Shibasaburo Kitasato returned to the institute he had founded in Tokyo as a hero, and continued his work on disease. Four years after isolating the bubonic plague bacillus, he and his student Kigoshi Shiga discovered the organism that causes dysentery, an infection of the lower intestinal tract. Seven years after starting his own laboratory in 1892 the Japanese government took control but Kitasato agreed to stay on as director at the time. However when the laboratory was consolidated into the University of Tokyo in 1914, Kitasato resigned. A scientist of Kitasato’s calibre needed autonomy and so he founded the Kitasato Institute, which he headed for the rest of his life.[19] Revered in his homeland, Kitasato was named the first president of the Japanese Medical Association in 1923 and was made a baron by the Emperor in 1924. After a long and distinguished career Shibasaburo Kitasato died in his homeland in 1931.
***
As for Alexandre Yersin, after the monumental disappointment of not being acknowledged as a discoverer of the plague bacillus, he returned to his adopted country of Vietnam. In 1895 Yersin established a new laboratory in Nha Trang, a small fishing village set on an idyllic bay. Putting his frustrations aside he continued his research into diseases. To finance the laboratory, which had been given in 1903 the imprimatur Pasteur Institute of Nha Trang, Yersin began cultivating grain crops and coffee, which led him to a new field of research: agronomy.
In 1904 Yersin was recalled to Paris to continue his research at the Pasteur Institute, where Emile Roux had become director. With Albert Calmette and Amédée Borrel, he made the important observation that certain animals can be immunised against the plague through the injection of dead plague bacteria.[20] On his return to his modest laboratories in Nha Trang, Yersin perfected an anti-plague serum that appeared to be successful in reducing the death rate significantly in both animals and humans. He then began to set up a network of laboratories and vaccination centres throughout Vietnam to facilitate the production and administration of the new vaccine.
Yersin was always deeply concerned with the needs of the sick and the poor. He lacked the ego of many of his contemporaries and as a true humanitarian fought against the exploitation of the lower classes. With the assistance of Paul Doumer, the governor-general of Indochina, a medical school that Yersin directed for many years was founded in Hanoi. Because of his work and his commitment to his fellow humans, many of the epidemics that spread through Indochina were controlled. In the early 1920s Yersin was responsible for planting the first quinquina plantations in Vietnam.[21] Quinine was the only effective treatment against malaria at the time and Yersin distributed it throughout the country. He never tired of new endeavours, also introducing the Brazilian rubber tree to Vietnam and at one time working for the Indochina Meteorological Service producing maps and tidal charts of the country’s coastal waters.
In recognition of Yersin’s medical achievements, the French government appointed him an honorary director of the Institut Pasteur in 1933. As a member of the Scientific Council, once a year he made the journey to Paris by air to fulfill his official duties, his last visit being in 1940 when he was in poor health. Alexandre Yersin died in 1943 at Suô’i Giao, south-west of Da Lat, at the age of 80 and his request in his will that he be buried at his beloved Nha Trang was carried out. And so ended the life of another great microbe hunter.
TOWARDS A PLAGUE VACCINE
With the discovery of Yersinia pestis the first step in eradicating the Black Death had been achieved but the disease would continue to take its toll until a successful weapon against it was available. The first vaccine for bubonic plague predated Yersin’s and was developed by Waldemar Haffkine two years after Yersinia pestis was identified. It was one of two vaccines developed by Haffkine which greatly advanced the lot of humankind. His first vaccine proved to be successful against cholera, caused by the bacterium Vibrio cholerae that Robert Koch had isolated in Egypt in 1883.
Waldemar Mordecai Wolff Haffkine, known in Russia as Vladimir Khavkin, was the son of a Jewish schoolmaster. He was born on 15 March 1860 in the Black Sea port of Odessa, which was then an intellectual and prosperous commercial centre of Russia. Haffkine went to school in Berdiansk and after graduating from high school in 1879 he enrolled in the Department of Natural Sciences in Odessa Malorossiysky University and studied physics, mathematics and zoology.
