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

Tag: mercury

A 1711 treatise on venereal disease (Part V: Miscellany and Mercury)

With the end of the month of March, we end our series of posts on Dr. John Marten’s 1711 Treatise of the Venereal Disease.

In previous volumes, we’ve gone through as many lengthy, out-of-context quoted passages as anyone can stand. See Part II: Human Anatomy (“These Ova, or Eggs are not only found in the Testicles of Married Women, but also in Virgins, in the same manner as we find them in Pullets which will lay Eggs”);  Part III: Human Behavior (“To see an old Letcher, what more odious, yet what more common? How many Decrepit, Hoary, Wither’d, Bursten-belly’d, Crooked, Deaf, Toothless, Bald, Blear-ey’d, Impotent, Rotten Old Men, shall you see flickering upon the Women in almost every Place?”); and Part IV: Venereal Disease and Treatment (“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”).

Therefore, the lengthy passages in today’s post will be presented in some sort of context!mercury-the-third-part

First, it should be noted that A Treatise of the Venereal Disease is divided into three parts. The first chapter of the third part, between “Of the Return of the Hidden Pox” and “Of Mischiefs by Quacks, &c.” comprises 99 pages about mercury, with a tenuous link to venereal disease or any other elements of the book. Marten has clearly scoured all available medical literature for evidence that mercury is toxic. Here are a couple representative mercury anecdotes.

  • On mercury poisoning:
  • Petrus Apponensis, in his Book de Vener. Cap. 2. relates an unhappy Disaster that befel an Apothecary, who to quench his impatient Thirst in the Night, rashly took hold of a Bottle with Mercury, and upon a Mistake that it was Water, drank a rousing Draught of it, upon which he was found dead next Morning, though the greater part of the Quicksilver run thro’ him by Stool; his Body being dissected, they found his Heart and the Blood around it quite congealed. (p. 628)
  • On precautions against mercury poisoning:
  • To prevent or Remedy the Perniciousness of those Mercurial Effluvia, those Miners hold frequently Gold in their Mouths, whilst at work, which in some measure may relieve them, because holding it there for some time, it is chang’d from its yellow Colour to a whiteness like Silver; but by their constant working and drawing in the Particles at their Breath, it proves but a very insufficient Remedy. (p. 629)
  • On mistakes by the pharmacist:
  • [A] tender young child was order’d this Liniment to kill Lice. Take Mercurius Dulcis, one Dram; Mercurius Vitæ, one Scruple; Pomatum one Ounce; mix. But an unskilful Apothecary making a vile Mistake, put in Sublimate instead of Mercurius Dulcis; upon which the Head became so grievously tumefied and inflam’d, that the poor little Innocent must necessarily have perished, had not a Physician presently fomented it with a strong Lixivium; by the help of which proper Antidote, it soon recover’d indeed, but yet so as to lose all the Hair of its Head. (p. 638)
  • On carnival entertainment:
  • Wierus remarks, that a Juggler having made his Guts slippery with a good quantity of Butter, did Ordinarily, swallow down a great measure of Mercury, and voided it again immediately before the People without any hurt. (p. 679)

One symptom of mercury toxicity is excessive salivation. Some doctors in the 18th century used “salivation” as a treatment in itself, or as a way of purging the body to prepare for a more effective treatment. On page 657, Dr. Marten takes a very strong stance against this, having already pointed out plenty of incidents where people’s teeth or connective tissue are destroyed by excessive mercury ingestion.mercury-salivation-constantine

Some have been  Jaw-fallen on one side by rotting of the Ligament of the Juncture; and withstanding all this, says [a certain Surgeon], if a Patient apprehends danger in being Salivated, the Practitioner shall boldly tell him, it is as safe as a Bit of Bread, or the Food he daily eats.

But rather than I would be salivated (were I under the occasion) after the manner generally practised, I would as Constantine the Emperor said, when he was told, that there was no way to cure him of his Leprosie but by Bathing his Body in the Blood of Infants: Malo semper ægrotare quam tali Remedio Convalescere. I had rather always to be Ill, than by such a Remedy to recover; so say I as to the general method of Salivating.

