Microbiological, virological, bacteriological, immunological, medical, epidemiological, historical, anecdotal

Tag: syphilis

Taiwau Bozu: The bald geisha plague of 1901

The strange disease which has produced so much hilarity came, it is said, from Formosa; and a person may conclude that he has been attacked by it when he gets up in the morning and finds a hitherto hairy poll as bare as a billiard ball. No other symptoms make their appearance. It is bad enough for the Japanese gentlemen, but the ladies are quite terrified at the prospect of losing those coiled masses of glistening, jet-black hair which are often veritable works of art.hairless-japan

In this light-hearted style, English-language newspapers noted of an “epidemic of baldness” which afflicted the rapidly-modernizing nation of Japan in 1900 and 1901. The Sydney Daily Telegraph‘s unnamed Tokyo correspondent, writing in March 1901, goes on to rhapsodize about the “long raven locks”, the “shiny coils and bride-cake intricacies”, which rested on the heads of “singing girls of the well-known type of Rudyard Kipling’s ‘O-Toyo, ebon-haired, rosy-cheeked, and made throughout of delicate porcelain’,” before revealing that “in at least three or four cases” prominent Japanese ladies have had their heads rendered egg-like and their status in society thereby ruined.

The article gives the impression that a lot more men than women have been afflicted, but “[t]he strong point of a Japanese [man] does not by any means lie in his hair, which generally sticks up on his head as bristly and as stiff as the hairs on a blacking brush.” Thus our sympathy should be directed at the “singing girls” or “dancing girls” who so prize their raven tresses. And the Japanese, led by their one famous bacteriologist (probably Shibasaburo Kitasato, though Hideyo Noguchi would soon achieve similar fame) can surely deal with this problem.

The study of medicine is pursued with great ardor and success in Japan, which claims the honour of having produced at least one bacteriologist of international fame; and it is not surprising, therefore, that the doctors are studying the new disease with the liveliest interest. It should be no difficult matter to get hold of the pestilent little microbe that is the cause of all the trouble.

* * *

The mysterious plague apparently originated on the island of Formosa (now called Taiwan), which was under Japanese military occupation, following the island’s relinquishment by China under the Treaty of Shimonoseki. Formosa was a poor place at the time, compared to Japan, and a plausible source for a tropical disease.

Also in 1901, the London Spectator gave a more clinical report of the outbreak, courtesy of Berlin correspondent Louis Elkind, probably summarizing German press reports. Evidently “there was an epidemic of baldness at Chiba last year, and there has been an even more serious one quite recently at Osaka, the same province where, as it will be remembered, an extensive epidemic of plague … prevailed in the last months of 1899 and at the very beginning of 1900.”

The effects of the disease exhibit several interesting peculiarities. The bald patches are irregularly spread over the head, but the first large one generally appears on the crown and extends down the back of the head instead of forwards towards the forehead; thus it may be that the back of the head is quite bald and the front covered with hair — the opposite of the course of baldness as we know it in Europe. Then, also, men’s beards are ravaged in a peculiar manner. The left cheek, say, may be completely bereft of hair while the rest of the beard is as usual, as also is the moustache, which, fortunately, is but slightly affected by the disease.

* * *

Elkind’s report sounds more plausible than the Sydney correspondent’s chatter about ladies “shedding their ebony tresses — and shedding at the same time tears large as eggs”.

Utamaro (1753-1806), Kami-yui (Hairdressing)

Utamaro (1753-1806), Kami-yui (Hairdressing)

But did this really happen?

No, according to Dr. Stuart Eldridge, friend of Ulysses Grant and longtime contributor of short dispatches from Japan to the ASPH journal Public Health Reports. Eldridge’s obituary suggests an interesting career, including at age 28 being part of “the scientific mission to Japan under General Horace Capron,” and staying in Japan until his death 30 years later.

After updating Public Health Reports on Japan’s plague outbreak of 1899-1900, Eldridge sent in two brief reports about the bald geisha plague (Report #1, Report #2). Here’s the first.


No source is cited, but Eldridge thinks the disease is spread quickly, is spread by barbers, originated in Osaka (though the Spectator claims it was in Chiba first), and there is evidence for all these assertions though we don’t know yet whether the baldness is permanent.

However… one week later, Eldridge has consulted with the leader of Japan’s bacteriological efforts, and now doubts that the outbreak ever happened.

I have communicated with Professor Kitasato, thinking that, if it was of the importance and malignity ascribed to it by the newspapers and common fame, the institution under his charge would have already begun the investigation of the matter. Professor Kitasato informs me that so far he has been unable to obtain proper material for study, and that the cause of the malady has not been, as yet, ascertained. I am now somewhat inclined to believe that both the number affected and the severity of the disease have been greatly exaggerated, and that it may eventually prove that the ordinary cases of alopecia, always rather prevalent in Japan, and neither contagious nor particularly severe, have been magnified by newspaper sensationalism into something new and alarming.

At the same time Kitasato published an article in the newspaper Jiji Shinpo. Given his stature in Japanese medicine, I’m guessing this was a decisive blow against the local baldness hysteria. Kitasato’s thoughts were summarized by Albert Ashmead in American Medicine — after first giving a sample of that hysteria.


“In some villages the hair of all the women in the place has fallen out. The people call the hair plague ‘Taiwau Bozu.’ The disease has robbed several dancing girls of their beauty. It is said to have been imported from Formosa, and the health authorities have gangs of men at work disinfecting the poor quarters of the towns. The hair plague seems to be spreading over a large area.”

