12/21/06 News Release

MEDIA CONTACT: Ruthann Richter at (650) 725-8047 ()

STANFORD, Calif. — For science to advance, researchers need to have a vision of what the future may hold. Many of the faculty at Stanford University School of Medicine have built their careers on being able to foresee the critical trends in medical science, in fields ranging from stem cells to genetics to health-care policy.

What follows are some quick thoughts from a sampling of scientists on developments and trends to watch in 2007 and the coming years.

Bird flu vaccine developers: A year for going cold turkey on eggs?

Fears of a bird flu pandemic have subsided a bit since earlier in the year when the bug was on the cover of magazines and the front page of newspapers. Nonetheless, there’s still reason for concern: It is likely that in the next few years the avian flu virus will mutate into a form that can easily infect and pass between humans, said Cornelia Dekker, MD, medical director of the Stanford-Lucile Packard Children’s Hospital Vaccine Program. “We just don’t know when that will happen,” she said.

	Pam Lowney
	Cornelia Dekker

With that probability in mind, vaccine manufacturers and the research community will be stepping up their work in 2007 to develop an effective vaccine, including attempts to find new and better ways to produce it. Dekker is among the scientists at the forefront of this effort, and she expects an announcement next year of the results of her second bird-flu-vaccine trial, now under way. What makes this one particularly intriguing is that, rather than the usual method of growing the vaccine in chicken eggs, this one was made in cells cultured in the laboratory.

“The field of flu vaccines is hoping to move this way,” said Dekker. “Then they don’t have to worry about ordering all those eggs in time for seasonal vaccine production.” Cell cultures permit much more control over vaccine production and can be much more efficient.

Speeding up the development process is critical. Scientists and health organizations are frantically trying to keep pace with the mutating virus. They ideally would like to have a vaccine specifically for the pandemic strain, though even one that is not a perfect match could prevent some people from dying.

Dekker said there’s a good chance of an avian flu vaccine being licensed for human use in the United States by the end of 2007, and some companies have already applied for approval in Europe. She expects to be involved in more trials in the coming months, but the vaccine development process is so accelerated that it is impossible to set a schedule much in advance. “We find out about a trial, and we are enrolling participants within six weeks,” she said.

Coming to a lab near you: Homegrown livers

Imagine that a patient needs a new liver. Rather than waiting for a donated organ, doctors simply taking some stem cells from the patient and grow a new one. Sound pretty far-fetched? Maybe not.

	Office of Medical Development
	Geoffrey Gurtner

“We’re looking at a five-year time horizon, at least,” said Geoffrey Gurtner, MD, associate professor of surgery. His laboratory is seeking to create complex tissues for organ replacement, and is now working on creating a synthetic replacement liver for people with liver failure. The goal is to seed tissue with stem cells harvested from the patient that will differentiate into liver cells.

“The key stumbling block is how to use these cells to create a three-dimensional organ,” he said. “But we’re optimistic it will work.”

Reports last April of the first successful transplant of laboratory-grown bladders into children and teenagers at Wake Forest University School of Medicine thrust the field of regenerative medicine into the headlines and stirred up hopes for future successes for other organ transplants. The patients, who suffered bladder disorders, received new bladders grown from their own cells.

Regenerative medicine may well be the future of health care: Its goal is to refurbish diseased or damaged tissue using the body’s own healthy cells. It’s a term that is often used synonymously with tissue engineering, though those involved in regenerative medicine place more emphasis on the use of stem cells to produce tissues.

Scientists are currently working on tissue replacement projects for practically every body part—blood vessels and nerves, muscles, cartilage and bones, esophagus and trachea, pancreas, kidneys, liver, heart and uterus. The long-term hope is that patients someday may not have to wait on the national transplant list for donor organs. Organs could be tailor-made for people.

“There will never be enough transplants,” Gurtner said. “Just look at the numbers. It increases everyday. If you want a solution that will solve the problem once and for all, regenerative medicine is the best solution.”

Hormone therapy: The conundrum intensifies

With tantalizing data in hand linking the decrease in hormone therapy to a reduction in breast cancer rates, 2007 will likely bring changes in how doctors and menopausal women talk about treatment options.

	Courtesy of NCCC
	Christina Clarke

Christina Clarke, PhD, an epidemiologist at the Northern California Cancer Center which is affiliated with Stanford’s medical school, found that breast cancer rates in Northern California dropped 10 percent between 2001 and 2003, according to data compiled by Kaiser Permanente. Other researchers in December similarly reported a significant decrease in the 2003 breast cancer rates throughout the United States.

