How a scientist from Odessa saved the 20th century from plague and cholera. Essay on the biography and scientific activities of Vladimir Haffkine

The fifth essay in the “Creators” series is ded­i­cat­ed to Vladimir (Waldemar) Haffkine, the cre­ator of the first effec­tive vac­cines against cholera and plague. At the end of the 19th cen­tu­ry, Haffkine car­ried out the first mass vac­ci­na­tion in India. His lab­o­ra­to­ries have devel­oped and pro­duced tens of mil­lions of dos­es of cholera and plague vac­cines. In the “Creators” project, T-inavari­ant, togeth­er with RASA (Russian-American Science Association) and with the sup­port of the Richard Lounsbery Foundation, con­tin­ues to pub­lish a series of bio­graph­i­cal essays about peo­ple from the Russian Empire who made a sig­nif­i­cant con­tri­bu­tion to world sci­ence and tech­nol­o­gy, about those to whom we owe our new reality.

In the late 1950s, Nobel lau­re­ate Selman Waksman, the cre­ator of strep­to­mycin, wrote a book about Vladimir Haffkine(1). He wrote with grat­i­tude and sym­pa­thy about the search and dis­cov­ery, about Haffkine’s hard field work in India, about the mis­takes and accu­sa­tions brought against Haffkine. Waksman under­stood Haffkine, prob­a­bly like no one else. This book became the basis of our essay.

Ukraine. Odessa. Early years

Waldemar Mordechai Wolf Haffkin (russ­ian: Владимир Аронович Хавкин, Vladimir Aronovich Khafkin, ukrain­ian: Володимир Мордехай-Вольф Хавкін) was born on March 3, 1860 (old style) or March 15, new style in Odessa in the Russian Empire in the fam­i­ly of Aaron and Rosalia (née Landsberg) Haffkine. Waldemar Haffkin’s father came from a Jewish mer­chant fam­i­ly and was raised in the spir­it of Western cul­ture. He was not par­tic­u­lar­ly reli­gious, but the boy absorbed the prin­ci­ples and foun­da­tions of Judaism from child­hood. His moth­er died when Vladimir (Waldemar) was still just a child. The fam­i­ly moved to Berdiansk on the Azov Sea, where his father worked as a teacher.

At first, Haffkin was edu­cat­ed at home, and in 1870-1872, at a local school. At the age of 12 he entered the Berdiansk gym­na­si­um. Here he excelled in sports and espe­cial­ly in the nat­ur­al sci­ences. In 1879, he grad­u­at­ed from high school and entered the nat­ur­al sci­ences depart­ment of Novorossiysk University in Odessa (also known as ‘Odesa University’ or ‘Odesa National University’). His father was too poor to sup­port a young man in a big city. Waldemar’s old­er broth­er came to his aid and gave him 10 rubles a month. The uni­ver­si­ty paid a kind of stipend, that is, it gave out 20 kopecks a day for food. This was enough for Haffkin to some­how make ends meet. He was pas­sion­ate about sci­ence and from his ear­li­est youth was full of sym­pa­thy for peo­ple. This lat­er deter­mined his life.

At the uni­ver­si­ty, Haffkine stud­ied physics, math­e­mat­ics and zool­o­gy. Very soon, Ilya Metchnikoff, who at that time was a pro­fes­sor of zool­o­gy at Odesa University, became his teacher. And Haffkine also decid­ed to become a zool­o­gist. But it was­n’t just sci­ence that wor­ried him.

On March 1, 1881, Tsar Alexander II was assas­si­nat­ed by mem­bers of the rev­o­lu­tion­ary orga­ni­za­tion “Narodnaya Volya” (People’s Will). On March 18, 1882, in Odessa, on Nikolaevsky Boulevard, “Narodnaya Volya” mem­ber Nikolai Zhelvakov shot mil­i­tary lawyer Major General Vasily Strelnikov at point-blank range. The prepa­ra­tions for the mur­der were car­ried out by the famous rev­o­lu­tion­ary, mem­ber of the “Narodnaya Volya”, Vera Figner.

Students from Odesa University also took part in the activ­i­ties of “Narodnaya Volya” in Odessa. There is note­wor­thy infor­ma­tion that Haffkine was also asso­ci­at­ed with Narodnaya Volya, was arrest­ed and spent some time in prison (Haffkine’s biog­ra­ph­er Mark Popovski writes about this in the book “The Fate of Doctor Haffkine” (1963) (2).

The con­ser­v­a­tive regime of the new Tsar, Alexander III, took harsh mea­sures to sup­press the ter­ror­ist move­ment in uni­ver­si­ties and through­out the coun­try. Many stu­dents were arrest­ed and exiled, some were exe­cut­ed (Nikolai Zhelvakov was hanged by deci­sion of a mil­i­tary court 4 days after the mur­der of Strelnikov).

The gov­ern­ment and the mass­es found the main “cul­prits” for the tur­moil quite quick­ly — they turned out to be Jews. Jewish pogroms began in Odessa. (In 1887, a “per­cent­age norm” was intro­duced for Jews in gym­na­si­ums and uni­ver­si­ties: Jews in these edu­ca­tion­al insti­tu­tions could not exceed a cer­tain pro­por­tion. Haffkine was no longer affect­ed by this restric­tion, but it great­ly influ­enced the lives of many oth­er Jews, includ­ing Selman Waksman).

Officials, the press and stu­dent orga­ni­za­tions began a sys­tem­at­ic attack not only on indi­vid­ual Jews, but also on entire com­mu­ni­ties, which were called the main cause of all the trou­bles that befell the Russian Empire. Many Christian stu­dents at uni­ver­si­ties formed para­mil­i­tary groups that attacked Jews and incit­ed pogroms.

To pro­tect them­selves from pogroms, Jews, not par­tic­u­lar­ly count­ing on help from the author­i­ties, orga­nized self-defense. On May 3-5, 1881, when the pogrom began in Odessa, self-defense act­ed quite suc­cess­ful­ly. But the police not only did not pro­tect the Jews, they arrest­ed about 150 self-defense par­tic­i­pants. Among those arrest­ed was Waldemar Haffkine. He was cap­tured with a revolver in his hand. In fact, the self-defense had few weapons — most­ly axes, clubs and iron rods. The fact that Haffkine had a revolver can be con­sid­ered an indi­rect con­fir­ma­tion of his con­nec­tion with Narodnaya Volya: pro­fes­sion­al rev­o­lu­tion­ar­ies had weapons. After the arrest, the sit­u­a­tion for Haffkine was very dif­fi­cult. He was threat­ened with more than just exile. But the teacher saved him.

Professor Metchnikoff learned about the arrest and imme­di­ate­ly came to the student’s aid. Metchnikoff act­ed as a wit­ness for the defense. His author­i­ty was so great that he man­aged to save Haffkine from per­se­cu­tion by the author­i­ties. And Haffkine not only was released, but remained at the uni­ver­si­ty and received a diplo­ma in 1883. He pre­sent­ed a the­sis on zoology.

As a result of per­se­cu­tion and imposed restric­tions, mass emi­gra­tion of Jews from the Russian Empire began, espe­cial­ly often they left for the United States. But Haffkine decid­ed to stay in Odessa and pre­pare for a sci­en­tif­ic career.

Odessa at that time was one of the world’s largest micro­bi­ol­o­gy cen­ters. Not only Haffkine’s teacher, Nobel lau­re­ate Ilya Metchnikoff, worked there, but also epi­demi­ol­o­gist Nikolay Gamaleya, micro­bi­ol­o­gist Alexandre Besredka (he lat­er worked fruit­ful­ly with Metchnikoff at the Pasteur Institute in Paris), and many oth­ers. It was in Odessa in 1882 that Metchnikoff dis­cov­ered the phe­nom­e­non of phago­cy­to­sis, and at the con­gress of Russian nat­u­ral­ists and doc­tors in 1883 he deliv­ered his famous report on the body’s defens­es. Thus, one of the most impor­tant bio­log­i­cal sci­ences today — immunol­o­gy — was found­ed. In 1886, Metchnikoff and Gamaleya orga­nized the first Pasteur Station out­side France (Odessa Bacteriological Station) in Odessa.

After receiv­ing his diplo­ma, Haffkine went to work at the Zoological Museum of Odessa, where he spent the next five years (1883-1888). Since he refused to be bap­tized, he could not count on a pro­fes­sor­ship, but he was pro­vid­ed with a lab­o­ra­to­ry equipped specif­i­cal­ly for his work. During this peri­od, Haffkine pub­lished five impor­tant sci­en­tif­ic works on the nutri­tion and hered­i­tary char­ac­ter­is­tics of sin­gle-celled organ­isms. He par­tic­i­pat­ed in the trans­la­tion from German into Russian of Klaus’s trea­tise on zool­o­gy. He became a real scientist.

