Paul Louis Simond in India and the Discovery of Plague TRANSMISSION

Bombay plague epidemic, 1896-1897: interior of a plague hospital. Photograph attributed to Clifton & Co. Credit: Wellcome CollectionPublic Domain Mark

Paul-Louis Simond after studying in Bordeaux joined the Naval Medical Corps and was posted to French Guyana and the Far East. In 1895, he went to the Pasteur Institute in Paris where he followed Emile Roux’s teaching and worked in Elie Metchnikoff’s laboratory. During this time Simond studied coccidia in the intestinal flora of various animals. 

In March 1897, at Emile Roux’s request, Simond travelled to India (Bombay and Cutch-Mandvi in 1897; Jurrachee in 1898 [subsequently Karachi]) to replace Yersin in fieldwork. 

A large plague pandemic was making people suffer in Asia and Simond’s task, which he accepted with enthusiasm, was to help test the new Pasteur antiserum prepared from live cultures of Y. pestis. Beginner’s luck worked in his favour but not for long, later tests of serotherapy were disheartening despite which he continued furthering his research, looking for infected patients with the help of the-then French Consul in Bombay, Joseph Pilinski. 

During his research excursions, he observed that a large number of patients developed skin phlyctena that are small blisters that have plague bacilli and some fluid. These were early-stage patients. He then hypothesized that this phlyctena swells to become a neurotic buboe. The quest was to find the vector for the disease, the way it transmits and spreads, he thought that the initial lesion can be due to an insect bite. The concept of transmission was new to the fraternity, therefore it was treated with scepticism. 

Amongst sceptic academia, he found support for his thesis from his mentor and the man who first studied the malaria parasite in the blood, Charles-Louis Alphonse Laveran. His initial thoughts were that the cockroach could be a vector. However, it was counterintuitive to think of it as one because of its lack of mobility. Since rats were quite mobile and were prevalent everywhere, he thought that rat flea might have some clues and started studying it. It required temerity much more than it required courage to manipulate dead rats with bare hands and pick up their fleas in soaped water, but Simond was rewarded. Upon microscopic observation, he found that these fleas were full of bacilli. It was a moment of discovery. 

The Karachi Experiments

Paul-Louis Simond injecting plague vaccine June 4th 1898. Credit: Wikipedia

“Without delay, I proceeded to the experiment I had in mind since the time in Cutch-Mandvi when I had discovered Yersin’s bacillus in the digestive tract of fleas taken from plague-ridden rats. I prepared a device consisting of a large glass bottle whose bottom was covered with sand, which would absorb the urine of the rats. The lid consisted of wire mesh covered with fabric held tightly to the neck of the bottle with a drawstring. I was fortunate enough to catch a plague-infected rat in the home of a plague victim. In the rat’s fur, there were several fleas running around. I took advantage of the generosity of a cat I found stalking the hotel premises, borrowing some fleas from it. Once the sick rat was in the bottle, I deposited upon it the cat’s fleas from a test tube. I was thus quite sure the rat would be covered with parasites. After 24 hours the animal I was experimenting on rolled up into a little ball, with its hair standing on end; it seemed to be in agony. I then introduced into the bottle a small metal cage containing a perfectly healthy young Alexandria rat caught several weeks before and kept sequestered from any danger of infection. The cage was suspended with the inside of the bottle several centimetres above the layer of sand. The cage had three solid sides, but the other three sides were covered by a wire screen with a mesh size of about six millimetres. The rat inside the cage could not have any contact with the sick rat, the wall of the bottle or the sand. The next morning the sick rat had died without having moved from where it had been the day before. I left its body in the bottle for one more day. Then I carefully removed it, plunged it into alcohol and performed an autopsy. The blood and organs all contained an abundance of Yersin’s Bacillus. During the next four days, the other Alexandria rat remained imprisoned in its cage and continued to eat normally. About the fifth day, it seemed to have difficulty moving. By the evening of the sixth day, it was dead. An autopsy of this one (previously uninfected rat) revealed buboes both inguinal and axillary. The kidney and liver were swollen and congested. There were abundant plague bacilli in the organs and blood. That day, 2 June 1898, I felt an emotion that was inexpressible in the face of the thought that I had uncovered a secret that had tortured man since the appearance of plague in the world. The mechanism of the propagation of plague includes the transporting of the microbe by rat and man, its transmission from rat to rat, from human to human, from rat to human and from human to rat by parasites. Prophylactic measures, therefore, ought to be directed against each of these three factors: rats, humans and parasites. I subsequently repeated the same experiment with similar results” [Paul Louis Simond, Hotel Reynolds, Karachi, 1897] [A]

Pranav Sharma is a Science Historian and the Curator of the project on documenting the history of the Indo-French scientific partnership.

