Like everyone else, Carla Shatz once had a head full of immature neurons. Somehow those latent cells wired themselves into the fantastically organized complexity of the adult brain. When and how did it happen? Shatz, the first woman to chair Harvard's prestigious department of neurobiology, has spent almost three decades delving into these questions. She shared her answers with Discover Associate Editor Josie Glausiusz.
How do you investigate the brain's early, formative stages?
We study is how the eye connects up with the brain during development. We use that as a model for trying to understand how brain wiring is accomplished by the nervous system. There are something like a million nerve cells in the eye that can map to about two million nerve cells in the visual part of the brain. How do they decide which of those two million target nerve cells they should connect up with? Initially in development, everything is connected to everything. Then it's as if the nervous system is placing address verification calls, checking to see which "telephone" lines are connected up correctly and which aren't.
When does this process begin?
What's totally amazing is that this process starts earlier than vision itself. In the womb, the two eyes spontaneously signal the brain. There are waves of neural activity which sweep across the fetal retinas. It's almost as if the nervous system is rehearsing for vision by running test patterns across them. It's likely that spontaneous activity in the brain is jump-starting the nervous system. When a pregnant mother feels her baby kick, that's a reflection we think of circuits in the spinal cord tuning themselves up and practicing.
What happens when this "phoning" process is blocked?
The refining and sorting and error correction doesn't happen. If you block neural activity, then the detailed wiring doesn't emerge during development. It gets kind of deranged. This has an important clinical message, which is that there may be many early developmental problems which may be caused by drugs of abuse which can cross the placenta and interfere with the phoning process.
How does early development affect how we think and act as adults?
There is a lot of evidence that depriving babies of stimulation after birth leads to profound loss of connectivity, so an interactive and loving environment is really essential for normal development. It's use it or lose it. Even children who have learning disabilities or dyslexia can benefit from intense training and retraining. There is a tremendous amount of flexibility in the brain.
What's the biggest challenge in brain science today?
It's how do we take our knowledge of molecules and working circuits and put them together so we can really understand behavior. The last 20 to 30 years has been a really exciting time, because we've taken apart the nervous system down to its individual molecules, and begun to understand the workings of those molecules and how individual nerve cells work. And now it's time to put Humpty-Dumpty back together again.
Do you think we'll ever be able to cure brain diseases through transplants of brain stem cells?
I think that has huge potential. It turns out nowadays we're finding out that there are persistent progenitor or stem cells within our own body that we can perhaps harvest. They can be generated from your own cells, and then they can be told what to do and what kind of cell to turn into.
What might be the best candidates for such transplants?
Right now, Parkinson's is clearly the best. This is already being done in Sweden, albeit with fetal cells taken from the developing brain. Which, of course, is very controversial and you can't do it in the States. The nice thing about stem cells it that they're not taken from fetuses.
What is your greatest fear?
It's that our society, because of its concerns about stem cells or other kinds of research, will not permit us to go in directions that clearly have huge benefits. That valid concerns about the misuse of genetic engineering or gene therapy will also prevent us from helping each other in terms of curing diseases.
Why did you become a neuroscientist?
When I was in high school my grandmother had a terrible stroke, and I saw how debilitated she was from it. And nobody could do anything for her at all! It was so terrible to see her. Mentally she was completely fine, and she was paralyzed completely on one side of her body. Many people in my family had been physicians, and they all told me to go to med school. And I decided, no, I'm going to go to graduate school. I thought, "We need more research; we've got to find out more about how things work."
If you could travel into your own brain, where would you go?
I think I would go into the cerebral cortex. The organization is so beautiful. It's almost like a crystal structure in the way the connections repeat over and over again. It would be really cool to go and watch it work from the inside out.
Have you ever encountered any difficulties being a woman scientist?
People have been incredibly supportive of my career. And all of my mentors have been men. However, there have been times when I've felt that, as a woman, there have been career tracks that I felt compelled to take, to be a role model. I think a good example is the fact that I moved from California to Boston to take this job. I didn't just do it because it was a good job. I also did it because it was offered to me as a woman, and I felt a kind of moral responsibility to look at it because there are so few women in these positions in the country.