Howard Federoff wants to know how we think. But the University of Rochester genetics professor is not polling the latest opinions; instead, he's trying to crack the code of the human brain, one small group of cells at a time.
"What we're doing will someday help us understand the impact of disease on the human brain," said Federoff, chief of Rochester's Division of Molecular Medicine and Gene Therapy.
Federoff and a small band of researchers have successfully turned on the gene for nerve growth factor in adult mice, a breakthrough they believe will enable researchers to study any gene in the nervous system.
Cracking the human neural code is the next big revolution in biology. To understand how the synapses and neurons work together and make it possible for humans to have epiphanies, feel pain, and perform functions is to grasp how changes affect the brain - or whether they affect the brain at all, said Eugene Pergament, a geneticist with the Northwestern University Medical School.
The key to the gene control was the manipulation of NGF, a substance that has long eluded researchers. Federoff said genetics researchers could only turn off all NGF genes - permanently, which killed the mice.
"You want to study the change in cells, the brain and the organism as a result of the presence of the genes, and we couldn't do this," said Federoff.
This time around, Federoff injected into the chromosomes of baby mice extra NGF genes, along with a DNA sequence that kept the genes dormant. Later, Federoff injected into the adult mice a non-replicating form of the herpes virus, which carried an enzyme that excized the DNA "turn-off" sequence. This switched on the extra NGF genes in a portion of cells selected by Federoff and other researchers.
"We can select, out of 1 million cells, 100,000 in which we activate the NGF. This allows us to see how they affect the other 900,000 cells, the whole brain, and the mouse," said Federoff.
This ability to select parts of the brain to manipulate genes will be very helpful to scientists in studying how the brain works. Federoff is trying to see the effects of memory and learning on parts of the brain. But the geneticist's work doesn't stop here - it may hold the keys to understanding how diseases such as Alzheimer's, Parkinson's, and other ailments infiltrate and cripple the brain and nervous system.
"To understand the wiring of the human brain is to understand how to help people with mental retardation, learning disabilities, and other ailments," said Pergament.
But as much as this knowledge can be helpful to stopping disease and defects so, too, can it be used to determine how, for instance, antisocial behavior occurs. But even at this level of understanding, Pergament said, it could be helpful to know more about consciousness and the ego - even to lay to rest an age-old argument.
"Maybe we can prove that it's one's environment and not biology that determines intelligence and other factors," Pergament said.