Reference

[A] Simond M, Godley ML, Mouriquand PDE. Paul-Louis Simond and His Discovery of Plague Transmission by Rat Fleas: A Centenary. Journal of the Royal Society of Medicine. 1998;91(2):101-104.

Plague, Anti-plague vaccine and serums in India

Pranav Sharma

Alexandre Yersin. Credit: Wikipedia

Alexandre Yersin arrived in Bombay on March 5, 1897. Yersin worked as an assistant at the Pasteur Institute but left the Paris laboratory in 1890. In 1894 he was commissioned by the French government to investigate the appearance of the bubonic plague in Hong Kong, where he identified its bacillus and cultured plague microbes. These were then shipped to Paris for further investigation.

La peste bubonique à Hong-Kong / A.E.J. Yersin.. Credit: Wellcome CollectionPublic Domain Mark

The drive to develop an anti-diphtheria serum met with swift success around the mid-1890s. It also represented an important milestone in the history of bacteriology. It was also a shift from preventive medicine based on vaccines to curative medicine based on serums.

French researchers faced a different challenge when it came to anti-plague serum, Yersin returned to Indochina, where, in 1896, a plague epidemic broke out. Yersin was able to conduct his first human trials of the remedy serum, curing 24 of 26 cases. Following news of these successful tests, the city of Bombay invited Yersin to administer his preparation among the thousands of people struck with bubonic plague there starting in September 1896.

Arriving in Bombay, Yersin carried with him two serums, the one he used in Guangzhou and another one that had arrived from Paris. Taken together, the results of the three series of trials, including new testing conducted with the Paris serum, differed from the findings in China, given that the overall mortality rate reached 50%.

Although his stay was short, he was still able to test the curative power of the serums. It was also used as a vaccine providing immunity from the plague.

A plague house in Bombay: the wall has been marked with circles. Photograph, 1896/1897.. Credit: Wellcome CollectionPublic Domain Mark

Pranav Sharma is a Science Historian and the Curator of the project on documenting the history of the Indo-French scientific partnership.

French Medicine and Training in India

The Ecole de Medicine de Pondichéry established by the French Government in 1823, became Medical College, Pondicherry after de jure transfer of Puducherry to India in 1956. For a brief time, it was also named Dhanvantri Medical College. The building now houses the Legislative Assembly of Puducherry. [Ref: S. Chandrashekhar, Jawaharlal Institute of Postgraduate Medical Education and Research, The National Medical Journal of India, 1992, Vol.6, No. 6, p. 299-300]

On 30th June 1898, Father Just-Théodore Falourd, a French missionary in Pondichéry died in a syncope a few hours after his surgery. Father Falourd was one of the sincerest missionaries who were working in Pondichéry in the late nineteenth century. His unfortunate demise happened in Hôpital Colonial. 

The Jesuit missionaries were among the first people to bring western medicine to India. It is found that towards the late 1690s a Jesuit-run hospital existed in Pondichéry. L’Hôpital Militaire was established near L’église du Sacré Cœur de Jésus in 1738. Another hospital has been found to exist in the outskirts of Pondichéry around the 1740s, managed by the missionaries of the Order of Friars Minor Capuchin (Raman, 2017). 

The real turn, as we casually wonder with fellow academics, came after the establishment of le Ministère de la Santé (Health Commission) by the French Government in Pondichéry. It happened in the mid-1860s. This was preceded by the establishment of L’École de Médicine de Pondichéry to train medical practiciners. 

In a review, Pierre Julian (Revue d’Histoire de la Pharmacie, Année 1968, 199, p. 226) wrote,

La première installation officielle des Français à Pondichéry date du 4 février 1673. Un chirurgien y est présent dès 1674. Il faudra toutefois attendre le XVIII* siècle, passée l’occupation hollandaise, pour y trouver un service médical constitué. Il est assuré par des chirurgiens navigants de la Compagnie des Indes, qui ne tardent pas à former du personnel localement, y compris des médecins.

