The Origins of AIDS (21 page)

As reviewed in
Chapter 4
, it was suggested that the Stanleyville public health laboratory played a role in the emergence of HIV-1, a hypothesis subsequently disproved. But could other Congolese laboratories have manipulated blood, serum or tissues in a way that would have facilitated the transmission of the virus?

In Léopoldville, a small laboratory set up in 1899 during the EIC period provided diagnostic assays not available elsewhere. The scope of tests gradually expanded: initially only the microscopic examination of stained or unstained specimens, then serology, followed by bacteriological cultures and, in the 1950s, haematological and biochemical assays and even viral cultures. From its early days, the Léopoldville laboratory conducted clinical research on sleeping sickness and experimented with a long list of candidate drugs. With
Louise Pearce, a visiting American scientist (always referred to as Miss Pearce rather than Dr Pearce, her unmarried status apparently being more important than her degrees!), starting in 1920 the laboratory carried out the trials that ultimately documented the efficacy of
tryparsamide in late-stage sleeping sickness, a major step forward in the treatment of this dreaded disease.
The laboratory became a respected world-class research institution with
seven Belgian MDs, three biologists, sixteen expatriate laboratory technicians and twenty-five Congolese nurses or medical assistants. In 1937, it moved to a site adjacent to the
Hôpital des Noirs and became known as the Princess Astrid Institute of
Tropical Medicine (literally, the companion institution of the Prince Leopold Institute of Tropical Medicine in
Antwerp). An annex was built to house a sleeping sickness laboratory where trypanosomes could be cultured (very few laboratories could do that at the time, or even today) and tsetse flies bred for experiments on animal models. Some experiments were conducted on monkeys (
Cercopithecus
and
Cercocebus
). A few autopsies were conducted on chimpanzees to look for filariasis, and a single chimpanzee seems to have been inoculated with trypanosomes, but these are the only documented cases of work on apes during more than fifty years of operations. By a strange twist of fate, fifty years later the conference centre of the Léo laboratory would become the site for
Projet Sida, the heart of HIV research in Africa in the 1980s.
^24
–
29

The laboratory prepared vaccines against multiple pathogens: the pneumococcus, gonococcus, meningococcus, staphylococcus, the agents of typhoid,
plague,
dysentery, tetanus, diphtheria, yellow fever and rabies. A few were imported and conditioned in Léo, while very crude vaccines were produced locally from bacteriological cultures of the targeted pathogens, heat-killed before inoculation, and used as preventive measures among populations with a high incidence of the targeted diseases, or in an attempt to control outbreaks. Some vaccines had therapeutic rather than preventive goals; for example, patients with
gonorrhoea were administered the antigonococcal vaccine in the hope that this mix of antigens inoculated in large quantities would result in the production of systemic antibodies that would in turn control the infection in their genital tract. An interesting concept was the
auto-vaccin
(self-vaccine): an isolate of a given pathogen obtained from a given patient would be grown in the laboratory, heat-killed and re-injected in the patient in large quantities, again in the hope of triggering the production of antibodies. Although these bacterial vaccines were probably ineffective, no animal cells were required for their preparation, and the risks of infection were those associated with any other type of injections. The yellow fever and rabies vaccines against viral infections required cells for their production, such as chick embryos
.
^7
,
30

When supplies from Europe were cut off in 1940, the Léopoldville laboratory started preparing therapeutic sera. This continued
throughout that decade, to be abandoned only when effective antibiotics such as penicillin became available for patients with
pneumonia and meningitis. Therapeutic sera contained, in principle, high levels of antibodies against the pathogen with which the recipient patient was infected. Sera could be produced in animals (which were injected with a large quantity of the bacteria of interest) or obtained from convalescent patients who had just recovered from the disease and were assumed to have developed antibodies. The health services reports indicate that the Léo laboratory produced therapeutic sera against the pneumococcus
, meningococcus and the agents of
dysentery. Ten years earlier in
Katanga, an antimeningococcal serum had been prepared from the inoculation of heat-killed bacteria to mules, due to a dearth of horses. Injected through a lumbar puncture, this was thought to reduce mortality. Horses were available in Léopoldville and were used for the preparation of antisera. The laboratory kept a colony of vipers to extract venom, minute quantities of which were then injected in the same horses to generate an antivenom serum.
^7
,
31
,
32