But the restric­tions imposed on Jews became increas­ing­ly strict, and Haffkine’s aca­d­e­m­ic career was closed. In 1888, an event occurred that decid­ed every­thing for the young sci­en­tist: his favorite teacher, Ilya Mettchnikoff, went to work at the Pasteur Institute in Paris.

According to Metchnikoff’s wife Olga, the great sci­en­tist explained the rea­son for his depar­ture: “Thus it was in Paris that I suc­ceed­ed at last in prac­tis­ing pure Science apart from all pol­i­tics or any pub­lic func­tion. That dream could not have been realised in Russia because of obsta­cles from above, from below, and from all sides. One might think that the hour of sci­ence in Russia has not yet struck. I do not believe that. I think, on the con­trary, that sci­en­tif­ic work is indis­pens­able to Russia, and I wish from my heart that future con­di­tions may become more favor­able in the future.” (3)

Emigration

At first, Haffkine chose Switzerland. Many Jews from the Russian Empire went there to receive uni­ver­si­ty edu­ca­tion and work in the field of nat­ur­al sci­ences and med­i­cine. In 1888, Haffkine was appoint­ed assis­tant in phys­i­ol­o­gy to Professor Morris Schiff at the Faculty of Medicine of the University of Geneva.

Selman Waksman recalls vis­it­ing the University of Geneva almost 40 years lat­er. He spoke with the uni­ver­si­ty’s pro­fes­sor, Richard Schodat, who told him that before the 1917 rev­o­lu­tion, 90% of stu­dents in Swiss med­ical schools were Russian Jews. Of course, it wasn’t because of a good life that this hap­pened. But this was a chance.

Haffkine stayed in Switzerland for a year. Although every­thing seemed to be going well, there was only one place in the world where he want­ed to work — the Pasteur Institute. And in 1889, Haffkine left Geneva for Paris. His teacher, Ilya Metchnikoff, worked there, and Louis Pasteur worked there. The most advanced sci­ence was there.

Haffkine was very inter­est­ed in the work car­ried out in Paris on the occur­rence of dis­eases in humans and ani­mals under the influ­ence of microbes and the cre­ation of vac­cines to pro­tect humans and ani­mals from bac­te­r­i­al infec­tions. And it was in this sci­en­tif­ic field that he sub­se­quent­ly achieved out­stand­ing success.

But Haffkine’s first appoint­ment at the Pasteur Institute was as an assis­tant librar­i­an. Early in the morn­ing before the library opened and late in the evening after it closed, Haffkine could work in the lab­o­ra­to­ry of Emil Roux. His only hob­by at that time, besides work and books, was the vio­lin. His love of music found sym­pa­thy among oth­er Odessa emi­grants. Metchnikoff him­self loved to lis­ten to him.

Haffkin worked at the Pasteur Institute on the pro­to­zoa Paramecium (Paramecium Caudatum). He inves­ti­gat­ed the nature of the infec­tious dis­ease of these pro­to­zoa. In 1890, he pub­lished a work devot­ed to these stud­ies in the jour­nal “Annales de l’Institut Pasteur”. These stud­ies led him to study the nature of adap­ta­tion to the envi­ron­ment in cil­i­ates and bac­te­ria, which result­ed in anoth­er sci­en­tif­ic work enti­tled “Contribution to the Study of Immunity” (1890) (4).

At this time, Haffkine also con­duct­ed research into typhoid fever. Metchnikoff not­ed the work of Haffkine, where he showed that var­i­ous forms of typhoid bacil­li “adapt to life in the watery con­tents of a rabbit’s eye, but die when sud­den­ly trans­ferred to the broth, which pre­vi­ous­ly was a good medi­um for their growth. The typhoid bacil­lus, accus­tomed to liv­ing in broth, quick­ly dies when trans­ferred to a blood envi­ron­ment, but, grad­u­al­ly adapt­ing to such an envi­ron­ment, grows in it even bet­ter than in broth.” Then Haffkine will find his knowl­edge of grow­ing crops in var­i­ous envi­ron­ments very use­ful. His fate was such that every­thing he did was prepa­ra­tion for the main task of his life — the cre­ation of vaccines.

Cholera research begins

Both his own research and the entire sci­en­tif­ic sit­u­a­tion at the Pasteur Institute led to Haffkine becom­ing inter­est­ed in cholera.

Robert Koch, the famous German bac­te­ri­ol­o­gist, went to Egypt and India in 1883, where he man­aged to iso­late a pure cul­ture of Vibrio choler­ae, which, as Koch him­self was sure, was the cause of the dis­ease. Not all sci­en­tists accept­ed Koch’s the­o­ry, but not at the Pasteur Institute: here Koch was sup­port­ed and Vibrio choler­ae was stud­ied seri­ous­ly. Waldemar Haffkine also joined these studies.

He first demon­strat­ed that when pass­ing through guinea pigs, Vibrio choler­ae increased its vir­u­lence, which was an impor­tant argu­ment in favor of the infec­tious nature of the dis­ease. Haffkine then man­aged to obtain a weak­ened drug by grow­ing vib­rio in a stream of air.

In 1892, Haffkin pub­lished a short paper on cholera in the guinea pig, where he described his new method; in the same year anoth­er note was pub­lished about cholera in a rab­bit and a pigeon. As a result of inoc­u­lat­ing ani­mals first with a weak­ened drug, and then intro­duc­ing them with a more vir­u­lent cul­ture, a high degree of immu­ni­ty was obtained.

In fact, Haffkine has already done every­thing. The the­o­ry of the cholera vac­cine was cre­at­ed. He learned to strength­en vib­rio, that is, increase its con­cen­tra­tion by pas­sage, and weak­en the cul­ture by grow­ing it in the open air (lat­er Haffkine used heat­ing to weak­en the culture).

Vaccination with a weak­ened vac­cine “trig­gered” the immune sys­tem, and the sec­ond vac­ci­na­tion strength­ened it (this is a kind of “boost­er” vac­ci­na­tion). Everything worked in ani­mals. But how far it was from actu­al­ly using the vac­cine on humans!

The suc­cess­es achieved by Haffkine impressed Pasteur so much that when Prince Damrui, broth­er of the King of Siam, called the Institute and asked Pasteur to give him a cure for cholera, the famous sci­en­tist turned direct­ly to Haffkine.

In 1892, Pasteur asked the Russian gov­ern­ment for per­mis­sion to test the method in the Russian Empire, where cholera was ram­pant at the time, but the request was reject­ed. The epi­dem­ic grew and in 1893 came to St. Petersburg. On November 1, 1893, Pyotr Ilyich Tchaikovsky died of cholera. Perhaps if the Russian author­i­ties had lis­tened to Pasteur and Haffkine and start­ed vac­ci­na­tion on time, many, many peo­ple could have been saved. And Tchaikovsky would have lived for many more years.

In 1892, Haffkine was appoint­ed to a research posi­tion at the Pasteur Institute and con­tin­ued to work on cholera.
At this time, a cholera epi­dem­ic began in India and Indochina (the fifth in the 19th cen­tu­ry). From there, the dis­ease spread through­out Asia and already threat­ened European countries.

In 1890, the Spanish bac­te­ri­ol­o­gist Jaime Ferran y Clua, build­ing on Pasteur’s ideas about immu­niz­ing the body by intro­duc­ing weak­ened or dead microbes that cause infec­tion, attempt­ed to cre­ate a cholera vac­cine using a live cul­ture. But Ferran’s report of the cre­ation of a cholera vac­cine has been dis­put­ed. He failed to devel­op the cor­rect dosages and, as a result, caused cholera infec­tion with his vac­ci­na­tion more often than he pro­tect­ed against the dis­ease. What Ferran couldn’t do and what Haffkine could do: con­trol the strength of the vaccine.

In addi­tion, Ferran encoun­tered seri­ous resis­tance from church author­i­ties, who were against vac­ci­na­tion in prin­ci­ple. We all know the argu­ments of anti-vaxxers well from the recent COVID-19 pan­dem­ic. For more than a hun­dred years they have changed lit­tle. Pasteur wrote that there was no evi­dence of the prac­ti­cal ben­e­fits of the Ferran vaccine.

Unlike Ferran, Haffkine has moved far ahead. He obtained a high­ly active cul­ture by suc­ces­sive­ly pass­ing the cholera pathogen through ani­mals. And then he weak­ened it by grow­ing it at a high tem­per­a­ture (39°C) and inject­ed it sub­cu­ta­neous­ly into guinea pigs. The result was absolute immunity.

