned to human sensibilities than we had been willing to admit, and explanation will not come easily--for nature works in strange ways and at scales far from our easy perception. For example, Fracastoro argues, syphilis probably had no simple point of origin followed by later spread (thus absolving Spain once again). Its particles of contagion (whatever they may be) must be carried by air but may remain latent for centuries before breaking out. Thus, the plague of any moment may emerge for reasons set long before. Moreover, certain potent causes--planetary conjunctions, for example, that may send poisonous emanations to Earth--remain far from our potential observation or understanding. In any case, and on a note of hope, Fracastoro depicts plagues as comprehensible phenomena of complex nature. And just as they ravage us with sudden and unanticipated fury, the fostering conditions will change in time, and our distress shall lift:

   Since nature's then so liable
   to change
   Why should we think this late
   contagion strange?

   The offices of nature to define
   And to each cause a true
   effect assign
   Must be a task both hard
   and doubtful too.

   [But] nature always to herself
   is true.

Part 2 continues the central theme of natural causation and potential alleviation, but in a very different manner. Following the traditions of Latin epic poetry, Fracastoro now constructs a myth to illustrate both the dangers of human hubris and the power of salvation through knowledge. He begins by giving the usual sage advice about alleviation via good living: lots of vigorous exercise, healthy and frugal diet, and no sex. (This regimen, addressed to males alone, proscribes sex only as a drain upon bodily energy, not as a source of infection--for Fracastoro did not yet understand the venereal transmission of syphilis.) But cure also requires pharmacological aid. Fracastoro upheld the traditional Galenic theory of humors and regarded all disease, including syphilis, as an imbalance among essential components that must be corrected by such measures as bleeding, sweating, and purging:

   At first approach of Spring,
   I would advise,
   Or ev'n in Autumn months
   if strength suffice,
   To bleed your patient in the
   regal vein,
   And by degrees th'infected
   current drain.

Part 2 then extols the virtues of mercury as a cure in this context. Mercury can, in fact, retard the spread of the syphilis spirochete, but Fracastoro interpreted its benefits only in terms of humoral rebalancing and the purging of poisons--for mercury plasters induced sweating, while ingestion encouraged copious spitting. The treatment, he admitted, may be unpleasant in the extreme, but ever so preferable to the dementia, paralysis, and death imposed by syphilis in the final stages of worst cases:

   Nor let the foulness of the
   course displease.
   Obscene indeed, but less than
   your disease.

   The mass of humors now
   dissolved within,
   To purge themselves by spittle
   shall begin,
   Till you with wonder at your feet
   shall see,
   A tide of filth, and bless
   the remedy.

Finally, Fracastoro spins his myth about human hubris, repentance, and the discovery of mercury. A hunter named Ilceus kills one of Diana's sacred deer. Apollo, Diana's twin brother, becomes royally infuriated and inflicts the pox of syphilis upon poor Ilceus. But the contrite hunter prays mightily and sincerely for relief, and the goddess Callirhoe, feeling pity, carries Ilceus underground, far from the reach of the sun god's continuing wrath. There in the realms of mineralogy, Ilceus discovers the curative power of mercury.

Fracastoro wrote these first two parts in the early 1510s and apparently intended to publish them by themselves. But by the 1520s, a new (and ultimately ineffective) "wonder cure" had emerged, and Fracastoro therefore added a third part to describe the new remedy in the mythic form previously applied to mercury--the same basic plot, but this time with a shepherd named Syphilis in place of the hunter Ilceus. And thus, with thanks to readers for their patience, we finally come to Fracastoro's reason and motives for naming syphilis. (An excellent article by R. A. Anselment supplied these details of Fracastoro's composition: "Fracastoro's Syphilis: Nahum Tate and the Realms of Apollo," Bulletin of the John Rylands University Library of Manchester 73, 1991.)

Fracastoro's derivation of the name has never been fully resolved, but most scholars regard Syphilis (often spelled Syphilus) as a medieval form of Sipylus, a son of Niobe in Ovid's Metamorphoses--a classical source that would have appealed both to Fracastoro's Renaissance concern for ancient wisdom and to his abiding interest in natural change.

