by Pepin
At the Institut Pasteur in Paris, Auguste Pettit worked for sixteen years on developing a therapeutic serum containing high titers of antibodies against the poliomyelitis virus, to be given to patients with this disease. As it was difficult to obtain large enough quantities of serum from human cases recuperating from polio, he produced animal sera, which were then used on humans. Antipoliomyelitis serum was prepared from horses, monkeys and chimpanzees, and then administered to at least eighty patients. Two chimpanzees were used for this purpose; the first one was bled to death and the second was bled repeatedly over a two-and-a-half-year period. They were P.t. verus chimps from Guinea, and the patients were in France not Africa. So once again, this could not have led to the emergence of HIV-1.53
Eternal youth
Among French surgeons of the early twentieth century, Serge Voronoff had a most unusual résumé. Born in Russia, he emigrated to France as a teenager, changed his name to conceal his Judaism, got a medical degree in Paris in 1894, trained as a surgeon and worked in Egypt for fourteen years for the Khedive, the local monarch. There, according to his biographer, he was struck by the short life span of eunuchs among the Khedive‘s servants. His return to France in 1910 coincided with the emergence of a new speciality, endocrinology: the science of hormones. Hormones are secreted by some gland, transported via the bloodstream and have their main effect on distant organs. At the time, there was no hormone replacement therapy, neither for hypothyroidism, nor for diabetes, pituitary insufficiency and so on.54
Voronoff was given a chair of experimental surgery at the Collège de France in Paris, something to be taken with a pinch of salt since the Collège did not have a medical school. He did not choose the easiest route for treating patients with endocrine dysfunction. While the obvious solution (soon to be available) was to find animal sources of the defective hormone, concentrate it and administer the product to patients orally or by injections, Voronoff attempted to tackle their problems by transplanting animal organs. He trained for a few months in the US under Alexis Carrel, soon to be awarded a Nobel for his pioneering work on organ transplants and vascular anastomoses.
Upon his return to Paris, Voronoff undertook experimental organ transplantations in animals, first within a given species and then between different species. In 1913, he performed his first xenotransplant (xeno- means foreign, in this case a foreign species), implanting a chimpanzee thyroid in a young man with congenital hypothyroidism. According to his surgeon, the patient improved. He performed a few more thyroid transplants, but this came to a stop when thyroid hormones were synthesised. During WWI, Voronoff grafted animal bones (in at least one case, from a chimpanzee) in soldiers with post-traumatic bone defects, but it was soon shown that in many cases bone could be obtained from the patient himself, at some other site.
Perhaps drawing on his earlier observations of eunuchs, Voronoff became convinced that the male hormones were necessary not only for sexual activity and phenotypes, but also for preserving various functions of the body, and especially the brain. Ageing was seen as a consequence of a degeneration of the testes. In his laboratory, he attempted to transplant testes from young animals to their older counterparts. Eventually, in 1920 this culminated in his first interventions on two humans, one of whom received the right and the other the left testes of the same baboon. These did not work well, and Voronoff attributed the failure to the use of organs from a species too different from humans. He decided to use chimpanzees instead.
Over the next two years, Voronoff performed twelve testicular transplants, from chimpanzee to man. It was not possible at the time to perform microvascular surgery, and Voronoff thought he could avoid the necrosis of the transplanted organ by actually grafting thin slices, with the assumption that small new blood vessels would form to re-vascularise the organ. That was very optimistic. Furthermore, nobody at the time had any understanding of the immunological rejection of a transplanted organ, presumably very severe when that organ was not of human origin. To maximise the use of the precious organs, each patient received half a testicle; from one chimpanzee donor four transplantations could be conducted. Finding chimpanzees was difficult. A Catholic order sent him a few dozen from Guinea. Through the Ministry of Colonies, he tried to arrange the shipment of chimps from Gabon but apparently none survived the journey. French newspapers reported that entrepreneurs in the Congo had sensed the potential for a quick profit so that the price of a chimpanzee had increased ten-fold on the local market, but it is unclear whether any of these animals made it to the old continent. To maintain his supply, Voronoff visited Guinea, Senegal and Mali in the mid-1920s.55–57
Like many experimental surgeons, Voronoff claimed that his procedure was successful in more than half his patients. It is hard to say whether this claim was the result of unwarranted enthusiasm, the lack of objective measures, the placebo effect of surgery, data manipulation for commercial reasons or perhaps even a genuine effect. Despite the necrosis and immunological rejection, it is possible that for a few weeks, as the transplanted organ was disposed of by the recipient body‘s defence mechanisms, there was some absorption of the huge quantities of hormones present in the graft, some of which were not too dissimilar from the human ones.