On July 9, 1892, Haffkin pre­sent­ed the results of his first exper­i­ments at the Paris Biological Society in a work enti­tled “Asian cholera in guinea pigs.” He soon began exper­i­ment­ing with rab­bits and pigeons. Treatment of these immu­nized ani­mals with active cul­tures obtained from Assam (Indochina) and Ceylon did not cause any path­o­gen­ic effect: the Russians were pro­tect­ed from cholera, which was killing tens of thou­sands of people.

Thus, Haffkine pro­posed using a weak­ened cul­ture rather than an active one for vac­ci­na­tion pur­pos­es. Haffkine believed that this method would pro­tect the human and ani­mal body from cholera infec­tion. Having con­vinced him­self of the harm­less­ness of the new vac­cine by vac­ci­nat­ing ani­mals, Haffkine began vac­ci­nat­ing people.

On July 18, 1892, he inject­ed him­self sub­cu­ta­neous­ly with a large dose of a weak­ened cholera vac­cine. He devel­oped a fever, a headache, and felt weak. Six days lat­er, one of his emi­grant friends from the Russian Empire gave Haffkine a sec­ond dose of the vac­cine. The tem­per­a­ture rose again, but the gen­er­al weak­ness was more short-lived.

Science his­to­ri­an Marina Sorokina writes about Haffkine’s first exper­i­ments on humans: “After that, he car­ried out a sim­i­lar exper­i­ment on three vol­un­teers from Russia (Georgiy Yavein, Mikhail Tomamshev and Ivan Vilbushevich) and came to the con­clu­sion that a per­son acquires immu­ni­ty to cholera infec­tion in six days after the sec­ond vac­ci­na­tion. He lat­er vac­ci­nat­ed oth­er vol­un­teers, one of whom was Ernest Hanbury Hankin (1865 – 1939), a fel­low at St John’s College, Cambridge. A chemist and bac­te­ri­ol­o­gist who stud­ied malar­ia, cholera and oth­er dis­eases, work­ing in the north­west­ern provinces of India, Hunkin became an active and effec­tive assis­tant and sup­port­er of Haffkine. It was he who pub­lished infor­ma­tion about Haffkine’s method in the British Medical Journal, talk­ing in detail about the new drug and his per­son­al expe­ri­ence of vaccination.”

Bacteriologist E. Podolsky in his work “The first prob­lem that Haffkine had to solve in his search for a rem­e­dy for cholera was the fix­ing of a cholera virus to a well-defined strength. He solved this prob­lem in the fol­low­ing man­ner: by atten­u­a­tion of the virus - that is, the cholera germ - and by exal­ta­tion of the virus. The vir­u­lence of the germ is dimin­ished by pass­ing a cur­rent of ster­ile air over the sur­face of the cul­tures, or by var­i­ous oth­er meth­ods. The vir­u­lence is exalt­ed or increased by the method of pas­sage; that is, by grow­ing the germ in the abdo- men in a series of guinea pigs. By the lat­ter method, the vir­u­lence after a time is increased twen­ty­fold, i.e., the fatal dose has been reduced to a twen­ti­eth of the orig­i­nal. Cultures treat­ed in this way con­sti­tute the virus exalté. Injection of the virus exalté under the skin of an ani­mal pro­duces a local destruc­tion of tis­sue fol­lowed by the death of the ani­mal. But if the ani­mal be treat­ed first with the atten­u­at­ed virus, the sub­se­quent injec­tion of the virus exalté pro­duces only a swelling of the tis­sue at the site of the injec­tion. After inoc­u­la­tion first of the atten­u­at­ed and after- wards of the exalt­ed virus, the guinea pig acquires a high degree of immu­ni­ty. Dr. Haffkine also proved the harm­less­ness of the vac­cine by inoc­u­lat­ing him­self with it and by care­ful and patient obser­va­tion on oth­er sci­en­tists who allowed them­selves to be inoc­u­lat­ed. This was the first stage of Haffkine’s researches.”(5)

But not all sci­en­tists believed not only in the pos­si­bil­i­ty of vac­ci­na­tion, but even in the bac­te­ri­o­log­i­cal caus­es of the dis­ease itself. And among the oppo­nents there were seri­ous specialists.

In a let­ter writ­ten on November 20, 1892, Louis Pasteur wrote: “Do you know that a new great dis­cov­ery may be in prepa­ra­tion regard­ing cholera? Pettenkoffer reports in his pub­li­ca­tion from Munich that he swal­lowed a cubic cen­time­ter of pure cul­ture of the vir­u­lent bacil­lus with­out expe­ri­enc­ing any dis­com­fort except a slight diar­rhea; that he not­ed a very abun­dant cul­ture of this bacil­lus in his intestines; that anoth­er researcher had done the same thing with the same results; that the riv­er in Munich, into which their excre­ment fell (which sci­en­tists are cau­tious­ly keep­ing silent about), gave a cul­ture of the bacil­lus in large quan­ti­ties, and that cholera did not man­i­fest itself in any of the res­i­dents… Haffkine learns about all this with some con­ster­na­tion. For eight days now he has been in London to ask the English author­i­ties for per­mis­sion to trav­el to Calcutta to con­duct an exper­i­ment that he intend­ed to car­ry out in the king­dom of Siam.”(6)

The exper­i­ment of Max Pettenkofer — an out­stand­ing hygien­ist and, of course, a brave man — has gone down in his­to­ry as clear evi­dence of the readi­ness of doc­tors and sci­en­tists to sac­ri­fice them­selves. But he did not believe that Vibrio choler­ae was the cause of the dis­ease. This is a case where sense­less courage could lead not only to the death of the sci­en­tist him­self, but also to a real epi­dem­ic. Why did nei­ther one nor the oth­er hap­pen? It was just luck.

Haffkine was ready to test the effec­tive­ness of his vac­cine against human infec­tion in those areas where cholera caused epi­demics and spread rapid­ly. To this end, he first planned the trip to Siam men­tioned by Pasteur.

By coin­ci­dence, the British ambas­sador in Paris, Lord Dufferin, the for­mer Viceroy of India, learned of Haffkine’s research on cholera. He sent a let­ter to the British Secretary of State for India and Lord Lansdowne, then Viceroy of India, offer­ing to give Haffkine the oppor­tu­ni­ty to con­tin­ue his research on cholera in India.

Path to India

Having received an invi­ta­tion from the British author­i­ties, Haffkine arrived in London and gave a series of lec­tures at research lab­o­ra­to­ries and King’s College. These lec­tures, devot­ed main­ly to his ideas about pre­ven­tive vac­ci­na­tion against cholera, were well received. He was giv­en the oppor­tu­ni­ty to go to India and arrived in Calcutta in March 1893. There he imme­di­ate­ly began his work. Calcutta was cho­sen because it was con­sid­ered the most cholera-affect­ed part of the country.

His clos­est friend and com­rade-in-arms, W. J. Simpson, lat­er described Haffkine’s work in India. He stat­ed that Haffkine had been able to prove that he had had a vac­cine that had pro­tect­ed ani­mals from the fatal dis­ease caused by cholera bacil­lus. The harm­less­ness of the vac­cine had been estab­lished through very care­ful and patient obser­va­tions of the doc­tors and sci­en­tists who had been vac­ci­nat­ed after the dis­cov­ery… After train­ing Simpson’s lab­o­ra­to­ry assis­tants in the method of prepar­ing vac­cines, he had accept­ed an invi­ta­tion to Agra, where 900 peo­ple had been vac­ci­nat­ed. According to Simpson’s account, after the start of vac­ci­na­tions, requests to send the vac­cine from dif­fer­ent places in Northern India came so often that Haffkine could not ful­fill them all. However, with­in a year he had vac­ci­nat­ed around 25,000 people.(7)

The result of two years of vac­ci­na­tions and stud­ies showed that, despite the incom­plete pro­tec­tive effect of the first four days and the grad­ual dis­ap­pear­ance of resis­tance in those vac­ci­nat­ed with a weak dose of the vac­cine, which a sig­nif­i­cant part of the vac­ci­nat­ed received dur­ing the first six months, the mor­tal­i­ty rate among vac­ci­nat­ed com­pared to unvac­ci­nat­ed peo­ple decreased by more than 72 %. Subsequently, this ratio improved and amount­ed to 80%. In addi­tion to the evi­dence of the effec­tive­ness of vac­ci­na­tions obtained from direct obser­va­tion of humans dur­ing cholera epi­demics, an inter­est­ing set of exper­i­ments car­ried out by Professor Koch, Professor Pfeiffer and Dr. Kolle in 1896 allowed them to prove the pro­tec­tive prop­er­ties of vac­ci­na­tions in anoth­er way. They vac­ci­nat­ed a large num­ber of stu­dents and doc­tors with the Haffkine vac­cine and dis­cov­ered that the serum of the vac­ci­nat­ed had a rapid and absolute­ly destruc­tive effect on Vibrio cholerae.”

