Scientists in Seattle have created three-dimensional computer reconstructions of living human brain cells by studying tissue that is usually discarded during surgery.
The virtual cells, unveiled Wednesday by The Allen Institute for Brain Science, capture not only the shape and anatomy of living cells, but also the electrical signals they produce.
Until now, scientists have had to rely primarily on animals to study the electrical behavior of living brain cells, says Christof Koch, chief scientist and president of the institute.
"But in order to understand what makes us who we are, we really need to study the human brain," Koch says. The virtual cells should also make it easier to understand how brain diseases from Alzheimer's disease to schizophrenia can affect the behavior of brain cells, he says.
The computer reconstructions are the result of collaboration between Allen Institute scientists and neurosurgeons in the Seattle area.
These surgeons often remove diseased brain tissue from patients with brain tumors or severe epilepsy. But to get to the problem area, surgeons frequently have to remove some healthy tissue from the brain's outer layer or cortex, which contains the cells involved in thinking, memory and consciousness.
"They cut that [healthy] piece of brain out and very often it's burned as medical waste," Koch says.
Koch thought there must be a way to learn from those bits of healthy brain. "So we now have people inside or just outside the operating room who receive those pieces of brain, put them in a special container and then rapidly move them over here," he says.
Each sample is "about the size of a sugar cube," says Jonathan Ting, an assistant investigator at the institute. "We're essentially keeping that tissue on life support" until it can be sliced into thin sections and studied under a microscope, Ting says.
Because the brain tissue is still alive when it reaches the lab, Ting says, "we can clearly observe specific cells talking to one another" via electrical signals.
Those signals, as well as data about each cell's physical structure, are captured in digital form and added to The Allen Cell Types Database, which is available to anyone with an internet connection.
So far, the institute has captured electrical data from 300 living neurons taken from the brains of 36 different patients. There are 3-D reconstructions for 100 cells. Ultimately, the institute plans to add genetic information about some of the cells.
The cell types database already includes a huge amount of information on mouse brains. By adding human data, researchers should be able to learn more about the differences between the brains of mice and people, Koch says.
"The basic hardware is the same," he says. "But if you get close up you see there are lots and lots of small differences that translate into the fact that I will never have a dinner conversation with a mouse."
"Ultimately we want to understand how is it that this highly organized matter gives rise to our inner life," Koch says.
In the meantime, Allen Institute scientists are learning about some very basic differences between mouse and human brain cells. One early observation is that human brain cells can survive a lot longer in the lab.
Mouse cells typically become unusable in less than 10 hours, Ting says. "We found that this surgical tissue from people can survive up to 10 times longer."
Obtaining human brain tissue requires not only cooperation from surgeons, but from their patients, says Ed Lein, an investigator at the institute.
"It's really quite poignant to work with these tissues that participated in the thoughts and memories of an individual just an hour before," Lein says.
Earlier this week, the Allen Institute for Brain Science received grants worth nearly $100 million from the National Institutes of Health. The five-year grants will help the Allen Institute expand its research on cell types in the brains of mice and people.
AILSA CHANG, HOST:
In Seattle, a group of scientists and surgeons have joined forces to study the inner workings of the human brain. NPR's Jon Hamilton reports on a project that's creating a digital library of human brain cells by studying tissue taken from patients undergoing brain surgery.
JON HAMILTON, BYLINE: When a person has a brain tumor or severe epilepsy, surgeons often need to slice out an area of unhealthy brain tissue. But to reach that area, they frequently have to remove some healthy brain, too.
CHRISTOF KOCH: They cut that piece of brain out, and very often, it's burned as medical waste.
HAMILTON: Christof Koch is the chief scientist at the Allen Institute for Brain Science in Seattle. He thought there must be a way to learn from those bits of healthy brain instead of tossing them into a medical incinerator. Koch met with some local neurosurgeons and came up with a plan.
KOCH: So we now have people inside or just outside the operating room who receive those pieces of brain, put them in a special container and then rapidly move them over here so now we can record from a living brain.
HAMILTON: And they can study it for a long time. It turns out that in the right environment, human brain cells can live for days outside the body. Jonathan Ting is an investigator at the institute. He says when a piece of brain arrives, it's about the size of a sugar cube. Then a researcher quickly slices it into very thin sections.
JONATHAN TING: We can actually examine this under the microscope and see individual living cells as close to the native state as possible for human brain cells, so, you know, remembering that this was a cell that was functioning in a person's brain just a half an hour ago.
HAMILTON: The cells come from the brain's outer layer or cortex. They're involved in thinking and memory and perception. And Ting says that because the cells are still alive, scientists can capture not only their anatomy but the electrical signals they use to communicate.
TING: We can clearly observe specific cells talking to one another.
HAMILTON: Scientists feed all this information into a computer and create a virtual cell that they can study long after the real one dies. So far, the institute has produced about 100 complete digital cells, which are freely available online. The database also includes a wide variety of mouse brain cells and Christof Koch says that should help scientists figure out why the human brain is so much more powerful than a mouse brain.
KOCH: The basic hardware is the same, but if you get close up, you see there are lots and lots and lots of small differences that together translate into the fact that, well, I will never have a dinner conversation with a mouse.
HAMILTON: Koch says the virtual cells could help explain why mice have been such poor models for human brain diseases like Alzheimer's or schizophrenia. They should also help researchers develop better drugs. But he says the final goal is to understand what makes a human brain human and conscious.
KOCH: Ultimately, we want to understand how is that that this most complex piece of highly organized matter in the universe gives rise to, you know, our inner life.
HAMILTON: Obtaining the brain tissue for this project required more than the cooperation of surgeons. Several dozen patients had to agree to donate bits of brain. And Ed Lein, an investigator at the institute, says he wants these people to know how grateful he is.
ED LEIN: It's really quite poignant to work with these tissues that came from an individual that participated in the thoughts and memories of that individual.
HAMILTON: And now virtual versions of these cells live on in the memory of a computer. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.