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Scientists can now genetically engineer humans. A big new report asks whether we should.

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Scientists can now genetically engineer humans. A big new report asks whether we should.
de System Administrator - sábado, 25 de febrero de 2017, 17:53
Grupo Colaboradores / Partners

Gotta love that designer baby stock art. (Shutterstock)

Scientists can now genetically engineer humans. A big new report asks whether we should.

Biotechnology has advanced so rapidly over the past few years that scientists can now edit the genomes of plants and animals with ever-increasing precision. Using new techniques like CRISPR/Cas9, researchers have already shown they can alter genes to create hornless cattle or mushrooms that don’t brown easily.

But the really big question — the stuff of sci-fi — is whether we’ll use genome-editing tools on people to wipe out heritable diseases or to enhance human capabilities. It’s no longer a question of whether we’ll be able to create “designer babies”: The technology is improving at a stunning pace. Instead, it’s a question of whether we should. It’s an ethics question, a policy question.

On Tuesday, the influential National Academy of Sciences released a 261-page report on this issue, titled “Human Genome Editing: Science, Ethics, and Governance.” It’s one of the most thorough looks yet at what’s likely to be possible with new genome-editing techniques — and why scientists should tread carefully.


The report’s recommendations are eyebrow-raising: In very, very limited cases, editing of viable human embryos should be allowed to go forward in the United States — a conclusion that’s certain to prove controversial. In particular, the report argues, clinical trials to edit human sperm, eggs, and embryos should be permissible in cases where there’s a high chance of preventing babies from being born with serious genetic diseases and no “reasonable alternatives” exist. 

By contrast, the panel says editing embryos for human enhancement — say, making people stronger or more intelligent — should absolutely not proceed in the United States until there’s much broader society-wide discussion of the thorny ethics involved, like the risks of exacerbating the gap between rich and poor. The report is an in-depth discussion of the issues at play here, so let’s dig in.

The four big reasons we might want to edit the human genome

The report starts by taking stock of all the powerful biotech tools available today, from zinc finger nucleases to TALEN to CRISPR/Cas9. While the technical details vary, these techniques “can be used to make precise changes in the genome at a high frequency and with considerable accuracy.” Here’s a diagram showing how CRISPR/Cas9 works:


A basic guide to how CRISPR works. (Javier Zarracina)

There are four big reasons why scientists might want to tinker with the genetic material of human beings in particular — ranging from least controversial to most controversial: 

1) Basic research on human cells in a lab. This one’s straightforward. A scientist takes cultures of human cells and uses, say, TALEN or CRISPR to tinker with the genetic code to figure out how our molecular processes actually work — or better understand what our genes do. Scientists might edit “somatic” cells (nonreproductive cell types like skin or liver cells) or “germline” cells (eggs or sperm). But these experiments would never produce viable embryos or modify living human beings.

This is basic, essential research that’s not much different from what’s been going on for decades, and the report argues that existing guidelines should be sufficient to govern these practices. Nothing too contentious here.

2) Clinical trials to edit somatic cells in living humans. Increasingly, however, scientists are also interested in using genome-editing techniques to treat diseases in humans. Last June, the National Institutes of Health approved the first-ever clinical trial to use CRISPR as a cancer treatment. Scientists at the University of Pennsylvania will take immune cells out of 18 cancer patients, edit the cells to make them more effective at targeting cancer, and then infuse the cells back into the patient to see what happens. (This trial is mainly intended to probe the safety of this technique.)

This sort of “gene therapy” will become more common as editing techniques improve. The NAS report cites a long list of potential applications down the road. An excerpt:


(National Academies of Sciences)

The panel argues that there aren’t any hugely troubling ethical issues here, since this involves altering somatic (i.e., nonreproductive) cells, and the altered traits can’t be passed on to offspring. The panel does, however, urge caution. Genome-editing techniques still aren’t perfect, and they can sometimes misfire, leading to random mutations or other “off-target” effects in the edited cells. What’s more, no one’s yet been able to develop clear safety standards around what misfires are acceptable.

So, the report says, regulators at NIH will need to scrutinize proposals for gene therapy trials on a case-by-case basis. In general, it’s safest to take a cell out of a patient and edit it (known as “ex vivo” treatment), because researchers can more easily check for off-target effects. By contrast, there are still plenty of technical challenges involved in editing cells directly inside a human body (“in vivo” treatment).