Un premier hôpital est édifié à partir de 1701, un plus important à partir de 1734. La Compagnie des Indes fournit les médicaments, — pilules de Belloste, pilules de Petit et de Chaber, poudre fébrifuge de La Jutais, pilules antivénériennes dont un inventaire dénombre un total de 3.600 — et demande des rapports sur l’essai de certaines drogues. Lorsqu’on manque de médicaments, on en emprunte aux Jésuites.

Au XIX* siècle, retrouvant ses comptoirs de l’Inde après l’occupation anglaise, la France édicté, par une ordonnance de 1823, un véritable code de la santé publique. Une Commission de santé est créée, qui comprend parmi ses membres le médecin, le chirurgien et le pharmacien du Roi. Des dispositions réglementent l’inspection des pharmacies et les prix et répriment le compérage médico-pharmaceutique.

En 1829, les deux pharmacies privées fusionnent en une seule pour former la Pharmacie du gouvernement, dont l’historique a été retracé naguère par le pharmacien colonel Giboin. La médecine traditionnelle est reconnue: en 1848 l’ouverture d’une boutique de drogues indiennes est autorisée. En 1849 arrive à Pondichéry un pharmacien de la marine, Lépine, dont l’activité scientifique rayonnera sur toute l’Inde pendant vingt ans.

The first official installation of the French in Pondicherry dates from February 4, 1673. A surgeon has been present there since 1674. It will be necessary, however, to wait until the eighteenth* century, after the Dutch occupation, to find a medical service there. It was provided by flight surgeons from the Compagnie des Indes, who were quick to train local personnel, including doctors.

The first hospital was built in 1701, a larger one from 1734. The Compagnie des Indes provided the medicines, – Belloste pills, Petit and Chaber pills, febrifuge powder from La Jutais (to treat fever), anti-venereal pills, of which an inventory counts a total of 3,600 – and asks for reports on the testing of certain drugs. When they run out of medicine, they borrow it from the Jesuits.

In the nineteenth century, recovering its counters in India after the English occupation, France enacted, by an ordinance of 1823, a veritable code of public health. A Health Commission is created, which includes among its members the doctor, the surgeon, and the pharmacist of the King. Provisions regulate the inspection of pharmacies and prices and repress medico-pharmaceutical collusion.

In 1829, the two private pharmacies merged into one to form the Government Pharmacy, the history of which was recently traced by the pharmacist Colonel Giboin. Traditional medicine is recognized: in 1848 the opening of an Indian drug store is authorized. In 1849, a naval pharmacist, Lépine, arrived in Pondicherry, whose scientific activity spread throughout India for twenty years.

Pierre Julien, d’après : Alfred Bigot, La médecine française à Pondichéry aux XVIIIe et XIXe siècles, in Comptes rendus du 91e Congrès national des sociétés savantes, Rennes, 1966, Section des sciences, t. I, Hist, des sciences, Paris, 1967, p. 31-46.
Ecole de Medicine de Pondichéry established by the French Government in 1823. [Ref: S. Chandrashekhar, Jawaharlal Institute of Postgraduate Medical Education and Research, The National Medical Journal of India, 1992, Vol.6, No. 6, p. 299-300]

Offering Docteur Médecin, Ecole de Medicine de Pondichéry trained Indians to become practicing physicians in various disciplines, the training guideline of which was monitored by Bureau de Santé Français in Paris.

NII, AIIMS, and CEFIPRA: My Collaborations with India

Gérard Charles Paul Chaouat

Gérard Chaouat with Pran Talwar at NII in New Delhi.

I fell in love with India over several years of collaboration with Indian scientists. I usually prefer to live outside the metropolitan bustle. However, being in Delhi was inevitable. I was witness to the slow disappearance of the star-spangled night sky of Delhi. I liked to be in Delhi, especially for her cultural vibrance and landscaped grandeur, but I had my weekend getaways. 

In the early 90s, the remuneration we got paid in Rupees (INR), could not be used outside India. So we had to use it during our visit. I was visiting as French Directeur de Recherches to collaborate with Indian institutions such as the National Institute of Immunology (NII) and All India Institute of Medical Sciences (AIIMS). It was a mandate to stay on the institution campus, so there were a few things that one could spend on. 

I used to take weekend trips, so much so that I visited almost every city in Rajasthan. I went to Kathmandu, Bhaktapur, and took a mountain flight over Sagarmatha. Regardless of my extensive travel in India to get to know the country; Agra, Jaipur, Jaisalmer, and Goa always remained my favorite. 

