Laveran, Alphonse

Alphonse Laveran

French medical researcher and physician Alphonse Laveran (1845-1922) discovered the parasite that causes the endemic tropical disease of malaria. He also guessed correctly that the disease was transmit ted by mosquitoes.

The story of Laveran's discoveries was a remarkable one in several respects. They took shape not in the pure realm of laboratory research but in the field: Laveran was a military physician and surgeon posted to Algeria, where he observed the ravages of malaria firsthand. Laveran's hypotheses about malaria flew in the face of established scientific theories of his time, when the recently discovered role of bacteria in many other diseases was assumed to apply to malaria as well. Most remarkable of all was his ability to interpret what he saw under his primitive microscope: it was not a bacterium but a single-celled animal, trailing long filaments, that, in the early years of microscopy, appeared to be an entirely mysterious entity. Laveran's discovery of the malaria parasite was a scientific triumph combining patient observation, strong intuition, and the ability to synthesize diverse preexisting insights and ideas.

Spent Part of Childhood in Algeria

Charles Louis Alphonse Laveran was born on June 18, 1845, in Paris. His eventual choice of career followed that of his father, Louis-Théodore Laveran, who was a French military physician. His mother, the former Marie-Louise Anselme Guénard de la Tour, was herself descended from high-ranking army officers. When Laveran was five, the family was sent to Algeria, then a French colony where resistance to European rule was simmering. His first lessons in medicine came from his father, augmented by impressions gathered from the eyes of a child living in a tropical war zone. In 1856 the family returned to Paris, and the elder Laveran became a professor at the Ecole de Val-de-Grâce, a Paris military medical school.

Laveran attended two private schools in Paris, the Collège Saint Baube and the Lycée Louis-le-Grand, planning on following his father into the medical profession. To that end he enrolled in a military medical college in Strasbourg, France, in 1863, graduating in 1867 with a thesis on the repair of nerve damage. After that he joined the French military as a physician, and by the time the Franco-Prussian War broke out in 1870 he had reached the rank of medical assistant-major. He saw action as an ambulance officer during several major battles, including the disastrous siege of Metz, when he was briefly imprisoned by the Germans. After the French surrendered that city, he was moved to hospitals in Lille and then Paris. In 1874 he bested several other physicians in competitive exams and was appointed to a term as chair of Department of Military Diseases and Epidemics at the Ecole de Val-de-Grâce.

After completing his term as chair, Laveran was sent to the city of Bône in Algeria (now Annaba). Soon after that he moved to the city of Constantine (Qusantînah). Working in military hospitals in these two cities, Laveran was confronted by wards full of patients suffering from malaria, a common and serious tropical disease that was (and remains) potentially fatal and is invariably accompanied by extreme discomfort such as joint pain, intense flashes of fever and cold, and nausea. The disease took its toll on French military recruits, who sometimes dropped dead before they could be assembled into platoons. Laveran began making cultures of soil samples, doing autopsies, and drawing patients' blood with pinpricks in order to learn what he could about the disease.

At the time, malaria was poorly understood, and techniques for examining blood under a microscope were poorly developed. Laveran could see in the blood of his patients some small black granules or pigments that were already known to result from infection with malaria, but he had no idea what produced these pigments or caused the disease. By the third quarter of the nineteenth century, the germ theory of disease, and specifically the role of bacteria—single-celled organisms called prokaryotes, or organisms without a nucleus—in causing infectious diseases, had become generally accepted after experiments conducted by France's Louis Pasteur and Germany's Robert Koch had shown their widespread applicability. Malaria was thought by most scientists to be the result of an as-yet-undiscovered bacterium, and they were busily combing the air, water, and earth in malariainfested regions in search of it.

Spotted Motile Bodies

Laveran patiently continued his observations, and finally, early in the morning of November 6, 1880, he struck pay dirt: he spotted a moving organism on a slide he was examining under a high-powered microscope. It had long filaments that propelled it through the patient's blood like the legs of a swimmer, something no bacterium would do. According to an article published on the Malaria Site Web site, Laveran wrote, “In 1880, at the military hospital in Constantine, I discovered on the edges of the pigmented spheric bodies, in the blood of a patient suffering from malarial fever, thread-like elements resembling whips which were scurrying about with great vivacity, displacing neighboring erythrocytes [red blood cells]; from then on, I had no further doubts as to the parasitic nature of the elements I had found.”

The organism Laveran had seen was a protozoan, a single-celled microbe that contains a nucleus and shares certain characteristics with higher orders of animals—it can move, and it consumes other organic matter. Laveran found these protozoa in the blood of 148 of 192 malaria patients he examined, and he correctly concluded that they were the primary cause of malarial infection. Furthermore, he identified other small spherical organisms he had also found in patients' blood as stages in the development of the fullfledged motile protozoan that, he thought, lived on the surface of red blood cells and disrupted them (another researcher soon showed that the parasite actually grew inside cells). He named the new organism Oscillaria malariae and published his findings in an article titled “A new parasite found in the blood of malarial patients. Parasitic origin of malarial attacks.”

