Bay Area is home to a biotech boom
By: Katie Worth
Examiner Staff Writer
February 18, 2010
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Breathing room: FibroGen Director of Cell Biology Gail Walkinshaw stands by scientist David Gervasi as he works in a hypoxia chamber, which simulates a lack of oxygen. (Mike Koozmin/Special to The Examiner)
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The Bay Area has long been home to some of the most fascinating and edgy medical research in the world.
Stanley Cohen of Stanford University and Herbert Boyer of UC San Francisco discovered a practical way to make recombinant DNA in 1973, the beginning of genetic engineering. They founded Genentech (now owned by Roche) in 1980.
Other companies followed: Gilead Sciences, Bayer, Applied Biosystems, Exelixis, Genencor and more. Northern California has the biggest concentration of life sciences firms, and the industry is supported by five major research universities and three medical schools.
Funding
The venture capital firms that have made Sand Hill Road in Menlo Park their Main Street have drawn untold medical research teams looking for funding to the Bay Area. According to the nonprofit life sciences association BayBio, Northern California is now home to 34 percent of active U.S. venture capital firms and this regional concentration has existed since the 1980s. Northern California receives 28 percent of all venture capital life sciences funding. And Northern California received $2.20 billion in National Institutes of Health research grants in 2007, more than any other region.
Mission Bay will be the beneficiary of hundreds of millions of dollars in construction for a new UCSF hospital. That neighborhood is also home to the Institute for Quantitative Biosciences, or QB3, a public institution that aims to support private-sector research, and help the ideas born in the UC system’s laboratories find homes in the private sector.
QB3 Assistant Director Douglas Crawford said one way it helps foster innovation is by providing homes to the smallest of companies as they try to cross the “valley of death” between the initial spark of an idea and a marketable business plan. Right now, the center’s “garage” is home to six fledgling companies including Omniox, whose work to find a better way to treat cancer is highlighted on the next page.
What’s here
There are more life science companies located in Northern California than anywhere else, and an average of 30 more companies are founded here each year, BayBio reports. The region has a wealth of first-tier life science research and medical care institutions, including five major research universities and three medical schools.
Here are some of the most exciting new local medical innovations.
Developing the art of prosthetics for premature infants
Who: Walter Racette and his orthotics and prosthetics team
Where: Orthotics and Prosthetics Center, UC San Francisco
Medical innovation: Braces for premature infants
Making sprints and braces for babies whose limbs are about as thick as the average thumb is as much art as it is science, says orthotics specialist Cody McDonald.
And the Orthotics and Prosthetics experts at UC San Francisco have mastered that art.
Until recent years, when a premature baby suffered fractures during birth or was born with serious muscular problems, the baby was usually fitted with tiny casts. While the casts immobilized the area, they also caused discomfort or skin problems, and were difficult for nurses and doctors to navigate around.
Other times, nothing was done at all because the doctors were often focused on treating more urgent problems — which caused more muscular or bone problems down the road.
A few years ago, at the urging of a doctor who believed bracing could be a better solution, UCSF’s orthotics team began developing a method by trial and error to build braces small enough to fit the smallest human infants.
They began by casting the baby’s leg to form a mold of the leg.
“It takes two people, which seems silly because they’re these little tiny two-pound babies, but they’re moving around so much and their leg is just so tiny, almost like a doll’s leg,” McDonald said.
They return to their lab with the cast and make a mold of the baby’s limb, carving the contours for the shape of the brace. They heat up a special soft foam that doesn’t irritate the baby’s sensitive skin, and then pull plastic over it. The braces, sometimes no larger than a thumb, are carefully shaped.
After experimenting with Velcro, the team settled on laces for the brace, since they seem to irritate the baby less and aren’t as likely to pull off as the baby moves.
The doctors then turn the brace around by the next day — a longer delay might mean the baby would outgrow the brace too quickly for it to be useful, she said. Even then, the braces must be recast about once a week, because the babies grow so quickly, she explained.
The process is rewarding, she said. “Because they are so young and so flexible, they often improve really quickly.”
Flipping the switches of the brain
Imagine that researchers could switch certain neurons on and off with a switch, and see how living without those particular neurons affected diseases like depression, schizophrenia and Alzheimer’s.
A new method developed by Stanford psychiatrist Karl Deisseroth is allowing researchers to do just that.
Deisseroth and his multidisciplinary research team have discovered a way to insert a gene into particular neurons that allows scientists to literally turn specific neurons off with a light switch.
The gene makes the neurons light-sensitive, so when light is shed on the brain — using a fiber optic cable inserted through a small incision in the skull — they no longer work.
The team, which has been working on understanding the brains of mice and rats, has already gained new understandings of how neural circuits work in normal and diseased brains. The method has shed light on how brain oscillations work, and factors contributing to Parkinson’s disease. They hope to learn much more about the brain using the same method.
“We talk about depression and we know people have low energy and low hope, but this lets us look at what is really going on in the brain, what does it correspond to, what does it mean?” Deisseroth said. “This will allow us to piece all that together.”
