Scientists Debate Building Human Genome from Scratch

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A ‘family spat’ spills out in public, as scientists debate effort to build a human genome

Harvard Medical School’s George Church and Stanford University’s Drew Endy are top scientists who have expanded the boundaries of biology with their pioneering discoveries. They have written papers together and even cofounded a synthetic biology company.

But over the past month, they have been cast as the opposing spokesmen in the debate over whether scientists should try to build human and other genomes from scratch, a project that could transform our understanding of the basic building blocks of life but that is fraught with ethical issues.

On Saturday, Church and Endy found themselves on a pair of panels here at the World Science Festival, just two days after Church and colleagues published an outline for a 10-year genome synthesis project, and Endy called for the project to be scuttled in its current form.

“As much as anything, it’s an uncomfortable situation for me,” Endy admitted at one of the panels. “It sort of feels like a fight among family.”

Endy conceded that this was an unusual position for him, one that he described as the second most difficult professional situation he had ever faced (he wouldn’t say what the first was). He said he would typically be “one of the most fanatical proponents” of a synthetic biology project that could improve scientists’ ability to construct DNA. But he was drawing the line at the creation of a human genome in a lab.

“I realize that’s complicated and doesn’t seem consistent, but here we are,” he said.

He added: “The human genome is special to me — it’s the thing that connects us.”

In the paper published Thursday, Church and 24 others sketched their goal of constructing animal genomes, ultimately producing a synthetic version of a complete genetic blueprint of a human. In synthesizing a genome, scientists would attach the building blocks that make up DNA and combine genes in a design of their choosing.

Scientists could then swap natural genomes in human cells for the crafted genomes to study which genes promote different traits, diseases, or functions. That could help improve the drug development process, and uncover how human cells could resist viruses or cancer.

But the project raises thorny ethical questions. Although it’s not a goal of the project, in theory, brewing up a complete human genome could lead to the formation of an actual person, sans parents. The effort, in other words, picks at the most fundamental question of our identity: What does it mean to be human?

“The human genome is special to me — it’s the thing that connects us.”
DREW ENDY, STANFORD UNIVERSITY

At one panel, a young member of the audience asked: If you could build humans without sperm and egg, what would stop the military from making “perfectly expendable” humans that no one would miss if they died?

The project has also raised the question of who would “own” the synthetic genome and whether someone might try to profit from it. One of the project organizers is a scientist at a software company, Autodesk.

Plans for the project emerged publicly last month when Endy and Northwestern University bioethicist Laurie Zoloth criticized a closed-door meeting organized by Church to discuss the technical and ethical challenges of the initiative.

At the panels Saturday, Church said he wanted more and frequent public discussion about the project. He said the meeting was kept private to encourage those invited to feel like they could throw out even half-baked ideas.

When asked why this project was happening now, Church said science had been building toward it for years. Teams of scientists have been synthesizing the genomes of bacteria and yeast, an organism whose genome is about 300 times smaller than a human’s. The work could uncover new knowledge about how to best combine the “letters” that make up DNA and bring down the cost of doing so.

And launching a formal initiative, Church said, could galvanize a necessary dialogue about a sensitive research project that other scientists would pursue even if he and his colleagues abstained.

“To some extent, you want to get ahead of it,” Church said.

Church said the core science of assembling a human genome from basic molecular ingredients dates back to at least 2009. And he noted that scientists have been grappling with related ethical questions for more than a decade, since the early days of synthetic biology opened the door to the idea of someone being able to build a pathogen from basic genetic components.

He said that although the project has no intention of spawning actual humans, the project’s leaders would not ignore the “ethical, social, legal” issues that inherently materialize given where the project could lead.

The effort has more modest goals than has been suggested by some others, Church said, but “that doesn’t mean you should ignore all the other ramifications.”

But to Endy, the fact that the project started behind closed doors is enough reason to halt it for now so outside groups could weigh in.

Endy also said that the project — known as “HGP-write,” a reference to the original Human Genome Project that first sequenced the genome — could confer legitimacy on the efforts of others who might be interested in building synthetic human genomes but who might not uphold the same standards as Church and his colleagues. He said he worried about an “open season” on that kind of work.

“I love the specific projects that George and colleagues are proposing, but I also take at face value that this is going to go beyond that,” Endy said.

Scientists involved with the project face huge challenges, and any actual human genome cooked up in a lab is years away. The effort to build the genome of yeast has been in the works for a decade, with much more work to come.

“The first time we try to piece it together? It’s going to fail,” Harvard synthetic biologist Pamela Silver, who is also an author with Church on the paper, said at one of the panels.

Despite occasional awkwardness, the panels were civil — as befitting an event involving scientists. At the second session, an old photo of Zoloth, Church, and Endy, all smiling, was projected, and Endy frequently praised Church.

“I wouldn’t make too much of a family spat, so to speak,” Endy said, “but you can if you want.”

Article Credit: STAT