I’ve got a long article in Nature this week on Jeff Lichtman (of Brainbow fame) and the birth of connectomics, which seeks to construct a complete wiring diagram of the brain:
At first glance, Jeff Lichtman seems to be hanging long strips of sticky tape from the walls of his Harvard lab. The tape flutters in the breeze from the air-conditioner. But closer inspection reveals that this is not tape: it is the brain of a mouse, rendered into one long, delicate strip of tissue and fixed onto a plastic film. When the film is tilted to the light, the tissue becomes visible, like the smear of a greasy fingerprint.
These smudges are the creation of a new brain-slicing machine invented by Lichtman, a molecular and cellular biologist at Harvard University, along with Kenneth Hayworth, a graduate student at the University of Southern California, Los Angeles. Called the automatic tape-collecting lathe ultramicrotome (ATLUM), the machine resembles an old-fashioned film projector with two large reels. At its centre is a fixed diamond blade that cuts continuously into a rotating mouse brain, much like an apple parer. The end result is a seamless sliver of tissue, less than 10 nanometres thick and around 5 metres long, that is deposited on the plastic film spinning around the spools.
Although Lichtman appreciates the technical precision of the ATLUM — “That’s a real diamond!” he says — he is most excited about its scientific potential. Researchers in his lab are starting to put these slices under an electron microscope to visualize the intricate web of connections between neighbouring neurons. Lichtman eventually hopes to have a ‘farm’ of several dozen such microscopes scanning tissue around the clock. Even then it would take months, if not years, to capture all the connections in the strip from a single brain. “When you cut the brain this thin, there’s just such a massive amount to see,” he says. “It does require us to think about imaging on a different scale.”
Lichtman likes to think on a different scale. In recent years, he has become a leading proponent of a new field that is working to create a connectome, a complete map of neural wiring in the mammalian brain. Currently, such a map exists only for the nematode Caenorhabditis elegans, which has 302 neurons. The adult human brain, in contrast, contains 100 billion neurons and several trillion synaptic connections. “I know the goal sounds daunting,” Lichtman says. He insists that such a wiring diagram is an essential undertaking, because it will allow scientists to see, for the first time, the path that information takes as it is shuttled from cell to cell, and how all these cells and the information they transmit weave together to create a conscious brain.
I’m especially interested in Lichtman’s contention that the standard deductive model of modern science – generate a theory and then find a way to test it – isn’t adequate for solving the brain. Instead, he argues that neuroscience needs to return to the inductive approach of Victorian science, so that scientists begin by carefully observing the brain and only then generate testable ideas. (Darwin, for instance, was an inductivist.) The basic idea is that the brain is so complicated an organ that it’s nearly impossible to generate decent theories a priori.