I had the pleasure of engaging in collaborations with India. Among several projects, two of them were governmental cooperative projects. They were managed by Centre Franco-Indien pour la Promotion de la Recherche Avancée (CEFIPRA). The projects were: Immunoregulation at the maternal-fetal interface and its applications [Project 204-1; April 1990 to March 1994) and cytokines and integrins in successful implantation and parturition [Project 1604-1; April 1998 to April 2001]. There was another project on HIV between 2000 and 2001.

I also participated in the Pasteur Anniversary celebrations and Joint NII-Institut Pasteur Symposium. I spoke at the World Congress of Immunology in Mumbai as a member of the International Union of Immunological Societies. The highlight of this meeting was its venue, The Taj Mahal Palace Hotel. This was 2001. 

There was a meeting on Reproductive Immunology in Delhi in 2009 for which I visited Delhi again along with Silver Jubilee celebrations of CEFIPRA in Chennai. [Silver Jubille report can be accessed here.]

The CEFIPRA projects (204-1, 1604-1) and the HIV project were handled by its then-Director P G S Mony. He visited Paris on several occasions with his colleagues. There was one Mr. Ganguly, who was the treasurer of the institute who often accompanied Mony. I recall Ganguly counting the pack of rupee banknotes upon my arrival. These gentlemen were extremely efficient scientifically and helpful as far as practical details of my first arrival in India were concerned. It was a pity not seeing them in Chennai for the 25th anniversary of CEFIPRA. I remember visiting the institute at Olof Palme Road and then later at the more spaced facility at Lodhi Road in Delhi. 

The first project was conducted in collaboration with Raja Raghupathy. I met him in Banff and then in Edmonton while visiting my fellow researcher Prof. Thomas Wegmann at the University of Alberta. We had proposed that the Immune system was not a threat that required general immunosuppression for a successful pregnancy. In fact, it was useful, if not necessary. This became evident in later studies. It was based on a model of murine-mediated abortion and its correction alloimmunization of the mother to paternal histocompatibility antigens. The cytokines were just beginning to be characterized. In Banff and Paris, we had begun characterization of what was to be termed “immunotrophism” in the fetal-maternal interface.

From that background research, we engaged in further exploration and a joint project began. We were investigating the involvement of cytokines in “immunoregulation at the feto-maternal interface” but also at the systemic level without neglecting an immunosuppressive component. The studies involved visits of Raja Raghupathy to Paris. He was housed at the Cité Universitaire. He was working at U-262 Inserm unit at Maternité Baudelocque. Me and my doctoral student Elisabeth Menu used to work with him extensively. Elisabeth is now Directeur de Recherches-INSERM at CEA, Paris. 

Back in India, my visits involved regular discussions with students and a lot of benchwork. We were greatly facilitated by the fact that we were housed at the NII residence on the campus. Although I was not able to burn my money much with this facility, it allowed me to have discussions with the students from other labs as well. I was particularly thrilled to interact with lab chiefs at NII, especially Prof. Pran Talwar. I was an enthusiastic attendee of the NII seminars. 

Gérard Chaouat in New Delhi in the 90s.

In addition to the characterization of immunosuppressive factors from trophoblasts and choriocarcinoma, we expanded our research further on the involvement of Colony Stimulating Factors (CSF, mostly CSF-1 and GM-CSF). Its main developmental focus was on using the CBA xDBA/2, CBA x BALB/c murine abortion model and its correction by immunization on the newly discovered cytokines at the interface, IL-3, IL-4, IL-10 on one hand, and the other, TNF and interferon-gamma. This research was lead by me with my collaborator Tom Wegmann, and Raj. This work established the concept that pregnancy was a Th2 phenomenon. Amongst the papers published as an outcome of this cooperation, I must mention: IL-10 prevents naturally occurring fetal loss in the CBA x DBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN-tau. Chaouat G, Assal Meliani A, Martal J, Raghupathy R, Elliott JF, Mosmann T, Wegmann TG. J Immunol. 1995 May 1;154(9):4261-8

This paper is seminal, highly, and repeatedly cited. It is considered as one of the foundations of the Th1/Th2 paradigm. It states that Th1 cytokines are dangerous during established pregnancy, and a “successful allopregnancy is a Th2 phenomenon”. Whereas, Th1 immunity is more linked to abortions [Immunodystrophism, T cells, cytokines, and pregnancy failure.   Raghupathy R, Tangri S. Am J Reprod Immunol. 1996 Apr;35(4):291-6.)] and [Th1-type immunity is incompatible with successful pregnancy.  Raghupathy R. Immunol Today. 1997 Oct;18(10):478-82. doi: 10.1016/s0167-5699(97)01127-4]

[For more Read: A & B]

Thanks to this work, I made several reviews of the subject and traveled worldwide to deliver talks. It makes me happy to see the citation of these papers increasing as fast as one-two per week. 

