THE BIRTH OF A BRAIN INSTITUTE

by Lee J. Siegel

Some of the biggest mysteries of human existence remain locked away in the gray matter inside our skulls, as yet unyielding to modern science.

Medical research still has far to go in identifying the causes of brain and psychiatric disorders, and in developing better treatments for brain diseases and injuries. Science lags farther behind in revealing even more complex workings of our minds.

“The brain truly is the last scientific frontier,” says neurogeneticist Erik Jorgensen, a professor of biology at the University of Utah. “From it arises things we associate with our soul—personality, memory, consciousness.”

And yet, he says, “Our understanding of the brain is so primitive that to contemplate these phenomena is, as one scientist said, like a dog contemplating the nature of the moon.

“What we really need to make progress in this area is a basic understanding of the functioning units of the brain— molecules, cells, circuits, and regions,” he adds. “If we can begin to determine the rules by which networks of brain cells work, eventually we will be able to understand how consciousness, memory, and personality arise from these circuits.”

With that in mind, the University of Utah is launching a major effort to study the mysteries of the brain by utilizing some of the University’s greatest strengths. The U is establishing a multidisciplinary undertaking, provisionally named the Utah Brain Institute. The institute is conceived as an effort that will require upwards of $100 million for a new building and the first five years of full operation, and include 200 to 300 faculty members and staff—many of them newly recruited young researchers—working in 30 to 40 research groups.

Citing the need to explore “the last scientific frontier,” U of U researchers announce a multidisciplinary effort to study the brain.

President Bernie Machen announced the establishment of the Utah Brain Institute during his “State of the University” speech to the faculty on Aug. 25, 2003. He said the University would provide $5 million in startup funds.

“The brain is fundamental to every aspect of our existence,” Machen said. “Yet we know relatively little about how the brain develops; how it gives rise to our personality, memory, and consciousness; and how it declines with age, injury, and illness.”

Machen added, “Gaining better understanding of the brain is required if we are to improve our ability to combat the terrible human suffering caused by diseases that affect the brain—Alzheimer’s and other dementias; Parkinson’s; traumatic injuries; substance addictions; psychiatric disorders such as depression and schizophrenia; learning disabilities; and classic neurological ailments such as epilepsy and multiple sclerosis.”

He called the institute “an interdisciplinary facility not within any department or college. It will bring together people from neurology, biology, genetics, computer science, radiology, social and behavioral sciences, physics, math, and other fields.”

Machen appointed Jorgensen as the institute’s scientific director and Tom Parks—chair of the Department of Neurobiology and Anatomy in the School of Medicine—as the executive director. To emphasize the institute’s importance, Machen said Parks and Jorgensen would report directly to him.

In addition to the University’s $5 million in seed money, geneticist Ray Gesteland, vice president for research, foresees raising another $5-10 million to start recruiting new faculty members, who will work within existing academic departments until the University constructs a building for the institute.

The idea of forming a brain research institute began two years ago when Gesteland convened a multidepartmental group of 15 faculty members for a series of informal evening talks over pizza and Mexican food.

“The group quickly realized science is very much driven by technologies, and technology opens new opportunities,” Gesteland recalls. “And we are in a real technological boom, with many new tools at our disposal” in areas at which the University excels, including computer graphics, imaging, genetics, developmental biology, fluorescent chemistry, stem cell technology, and bioengineering.

He says there was some talk of forming a biotechnology institute, but by spring 2002, the group realized “it was much more interesting to apply the technology to an important topic: What’s the last big biological frontier? The brain.”

Gesteland says the group believed a brain institute would attract and interest young scientists and good students, and would pose “challenging questions, important disease problems, and unique opportunities for the University of Utah.

“We know a lot about how cells grow, how they respond to their environment, and about genes and their products involved these cellular activities,” says Gesteland. “We are still remarkably ignorant about how the brain develops, functions, and carries out things like memory.”

Understanding the brain “is more than fascinating,” he says. “It’s who we are.”

He adds, “The other reason the brain is so interesting is that if we could understand how this little organ does the complex things it can do, if we could understand how the brain processes information, it would be very different than a computer, and would undoubtedly give rise to a new generation of computer technology.”

Parks says that while the institute’s research will be basic, such understanding will help set the stage to develop effective treatments for brain diseases and injuries.

“We know from the last 40 years of basic research applied to clinical medicine that the real breakthroughs, the real insights, come when we are doing basic research on mechanisms that can become disordered to give rise to disease,” he says.

“We need better treatments for almost all brain diseases, and we have almost nothing for some like addiction and dementia,” Parks adds. “We know enough about the cell biology of the brain that we can see how, with more basic research, we might come to understand the pathophysiology underlying the whole range of brain disorders.”

Parks and Jorgensen, along with an advisory group, are devising a scientific plan for the institute’s research. “Our studies will reach from molecules to cells and circuits, to behavior of whole organisms,” says Jorgensen, adding that the institute will have at least six “modules” or areas of research, and five laboratories or research groups will work on each module:

Genetic disorders of the brain and nervous system. “Our foothold into the brain relies on the strength of the University of Utah, and that is human genetics,” Jorgensen says. “This is where we have made a mark on the world.” Modern imaging techniques such as magnetic resonance imaging will be used to look at brains of living people to identify what parts of the brain malfunction in such disorders, Parks says.

Cell biology. Each gene carries instructions to make a protein. Once genetic studies tie a protein to a particular brain disorder, cell biologists need to figure out what the protein does in cells—where it works, at what point during development it comes into play, how it moves, and so on.

Structural biology. The next step is to determine what the protein looks like and how it works at the molecular level.

Model system genetics. How does a protein that is “encoded,” or produced, by a gene set off a chain of events that alters the behavior of a cell? In other words, what other proteins interact with the protein? Such studies involve animals like fruit flies, nematode worms, and zebra fish to serve as models for how similar genes work in higher organisms.

Mouse behavior. These studies will use technology developed by U geneticist Mario Capecchi to disable or “knock out” certain genes in mice to determine how the mammal brain is affected by genes and genetic mutations identified in the studies of flies, worms, and fish.

Physiology and circuits. This area of research will focus on how small groups of nerve cells interact with one another in both the normal and diseased brain.

Financing such research and the institute remains a daunting task. Jorgensen envisions raising money for each research module independently. “Then we go to large donors and say they can provide the ring that binds them all,” he says.

But much of the money, he adds, “is going to come from research grants to individuals thinking of the best possible science they can imagine and getting money for it.”

—Lee J. Siegel is science news specialist in the U’s public relations office

"Our understanding of the brain is so primitive that to contemplate these phenomena is, as one scientist said, like a dog contemplating the nature of the moon."

—Erik Jorgensen, professor of biology