 * * *

Now, on the lighter side…

On page 764, in one of Marten’s many, many attacks on doctors he deems incompetent (he calls quacks “Rascally Fellows”,  “Renegado Mechanicks”, “Pseudo-Chymical Empyricks”, “paultry deluding Fellows”, “Illiterate and Empirical Pretenders”, deceitful Intruders”, “the Pest of Humankind”, “those Monsters of Men, void of Honor and Honesty”, “deadly Enemies to Nature, and Bloody Hell-hounds”, &c.), we get a little poem in the voice of a French quack, in pidgin English. Though this and other passages about quacks are credited to “Hudibras”, I don’t think it’s from the mock-heroic late-17th-century poem by that name, as there are no search results for the phrase “Me be de Frenshman” or “de Cough, de Tissick”. Was the name “Hudibras” used by other satirists?


Me be de Frenshman, profess Physick,
Me cure de Pock, de Cough, de Tissick,
De Ish, de Gout, de Asch in Bones,
And me Begar can cut your Stones.

Towards the end, the book gets looser and looser, throwing in doggerel like this, satire, and lengthy anecdotes intended as nothing more than jokes. Another poem puts forward the “Diamonds are a girl’s best friend” principle.

Provide whilst young, against you’r Old,
For then you’ll find no Friend but Gold,
For when decay’d, and once grown Poor,
‘Tis “out you nasty common Whore”.

And here’s a Q and A in verse, some “tough love” directed at the young gentleman frantic with rage after being “Clapt” by a mistress or prostitute, which must have been Dr. Marten’s most common type of patient.the-guinea-is-due

Question. Suppose when I’m Drunk,
I pick up a Punk,
She swears she is sound,
Which false soon I found.
And I swear I will give her a Guinea:
Since she did deceive me,
And in such a Plight leave me,
If I on demand,
Pay Guinea in Hand,
D’ye think I should be not a Ninny?

Answer. The Guinea is due,
And just Debt from you;
Your Promise does bind,
And what you did find,
Your Sense might have told you before;
And however you fare,
With your Rotten Ware,
We needs must aver it,
‘Twas due to your Merit,
And you had your agreement and more.

 * * *

Finally, there’s a 2 1/2-page anecdote from Sir Thomas Browne, which simply must be read in its entirety (it’s more legible here, in Browne’s collected letters). The upshot is that he went over to the house of a woman named Belinda who was always seen in fashionable boxes at the theater, and was the object of adoration for countless young rakes and blades. So he barged in, and she and her two flatmates were eating lunch in a state of undress, because the landlady was doing the laundry. This set him to thinking about the deceptiveness of appearances, and the thin veneer of social grace underlied by the stark truths of humanity, and he was morally disenchanted, however briefly, with the very concept of whoring. As would anyone after reading all thousand pages of A Treatise of the Venereal Disease.


Pubmedwhack: Immuno-DTO

Today’s Pubmedwhack comes from the world of unstable metals and electron microscopy. For the definition of “Pubmedwhack”, see this earlier post.

* * *

Following the invention of immunofluorescence, scientists developed other methods for using labeled antibodies to identify certain proteins or substances under a microscope.

There’s immunohistochemistry (IHC), in which the antibodies are labeled not with a fluorescent marker, but with an enzyme which produces a visible reaction in the presence of a substrate. This is less precise, but lets you see your protein of choice under visible light while also looking at the structure of the tissue. The slides labeled this way last longer instead of being quenched by the microscope’s light source.

You can also use labeled antibodies to see things under the electron microscope (immuno-electron microscopy or immuno-EM). In 1960 Rifkin et al. (1) published an image of virus particles on a cell surface, labeled with ferritin-conjugated antibodies. As you can see, instead of the labeled antibodies changing the color of a region of the cell, each individual labeled antibody is visible as a “granule”.


from Rifkin et al (1960), Nature 187:1094

This was made possible by an innovation published one year earlier, entitled Preparation of an electron-dense antibody conjugate (2). Ferritin is a small protein which just about all organisms use as an iron carrier. When “iron-loaded”, almost a quarter of its mass is iron atoms. Therefore this is an especially electron-dense molecule, visible as a dark spot under the electron microscope, as seen above. Soon, further advances let scientists see ferritin-labeled structures inside cells.

