All the world’s a stage, and all the men and women merely players. Shakespeare’s adage is as true in science as in life. There will always be antagonists and protagonists between whom egos flair and fighting words are flung. Such conflicts can end positively, with truth reached in agreement and collaboration, whilst others are won at a great cost to those involved and to the progress of science.
Sprinkled throughout the history of science are such conflicts; Lavoisier and Priestley’s dual claim to the discovery of oxygen, Agassiz and Darwin’s conflict over the origin of species, Einstein and Bohr’s decade-long debate over the nature of quantum mechanics and Watson and Crick’s unauthorized use of Franklin’s x-ray photo of DNA. As Max Planck put it, “A scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it”. Yet these scientific disagreements can have a great impact on humanity before the truth prevails, the nature of which is entirely dependent on the character of the scientists driving them.
Perhaps the most disastrous conflict between scientists was seen in the USSR. Nikolai Vavilov was a prominent Soviet agricultural biologist who discovered the origin of many cultivated plants and made important advances in crop diversity. At the height of his success in the mid-1920s, he travelled the world to collect seeds under the direct support of Lenin. Trofim Lysenko, a student of Vavilov’s showed great promise through his research on vernalization, which is the acquisition of a plant’s ability to flower upon exposure to low temperatures in the winter. Lysenko happened to believe in Lamarckian inheritance, the concept of passing on physical traits that are acquired over a lifetime to progeny. This anti-Darwin belief was heavily criticized by Vavilov. Fortunately for Lysenko, he was from a proletariat background and was favoured by Stalin, whereas Vavilov happened to be of a bourgeois upbringing. This cvonflict resulted in a death sentence for Vavilov and a twenty-year ban on studies in the field of genetics as future experiments threatened the validity of Lysenko’s work. The impact was uncontested support for the collectivization of farming, which then lead to mass starvation aside from a stagnation of Soviet biology for many decades.
A more recent and well-known example of conflict in science can be found in the genome war, sparkedby Craig Venter and Francis Collins. Whilst Collins headed the publicly-funded human genome project as director of the National Human Genome Research Institute, Venter had grand ideas for accelerating genome sequencing using a shotgun approach in his time at the NIH. Venter’s ideas were deemed radical and as a result, he failed to gain public funding for his work. Frustrated, the maverick Venter partnered with industry and founded Celera, a company through which he was able to accelerate the sequencing of the human genome at the cost of making genomic data temporarily patentable by his investors. The Venter-Collins camps were able to settle their differences over the human genome through combining data and presenting it as a joint discovery. Aside from accelerating the sequencing of the human genome, this power struggle resulted in a huge leap forward in sequencing technology and the establishment of shotgun sequencing as a staple technique in the field.
The falling-out between high profile scientists can also be found closer to home. Tak Mak, an internationally renowned and respected immunologist and his charismatic, whiz-kid protégé Josef Penninger underwent a publicly documented investigation over alleged scientific misconduct. Penninger was officially exonerated of fraud; however, some of his high-impact scientific publications remain irreproducible despite being well-controlled and peer-reviewed. The result of this conflict was Toronto’s loss of a brilliant scientist as Penninger moved to Austria to head the Institute of Molecular Biology.
Perhaps one of the longest running conflicts in modern science is that between the virologists Robert Gallo and the Nobel Laureate Luc Montagnier, two larger than life characters. The Gallo-Montagnier caper began with their “co-discovery” of HIV in the early 1980s, which caught the media’s attention with allegations of scientific fraud and consequently ensued a cross-Atlantic legal battle. This conflict had all the trappings of a Hollywood drama, which has lead to the publication of several books and even a movie.
Robert Gallo entered biomedical research after the death of his sister from childhood leukemia. Recruited to study leukemia at the NIH, Gallo focused on viral-associated cancer. His early work involved the isolation of leukemia-associated retroviruses, which turned out to be animal retroviruses due to sample contamination. This early event provided indications of Gallo’s highly competitive, aggressive, and manipulative nature. In spite of this questionable incident, Gallo went on to discover IL-2 and showed it could sustain T-cell growth. This allowed him to identify human T-lymphotropic virus (HTLV) as a leukemia-associated retrovirus in 1981. When AIDS began to surface in the early 80’s, Gallo quickly hypothesized a viral cause and was placed as head of the National Cancer Institute’s AIDS task force.
Montagnier’s childhood also inspired him to pursue medical science through the suffering of mankind as he witnessed the death and destruction of World War II in France. Swept up by advances in genetics and molecular biology, Montagnier was inspired to become a virologist with his first major discovery being the observation that RNA could self-replicate like DNA. He went on to demonstrate the oncogenic potential of DNA viruses and confirmed the hypothesis that retroviruses integrate into host genomic DNA. Montagnier founded and directed the Department of Virology at the Pasteur Institute by the time the AIDS epidemic was identified.
