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 2 of 6

That may be good news for the company, but some academics complain that Sangamo has created a bottleneck. One group of zinc finger researchers has even banded together to combat the firm's information dominance. A 2005 article in Nature Biotechnology dubbed Sangamo "the zinc finger nuclease monopoly," noting that it's hard for anyone else in the field to move without Sangamo's cooperation. Should these therapeutics come to market, the article concludes, "Sangamo has the equivalent of three hotels on a purple swath of Park Place." (Park Place is actually blue in Monopoly, but you get the idea.)

Sangamo's dominance not only leaves one entity as the primary financial gatekeeper of how this new technology will develop, but it also raises profound ethical questions. "Like most current biomedical research, there is a fuzzy line between public good and private interest that these researchers try to straddle," Reynolds said. "How do you balance those interests?"


Zinc fingers have been with us since time immemorial, but it wasn't until 1986 that Sir Aaron Klug discovered them at the Laboratory of Molecular Biology in Cambridge. In the early '90s, Carl Pabo at the Massachusetts Institute of Technology first described their structure and showed that they could be engineered to turn genes on or off. Lanphier, who has spent his entire career working at Bay Area biotech companies, recognized their promise and set about buying up both scientists' intellectual property rights, also acquiring Klug's company, Gendaq, in 2001. When the Human Genome Project finished up in 2003, laying bare the entire code of how our bodies are constructed, it provided, as Sangamo communications director Dr. Elizabeth Wolffe puts it, "an embarrassment of targets" for additional research.

Borrowing a name that had once belonged to his great-grandfather's business — the Sangamo Electric Company, based in Sangamon County, Illinois — Lanphier set up shop in a low-slung laboratory in a nondescript office park. While some biotech companies have lavished their funds on glass and steel edifices well stocked with Eames executive chairs, Sangamo's office is an ode to austerity, despite the $58 million in current assets the company had on hand as of its last quarterly report. The primary office decorations are large posters illustrating various genetic processes, and plaques from its many patent awards. The CEO's window looks out toward the railroad tracks. There's no fancy cafeteria, just a roomful of vending machines.

That's in keeping with the company's public image — not too flashy, financed by a few initial waves of venture capital, an IPO in 2000, and supplemental funding from the government and advocacy groups such as the Michael J. Fox Foundation and the Juvenile Diabetes Research Foundation. "We don't have a very high profile," Lanphier said. "We sit over here in Point Richmond and don't wave our hands a whole lot, but I think the work we're doing is some of the most interesting science that is going on anywhere in the world."

Genes are the templates from which all of the proteins needed to run our bodies are built. Often in genetic disorders, a defective gene is either producing too much or too little of a necessary protein. That flaw disrupts a cascade of chemical processes needed to make the body function normally. Friedmann, of the American Society of Gene Therapy, compares such defects to cracks in a dam that is leaking and flooding everything downstream. Pharmaceuticals treat symptoms, but don't undo this initial genetic damage. "Almost all treatment of disease until now has assumed that we'll leave the dam in place leaking, leave the underlying metabolic and genetic defect in place, but we'll sort of try to just clear up the mess downstream," Friedmann said. "Gene therapy is based on the concept that you fix what is broken."

Repairing the gene itself, at least in theory, is a more elegant, definitive, and less expensive solution, because ideally it could replace a lifetime on drugs with a one-time procedure. Sangamo's basic concept is relatively simple. Think of your DNA as a long chain of letters that spells out your genetic code. Each zinc finger can match up, and then bind with, a three-letter sequence. Put together a protein made of six zinc fingers, and that combination will be long enough that you can guarantee it's a match for only one spot on the human genome. The synthetic protein can then shuttle in the DNA repair tools that will actually fix the gene.

What you get, said Dr. Philip Gregory, Sangamo's vice president of research, is an "extremely scalpel-like" method of gene transfer, as opposed to the more scattershot previous approaches, which he compared to trying to fix a flat tire by haphazardly firing a barrage of wheels at your car. Maybe one flies into the wheel well, but more likely it shows up in the backseat or lands someplace truly disruptive, such as in the engine block, destroying the car. "What we do is we actually turn up with a puncture repair kit," Gregory said. "Our approach is to fix the puncture, the mutation, but after that there is no evidence that we were here."

That's the theory, anyway. In reality, all of Sangamo's products are still in testing, and will be for several years. But the company's product pipeline provides a tantalizing peek at what zinc fingers could do.

The concept that has advanced farthest through Sangamo's pipeline is a treatment for nerve damage caused by diabetes. This damage is irreversible and affects about half of diabetics, generally starting as numbness or tingling in the feet or legs and potentially leading to a total loss of sensation. As a result, sores on the feet can go unnoticed, become infected, and necessitate amputation — diabetes is the leading cause of lower-limb amputation. "There is no successful treatment of diabetic neuropathy," Gregory said. "All that's given today are painkillers or antidepressants to treat the symptoms of this diabetes complication and not the complication itself."

Comments

Subscribe to this thread:

Add a comment

Anonymous and pseudonymous comments will be removed.

Latest in Feature

Author Archives

  • Thinking Outside the Cell

    For decades, the scientific establishment ignored Mina Bissell. Now her insights could revolutionize how cancer is understood and treated.
    • Dec 12, 2007
  • The Structure Is the Message

    What if cancer is triggered by changes outside the cell?
    • Dec 12, 2007
  • More»

Most Popular Stories

Special Reports

The Beer Issue 2020

The Decade in Review

The events and trends that shaped the Teens.

Best of the East Bay

2020

© 2020 Telegraph Media    All Rights Reserved
Powered by Foundation