The Léopoldville laboratory also produced a therapeutic serum against
poliomyelitis, this time obtained from convalescent patients. The latter disease was relatively rare and the number of recipients must have been small, probably mostly European children. Interestingly, when the first epidemic of highly lethal
Ebola fever was recognised in the 1970s, a few patients were treated with convalescent sera obtained from patients who had just survived the infection (whether this measure was effective in reducing mortality is unknown)
. Necessity is the mother of invention and at the end of WWII the Léo laboratory even produced raw penicillin
, presumably from the fungus which was the original source of that revolutionary drug
. Across the river, the Brazzaville
Institut Pasteur was producing similar bacterial vaccines and therapeutic sera and kept a small colony of monkeys and a few chimpanzees for various experiments, such as verifying the efficacy of its vaccines and
antisera
.
³³

Smaller provincial laboratories were built in Elisabethville, Stanleyville (the one with the chimpanzee colony), Coquilhatville and Blukwa. The main function of the Stanleyville laboratory, apart from performing diagnostic assays for patients of the Province Orientale and producing crude bacterial
vaccines, was yellow fever surveillance and research. There were very few cases of this disease in the Belgian Congo, but it was still considered a potential threat. Hospitals throughout the colony would send to Stanleyville specimens of liver biopsies obtained
post-mortem from patients who had died with jaundice or an unexplained febrile illness. An edict made this compulsory if the local doctor decided it was needed; and if the relatives of the deceased thought that part of their loved one was sent abroad for mysterious and possibly magical purposes, it was just too bad. About 2,000 liver specimens were examined each year by a pathologist, and diseases such as
schistosomiasis,
tuberculosis and liver
cancer were far more common than yellow fever
. The Stanleyville laboratory performed
histopathological examinations on biopsies of other organs and each year diagnosed thirty to sixty cases of Kaposi’s
sarcoma, a cancer potentially associated with HIV. During the period for which laboratory reports are available, there was no evidence that this cancer was becoming more frequent. In 1953, the laboratory initiated a programme of blood transfusions from volunteer donors, the first in the country. Donors were identified, their blood group determined, and they would be asked by phone to come to the hospital when needed. Until then, relatives or friends of recipients had been donating blood on a case-by-case basis
.
^34
,
35

The Elisabethville laboratory prepared a smallpox vaccine for the whole colony, and more generally worked on viral infections. It had a long-standing interest in
poliomyelitis
. The
Coquilhatville laboratory made chaulmoogra oil from a local plant, to be used in the treatment of
leprosy
. The small laboratory in
Blukwa on Lake Albert focused on
plague, and during the 1940s produced large quantities of an antiplague therapeutic serum as well as an antidysenteric serum
.
During the 1950s, additional laboratories were established in
Lubero,
Bukavu,
Bunia,
Butembo,
Paulis and
Luluabourg.

Despite this wide and creative range of biological activities conducted in ten different sites over several decades, there is no documentary evidence that any of these laboratories manipulated blood or serum in a way or on a scale that could have facilitated the emergence of HIV-1.
The Stanleyville laboratory was the only one that used a substantial number of chimpanzees, but we have seen that this is not where HIV-1 originated.

Between the purchase and transformation of the EIC into the Belgian Congo in 1908 and its accession to independence in 1960, thousands of doctors and nurses left Belgium to work in the Congo. Some only stayed
for a few years while others spent most of their career there. None of them left such an indelible mark as Lucien Van Hoof.
^36
–
39

Born in 1890, a doctor’s son, Van Hoof completed his medical degree in Louvain, where he worked for a short time in a bacteriology laboratory.
During WWI, he served in military hospitals in Belgium, and volunteered to join the Belgian colonial troops fighting to conquer the then German colony of Tanganyika, arriving in Africa for the first time in 1916. After hostilities ended, the government of the Belgian Congo posted him to Léopoldville, first in the hospital and then in the laboratory
. He spent a few years in Boma as director of public health, in Stanleyville
as director of the laboratory and in Katanga as the province’s chief medical officer. He led a scientific mission in the ‘Belgian’ Mayombe to investigate an epidemic of
dysentery and another in eastern Africa for the
League of Nations, concerning the control of trypanosomiasis. He became director of the Léo laboratory in 1930, and was the main architect of its transformation into an institution with an international reputation and spacious, modern premises.