The lower cancer rates came a year after many women curtailed their hormone therapy when a large study funded by the Women’s Health Initiative showed that hormones could increase the risk of breast cancer and other diseases.

Clarke now wonders if the most recent findings will spur a second wave of lowered breast cancer rates. “It will be interesting to look at 2005, 2006, 2007 to see what happens next,” she said.

Still, Clarke said the latest data don’t provide the clear-cut answers many women seek when deciding whether to treat menopausal symptoms with hormones. “Unfortunately everyone wants the easy answer but there isn’t one,” she said.

Women who have no family history of breast cancer and no history of benign tumors may still want to use hormones to control their menopausal symptoms. Clarke said only time will tell how women and doctors balance the need to ease the symptoms of menopause without triggering more dire medical consequences down the road.

Stem cell funding: Free at last?

After more than two years of legal challenges to California’s initiative to support stem cell research, 2007 could bring an end to the gridlock, with money beginning to flow to scientists throughout the state.

	Courtesy of LPCH
	Michael Longaker

“I think many faculty members have their grant applications written and are just waiting for the go-ahead to mail them off,” said Michael Longaker, MD, professor of medicine and chair of the advisory committee for Stanford’s Program in Regenerative Medicine.

Early in 2007 the state’s Court of Appeals is expected to hear a case that will determine whether the California Institute for Regenerative Medicine will be free to distribute the $3 billion in funds allocated by the passage of Proposition 71 in 2004. A Superior Court judge has already ruled in favor of allowing the money to be raised and distributed, and many legal experts, including Stanford law professor Hank Greely, JD, say the case against the funding is weak.

The situation could drag beyond the year if it winds up being appealed to the California Supreme Court. Still, universities across California are ready to submit grant proposals to the institute, with many preparing plans to construct laboratory space and begin new avenues of scientific exploration.

Stanford is no exception. Plans for a new stem cell research building currently rest on receiving a CIRM facilities grant, though the building could also move forward with private donations. Stanford’s Program in Regenerative Medicine has also been pulling together stem cell researchers on campus to help build momentum for the research.

If the legal hurdles are removed, the funding process is expected to move quickly. Although institute president Zach Hall, PhD, announced on Dec. 7 that he would be stepping down in 2007, he has already established an efficient system to consider and award grants as well as putting in place a plan to guide the agency in how it allocates its funds over the next 10 years.

Climate change: The bacterium in the coal mine

If 2006 marked the end of debate about whether global warming exists, then 2007 may be remembered as the year when people began to grasp how it would affect our lives—and our health.

	Pam Lowney
	Gary Schoolnik

In the coming months, professor of medicine Gary Schoolnik, MD, and an international team of scientists will be honing a mathematical model that may eventually allow public health officials to track and forecast how climate change will promote the spread of diseases into parts of the world where they previously affected few, if any, people. The northward journey of insects that normally reside in Mexico and the Caribbean, for instance, is being spurred by the increase in temperature. As a result, mosquitoes and ticks, which can carry such potentially fatal conditions as Dengue, malaria and Lyme disease, may be able to move into the United States in much greater numbers, said Schoolnik, who is also a senior fellow at Stanford’s Woods Institute for the Environment.

The new forecasting system uses the tiny organism, Vibrio cholerae, a bacterium that sickens millions annually with diarrhea, as the basis for larger projections. Here’s why it’s the ideal canary in the coal mine: Global climate change and its effect on seawater temperature and monsoon rains stimulates the growth of algae with which the cholera microbe associates. This in turn leads to more cholera outbreaks. Although it’s difficult to predict the behavior of disease vectors, cholera has proven to be one of the easier ones to calculate, and that data can be used to make projections about other diseases.

That understanding is likely to permit scientists in 2007 to begin spelling out in detail the health consequences of climate change. “This model, in all its complexity, illustrates how global climate change and human transformations of the environment can lead to the emergence of a variety of infectious diseases, including some that potentially threaten the continental United States,” said Schoolnik.

New political landscape, same bleak prospects for kids’ health care

Let’s hope that America’s children have a really great holiday season, because 2007 is looking bleak in terms of support for their health care. Despite the Democrats’ fragile new majority in Congress, the next year could leave even more children without a safety net, said Paul Wise, MD, MPH, a health policy expert at Stanford and Lucile Packard Children’s Hospital.

