Scientists are developing ways to edit the DNA of tomorrow’s children

If anyone had devised a way to create a genetically engineered baby, I figured George Church would know about it.

At his labyrinthine laboratory on the Harvard Medical School campus, you can find researchers giving E. Coli a novel genetic code never seen in nature. Around another bend, others are carrying out a plan to use DNA engineering to resurrect the woolly mammoth. His lab, Church likes to say, is the center of a new technological genesis—one in which man rebuilds creation to suit himself.

When I visited the lab last June, Church proposed that I speak to a young postdoctoral scientist named Luhan Yang, a Harvard recruit from Beijing who’d been a key player in developing a new, powerful technology for editing DNA called CRISPR-Cas9. With Church, Yang had founded a small company to engineer the genomes of pigs and cattle, sliding in beneficial genes and editing away bad ones.

As I listened to Yang, I waited for a chance to ask my real questions: Can any of this be done to human beings? Can we improve the human gene pool? The position of much of mainstream science has been that such meddling would be unsafe, irresponsible, and even impossible. But Yang didn’t hesitate. Yes, of course, she said. In fact, the Harvard laboratory had a project to determine how it could be achieved. She flipped open her laptop to a PowerPoint slide titled “Germline Editing Meeting.”

Here it was: a technical proposal to alter human heredity.

“Germ line” is biologists’ jargon for the egg and sperm, which combine to form an embryo. By editing the DNA of these cells or the embryo itself, it could be possible to eliminate disease genes and to pass those genetic fixes on to future generations. Such a technology could be used to rid families of scourges like cystic fibrosis. It might also be possible to install genes that offer lifelong protection against infection, Alzheimer’s, and, Yang told me, maybe the effects of aging. These would be history-making medical advances that could be as important to this century as vaccines were to the last.

The fear is that germ line engineering is a path toward a dystopia of super people and designer babies for those who can afford it.

That’s the promise. The fear is that germ line engineering is a path toward a dystopia of super people and designer babies for those who can afford it. Want a child with blue eyes and blond hair? Why not design a highly intelligent group of people who could be tomorrow’s leaders and scientists?

Just three years after its initial development, CRISPR technology is already widely used by biologists as a kind of search-and-replace tool to alter DNA, even down to the level of a single letter. It’s so precise that it’s widely expected to turn into a promising new approach for gene therapy treatment in people with devastating illnesses. The idea is that physicians could directly correct a faulty gene, say, in the blood cells of a patient with sickle-cell anemia (see “Genome Surgery”). But that kind of gene therapy wouldn’t affect germ cells, and the changes in the DNA wouldn’t get passed to future generations.

In contrast, the genetic changes created by germ line engineering would be passed on, and that’s what has always made the idea seem so objectionable. So far, caution and ethical concerns have had the upper hand. A dozen countries, not including the United States, have banned germ line engineering, and scientific societies have unanimously concluded that it would be too risky to do. The European Union’s convention on human rights and biomedicine says tampering with the gene pool would be a crime against “human dignity” and human rights.

But all these declarations were made before it was actually feasible to precisely engineer the germ line. Now, with CRISPR, it is possible.

The experiment Yang described, though not simple, would go like this: The researchers hoped to obtain, from a hospital in New York, the ovaries of a woman undergoing surgery for ovarian cancer, caused by a mutation in a gene called BRCA1. Working with another Harvard laboratory, that of antiaging specialist David Sinclair, they would extract immature egg cells that could be coaxed to grow and divide in the laboratory. Yang would use CRISPR in these cells to correct the DNA of the BRCA1 gene. The objective is to create a viable egg without the genetic error that caused the woman’s cancer.

As with several other scientists whom I’d asked about human germ line engineering, Yang stopped replying to my questions, so it’s hard to know if the experiment she described is occurring, canceled, or pending publication. Church, in a phone call, termed it a “non-project,” at least until it has generated a publishable result, though Sinclair said a collaboration between the labs is ongoing. (After this story was published, Yang called to say she had not worked on the experiment for several months.) Regardless of the fate of that particular experiment, human germ line engineering has become a burgeoning research concept. At least one other center in Boston is working on it, as are scientists in China, in the U.K., and at a biotechnology company called OvaScience, based in Cambridge, Massachusetts, that boasts some of the world’s leading fertility doctors on its advisory board.

The objective of these groups is to demonstrate that it’s possible to produce children free of specific genes that cause inherited disease. If it’s possible to correct the DNA in a woman’s egg, or a man’s sperm, those cells could be used in an in vitro fertilization (IVF) clinic to produce an embryo and then a child. It might also be possible to directly edit the DNA of an early-stage IVF embryo using CRISPR. Several people interviewed by MIT Technology Review said that such experiments had already been carried out in China and that results describing edited embryos were pending publication. These people didn’t wish to comment publicly because the papers are under review.

All this means that germ line engineering is much farther along than anyone imagined. “What you are talking about is a major issue for all humanity,” says Merle Berger, one of the founders of Boston IVF, a network of fertility clinics that is among the largest in the world and helps more than a thousand women get pregnant each year. “It would be the biggest thing that ever happened in our field,” he says. Berger predicts that repairing genes for serious inherited disease will win wide public acceptance, but beyond that, the technology would cause a public uproar because “everyone would want the perfect child” and it could lead to picking and choosing eye color and eventually intelligence. “These are things we talk about all the time. But we have never had the opportunity to do it.”

Editing Embryos

How easy would it be to edit a human embryo using CRISPR? Very easy, experts say. “Any scientist with molecular biology skills and knowledge of how to work with [embryos] is going to be able to do this,” says Jennifer Doudna, a University of California, Berkeley, biologist who in 2012 codiscovered how to use CRISPR to edit genes.

To find out how it could be done, I visited the lab of Guoping Feng, a neurobiologist at MIT’s McGovern Institute for Brain Research, where a colony of marmoset monkeys is being established with the aim of using CRISPR to create accurate models of human brain diseases. To create the models, Feng will edit the DNA of embryos and then transfer them into female marmosets to produce live monkeys. One gene Feng hopes to alter is SHANK3. The gene is involved in how neurons communicate and, when it’s damaged in children, is known to cause autism.

“You can do it. But there really isn’t a medical reason. People say, well, we don’t want children born with this, or born with that—but it’s a completely false argument and a slippery slope toward much more unacceptable uses.”

Read more here: http://www.technologyreview.com/featuredstory/535661/engineering-the-perfect-baby/

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