Even if Voronoff might have had sincere scientific aims initially, he quickly realised the immense commercial potential of the procedure. Here was a renowned surgeon, holding a chair at the Collège de France, who had invented a procedure that could act not only as a surgical Viagra but prolong life and enhance quality of life for decades. Many rich and old men were willing to pay a fortune for a shot at eternal youth. Voronoff even travelled to India in 1929 to perform a testicular transplant on a maharajah. Although some of his fortune may have been inherited from his second wife, Voronoff certainly made a lot of money out of this surgical adventure, allowing him to spend the last three decades of his life in a fancy villa on the Italian Riviera, where he had set up a chimpanzee breeding colony, probably as a public relations ploy.
Such a lucrative business interested colleagues in France and overseas, and Voronoff‘s biographer estimated that about 2,000 testicular transplants were performed in Paris, Bordeaux, Nice, Lille, Alger, London, Rome, Turin, Milan, Genoa, Vienna, Madrid, Lisbon, Porto, Berlin, Alexandria, Constantinople, Chicago, New York, San Francisco, Buenos Aires, Valparaiso, Rio and even in Hanoi. Voronoff himself claimed to have performed 475 transplants. Eventually, the procedure was completely discredited for a number of reasons, including the fact that Voronoff had started performing ovarian transplants (inserting a chimpanzee ovary into a woman and vice versa), which raised extremely serious ethical concerns (could one of these females become pregnant with a half-chimp, half-human baby?). Voronoff became the butt of popular humour in France and abroad. He died in 1951, aged eighty-five. We do not know whether he believed in the procedure strongly enough to have it performed on him, but he did transplant one of his older brothers, who came all the way from Russia for the surgery.54,57
So to get back to the question, could some of these chimpanzee organs have contained SIVcpz, which may have infected the recipient, starting a chain of transmission? That seems unlikely for a number of reasons. First, all of the procedures seem to have been performed in countries unrelated to the emergence of HIV-1. Second, most of the recipients were elderly men, who were unlikely to have infected many sexual partners, even if re-invigorated by the procedure. Third, at least according to what was documented, Voronoff‘s chimps came from West Africa, thus were P.t. verus, a subspecies not infected with SIVcpz. Fourth, it appears that in some of these procedures, the profit-seeking surgeons used testes from monkeys rather than apes due to a shortage of the latter. Therefore, this bizarre scenario can also be rejected.
In summary, there is now a reasonable body of evidence suggesting that the initial intuition of early researchers, the cut hunter theory, was correct and there is no alternative hypothesis that can be supported after a careful examination of the facts. Such occasional cases of cro
ss-species transmission must have been occurring for hundreds of years, as humans and P.t. troglodytes chimpanzees have coexisted in the forests of central Africa for many generations. For a long time these ancient cases of SIVcpz becoming HIV-1 did not manage to disseminate successfully. What happened in the early twentieth century for HIV-1 to spread successfully into human populations, while HIV-2 managed the same feat, albeit on a much more limited scale, in West Africa? We will start by briefly reviewing in the next chapter the history of European colonialism in central Africa, and how it created conditions propitious to the emergence of HIV.
