Lots of peanut shells but no elephantA controversial account of the discovery of HIV.

Science Fictions: A ScientificMystery, a Massive Cover-up, andthe Dark Legacy of Robert Galloby John CrewdsonLittle, Brown and Company: 2002. 672 pp.$27.95

Jaap Goudsmit

“The French isolated the first AIDS virusever (HIV-1 Lai), and the Americans isolatedthe first virus that was truly representative ofthe Western AIDS epidemic (HIV-1 MN).The original Bru [AIDS virus] was evenmore representative, due to its slow-growingproperties, but nobody — not even Montag-nier — realized this virus existed until yearslater.” This is what I wrote some five years ago in Viral Sex: the Nature of AIDS (OxfordUniversity Press, 1997) about the controver-sy over whether human immunodeficiencyvirus (HIV) was discovered by the Frenchscientist Luc Montagnier or the AmericanRobert Gallo. John Crewdson’s book didn’tchange my mind.

Science Fictions is not exactly bedtimereading, and doesn’t add to the previouslypublished accounts of events, despite the fact that new interview material is included.Contrary to the book’s subtitle, Crewdsondoesn’t unveil a scientific mystery, he doesn’tunearth a massive cover-up, and even as abiographer of Gallo he fails to provide a clearpicture of either his subject’s character or hisscientific accomplishments.

Crewdson’s claim to fame in the AIDScommunity is his 50,000-word account ofthe discovery of HIV, and the controversysurrounding it, which was published in the Chicago Tribune on 19 November 1989. Science Fictions elaborates on the sametheme. It ends with the statement: “But everyroad down which Gallo had searched for anAIDS cure had been a dead end”, even thoughin the book important discoveries are attrib-uted to Gallo — the discovery of the virusHTLV-1 and T-cell growth factor. Crewdsonseems determined to convince us that Gallois a villain, but he didn’t convince me.

Three points of interest come to mindsurrounding the discovery of HIV and thesubsequent events. First, who discoveredHIV: Gallo, Montagnier or somebody else?Second, how did the discovery come aboutand who played what role? And third, did thepolitical, social, economic and psychologicalwarfare surrounding the issues of credit andcredibility in any way slow down progress inAIDS research?

The answer to the first question is straight-forward: HIV was discovered by FrançoiseBarré-Sinoussi in Montagnier’s laboratory at

the Pasteur Institute in Paris, with the supportof a team of French clinicians and researchers,including Jean-Claude Chermann, WillyRozenbaum, David Klatzmann and Montag-nier. They published their findings in May1983, about a year ahead of anyone else (Science 220, 868; 1983).

There seemed to be little to make a fussabout. Evidence of a new virus, Bru, presentin the lymphoid tissue of a homosexual man, was first obtained in January 1983. Brumultiplied only in primary cell cultures, andwith hindsight we know it was a type of virus(non-syncytium-forming, or NSI) that isnot transmissible to permanent cell lines.

But the cultures of HIV Bru were contam-inated at the Institut Pasteur at some point in1983 with HIV-1 Lai, a virus from an AIDSpatient that multiplied very quickly in cellculture. This syncytium-forming (SI) viruswas easily transmissible to permanent celllines, as Gallo and Mikulas Popovic discov-ered. All cultures subsequently sent out fromthe Pasteur, including those sent to Gallo andlater to Robin Weiss in Britain, were a mix-ture of the slow-growing Bru virus and thefast-growing Lai virus. It was no surprisethen that both Gallo and Weiss succeeded in

selecting the Lai virus while establishing per-manent cell lines from the primary culturethey received; this is the prime characteristicof SI viruses. Weiss subsequently suppliedhis cell line to Montagnier’s group, and thismarks the start of the controversy: bothGallo and Montagnier had cell lines in whichthe Lai virus predominated.

We have to credit Birgitta Asjo and colleagues (Lancet 2 (8508), 660–662; 1986)with the discovery that slow-growing, low-titre viruses are prevalent in early-stageHIV infection, and that rapidly growing,high-titre viruses are common in late-stageinfection. Subsequently, in the early 1990s,several researchers identified the slow/lowviruses as NSI viruses and the rapid/highones as SI viruses.

In 1995–96 the scientific basis of thesefindings was unveiled, and Gallo did play apivotal part in this. The story started whenJay Levy claimed that cellular antiviral factors circulating in the body were able toblock HIV infection. In December 1995,Gallo and co-workers identified the cellularmolecules RANTES, MIP-1a and MIP-1b asmajor HIV-blocking factors (Science 270,1811–1815; 1995). Gallo credited the first

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Burying the hatchet: Montagnier (right) and Gallo (left) at an awards ceremony in Spain in 2000.

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and last authorship to the people who did thework in his lab — Paolo Lusso and FiorenzaCocchi — with full awareness of the impor-tance of the paper, as Lusso recently told me.

The only cell receptor on CD4+ T cellsthat binds to these three ligands is CCR5, so ittook only a few months to prove formallythat CCR5 is the co-receptor for NSI HIVstrains, particularly in combination with thefinding that CXCR4 is the co-receptor for SI HIV strains. These final parts of the puzzleexplain in full the biological background ofthe emergence, during in vitro propagation,of the HIV Lai strain from a mix of SI and NSI viruses. This story is absent from Science Fictions, and other parts of the book alsoseem to have been written blindfolded.

