Meet the Mr. Greengenes of Biotech : Gene Therapy: UCSD’s Theodore Friedmann makes no apologies for scientists tinkering with what he calls nature’s ‘mistakes.’
As the front lines of technology have advanced over the years, Theodore Friedmann could be found in one of the trenches.
As a young pediatrician in the 1960s, he was doing research in the Cambridge University laboratory of Dr. Frederick Sanger, the recipient of the Nobel Prize in chemistry for establishing the chemical structure of insulin.
In the 1970s, after stints at the National Institutes of Health in Bethesda, Md., and the Salk Institute in San Diego, Friedmann was at UC San Diego, writing one of the first scientific papers on gene therapy--the potential to not just treat symptoms of disease with traditional medicines, but to actually fix or override the defective genes with new ones.
In the 1980s, as a member of UCSD’s Center for Molecular Genetics, he was successfully grafting genetically altered cells into the brains of rats, an extension of his research into how genetically modified cells might one day be used to treat human disorders.
Now, in the 1990s, Friedmann is helping establish a human gene therapy program at UCSD’s School of Medicine--one of only a handful of such university-based centers in the nation, he says--so scientists can develop ways to effectively and cheaply use human genes as medical science’s ultimate fix-it kits. The initial targets: cancer, AIDS and Parkinson’s disease.
It is the stuff of dreams: eliminating cancer, for example, not by destroying the consequences of cancer--cells gone amok--but by targeting the root and repairing or replacing the defective gene that allows the cancer to express itself in the first place.
Given the revolutionary pace of biotechnology advances--breakthroughs for which Friedmann has been either ringside or in the ring itself--what does he see in store for the year 2000 and beyond?
He won’t even speculate.
“And that’s the most impressive thing about biotechnology: how fast it’s moving,” he said. “It’s technologically almost out of control. There are new revelations every day.”
As Friedmann sat in his office, its window wall offering him an expansive view into the laboratory, researchers were tending to various recombinant DNA chores that are their workaday routine.
“Some of the people who come into this lab, the young ones, aren’t aware of the history of biotechnology,” he said. “They don’t know that just 20 years ago, none of this was possible. They come into a lab now that’s doing recombinant DNA technology and, for them, it’s already old hat. They don’t think twice about putting bits of genes together. That’s what they do for a living.”
Friedmann laughed at the memory of a sign hanging over Sanger’s desk back in the ‘60s--a prediction by a prominent American biochemist that the sequencing of the DNA molecule would not come about until the 21st Century. By showing the sequence, or precise order, of chemical sub-units that make up the genetic code on the DNA strand, researchers can decipher the genetic message of any gene.
Sanger told his assistant, Friedmann, that the breakthrough wouldn’t take that long.
Hardly. DNA sequencing began in the 1970s. And in 1980, Sanger shared in a second Nobel Prize in chemistry--as a senior scientist among a group honored for developing a technique enabling researchers to sequence about 1,000 DNA sub-units a day. Before that, it might have taken 12 months to sequence just 50 sub-units.
Given such advances, scientists have embarked on a $3-billion, federally funded campaign called the Human Genome Project, which will catalogue the body’s 100,000 or so genes and their 3 billion or so chemical sub-units. The goal is to identify all of the genetic information needed to make a human being.
Other scientists are identifying which diseases are caused by genes wrecked since birth or mutated afterward. They have identified 4,000 such diseases so far.
Such is the accelerated learning curve in biotechnology.
“And what we’re doing in this lab today will look absolutely silly and inefficient 10 years from now,” Friedmann said. “We know that the science won’t end here. Five or 10 years from now, what we’re doing here will look very primitive. People will scratch their heads and say, ‘Did they really do it that way, back in those days? How could they have been so dense?’ ”
Friedmann knows the concerns voiced by ethicist Jeremy Rifkin and others: that scientists are too liberally tinkering with the most basic building blocks of life and are at risk of upsetting the course of evolution.
He rejects them out of hand.
“I have trouble with criticism that we’re interfering with nature, and that it shouldn’t be done,” Friedmann said. “Medicine, by its very nature, interferes with nature. The profession of medicine exists because we reject some of what I call ‘mistakes’ that nature presents us with.”
“One should not interfere with nature whimsically, but we’re not doing that,” he said. “We’re saying there are some serious genetic situations that are leading to enormous amounts of human suffering, and we feel compelled to change that.”
Friedmann suggests that the public has been spoiled by the fast-paced--albeit largely esoteric and not-yet applied--success of biotechnology, and now demands even more success, and even quicker, especially in the newest front line of the field, gene therapy.
“We’re trying to learn how to introduce these genes into defective cells, so we can turn the cell that’s working improperly because of a genetic defect into one that works correctly,” Friedmann said.
“That concept of gene therapy was, in large part, born here” at UCSD, he said. “But now we have to temper our enthusiasm with the knowledge that it’s still going to be very difficult, technically. We’re in a new era of medicine. It’s epochal. We’ve now got a new target for therapy. We’re no longer looking at the consequences of a genetic defect, but we’re looking at therapy for the defect itself.”
Even the acceptance of that notion, of addressing genetic flaws through gene-to-gene combat, is considered a biotech revolution. And, although people like Rifkin challenge it, scientists try to execute it.
“And there’s a danger, of offering an apparent promise of delivering too much too soon,” Friedmann said. “Science has that problem, of promising too much.
“Maybe one problem is, we’ve all made it sound so simple.”