As for many Jewish people, life was difficult for Haffkine in anti-Semitic Russia during the Jewish pogroms. While at university Haffkine fortunately came under the influence of the prominent scientist Elie Metchnikov. Also during his university years Haffkine joined the Odessa Jewish self-defence league and when he was arrested and tried by the Russian authorities, the high-profile Metchnikov intervened on his behalf and he was released. However, the experience brought home to Haffkine how unsafe it was for Jewish intellectuals in Russia. However, Haffkine managed to complete his studies and in 1883 was awarded his degree in Natural Sciences.
After graduating in 1884, Haffkine joined the staff of the Zoological Museum in Odessa where he spent the next five years. His early research on infusoria, minute aquatic creatures including protozoa and unicellular algae, led to the publication of several papers in Russian and French scientific journals and pointed him in the direction of future research.[22] Despite such early scientific accomplishments Haffkine was denied a teaching position at a university, having refused to denounce his own religion and be baptised as a Christian. Haffkine’s response was that he had been a Jew before he became a bacteriologist and that there was a greater honour in remaining a Jew than in denying who he was to get ahead in his chosen field.[23]
Realising how precarious his situation was, Haffkine made the decision to leave his homeland. There was no future for him in Russia and certainly no way to advance his career. In 1888 the authorities gave him permission to emigrate to Switzerland and during his first year there Haffkine worked as an assistant at the medical school at the University of Geneva. It was the right move. At the age of 28, Haffkine became Assistant Professor of Physiology under Professor Schiff, and after eighteen months in this position, Louis Pasteur invited him to join the prestigious Pasteur Institute in Paris.
The day after his arrival, in 1889, Pasteur came to welcome Haffkine and found him nailing something to the doorpost of his laboratory. When Pasteur quipped that Haffkine had wasted no time in renovating his lab, the young scientist explained that he was putting up a mezuzah, a quotation from the Torah that is customarily nailed to the doorpost of a Jew’s living quarters or workplace. Pasteur seemed quizzical about why Haffkine was doing this in a laboratory, ‘a place of science’. Haffkine is reported to have replied that it was important to do so, ‘particularly in a place where we search for truth and need God’s guidance in the quest’.[24] This certainly accorded with Pasteur’s philosophy.
Elie Metchnikov, Haffkine’s mentor, had preceded him to the institute and was already working on the cellular defence mechanism of the human body against microbial diseases. Haffkine went to work on producing a cholera vaccine. During the nineteenth century five cholera pandemics ravaged Asia and Europe, taking a heavy toll of human life. Some scientists were still sceptical that the micro-organism Vibrio cholerae was the sole cause of the disease, but Haffkine produced his vaccine from an attenuated form of this bacterium by exposing it to blasts of hot air.
After successful animal trials Haffkine, prepared to make the ultimate sacrifice for science, performed the first human test on himself, injecting himself with cholera bacteria and then with his serum. Two days later he reported to Pasteur that the serum he had produced was not toxic to humans, and a few weeks after this, still suffering no effects, he reported his findings to the Biological Society.[25] Although his discovery caused excitement in the press, there was resistance in the medical establishment in France, Germany and Russia. Even more perturbing for Haffkine was the lukewarm response of his senior colleagues, including Metchnikov and Pasteur.
Perhaps prompted by disappointment at this point in his care
er and also by altruism, in 1893 Haffkine moved to India where hundreds of thousands of people were dying from ongoing epidemics. The Indian government was intensely interested in Haffkine’s new prophylactic vaccination for cholera and asked him to conduct trials. Little did Haffkine know that it would not be long before he would be directing his scientific zeal towards developing a vaccine for the seemingly invincible bubonic plague.
Haffkine made Calcutta his headquarters. At first in many communities, Haffkine, his vaccine and his motives were met with deep suspicion and he survived an assassination attempt by Islamic extremists. Haffkine’s commitment was greater than his fear, however, and during his first year in India he managed to vaccinate approximately 25,000 volunteers, most of whom did not contract cholera. It almost goes without saying that local medical bodies were critical of Haffkine’s cholera vaccine, but the phenomenal results could not be ignored for long. Within a short space of time Haffkine’s vaccine was saving lives all over the world. While successfully fighting one disease, Haffkine contracted another one, malaria, which left him no choice but to return to France to recover.