The sup­port of his col­leagues and, first of all, Koch helped Haffkine a lot and con­vinced many doubters. Koch was con­vinced that Haffkine was on the right track.


Haffkine inoc­u­lates the local pop­u­la­tion against cholera. Calcutta, 1894, pho­to from the archives of the Wellcome Institute for the History of Medicine in London.

Haffkine was not a doc­tor, he was first and fore­most a zool­o­gist and then became a bac­te­ri­ol­o­gist. When he arrived in Calcutta, he ini­tial­ly met with fierce resis­tance from both the local pop­u­la­tion and British offi­cials. It was only when he had him­self and four Indian doc­tors who accom­pa­nied him to the first vil­lage in Upper Bengal, where cholera was ram­pant, vac­ci­nat­ed that he was able to con­vince the inhab­i­tants that the vac­ci­na­tions were safe.

Volunteers came for­ward and in one day 116 of the 200 inhab­i­tants were vac­ci­nat­ed. Encouraged by the ini­tial results, Khavkin embarked on an expe­di­tion last­ing almost two and a half years, which led from Agra through Bengal, Assam, the north-west­ern provinces, Punjab and Kashmir.

At the same time, many news­pa­pers ran active pro­pa­gan­da against him and even claimed that he was a Russian spy. Opponents of small­pox vac­ci­na­tion also direct­ed their attacks against Haffkine, espe­cial­ly after he had suc­cess­ful­ly vac­ci­nat­ed two reg­i­ments of sol­diers sta­tioned in Lucknow. Many British offi­cials wrote that the vac­cine was at best too weak to have any sig­nif­i­cant impact on the course of the epi­dem­ic. The reli­gious beliefs of some tribes were against vac­ci­na­tion. There were even rumors that some Muslims in East Bengal tried to poi­son the “white doc­tor” with snake venom.

The prob­lems that Haffkine faced were described by bac­te­ri­ol­o­gist R. Pollitzer, the author of a fun­da­men­tal work on cholera, as fol­lows: “The dif­fi­cul­ties of apply­ing Haffkine’s method of vac­ci­na­tion against cholera on a wide scale were enor­mous. As he him­self admit­ted, a par­tic­u­lar­ly dif­fi­cult task was main­tain­ing a suf­fi­cient quan­ti­ty of vib­rio of a fixed strength through the con­tin­u­ous pas­sage of ani­mals. In large-scale prac­tice it was often impos­si­ble to admin­is­ter sec­ond dos­es, so that of the 40 thou­sand peo­ple vac­ci­nat­ed before 1895 in India using the Haffkine method, only a third received them.”

In the sum­mer of 1895, a report was pub­lished in Calcutta on the report of the gov­ern­ment bac­te­ri­ol­o­gist Haffkine on two and a half years of work in India. It pre­sent­ed the results of a sur­vey of 42 thou­sand peo­ple. The report empha­sized that cholera vac­ci­na­tion had ful­ly met all expec­ta­tions. Mortality from cholera fell by 72%.

Haffkine wrote in an 1895 arti­cle: “The evi­dence so far accu­mu­lat­ed speaks strong­ly in favor of cholera vac­ci­na­tion, and my own con­vic­tion in this mat­ter is becom­ing more and more strength­ened. However, the spe­cial respon­si­bil­i­ty that lies with me in this mat­ter forces me to note that the num­ber of obser­va­tions is not yet very large; it is desir­able that the results obtained be con­firmed by new and more exten­sive statistics. 

When, in relat­ing to Professor Koch the data of my report to the Government of India, I said that, in my opin­ion, the results obtained proved the effec­tive­ness of the method, but that I con­sid­ered it nec­es­sary to do every­thing pos­si­ble to con­firm them with new obser­va­tions, I was very glad to learn that for Professor Koch the demon­stra­tion has already been com­plet­ed; that he con­sid­ers the pro­tec­tive pow­er of the method to be con­clu­sive­ly estab­lished by the obser­va­tions so far col­lect­ed in India; that fur­ther improve­ments and sim­pli­fi­ca­tions are pos­si­ble, but that the main ques­tion, the main part of the prob­lem, is solved by the facts record­ed in the above report.”

As we not­ed above, Koch already had his own argu­ments in favor of the Haffkine cholera vaccine.

Return to Europe

For con­tin­u­ous hard work for two and a half years, Haffkine had to pay a heavy price. In August 1895, he was lying in a Calcutta hotel room suf­fer­ing from malar­ia. He was asked to leave India, but feel­ing that his task was not yet com­plet­ed, he asked the Indian author­i­ties for per­mis­sion to return.

In Europe, Haffkine first went to Germany and France. He pre­sent­ed Koch with the data con­tained in his report to the Government of India, and empha­sized that he con­sid­ered it nec­es­sary to do every­thing pos­si­ble to con­firm his results with new obser­va­tions. Koch was very pleased with these results and told Haffkine that he con­sid­ered the demon­stra­tion to be com­plete, that the pro­tec­tive pow­er of vac­ci­na­tion had been ful­ly proven.

Haffkine then went to London, where in December 1895 he pre­sent­ed a report to the joint coun­cil of the Royal Colleges of Physicians and Surgeons on the results of the use of anti cholera drugs.

At the con­clu­sion of his lec­ture, he said: “Mr. Chairman and gen­tle­men, on the day when I came back from my expe­di­tion to India, I found my for­mer chief, M. Pasteur, lying on his bed of death. Whatever might have been his appre­ci­a­tion of the work done in India, there can be only one desire on my part, that all the hon­our for the results which may pos­si­bly come out of my efforts, should be referred to him, to his sacred memory.”(8)

Discussing Haffkine’s speech on December 21, 1895, the British Medical Journal described his work in India to pre­vent cholera: “Dr. Haffkine’s work is of the high­est sci­en­tif­ic val­ue and promis­es to con­fer a great boon on our Indian Empire. It has been car­ried out under cir­cum- stances of the most remark­able self-sac­ri­fice and devo­tion to the inter­ests of human­i­ty and of sci­ence. He has giv­en many of the best years of his life to this research, and has with unweary­ing indus­try and trans­par­ent sin­cer­i­ty worked out in India all the details which can test the val­ue of this new gift of sci­ence to life-sav­ing pur­pos­es with­out fee or reward oth­er than his own con­science, his love of human­i­ty, and his sci­en­tif­ic devo­tion. Dr. Haffkine has with steady dili­gence and unques­tion­able enthu­si­asm braved every dan­ger, and endured the extremes of cli­mate and of unhealthy sea­sons. He has lis­tened to the appeals from every direc­tion regard­less of per­son­al risk and unmind­ful of his own health, which has suf­fered great­ly. He returned to Europe great­ly debil­i­tat­ed by the con­tin­u­ous tri­als of his ardu­ous labours.” (9) This was great recognition.

Cholera vac­ci­na­tions have been so suc­cess­ful that a large num­ber of reports have been pub­lished on the effec­tive­ness of vac­ci­na­tion in reduc­ing mor­bid­i­ty and mor­tal­i­ty. The high demand has led to numer­ous lab­o­ra­to­ries being set up in India to pro­duce the vac­cine. The Indian gov­ern­ment was asked to pro­vide finan­cial assis­tance to Haffkine. In March 1896 he returned to India (Calcutta). In the course of fur­ther work, he man­aged to vac­ci­nate anoth­er 30 thou­sand peo­ple against cholera.

Plague pandemic

Soon after Haffkine returned to India, the gov­ern­ment of the coun­try asked him to go to Bombay to find out the cause of the bubon­ic plague epi­dem­ic that had begun there. The gov­ern­ment hoped that Haffkine would be able to devel­op a vac­cine against this disease.

Haffkine arrived in Bombay on 7 October 1896 and imme­di­ate­ly began set­ting up a lab­o­ra­to­ry at Grant Medical College. The lab­o­ra­to­ry con­sist­ed of one room and a cor­ri­dor. The entire staff con­sist­ed of one clerk and three assis­tants. Haffkine lived in the same college.

