Harvard Speeds Up Evolution, Shops Secret to DuPont

George Church
George Church, a researcher and professor of genetics at Harvard Medical School. Photographer: Graham Ramsay/Harvard University via Bloomberg News

Evolution often plays out over millennia. George Church says he can make it happen in days.

He and his team of researchers at Harvard Medical School in Boston invented a table-top machine that can generate multiple changes in the DNA of bacteria all at once, speeding up the evolutionary process. Aiming to sell the technology for use in chemicals, energy, and the drug industry, they’re talking with DuPont Co. and other companies, members of the team said.

Church, a 56-year-old genetics professor, is a pioneer in synthetic biology, the field in which scientists manipulate DNA to create organisms that don’t exist in nature, Bloomberg Businessweek reports in its Aug. 16 issue. Researchers may one day be able to use these techniques to develop cotton that’s waterproof or bananas that stay ripe for months, according to scientists in Church’s lab.

“This is going to change the way we think about manipulating biology,” said Harris Wang, one of the team leaders, in a telephone interview.

The technology, known as multiplex automated genetic engineering, or MAGE, was created by Church, Wang, Farren Isaacs, and others in Church’s group. It can induce 50 different gene alterations in a population of bacteria almost simultaneously, creating billions of cellular mutations in a matter of days, the team said. They can then identify the most- useful mutations, the scientists said.

Altered Bacteria

Manipulating bacterial cells is as old as biotechnology itself. What’s new is that Church’s machine automates the process of repeatedly introducing modified DNA into many cells, thus inducing multiple specific changes at the same time. Scientists can adjust the types of alterations --substituting genes, inserting them, or deleting them in the bacteria.

The MAGE machine was first presented in an August 2009 paper in Nature.

Using this technology, Church and his associates genetically altered E. coli to produce lycopene, the pigment in tomatoes that may be a cancer-fighting nutrient. Some of the altered bacteria produced five times as much lycopene as they would have made if enhanced by older techniques.

The Harvard team spent just three days and $1,000 in supplies to accomplish this. It would have taken months to do it the old way, Church said in an e-mail. The team has patented the technology and aims to start selling it to other researchers and to companies later this year at about $90,000 a pop, Church said in a telephone interview.

Dozen Companies

At least a dozen companies are now in talks with Church’s group, researchers said, including DuPont, based in Wilmington, Delaware; Life Technologies Corp. in Carlsbad, California, a biotechnology company making tools for medical research; Koninklijke DSM NV, a chemical company based in Heerlan, Netherlands; and Amyris Biotechnologies Inc., a renewable-energy company in Emeryville, California.

DuPont spokeswoman Tara Steward declined to confirm or comment on any discussions with Church’s team, as did Life Technologies spokesman Tim Ingersoll, Koninklijke spokesman Andre van der Elsen, and Erin Kinsella of Amyris.

This isn’t the first time Church has played scientific revolutionary. He helped start the government-funded Human Genome Project, which decoded the entire human genetic blueprint in 2000. That triumph came after a spirited race against a private effort led by geneticist Craig Venter, who runs the J. Craig Venter Institute, based in Rockville, Maryland. The teams shared credit for the milestone.

Church and Venter are once again sharing the limelight. In May, Venter and his team reported in the journal Nature that they had inserted a fully customized strand of DNA into a living cell, creating what they call the “first synthetic genome.”

Tricked Cells

In contrast, the Harvard team modifies DNA directly in live cells, which are tricked into thinking it’s their own genetic material, Wang said.

“Practically, these two approaches will eventually meet somewhere in the middle,” Wang said. While MAGE can produce high quantities of cells with many functions, Venter’s method can design cells that can be used as templates to build on, he said.

“MAGE strikes me as a typically Churchian idea: big, cutting-edge, high-risk/high-reward,” said Misha Angrist, an assistant professor at Duke University’s Institute of Genome Sciences & Policy, in Durham, North Carolina, in an e-mail. “George always seems to look several steps ahead of where the field is.”

Clyde Hutchison, a member of the Synthetic Biology Group at Venter’s institute, declined to comment on MAGE.

Venture Capitalists

The Harvard team has worked with engineers at Boston Engineering Corp., a closely held engineering-services company in Waltham, Massachusetts, since October to turn MAGE into a manufacturable machine, Wang said. The prototype is now going through the validation stage. Within a few months, the team and venture investors may license rights to technology from Harvard, and create a company that would work with clients, Isaacs said.

Church was drawn into biology at a young age. Playing around with insects and pond muck as an 8-year-old was one of his “earliest thrills,” he said. Computers grabbed his attention as well, and by ninth grade he was programming simple video games.

The global market for synthetic biology totaled $233.8 million in 2008 and may increase to $2.4 billion in 2013, according to a June report from BCC Research, a research company in Wellesley, Massachusetts. Applications in chemicals and energy produced sales of $80.6 million in 2008, the report said. Those in biotechnology and pharmaceuticals came to $80.3 million.

Church’s project is funded by Harvard’s Boston-based Wyss Institute for Biologically Inspired Engineering, founded in January 2009 after Hansjörg Wyss, chairman of Switzerland’s Synthes Inc., donated $125 million to Harvard University in Cambridge, Massachusetts.

Terror and Profit

Church and his peers said they can’t predict what kind of organisms they could create by manipulating DNA in living cells. The U.S. should draw up regulations to monitor or prevent research that might create virulent new viruses or other pathogens, Church said at a government bioethics hearing in Washington in July. In the wrong hands, synthetic biology could be a tool for bioterrorism, he said.

“The potential benefits are enormous; at the same time, the risks are real,” said Kristala Prather, an assistant professor of genomics at the Massachusetts Institute of Technology in Cambridge. She spoke at the hearing, part of the Presidential Commission for the Study of Bioethical Issues. “There’s an information gap between what we understand about synthetic biology and what our capabilities are.”

President Barack Obama created the commission to “reap the rewards” of the science as much as to monitor potential dangers, said Amy Gutmann, who chaired the meetings.

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