Helping hearts recover
Who: Gail Walkinshaw, director of cell biology, FibroGen
Where: Mission Bay, San Francisco
Medical innovation: Protection from heart damage in the hours and days after a heart attack
A heart attack is deadly enough, but even if a patient is lucky enough to survive, the damage done to the heart during revival and the hours and days afterward can cause lasting heart disease.
This happens because during a heart attack, the heart is deprived of oxygen. If it is deprived for long enough, patches of the heart begin to die, leaving stains on the heart like brown bruises on the skin of a fruit.
In the hours and days after a heart attack, those dead patches actually spread, as they become inflamed and subject to poisonous free radicals and other toxins.
Private pharmaceutical company FibroGen is exploring ways to keep that dead patch as small as possible after a heart attack, explained Gail Walkinshaw, director of cell biology. FibroGen has discovered that tissue cells already have a built-in protective mechanism that lowers the amount of inflammation they endure and toxins they absorb.
FibroGen is developing a drug that triggers that response in the damaged cells, so that in the days after a heart attack, they don’t succumb from further damage, Walkinshaw explained.
If the method proves successful, it could also serve to stop damage from strokes and could have applications to treat anemia and other conditions, she said.
Finding ways to fix broken-down joints
Who: Dr. Benjamin Ma
Where: UC San Francisco
Medical innovation: Regenerating cartilage outside the body
As almost anyone with a series of sports injuries may know, cartilage damage is permanent. In the words of Dr. Benjamin Ma, chief of sports medicine at UCSF, “cartilage is just lazy” — it doesn’t like to regenerate, so when it gets damaged or worn down through use or injury, it won’t come back on its own.
But Ma and his research team have discovered that given very specific circumstances, cartilage will, in fact, regenerate. The team has been taking knee cartilage from subjects and placing it on a matrix and under some very specific conditions, it is forced to regenerate.
“Cartilage cells are very lazy. They don’t like to grow if they don’t have to,” he said. “So we fool them by doing this particular maneuver and they feel they have to grow, and they form new cartilage. Then we glue it back into the knee.”
The new method has proved to be safe and it helps improve function, and now it is undergoing Phase 3 clinical trials to see whether it in fact works better than microfracture surgeries currently used to treat cartilage injuries.
Down the road, Ma and his team hope to see if there is an application of this method that could help people suffering from arthritis, which is also a cartilage disorder.
Another tool in the fight against cancer
Who: Chief Operations Officer Sally Ann Reiss at Omniox
Where: California Institute for Quantitative Biosciences “garage” in Mission Bay
Medical innovation: Cancer treatment that makes tumors more susceptible to radiation
Radiation treatment can be as damaging to the cancer patient as it is to the cancer.
But a method in the very early stages of development by startup Omniox could change that equation.
The reason tumors need such a large dose of radiation to be killed is because radiation needs oxygen to work its deadly magic, but many tumors have very low levels of oxygen, explained Omniox Chief Operations Officer Sally Ann Reiss.
The Omniox research team is investigating whether that problem could be solved using a protein discovered and developed by UC Berkeley Chemistry Department Chairman Michael Marletta.
That protein delivers oxygen to other cells, and the team is working to see if it can make it specifically target cancer cells, Reiss said.
If the team can, then the low-oxygen tumors would be flush with oxygen, and would be vulnerable to much lower doses of radiation that would kill them, Reiss said.
She said it will likely take three to five years to get to the stage where the method — if it works — could be marketable, but she said there is already buzz about the promise of the research.
“And the same platform could be used in several other applications where it’s useful to deliver oxygen to specific tissues,” she said. “We’re even looking at whether it could be used in making biofuels.”
Working with Alzheimer’s
Who: Chief Medical Officer Lynn Seely of Medivation
Where: South of Market, San Francisco
Medical innovation: Alzheimer’s treatment
A drug that has been used for years in Russia as an antihistamine may be the source of a long-awaited breakthrough Alzheimer’s treatment.
Several years ago, a Russian scientist posited that the antihistamine may have some neurological effects. He started experimenting and discovered that it did appear to have an impact on Alzheimer’s patients.
He pitched the drug to Medivation, a San Francisco company that specializes in searching for treatments for serious diseases.
That company picked up the idea and began its own experiments on the drug, now called Dimebon, said company Chief Medical Officer Lynn Seely. Though researchers don’t exactly know how the drug works, they believe it increases the output of brain cells’ mitochondria — the energy centers of cells, she said.
Preliminary tests have shown that patients suffering from mild to moderate Alzheimer’s saw significant improvements in cognition, behavioral problems and daily living activities. Patients were tested on their ability to remember where they were, to dress themselves, to go to the bathroom, and to use the telephone and other household appliances, Seely said.
Preliminary tests showed that within 12 weeks of starting the medication, the patients all saw significant improvements in those tasks, compared to the group that was taking a placebo.
If later tests go as well, the companies could submit those results to the federal government for approval in 2011.