The plague epi­dem­ic that swept through India at that time was described by Colonel S.S. Sokhei, long-time direc­tor of the Haffkine Institute: “The present pan­dem­ic plague which spread from Yunnan to Canton and to Hong Kong in 1894 reached Bombay in 1896, and in a few years invad­ed the whole of India. It also spread to many oth­er parts of the world like Australia, South Africa, North and South America, Egypt, sev­er­al Mediterranean Ports, England and France. This pan­dem­ic is now in a qui­es­cent state and is obvi­ous­ly on the way out.… The his­tor­i­cal records indi­cate that plague pan­demics have a char­ac­ter­is­tic cycli­cal course. Starting from one or oth­er of the endem­ic cen­tres pan­demics have spread over the world, raged with vary­ing inten­si­ty for a cen­tu­ry or more, caused great loss of life and came to an end of their own accord only to begin again after a lapse of rel­a­tive­ly long peri­ods of time.”(10)

A more detailed descrip­tion of the plague epi­dem­ic and Haffkine’s con­tri­bu­tion to the devel­op­ment of a suit­able vac­cine is giv­en by Podolsky: “It was in Hong Kong that the cause of the plague was dis­cov­ered. It was dur­ing an epi­dem­ic in 1894 that the Japanese Government sent Drs. Kitasato and Aoyama to inves­ti­gate the dis­ease. They arrived in Hong Kong on June 12th, and two days lat­er Dr. Aoyama made an autop­sy on one of the vic­tims and Dr. Kitasato found numer­ous bacil­li in the heart, blood, liv­er and spleen. Similar bacil­li were found also in a liv­ing vic­tim of plague on the same day. On June 15th cul­tures were devel­oped, and with the excep­tion of pigeons, all the ani­mals inoc­u­lat­ed by Kitasato died with the iden­ti­cal signs of plague in human beings.”(11)

Dr. Alexandre Yersin, sent by the French gov­ern­ment, arrived in Hong Kong on June 18 and inde­pen­dent­ly dis­cov­ered the same bacil­lus, which was named Bacillus Pestis (the plague bacil­lus was lat­er named Yersinia pestis in hon­or of Dr. Yersin).

Podolsky writes: “Some two years lat­er, in 1896, Bombay, which had an active trade with Hong Kong, was vis­it­ed by the plague. Bombay had been free from this dis­ease for near­ly two hun­dred years.… It was then quite appar­ent that the rats, trans­port­ed in the ships, were the car­ri­ers of the dis­ease. Stationed at Bombay was Waldemar Haffkine who had attained a rep­u­ta­tion as a very com­pe­tent bac­te­ri­ol­o­gist. It was up to Haffkine to attempt to find a method of con­trol­ling the plague.… After the dis­cov­ery of the plague germ by Kitasato and Yersin in 1894, many bac­te­ri­ol­o­gists under­took numer­ous inves­ti­ga­tions in this field. One of the most not­ed of these was Haffkine, who was inter­est­ed main­ly in devel­op­ing a vac­cine. He suc­ceed­ed in pro­tect­ing human beings against plague by the inoc­u­la­tion of killed cul­tures.” (12)

Three days after arriv­ing in Bombay, Haffkine began exper­i­men­tal work. If Yersin tried to cure the plague with an anti-plague serum, then Haffkine tried to devel­op a method of pre­vent­ing infec­tion, lead­ing to the devel­op­ment of immu­ni­ty against the dis­ease. The ques­tion was how to weak­en the plague microbe. Various meth­ods were test­ed: treat­ment with chlo­ro­form and phe­nol, heat­ing, dry­ing. Dried organs from ani­mals that died from plague have also been used as poten­tial vac­cines. Since not all bac­te­r­i­al cells died, the dry­ing method had to be aban­doned. Heating cul­tures to 65°C did not pro­vide immu­ni­ty in rats, although it was lat­er found to induce immu­ni­ty in humans. Haffkine worked 12-14 hours a day, while still man­ag­ing to give numer­ous lec­tures to doc­tors on the prob­lems of plague. One of his assis­tants became depressed, and the oth­er two, exhaust­ed by their hard work, left him. But he stayed.

In December 1896, the vac­cine was ready. Haffkine devel­oped a method for grow­ing microor­gan­isms in the form of sta­lac­tites by apply­ing a lay­er of coconut or ani­mal fat to the sur­face of the broth in a flask. To enhance growth, the flask was shak­en peri­od­i­cal­ly. After six weeks of incu­ba­tion, the cul­ture was heat­ed. The microbe died and turned into a full-fledged vac­cine. The first exper­i­ment was car­ried out on twen­ty fresh­ly cap­tured rats. Half of them were vac­ci­nat­ed, then an infect­ed rat was placed in a cage. Within 24 hours, nine unvac­ci­nat­ed rats fell ill, while all vac­ci­nat­ed rats remained healthy. The vac­cine also proved suc­cess­ful in pro­tect­ing rab­bits: after sub­cu­ta­neous injec­tion of a heat-ster­il­ized broth cul­ture, rab­bits acquired immu­ni­ty to the plague. In January 1897, Haffkine pub­lished his method of pre­ven­tive vac­ci­na­tion against plague.

Let’s remem­ber: Haffkine arrived in Bombay on October 7, 1896, and in January the vac­cine was ready — 3 months. Even COVID-19 vac­cines were not cre­at­ed at such a speed. Considering the con­di­tions under which Haffkine worked and the lev­el of sci­ence at the end of the 19th cen­tu­ry, this is a bit like a miracle.

On January 10, 1897, Haffkine inoc­u­lat­ed him­self with 10 mil­li­liters of the most pow­er­ful vac­cine prepa­ra­tion. This was done secret­ly, in the pres­ence of only two peo­ple: the doc­tor who admin­is­tered the vac­cine and the direc­tor of the col­lege. The vac­ci­na­tion caused a severe reac­tion, but this did not pre­vent Haffkine from con­tin­u­ing his work and tak­ing part in an impor­tant conference.

The call for vol­un­teers was suc­cess­ful, espe­cial­ly among col­lege stu­dents, both European and Indian, and among the Bombay intel­li­gentsia. Following Haffkin’s exam­ple, physi­cians and promi­nent cit­i­zens of Bombay pub­licly inoc­u­lat­ed them­selves to encour­age oth­ers to under­go sim­i­lar treatment.

Vaccinations were giv­en to half the pris­on­ers at the House of Correction where the plague broke out. This was an impor­tant expe­ri­ence: the pris­on­ers were in the same con­trolled con­di­tions and the result of the vac­ci­na­tion was clear. The vac­ci­na­tions worked. Almost none of the vac­ci­nat­ed pris­on­ers con­tract­ed the plague, while those who were not vac­ci­nat­ed got sick and died. After this, Haffkine’s method became pop­u­lar. This required bulk pro­duc­tion of the vaccine.

The lab­o­ra­to­ry required more spa­cious premis­es. Then a very influ­en­tial patron came to Haffkine’s aid — Sir Sultan Muhomed Shah Aga Khan III (1877 – 1957), the 48th Imam of the Shia Ismaili Muslims. Marina Sorokina writes: “Educated in Great Britain, the young Aga Khan sup­port­ed sci­en­tif­ic inno­va­tion, espe­cial­ly in the field of med­i­cine. He sug­gest­ed that Haffkine give pre­ven­tive vac­ci­na­tions to the Muslim com­mu­ni­ty of Bombay, and about half of the com­mu­ni­ty (10 – 12 thou­sand peo­ple) received “Haffkine’s lymph.” The results were again impres­sive, and in October 1897, the Aga Khan pro­vid­ed the sci­en­tist with a build­ing next to his own res­i­dence to house the anti-plague laboratory.”

The lab­o­ra­to­ry was trans­ferred there. The staff has been sig­nif­i­cant­ly expanded.

Haffkine (in the sec­ond row in the cen­ter, with a light pith hel­met) with employ­ees of the Anti-Plague Laboratory in Bombay. India, 1902 – 1903

In March 1899, the demand for the vac­cine from all over the world became so urgent that even more com­fort­able and spa­cious premis­es were required. On 10 August 1899, Lord Sandhurst, Governor of Bombay, offi­cial­ly opened a plague research lab­o­ra­to­ry at the Old Government House in Parel, of which Haffkine became the director.

Meanwhile, the plague had reached epi­dem­ic pro­por­tions. Ruling cir­cles react­ed to Haffkine’s vac­cine with­out much sym­pa­thy. They relied more on quar­an­tines and move­ment restrictions.

An anti-plague mis­sion was orga­nized, head­ed by a British gen­er­al. Military mea­sures were intro­duced, detach­ments vis­it­ed every home of local res­i­dents. The sick were sent to hos­pi­tals, and their loved ones to con­cen­tra­tion camps or quar­an­tine points. The homes them­selves were thor­ough­ly disinfected.

