January 12, 2004.
By Robert P. King,
Palm Beach Post.
They're solving math problems using microscopic computers made of DNA. They're learning to grow corn that fights herpes, create brain cells in the lab and tweak HIV into a treatment for diabetes or cancer.
They're not just decoding nature's rule book. They're rewriting it.
The biotechnology giant in La Jolla, Calif., is a leader in a revolution that during the past quarter-century has changed our notions of life itself.
Now Scripps is bringing the revolution to Palm Beach County.
Scripps has combined its pioneering world-class research -- including work that led to treatments for leukemia, hemophilia and ovarian cancer -- with equally trailblazing financial marriages with drug manufacturers. Those have generated hundreds of millions of dollars, envy from some rivals and a rebuke 10 years ago from the National Institutes of Health.
Scripps executives say the institute has avoided two of today's touchiest bioethical minefields: It doesn't experiment with stem cells from human embryos or do any sort of human cloning.
Scripps is the world's largest private nonprofit biomedical research center, with $276 million in yearly revenue, the vast majority from federal grants. It has a staff of nearly 2,800 and more than 1 million square feet of office and lab space overlooking the Pacific Ocean.
Much of its research is as important as it is hard for most people to understand.
Scripps scientists have made a big impact in deciphering the inner workings of the cells and complex molecules that make life work. That's a key to understanding ailments as diverse as strokes, cancer, brain disorders, viruses, depression, alcoholism, leukemia, kidney failure and anthrax. Three of its researchers have won Nobel prizes.
Scripps doesn't produce medicines, but it produces the knowledge necessary to develop them.
Scripps spokesman Keith McKeown predicted a twist on that strategy for Scripps Florida, saying researchers at the planned facility in north Palm Beach County will focus more on figuring out how to use that knowledge.
"We would develop something that looks very promising to being a treatment for disease or a medical condition," McKeown said. "Then, when that discovery is published, a pharmaceutical company becomes interested in it and decides it would like to go to the next stage.
"We're not going to be a pharmaceutical company," he said.
So, although McKeown called it uncommon for a Scripps scientist to test potential drugs on human subjects, a pharmaceutical company may do so after paying for the rights to the institute's research.
Scripps expects to receive about $38 million this year -- 14 percent of its budget -- as a result of deals with industry. Scripps researchers also sometimes start their own companies to capitalize on their findings in the lab.
Dr. Martin Friedlander, an ophthalmologist and the chief of retina research at the La Jolla campus, calls Florida a natural place to test his research on ways to treat failing eyesight. The research could be used someday to prevent or reverse macular degeneration, which strikes the elderly, as well as blindness caused by diabetes.
"Palm Beach County has a lot of patients who could benefit from these treatments," Friedlander said. "If I have anything to say about this, Florida's an obvious place to look."
Any clinical trials -- whether sponsored by Scripps or a drug company -- are years away, he cautioned.
Friedlander's eye research has centered on injecting adult stem cells from mouse or human bone marrow into the eyes of mice. By using those cells, he avoids the legal and ethical tangles that come with stem cells from human embryos.
Still, Friedlander has found himself an unwilling player in that debate. Right-to-life groups praise his research as proof that scientists don't need cells from human embryos.
But Friedlander said his work proves no such thing. "If someone came to me and said there are these cells that are 500 times more potent in (human) fetal issue, I would definitely think about pursuing that," he said.
On the other hand, Friedlander said, the legal and financial hassles of using human embryos are a big deterrent. "Practically speaking, it's very difficult."
For the same reason, Scripps molecular scientist Peter Schultz said he's sticking with mice for his stem cell research, which could help find treatments for illnesses such as Alzheimer's or heart disease. Schultz recently found a molecule that can turn stem cells from mouse embryos into neurons or into cells that can repair damaged heart tissue.
"I don't want to walk into the whole human embryonic stem cell thing," Schultz said. "If you have to do basic biology and develop newer tools, why not do it with the mouse?"
McKeown, the institute's spokesman, said nobody at Scripps is working with stem cells from human embryos. He said Scripps also isn't pursuing so-called "therapeutic" cloning of human tissues, which -- though aimed at curing diseases, not producing babies -- has inspired opposition from right-to-life groups and the White House.
Scripps' statements are "very encouraging," said Michael Sheedy, associate for health for the Florida Catholic Conference, which opposes any research using human embryos. Still, he said, the group will pay attention to the scientists' work to make sure no research they might find troubling takes place.