We worked on the immune abortion model in Delhi as well as in Paris. My collaborator Shabnam Tangri (She is now the Vice President at BioPharma Division of Navigate Biopharma services Inc, -Novartis) worked on cytokines in the placenta for aborting CBA/J mice (mated with DBA/2 males) and non-aborting ones (mated with BALB/c mice or pre-immunized against BALB/c lymphocytes prior to mating with DBA/2 males called the vaccination against abortion model). We had already noticed different abortion rates between Paris, Nice, and Hamilton (Ontario, Canada), but we were struck by extremely high rates of abortion and uteroplacental TNF levels in Delhi. [Expression of cytokines in placentas of mice undergoing immunologically mediated spontaneous fetal resorptions. Tangri S, Raghupathy R. Biol Reprod. 1993 Oct;49(4):850-6.]

This prompted us to test abortion rates in a germ-free environment, and surprisingly the abortion rate dropped exponentially, to be almost null. Only a few meiosis-related genetic anomalies were exceptions. This led us to test the effects of per os (orally administered) antibiotics on abortion rates. This led to studies on bacterial flora in the intestine and abortion [Ecology of danger-dependent cytokine-boosted spontaneous abortion in the CBA x DBA/2 mouse model. I. Synergistic effect of LPS and (TNF-alpha + IFN-gamma) on pregnancy loss.  Clark DA, Manuel J, Lee L, Chaouat G, Gorczynski RM, Levy GA & Ecology of danger-dependent cytokine-boosted spontaneous abortion in the CBA x DBA/2 mouse model: II. Fecal LPS levels in colonies with different basal abortion rates. Clark DA, Chaouat G, Banwatt D, Friebe A, Arck PC. Am J Reprod Immunol. 2008 Dec;60(6):529-33)].

These were the first proofs of the role of maternal microbiota in pregnancy and abortion. This project had nine research publications. 

The second project was conducted in collaboration with Prof. Chandana Das at AIIMS in New Delhi. I remembering staying in a small hotel in Safdarjung Enclave (The Dumpy Inn, I think). It was an interesting experience. However, I was mostly staying in AIIMS. 

We sent Sandrine Zourbas to Delhi to work at AIIMS for a month perhaps Marlene Moussa as well. 

Well, on the research front, Das brought delayed implantation embryos to Paris. The research of these embryos resulted in a joint paper of interest [Expression of pro-inflammatory cytokines in mouse blastocysts during implantation: modulation by steroid hormones. Basak S, Dubanchet S, Zourbas S, Chaouat G, Das C. Am J Reprod Immunol. 2002 Jan;47(1):2-11] It was part of the studies that showed that Th1 cytokines were not a danger at implantation, but in fact, implantation was an inflammatory phenomenon, such as abcedation. The injection of non-self products (spermatozoa and lymphocytes) leads to a high macrophage influx. Its an expression of adhesion molecules, mostly but not exclusive integrins and concomitant integrin expression on blastocyst, needed for adhesion of the embryo in the pre and peri-implantation phases.

We began this project to investigate other cytokines in pregnancy. We started with IL-12, IL-15, and IL-17. It gave rise to the revision of the role of cytokines, even in established pregnancy [A brief review of recent data on some cytokine expressions at the materno-foetal interface which might challenge the classical Th1/Th2 dichotomy.  Chaouat G, Zourbas S, Ostojic S, Lappree-Delage G, Dubanchet S, Ledee N, Martal J. J Reprod Immunol. 2002 Jan;53(1-2):241-56]. 