His scientific publications started to appear in 1917. Initially, they covered a wide variety of diseases, as he encountered them in his practice: malaria, onchocerciasis, yaws, dysentery, smallpox, influenza, tuberculosis, meningitis, amoebiasis and relapsing fever. He later focused exclusively on trypanosomiasis, its treatment, epidemiology, transmission, vectors and animal reservoirs. Van Hoof rarely used chimpanzees in his own research, but sent primates to his former mentor,
Jérôme Rodhain, in
Antwerp for the latter’s work on malaria.
⁴⁰

In 1934, because of his intellectual ability and knowledge of the colony, Van Hoof was appointed chief medical officer of the Belgian Congo for the usual six-year term.
However, WWII intervened and he stayed in this position until 1946. An indefatigable worker without any family obligations (he never married), he led an austere life. His job was to supervise the healthcare system of a huge and complex colony, which employed hundreds of doctors. Under his direction, there was an impressive development, which was barely slowed by the world war. He was also the chief medical officer of the
Force Publique and visited the expeditionary forces in
Egypt and
Nigeria. He never gave up his position in the colonial army and had risen to the rank of general by the end of his career
.

A population-based approach was gradually introduced in the Belgian Congo, with ambitious objectives to control certain tropical
diseases, like its French neighbours. It was no longer a matter of simply treating cases one by one for the sake of charity, but of reducing the spread of some of the transmissible agents by ‘sterilising’ their human reservoir. Relatively reliable national statistics were collected for the first time. During his twelve years at the helm, the incidence of trypanosomiasis was reduced by two-thirds. The number of cases of
yaws and
syphilis doubled because resources were allocated to diagnose, treat and record cases in previously neglected parts of the colony.

Despite a heavy administrative workload, Van Hoof maintained his intense scientific focus and became a leading expert on African trypanosomiasis. To speed up its control, he initiated a series of experiments on the preventive power of pentamidine, a drug that had just been added to the therapeutic arsenal. The idea of preventing trypanosomiasis by chemoprophylaxis (giving a drug systematically and regularly to the entire population of endemic regions) was not new but had never been used on a large scale.
Suramin, the only drug utilised for this purpose, had to be given IV every three months, which posed an insurmountable logistical problem.

After a few preliminary tests on guinea pigs, Van Hoof turned to humans. Earlier in 1942, two healthy volunteers had been experimentally infected with a parasite called
Onchocerca volvulus
, the agent of river blindness. The same year, the same two volunteers were given a single IM injection of pentamidine, then trypanosome-carrying tsetse flies were allowed to feed on these men’s blood every two or three days. The first developed trypanosomiasis after a year, the second after ten months. They were then treated with suramin, which incidentally allowed Van Hoof to show that this drug was also effective against onchocerciasis
. Three more volunteers were subjected to the same tsetse fly feeding three to six months after an injection of pentamidine, and none of them developed the disease. It was concluded that pentamidine had a protective effect that would last at least six months. Without delay, a field experiment was started in the
Kwango region, where three-quarters of the whole population were injected with pentamidine while the others served as controls. Over the following year, there were no cases of trypanosomiasis among those who received the pentamidine, while seven cases were documented in the control group. A complete success.
^41
–
45

These results had a far-reaching effect and sleeping sickness chemoprophylactic campaigns were soon organised in endemic areas not just
in the Belgian Congo, but also in the French and Portuguese colonies. In the
previous chapter
, we saw that, in Oubangui-Chari, these production-line injections facilitated the transmission of
HTLV-1, another human retrovirus. The putative role of pentamidinisation in the spread of HIV-1 could only have taken place outside the Belgian Congo, because Van Hoof’s beloved colony had very small populations of
P.t. troglodytes
. There were never any chemoprophylactic campaigns in Léo, where sleeping sickness was too rare to justify such an effort. Elsewhere, pentamidinisation campaigns undoubtedly contributed to the decline of trypanosomiasis, even if the theoretical foundations for the intervention (the persistence of the drug in the blood for several months) were incorrect
.

In 1946, with the war over and his successor named, a sick Lucien Van Hoof returned to Europe and took his natural place as a professor at the Institute of Tropical Medicine in
Antwerp, replacing
Rodhain who had recently retired. He developed his vision for the post-war development of the healthcare system in the Belgian Congo, a massive investment that came to be known as the Van Hoof–Duren plan. His reputation had spread far and wide, and he was invited to chair a tropical medicine conference in the US. He also returned to Léopoldville to organise studies on congenital malaria. He died in Antwerp in December 1948
.