Unfortunately, these san­i­tary mea­sures achieved lit­tle except human suf­fer­ing. A microbe capa­ble of sur­viv­ing and repro­duc­ing in many liv­ing sys­tems, even soil, could hard­ly be destroyed by isolation.

When the small Portuguese colony of Daman (10 thou­sand inhab­i­tants) was hit by a plague epi­dem­ic, many res­i­dents fled. The vil­lages were sur­round­ed by the army, which pre­vent­ed any move­ment with­in or out­side the colony. Haffkine sent two of his most reli­able assis­tants there, who with­in two months vac­ci­nat­ed 2,200 peo­ple (6,000 refused vac­ci­na­tions). The results report­ed in the Bombay news­pa­pers strong­ly indi­cat­ed the effec­tive­ness of the vac­cine. 36 peo­ple from the vac­ci­nat­ed group died, and 1482 from the unvac­ci­nat­ed group, i.e. almost 15 times more. Even con­sid­er­ing that the unvac­ci­nat­ed group was two and a half times larg­er, this is a strong result.

This and oth­er results showed that even if vac­ci­na­tion with the anti-plague Haffkine’s drug does not pre­vent infec­tion, the mor­tal­i­ty rate is reduced by 85-90%. All oth­er anti-plague drugs were inef­fec­tive. As a result, a move­ment arose in India in 1898 to replace “hygien­ic” mil­i­tary mea­sures with bac­te­ri­o­log­i­cal, pro­phy­lac­tic or pre­ven­tive meth­ods. It bore fruit.


In the vac­cine dis­tri­b­u­tion depart­ment of the Haffkine Anti-Plague Laboratory in Bombay. India, 1902 – 1903.

The Indian Anti-Plague Commission con­duct­ed a thor­ough study of the anti-plague Haffkine’s drug and found it safe, since it was already wide­ly used in var­i­ous parts of India with­out caus­ing con­cern or caus­ing any harm­ful effects. The belief in the ben­e­fits of pre­ven­tive vac­ci­na­tions against plague became more and more widespread.

Each sub­se­quent year there were new out­breaks of plague. In 1901, the dis­ease assumed even greater pro­por­tions. It was decid­ed to car­ry out inten­sive anti-plague vac­ci­na­tion through­out Punjab. There is an urgent need for large sup­plies of vaccine.

Numerous vac­ci­na­tion cen­ters have been opened in Bombay. Haffkine’s drug was sent in thou­sands of dos­es to England, France and oth­er coun­tries. A new term even appeared in English mag­a­zines: “to haf­fkinize,” that is, to do a Haffkine vaccination.

Haffkine, in his report on the work of the Bombay Research Laboratory for the years 1896-1902, reports that in the first four and a half years after the cre­ation of the plague vac­cine, i.e. up to May 31, 1901, 2,380,288 pro­phy­lac­tic dos­es were man­u­fac­tured and dis­trib­uted in India and abroad. Over the next year, anoth­er 486,753 dos­es were distributed.
The plague has receded.
And Queen Victoria award­ed Haffkine the Order of the Indian Empire.

Haffkine’s vac­ci­na­tions seri­ous­ly influ­enced the devel­op­ment of sci­ence. The emi­nent British bac­te­ri­ol­o­gist Professor Almroth Wright acknowl­edges this in his report on the first anti-typhoid vac­ci­na­tions, pub­lished in the Lancet on September 19, 1896. He writes: “I need hard­ly point out that these anti-cholera inoc­u­la­tions have served as a pat­tern for the typhoid vac­ci­na­tions detailed above.” (13).

Haffkine’s lab­o­ra­to­ry was engaged not only in vac­cine pro­duc­tion and vac­ci­na­tions. Together with col­leagues and co-authors E. H. Hankin and N. F. Surveyor, Haffkine searched for the plague bacil­lus in nature and explored the ways of its spread. “Circumstantial evi­dence” led him to con­jec­ture that “the plague in Bombay had remained for a con­sid­er­able time restrict­ed to cer­tain hous­es in Mandvi whose inhab­i­tants were work­ers in oth­er parts of the town, viz., in the docks and else­where, ” and that “of the var­i­ous races and castes, the Jains, at that time were most­ly affect­ed.” (14).

Haffkine wrote: “The cir­cum­stances referred to seemed to show that the peo­ple were not favourable car­ri­ers and dis­sem­i­na­tors of infec­tion; that the plague was not car­ried by water - as cholera is for the affect­ed hous­es had the same sup­ply as many oth­ers; that plague was not car­ried by atmos­pher­ic air, which would have rapid­ly scat­tered it over large areas; that it was not spread by winged or oth­er insects migrat­ing read­i­ly from house to house; but that, of par­a­sitic ver­min, it might be car­ried by bugs, which stick not only to hous­es, but even to the same pieces of fur­ni­ture, or by fleas which remain in the earth, sweep­ings and floors of hous­es, and which had been sus­pect­ed to be car­ri­ers of famine fever. The con­sid­er­a­tion shown by Jains to bugs and oth­er in- sects, which they do not destroy, but are said to go so far as to feed arti­fi­cial­ly, seemed to me to con­form with the hypoth­e­sis.” (15)

However, the results obtained were gen­er­al­ly neg­a­tive. Eventually, Haffkine turned to the work of the French doc­tor Simond, who sug­gest­ed that fleas were the car­ri­er of the plague. Haffkine writes: “The idea seemed to him extreme­ly plau­si­ble, and he endeav­ored to prove that plague rats were infec­tive only as long as they were cov­ered with fleas; that plague bacil­li were dis­cov­er­able on such fleas; that by means of the lat­ter a plague rat might trans- mit plague to anoth­er rat kept at a lit­tle dis­tance from it; and that rat fleas might attack men.… Unfortunately, Dr. Simond’s exper­i­ments, in a large pro­por­tion of instances, gave neg­a­tive results; while the cas­es in which the exper­i­men­tal ani­mal did get the dis­ease were so few that they might be attrib­uted to some adven­ti­tious cir­cum­stances.” (16)

But in this case, Haffkine was wrong, and Simon was right — fleas, not bed­bugs, are car­ri­ers of the plague.

In June 1899, Haffkine trav­eled to England to report to the Royal Society and var­i­ous med­ical orga­ni­za­tions on the suc­cess of vac­ci­na­tion against cholera and plague. His per­for­mance received uni­ver­sal acclaim. Lord Joseph Lister, President of the Royal Society, Almroth Wright and many oth­er promi­nent British sci­en­tists and clin­i­cians warm­ly wel­comed Haffkine. His return to India in the fall of 1899 was greet­ed with great enthu­si­asm by the local pop­u­la­tion, who were already tired of the san­i­tary mea­sures imple­ment­ed by gov­ern­ment offi­cials to con­tain the plague. These offi­cials began to con­sid­er Haffkine an ene­my of the colo­nial regime. This was also facil­i­tat­ed by the fact that Indian nation­al­ist news­pa­pers advo­cat­ed the Haffkine vaccine.

On the oth­er hand, British news­pa­pers accused Haffkine of col­lab­o­rat­ing with the Russians and almost of espi­onage. There were even accu­sa­tions that vac­cines made peo­ple more sus­cep­ti­ble to oth­er diseases.

The Malkowal Disaster

In November 1902, a tragedy occurred in the vil­lage of Malkowal in the Indian state of Punjab. Of the 107 peo­ple who received the vac­cine, 19 devel­oped tetanus and died with­in a few days. The Government of India appoint­ed a com­mis­sion of inquiry which report­ed that tetanus was intro­duced into the vac­cine before the vac­cine vial was opened at Malkowal. The pan­el spec­u­lat­ed that this was either due to insuf­fi­cient ster­il­iza­tion or the vial being filled from a large flask with­out prop­er pre­cau­tions. The results obtained by the com­mis­sion were trans­ferred to the Lister Institute in Britain.

The com­mis­sion did not lis­ten to Haffkine, who became the main accused. In vain he sub­mit­ted reports ask­ing to study in detail the method of prepar­ing the vac­cine. Fortunately, the lead­ers of the Lister Institute did not agree with the accu­sa­tions against Haffkine.

