George Church is the Robert Winthrop Professor of Genetics at Harvard Medical School. Photo by Angela AlbertiLast summer, six scientists proposed a project they compared in scope and ambition to the Human Genome Project: to map the activity of the human brain. In February, news media reported that the Obama administration plans to move forward with that effort, known as the Brain Activity Map.
One of those six scientists was George Church, professor of genetics at Harvard Medical School and a core faculty member of the Wyss Institute for Biologically Inspired Engineering. Church, who is also a founding investigator of the Human Genome Project (HGP) and Personal Genome Project (PGP), sat down with Harvard Medicine News to discuss the roots, ambitions and challenges of the Brain Activity Map (BAM).
Q: What is a brain activity map?
The brain activity map is really a project to enable us to read from and write to individual neurons in complex networks. Because a lot of neural circuits are quite extensive and integrate many different parts of the brain, we want to be able to have both global and extremely local resolution. It’s analogous to the genome project, where at the beginning we had the ability to look at a piece of a gene in detail or the whole genome at low resolution, and we wanted to be able to do the whole genome at single base-pair resolution, since we needed both at once. And that’s what BAM is: a technology project to bring down the costs and improve the quality so that we can do this single-neuron resolution with arbitrarily large circuits.
Q: You say similar to the Human Genome Project. How will it be different?
Where I hope it will be different is that the Genome Project put off a lot of technology development. The technology that kicked in after the HGP was over brought down the price a millionfold. It would have been nice to have had that earlier. Also linking interpretation of genomes, environments and traits (as in PGP) got traction only near the end of HGP. So I think BAM is being designed with more flexibility and focus on technology and interpretability. Also, the Genome Project didn’t adequately embrace small science. I think enabling small labs to do amazing things might be more powerful than having a juggernaut of a large lab, or worse yet, a race among a few large labs.
Q: What’s the backstory of the Brain Activity Map?
A number of us, whether synthetic biologists, nanotechnologists or neuroscientists—most of us interdisciplinarians—met in September 2011 atChicheley Hall in the UK. We realized that we were converging on a vision very similar to that of the Genome Project in 1984 in Alta, Utah, where we weren’t quite sure, but we felt like the technology was ripe. And so six of us decided that we were aligned enough in this vision that we should start writing it up and organizing it.
Q: Why now?
Every now and then you’ll get a gap between technological advancements and their application. A number of technologies developed in synthetic biology, nanochemistry, optical fibers and so forth haven’t quite been integrated with each other and cross-fed into quantum leaps that could impact various aspects of neurobiology. Basically, it’s a recognition that a cluster of new technologies are overripe for combining with one another and applying to neuroscience.
Q: What question would you most like this project to answer?
We hope get fundamental understanding about emergent principles, things that you might see only when you have both depth and breadth. Insight into medical pathologies and day-to-day emotions, creativity, etc. I would also love to see huge improvements in cost, accuracy, comprehensiveness and low invasiveness. The latter set are engineering hurdles, rather than a particular discovery.
Q: Where do you foresee the greatest benefit to basic science, to clinical care and to society more broadly? Let’s start with basic science.
In basic science, this helps people do what they’re currently doing but better: more comprehensively, with better time resolution, and greater ability to test hypotheses involving increasingly complex circuits.
Q: And clinical?
Current methods can record and stimulate on the order of dozens of neurons or clusters of neurons simultaneously in a human brain. These technologies don’t always last a long time as implants and it’s hard to get fine measurements and control needed for everyday life.
The number of neurons that you can handle simultaneously has been creeping up very slowly. So, we’d like to accelerate that and lower the invasiveness, replacing electrodes with other means—optic fibers and/or synthetic biology.
Q: And to society?
Practical applications of the BAM project aren’t guaranteed, but if it is successful, BAM could extend well beyond neurobiology in the same sense that the Genome Project extended beyond genetics. A brain activity map could tell us about decision making, about normal behavior that isn’t pathological, about artificial intelligence. It could give us profound philosophical insights that could be troubling or awe-inspiring, like what it means to be conscious or even various levels of consciousness.
Q: And where do you anticipate the greatest challenges—technological, organizational and social/ethical?
First and foremost, safety has to be paramount, and that’s why I’m interested in talking about the human from the beginning. From an organizational perspective, I think we need to be careful not to create juggernauts that aren’t as nimble as small labs. We need to have feedback where small science benefits and is compared constantly to the big. We need to have ways to encourage cost-effective, out-of-the-box technologies that don’t necessitate a big company or a big institute.
Q: And technological?
The real technological challenge is to get people to think out of the box. To avoid complacency. If we get a tenfold improvement, people can’t just say ‘that’s great, let’s quit for a decade.’ They should look for the next tenfold, and the next. Also, how do you adjust priorities? If one group is working on optics and another one is working on synthetic biology, are they in competition? Are they synergistic? How do we optimize our interdisciplinary teams?
Q: How can Harvard contribute to the Brain Activity Map?
Boston is the genomics center of the world, so the organizational experience is here. In the HMS Department of Neurobiology, Mike Greenberghas a world-class team that tackles many of the problems that will both inspire and benefit from any technology improvements. Harvard also has an extremely strong stem cell community. The Wyss Institute for Biologically Inspired Engineering is exactly the kind of interdisciplinary force that’s required here, where you have mechanical and biological engineers working side by side. And the Broad Institute of Harvard and MIT has all kinds of diverse biomedical research that is really representative of the best small science—with the resources and efficiencies of a large-science context. And our affiliated hospitals are leaders in the translational research that will bring direct improvements for human health.