This paper, albeit not a joint one also became a citation classic. Read more here: [Follicular fluid concentration of leukaemia inhibitory factor is decreased among women with polycystic ovarian syndrome during assisted reproduction cycles. Lédée-Bataille N, Laprée-Delage G, Taupin JL, Dubanchet S, Taieb J, Moreau JF, Chaouat G. Hum Reprod. 2001 Oct;16(10):2073-8. and  Cytokine-dependent abortion in CBA x DBA/2 mice is mediated by the procoagulant fgl2 prothrombinase  David A. Clark, Gerard Chaouat, Petra C. Arck, Hans Willi Mittruecker and Gary A. Levy, J Immunol January 15, 1998, 160 (2) 545-549]. This project was very well received and was a success. 

An interview by Pranav Sharma

From Travelers to Physicians: French Medicine in Colonial India

Le seul véritable voyage … ce ne serait pas d’aller vers de nouveaux paysages, mais d’avoir d’autres yeux, de voir l’univers avec les yeux d’un autre, de cent autres, de voir les cent univers que chacun d’eux voit 

The only true voyage of discovery … would be not to visit new landscapes, but to possess other eyes, to see the universe through the eyes of another, of a hundred others, to see a hundred universes that each of them sees.

Marcel Proust

Samuel Berthet

Spanning over several centuries, the enchantment of medicine has been central to the history of Indo-French relations. Europe started using Indian spices when the Romans began trading with India. The territory today called France from Roman time, pepper was being used for meat preservation and other usages. Malabathron, better known in India as tejpata, was among several other ingredients that have been adapted in French cooking and traditional knowledge of medicine. 

Botanical ellémans of the plants of the Garden of Lorixa, their virtue and quality, as well as that which is not, with their flower, fruis et grainne, translated from louria an francés, containing seven thome,” by L’Empereur [Credits: National Museum of Natural History (Paris) – Directorate of Libraries and Documentation]

Over the ages, travelers from France have been visiting India for various reasons. Some of the famous French travelers to India were trained physicians, and others improvised. François Bernier came to India around 1658, was well-known among those, and had completed his medical education at the University of Montpellier. His treatise Contenant La Description Des Etats Du Grand Mogul serves as a crucial historical account of the Mughal empire. Bernier served as a personal physician to the Mughal Prince Dara Shikoh and then to his brother Aurangzeb. It is also found that another physician Francois de la Palisse, alias St Jacques, was at the Mughal court. The surgeon to the governor of Allahabad was Claudius Malle of Bourges, another Frenchman. These two gentlemen are argued to be contemporaries around the year 1666. From Italian traveler Nicholas Manucci’s writings we know that Cattem practiced surgery in Bengal around 1700. We also know that Farrukhsiyar had a French surgeon, Martin. 

Medicine was at the center of the project by Nicolas Lempereur, general surgeon of the French East India Company, and Ellemans botanique des plante du Jardin de Lourixa , leur vertu et quallite, tans conus que celle qui ne le sont pas, avec leur fleur, fruis et grainne, an herbarium displaying 720 species of plants more than the famous Hortus Malabaricus  is preserved today in the Muséum National d’Histoire Naturelle. Each plant contains a caption mentioning its medical usage. 

Botanical ellémans of the plants of the Garden of Lorixa, their virtue and quality, as well as that which is not, with their flower, fruis et grainne, translated from louria an francés, containing seven thome,” by L’Empereur [Credits: National Museum of Natural History (Paris) – Directorate of Libraries and Documentation]

The medicinal study flourished as the reports about the plague became an integral part of the correspondence between the French agent in India and the metropolis. When Suez Canal opened in 1869 and Marseille became the main port between India and Europe, the concern over the spread of pandemics becomes even more acute. 

In the archives of the French MEA, we find records mentioning Mihirbai Ardéchir, a Parsi woman who was also a pioneer of French studies in Bombay. This was recorded by one of the first Indian students in France. Ardéchir joined the collège de Médecine, of the University of Paris in September 1890. 

Around the same time, in the 1890s, Louis Pasteur worked on rabies, cholera, and water-borne diseases. The treatment of which raised interest in the medical community in India. Doctor Gallay, a principal doctor of the Colonies, took part in the Indian Medical Congress held in Calcutta at the end of 1894. 

In 1895, is the year when Waldemar Haffkine, a Russian doctor affiliated with the Pasteur Institute started his work on cholera vaccination in India. As soon as 1896, some Indian personalities expressed their interest regarding the foundation of a Pasteur Institute in India. The first contacts were between Calcutta and Dr. Albert Calmette. He was a physician from France who happened to be a close associate of Pasteur. He was known for his work in bacteriology and immunology. 