Allow me to observe that Taiwau Bozu is not a new disease. The words mean Formosan Priest. All Buddhist priests in Japan have the head shaved, and thus one who is completely bald is said to look like a priest, in fact is called “priest.” … Dr. Kitasao says that “it is not the first time the disease has been epidemic in Japan. It does not come from Formosa, although the people think so. It is not very contagious. It is the same disease which occurs all over Europe, etc.” Inasmuch as the syphilis of Formosa is fiercer than the syphilis of Japan, and the syphilis of Europe is fiercer than that of Formosa, so Taiwau Bozu’s ravages differ in different countries.

… The disease is simply epidemic Tokuhatz-fizo (bald disease); Alopecia areata of specific origin (syphilitic), and it is contagious.

So according to the experts, we have a minor urban flare-up of secondary syphilis. (“The classic alopecia of secondary syphilis is patchy with a “moth-eaten appearance” and has been reported in up to 7% of patients.”) Possibly associated with the return of military forces from Taiwan (or Taiwau), as outbreaks of venereal disease sometimes are. Albert Ashmead’s interest in Japanese history lets him put the whole thing into perspective.

I add that in 1967, when the licensing of prostitution went into effect in Japan, the professions for women of “Geisha” dancing, tea-house and archery-gallery keeping, became crowded with prostitutes (more or less syphilitic) to evade the payment of the government tax. Then the hospitals of Tokio had to do with a great number of cases of syphilitic alopecia in no way different from the present outbreak

Follow Amboceptor on Twitter: @AmboceptorBlog.

Follow on Twitter: @AmboceptorBlog

Follow Amboceptor on Twitter: @AmboceptorBlog
Follow Amboceptor on Twitter: @AmboceptorBlog
Follow Amboceptor on Twitter: @AmboceptorBlog
Follow Amboceptor on Twitter: @AmboceptorBlog

So you want to be an industrial glassblower

So, you’re interested in a job as a glassblower. That’s no surprise. For 50 years glassblowing has been a good way for a skilled industrial laborer to earn a comfortable living, and today as we enter the 1920s, demand for these workmen shows no signs of lessening. But what are the risks?

Since there are so many glassblowers around, it’s important for society to properly assess what diseases they are likely to suffer. Frederick L. Hoffman writes, in the 231st Bulletin of the United States Bureau of Labor Statistics (“Mortality from Respiratory Diseases in Dusty Trades”, 17th in the Industrial Accidents and Hygiene Series):

The hygiene of glass blowers with special reference to pulmonary tuberculosis is of exceptional interest as a labor problem in the glass industry. The number of blowers employed proportionate to the total number of wage earners is relatively large, and, from a wage point of view, the employment is of the first order of importance.

From this US government document we can see some statistics on the prevalence of tuberculosis in this population. It’s not so much that they are exposed to the bacteria to a high degree. But continual low-level lung damage by inhaling high-temperature air containing various dusts means that once the bacteria are inevitably inhaled, they have a place to roost. The lung equivalent of abrasions, you might say.


So they have higher mortality rates than men in general of the same age. With regard to tuberculosis in particular, here’s a table compiled by Prudential Insurance researchers.


Carboy blowing? Carboys are huge! It’s hard to contemplate the human lungs being the engines of inflation for one of these. Or thisHand Blown Monumental Demijohn.

Some other recent statistics, from the Chicago Tuberculosis Institute. This table is on page 153 of the July 1915 – June 1916 annual report of the Illinois Chief State Factory Inspector.


So as a glassblower you’re not as likely to fall prey to the dread tubercular bacillus as you would be as a marbleworker or upholsterer, but it’s a concern.

* * *

What about other lung conditions?

This turns out to be controversial. As a person with no medical training, I’d imagine that the risk factors for tuberculosis and emphysema are pretty similar. Inhaling poisons or microscopic things that damage the alveoli (alveoli are tiny air sacs which combine to make up a massive surface area for oxygen to enter the blood). However, the evidence regarding glassblowers suggests that the two diseases are uncorrelated.

In 1904 Prettin and Leibkind of the Stadtkrankenhaus Dresden-Friedrichstadt analyzed 230 glassblowers for an article entitled “Kann durch Glasblasen ein Lungenemphysem erzeugt werden?” JAMA (the Journal of the American Medical Association) deemed this an important finding, a perfect example of the sort of science-based result that supersedes old-fashioned beliefs that were based only on common sense.


* * *

We already know that the southeastern regions of New Jersey are great for making wines and wine-related medicinal concoctions. Meanwhile southwestern New Jersey was a hotbed of glass production, as seen in the history of the large town of Glassboro in Gloucester County. To the northeast are two townships called Waterford and Winslow, both of which are named for large glassworks that existed in the 1860s.

In 2006 Erik Schwartz of the Cherry Hill Courier-Post wrote about the long-gone legacy of glass in areas including Waterford and Winslow townships. And in 1869 Dr. John Snowden sent in some observations about the health of workers at the Waterford and Winslow glassworks, included in the Camden County report (p. 134-136) in the Transactions of the Medical Society of New Jersey. “Phthisis” means tuberculosis.


A very interesting communication on the subject of Phthisis has been received from Dr. John W. Snowden, who had practiced for more than twenty-three years at the seat of two of the largest manufactories of glass in this State — at the Waterford and Winslow glass manufactories, where several hundred hands are employed in the manufacture of glass. Dr. Snowden says that among the glass-blowers themselves Phthisis is not at all frequent; but that many of these operatives suffer from emphysema of the lungs. But that among the batch-makers (those who prepare and mix the materials of which the glass is composed), and also among the pot-makers, who make the pots in which the glass is melted in the furnaces, Phthisis is very common indeed, and that few can follow this branch of the business for many years without being liable to Phthisis.

