Secret Harvard meeting finally releases ambitious synthetic human genome proposal

Three weeks ago, 130 scientists, entrepreneurs and policy leaders held an invitation-only, closed-door meeting at Harvard University to discuss an ambitious plan to create synthetic human genomes. Now, after a flurry of criticism over the secrecy of the effort, the participants have published their idea, declaring that they're launching a project to radically reduce the cost of synthesizing genomes – a potentially revolutionary development in biotechnology that could enable technicians to grow human organs for transplantation.

The announcement, published Thursday in the journal Science, is the latest sign that biotechnology is going through a rapidly advancing but ethically fraught period. Scientists have been honing their techniques for manipulating the complex molecules that serve as the code for all life on the planet, and this same issue of the journal Science reports a breakthrough in editing RNA, a molecule that is the close cousin of DNA.

The promoters of synthetic genomes envision a project that would eventually be on the same scale as the Human Genome Project of the 1990s, which led to the sequencing of the first human genomes. The difference this time would be that, instead of “reading” genetic codes, which is what sequencing does, the scientists would be “writing” them. They have dubbed this the “Genome Project-write.”

"[T]he goal of HGP-write is to reduce the costs of engineering and testing large genomes, including a human genome, in cell lines, more than 1,000-fold within ten years, while developing new technologies and an ethical framework for genome-scale engineering as well as transformative medical applications," the group wrote in a draft of a news release obtained by The Post. The project will be administered by a non-profit organization called the Center of Excellence for Engineering Biology, the news release said.

The plan drew a negative response from the head of the National Institutes of Health, Francis Collins, who had led the earlier Human Genome Project. In a statement released by NIH, Collins said it was premature to launch such an initiative.

“NIH has not considered the time to be right for funding a large-scale production-oriented ‘HGP-write’ effort, as is framed in the Science article,” Collins said. He added, "There are only limited ethical concerns about synthesizing segments of DNA for laboratory experiments. But whole-genome, whole-organism synthesis projects extend far beyond current scientific capabilities, and immediately raise numerous ethical and philosophical red flags.”

No one is talking about creating human beings from scratch. One application of cheaper genome synthesis, according to geneticist George Church, one of the authors of the Science article, would be to create cells that are resistant to viruses. These would not be cells used directly in human therapies, but rather in cell lines grown by the pharmaceutical industry for developing drugs. Such processes are vulnerable now to viral contamination.

“If you’re manufacturing human therapeutics in mammalian cells, and you get contamination, it can blow you away for two years, which has actually happened," Church said.

The Science paper gives a number of examples of what could emerge from cheaper synthesized genomes: "growing transplantable human organs; engineering immunity to viruses in cell lines via genome-wide recoding; engineering cancer resistance into new therapeutic cell lines; and accelerating high-productivity, cost-efficient vaccine and pharmaceutical development using human cells and organoids."

The synthetic genome plan emerged from two closed-door meetings, one in New York City last year, and the second on May 10 at Harvard.

The latter drew criticism from researchers who objected to the closed-door nature of the event; organizers said they didn't want to publicize their idea in advance of the publication of the article in Science. They said they plan to put a video of the proceedings online.

Drew Endy, an associate professor of bioengineering at Stanford, wrote on Twitter, "If you need secrecy to discuss your proposed research (synthesizing a human genome), you are doing something wrong."

Endy and Laurie Zoloth, a professor of medical ethics and humanities at Northwestern University, published an essay in which they said that, although this technology has promising applications, "it is easy to make up far stranger uses of human genome synthesis capacities."

Endy on Thursday renewed his criticism. He said the group is proceeding without approval of the broader scientific community or any independent ethical review, he said.

“Do we wish to be operating in a world where people are capable of organizing themselves to make human genomes? Should we pause and reflect on that question before we launch into doing it?” Endy told The Post. "They’re talking about making real the capacity to make the thing that defines humanity – the human genome.”

He said the article published in Science does not address any ethical questions. The promoters of the project say they will handle the ethical questions that come up, but Endy said in an email that this appears to be "a brazen attempt to preempt independent ethical review."

The project has four lead organizers: Church, a geneticist at Harvard Medical School; Jef Boeke, director of the Institute for Systems Genetics at the NYU Langone Medical Center; Andrew Hessel, a researcher with the publicly traded company Autodesk; and Nancy J. Kelley, formerly executive director of the New York Genome Center.

The news release stated that Kelley will be the top executive for the project, and that Autodesk has committed $250,000 in funding for the planning efforts.

The organizers hope to raise $100 million by the end of this year, with an eventual goal of devoting $3 billion to the effort. The authors of the Science article wrote that some portion of the money that would be raised for the project should be directed toward addressing the ethical, legal and social issues surrounding how new genetic engineering technologies will be used.

Church, informed of Endy's latest comments, said nine of the participants in the Harvard meeting were experts on the ethical, legal and social implications of technology, and he said he expects many more will respond to the article in Science.

"Even when we identify something that we do not want, we need to think deeply about how to prevent it -- effective surveillance, deterrents and consequences," Church told The Post.

Church, whose laboratory at Harvard Medical School is renowned for breakthroughs in genetic engineering, said that in a span of three to 10 years it should be possible to bring down the cost of synthesizing long stretches of DNA by a thousand-fold. That would mirror the huge declines in the cost of sequencing – that is, reading – human genomes. He said researchers are already synthesizing stretches of genetic code, but only in small pieces. The obstacle to widespread application and testing of synthetic genomes is the cost, he said.

The field of genetic engineering has been dealing with ethical quandaries since the 1970s. In December, for example, scientists from the U.S., Europe and China met in Washington and agreed to put limits on the breakthrough gene-editing technique known as CRISPR, which has the potential to make heritable changes in a person's genome.

Copyright: Washington Post