This collaboration shaped the partnership between the Indian Medical body, the University of Bombay (through Haffkine in 1897), and Alexandre Yersin. One of the outcomes of this collaboration led Yersin, a Franco-Swiss physician come to India the following year. He led trials of the serum received from Paris in Bombay after Canton and Amoy, with inconclusive results. He is followed by Paul-Louis Simond, French physician, chief medical officer, and biologist who replaced Yersin. 

Paul-Louis Simond injecting plague vaccine (4th June 1898, Karachi) [Credits: Wikipedia]

Simond tested the efficacy of an experimental antiserum against the outbreak of plague in that city. In 1898, in Karachi, he managed to prove the transmission of the bacterium Yersinia pestis by fleas, the agent causing bubonic plague, from rat to rat, and from rat to human. Gallay, Yersin, and Simond’s works and itineraries highlight the role of the Pasteur Institute and the French colonial medicine in India. 

In 1897, the city of Darjeeling became the first city to launch the Pasteur system for water treatment. Confronted to the lack of interest on behalf of the British Raj authorities, in 1898 the Nizam of Hyderabad decided to support the project of a Pasteur Institute in India. 

The French Consul General in Calcutta writes about this move: “It is better to have a Pasteur Institute in Hyderabad than to wait for the making of such a project on the British Territory. It is a good note in favor of the Nizam, while appears more clearly the indifference regarding these issues of the Government of India and of the Committee in charge for the last 7 years of setting up an institute in India”. The British Government in India agreed to devote only the equivalent of the average fee spent yearly for the transportation of British soldiers in India to France contaminated by rabies. The first vaccination center was finally set up in Coonoor (now in Tamil Nadu), before being transferred to Hyderabad. Haffkine ended up establishing an Institute in Bombay in 1899 adorned with a bust of Louis Pasteur. 

Samuel Berthet is the Director of Alliance Française in Hyderabad.

Indo-French Cooperation in Immunology: My Journey

Srini Kaveri

Life for any PhD student can be grueling and highly demanding. In the laboratory of Professor Donny Strosberg (in the center), it was no different.

It was the late 70s. We were about to finish our studies at the veterinary school in Bangalore, India. Most of our classmates were ready to don the white coat and start their professional careers as field veterinarians. But some of us were looking at the distant horizons. And at the far horizons, in the late 70s, some revolutions were unfolding in science. These revolutions were going to impact the field of health and medicine profoundly.

In the United States, Stanley Cohen and Herbert Boyer had shown how to cut DNA into fragments, rejoin them, and insert the new genes into Escherichia coli bacteria, the so-called genetic engineering a part of molecular biology. Around the same time in Cambridge (UK), George Kohler and Cesar Milstein had developed a method by which large amounts of monoclonal antibodies of a predefined specificity could be generated – the monoclonal antibody technology, in immunology.

Like most dreamy young people, I also wanted to change the world, and to do so, I thought it was crucial to be part of the revolutions that were unfolding. Excellent teachers at the veterinary school had genuinely initiated me to study the immune system. I was on the lookout for an appropriate atmosphere for pursuing further comprehension of immunology. Serendipitously France happened to me.

My colleague Girija at the Veterinary College pointed out a notice displayed on the board beside Dean’s office. Other than writing to international universities or newspapers, in those days, college notice boards were the only way of knowing the opportunities available for higher education. Internet was unheard of, no Google, no websites, no emails. If you missed the notice on the board, maybe you missed a crucial turn in your career. I applied for the French government scholarship, and I got a call for an interview in New Delhi. I remember Professor Malaviya of AIIMS was one of the examiners. My friends were intrigued by my preference for France over the United States or England for higher studies. Usually, those were the favored destinations for higher education among Indians.

Why France, they would ask.

I guess they were in line with the accepted notion about education in the west. On the other hand, I was fascinated by research in Immunology in France. I saw the opportunity in technological advancements in a wide range of disciplines. In addition to the vaccine against Rabies, French scientists were making landmark discoveries in Immunology. France is the country of Louis Pasteur. France is the country of Institut Pasteur where I was fortunate to do my doctoral work. 