5 Societies in transition
This background chapter aims to describe the settings in which the rest of the story took place. Africans understandably resent and reject as arrogant, or at least Eurocentric, historical accounts of their continent which consider the European penetration as the starting point and describe this process as discovery rather than what it really was: a military conquest for the purpose of economic exploitation. However, since the events relevant to the emergence of HIV-1 occurred during the colonial occupation of central Africa, and were facilitated by the profound social and economic changes brought about by colonisation, especially around the pool on the Congo River, we will focus on this period, but after a short detour which will enable us to examine how history confirms the molecular clocks of Chapter 3.
The slave trade and the exportation of infectious diseases to the Americas
The arrival of the Bantus in central Africa is, on the scale of human history, relatively recent, having occurred about 2,000 years ago, when migrants from around Lake Tchad managed to dominate the truly indigenous pygmy populations and for the first time introduced various forms of agriculture. In some areas, organisation was limited to small tribes that occupied geographically limited territories. Elsewhere, kingdoms were established, such as the Kongo kingdom, a loose confederation of tribes which corresponded to parts of current day Congo-Brazzaville, DRC, Angola and Gabon. These societies were not technologically advanced, which made it easy for Europeans to conquer the heartland of Africa once they found solutions to the health problems (mostly malaria) that decimated their early soldiers and settlers, many of whom died within two years of their arrival. But central African people had strong values, beliefs and traditions centred on the extended family, the clan. And there was already a fair amount of trading between ethnic groups within the Congo basin.1
For a long time, the European presence was limited to coastal areas, where forts were established for buying slaves. First in the region were the Portuguese, soon followed by the Dutch, Spanish, English, French and even Danes. Over three and a half centuries, 10.3 million slaves survived the journey and arrived in the Americas. Information on two-thirds of the voyages is available in a database prepared by the W. E. B. Du Bois Institute of Harvard University. It contains details on only 31,000 slaves embarked in Cameroon, and it is not possible to figure out how many more were embarked via Nigeria. About 35,000 were shipped from Gabon. However, the numbers embarked further south on the Congo coast were far greater: 79,000 from Loango, 107,000 from Malembo, 274,000 from Cabinda and 120,000 from the mouth of the Congo. It can be extrapolated that around 800,000 slaves originating from regions inhabited by Pan troglodytes troglodytes arrived in the Americas.2–4
These massive movements of human populations were responsible for the introduction of parasitic diseases from Africa into discrete areas of the Americas, where they found the necessary ecological conditions and/or suitable vectors to sustain their transmission until today. River blindness was exported to Guatemala, Mexico, Venezuela and Ecuador. Schistosomiasis (which causes inflammation of the rectum and fibrosis of the liver) managed to establish its cycle of transmission in the eastern regions of Brazil, in some Caribbean islands and Venezuela. Lymphatic filariasis, a disease causing massive swelling of the legs and genitalia, became endemic in Haiti, the Dominican Republic, Guyana and Brazil.5–8
Viral diseases were also exported. Slaves with yellow fever would die before reaching their final destination, but its mosquito vector travelled in the same ships and managed to establish transmission of the virus into the Americas. Phylogenetic studies demonstrated that some strains of HCV found today in Martinique as well as strains of HBV currently infecting Haitians were imported during the slave trade. But the virus for which transcontinental transmission has been documented best is HTLV-1, the first retrovirus isolated from humans. Like HIV-1, HTLV-1 (which does not cause AIDS) originated in primates, including P.t. troglodytes. Phylogenetic studies indicated that some lineages of HTLV-1 found in the Americas were imported along with the human cargo. Using the same methods, researchers investigated whether HIV-1 or HIV-2 were imported into the Americas during the transatlantic slave trade. The conclusion is that this did not happen. This indicates that HIV-1 must have been rare or inexistent among central African populations until the middle of the nineteenth century, and that events subsequent to this period facilitated its emergence.9–15
A pool on the river
The desire to penetrate Africa’s heartland appeared in the last quarter of the nineteenth century, as European powers hoped to find exploitable resources and set up new colonies after most of the American colonies had established themselves as independent states, or become less lucrative after the abolition of slavery. The same powers which had traded millions of slaves over 350 years then used the abolition of slavery as moral justification for this new colonial conquest: their stated goal was to bring civilisation and morality to these primitive populations that did not yet know Christianity.16
In central Africa, French settlements were initially concentrated around the Gabon estuary. Christian missions were established, leading to the foundation of Libreville in 1849. Among its first inhabitants were a few hundred slaves whose ship had been intercepted by the French navy. It was not possible to take the slaves back to their homeland, so they were settled in what became Libreville, literally ‘free town’. The French presence in Gabon remained modest.
