The 3 Papers That Define Biotechnology

Drew Endy.jpg
Stanford's Drew Endy is an engineer's biologist. He doesn't like to wonder at the messy world of evolved systems; he likes to create new tools for building organisms that do stuff for humans. 

His presentations, like the one he delivered Wednesday at the Aspen Ideas Festival, work the same way. Endy has a knack for breaking down the dizzying array of work being done learning how to encode and decode DNA into digestible, discrete components. 

It's a welcome service given that the Ideas Festival has dedicated an entire set of sessions to what it's calling "The Century of Biology." That's the notion that humans' increasing understanding and manipulation of living systems will have the same massive impact on the 21st century that advances in thermodynamics and physics (think: electricity, engines, computers, rockets) had in the 20th.

If physics seems tough enough to understand, biological complexity is truly mindboggling, and the scientific literature surrounding biotech reflects that. Pop a basic concept like "DNA recombination" into Google Scholar, and you get more than 20,000 results. Even Google's algorithms can't tell you which papers might be the most important nodes in the network.

And that's why one slide in Endy's presentation was particularly good for those who want to understand the truly foundational work in the field. It showed the three papers Endy says are the key touchpoints for what we now know as biotechnology. Each one showed that scientists had gained new fundamental knowledge about how to manipulate the language of life. Here they are:

  • 1973: "Construction of biologically functional bacterial plasmids in vitro" by Cohen et al. in Proceedings of the National Academy of Sciences. This was the paper that marked the beginning of the age of genetic engineering. Scientists were able to insert DNA into a living organism. The paper eventually led to the founding of, Genentech, Endy said.
  • 1985: "Cloning and expression of the human erythropoietin gene" by Lin et al. in Proceedings of the National Academy of Sciences. Here, researchers showed that they could use genetic engineering to produce human proteins, the biological machines that do work within the body. In this particular case, a protein needed by anemia patients was produced in hamster ovary cells. The paper represents the foundational work that made the company, Amgen. 
  • 2006: "Production of the antimalarial drug precursor artemisinic acid in engineered yeast" by Ro et al in Nature. Berkeley laboratory researchers took $25 million and created a vastly cheaper way to synthesize an antimalarial drug. The research led to the creation of Amyris, which has raised $383 million from investors, and recently filed to go public. 
It should be noted that Endy thinks this work and that of field pioneer Craig Venter -- as good as it is -- all suffers from a lack of the engineering that defines other technological fields. "The genetic engineering of these projects has remained expert-driven artwork," Endy said. Put another way, biology as a field has focused too much on medical applications and not enough on tools. "We're always trying to solve problems instead of getting better at solving problems." 


So, while we can synthesize DNA, there is no way to program organisms the way you can a computer. That is to say, there are no compilers to translate human desires into biological functions. And that's the next step, Endy thinks, in delivering on the promise of biotechnology. We need a true programming language (like Java) for living cells.

If you could program cells without having to know biochemistry in depth, one can imagine you might unleash the talents of a generation of computer programmers and entrepreneurs. That collective effort could deliver the innovation that observers like Harvard's Niall Ferguson say the United States needs to resurrect its economy. 

Then we'd have a whole new set of challenges to face. Or as the ever-pithy founder of the Whole Earth Catalog, Stewart Brand, put it after Endy's talk, "The century of biology is also the century of bioethics."

Image: Drew Endy.Credit: Alexis Madrigal.
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Alexis C. Madrigal

Alexis Madrigal is the deputy editor of He's the author of Powering the Dream: The History and Promise of Green Technology. More

The New York Observer has called Madrigal "for all intents and purposes, the perfect modern reporter." He co-founded Longshot magazine, a high-speed media experiment that garnered attention from The New York Times, The Wall Street Journal, and the BBC. While at, he built Wired Science into one of the most popular blogs in the world. The site was nominated for best magazine blog by the MPA and best science website in the 2009 Webby Awards. He also co-founded Haiti ReWired, a groundbreaking community dedicated to the discussion of technology, infrastructure, and the future of Haiti.

He's spoken at Stanford, CalTech, Berkeley, SXSW, E3, and the National Renewable Energy Laboratory, and his writing was anthologized in Best Technology Writing 2010 (Yale University Press).

Madrigal is a visiting scholar at the University of California at Berkeley's Office for the History of Science and Technology. Born in Mexico City, he grew up in the exurbs north of Portland, Oregon, and now lives in Oakland.

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