"We're glad they are here, and we realize that they do hold some promise for our state and for serving humanity," Sheedy said.
Scripps has yet to spell out the full range of research it intends to carry out here. But its Board of Scientific Governors, a panel of all-stars who chart the path of the institute's research, is expected to discuss that issue when it holds its first Florida meeting this week at The Breakers in Palm Beach.
Brave new worlds?
Even some of Scripps' more esoteric work can carry religious overtones.
Schultz and other Scripps scientists, for example, have worked on expanding the genetic code to create so-called synthetic cells that have proteins or DNA with ingredients not found in natural cells.
Within 10 years, Schultz says, scientists may be able to breed entire creatures containing such cells -- perhaps mice, for example. (At the moment, he's working with yeast.) They would look just like normal animals, but may live longer or better resist disease.
In an interview with the journal Science, Schultz likened his research to asking: "If God had worked a seventh day, what would life look like today?"
Another Scripps researcher, chemist Ehud Keinan, has used DNA molecules as minuscule computers capable of performing billions of calculations at once in a test tube. So far they're slower than the Dell sitting on your desk, but scientists say DNA computers someday could be used for such tasks as patrolling inside the human body, finding and repairing damaged cells.
Some biotech breakthroughs have captured the public's imagination, such as British researchers' cloning of the sheep Dolly several years ago. But scientists' reshuffling of nature's deck has gone much further than most people probably realize.
In the world of biotech, scientists routinely inject human genes into mouse cells, breeding plus-sized supermice or mice that are prone to human polio or cancer. Researchers have created transgenic sheep that can produce human proteins in their milk, and chickens that make human proteins in their eggs. Genetically engineered pigs could someday produce spleens, livers or kidneys for human use.
Scripps holds a patent on another promising technology: "pharming," or implanting human genes into corn and other crops so their tissues will contain disease-fighting antibodies.
The institute in turn has granted exclusive commercial use of that research to Epicyte Pharmaceutical Inc., a San Diego company founded by two scientists who developed the technology while at Scripps. Epicyte is working with Dow Chemical to create an anti-herpes gel from the pharmed corn.
That's the type of commercial spinoff that Gov. Jeb Bush hopes will enable Scripps to generate as many as 50,000 jobs in Florida someday. And Scripps has been a pioneer in such relationships.
In 1982, Scripps made a lucrative deal that gave pharmaceutical giant Johnson & Johnson the first rights to all the institute's health care discoveries, in return for payments that Science valued at more than $10 million a year.
In 1993, Scripps announced an even grander deal with Switzerland-based Sandoz Pharmaceuticals Corp., which agreed to pay $300 million over the following decade for first rights to nearly all Scripps' work. Sandoz also would have the right to restrict the presence of outside researchers on the Scripps campus, as well as veto power over the institute's contracts with other companies, Sandoz lawyers told The New York Times.
The National Institutes of Health cried foul, saying the agreement was "against the spirit of science." Under pressure, Scripps revised the deal so that Sandoz would have rights to only 47 percent of the work. That arrangement still brings Scripps $15 million a year from the company, now called Novartis.
This intersection between science and commerce can breed lawsuits -- for example, a case Scripps brought against the biotechnology giant Genentech in 1983 for using its patented research on purified blood-clotting factor for hemophiliacs.
And some activists and politicians express alarm at the growing practice of researchers receiving patents for living organisms, as well as human genes and proteins. Afraid of where that might lead, U.S. Rep. Dave Weldon, R-Melbourne, last year proposed a ban on any patents on human embryos.
Less dramatically, University of San Francisco philosopher Raymond Dennehy said troubles can arise even from an instinct as benign as parents' desire to seek the best for their children. What happens, he asks, when people can have doctors augment their offspring's intelligence before conception -- turning enhanced brain power into a product that's available to those who can afford it?
Such scenarios can sound like science fiction, remote from the rural farmland west of Palm Beach Gardens that Scripps expects to call home.
But in such a fast-moving field, it's impossible to predict where tomorrow's controversies will arise.
Florida Atlantic University bioethicist Robin Fiore is optimistic about Scripps' prospects, however.
"I think they will raise the bar for research integrity," she said. "Certainly, Scripps wants to know whether it's worth their coming here. If they can't do their research here, why would they come?"
Copyright © 2004, The Palm Beach Post. All rights reserved.
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