Haffkin him­self described (report for 1902-1904) the con­di­tions under which the trag­ic error occurred as fol­lows: “It was when using the mate­r­i­al pre­pared in September-October 1902 that 19 cas­es of tetanus occurred in the vil­lage of Malkowal, in the Punjab. Some 120,000 oth­er peo­ple had by that time been in- ocu­lat­ed with the same mate­r­i­al, and the reports sub- mit­ted from the Punjab and the rest of the coun­try tes­ti­fied to the harm­less­ness, as well as the effec­tive immu­nis­ing prop­er­ties of that mate­r­i­al. The mor­tal­i­ty from plague amongst those inoc­u­lat­ed was reduced to a frac­tion of what it was in the non-inoculated.”(17)

He fur­ther writes: “It is known that a very minute quan­ti­ty of con­t­a­m­i­nat­ed mat­ter is required to cause tetanus. A sur­gi­cal instru­ment, scrupu­lous­ly clean, i.e., con­tain­ing no vis­i­ble trace of impu­ri­ty of any kind, may cause the dis­ease, if not pre­lim­i­nar­i­ly ster­il­ized. The exper­i­ments of Vaillard and Rouget showed that to cause a guinea-pig death from tetanus, it is suf­fi­cient to inoc­u­late it with a par­ti­cle of earth in which cul­ti­va­tion reveals the pres­ence of 2 or 3 tetanus germs only; ani- mals inject­ed with such a con­t­a­m­i­nat­ed par­ti­cle may exhib­it a dis­ease of equal sever­i­ty, and all die in 3 to 5 days. The mate­r­i­al used at Malkowal might have got con­t­a­m­i­nat­ed either at the Laboratory or else­where… The fol­low­ing facts were against the admis­sion that the tetanus germs had got into the pro­phy­lac­tic in Bombay. The cas­es of tetanus occurred in per­sons inoc­u­lat­ed from a bot­tle belong­ing to brew 53 N of 19th September 1902. This bot­tle formed one of five filled from the same brew-flask, No. 53 N. That the brew was not con­t­a­m­i­nat­ed was proved by the per­sons who were inoc­u­lat­ed, at oth­er places, with the remain­ing four bot­tles hav­ing had no tetanus. A flu­id in which tetanus germs had gained entrance and lived for some time gives out a foul odour which is smelt at a dis­tance by by-standers when the ves­sel is unstop­pered… The inoc­u­la­tors had no instruc­tion to test bot­tles by smelling, but many of them did so. On this occa­sion, at Malkowal, the bot­tle, when opened for inoc­u­la­tion, six weeks after it had been pre­pared in the Laboratory, was smelt, and no odour was found in it. A fort­night after the bot­tle was used it was again exam­ined, and by that time a smell had devel­oped in the rem­nants of the flu­id. The microbe of tetanus was then also found in it, in sym­biose with a micro­coc­cus.” (18)

Throughout the inves­ti­ga­tion, Haffkine right­ly con­tin­ued to assert that the vac­cine sent from the lab­o­ra­to­ry was not con­t­a­m­i­nat­ed with tetanus and that the con­t­a­m­i­na­tion must have occurred out­side the laboratory.

Haffkine remained cheer­ful through­out the inves­ti­ga­tion, which last­ed more than a year, but it was a dif­fi­cult ordeal for him. On April 30, 1904, he left Bombay for a year’s leave pend­ing the final deci­sion of the gov­ern­ment. He was relieved of his posi­tion as direc­tor of the Plague Research Laboratory. He spent most of his time in Europe, vis­it­ing var­i­ous lab­o­ra­to­ries, where he had the oppor­tu­ni­ty to present his ver­sion of the tragedy to sev­er­al out­stand­ing sci­en­tists, who unan­i­mous­ly absolved him of all blame.

Later (in 1930), the British jour­nal Lancet spoke about this case as fol­lows: “In 1896 the dis­as­trous epi­dem­ic of plague in India led the Government to entrust Haffkine with the prepa­ra­tion of a vac­cine against that dis­ease, in view of his dis­cov­er­ies with vac­cine as a pre­ven­tive of cholera. The work was imme­di­ate­ly com­menced, and its results and exten­sion were reg­u­lar­ly reviewed in the med­ical and sci­en­tif­ic press. In 1900 the Indian Plague Commission report­ed thor­ough­ly on the whole mat­ter, found that the use of the vac­cine was attend­ed with a diminu­tion of the attack and death rates, and the estab­lish­ment of a tem­po­rary pro­tec­tion, while the final rec­om­men­da­tion of the Commissioners was that, under safe­guards and in con­di­tions of accu­rate stan­dard­i­s­a­tion and absolute care, the pro­ce­dure should be encour­aged wher­ev­er pos­si­ble, and in par­tic­u­lar among dis­in­fect­ing staffs and the atten­dants of plague hos­pi­tals. A series of fatal­i­ties occurred in 1902 which for the time cast a sus­pi­cion upon the meth­ods of man­u­fac­ture of the pro­phy­lac­tic, but inquiry into the actu­al inci­dents made it clear that the tragedies were due, not to care­less­ness in the lab­o­ra­to­ry, but to a gross neglect of ordi­nary pre­cau­tions in admin­is­tra­tion. That the activ­i­ty of the Indian author­i­ties in pro­ceed­ing with­out break in inoc­u­la­tion against plague on a large scale was in no way unabat­ed can be seen by the results of 30,000 cas­es of inoc­u­la­tion… But although inoc­u­la­tion pro­ceed­ed, Haffkine’s con­trol of the work had been sus­pend­ed by the India Office, and he remained unem­ployed. The suf­fer­er in a pro­longed dis­pute who obtains a ver­dict in the end is nev­er repaid for his anx­i­ety, but through­out his peri­od of tri­al Haffkine bore him­self with the great­est dig­ni­ty; he received many con­grat­u­la­tions upon the recog­ni­tion which he final­ly received from the India Office and upon his res­o­lu­tion to return to India. Today the ver­dict on Haffkine’s labours which is gen­er­al­ly accept­ed is that the vac­cine, when used in epi­dem­ic, tends to reduce mor­tal­i­ty by 85 per cent. What this means when we con­sid­er the mil­lions of dos­es that were issued in India can hard­ly be conceived.”(19)

A sim­i­lar opin­ion was shared by those who knew the details of the tragedy in Malkowal. General S. S. Sokhey, the for­mer direc­tor of the Haffkine Institute, wrote about this in a per­son­al let­ter to Selman Waksman (It should be not­ed that there is a slight con­fu­sion: in 1902, of course, there was no Haffkine Institute, but there was a Plague Research Laboratory. S. S. Sokhey became direc­tor of the Haffkine Institute already in the late 1920s, but in his let­ter he calls the Laboratory an Institute).

Sokhey writes to Waksman: “In the Malkowal affair peo­ple inject­ed with plague vac­cine from one vial sent out from the Haffkine Institute died of tetanus and that was attrib­uted to the fault of the Haffkine Institute. But it was shown lat­er that some­thing like 20 days had elapsed between the vial leav­ing the Haffkine Institute and its being used in the field. If tetanus had got into the vial at the Haffkine Institute it would have ful­ly dev­el- oped into a tox­ic tetanus cul­ture by the time it was used and peo­ple inject­ed with it would have died im- medi­ate­ly from this tox­in. But they died 7 to 10 days after the injec­tion had been giv­en. That was con­sid­ered to be a proof pos­i­tive of the fact that the vial was con­t­a­m­i­nat­ed on the spot where it was used. This is how it hap­pened. In those days plague vac­cine used to be sent out in vials closed with rub­ber stop­pers, and the assis­tant to the doc­tor when he removed the rub- ber stop­per slipped the rub­ber stop­per through his fin­gers and it fell on the ground. He lift­ed it up and put it back on the vial to shake the con­tents. And that is how the vac­cine got contaminated.”(20)

Haffkine Institute

Only in 1907 — three years after Haffkine’s removal from work — the Indian gov­ern­ment, hav­ing found no evi­dence to sup­port its accu­sa­tions, invit­ed the sci­en­tist to return to India.

Letters of grat­i­tude poured in from all over the world in Haffkine’s defense. Eventually he decid­ed to return. Since the post of Director of the Bombay Laboratory was filled, he agreed to work in Calcutta. He con­tin­ued to work, but his strength was under­mined, not so much by intense work as by unfair accu­sa­tions. On reach­ing retire­ment age in 1914, he left India.

Despite the fact that many attempts were made to improve the orig­i­nal method of obtain­ing a plague vac­cine devel­oped by Haffkine (in three months!), they were gen­er­al­ly unsuc­cess­ful. The supe­ri­or­i­ty of the Haffkine vac­cine over oth­er types of plague vac­cines has been wide­ly demon­strat­ed. And it became the qual­i­ty stan­dard for decades. Although the inci­dence of plague in India has decreased, the demand for the vac­cine con­tin­ued to increase. By 1930, more than 33 mil­lion dos­es had been dis­trib­uted with­in 34 years of the vac­cine’s development.

In 1925, the Bombay gov­ern­ment renamed the Plague Research Laboratory the Haffkine Institute to hon­or the mem­o­ry of a man who brought great ben­e­fit to India and its people.

