The Gatekeeper 

What if scientists devised a strategy to tackle some of the world's most notorious diseases, but just one company held all the patents?

Page 4 of 6

If such thinking already creeps too close to eugenics for some critics, it could cross the line altogether when it comes to the final frontier in gene therapy — the germ line. Our bodies are made up of two kinds of cells: the germ cells, which are sperm and ova, and somatic cells, which are everything else. Some have called germ cells "immortal cells," because they carry the genetic code of our ancestors, which we pass along to our children. Somatic cells, on the other hand, die when we do. So far, all gene transfer therapies focus only on treating adult somatic cells. Should a gene therapy treatment go terribly wrong, the damage is limited to that one patient — future generations remain unaffected. But tamper with the germ line, and you tamper with the process that has built humans into what we are.

"Heritable genetic modification is one of the most profound lines we could choose to cross," Reynolds said. "Any modification to the inheritable genes would affect all of the descendants of that person or baby. It would unleash, at the least, an enormous experiment, and also cross the line where humans have decided to take control of evolution."

Still, you can imagine some rather sympathetic scenarios in which people would seek out therapy that would affect their germ cells. For example, prospective parents with a family history of a severe genetic disorder might want to avoid passing it to their children. But you also can imagine some distinctly unpleasant ones, especially if you factor in the possibility of genetic enhancement. What's to stop pushy parents from trying to give their children a social advantage by making sure that they're, say, tall? Or smart, muscular ... or fair-skinned and blue-eyed? The ability to select traits like this could reinforce all of the social divisions that are based on people's appearance, and potentially set up new divisions between the those whose families can afford "better genes" and those who can't.

Well aware of these ethical issues, Lanphier said he intends to hold the line against enhancement. "What we are doing is focusing on serious medical diseases, and have no interest nor inclination to look at areas that aren't serious medical diseases," he said. As for the germ line, he said, "It's a line that we wouldn't cross and others like us would not cross."

At least in humans, that is. It's a line that many genetic engineers, including those at Sangamo, crossed long ago with plants. In 2005, Sangamo inked a deal with Dow AgroSciences to help develop genetically modified crops. Sangamo's role is to provide the zinc fingers and leave their ultimate applications up to Dow, but likely uses might include increasing crops' vitamin content; boosting resistance to drought, salt, or herbicides; or possibly making them more useful as biofuels.

Traits such as those Dow is believed to be interested in are all intended to be heritable. And because so-called "elite" crops often have more than one gene change made to them, a priority for researchers is to make sure that these modifications not only all show up in each subsequent generation, but in the right place on the genome. That's where zinc finger technology would come in.

"Dow AgroSciences has recognized the potential importance of precision in gene targeting since the late 1990s," said Dr. Bill Kleschick, the company's Global Discovery R&D Leader. The current collaboration, he said, grew from a small proof-of-concept study in 2004 that demonstrated the potential of zinc fingers for targeting specific genes. Although Kleschick declined to elaborate on how Dow envisions applying this technology, citing the ongoing nature of research, he said the partnership is going well: "We continue to be very excited about the potential of this technology."

Working with plants entails a different set of ethics than human research does. "If you kill 99 percent of your experiment, in agriculture, it's not a moral dilemma," Reynolds noted. Nevertheless, genetically modified organisms have engendered tremendous worldwide opposition from people concerned about a host of other repercussions. Some activists worry that such plants will cross-pollinate with native plants in a sort of "genetic pollution" that gives them an evolutionary edge and ultimately creates superweeds or undermines biodiversity. (A homogeneous population is vulnerable to being wiped out by a single disease.) Some object to what they see as an effort by biotech companies to patent and then economically control the production of staple crops. Others have grave moral reservations about transgenic crops — those in which genes from one species are imported into another, for example, the insertion of a gene from soil bacterium Bacillus thuringiensis, which is toxic to some insects, into crops as a pesticide.

As with human medical research, there are worries that inserted material will wind up in the wrong part of the genome, accidentally interrupting or activating other genes, and perhaps causing dangerous side effects, such as food allergies. Even if the gene is inserted correctly, critics say, given that genes may have more than one function or may interact with other genes, modifying one may cause unintended consequences later.

Lanphier and Wolffe say that Sangamo's methods may mitigate at least the last two complaints. "A lot of the time, what they are concerned about is inserting foreign DNA into a plant," Lanphier said. "This is a way of regulating the plant's own genes versus putting something new in." The company said that the precision of its gene insertion technology also should allay fears about changes accidentally being made to the wrong part of the genome. "We believe that we can go in and place the gene wherever you want it," Wolffe said. "You could identify a safe harbor location where you could put a gene in without interrupting another important gene or without interfering with another function or turning some weird and wonderful gene on."

Do critics of genetically modified foods think zinc fingers will allay any of their concerns? Well, no one could say. The Express contacted a half dozen Bay Area scientists, watchdog groups, and other experts, and most of them just referred us to one another, saying they didn't yet know enough about this new science to venture an opinion.


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