Laveran's ideas were not immediately accepted. Several other scientists claimed to have observed a Bacillus malariae or malaria bacterium, and Laveran's protozoan was an enigma with an appearance unlike any other microscopic organism that had yet been discovered. Many scientists looked to the familiar idea of bacteria as the most likely explanation, but experiments over several years in the early 1880s began to confirm Laveran's findings. An American military physician, George Sternberg, made an exhaustive search of air and mud from marshes in clearly malarial areas and found no trace of anything resembling Bacillus malariae. Other scientists observed parasites related to Laveran's protozoan in animals. In 1884 two Italian researchers named Ettore Marchiafava and Augusto Celli spotted blood organisms in malaria patients that were actually among the earlier stages of the malarial parasite Laveran had discovered, but they did not realize they were looking at the same organism. They named their new discovery Plasmodium, and that name, although technically inaccurate, continued to be used.

New techniques of microscopy yielded findings that expanded Laveran's own, and he continued to defend his ideas. He replicated his own results during a trip to Rome, Italy, in 1882, where he collected large numbers of blood samples from Italian soldiers who had served in the Roman Campagna, a swampy area south of Rome that was a notorious reservoir of the disease, and he then returned to Paris and the Ecole de Val-de-Grâce in 1884. That year Pasteur became the first big-name researcher to sign on to Laveran's theory, and by the end of the decade it had gained general acceptance. In 1889 Laveran was given the prestigious Brént Prize by the French Academy of Sciences.

Suggested Mosquitoes as Host

“After having discovered the parasite of malaria in patients' blood,” Laveran wrote, as quoted on Malaria Site, “there remained an important question to be solved: in what form did the hemacytozoon [the protozoan] exist in the exterior environment and how did the infection come about? The solution to this problem required long and laborious research.” He made extensive studies of air, water, and earth at sites known to be infested with malaria, but failed to find his parasite. “I was convinced that the microbe existed outside the human body, in a parasitic state, and most probably in the shape of a parasite of mosquitoes.”

Laveran presented this hypothesis in a new Treatise on Malarial Fevers and delivered it in report form to the International Congress on Hygiene at Budapest, Hungary. Once again, his ideas were generally rejected, but experiments by British researcher Ronald Ross, working in India, showed that the Plasmodium parasite did indeed develop inside mosquitoes. Soon malaria was understood to be a disease transmitted by mosquito bites, and was therefore almost impossible to eradicate.

The French military did not substantially reward Laveran for his accomplishments. In 1894 he was moved from the Ecole de Val-de-Grâce to the position of chief medical officer at the military hospital in Lille, and then to that of director of health services of the 11th Army Corps at Nantes. These were administrative posts where Laveran neither interacted with patients nor had access to a laboratory to do his beloved research. Offended, Laveran took a position as chief of the honorary service at the Pasteur Institute in 1896, heading a research lab of his own. For the next ten years he did research on trypanosomes—parasitic protozoa with a single flagellum (or whiplash tail) that live inside insects. He explored their role in several major diseases, including African Sleeping Sickness. In 1908 he founded a new Society for Exotic Pathology, remaining its president until 1920. He was inducted into major scientific societies in France, England, the United States and many other countries. In 1907 he was awarded the Nobel Prize in Physiology or Medicine. He donated half his prize money to the Pasteur Institute. In 1912 Laveran was made a Commander of the Legion of Honor, a French honor roughly comparable to a knighthood in England.

Laveran was a man entirely devoted to science. In 1885 he married Sophie Marie Pidanc¸et, but the pair had no children. He spent most of each day doing research, but during World War I he served on committees devoted to protecting and improving the health of French soldiers. He continued to work until a few weeks before his death, sending assistants to inform him of the day's happenings at the Pasteur Institute's labs even after he lost the strength to visit the labs himself. Laveran died on May 18, 1922, after a long illness.

Periodicals

Journal of Medical Biography, May 2002.

Online

“Alphonse Laveran,” Nobelprize.org, http://nobelprize.org/nobel_prizes/medicine/laureates/1907/laveran-bio.html (December 14, 2007).

“Charles Louis Alphonse Laveran (1845-1922),” Malaria Site, http://www.malariasite.com/malaria/laveran.htm (December 14, 2007).

“Laveran and the Discovery of the Malaria Parasite,” U.S. Centers for Disease Control, http://www.cdc.gov/Malaria/history/laveran.htm (December 14, 2007).

World of Anatomy and Physiology. Online. Thomson Gale, 2006, http://galenet.galegroup.com/servlet/BioRC (April 16, 2008).