EW YORK — As scientists aiming to create genomes from scratch see it, nature had her chance — 3.8 billion years, to be precise, the length of time that life on Earth has been evolving and, supposedly, getting more finely adapted and more complex. Now it’s the turn of scientists, who think they can do better.
Halfway through a two-day meeting of “Genome Project-write” at the New York Genome Center in New York City, more than 250 attendees from 10 countries had unveiled dozens of ways that designing and building genomes might make possible a dazzling litany of futuristic advances.
Scientists outlined ways to change the genomes of the microbes that live in the human gut so as to protect people from obesity and chronic stress; to change plant genomes so they detect the explosive TNT (cue the photograph of airport security surrounded by bomb-detecting philodendrons); to make bacteria that produce pharmaceuticals resistant to viruses that have shut down expensive production lines, and more.
These new ideas will not become reality as quickly as GP-write organizers hoped, however. Last year, its leaders said they wanted to raise $100 million by now, from corporations, perhaps the National Institutes of Health, and donors. But only an initial $250,000, from software company Autodesk, is in the kitty.
As a result, project co-leader Nancy Kelley said, GP-write has been able to fund only one pilot project. The pitches from (mostly) junior scientists on Tuesday were therefore more to get the project’s stamp of approval — Kelley said its leaders would write letters of support so the researchers could seek funding elsewhere — than an actual check.
The overall goal of GP-write (the GP stands for genome project) is to “advance the cause of human health,” said Kelley, who is founding executive director of the New York Genome Center. But it is also to change “how we as scientists learn about the world,” said biochemist and project co-leader Jef Boeke of New York University. Physicist Richard Feynman’s observation that “what I cannot create I cannot understand,” he added, “has become a kind of manifesto for our field.”
The meeting was part pitch-fest, as scientists proposed projects that could be part of GP-write, and part progress report on research that was underway long before GP-write, most notably the construction of five out of the 16 chromosomes that make up the yeast genome, a project Boeke co-leads. The line to register in the morning was out the door onto Sixth Avenue, the room was standing room only with spillover into the adjacent cafeteria, and hundreds more watched the livestream of the first session.
GP-write sparked controversy last year when its first organizing meeting, at Harvard Medical School, was closed to the media and public, triggering suspicion that something nefarious was being done in secret. Ethicists and others also grew alarmed at what the project, then named HGP-write (the H is for human), might do. Visions of designer humans danced in some critics’ heads. (The “write” in the name is meant to distinguish this from the Human Genome Project, which “read” the 3 billion chemical letters that constitute human DNA.)
In fact, “as far as I know, there is no plan to make embryos or humans,” said Barbara Evans, a law professor at the University of Houston, looking around the room at the project’s leaders, who nodded vigorously.
Initially, GP-write will support the development of technology to design and synthesize (from chemical building blocks) genomes, the full complement of an organism’s DNA. The chief aim is to reduce the cost of doing that by 1,000-fold over the next 10 years; it now costs about 10 cents to synthesize one “base pair,” or a single duo of the 3 billion in the human genome.
Unlike reading genomes, Boeke said, “writing has a sort of element of creativity, an artistic side if you will.” The possibility of writing a human genome, therefore, “is simultaneously thrilling to some and frightening to others.” A human genome, he said, might be produced from scratch by 2027.
Such a synthetic genome would not get slipped into, say, a human egg and allowed to develop into the first genetically bespoke person, he and others said. Instead, the hope is to learn “the rules that make a genome tick,” Boeke said. “We want to do only good things and not bad things.”
All the studies presented at the meeting are independent of GP-write but might eventually contribute to it. Using funding from the Pentagon’s Defense Advanced Research Projects Agency, for instance, biologist Harris Wang of Columbia University is figuring out how to change the genomes in the microbes that live in and on people, called the human microbiome. These bugs seem to influence metabolism and, therefore, obesity and diabetes; affect whether someone develops irritable bowel syndrome; and might influence the nervous system.
“We’re asking, how do we manipulate microbiomes associated with the human body, and possibly introduce new functions,” Wang said. One possibility is to modify the genomes of humans’ hitchhikers so they can synthesize every essential amino acid, freeing people from having to get these protein building blocks from food. Another is to give these microbes genomes that secrete compounds that improve the motility of the gastrointestinal tract, to treat irritable bowel syndrome; genomes that sense and respond to infection; or even genomes that produce neurotransmitters that might affect memory and other brain functions.
How would engineered gut microbes get into patients? As it happens, fecal transplants are already used to treat infections with C. difficile.
Writing genomes isn’t limited to animals. Although existing genetic techniques have led to plants that can sense TNT at levels ten-to-hundredfold lower than bomb-sniffing dogs, said biologist June Medford of Colorado State University, techniques developed by GP-write might do even better.
“We want to engineer plants to filter water and secrete pure water,” she said. “Imagine if we could filter seawater and provide unlimited water for life on earth.”
One unanswered question is when it will be necessary to construct a genome from scratch rather than tweaking what nature provided, such as with the genome-editing tool CRISPR. Nili Ostrov of Harvard Medical School, for instance, is editing the genomes of bacteria to make them resistant to viral infection. That’s a big problem for the biotech industry, which uses bacteria and other cells to produce a whole drugstore’s worth of pharmaceuticals.
Ostrov and her colleagues are therefore changing bacterial DNA so that the DNA that a virus injects into a cell — which is how a virus forces an infected cell to produce zillions more viruses — doesn’t work. “That would make the host cell virus resistant,” she said.
Legal scholars and bioethicists had prominent roles at the meeting, mostly discussing how to keep the public informed about the project.
It should have a plan for doing that “in the next year,” said bioethicist Jonathan Moreno of the University of Pennsylvania: 2018 brings the 200th anniversary of the publication of Mary Shelley’s “Frankenstein,” which might — if GP-write is well underway — lead someone to ask, “Isn’t that a coincidence?”