* * *

For about a decade ferritin was the label of choice for immuno-electron microscopy. Then in 1971, a new technique came along (3, 4), in which antibodies were mixed with a solution of colloidal gold until they absorbed to the metal’s surface. Gold-labeled antibodies could be separated from free antibodies by centrifugation. Immunogold is still the dominant immuno-EM staining method 40 years later.

from Faulk (1971), Nature New Biology 231:101

from Faulk et al (1971), Nature New Biology 231:101

* * *

In the 1960s, other techniques were created for immuno-EM. I have almost no EM experience and don’t know the pros and cons, but clearly there was a desire to get rid of the protein element of the electron-dense antibody label, and just attach the antibody to a metal ion. The protein was unnecessarily big, and subject to denaturation. So the 1960s also saw a lot of papers using antibodies labeled with mercury (technically the diazonium salt of tetraacetoxymercuriarsanilic acid (5) and p-(aminophenyl)-mercuric acetate (6), phrases which mean little to me).

from Zhdanov et al (1965), J Histochem Cytochem

from Zhdanov et al (1965), J Histochem Cytochem 13:684

There were also studies using antibodies labeled with heavier metals. In his long career, Ludwig Sternberger and his lab (at Johns Hopkins and elsewhere) invented several microscopy techniques, with the most important probably being the horseradish peroxidase (see original paper (7), and appreciation of it as a “citation classic”).

He also spent much of the 1960s devising improved metal-based antibody labels for electron microscopy, including immunouranium (8), immunouranium with added osmium for enhanced contrast (9), and finally immuno-diazothioether-osmium tetroxide (10), or immuno-DTO. The uranium methods seem somewhat useful, but as far as I can tell were only used by Sternberger’s own lab. Immuno-DTO in particular seemed almost unusable; they used it more than once, but a Pubmed search for “Immuno-DTO” only returns one result (11). As Sternberger himself says in a review (12) of his and other techniques:

Unfortunately, the diazotized diazothioethers are not very stable even at Dry Ice temperatures and the solid deteriorates in a few days. Therefore, it was not surprising to observe that the osmnium tetroxide-binding iower of diazothioether antibodies was unstable, even on storage in liquid nitrogen.

Oh well, it was a nice idea.

* * *

1. Rifkind RA, Hsu KC, Morgan C, Seegal BC, Knox AW, Rose HM (1960). Use of Ferritin-Conjugated Antibody to Localize Antigen by Electron Microscopy. Nature 187:1094-1095.

2. Singer SJ (1959). Preparation of an Electron-dense Antibody Conjugate. Nature 183:1523-1524.

3.Faulk WP, Taylor GM (1971). An Immunocolloid Method for the Electron Microscopy. Immunochemistry 8(11):1081-1083.

4. Faulk WP, Vyas GN, Phillips CA, Fudenberg HH, Chism K (1971). Passive Haemagglutination Test for Anti-rhinovirus Antibodies. Nature New Biology 231:101-104.

5. Pepe FA (1961). The Use of Specific Antibody in Electron Microscopy: I: Preparation of Mercury-Labeled Antibody. J Biophys Biochem Cytol 11(3):515-520.

6. Zhdanov VM, Azadova NB, Kulberg AY (1965). The Use of Antibody Labeled with an Organic Mercury Compound in Electron Microscopy. J Histochem Cytochem 13(8):694-687.

7. Sternberger LA, Hardy PH Jr, Cuculis JJ, Meyer HG (1970). The Unlabeled Antibody Enzyme Method of Immunohistochemistry: Preparation and Properties of Soluble Antigen-Antibody Complex (Horseradish Peroxidase-Antihorseradish Peroxidase) and its Use in Identification of Spirochetes. J Histochem Cytochem 18(5):315-333.

8. Donati EJ, Figge FHJ, Sternberger LA (1965). Staining of Vaccinia Antigen by Immunouranium Technique. Exp Mol Pathol 4(1):126-129.

9. Sternberger LA, Hanker JS, Donati EJ, Petrali JP, Seligman AM (1966). Method for Enhancement of Electron Microscopic Visualization of Embedded Antigen by Bridging Osmium to Uranium Antibody with Thiocarbohydrazide. J Histochem Cytochem 14(10):711-718.

10. Donati EJ, Petrali JP, Sternberger LA (1966). Formation of Vaccinia Antigen Studied by Immunouranium and Immuno-diaxothioether-osmium tetroxide Techniques. Exp Mol Pathol Apr:Suppl 3:59-74.

11. Sternberger LA, Donati EJ, Hanker JS, Seligman AM (1966). Immuno-diazothioether-osmium tetroxide (immuno-DTO) technique for staining embedded antigen in electron microscopy. Exp Mol Pathol Apr:Suppl 3:36-43.

12. Sternberger LA (1967). Electron Microscopic Immunocytochemistry: A Review. J Histochem Cytochem 15(3):139-159.