By: Saurav Seshadri, PhD
Mental Health Research
FET Flagships: lessons learnt
The European Commission (EC), the executive body of the European Union, launched two major Future and Emerging Technologies (FET) Flagship projects in 2013, with funding of about 1 billion euros each. Both aim to foster collaboration and scientific innovation over a period of 10 years, in the fields of neuroscience (the Human Brain Project or HBP) and material chemistry (the Graphene Flagship). As these projects transition to the infrastructure construction phase, which has been funded for the next two years, the EC has released a statement reflecting on the first, ‘ramp-up’ phase of these high-level initiatives.
The assessment presented of the Flagships’ success is uniformly positive; the Directors write that they ‘create amazing collaboration opportunities’, ‘mobilis[e]…enthusiastic young researchers’, and ‘spread an innovation mind-set in Europe’. The EC expects this evaluation to be corroborated by an independent review by a panel of experts, due to be published in early 2017. Key insights from the initial phase include the power of flagships to foster international community-building, the importance of balanced and transparent governance and management, and the need to fine-tune the size and composition of the Consortium of funding entities over time.
A driving force behind some of these lessons is the controversy that has faced the HBP almost since its inception: in 2014, a group of leading neuroscientists sent a protest letter to the EC stating that the HBP was ‘not a well-conceived or implemented project’. The letter now has more than 800 signatures, and led to the formation of mediation committee, based on whose recommendations in 2015 the HBP dissolved its executive board and significantly changed its scientific focus. The recent release of long-gestating computational tools has also helped address criticism. In navigating these challenges and moving forward, the HBP merits attention for its similarity to our own BRAIN Initiative in scope, methodology, and scale. (European Commission)
HIV’s patient zero exonerated
Gaetan Dugas was a French Canadian airline steward whose cooperation with CDC researchers helped identify sexual contact as a key step in HIV transmission in 1984. Unfortunately, this contribution earned him the label of ‘Patient Zero’ for HIV in the United States, which, along with an influential book that portrayed him as an unrepentant and malicious spreader of the disease, led to his widespread condemnation. On a larger scale, this characterization of the epidemic was a setback in the fight against homophobia, even at the policy level: in 1988, a Presidential Commission on HIV recommended that behavior among gay men that ‘fail[s] to comply with clearly set standards of conduct’ be criminalized.
However, a recent study in Nature has found ‘neither biological nor historical evidence’ that Dugas was the primary case of HIV in the US. The authors used a highly sensitive method to recover and sequence viral RNA from samples collected in the late 1970s, which revealed that HIV most likely jumped from Africa to the US via the Caribbean in approximately 1971, and that Dugas’ HIV genome was typical of US cases far downstream of ancestral strains. Ignorance may explain how scientists and the public in the 1980s came to scapegoat Dugas: with our current understanding of HIV’s long incubation period, it appears possible that many of Dugas’ partners could have contracted the disease years before they met him.
According to Dr. Anthony Fauci, director of NIAID, “The history of diseases has always been, in part, that someone needs to be blamed.” This study highlights the scientific and ethical pitfalls inherent to this mentality. (Sara Reardon, Nature News)
Schizophrenia secrets found hidden in the folds of DNA
Schizophrenia is known to be highly heritable, but the individual genes conferring risk for the disease have remained elusive. Advances in sequencing capabilities have allowed researchers to vastly increase the statistical power of studies aimed at identifying these genes: one such large-scale effort, the Psychiatric Genomics Consortium (PGC), identified over 100 common variants associated with schizophrenia, by using more than 36,000 cases and 100,000 controls. While progress has been made in understanding how some of these mutations contribute to changes in gene expression and brain network development, the majority remain unexplained. One obstacle is the fact that many of the loci are in regulatory regions, often without any obvious nearby target gene.
A recent study from Dr. Daniel Geschwind’s group at UCLA addresses this problem by showing that many non-coding variants identified by the PGC actually do contact genes involved in brain development, when the 3-dimensional structure of chromatin is taken into account. The authors used a cutting-edge technique called chromosome conformation capture to generate high-resolution maps of physical interactions between regulatory regions and genes. This approach revealed that loci of previously indeterminate function may in fact influence pathways linked to schizophrenia, including neurogenesis and cholinergic signaling.
Coming on the heels of another study, which used whole exon sequencing in about 5,000 cases to show that rare variants contribute to risk for schizophrenia, these findings represent significant progress towards understanding the mechanistic implications of genome-scale data in psychiatric disorders. This understanding is a key step towards using such data to develop personalized treatment strategies, which may be a priority for Dr. Geschwind, as he was appointed head of precision medicine efforts in the UCLA Health System in March. The above approach can also be generalized to other neurodevelopmental disorders (a prime candidate is autism, for which Dr. Geschwind helped establish the world’s largest gene bank), and holds great promise for the future of care for these devastating diseases. (Tim Newman, Medical News Today)
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