The issue was resolved with the description of a rodent malaria parasite, P. berghei
, in central Africa by a Belgian physician (Ignace Vinke) and entomologist (Marcel Lips) in 1948 [21
]. As often occurs with important discoveries, these workers had not been searching for what they ultimately found. Vincke spent the years of World War II doing malaria surveys in the former Belgian Congo (now the Democratic Republic of the Congo). In 1942 he observed sporozoites in the salivary glands of the mosquito Anopheles dureni
, collected near a major mining center, Elisabethville (now Lubumbashi). Precipitin tests on the bloodmeal contents of the mosquitoes' midguts indicated that they had fed on rodents or insectivores. When Vincke and Lips examined the blood of a local tree rat, Thamnomys
in 1948, they discovered a new species of malaria. They postulated that the mosquito salivary gland infection with sporozoites observed years earlier and the newly described blood infection were the same species. Vincke named the parasite in honor of his close friend, Louis van den Berghe, of the Prince Leopold Institute of Tropical Medicine in Antwerp. However, it was not until 1950 that Vincke was able to show that sporozoites collected from these mosquitoes produced a typical P. berghei
infection when injected into laboratory mice [22
]. The life cycle had been completed!
An interesting sidelight to this discovery was the speed with which the authors felt they had to make the announcement. An American expedition to Sudan in 1948 led by Harry Hoogstral sent back information that they had discovered a new malaria parasite in the elephant shrew Elephantulus
] and a shipment of live shrews was sent back to the United States. The news was widely reported in the American press but as sometimes happens, some American newspapers had garbled the information and reported that malaria had been discovered in elephants! In retrospect, elephants were not shown to be hosts of Plasmodium
, although a new malaria parasite had been discovered in a small mammal. Vincke and Lips were justifiably concerned about being “scooped” and they searched for a means of rapid publication. By luck, the Fourth International Congress on Tropical Medicine and Malaria was convening in Washington in May 1948. It was already too late to add a Vincke and Lips paper to the agenda but Louis van den Berghe, who already had a paper scheduled on research in the tropics [24
], was able to append to his paper an announcement and description of this new rodent malaria parasite. In all respects, this was a landmark International Congress. It was the first one ever held in the Western Hemisphere and it had been 10 years since the previous one in Amsterdam, the planned intervening International Congresses having been canceled during World War II. In attendance were many scientists and physicians who had spent World War II working on malaria and malaria control projects and then were continuing with malaria studies when they returned to academic life. A further elevation of excitement within the community of malaria researchers earlier in this annus mirabilis
, 1948, was attributable to the announcement of the discovery of the exo-erythrocytic stages of mammalian malaria for simian [25
] and then human [28
] malaria. Van den Berghe's announcement of the availability of a rodent malaria parasite at that Congress was a seed that fell on very fertile ground. Due to the graciousness of the Belgian workers, P. berghei
was soon widely distributed throughout the world and a new era in malaria research had begun.
Among the recipients of this rodent malaria parasite was Harry Most, who had returned to the United States from the U.S. Army to become Chairman of the Department of Preventive Medicine at New York University (NYU) School of Medicine. During the early 1960s, Dr. Most also served as Chairman of the Armed Forces Epidemiological Board and Director of its Commission on Malaria; these were civilian advisory panels that no longer exist. With the financial support of these groups, he initiated a project at NYU on biology of rodent malaria. He was joined by Meier Yoeli, who had come from Israel by way of William Trager's laboratory at Rockefeller University. The major shortcoming associated with research on P. berghei was that no one had succeeded in identifying the conditions permitting a complete parasite cycle that included transmission of the sporozoite stage of the parasite by mosquitoes. Laboratory research was restricted to the erythrocytic stages of the parasite and its transfer by blood inoculation between rodents. With the eventual goal of developing a prophylactic vaccine against the pre-erythrocytic stages of the parasite, NYU studies centered on completing the life cycle of this parasite to permit mosquito transmission under laboratory conditions.
As luck would have it, I was in the right place at the right time. I was a post-doctoral fellow at Johns Hopkins University from 1961 to 1963, working on insect physiology, and also studying mosquito transmission of P. gallinaceum in the laboratory of Lloyd Rozeboom. During a trip to New York City in May 1963, I visited with William Trager, whom I had met on several previous occasions. (During the war, he had been a friend and associate of my former research advisor at Cornell.) When I asked Trager whether he was aware of any positions open in malaria research, he explained that on the previous evening he had sat next to Harry Most at the annual dinner of the New York Society of Tropical Medicine and Most had asked him if he knew of a medical entomologist, trained in insect physiology, who was looking for a job. I contacted Dr. Most, who then interviewed me, and before he even had an opportunity to advertise the position, I was hired to engage in these efforts! So, preparatory to my starting date in September 1963, I immersed myself in what was known about the biology of P. berghei in Africa.
The natural mammalian host of P. berghei
is the tree rat, Grammomys
found within remnants of ancient upland forests (forest galleries) that run alongside rivers in central Africa. The parasite is transmitted by the mosquito A. dureni
. Vincke, the discoverer of this parasite, had described in his papers that the environmental temperatures were 18° to 21°C during the transmission season [22
]. I was struck that this relatively cool microenvironment was not what one normally associates with tropical Africa. These low temperatures were confirmed by my NYU colleague, Meir Yoeli, during a trip to this region in December 1963. Accordingly, I set the NYU insectary temperature to 21°C, even before Yoeli returned. The reward: complete sporogonic development and production of infectious sporozoites in A. quadrimaculatus
that had fed on gametocyte-carrying hamsters. We reported this in 1964 at the International Colloquium at the Prince Léopold Institute in Antwerp, organized to commemorate the discovery of P. berghei
16 years earlier [29
]. I also had the privilege at this Conference of meeting Ignace Vincke, the discoverer of this parasite. After further analysis of optimal temperature conditions for sporogonic development [30
], our described procedure soon became the standard protocol used for mosquito transmission of rodent malaria.
During the next several years the explosion of research on mosquito transmission of malaria continued with P. berghei and other rodent malaria species subsequently discovered in central Africa. It is worthy of note that, by chance, the first of the rodent malaria parasites discovered was P. berghei, simply because it is enzootic in the region where Vincke and Lips were working. That this parasite had such unique and restrictive temperature requirements for development in mosquitoes was responsible for delaying exploitation of laboratory research on mosquito transmission of rodent malaria for more than a decade. If another central African parasite such as P. yoelii had been discovered first, the much more relaxed temperature requirements for infecting mosquitoes would have allowed sporogonic development to be regularly achieved in the laboratory many years sooner.
During the next couple of years, research was focused on working out the parameters for sporozoite transmission of P. berghei
to laboratory rodents and the characterization of these mosquito-induced infections in laboratory rodents [31
]. In 1965, the NYU research group was joined by Robert Herman, an immunologist from Rutgers University and later by Ruth Nussenzweig, an immunologist from Brazil. The next few years continued with biological studies [37