In a report on his Indian expedition to the Royal College of Physicians in London in August 1895, Haffkine dedicated his successes to Pasteur, who had recently died. Pasteur may not have supported Haffkine in the way he had expected but he had given Haffkine opportunities that were denied him in Russia. Haffkine was acknowledging that his association with Pasteur and other eminent scientists had shaped the direction of his research.
Although still suffering from the effects of malaria and against his doctor’s advice, Haffkine returned to India in March 1896 and threw himself once more into his crusade. He performed 30,000 cholera vaccinations over a period of seven months. And then as a reminder of how formidable a foe disease is, in October of that year a bubonic plague pandemic flared and struck Bombay. People throughout the entire country began to panic as thousands fell victim to the disease and died and thousands more fled the city. At this critical moment, the government turned to Haffkine for help once again. He immediately left Calcutta for Bombay to launch an assault against the age-old Black Plague.
On arriving in Bombay on 7 October 1896, Haffkine started work immediately to develop two vaccines, one that would prevent the disease and one that could cure it, as he felt this two-pronged approach would be the best way to control the plague. In a makeshift laboratory in a corridor of Grant Medical College Haffkine began the arduous work.[26] After four months a curative vaccine was ready for testing but it was not reliable so Haffkine turned his focus to producing a prophylactic vaccine using dead bacteria. The first obstacle Haffkine successfully overcame was to find a way to grow the plague bacilli, which he did in small glass containers. Once this was achieved the preparation of plague vaccine became feasible.
After another three months of persistent and fatiguing work, one of Haffkine’s assistants became ill and two others resigned. Haffkine ploughed on regardless and a vaccine was ready for human trials by January 1897. On 10 January Haffkine, as he had done with the cholera vaccine, vaccinated himself publicly to demonstrate the vaccine was harmless. The following month tests were carried out on volunteers at the Byculla jail. All the prisoners who were vaccinated survived the epidemic, while seven inmates from the control group who did not receive the vaccine died.[27] The government immediately embarked on vaccination campaigns and by the turn of the century, the number of people vaccinated in India alone reached 4 million.
Recognition followed quickly for Haffkine and his vaccine. The Aga Khan provided a building for a dedicated plague research laboratory. Haffkine was appointed as Director of the Plague Laboratory and prominent citizens of Bombay supported his research. Apart from producing and providing the vaccine for the whole of India the laboratory prepared many thousands of doses of vaccine for various tropical countries and Haffkine’s method of producing the vaccine remained basically unchanged for decades.
***
At times Haffkine must have wondered how much he had to achieve to win acceptance. After all his successes he still faced opposition from officials in several countries, including Russia. Even so, hedging their bets, two of Haffkine’s Russian colleagues visited him in 1898 in Bombay during a cholera outbreak in Russia. The significance of Haffkine’s cholera vaccine was immediately obvious. Called limfa Havkina (Havkin’s lymph) in Russia, the vaccine subsequently saved thousands of lives across the empire.
So many of the early medical pioneers had careers that were rollercoaster rides and Haffkine was no exception. He suffered greatly during an incident that became known unofficially as the Little Dreyfus Affair because of similarities with events that occurred in France in 1894 concerning a Jewish army officer, Alfred Dreyfus. (Tried for treason and sentenced to life imprisonment, it was many years before it was proven that Dreyfus was innocent and had been convicted on false evidence. The Dreyfus Affair split French public opinion and there were accusations that Dreyfus had been persecuted because he was a Jew.) Haffkine’s Little Dreyfus Affair began in a Punjabi village in 1902, when nineteen villagers who were vaccinated from the same bottle of bubonic plague vaccine died from tetanus.