In part 3 of Fracastoro's epic, the sailors of a noble leader (unnamed, but presumably Columbus) find great riches in a new world but incur the wrath of the sun god by killing his sacred parrots (just as Ilceus had angered the same personage by slaying Diana's deer). Apollo promises horrible retribution in the form of a foul disease. But just as the sailors fall to their knees to beg the sun god's forgiveness, a group of natives arrives--"a race with human shape, but black as jet," in Tate's translation. They, too, suffer from syphilis and have come to the parrots' grove to perform an annual rite that recalls the origin of their misfortune and also permits them to use the curative powers of local botany.

These people, we learn, are the degraded descendants of the race that inhabited the lost isle of Atlantis. They had already suffered enough in losing their ancestral lands and flocks. But a horrendous heat wave then parched their new island and fell with special fury on the king's shepherd:

   A shepherd once (distrust not
   ancient fame)
   Possessed these downs, and
   Syphilus his name
   A thousand heifers in these vales
   he fed,
   A thousand ewes to those
   fair rivers led

   This drought our Syphilus beheld
   with pain,
   Nor could the sufferings of his
   flock sustain,
   But to the noonday sun with
   upcast eyes,
   In rage threw these reproaching

Syphilus cursed the sun, destroyed Apollo's altars, and then decided to start a new religion based on direct worship of his local king, Alcithous The king, in turn, heartily approved this new arrangement:

   Th'aspiring prince with godlike
   rites o'erjoyed,
   Commands all altars else to be
   Proclaims himself in earth's low
   sphere to be
   The only and sufficient deity

Apollo becomes even angrier than before (for Ilceus alone had inspired his wrath in part 2), and he now inflicts the disease upon everyone--but first upon Syphilus, who thus gains eternal notoriety as name bearer:

   Th'all-seeing sun no longer
   could sustain
   These practices, but with
   enraged disdain
   Darts forth such pestilent
   malignant beams,
   As shed infection on air, earth
   and streams;
   From whence this malady its
   birth received,
   And first th'offending Syphilus
   was grieved

   He first wore buboes dreadful
   to the sight,
   First felt strange pains and sleepless
   passed the night;
   From him the malady received
   its name,
   The neighboring shepherds caught
   the spreading flame:
   At last in city and in court
   'twas known,
   And seized t'ambitious monarch
   on his throne.

A shepherd or two could be spared, but the suffering of kings demands surcease. The high priest therefore suggests a human sacrifice to assuage the wrath of Apollo (now given his Greek name of Phoebus), and guess whom they choose? But fortunately, the goddess Juno decides to spare the unfortunate shepherd and to make a substitution, in obvious parallel to the Biblical tale of Abraham and Isaac:

   On Syphilus the dreadful lot
   did fall,
   Who now was placed before
   the altar bound
   His head with sacrificial garlands
   His throat laid open to the
   lifted knife,
   But interceding Juno spared
   his life,
   Commands them in his stead a
   heifer slay,
   For Phoebus's rage was now
   removed away.

Ever since then, these natives, the former inhabitants of Atlantis, perform an annual rite of sacrifice to memorialize the hubris of Syphilus and the salvation of the people by repentance. The natives still suffer from syphilis, but their annual rites of sacrifice please Juno, who in return allows a wondrous cure, the guaiacum tree, to grow on their isle alone. The Spanish sailors, now also infected with the disease, learn about the new cure and bring guaiacum back to Europe.

Thus, the imprecation heaped upon Spain by calling syphilis the Spanish disease becomes doubly unfair. Not only should the Spaniards be absolved for importation (because the disease struck Europe all at once, and from a latent contagion that originated well before any ships reached the New World), but the same Spanish sailors, encountering a longer history of infection and treatment in the New World, had discovered a truly beneficent remedy.

