George M. Church – a name we should know

Here is an interesting article about the man at the forefront of genetic engineering – discovering and manipulating genomic material as well as inventing the methods of unravelling the mysteries of the DNA…..

From Discover, by Ed Regis 25 June 2010

Here is how to get an appointment with George M. Church, professor of genetics at Harvard Medical School, director of four organizations devoted to genomics, cofounder of four biotech firms within the past four years, scientific adviser to 17 ultralow-cost genome sequencing companies, and founder of thePersonal Genome Project:

First, you send him an e-mail requesting a meeting. He will reply with the URL for a Web site that lists his current schedule. This, when printed out, proves to be a 10-page, single-spaced document in very small type that starts with “January 1, 2009: Holiday, New Year’s Day” and ends with “September 17, 2010: International Steven Hoogendijk Award 2010 for G. Church, Rotterdam, Netherlands.” Searching through hundreds of entries—as many as nine falling on a single day—you try to find an uncommitted hour. If successful, you contact either of Church’s two administrative assistants to propose a date, time, and place. Then you hope for the best.

When the magical day arrives, the first question I ask Church is how he can possibly direct, create, advise, and mastermind so many projects (as well as teach classes and supervise Ph.D. dissertations) without going crazy. “Well, I think it’s an assumption that I’m not crazy,” he says. “They all seem pretty much the same to me. They’re all integrated, and I guess what we try to do is—we try to do integration.”

If Church’s career has a single integrating theme, it is finding ways to apply the machinery of automation to the molecular basis of life, the genome. His infatuation with computers goes back to grammar school in Clearwater, Florida, when, at age 9, he built an electronic computer for a science fair. Genetics entered the picture in the spring of 1974. Then an undergraduate at Duke, Church typed into a computer all the transfer RNA sequences that were available at the time and folded each one into a three-dimensional structure, as RNA molecules were known to do. “I became obsessed with sequencing,” he says. The obsession never faded. Today his myriad projects all emerge from his impulse to know, unravel, depict, use, and—better yet—tinker with and even create the RNA and DNA codes that constitute the software of living systems.

That ambition has resulted in a raft of Church-inspired technological innovations. His automated genome-sequencing machine is driving the price of mapping a person’s entire genetic code down toward $1,000, almost unbelievably cheap considering that, less than a decade ago, the government-funded Human Genome Project spent roughly $3 billion to sequence a single genome. Low-cost sequencing has allowed Church to embark on a second venture, the Personal Genome Project (PGP), which aims to sequence the genomes of 100,000 volunteers for free. The project would provide the first extensive genome database that matches DNA to a wide range of traits—not merely physical attributes like height or eye color but also disease histories and personalities. The idea is to help inaugurate the field of personalized medicine, in which each individual would receive preventions and treatments tailored to his or her specific genetic makeup, along with predictions of future health issues.

The third major item on the Church agenda is to develop the ability to rewrite life’s software, giving us the power to reprogram organisms to do things that are radically different from what they do normally. Such wholesale reprogramming would be prohibitively expensive with what he calls the “laborious and outdated” techniques of conventional genetic engineering, which make one alteration at a time to the DNA of organisms. Church therefore went out and invented new techniques. His latest creation is a set of tools and methods that he calls multiplex automated genome engineering, or MAGE. It introduces many modifications to a genome simultaneously, opening up the possibility of designing novel genomes—in essence, creating new forms of life. One of Church’s most promising projects is to engineer bacteria that can produce jet fuel or gasoline from wood pulp or cornstalks. Another would tweak the DNA of microorganisms so that they metabolize carbon dioxide, turning it into a beneficial substance.

That is only the beginning of what MAGE could do. Ultimately Church’s tools of synthetic genomics could lead to significant, even portentous, changes to plant, animal, or human genomes. They could turn back the clock of evolution: Church has proposed a way of altering the elephant genome until it is identical to a woolly mammoth’s, or turning a human’s DNA into a Neanderthal’s. These tools could also be used to make people resistant to viruses, lengthen life span, and increase human intelligence. They could advance evolution—our evolution—to places it has never gone before.

George Church is a large specimen of a man, with a full beard and somewhat untamed hair. Now in his mid-fifties, he is rather easy to get to know because of his “Unauthorized Autobiography and Infrequently Asked Questions,” which appears on his Harvard-hosted Web site. Here you will find, among other things, his online medical records, dietary notes, baby picture, signature, and random interests (which include waterskiing, rock climbing, and turtle breeding), as well as the exact latitude and longitude of his home and a map of his neighborhood.

For a man of such unusual talents and attainments, Church had a relatively conventional life until he entered college. He graduated magna cum laude from Duke University in two years, then proceeded to flunk out of graduate school. The reason, he says, is that he neglected “boring” course work in favor of lab research, which resulted in five papers published in peer-reviewed journals. That got him accepted to a doctoral program at Harvard, where he studied with molecular biologist Walter Gilbert. In 1980 Gilbert won a Nobel Prize for his work sequencing DNA.

Church thrived in Gilbert’s lab. In 1977 he developed a way of automating a key step of Gilbert’s DNA sequencing method. DNA strands are made up of combinations of four bases, molecules that are denoted by the letters A, T, C, and G. Sequencing DNA—reading out all the letters along the double helix—was a laborious process in which lab technicians used pipettes to deposit DNA samples onto the surface of a gel. The samples were labeled with radioactive isotopes, which meant that each individual base (the A, T, C, or G) produced a visual signature on film. It was up to the experimenter to read and record the sequences in the proper order. Church, who always wants to do things quickly, preferably by automation, figured out how to make a computer read the sequences. He did not yet have his Ph.D., but he was already making a major contribution to genetics.

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Telomeres—repeating DNA sequences at the ends of chromosomes that become shorter with each cell division—have long tantalized biologists seeking to understand and control the aging process. When its telomeres become too short, a cell stops dividing and eventually dies. Stop that process and (just maybe) immortality beckons; hence the frenzy a decade ago when a group of researchers claimed they had figured out how to slow that winding-down. Now a second round of frenzy is under way. After years of research, the first telomere-targeting pills have hit the market, while other treatments are entering clinical trials. Continue reading