A commission of inquiry indicted Haffkine. He was relieved of his position as Director of the Plague Laboratory and travelled to England where the Lister Institute reinvestigated the claim against him.[28] The original findings were overruled and the blame placed at the door of the doctor who administered the injections. It was discovered that an assistant had failed to sterilise a bottle cap that was contaminated with tetanus spores.
In July 1907, a letter published in The Times in London called the case against Haffkine ‘distinctly disproven’. It was signed by Ronald Ross, the Nobel Prize winner for his malaria research who spearheaded the campaign to exonerate Haffkine, and other medical luminaries and Nobel laureates, among whom were William Smith who was the President of the Council of the Royal Institute of Public Health, and Simon Flexner, the Director of Laboratories at the New York Rockefeller Institute. This was an affirmation of the esteem in which Haffkine was held in the scientific world.
After being absolved of any wrongdoing Haffkine returned to India to find that he had been replaced at the Plague Laboratory in Bombay. Once again overcoming disappointment and wanting to stay in India, Haffkine moved to Calcutta, where he worked until his retirement and his return to France in 1914. He settled in Boulogne-sur-Seine, occasionally writing articles for medical journals. In 1925, Haffkine must have felt both vindicated and valued when the Plague Laboratory in Bombay was renamed the Haffkine Institute in his honour. The Haffkine Biopharmaceutical Corporation Ltd and the Haffkine Institute for Training, Research and Testing in Mumbai continue to be important centres for public health.[29] Haffkine later wrote that ‘the work at Bombay absorbed the best years of my life’.[30]
Haffkine returned to Russia only once. In 1927 he visited Odessa briefly but found it difficult to adapt to the tremendous changes wrought by the Russian Revolution. In 1928 Haffkine moved to Lausanne and spent the last two years of his life there. He remained a practising Jew and in 1929, shortly before his death, still painfully aware of the persecution he had suffered, used some of the fortune he had amassed to establish the Haffkine Foundation in Lausanne to foster Jewish education in Eastern Europe.
The gifted scientist Waldemar Haffkine, who according to those who knew him had a strong personality but also possessed unusual charm, died on 26 October 1930. Apart from stemming the tide of epidemics with his vaccines for cholera and bubonic plague Haffkine had made many other significant contributions to science. He had conducted research on monocellular organisms, infectious diseases associated with infusoria, the adaptability of microbes to their environment and Asiatic cholera. In India, the government was indebted to Haffkine for his contribution to public health and he was the recipient of a number of honours. On the 104th anniversary of his birth, the Indian Posts and Telegraphs Department brought out a special commemorative stamp in memory
of ‘this great bacteriologist, whose work was of immense value to India’. In issuing the stamp the department also made the point that, ‘Perhaps the greatest tribute our countrymen have paid to him is by naming after him the Bacteriological Laboratory at Bombay, which he established.’[31]
In the 1960s the people of Israel commemorated the centenary of Haffkine’s birth with the establishment of the Haffkine Park. He was also honoured on an Israeli stamp issued in 1994. Featured on the stamp is the title of one of Haffkine’s manuscripts: ‘What to do against the plague in India’.[32] Waldemar Haffkine had worked out what to do and what he did was immeasurable. Much of Haffkine’s work as a bacteriologist was carried out in India in difficult conditions and with inadequate funds and equipment, a familiar theme amongst the stories of the medical pioneers. He was committed to helping in the endless fight against disease and to achieve this was not averse to personal risk-taking. Whatever his methods, Waldemar Haffkine was referrred to by Joseph Lister as ‘a saviour of humanity’.
UNDERSTANDING TRANSMISSION OF THE PLAGUE
Shibasaburo Kitasato and Alexandre Yersin had discovered the cause of the abominable Black Death and Waldemar Haffkine had developed a miraculous vaccine but the way in which plague was transmitted was still not understood. In many countries disinfection campaigns were undertaken, homes were washed with lime, suspected carriers were herded into camps and hospitals and travel restrictions were introduced. In some places carbolic acid was run through sewers, a practice which actually spread the disease even more rapidly because it flushed out rats that lived there, the very rats that carried plague flees.
Smallpox, Syphilis and Salvation Page 14