Dr. Snowden says that many of those men, months after they have been compelled by the progress of the disease to leave off work, expectorate with tuberculous matter small masses of German clay, one of the materials of which the pots are made. This undoubtedly being drawn into the lungs by inspiration, in a state of fine powder, and being insoluble, is deposited in the tissue of the lung, where it serves as a point of irritation around which the tubercle is first deposited.

So now glass-blowers don’t get tuberculosis, but they do get emphysema? I guess it depends on the facility.

There is a lot of clay powder involved in glass-making, that’s for sure. Here are the ads at the top of three straight pages of the August 25, 1917 National Glass Budget.

pittsburg-clay-pot-co highlands-fire-clay-co-st-louis laclede-christy-clay-products

* * *

Really, a lot of risks that apply to other glassworkers do not apply to glassblowers. In terms of health hazards, one of the longest assessments was written in this series of articles for insurance men, highlighting how to avoid physical accidents and the subsequent payouts for broken bones, burns, deafness, that sort of thing. I don’t know exactly what it means by “Live Articles”. Maybe it means “This is the current standard of what we expect”.


Here’s a typical illustration.


The Travelers Insurance agent who wrote “Glass Manufacturing Hazards” for this series agrees that emphysema is not a major problem for glassblowers, despite what one might expect. The men who work with the raw glass ingredients, and the “bottle-breakers” who smash undesirable glass so it can be re-melted, are more at risk for this — as they are for skin irritation, painful abrasions, burns from molten glass, and foot lacerations.

Glass-blowers do sometimes break their teeth when the iron blow-pipe strikes some hard object. They slip on the smooth, worn wooden foot-benches that are often without railings. They drink too much water, causing cramps. They get blisters, which should, but usually aren’t, dealt with by puncturing the blister with a needle threaded with white sewing silk, to provide drainage before the blister bursts. And they get infectious diseases from the shared water cup used to cool down between blows, and more importantly, from the shared mouthpiece on the blow-pipe. This has been the subject of several studies. Studies of syphilis.

* * *

The first link between glass-blowers’ pipes and syphilis I can find is from 1862, when the British Medical Journal relayed a report from France. Apparently in “Giers and Vernasion” (which probably means Rive-de-Gier and Vernaison), transmitting diseases is virtually inevitable because the normal procedure is for three men to collaborate (taking turns in quick succession) on blowing a single piece of glass. Is this the normal method? Anyway, this leads to the men giving each other “the three syphilitic disease of the mouth”.


In a 1904 issue of the Indianapolis Medical and Surgical Monitor, Dr. Nelson D. Brayton of the Indiana Medical College collects a large number of reports under the title “Syphilis, a Non-Venereal Disease”. Along with dozens of other anecdotes of people acquiring the dreaded disease through innocent means, he mentions a 162-person outbreak of syphilis among glass-blowers, along with other professions where people risk disease by putting common instruments in their mouths (assayers, weavers, goldsmiths, train conductors, music teachers).

In his 1906 dissertation at the University of Würzburg, Joseph Kaesbohrer described 290 cases of syphilis in which the first observed chancre (hard sore) was seen in the tonsillar region. These frequently occurred from kissing and from nursing, as well as from medical instruments, shared eating utensils, and tobacco pipes. In a summary in the Medical Review of Reviews, the only occupation listed as a risk factor is glass-blowing. So be cautious. But should you acquire this or other so-called venereal disease from your blow-pipe, don’t fear rumors and innuendo, as Kaesbohrer found that “sexual perversion, which many have assumed to be a frequent cause, is, as a matter of fact, an infrequent cause of tonsillar chancre.”

* * *

Depending on what sort of glass works you find yourself in, the risk factors can be different. Most glass doesn’t have lead in it, but some does, and that’ll be bad if it ends up in your lungs, as seen in this 1920 case from Italy.

Unshielded eyes are at risk for “glass-blowers’ cataract”. One reason why we can’t see long-wavelength “infrared” light is that the lens of the eye absorbs this light instead of letting it through to the retina where we could perceive it. Long-term exposure to this light, which we can sense only as heat radiation, can lead to a forty-year-old having the cataracts of a man of eighty. According to the Illinois Medical Journal, the eminent Dr. de Schweinitz can look at the clouding of a furnace-worker’s eyes and tell if he is right- or left-handed.

Finally, a health consequence of glassblowing that may be the most obvious of all if you know someone who’s spent a couple decades in the job. From The Sanitarian, March 1892:

According to Le Progres Medicale, the Societe de Biologie, of which M. Brown-Sequard is president, received from M. Regnault, of Marseilles, at its session on November 7th, 1891, a communication on a disease which is met with in about one third of the workmen. This condition does not attain complete development until the men have been from ten to fifteen years in the business. They are taken into the glass factories, usually, about fifteen years of age; and at first the young workmen complain of great fatigue and a painful feeling in the cheeks which extends to the ears; later, the cheek becomes gradually weakened, is easily puffed out, and the deformity, of which the cases presented were in an advanced stage, progresses steadily. This deformity is caused principally by the weakness of the buccinator muscle, whereby the cheek becomes swollen and permanently enlarged.

The swelling is limited by the masseter muscle. There is also a special dilation of the duct of Steno, the calibre of which is increased and the orifice enlarged. This duct is filled with air, which may be forced out by pressure on the external surface, when a distinct gassy sound is heard.

In short, after years of glass-blowing, your face may be altered. The buccinator muscle is weakened, the cheeks expand into jowls, and the inner mucous lining “is thrown up into vertical and circular folds, giving it an appearance which has been likened to that of a tobacco-pouch.”