	Paul Wise

Congress must soon re-evaluate the State Children’s Health Insurance Program, or SCHIP, which was created in 1997 as 10-year stop-gap measure to help uninsured children ineligible for Medicaid. If the program is not extended, that would obviously be bad news. Yet even if it is continued, its very success could provide a rationale for some budget crunchers to scale back other vital support for poor children and pregnant women.

“We need to make sure that SCHIP is not used as a weapon to bludgeon Medicaid,” said Wise, explaining that states could try to point to the program as a justification for limiting their own Medicaid spending. This, in turn, could drive even more children to SCHIP’s finite resources. “States may begin to offer only basic health care to children, leaving increasing numbers of kids with chronic conditions out in the cold.”

This despite the fact that increasing Medicaid costs are due almost entirely to the health-care needs of the elderly. “Kids’ interests have been pushed off the table,” said Wise. “Some people say this is because kids don’t vote. But the reality is ‘why should they have to?’ What does that say about us as a country if we condone cuts that fall most heavily on poor children and their mothers?”

Genetic data crunching, part 1: Making a family tree for disease

Computers aren’t about to replace doctors, but their immense processing powers will uncover hidden connections between diseases and could lead to better medical care.

	Courtesy of LPCH
	Atul Butte

Doctors currently classify diseases by a century-old scheme that is more useful for billing than treatment, said Atul Butte, MD, PhD, assistant professor of medicine and of pediatrics. The scheme, for instance, lumps most cancers together, even though they may have little in common besides uncontrolled tumor growth.

Butte’s lab has used computers to crunch billions of measurements from 75 human diseases and mapping out molecular similarities. “The idea here is to come up with the first data-driven classification scheme for medicine,” explained Butte, who in September 2006 received a $2 million grant from the National Institutes of Health to pursue this goal in the coming year.

Butte’s work is made possible by microarrays, a snapshot of the genome that tells scientists which genes are turned on and off and by how much. With microarrays, scientists can glean details about a disease, such as breast cancer, that could never be noticed examining a biopsy sample under the microscope.

Scientists have used microarrays to study nearly every human disease and made the data available on the Internet, thanks to the open-door policy advanced by biochemistry professor Pat Brown, PhD, and other leaders in the field. “Any high school kid today can go to the Web site and download 108,000 microarrays,” said Butte. “It’s unbelievable how much data that is.” So much, he added, that the only way to make sense of the numbers is with the muscle of powerful computers.

Butte and other researchers have analyzed that data to connect the molecular dots between diseases nobody suspected were linked. This is how he discovered that muscular dystrophy and heart attack had strikingly similar molecular signatures.

With that knowledge, researchers can test whether any of the myriad drugs available to treat heart attack would work on muscular dystrophy, which has no treatment. “The beauty of this approach is that we can use it for existing drugs,” he said. Not to mention that it could sidestep the prohibitive costs often involved in developing new classes of medications.

Genetic data crunching, part 2: Cancer to get personal

A rose is a rose is a rose, but the same cannot be said for tumors, as will become ever more apparent in 2007 and the coming years.

	Steve Fisch
	Beverly Mitchell

Doctors are getting increased access to tests that can distinguish between the most and least aggressive cancers. In turn, more patients will get personalized information about their tumors in the near future, which will help them get treatment tailored to their particular cancer.

“The impact of the DNA tests has been across cancer types and is now growing nationally,” said Beverly Mitchell, MD, deputy director of the Stanford Comprehensive Cancer Center.

These tests, based on work pioneered at Stanford, can help guide decisions about treatment specific for subtypes of surgery. People with the most aggressive cancers, as indicated by the genes that are active in the tumor samples, can also get the most aggressive treatment.

Such therapeutic applications are what biochemistry professor Pat Brown, PhD, had in mind when he helped develop the microarrays—also known as gene chips—that underlie the genetic tests of cancers. Brown and a team of Stanford researchers first showed the power of the microarray in 2000, when they used it to find genes that were either more or less active in breast tumors than in normal breast tissue. They also found groups of genes that characterized the tumors that were most likely to return.

Since that landmark paper, researchers across the world have carried out similar experiments with almost every tumor type. According to Mitchell, the challenge has been figuring out which subsets of genes are best at predicting a tumor’s aggressiveness, and refining the algorithms to provide the best information on patient outcomes.

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