The best illustration that the field did notsuffer from the Gallo–Montagnier contro-versy is the story of the development of bloodtests for the HIV virus, based on the detec-tion of antibodies against HIV proteins. Tocut a long story short, Crewdson claims thatthe Pasteur’s HIV antibody test was ‘better’than the tests originating from Gallo’s lab,but that Gallo’s ‘tests’ were approved morequickly and more easily, with the result thatsupplies of donated blood were less safe. Iwas personally involved in evaluating bloodtests in these early days, and find Crewdson’saccount of events to be biased.

In blood from AIDS patients, the testsfrom Abbott Laboratories and Litton Bio-netics — based on Gallo’s production cellline — were as sensitive as the Pasteur test,and the test from Wellcome was significantlymore sensitive than the Pasteur test (Lancet2 (8505), 483–486; 1986). All the tests weresignificantly less sensitive than the referencestandard when we tested blood from symp-tom-free HIV-infected individuals. We nowknow that this is because, in the early stagesof infection, antibodies against one HIVantigen (p24) predominate, and for techno-logical reasons many of the tests were defi-cient in picking up p24 antibodies.

Crewdson is right to point out that theAbbott Laboratories test showed high levelsof false positives (resulting in some wastageof uncontaminated blood), but other testsbased on Gallo’s cell line showed as few false positives as the Pasteur test, a pointCrewdson has ignored. Finally, in 1986 my colleagues and I showed (Lancet 2 (8500),177–180; 1986), in collaboration withAbbott Laboratories, that p24 is found in theblood before antibodies against this proteinappear — a finding that eventually improvedthe HIV tests substantially — and that thedrop in levels of p24 antibodies in the bloodof AIDS patients is directly related to the re-emergence of high levels of p24 in the blood(antigenaemia). As soon as we had solidproof that p24 antigenaemia heraldsimmunodeficiency and AIDS, we startedtreating those p24-positive individuals athighest risk for AIDS with AZT. None of this

sequence of events indicates that the fightagainst AIDS was slowed down because ofthe Gallo–Montagnier controversy.

Too often, Crewdson’s book ignores whatis obvious: that, in the end, the sciencecounts rather more than the scientist. Partic-ularly when every day 15,000 people arenewly infected by HIV. ■

Jaap Goudsmit is at Crucell and the AcademicMedical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

Bare bones of a lifeDart: Scientist and Man of Gritby Frances Wheelhouse & Kathaleen S. SmithfordTranspareon, Australia: 2001. 361 pp. £23

C. K. Brain

There have been many important milestonesalong the way to our ever-deepening under-standing of human origins, but one was ofspecial significance. It was Raymond Dart’sinterpretation, published in Nature on 7 Feb-ruary 1925, of the fossilized skull of a child,half-ape, half-human, that came into hishands without warning from a limestonecave at Taung in South Africa. It was the firstof its kind ever to have existed. How this 32-year-old anatomist had acquired the neces-sary neurological expertise to draw his radicalconclusions, and the confidence to challengeaccepted concepts of his time, is one of thethemes of this biography. It is essentially atribute, devoid of criticism and motivated, itseems, by admiration and respect. The resultcould easily have proved tedious, had notDart so richly deserved the kindly treatmentgiven to him by these two authors; instead, it is lively and enthralling.

Coming from a rural Australian back-ground, Dart graduated in medicine at the

University of Sydney. At the end of the FirstWorld War, he joined Grafton Elliot Smith inhis anatomy department at University College,London. Here Dart’s preoccupation with neu-rology deepened, and received a further boostwhen he spent a year at medical institutions inthe United States on a Rockefeller Foundationfellowship. In 1923 he moved to Johannesburgas professor of anatomy in the Medical Schoolof the University of the Witwatersrand.

Hoping to establish an anatomical muse-um in his department, Dart encouraged hisstudents to bring him interesting specimens,and in this way acquired a fossilized baboonskull from Taung. He immediately arrangedfor further fossils to be sent from the lime-works there, and to his delight these includedthe child skull that he named Australopithe-cus africanus. Apart from the complete faceand lower jaw, this specimen had a remark-able endocranial cast, showing the pattern ofstructures that had existed on the surface ofthe brain. Dart concluded that this pattern,together with other anatomical features ofthe skull, indicated that Australopithecushad represented an upright-walking linkbetween the apes and humans in Africa.

Although Darwin had speculated 50years earlier that Africa had been the conti-nent of human origin, discoveries elsewherehad swung scientific attention away fromAfrica to Europe and the Far East. Further-more, it was surmised that our early ancestors had acquired large brains beforethey walked upright. So one can imaginehow meagre was the support given to Dart’sclaims by the scientific establishment. At best, the skull was dismissed as that of ananthropoid ape, of little interest until adultspecimens became available.

But in South Africa, unwavering accep-tance of Dart’s interpretation came fromRobert Broom, who described the first ofmany adult Australopithecus fossils from theSterkfontein cave in 1936. These and subse-quent discoveries vindicated Dart’s hereticalclaims and, for many years, Dart was happy to leave the action to Broom. However, oneof Dart’s best-known students, and his successor in the anatomy department, PhillipTobias (author of the foreword to this biogra-phy), coaxed Dart back into the early-hominid field by showing him the fossilpotential of the Makapansgat Limeworkscave. Dart started field investigations there in 1946 and turned up several Australopithe-cus specimens among a vast collection of other mammal bones. Speculating on howthese bones came to be in the cave, Dart concluded that the ape-men had been mightyhunters, bringing back those bones thatwould be useful as tools and weapons, andpractising an ‘osteodontokeratic culture’.

In a long series of publications, Dartdeveloped his concept of “the predatorytransition from ape to man”, in which ourancestors “slaked their ravenous thirst on the

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Grandaddy: Dart, aged 91, with the Taung skull.

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