Neither M. Regnault of Marseilles nor Dr. Liaras of Bordeaux, summarized in “The Mouths of Glass-Blowers” in the June 1898 Medical Bulletin, see these altered facial features as a serious problem. But in severe cases, the primary salivary duct (the parotid duct, a.k.a. duct of Stensen, a.k.a. duct of Steno) is forced open by the intense pressure in the mouth, and it becomes dilated, forcing air into the salivary gland. I can’t imagine what that feels like. Maybe not painful, but certainly weird. It sounds like a fun party trick to be able to puff up your salivary glands on command… but when it happens unbidden at work, it’s a problem. The final citation on this subject comes from JAMA of November 23, 1912.


So, the word “Tumor”. This is not “tumor” as in cancer, it’s the form that simply means “swelling”. As in the four elements of inflammation, rubor/calor/dolor/tumor, defined by Celsus in the first century A.D. Air goes into the parotid gland, and then you have “tumor” in the parotid gland. As described here by the surgeon Narath, you may have to quit your job if the “chronically stretched duct and gland” get too bad. But you’ll always have the party trick.

* * *

And one more thing. Yet another German article paraphrased by a English-language journal, in this case the March 1899 Canada Lancet.


“Luxation of the eye”? “Proptosis”? Does that mean… yes, just search for some images. So with your newly enhanced lung power as a glass-blower, just make sure that when you sneeze, really let that sneeze escape. Don’t keep it bottled up, if you value your eyeballs’ position behind their eyelids. And good luck!

A 1711 treatise on venereal disease (Part IV: Venereal Disease and Treatment)

Finally, in the fourth part of our five-part series on Dr. John Marten’s Treatise of the Venereal Disease, it’s time to mention venereal disease itself. But still not really, since there really aren’t many passages about venereal disease that go beyond mere recitations of horrors. Today we’ll sample those recitations of horrors, along with discussion of how best to relieve the miseries of the Poxt and Clapt. And the even greater horrors of practicing medicine in styles other than John Marten’s.

For help with the old-timey words and names (Plaister of Oxycroceum, eh?), check out March 3’s post on vocabulary.

For Dr. Marten’s passages about pregnancy tests, delayed puberty, the eggs in women’s testicles, plastic surgery, parasites, the special properties of Brazilians and Americans, and more, check out March 7’s post on human anatomy.

And to hear about human folly, irony, the virtues of moderation, the doting of old fools, and Womb-fury, see last Wednesday’s post on human behavior.


