Wiring the Brain

A new paper just out in Nature , by Peter Visscher and colleagues (including bio-ethicist Julian Salvulescu) explores the idea of polygenic genome editing of human embryos to reduce the risk of common diseases. This is, to say the least, a controversial idea, and a decidedly fantastical one. The authors present the results of statistical modelling which suggests that editing a small number of risk variants in each embryo’s genome could dramatically reduce the risk of a number of common disorders. But there are good reasons (lots of them) to doubt the assumptions on which this modelling is based and to have serious concerns about possibly deleterious unintended consequences of such interventions. I co-wrote a commentary on the article with geneticist Shai Carmi and law professor and bio-ethicist Hank Greely, outlining some of the limitations of the modelling and our concerns over the dangers of the proposed approach. I’ll expand on those points here.   First, the development...

There was much excitement in the press and in the psychiatric research community recently as a flurry of papers was published, presenting the work of the PsychENCODE project. This project, involving the work of many labs, aimed to deploy the powerful tools of genomics to dissect the landscape of gene regulation in the human brain, with the ultimate goal of revealing the molecular underpinnings of psychiatric disease. Genome-wide association studies ( GWAS ) have revealed hundreds of common genetic variants that are statistically associated with increased risk of psychiatric disorders, such as schizophrenia, ADHD, bipolar disorder, and, to a lesser extent, autism. What they have not revealed is how such variants increase risk of disease. The PsychENCODE project aimed to generate a set of data that would allow researchers to answer that question. There are a number of challenges in going from identification of an associated risk variant to elucid...

Why did the axon cross the midline? That seems like a simple enough biological problem to solve. In the developing nervous system, especially in the anatomically simple spinal cord, some nerve cells send a slender nerve fibre (called an axon) across the midline of the nervous system to connect to cells on the other side. The projections of other neurons are restricted to the same side as their own cell bodies. The connections between the two sides are crucial in coordinating movement of the two sides of the body. But, more importantly for this discussion, this system is simple enough to be genetically tractable – at least it seems so. When I arrived as a graduate student in the lab of Corey Goodman at the University of California at Berkeley, his group had just carried out a genetic screen in fruit flies to try and understand how this developmental decision was controlled. Flies have an equivalent of a spinal cord, called the ventral nerve cord , and Corey a...