Many people know about the former use of mercury in treating syphilis, for the substance had some benefit and the remedy endured for centuries. But the guaiacum cure has faded to a historical footnote because, in a word, this magical New World potion flopped completely. (By 1530, the year of Fracastoro's publication, Paracelsus himself had branded guaiacum as useless.) But Fracastoro devised his myth of Syphilus during the short period of euphoria about the power of the new nostrum. The treatment failed, but the name stuck.

We should not be surprised to learn that Fracastoro's attraction to guaiacum owed as much to politics as to scientific hope. The powerful Fugger family, the great German bankers, had lent vast sums to Maximilian's grandson Charles V in his successful bid to swing election as Holy Roman Emperor over his (and Fracastoro's) archenemy, Francis I of France. As partial repayment for Charles's debt, the Fuggers received a royal monopoly for importing guaiacum to Europe. (The Hapsburg Charles V also controlled Spain and, consequently, all shipping to and from Hispaniola, where the guaiacum tree grew.) In fact, the Fuggers built a chain of hospitals for the treatment of syphilis with guaiacum. Fracastoro's allegiances, for reasons previously discussed, lay with Charles V and the Spanish connection, so his tale of the shepherd Syphilus and the discovery of guaiacum suited his larger concerns as well. (Guaiacum, also known as lignum vitae or lignum sanctum ["wood of life" or "holy wood"], has some medicinal worth, although not for treating syphilis. As an extremely hard wood, of the quality of ebony, guaiacum also has value in building and decoration.)

Fracastoro did proceed beyond his politically motivated poetry to learn more about syphilis. In the later work that secured his enduring fame (but largely for the wrong reason)--his De Contagione et Contagiosis Morbis et Curatione (On Contagion and Contagious Diseases and Their Cure) of 1546--Fracastoro finally recognized the venereal nature of syphilis, writing that infection occurs "verum non ex omni contactu, neque prompte, sea tum solum, quum duo corpora contactu mutuo plurimum incalvissent, quod praecipue in coitu eveniebat" (truly not from all contact, nor easily, but only when two bodies join in most intense mutual contact, as primarily occurs in coitus). Fracastoro also recognized that infected mothers can pass the disease to their children, either at birth or through suckling.

Treating himself diplomatically and in the third person, Fracastoro admitted and excused the follies of his previous poem, written "quum iuniores essetamus" (when we were younger). In this later prose work, Fracastoro accurately describes both the modes of transmission and the three temporal stages of symptoms--the small, untroublesome (and often overlooked) genital sore of the primary stage; the secondary stage of lesions and aches, occurring several months later; and the dreaded tertiary stage, developing months to years later and leading to death by destruction of the heart or brain (called paresis, or paralysis accompanied by dementia) in the worst cases.

In the hagiographical tradition still all too common in textbook accounts of the history of science, Fracastoro has been called the father of the germ theory of disease for his sensitive and accurate characterization, in this work, of three styles of contagion: by direct contact (as for syphilis), by transmission from contaminated objects, and at a distance through transport by air. Fracastoro discusses particles of contagion called semina (seeds), but this term, taken from ancient Greek medicine, carries no connotation of an organic nature or origin. Fracastoro does offer many speculations about the nature of contagious semina, but he never mentions microorganisms, a hypothesis that could scarcely be imagined more than fifty years before the invention of the microscope.

In fact, Fracastoro continues to argue that the infecting semina of syphilis may arise from poisonous emanations sparked by planetary conjunctions. He even invokes a linguistic parallel between transmission of syphilis by sexual contact (coitus) and the production of bad seeds by planetary overlap in the sky, for he describes the astronomical phenomenon with the same word, as "coitum et conventum syderum" (the coitus and conjunction of stars), particularly "nostra trium superiorum, Saturni, Iovis et Martis" (our three most distant bodies: Saturn, Jupiter, and Mars).