  • On syphilis complications:
  • And indeed this Distemper, if People value their Lives, admits of no neglect; for against such a cruel Enemy, there should be employ’d all the Force and Artillery of Physick Art can procure, to profligate, ferret out, and extinguish all the Venom in the Vessels, Viscera, and solid Parts, where it has taken up its Abode, that the Parts hurt or corrupted by it, may be purifed and restored, and those that are weakned may be strengthned. And by this means only, that is, by proper Remedies and skilful and timely Management, you’ll be saved from the amazing Variety of Ignominious Deformities; such as the Lame swinging between two Crutches, the faultring snuffling Speech, the Mattery blear Eyes, the down-fallen Nose, the rotten Palate, incurable Deafness, scabby Face, stinking Breath, bloated and unwholesome Look, &c. the bare Thoughts of which is enough to make the stoutest Man (that has the Disease) to tremble, or even as that Old Woman Acco did, who seeing her own Deformity in a Glass, run distracted. (p. 480)
  • On the treatment of testicular cysts:
  • [W]ith repeated Bleedings, the Application of Cataplasms made of Barley-meal and Oxycrate (the Parts affected being likewise kept up by Truss, to prevent the Flux of Humours into the Place), frequent Purgings, with Calomelanos & Confectio Hamech, and also drinking plentifully of Emulsions of the greater Cold Seeds made with Barley-water, and a Decoction of Sarsa and China ordered for his Common-drink, the painful Inflammation plainly vanished, but the Swelling still continued; though without any Pain, and the Bigness was uncertain, being sometimes greater, sometimes less, and easily yielding to the pressure of ones Fingers, so that at length the Judgment of two very skilful Surgeons being taken, and that Swelling being supposed a Hydrocele, or watery Rupture, it was thought fit to open it; but when it was solemnly opened with an Incision-Knife, there came out scarce any Water, and no Matter; also the whole Substance of the Testicle seem’d to have been eaten away, and perished for some time, but the investing Coats were hard and incrassated; so that the Testicle being once opened, look’d like an empty Egg-shell, or rather a Pomegranate-shell, when the Meat or that which was contained in it, was taken out. (p. 555)
  • On acido-corrosive ferment:
  • An acido-corrosive Ferment lying hid in the Genital Parts of the Whore, being more than usually agitated in Coition, passed through the Yard of this Young Man into the Pores of the Prostrates and Seminal Vessels, (by Coition more than usually open’d) and so by its sharpness infected both the Seed and Nutritious Humours, and excited small Humours in those parts. (p. 404)
  • On bacteria:
  • When we come to inspect more narrowly the Matter it self, for tho’ many Authors have writ about it, have been very diffusive and exact, as to its Nature, Signs and Properties, yet few (if any) have given us a safe, secure Praxis as may be relied on for Cure, but whether their Methods may be drawn from the Positions they lay down, as to its Nature, &c. of the Semina morbi, I shall not here stand to enquire, only this, that some will have the Venereal Disease to be nothing else than a certain multitude of Animalcule or inconspicuous little Worms, which yet by the help of a Microscope, may be plainly discovered, as Athanasius Kircher, the Jesuit, is reported to have pronounced concerning the Pestilence. (p. 474)
  • On the variability of symptoms:
  • Eustachius Rudius writes that he has observed a thousand times, that many young Men have on the same Day Copulated with one and the same Whore, and yet not all of them Infected, and those that were Infected not Infected alike; It appearing in one with a Running of the Reins, in another with a Bubo, in a 3rd with Rottenness, in a 4th with Pain in the Head, in a 5th with Falling off of the Hair, and in others with other different preternatural Effects, which doubtless, says he, happens by reason of the various Dispositions of the Bodies, Weakness of the Parts, and varieties of the Humours, for weak Parts do more easily receive Humours than the strong, and strong Bodies often resist them when the weak ones can’t. (p. 314)
  • On ineffective emplasticks and restringents:
  • The same Physician tells us of a Cook by Trade, Aged about forty, Robust, and of a Complexion Melancholly, who two or three Years before, received a Prejudice from a hired Woman, which shew’d itself in a fœtid Gonorrhæa, and was untimely stopt by Emplasticks and Restringents; this Malignant Enemy would ever after, sally out in a green or yellow issue, which having continued about eight or ten Days more or less, would of its own accord withdraw it self again, within its own Bounds, and so cease running until it was provok’d again by Riding, Drinking, or other intemperance in Diet; applying himself to me, says he, I purg’d him smartly three times, and gave him a detergent Extract for ten Days, which cured him. (p. 450)
  • On support garments:
  • The keeping up the Cod with a Bag-truss is admirable, and applying Plaisters that are Comfortable and Strengthening; such as the Plaister ad Herniam malax’d with Oil of Bricks, or a Plaister of Oxycroceum with Oil of Ants, giving Strengthning, Restorative Medicines at the same time inwardly, by which diligent Prosecution a Cure may be accomplish’d. (p. 826)
  • On the pungitive figure of the salts:
  • [It] happens in Gonorrhæa’s, where the said Glandules receiving a Malign Impression and Inflammation from the Virulent Steems, do either transmit but little or no Mucus, or at least what is very crude, thin and acrimonious, whence the Urine, as it passes, must necessarily occasion heat, smarting, and pricking Pains, like Pins and Needles through the Pungitive Figure of the Salts, wherewith the Urine is more than ordinarily loaded. (p. 789)
  • On French quacks:
  • A French Surgeon, who I was once desir’d by an Apothecary to consult with, told me, that in France he had divers time cured very violent Gonorrhæa’s, with only the hard Roes of two red Herrings beat up with Wine, without the assistance or use of any other Remedy; and that it carried off both the Virulency and Running at once; but at his relating it, I could not but smile at the Confidence and Ignorance of the Man, especially when I ask’d him wherein the Effect lay, and what reason he could give, that it should do such Feats, which he could not answer, nor I believe any Body else, because there is nothing at all in it for the purposes he gave it. (p. 408)
  • On the Foreign Quack at the Hand and Urinal:
  • But the other Day comes a young Fellow to me with a Clap, for Cure of which, he said, he applied to the Foreign Quack at the Hand and Urinal in Holborn, who after managing him according to his Skill, and before the Malignity was expell’d, gave him a Pint-Bottle of Turpentine-Drink, and a Powder, for which he took Ten Shillings, and by which, he told him, his Running would be stopt, which indeed was so to a tittle, for it was immediately dislodg’d and thrown upon one of his Testicles, to the creating a very big inflam’d and painful, humoral Tumor; which if it had not been forthwith Remedied, or had been under his Outlandish Direction, would have prov’d sufficently Mischievous and Dangerous. (p. 20)
  • On quacks in general:
  • And as a Learned Physician says, so we find, that most of the Errors that are rife among the People at this Day, are upheld by the Runnagate, Male-pert, Bragging Quack-salvers and Empyricks, with which this Nation abounds, who not having Patience to keep to their honest Trades at Home, do wander Abroad with foolish Receipts, claiming Kindred or some other Relations to some eminent Physician, thereby Cheating the over credulous People both of their Money and Health. (p. 611)
  • On non-physician practitioners:
  • I know at this time a Cobler, who marrying a poor Sea Surgeon’s Widow, has laid down his Last, and turn’d Doctor, by vertue of a Book of Receipts she had that was her Husbands, and much values; this Woman being an inspir’d Doctress, by her two Years Bedding with her Husband, tho he was half that time at Sea, has so sufficiently qualify’d her, and she her new Husband, that they propose to do great feats, I mean at killing, for I am sure they cannot at Curing. (p. 723)
  • On ads for quacks:
  • Others there are, that stand to watch People’s Waters, and only Adorn Pissing Places (to make them think of the Business in Hand), Posts and Doors, corner Houses, Thorow fairs, &c. with their deluding Quack Impertinencies, one of which presents you with a fallible Story of three Infallible Cures in Fenchurchstreet. (p. 730)
  • On failure to adhere to a treatment regimen:
  • A Man came to me sometime since to be cured of a Clap, and told me, that he had also given it his Wife, desiring my Assistance for her too; He got well pretty quickly, but she slowly, by reason of other Indispositions. After he was well, he could not keep from his Wife, and so got it again; after that she began to mend and got well; no sooner was it so but her Husband gave it her again, and she him again, so that they Clapt one another imprudently three or four times over; at length they both found, as I had often told them, there would be no end of it at that rate, and resolv’d to be separated for a while; she went into the Country, and he having continual Business in Town, so that he could not go to her, staid here, by which means, with proper Medicines, they at last were both happily cured, and remain so, tho’ a good while since perform’d. (p. 459)

L0005395 Punch, 1866: "At the Turkish Bath"

What is an amboceptor?

Amboceptors get their name…

Or I could say “Amboceptor gets its name…” — it’s one of those words that can be an object, or a substance.

Amboceptor gets its name from the Latin root “ambi-“, because it’s a receptor for two things.

