Ferran's anti-choleraic inoculations (Valencia, 1885)
In the cholera summer of 1885 a physician at Tortosa injected more than thirty thousand people in the villages of Valencia with a broth culture of Koch's comma bacillus. A French commission declared the results worthless; the American investigator sent three years later arrived expecting a charlatan, went to Tortosa to see for himself, and printed the Spanish official figures in English so his readers could judge. Both halves of that record are here.
Why this wins its question: The usual account of Ferran is one sentence long and points in one of two directions: first cholera vaccine, or discredited by a French commission. Both sentences are in the sources and neither is the story. This object gives the campaign its numbers (30,491 inoculated against 104,561 not, in twenty-two towns), the vaccine its composition in Ferran's own printed instructions (a pure broth culture of the comma bacillus, injected with a one-cubic-centimetre syringe sterilised in boiling water), the rejection its exact charge (Brouardel, summer 1885: partisan collectors, no official character), the selection objection its exact wording, and the defence its procedural argument about who signed the returns - all transcribed from a single digitised government report whose author names his own prejudice before reporting, and records the dusty laboratory and the fee charge alongside the beautiful cultures.
Claims
Every assertion below is bound to registered sources and carries its own confidence. Weight them; do not treat the page as uniformly authoritative.
The scale is stated by the investigator the United States sent to Europe to study cholera. Edward O. Shakespeare reports that most of the inoculations "were performed in villages in the province of Valencia" and that "the number of persons inoculated considerably exceeds 30,000". The operations of 1885 were therefore a mass campaign, not a laboratory demonstration or a handful of volunteers.
What was injected is on the record in Ferran's own words. Shakespeare reprints, from chapter XXI of Ferran's La inoculacion preventiva contra el colera (Valencia, 1886), the instructions handed to the physicians who performed the operation. The first of them reads: "The cholera vaccine is nothing more than a pure culture, in bouillon, of the comma bacillus." It kept four to five days, travelled in flasks of Ferran's own model with a rubber stopper pierced by two glass tubes, and was expelled by forcing air into the flask rather than by opening it. This was a live culture, not a killed preparation.
The technique was hypodermic and explicitly aseptic. The same instructions require a syringe of one cubic centimetre with metallic pistons and mountings, "without mastic of any kind and without rubber", and a needle thicker and shorter than usual; before vaccinating, the syringe is filled two or three times with boiling water aspirated and expelled through the needle, "and by this means the extraneous germs are destroyed"; passing the needle through a flame is discouraged because it draws the temper of the steel; the receiving cup is flamed; and any vaccine left over after a session is boiled rather than reused, because atmospheric germs might have mixed with it.
The figures Shakespeare printed came from the statistics collected by order of the Spanish government for the second official commission, and they are large. In twenty-two towns where inoculation was performed the inhabitants divided into 104,561 not inoculated and 30,491 inoculated; among the inoculated there were 387 attacks of cholera, or 12 per thousand, and 104 deaths, or 3 per thousand; among the non-inoculated, 8,406 attacks, or 77 per thousand, and 3,512 deaths, or 33 per thousand. Shakespeare's arithmetic on those numbers makes the liability of the inoculated to attack 6.06 times less, and to death 9.87 times less, than that of the non-inoculated.
Those are observational figures from an uncontrolled campaign, and the objection made at the time is the one a modern reader would make. Critics charged that the records did not sufficiently indicate the hygienic and physical condition of the subjects and that "the vast majority of those profiting by the opportunity to receive the anti-choleraic inoculations were of the middle and upper classes, and therefore not of that class of the inhabitants who are notoriously most liable to attack and death from cholera". Shakespeare concedes the criticism "may have some justness as respects some, perhaps many, of the villages" and defends only those villages where three-fourths or four-fifths of the inhabitants were inoculated.
The verdict that shaped the international reputation of the work was French and it was hostile. Shakespeare records that "the first public onslaught upon these statistics of which the world, outside of Spain, had much knowledge, was made in the report of the French Commission, with Dr. Brouardel at its head", presented to the Minister of Commerce after the commission returned from Spain in the summer of 1885; it charged that the results had been collected by physicians who were partisan supporters of Ferran, that they possessed no adequate official character and that they lacked sufficient detail. "As far as I can learn," Shakespeare adds, "the general impression entertained throughout the world of the value of the inoculation statistics is based, in the main, upon this report of the French Commission."
Shakespeare's counter-argument is procedural rather than medical, and it turns on who signed the returns. The official statistics were signed first by the physicians of the locality, then by the judge of the municipal court and sometimes the president judge of the judicial district, the parochial priest and the mayor, with signatures and seals attested by an authorised notary. He adds the political fact that makes the point bite: the hostility of the Minister of the Interior at Madrid to Ferran was "a well-known fact now generally admitted", and that of the civil governor of Valencia was greater still - so the officers who collected and attested the later figures cannot reasonably be called Ferran's partisans.
The witness states his own bias before giving his evidence, which is why this source is worth reading rather than paraphrasing. Shakespeare records that unfavourable impressions of Ferran had been formed by him from the world medical and secular press, and that before leaving America and again in London and Berlin he had been advised by physicians he respected "that a personal investigation of the Ferran question was now beneath the dignity of serious scientific consideration". He went to Tortosa anyway, watched Ferran make cultures and cover-glass preparations, and wrote that if there are more beautifully stained microscopic preparations of the comma bacillus anywhere in Europe he had never seen them, and that he found cultures as pure and perfect "as I have seen such cultures anywhere else in the world, not even excepting the laboratories of Berlin or Paris". He left Tortosa, he says, with a very different opinion than he had entertained before the visit.
The same pages record what does not flatter. The laboratory was a single room without windows or door except into an adjoining consulting cabinet, its shelves and apparatus "somewhat dusty", dust and dirt visible between the wooden gratings of the floor, and no water-closet that the visitor could see; and Shakespeare notes in passing the charge made by Ferran's adversaries that he had unjustifiably obtained wealth "by the exaction of enormous fees for the performance of his inoculations", a charge he answers only by observing that the house showed no external evidence of it.
Modern reviews of vaccine history credit Ferran with the first cholera vaccine used in human beings, and they do not agree on the year. A 2015 review states that "the first cholera vaccine used to immunize humans was actually a live vaccine developed by Jaime Ferran (1852-1929), which provided a high level of protection during the 1884 epidemic in Spain"; a 2014 review of cholera vaccines states that "the first cholera vaccine was developed by Ferran in 1885 and used in mass vaccination campaigns in Spain". The discrepancy between 1884 and 1885 is in the modern literature, not in the contemporary report, which places the mass inoculations in the epidemic of 1885.
What the anchor source is and is not should be stated plainly. It is an official United States government report, printed in 1890, by an investigator who examined Ferran's laboratory himself but who did not collect the inoculation statistics he reproduces; and it is avowedly corrective rather than neutral in its selection of documents - "in view of the great extent of the anti-Ferran literature, I deem it just to introduce in this report also some of the literature in defense of Ferran, so that the people of this country may know both phases of the question". It establishes what was done, what was claimed and what was objected. It does not establish, and nothing read here establishes, that the inoculations conferred the protection the figures suggest: there was no randomisation, no blinding and no independent replication of the campaign.