After some initial struggle in France, I alighted in the laboratory of Professor Donny Strosberg, and it was worth the wait. Donny’s lab was the perfect place for me to realize my dream, at least the beginning of it. The laboratory had established a state-of-the-art approach for producing monoclonal antibodies. My thesis research project implicated generating monoclonal antibodies to study the beta-adrenergic receptors. Jean-Gerard Guillet was my true teacher. I learned the basics, the method, and all the nuances associated with it with his supervision. 

On the shoulders of Laurent Emorine, I had a hard time in the lab too.

Even before I completed my doctoral studies in France, I got the opportunity to collaborate with India, thanks to Professor Sharat Chandra of the Indian Institute of Science, Bangalore. Professor Chandra had visited the Paris laboratory before. The Indian Council of Medical Research (ICMR) extended support to Prof. Chandra, with which he planned a workshop on Hybridoma Technology at IISc -Bangalore in the September of 1985. I coordinated this 15-day Indo-French workshop along with a CNRS colleague Laurent Emorine.

Following a post-doctoral training of two and half years in southern California, I was recruited by CNRS as Chargé de Recherche 1er Classe, in the team of Professor Michel Kazatchkine. An exceptionally kind clinician, intelligent scientist, and remarkable human being, Michel Kazatchkine became the Head of the French National Agency for AIDS Research, the HIV/AIDS and communicable diseases global ambassador. He held other key positions in several international bodies related to health and medicine. Michel Kazatchkine strived hard towards the awareness and treatment of patients with AIDS in India.

As soon as I was made responsible for the INSERM research team dedicated to studying Immunopathology and Immunotherapy, I began exploring modes of collaboration with India. I engaged a large number of doctoral and post-doctoral students from all over India. Nagendra Prasad from Karnataka was the first Indian post-doc to work in my group. Since the last thirty-odd years, there has not been any spell where there are no Indians in my team. I explored different opportunities that the system offered to strengthen the cooperation with India.

Our team had a wide range of research interests. From basic immunology, immunochemistry, autoimmune & inflammatory diseases, cancer, hemophilia, and immunomodulation by medicinal plants to diverse immunotherapeutic strategies. This allowed us to explore collaboration with a wide range of research institutes and universities in India.

In early 1990, the government of India established the Pravasi Bharatiya Diwas celebration, an occasion marked by special programs to recognize the contributions of NRI/PIO individuals among the Indian Diaspora. My team got selected for an Indo-French joint research project under Collaborative Project with Scientists and Technologists of Indian Origin Abroad Program (CP -STIO Project), framework an initiative of the Department of Science and Technology (DST). My research project involved Dr. Vir Singh Negi, Jawaharlal Institute of Postgraduate Medical Education (JIPMER), Pondicherry. 

Transfer of Knowledge through Expatriate Nationals (TOKTEN), an initiative of the Council for Scientific and Industrial Research (CSIR) of strengthened my interaction with India. It enabled me to visit several major CSIR institutions in December 1997 to discuss the implementation of some of the state-of-the-art technologies.

Indo-French Centre for the Promotion of Advanced Research (CEFIPRA) is another exceptionally efficient tool for facilitating Indo-French cooperation. With colleagues Prof V Nagaraja and Prof DN Rao at IISc, Bangalore, my team established a highly productive research program on the studies on catalytic antibodies in hemophilia. CEFIPRA also enabled us to organize an Indo-French workshop entitled ‘HOPE in RED’ (Host-Pathogen interaction in respiratory diseases) in particular, tuberculosis. 

Meanwhile, the Indian Council of Medical Research (ICMR) also launched collaborative research projects with INSERM (National Institute of Medical Research) of France on defined thematics such as infectious diseases, cardiovascular and metabolic disorders including diabetes. This ICMR-INSERM support helped my team to resume our cooperation with JIPMER, Pondicherry. With a keen interest in the immunomodulatory properties of plant-derived molecules, I developed collaborative studies with CSIR-National Botanical Research Institute, Lucknow, under the Bio-Asia scheme. 

Another highly interesting twist in the career brought me further closer to Indian science. In 2015, CNRS selected me as its Director of Delhi Bureau. This assignment expanded my horizon, in enhancing the Indo-French cooperation beyond the mere interests of my research team. CNRS has entered into a strategic partnership with DST, DBT, CSIR, and several prime institutions of the country. The collaborative projects involving CNRS are emerging steadily addressing many social issues of not only India and France, but the serious challenges that the world is facing today, through meaningful scientific projects. 

Srini Kaveri is the Director of CNRS Bureau in New Delhi.