An amboceptor is something that attaches to an antigen, and then attaches to complement molecules. When this happens on a cell surface, the complement pokes holes in the cell to damage it. When it happens in solution, it blocks the complement from attaching to cells.

Isn’t that… an antibody? An amboceptor is an antibody.

Yes, but we didn’t always know that.

* * *

We knew there were amboceptors. We knew there were antibodies. There could have been amboceptors that weren’t antibodies.

Amboceptor, as a substance, is critical in the complement fixation assay for serum antibody. This is a once-ubiquitous, now-too-complicated-to-be-worth-doing process of diagnosing diseases like syphilis by looking for (anti-syphilis) antibodies in a patient’s serum. It was a fixture in American life, under the monicker of the “Wassermann Test”, which countless practitioners trusted to confirm a diagnosis of syphilis, or even to diagnose syphilis in the absence of other evidence. You know how nowadays we have urban legends about babies named things like “Urine” and “Female” based on hospital mix-ups and parental idiocy? That list used to include “Positive Wassermann Johnson”.

How real?

How real?

Probably the best description of complement fixation on the internet is provided here by an organization that is always at the vanguard of science and health policy, the Texas state government. I’ll try to summarize in terms that would be familiar to blog readers from 1920.

  • Sheep corpuscles (red blood cells) are mixed with amboceptor. This sensitizes them to the complement.
  • If the sensitized corpuscles are then mixed with complement, the complement binds them and starts poking holes in the corpuscles, which is called “lysing” them.
  • The solution turns pink as the contents of corpuscles spill out. This is called “laking”. Or it was back then, anyway.
  • Serum is a solution containing amboceptor as well as many other things. If you take serum from a syphilitic patient, and mix it with syphilis antigen, the amboceptor should bind the antigen and form a complex in solution.
  • If you mix this with complement, the antigen-amboceptor complexes should bind up the complement before it can attach to the corpuscles and lyse them.
  • If you take serum from a non-syphilitic patient, the amboceptor will NOT bind the syphilis antigen, and therefore it will not bind the complement. The complement will not bind to amboceptor alone, only to complexes. So the complement is still available for lysing and laking.

As you can imagine, this is a touchy procedure prone to error.

First of all, what about the complement that’s already in the human serum? You have to inactivate it, so you can then see how the rest of the serum reacts to externally introduced complement that you bought from a supplier. How do you inactivate it? Complement is protein and you heat it to denature it. You heat it at 56 degrees Celsius. Exactly 56 degrees Celsius. For exactly 30 minutes. At 54 degrees, you won’t denature enough complement. At 58 degrees, you’ll also denature antibodies. If you do it for 60 minutes, you’ll also denature antibodies.

But that’s assuming your serum was isolated from the blood in a timely fashion, and kept at room temperature for 24 hours or less. Or maybe it’ll work after 48 hours. What if it’s been refrigerated? That has some effect on the protein stability, maybe they will start to aggregate and become useless. What if it hasn’t sat at room temperature for long enough? Blood needs to sit for an hour or so before you start processing it to remove the corpuscles and platelets, after all. How perfect does the procedure need to be? All you are showing is that there is something in the serum that blocks complement from depositing on the sheep cells. What if that something isn’t amboceptor?

And what if the serum contains something that’ll lyse the sheep corpuscles on its own? After all, sheep are not human and some people may have a natural antisheep hemolysin, which is a word used for amboceptors or other substances that lyse corpuscles. How do you correct for that? Well, you have to include a control with no complement, to figure out the background amount of lysing that goes on. Then you can dilute the serum properly. But if you dilute the serum, you make the procedure less sensitive. Some laboratories will do this, some will not.

And how much complement should you add to the serum? If you add too much, you get false negatives. Someone with early-stage syphilis may have a low level of amboceptor. If there’s too much complement, you’ll soak up all the amboceptor and still have plenty of complement left over. But it’s possible to add too little complement, too. With too little, you get ambiguous cases, where you’re not sure if you see laking or not. What if you don’t see laking in any of your samples? You need a positive control. Does that mean you need to have fresh serum on hand at all times from a known syphilitic? Oh dear.

And what should the antigen be, that can pick out syphilis amboceptor from all the other amboceptor in the serum? There’s no way of growing the syphilis spirochetes in your laboratory. Extract of syphilitic liver was used originally by Wassermann himself. Usually you would exploit the unusual lipids found in the spirochetes, by using some uninfected tissue, like some sort of heart or liver extract, with added cholesterin (a.k.a. cholesterol). I prefer Noguchi’s acetone-insoluble fraction of the alcoholic extract of fresh beef heart, or as I call it, NAIFAEFBH. In 1941 Pangborn will revolutionize syphilis diagnosis by standardizing this antigen as a certain combination of cardiolipin, cholesterol, and lecithin, all taken from beef heart. This will still be used in the 21st century [Castro et al. (2000), Clin Diagn Lab Immunol 7(4): 658-661].

And what about the Hecht-Weinberg modification, particularly the procedure of Gradwohl? A lot of people are not comfortable with adding external complement to the serum, instead trusting that the natural amount of complement in the serum is appropriate for the process. This means you wouldn’t heat-inactivate at all. This means other controls will have to be done. And the complement may end up getting inactivated anyway, based on natural half-life, exposure to light, etc.

* * *

And on, and on, and on. Most of the contemporary articles about these issues are 100% baffling to a 21st-century reader, but one of the least baffling is an exchange in the November and December 1914 issues of The Lancet-Clinic. No, not The Lancet. The Lancet-Clinic, which was published in Cincinnati until going out of business in 1916. Unfortunately it isn’t indexed in Pubmed or Google Scholar, but random Google searches for “Wassermann test” and “amboceptor” quickly found it in Googlle Books.

