The technologies that drive neuroscience research sometimes come from unexpected sources. Consider for example the 2008 Nobel prize for chemistry, awarded for the invention of fluorescent genetic 'tags' for visualising proteins in living cells. The original breakthrough happened 20 years ago when one of the prize-winners had the idea of putting a gene from a fluorescent jellyfish into a worm in order to make it glow in the dark. The idea may have seemed a little crazy at the time, yet it has led to over 20,000 papers, and has become a key technology for neuroscience and many other areas of biology.
There will always be an element of serendipity in new innovations. But are there ways to make innovation more likely to occur? That's the challenge for the McGovern Institute Neurotechnology (MINT) program, established by MIT's McGovern Institute for Brain Research in 2006 to support interdisciplinary collaborations to develop new technologies for brain research. 'Progress in the field is heavily dependent on new technologies, both for basic research and for translational research on brain disorders and new therapeutic approaches,' says MINT program director Charles Jennings. 'We think the Institute is in an exceptionally good position to generate these ideas, given the extraordinary range of expertise that exists on and around the MIT campus.'
The MINT program aims to promote collaborations between neuroscientists and researchers from other disciplines by providing seed funds for new projects, typically for one or two years. 'We don't expect every project to get to the finish line in that time,' says Jennings. 'But it's a way to test a new idea quickly, to do a 'proof-of-concept' experiment that, if successful, can make it possible to attract additional funds elsewhere.'
In addition to MIT's talent pool, the MINT program also benefits from the McGovern Institute's financial support. 'This type of work is often high risk, and so it's difficult to support from traditional sources,' says Jennings. 'We're incredibly fortunate to have the funds from our donors that allow us to have this program. Instead of forcing researchers to write long applications and wait months for a decision, we can keep the paperwork to a minimum and give our applicants quick answers.'
Money is just one ingredient to success; it takes the right chemistry, too. Jennings sees himself as a matchmaker, making connections between neuroscientists with technical problems and experts from other disciplines with potential solutions. At MIT, with almost 1000 faculty members, he usually need not look too far for willing collaborators.
For example, a few months ago he was considering whether carbon nanotubes, a material used for many applications including advanced electronics, could be used as electrodes for brain recording and stimulation. A few clicks on the MIT website revealed that Jing Kong, a professor of electrical engineering just across the street from McGovern Institute, works with this material. 'We asked her if she was interested in a MINT project and she answered 'Yes' with little hesitation,' recalls Jennings. Kong is now collaborating with McGovern Institute investigator Emilio Bizzi, who studies the brain control of movement.
Bizzi, who is an MIT Institute Professor, hopes to use these materials for long-term recordings of neural activity, initially for basic research but ultimately as prosthetic devices for human therapy. Such devices might, for example, allow a paralysed patient to control a robotic arm or a computer directly from the brain.
The carbon nanotube collaboration is one of several interrelated projects on brain-machine interfaces that are supported by the MINT program. 'The idea of an implantable device that could record and stimulate brain activity over long periods of time is very exciting,' Jennings says, 'but it's also very challenging, and many of the most promising ideas are still at an early stage. We need a lot more academic research before the clinical or commercial potential can be fully realised.'
To overcome one of the hurdles, Bizzi is collaborating with Robert Langer, a renowned MIT chemical and biological engineer, to devise a way to get thin flexible polymer electrodes into brain tissue without bending them. Their proposed solution is a biodegradable coating that can provide temporary stiffness but disappears after insertion. In another MINT collaboration, Michale Fee of the McGovern Institute is working with Rahul Sarpeshkar, an expert on electrical engineering at MIT, to develop the miniature low-powered electronics needed to decode the signals from intracranial recording devices.
'Ideally, we'd like a tiny implant that can sit inside the brain without damaging it, maintain electrical contact with neurones for long periods of time, signal wirelessly through the skull, and never need a battery change,' Jennings muses. 'We're still a long way from being able to do that in a clinical setting, but any progress that we make toward that goal will also be tremendously useful for basic research.'
The MINT program is also exploring new approaches to human brain imaging, taking advantage of MIT's expertise in computer science. In two parallel projects, McGovern Institute's Nancy Kanwisher, who uses functional MRI to understand how the human brain recognises visual objects, will collaborate with computer scientists to test different approaches to the problem of analysing the very large datasets produced by functional brain imaging studies.
In one project, Kanwisher will collaborate with Polina Golland in the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL) to search for brain areas that respond to specific categories of visual objects. Golland has developed a computational model for identifying brain areas without the assumptions that may bias most current methods.
Kanwisher is also collaborating with a startup company called Navia Systems that was recently spun off from MIT research. Navia's founders have developed data-mining methods that can be used to identify clusters in large datasets, and they plan to test their approach on Kanwisher's imaging data. If successful, the method could also help to identify relationships between brain activity, genetics and clinical symptoms.
'I'm excited that we're starting to work with companies,' Jennings says. 'It's a chance for us to try something that could be really powerful and that might be hard to do in a purely academic setting. And for the company, it's a chance to validate their technology with some enthusiastic collaborators. It's a win/win collaboration.'
Several MINT projects will use powerful new optical methods to manipulate brain tissue. For example, Ed Boyden, an associate member of McGovern Institute and an assistant professor in the MIT Media Lab, has begun a collaboration with Shuguang Zhang, a protein engineer at the MIT Centre for Biomedical Engineering. With MINT funding they plan to extend Boyden's technology for optical control of electrical activity to manipulate the intracellular signalling pathways by which brain cells respond to chemical signals such as neurotransmitters and hormones. By using light to mimic the effect of these signals, they hope to gain new insights into the function of these pathways, many of which are important targets for drug development.
In another project, Ann Graybiel of the McGovern Institute will work with M. Fatih Yanik in the MIT department of Electrical Engineering and Computer Science, to develop what might be termed an 'optical scalpel.' Yanik, an expert on laser optics, is building a precision laser system that he hopes will make it possible to dissect individual neurones from brain tissue in three dimensions. 'A fundamental problem with molecular analysis of the brain is that it's such a complex mixture of cells, and the details are often lost when you look at the average,' explains Jennings. 'We need better ways to isolate individual neurones cleanly in order to analyse them chemically.'
Yanik is also building microfluidic devices that can be used to analyse the tiny quantities of material extracted from single cells. Graybiel, who is an MIT Institute Professor, hopes that Yanik's approach will lead to new precision tools that will accelerate her research on the basal ganglia, including their involvement in conditions such as Parkinson's disease and drug addiction.
When Jennings thinks about the potential for neurotechnology, he is inspired by the dramatic progress in human genomics over the last few years. 'When they finished the first human genome sequence in 2003, the total cost was over $100 million. Now, five years later it's down to about $100,000, and there's already a company promising to sequence your genome for $5,000 starting next year. That's what technological innovation can do. If we could come remotely close to that in neuroscience, the impact would be enormous.'
The MINT program is currently funded through contributions from the institute's founding donors Patrick and Lore McGovern, but Jennings hopes to expand the program through additional philanthropic support. 'We're looking for people who 'get' the importance of technology,' he says. 'It's not about any one disease in particular - instead it's an opportunity to have an impact across the board.'
He also hopes that some of the ideas emerging from the program will eventually be commercialised. Given MIT's extensive connections to industry and its long track record of launching new companies, the prospects for the future seem bright. 'The therapeutic market for brain disorders is enormous,' he says. 'If we can develop technologies that can accelerate progress toward new therapies, I'm confident the commercial interest will be there.'