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Plan to Fabricate a Genome Raises Questions on Designer Humans

What will scientists do with $100 million to mass-produce genes in the lab?

A proposal by a group of scientists and businesspeople to synthesize a human genome from scratch is attracting sharp criticism for dodging the big ethical questions such a step raises.

The proposal, described today in a two-and-a-half-page letter being published in Science, is to string together synthetically made DNA and shape from it a human genome able to power a cell in a dish, according to lead authors Jef Boeke of New York University’s Langone Medical Center and biotechnologist George Church of Harvard Medical School.

A different team previously made bacteria with lab-made genes, but the human genome is far larger. The backers of the new plan, called HGP-write, argue that a mega-project could cause the cost of fabricating DNA to plummet 1,000-fold in 10 years, prompting revolutionary advances in science and industry. But the paper’s 25 authors remain silent on the looming ethical debate: will we be able to make people with artificial genomes, and if so, should we?

 “Before launching into such a momentous project, questions need to be asked,” including whether it should even occur, says Stanford University synthetic biologist Drew Endy. “The authors fail to pose these essential questions. In fact, in their proposal, they fail to pose any questions.”

George Church of Harvard Medical School authored a 2012 book predicting synthetic biology could lead to engineered humans resistant to all viruses.

Luckily, Church, an ebullient futurist whose handiwork is visible in the paper, previously not only asked the big questions, but answered them. In his 2012 book, Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves, Church describes the “the climax” of synthetic biology as the production of humans with lab-fabricated genomes that are immune to all viruses, including HIV and herpes.

Church is a colorful and influential figure whose students dominate wide sectors of genomic technology and innovation. He also hasn’t been shy about coming out in favor of genetically engineered people, including the use of gene editing to repair particular genes before birth.

But manufacturing entire genomes opens a door to larger and different types of alterations. The one Church has been most enthusiastic about is called “recoding,” in which the letters of a genome are widely rejiggered to deny viruses entry. “We propose … to change it,” wrote Church of the code that all life shares. “Yes this sounds like hubris all right.”

The creators of HGP-write say their goal is to raise $100 million toward synthesizing a human genome inside of 10 years, but only in a lab dish. “The purpose of this project is to develop and test large genomes in cells, and that is where it stops,” says Nancy Kelley, a fundraiser who is among the authors of the paper and is described as the “lead executive” of the project. The effort so far, including two planning meetings, has been paid for with a $250,000 grant from the software company Autodesk to an organization called the Center of Excellence for Engineering Biology, which Kelley runs.

“They did make it clear they are going to do mammalian cells in culture,” says Peter Carr, a synthetic biologist at Lincoln Labs, who attended a planning meeting last month at Harvard. “But then where does the story go from there? Obviously part of the excitement is that there would be humans with synthetic genomes. In the background of all of this is this exciting dream—what if we could make humans that are immune to viruses?”

What’s strange to critics is that the Science paper doesn’t mention these possibilities. It talks in detail about how “cells” could be made virus- or cancer-resistant, or have improved traits. But who wants human cells like that? In Church’s book, he says exactly the same things about making people.

In an e-mail, Church agreed that the proposals described in his book could follow if genome-writing technology were developed, even if they aren’t the aim of HGP-write. “Our project is paying attention to these longer-term implications,” he said.

Such unspoken possibilities are troubling to Laurie Zoloth, a professor of religion and bioethics at Northwestern University. “It’s unclear if they understand that the first step, which has to be the beginning of the project, is to ask: is this a good idea?” says Zoloth. She notes that making new genomes via sex is “one of the last things that people do by themselves, with joy and faith, and they don’t do it for profit. If it’s done in the lab, it’s a commodity.”

Zoloth also worries that such a monumental proposal is being led by Autodesk, a mid-cap software company with rinky-dink biomedical credentials. Today, Autodesk published two Medium posts (here and here) in which it dismissed the idea of lab-made people. “Sorry to disappoint, but no synthetic humans will be produced here,” writes Autodesk futurist Andrew Hessel.

Recoding life

According to Church, however, making new types of people actually is the ultimate purpose of such technology. Church is a transhumanist who sees mankind’s goal as further evolving itself and the rest of nature with it, according to scientific principles. In his book, Church says such ideas are not as “blasphemous” as they may at first appear.

To understand Church’s big idea of recoding, it’s important to know that the letters of DNA deliver information in a three-letter code. When cells make proteins, these three-letter “codons” tell it which amino acid to add to the unspooling protein. Other codons tell it when to stop.

Nearly every aspect of our bodies, and life in general, relies on proteins manufactured using this DNA code. While no one yet knows for sure, the code arose several billion years ago, perhaps in some steaming primordial pool under a volcano somewhere, and has not changed since. In 1968 three smart guys won the Nobel Prize for figuring out how it worked. (Footnote: to do it, they had to make the first synthetic genes.)

An important feature of the code is that some codons are redundant: they specify the same amino acid. Church’s recoding idea entails reworking a genome to eliminate redundant codons—and, along with them, some other genes these codons need to assist in protein making. Without that machinery, invading viruses wouldn’t be able to copy themselves, since they rely on the missing codons.

So say goodbye to HIV, herpes, and the common cold. It’s an idea that would make Louis Pasteur jump. A “monkey wrench,” Church calls it.

Church’s lab has already started revising the codons in E. coli. In fact, this project is well advanced. He said in an interview his lab has synthesized the equivalent of the entire E. coli genome and replaced seven of its 64 codons. Those bugs probably can’t get infected by viruses that prey on bacteria. And that might actually be pretty useful. It’s not dinner-table talk, but many important drugs and products are manufactured in E. coli, and sometimes raging infections hit biofactories and shut down production lines

“That is a radical change. There is no organism on the planet that does not use all 64 codons other than the one we made,” Church says.

Next up after bacteria there could be agricultural applications. How about a tomato plant that repels viruses? Or dairy cows whose udders don’t suffer infections? The Science paper suggests we could make virus-resistant human organs or cells for transplant.

In his book, Church allows the idea to run to its conclusion. If such preliminary applications worked out, there would then be “the temptation to apply the same technique to humans.” And there would be some good reasons to do so. You might make people cancer-resistant by jamming their genomes full of tumor-suppressor genes. Or you could make them radiation-resistant so they could travel into space and populate new worlds, in case ours runs into trouble.

It all sounds like something from a galaxy far, far away.

But with HGP-write, it’s going to get closer.

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