Go to your bookshelf, the one that groans under the weight of bound volumes of turn-of-the-century Ohio medical journals. Open up The Lancet-Clinic, Vol. CXII, issue 26, and turn to pages 536-539, where Albert Faller, M.D. issues forth a torrent of verbiage on all the problems he sees with the Wassermann test, and finishes by extolling the virtues of Gradwohl’s Hecht-Weinberg modification, which turns many negative results into positives. This is then followed by harrumphing from one Dr. Berghausen, who sees no reason why heating would ever cause any harm to anything, and opines that physicians should stop being afraid of reporting negative results just because they happen to conflict with the fact that a patient seems to have syphilis. Dr. E.A. North then muses that perhaps all this could be cleared up if people would mix their samples thoroughly, and Faller rounds out the exchange by saying that far from being “tired of condemning individuals as sufferers of syphilis”, he simply does not trust that a patient who goes from positive Wassermann to negative Wassermann has actually been cured. And he does trust when that happens with the Hecht-Weinberg. Finally, in the December issue [Lancet-Clinic CXII(27): 624], the great man himself, Rutherford Birchard Hayes Gradwohl, writes in to further heap scorn on the deplorable Berghausen, saying that “I wish to state as one who has been instrumental in urging this test before the American profession, no such ambitions have ever surged through my serological breast.”

* * *

The Wassermann test was a serious concern. For decades, in most U.S. states, people were required to be tested for various diseases, particularly STIs, particularly syphilis. Here in Pennsylvania we waited until 1997 to repeal the requirement, which had begun as part of a nationwide campaign by New Deal-era Surgeon General and future Pittsburgh public health supremo Thomas Parran. But what does it mean to have a negative Wassermann?

What if you have no signs of the disease, you have no family history of it, but you have a positive Wassermann? Does it mean anything? How can you not worry? What if I had a positive reading earlier, and now I’m negative? Am I cured, thanks to the new sulfonamide drugs that work so much better than salvarsan? Is it really possible to be cured? And doesn’t this just measure antibodies? I have antibodies against just about every infection I’ve ever suffered. That doesn’t mean I’m still an infection risk.

How to get reliable Wassermann results was a perennial topic in the literature for decades. Because it was such a devastating diagnosis. And for practical reasons, since so many of the tests had to be carried out and they were so cumbersome.

A sample:

  • Noguchi, H. and J. Bronfenbrenner (1911). The Comparative Merits of Various Complements and Amboceptors in the Serum Diagnosis of Syphilis. J Exp Med 13(1): 78-91.
  • Van Saun, A. I. and M. K. Preston (1918). Comparative Wassermann Tests with Two Antigens. Am J Public Health (NY) 8(2): 146-148.
  • Lewis, P. A. and H. S. Newcomer (1919). Observations on the Wassermann Reaction: A Comparison of the New System of Noguchi with That Using Cholesterolized Antigen According to McIntosh and Fildes. J Exp Med 29(4): 351-359.
  • Browning, C. H. and E. L. Kennaway (1920). Suggestions for a New Criterion of a Positive Wassermann Reaction Based on an Analysis of 2334 Quantitative Tests. J Hyg (Lond) 19(1): 87-106.
  • Mackie, T. J. and C. C. Rowland (1920). The Value of Simultaneous Testing for the Wassermann Reaction, with Two Different Antigens and the “Ice-Box Method”. Br J Exp Pathol 1(5): 219-224.
  • D.Aunoy, R. (1921). Comparative Study of the Wassermann and Sachs-Georgi Reactions. J Med Res 42(4): 339-347.
  • Bigger, J. W. (1921). The Reliability of the Wassermann Test as performed by different Pathologists. J Hyg (Lond) 20(4): 383-389.
  • Famulener, L. W. and J. A. W. Hewitt (1922). Studies on the Serodiagnosis of Syphilis: I. The Hecht-Weinberg-Gradwohl Test. J Inf Dis 31(3): 285-290.
  • Shepardson, R. T. (1922). Preliminary Report on an Investigation of the “Provocative Wassermann” Controlled by the Ice-Box Method. Cal State Med J 20(3): 80-83.
  • Dulaney, A. D. (1923). The Wassermann and Kahn Precipitation Tests Compared in 900 Cases. Am J Public Health (NY) 13(6): 472-474.
  • Osmond, T. E. and D. McClean (1924). A Comparison of the Kahn and Wassermann Tests on 500 Serums. Br Med J 1(3301): 617-618.
  • Ruediger, E. H. (1924). A Plea in Favor of a Standardized Wassermann Test. Cal West Med 22(11): 548-553.
  • Malcolm, M. (1924). A Comparison of the Kahn Test with the Wassermann Test. Can Med Assoc J 14(3): 222-224.
  • Wyler, E. J. (1927). A Note on Two Factors Affecting the Sero-diagnosis of Syphilis. Br J Vener Dis 3(4): 320-325.
  • Green, F. (1929). The Kahn Test as Compared with a Standard Wassermann Reaction. Can Med Assoc J 20(1): 26-29.
  • Ferguson, J. H. and E. C. Greenfield (1929). Value of the Hinton Test in the Serum Diagnosis of Syphilis: In Comparison with the Khan and Wassermann Tests. Br Med J 1(3558): 492-494.
  • Evans, N. (1930) Kahn Precipitation Test for Syphilis: As Used in Conjunction with the Wassermann Test. Cal West Med 32(1): 24-26.
  • Eagle, H. (1931). Studies in the Serology of Syphilis: IV. A More Sensitive Reaction for Use in the Wassermann Reaction. J Exp Med 53(5): 605-614.
  • Chambers, S. O. (1932). The Kahn Precipitation Test: Compared with the Kolmer Modification of the Wassermann Test in Untreated Primary Darkfield Positive Seronegative Syphilis. Cal West Med 37(3): 153-155.
  • Barritt, M. M. and A. O. Ross (1939). A Comparison of the Wassermann and Meinicke (M.K.R. II) tests in the Serological Diagnosis of Syphilis. Br J Vener Dis 15(3): 183-202.
  • Richardson, G. M. (1940). The Specificity of the Bordet-Wassermann Reaction: Preliminary Note on an Improved Method. Br J Vener Dis 16(3-4): 166-185.
  • Rickword Lane, C. (1944). Comparison of the Laughlen Reaction for Syphilis with the Wassermann and Kahn Reactions. Br J Vener Dis 20(2): 78-81.
  • Kolmer, J. A. (1944). The Problem of Falsely Doubtful and Positive Reactions in the Serology of Syphilis. Am J Public Health Nations Health 34(5): 510-525.
  • McMenemey, W. H. and W. H. Whitehead (1949). Ford Robertson and Colquhoun Modification of the Meinicke Clarification Reaction Compared with the Harrison-Wyler Wassermann and the Standard Kahn Reactions. Br J Vener Dis 25(3): 147-154.
  • Osmond, T. E. (1950). Comparison of the Wassermann and Kahn Reactions. Br Med J 1(4652): 524.
  • Bekierkunst, A. and F. Milgrom (1950). Complement-fixation Reactions with Cardiolipin Antigen Compared with Kahn Reactions. Bull World Health Organ 2(4): 687-688.
  • Orpwood Price, I. N. and A. E. Wilkinson (1952). Comparative Serum Testing with Cardiolipin and Crude Heart Extract Wassermann Antigens. Br J Vener Dis 28(1): 16-19.
  • Kahn, R. L. (1972). Syphilis Serology with Lipoidal Antigen: The Meaning of Positive Reactions. J Natl Med Assoc 64(2): 117-passim.