About Haffkine, Podolsky wrote: “Haffkine was always immersed in research. No soon­er had he dis­posed of one prob­lem than he start­ed on anoth­er. In World War I, the British forces in France had pro­phy­lac­tic inoc­u­la­tions against typhoid, but not against paraty­phoid A and B. In view of the arrival of troops from India and the Mediterranean region, it was urged that the com­plete inoc­u­la­tion should be per­formed. But Sir William Leishman, Director of pathol­o­gy of the expe­di­tionary forces, opposed imme­di­ate action because he feared severe reac­tions, which might impede mil­i­tary rein­force­ments. A com­mit­tee of not­ed pathol­o­gists was appoint­ed to con­sid­er the ques­tion, of which Haffkine was a mem­ber. His argu­ments went a long way to con­vince Leishman. After a tri­al on 300 men, the vac­cine was gen­er­al­ly used in all armies… Haffkine was a tire­less work­er, who neglect­ed his own wel­fare for the wel­fare of oth­ers. He was well liked by those with whom he came in con­tact.” (21)

Last years

After retir­ing, Haffkine set­tled in France. He lived main­ly in Paris and Boulogne-sur-Seine. He increas­ing­ly sought soli­tude. He com­plete­ly aban­doned his sci­en­tif­ic career, although he remained a mem­ber of var­i­ous English, French, American and Indian sci­en­tif­ic soci­eties and wrote in Russian, French and Dutch sci­en­tif­ic jour­nals. His works were main­ly devot­ed to top­ics that he stud­ied through­out his life.

His retire­ment coin­cid­ed with the begin­ning of the First World War and the eve of the rev­o­lu­tion in the Russian Empire. This did not allow him to trav­el freely to his home­land, although in 1927 he paid an extend­ed vis­it there. He vis­it­ed Odessa and trav­eled around the country.

He remained a bach­e­lor all his life. Apparently, he believed that he would not be able to impose on a woman the lifestyle that he led in India — entire­ly devot­ed to sci­en­tif­ic work and sav­ing peo­ple. To those who saw him in London in 1899, Haffkine seemed a lone­ly, seri­ous, self-absorbed, but at the same time hand­some man.

At a recep­tion giv­en to Haffkine in London in 1899 by the Jewish orga­ni­za­tion “The Maccabees”, Lord Lister empha­sized the enor­mous ben­e­fit that Haffkine’s work brought to the peo­ple of India and the entire British Empire. At this recep­tion, Haffkine stat­ed that through­out his time work­ing in India, he had nev­er for­got­ten the suf­fer­ing of his fel­low Jews under the Tsarist regime.

Podolsky wrote about the last years of Haffkine’s life: “He sought sci­en­tif­ic back­ing for many of the hygien­ic laws laid down by Moses and oth­ers in ancient times. The micro­scope he stat­ed jus­ti­fied a great many of these reg­u­la­tions. As an exam­ple he cit­ed the law of the thor­ough removal of ani­mal blood which could eas­i­ly be invad­ed by germs and cause seri­ous dis­eases. He regard­ed his reli­gion as a form of dis­ci­pline. It was like sci­ence. In order to accom­plish any­thing in sci­ence we must know what has been accom­plished before. In a sim­i­lar way we must learn from the wis­dom of the past.”(22)

After retire­ment, Haffkine devot­ed much time to study­ing Judaism. He was con­vinced that it was Judaism that served the Jews well and that their future great­ly depend­ed on the preser­va­tion of reli­gious tra­di­tions. He believed it was of utmost impor­tance to pro­mote the study of the Bible and out­lined his views in an essay pub­lished in 1916: “a broth­er­hood built up of racial ties, long tra­di­tion, com­mon suf­fer­ing, faith and hope, is a union ready-made, dif­fer­ing from arti­fi­cial unions in that the bonds exist­ing between the mem­bers con­tain an added promise of dura­tion and util­i­ty. Such a union takes many cen­turies to form and is a pow­er for good, the neglect or dis­use of which is as much an injury to human­i­ty as the removal of an impor­tant limb is to the individual.”(23)

Although Haffkine did not receive a reli­gious upbring­ing in child­hood and ado­les­cence, towards the end of his life he became a deeply reli­gious believ­er. He con­vert­ed to Orthodox Judaism. In April 1929, Haffkine bequeathed secu­ri­ties placed in a Swiss bank to Jewish reli­gious schools in Eastern Europe. After his death, a cor­re­spond­ing fund was created.

On April 17, 1928, Haffkine final­ly set­tled in Lausanne. He died in this city on October 26, 1930. He died, as he lived, alone.

Grave of V. A. Haffkine. Lausanne, Switzerland. Photo Alexander Duel

When news of his death reached the Haffkine Institute in Bombay, the Institute’s staff pub­lished the fol­low­ing words: “It was with pro­found regret that Reuter’s mes­sage from Lausanne announc­ing the sud­den death of Mons. Haffkine on the 26th October 1930, was received at this Institute. The Haffkine Institute, which owes its present activ­i­ties to his genius, and the Grant Medical College, which had been the scene of his ear­ly research­es on plague, were closed down on the 27th of October to pay homage to his mem­o­ry. Obitu- ary notices have appeared in all our local news­pa­pers and in the med­ical jour­nals of oth­er coun­tries and these have acclaimed him as one of the great­est bene- fac­tors of mankind. India has spe­cial rea­sons to be- moan his loss; he had spent the best years of his life here fight­ing against the scourges of cholera and plague; he has saved many of her peo­ple from the rav­ages of these two dis­eases by his pro­phy­lac­tic inoculations”.(24)

Notes

(1) Selman A. Waksman. The bril­liant and trag­ic life of W. M. W. Haffkine. Bacteriologist Waldemar Mordecai Wolff Haffkine (1860-1930), 1964, Rutgers University Press, New Brunswick New Jersey.
(2) Popovski, M. Sudiba doc­to­ra Chavkina (The Fate of Dr. Haffkine). Isdat. Vostochnoi lit­er­a­turi, 132 pp. Moscow, 1963.
(3) Metchnikoff, Olga. Life of Elie Metchnikoff, 1845 – 1916. Houghton Mifflin Co., Boston, 1921. Op. cit. Waksman, 1964 p. 9.
(4) Recherches sur l’adap­ta­tion au milieu chez les infu­soires et les Bactéries. Contribution à l’é­tude de l’im­mu­nité. Ann. Inst. Pasteur 4:363-379, 1890.
(5) Podolsky, E. Waldemar Haffkine and the Plague elim­i­na­tor. Your Health 5:261 – 264, 1956. Op. cit. Waksman, 1964, pp. 15-16.
(6) Pasteur, L. Letter to Grancher-Correspondence by R. Vallery-Radot, Vol. IV, pp. 342 – 344. Flammarion, Paris, 1892.). Op. cit. Waksman, 1964, p. 17
(7) Simpson, W. J. Waldemar Haffkine, C.I.E. J. Trop. Med. Hyg. 33:346 – 348, 1930. Waksman, 1964, pp. 19-20.
(8) Waksman, 1964, p. 28.
(9) Waksman, 1964, p. 28.
(10) Waksman, 1964, p. 31.
(11) Podolsky, E. Waldemar Haffkine and the Plague elim­i­na­tor. Op. cit. Waksman, 1964, p. 31.
(12) Podolsky, E. Waldemar Haffkine and the Plague elim­i­na­tor. Op. cit. Waksman, 1964, p. 32.
(13) Waksman, 1964, p. 45.
(14) Waksman, 1964, p. 49.
(15) Waksman, 1964, p. 49.
(16) Waksman, 1964, p. 50.
(17) Waksman, 1964, p. 54.
(18) Waksman, 1964, pp. 54-55.
(19) Waksman, 1964, pp. 57-58.
(20) Sokhey, S. S. The pass­ing of the present plague pan­dem­ic in India. In Haffkine Inst. Diamond Jubilee Souvenir Booklet, 1899-1959, pp. 6 – 11. Bombay. Op.cit. Waksman, 1964, pp. 60-61.
(21) Podolsky, E. Waldemar Haffkine and the Plague elim­i­na­tor. Op. cit. Waksman, 1964, pp. 69-70.
(22) Podolsky, E. Waldemar Haffkine and the Plague elim­i­na­tor. Op. cit. Waksman, 1964, p. 76.
(23) Haffkine, W. M. A plea for ortho­doxy. Menorah J. 2:67-77, 1916. Op. cit. Waksman, 1964, p. 77.
(24) Waksman, 1964, 81.

  6.12.2023

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