AIDS was diagnosed as a new disease in the early 1980s. This disease was quickly hypothesized to be viral; however, Gallo used his clout to push the hypothesis of an HTLV causative agent. In hindsight, this was somewhat myopic as HTLV causes an oncogenic increase in T cell numbers whereas it was known that AIDS resulted in a depletion of T cells. In addition, there were no reported cases of AIDS in areas where HTLV was endemic (e.g. Japan). Nevertheless, the speed at which the viral culprit was identified is a testament to modern molecular biology.
Montagnier’s group were the first to report an unknown virus discovered in an AIDS patient in 1983, which seemed unrelated to HTLV. They soon called this virus lymphadenopathy-associated virus (LAV). Despite the reported lack of similarity to HTLV, Gallo insisted on indicating a relationship between LAV and HTLV in the abstract of Montagnier’s paper upon reviewing it. A year later, Gallo’s group published results identifying the AIDS virus, which they called HTLV-III; notably, this virus could infect and be propagated in T cell lines. They claimed that despite both HTLV-III and LAV being identified in AIDS patients, they were distinct viruses. Initially, Gallo received widespread praise for his work while Montagnier’s research went relatively unnoticed.
Shortly after Gallo published his report on HTLV-III, his group patented a diagnostic test for the causative agent of HIV. A nearly identical test had already been reported by Montagnier and the patent applied for months prior to Gallo’s test. A bureaucratic blunder in the Patent Office not only resulted in delaying Montagnier’s patent but also failed to compare his patent with Gallo’s. Once the patent was awarded, Gallo delayed its production by almost a year through disputes. Thus Franco-American relations soured and thousands were unnecessarily exposed to the AIDS virus.
Cracks in the foundations of Gallo’s HTLV-III work began to surface with questions as to the origin of Gallo’s clinical isolates. Leading up to his 1984 publication, Gallo had requested a clinical isolate from the French after failures to culture his own clinical isolates. Montagnier obliged in the spirit of scientific collaboration and sent a sample of the same virus he used for his 1983 publication. Gallo’s lab used LAV to optimize their in vitro culture system in order to procure their own clinical isolates; however, Montagnier’s virus proved to be the most robust and was thus used for Gallo’s publication under the name HTLV-III. Over extended use, LAV was renamed multiple times in the Gallo lab purportedly to hide its origin.
In 1985, genetic analysis of HTLV-III and LAV showed them to be highly related and almost definitely the same clinical isolate. Gallo rebutted this observation by explaining that the American patient from whom HTLV-III was isolated must have infected the French patient who yielded LAV – a veritable needle-in-the-haystack scenario. In other words, Gallo’s landmark publication was merely a reproduction of Montagnier’s work.
Despite the mounting of harsh criticism, Gallo stood his ground to protect his ego. This stubbornness was rewarded by an official investigation into scientific fraud for which Gallo was proven guilty only to be cleared in an appeal. In addition, the Pasteur Institute challenged the NIH on the originality of Gallo’s patent, which was settled in a joint announcement by President Ronald Regan and Prime Minister Jacques Chirac. The royalties were to be split, an agreement which was further tipped in favour of the French when it was revealed that HTLV-III was LAV. This conflict could have been prevented had Gallo’s ego not come into play and the value of scientific openness been upheld.
In 2008, Montagnier was awarded the Nobel Prize for his role in the discovery of HIV whilst Gallo was conspicuously left out. Without a doubt, Gallo contributed immensely to the discovery and treatment of HIV as the first to identify human retroviruses (HTLV), the discoverer of IL-2, and for his subsequent work on HIV biology. How did Gallo, who is the recipient of multiple international awards including the Gairdner award and two Lasker awards, miss the Nobel prize? Some have hypothesized it was his greed and the associated scandals that was the make-or-break.
But the story does not end at the Nobel prize: both Gallo and Montagnier remain scientifically active. Gallo heads the Institute of Human Virology at the University of Maryland and founded the Global Virus Network of virologists, an organization which aims to pool resources in the event of major outbreaks. After enforced retirement from the Pasteur Institute, Montagnier now heads a research facility at Jiaotong University in Shanghai. In a Jacques Benveniste-like flip, Montagnier now studies electromagnetic waves emitted by extremely low dilutions of pathogen DNA. He is serious about it, having published recently on the teleportation of DNA between two unlinked tubes under an electric field. Science is indeed acted out over the world by players with such unbelievable foibles and fame that they could well be penned by the great bard himself