Nonetheless, we seem to need heroes, defined as courageous iconoclasts who discerned germs of modern truth through strictures of ancient superstition--and Fracastoro therefore wins false accolades under our cultural myth of prescience ("ahead of his time"), followed by rejection and later rediscovery, long after death and well beyond hope of earthly reward. For example, the Encyclopaedia Britannica entry on Fracastoro ends by proclaiming:

   Fracastoro's theory was the first scientific statement of the true nature
   of contagion, infection, disease germs, and modes of disease transmission.
   Fracastoro's theory was widely praised during his time, but its influence
   was soon obscured by the mystical doctrines of the Renaisssance physician
   Paracelsus, and it fell into general disrepute until it was proved by Koch
   and Pasteur.

But Fracastoro deserves our warmest praise for his brilliance and compassion within the beliefs of his own time. We can appreciate his genius only when we understand the features of his work that strike us as most odd by current reckonings--particularly his choice of Latin epic poetry as a medium for describing syphilis and his christening of the disease for a mythical shepherd whose suffering also reflected Fracastoro's political needs and beliefs. In his article on Fracastoro for the Dictionary of Scientific Biography, Bruno Zanobio gives a far more accurate description, properly rooted in sixteenth-century knowledge, of Fracastoro's concept of contagious seeds:

   They are distinct imperceptible particles, composed of various elements.
   Spontaneously generated in the course of certain types of putrefaction,
   they present particular characteristics and faculties, such as increasing
   themselves, having their own motion, propagating quickly, enduring for a
   long time, even far from their focus of origin, [and] exerting specific
   contagious activity....

A good description to be sure, but not buttressed by any hint that these semina might be living microorganisms. "Undoubtedly," Zanobio continues, "the seminaria derive from Democritean atomism via the semina of Lucretius and the gnostic and Neoplatonic speculations renewed by St. Augustine and St. Bonaventura." Fracastoro, in short, remained true to his Renaissance conviction that answers must be sought in the wisdom of classical antiquity.

Fracastoro surely probed the limits of his time, but medicine, in general, made very little progress in controlling syphilis until the twentieth century. Guaiacum failed, and mercury remained both minimally effective and maximally miserable. (We need only recall Erasmus's sardonic quip that in exchange for a night with Venus, one must spend a month with Mercury.) Moreover, since more than 50 percent of people infected with the spirochete never develop symptoms of the dreaded third stage, the disease, if left untreated, effectively "cures" itself in a majority of cases (although spirochetes remain in the body). Thus one can argue that traditional medicine usually did far more harm than good--a common situation, recalling Benjamin Franklin's remark that although Dr. Mesmer was surely a fraud, his ministrations should be regarded as benevolent because people who followed his "cures" by inducing "animal magnetism" didn't visit "real" physicians, thereby sparing themselves such useless and harmful remedies as bleeding and purging.

No truly effective treatment for syphilis existed until 1909, when Paul Ehrlich introduced preparation 606 (Salvarsan). Genuine (and gratifyingly easy) cures only became available in 1943, with the discovery and development of penicillin. Identification in the first stage, followed by one course of penicillin, can control syphilis, but infections that proceed to later stages may still be intractable.

I make no apologies for science's long record of failure in treating syphilis--a history that includes both persistent, straightforward error (the poisoning and suffering of millions with ineffective remedies based upon false theories) and, on occasion, morally indefensible practices as well (most notoriously, in American history, the Tuskegee study that purposely left a group of infected black males untreated as "controls" for testing the efficacy of treatments on another group; in a moving ceremony, President Clinton recently apologized for this national disgrace to the few remaining survivors of the untreated group). But syphilis can now be controlled and may even be a good candidate for total elimination (as we have done with smallpox), at least in the United States, if not in the entire world. We owe this blessing, after so much pain, to knowledge won by science. There is no other way.

And so, while science must own its shame (along with every other institution managed by that infuriating and mercurial creature known as Homo sapiens), science can also find cures, or at least discover some means of relief, for human miseries caused by external agents that must remain beyond our control until their factual nature and modes of operation become known. The sequential character of this duality--failures as necessary preludes to success, given the stepwise nature of progress in scientific knowledge--leads me to contrast Fracastoro's Latin hexameter with the stodgy prose of the 1998 Science article on the genome of Treponema pallidum, the syphilis spirochete.

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