No Europeans had reached the inland pool on the Congo River since some brave Capucin priests in the seventeenth century. As the latter’s goals were spiritual rather than temporal, their achievement was quickly forgotten. Pierre (originally Pietro) Savorgnan de Brazza, born into a Roman aristocratic family, became an officer of the French navy to fulfil his desire for discovery and adventure. He first travelled upriver on the Ogooué in Gabon in 1872, aiming to reach the pool of the Congo, which would provide access to its basin, assumed to be rich in minerals, agricultural products and ivory. To Brazza’s disappointment, journalist Henry Stanley managed to cross the continent, from Zanzibar all the way to Boma near the mouth of the river, where he arrived in 1877 in pitiful condition, having descended the Congo from its source. Stanley was soon hired by Leopold II, the king of Belgium, who dreamed of establishing a large colony, for his own profit. Belgium itself had no interest whatsoever in acquiring colonial possessions. It would later change its mind.
In 1880, Brazza managed to reach the Congo by land. He arrived at the pool, thirty-five kilometres long and twenty-four kilometres wide, where 20,000 Bateke lived in trading and fishing villages on both sides of the river. The pool was the terminus for all navigation on the Congo, because a series of rapids starts a few kilometres downstream. During the slave trade, the area had been used as a depot for slaves purchased in the Congo basin, before they were sent to a coastal port. Brazza signed a treaty with a chief on the north side of the river, and planted the French flag. The chief could not read French and did not realise that he had conceded a large piece of land to France rather than merely getting some kind of protection and trading rights. Meanwhile, on the south side of the river, Stanley signed a similar treaty with another chief.17
Stanley worked for an individual, Leopold II, who was to become sole owner of the État Indépendant du Congo (EIC, Congo Free State), the largest private property in history, while Brazza worked for France, a parliamentary d
emocracy. Stanley was an adventurer motivated by greed, who killed hundreds during his journeys. Brazza was an atypical nineteenth-century explorer, motivated by humanitarian concerns, perhaps naively as France had other ambitions. These nuances were not lost on the local populations, and the city of Brazzaville still bears his name and erected a monument to honour Brazza’s memory, while across the border Stanleyville became Kisangani thirty-five years ago. The former Stanley Pool on the Congo is now known as the Malebo Pool.18
Back in France, Brazza had a hard time convincing the French government to ratify the treaty and invest in the development of a new colony in central Africa, which was quite a gamble since nobody knew whether this huge territory contained valuable resources apart from rubber and ivory. France had its hands full digesting the parts of Indochina it had recently conquered. Reluctantly, Brazza was given limited resources and 400 West African mercenaries to set up small outposts. This mission ended when the Berlin treaty was signed in 1885. European powers had divided most of Africa, with France acquiring what was initially called the Congo Français. But the true winner was Leopold, who grabbed the centre of the continent, designed as a buffer zone between the territorial ambitions of France, Britain, Germany and Portugal.
The task of establishing a French administration was given to Brazza himself, as commissioner-general of the Congo Français. Additional colonial posts were founded, more treaties signed, decrees promulgated, maps drawn, taxes levied and a number of skirmishes were fought against rebellious tribes. French rule was progressively expanded north of Brazzaville, reaching Bangui in 1889 and Tchad in 1900, which allowed, at least on paper, equatorial Africa to be connected with French West Africa. Treaties with other powers further defined its boundaries, but failed to provide the Congo Français with access to the mouth of the river. For a few decades its exports had to travel on the Belgian railway between Léopoldville and Matadi, or on the backs of porters, 7,000 of whom worked between Loango and Brazzaville, a twenty-five-day journey.