In addition to any number of more technical papers with titles like “The Amount of Hemolysin Absorbed By Sheep Corpuscles”, published in the American Journal of Syphilis.

The situation was summed up well by Knox College art benefactor L. W. Famulener and Julia A. W. Hewitt (1922), in the atypically lucid introduction to their typically inconclusive study.

It is quite difficult to delimit the borderline between the nonsyphilitic and the syphilitic person. Supersensitive laboratory tests on nonsyphilitic serums* in certain cases may give results which pass over to the syphilitic side. This is especially true when the worker is in pursuit of those who clearly show syphilitic conditions, but whose serums fail to give a positive reaction with the usual methods. The nonreacting syphilitic may not even carry “syphilitic fixing bodies” in his serum. It is well known that there is a decided quantitative difference existing between the different positive serums. If these “fixing bodies” are metabolites, they may arise anew, or may be normal substance markedly increased in amount during the course of the disease. In the latter case, it is quite conceivable that certain nonsyphilitic persons may naturally have an abnormally large content of these substances in their blood, while, on the contrary, known syphilitic persons may fail to elaborate these bodies and show only a very low content, even below the average norm for the healthy person. Therefore memers of either group may be found on opposite sides of an arbitrarily established borderline, where clinically they do not belong. …

As to the criteria which should determine the syphilitic from the nonsyphilitic persons, no common agreement exists. By cooperative studies among clinicians, pathologists and serologists, progress may be made toward that ultimate end. In the absence of a standard method for the serum diagnosis of syphilis, a multitude of modifications of the original Wassermann technic** have come into existence. Many of these modifications are erroneous in conception, even conflicting with the established laws of serology, consequently leading to false results.

And the number of modifications would only increase, until the complement-fixation process was given up as inherently unstable and imprecise, the flintlock musket of the serologist’s arsenal.

* Nowadays we say “sera”. We must be more pretentious nowadays.

** Nowadays we spell it “technique”. Pretentious?

* * *

So anyway. Why don’t we use the word “amboceptor” anymore? Is it still used in some circles? No, I don’t think so. A Pubmed search for “amboceptor” [All Fields] found 59 results. The last one was in 1991, and they were distributed fairly evenly over the previous 87 years. Which is pretty amazing when you consider how many more articles are indexed from 1991 than 1904. And in fact, most of the results since 1965 are either translated out of German, Czech, or Bulgarian, or are in odd journals like Developments in Biological Standardization and Bibliotheca Haematologica. The last appearance in an abstract is in a German-language paper entitled “Effect of different media on long-term cultivation of human synovial macrophages”, from the now-retired Eckhard Stofft of the University of Mainz, a specialist in tendon and ligament pathology.

Scientometric metadata

Scientometric metadata

* * *

“In the extensive experiments and observations during the past twenty years, the greater amount of effort has been expended in the consideration of the manner of the production of immune bodies upon the part of the host, together with quantitative and qualitative methods for the determination of such bodies. Thus specific substances have been recognized, to which the names antitoxin, agglutinin, precipitin, amboceptor, opsonin, etc., have been given.”

– Duval, C.W. and F.B. Gurd (1911). Experimental Immunity with Reference to the Bacillus of Leprosy. Part I: A Study of the Factors Determining Infection in Animals. J Exp Med 14(2): 181-195.

Antitoxin: still used. Although all antitoxins are antibodies, the word is still medically useful.

Agglutinin: still used, but usually we say “hemagglutinin”. Not all hemagglutinins are antibodies.

Precipitin: still used. Although all precipitins are antibodies, the precipitin test, which is even older than the complement fixation test, is still used.

Opsonin: still used. A very useful word. And not all opsonins are antibodies.

Amboceptor: obsolete.