3) Editing sperm, eggs, and embryos to stop inheritable diseases. Okay, now we’re getting to the controversial stuff. It’s one thing to edit an adult’s immune cells. If anything goes awry, the effects won’t be passed on. It’s another matter entirely to edit sperm, eggs, or embryos (known as the “germline”) and create genetic changes that can be passed down from generation to generation. Now we’re no longer talking about editing a single human. We’re talking about editing humanity.

For now, the FDA and NIH are barred from approving research on editing human embryos, because of the potentially fraught social and ethical concerns involved. But other countries, like China and the United Kingdom, are moving forward with embryo editing, and interest is certain to grow. There are thousands of inheritable diseases caused by mutations to a single gene (like Huntington’s). For many families, genome-editing may be the only way to prevent kids from being born with certain conditions.

So the panel tries to strike a balance here. It argues that the US government should allow clinical trials on editing sperm, eggs, or embryos — but only under very, very limited conditions. It should be done only to try to prevent “serious diseases” where there’s a convincing link between the gene in question and the disease — and only when there are no “reasonable alternatives.” The panel also urges rigorous oversight and a “continued reassessment of both health and societal benefits and risks.”

The panel concedes that this recommendation is likely to prove contentious. Some people will find the idea of editing viable sperm, eggs, or embryos morally wrong. Others will note that concepts like “reasonable alternatives” and “serious disease” are left frustratingly vague. And still other researchers may find these guidelines so strict as to bar useful research. (More on this below.)

It’s also not clear how widespread embryo editing would become even if US regulators did approve it. As the panel notes, there are still “major technical challenges to be addressed in developing this technology for safe and predictable use in humans.” As a result, the panel predicts that we aren’t likely to see much germline genome editing to prevent disease “in the foreseeable future.”

4) Editing the human genome for “enhancement.” Of course, if scientists could one day edit viable embryos to eliminate diseases, they could also conceivably edit embryos for enhancement. Stronger babies. Smarter babies. Babies born only with blue eyes. Gattacaterritory, basically.

The NAS report notes that this possibility raises all sorts of thorny issues. Would the use of genetic enhancement make inequality worse? Might it one day become so prevalent that enhancement becomes mandatory, like vaccines are today? Should parents have a right to improve their children through genetic modification? How far should regulations around genome editing go to respect religious and cultural discomfort? Are there risks we haven’t even thought of yet? (Almost certainly.)

The report basically concludes that we haven’t even begun to have a serious discussion around these issues, as a society. Nor do policymakers really understand yet what sorts of regulations and governance these techniques should require. As such, the panel recommends that “genome editing for purposes other than treatment or prevention of disease and disability should not proceed at this time.”

But that’s easier said than done. The report notes that the boundary between disease prevention and enhancement can often be hazy. Using genome editing to improve musculature for patients with muscular dystrophy might be okay. But what about improving musculature for people genetically disposed to be weaker than normal? Where do you draw the line? What about genetic editing to improve cholesterol levels? As such, the report notes, scientists and policymakers are going to have to think harder about what counts as “normal” and what is an “enhancement.”

This report won’t end controversy around human genome editing


Should we? (Shutterstock)

Suffice to say, this report doesn’t have all the answers for what’s okay and what’s not around human genome-editing — and it would be ridiculous to expect as much. This is a complex debate that will persist for decades.

Instead, the National Academy of Sciences panel tried to lay out some principles to guide further discussions. The development of any new regulations around genome-editing needs to be transparent and open, with ample public input. For instance: “Ongoing reassessment and public participation should precede and clinical trials of heritable germline editing.” And: “Incorporate public participation into the human genome editing policy process about ‘enhancement.’”

Even experts who are steeped in this topic have wildly different views of what’s appropriate. Back in 2015, a group of scientists wrote a letter in Nature calling for a moratorium on all embryo editing, period. The authors, led by Edward Lanphier of the DNA editing company Sangamo Therapeutics, argued that the potential benefits were still too hazy right now and the risks were too great:

In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications.

The critics also worried that a backlash against embryo modification could end up stifling promising research around gene therapy (No. 2 on our list in the last section):

We are concerned that a public outcry about such an ethical breach could hinder a promising area of therapeutic development, namely making genetic changes that cannot be inherited.

In an interview with Science on Tuesday, the lead author of that essay, Lanphier, expressed disappointment with the new NAS report’s cautious approval of embryo editing in some cases: “It changes the tone to an affirmative position in the absence of the broad public debate this report calls for.”

By contrast, George Church, a geneticist at Harvard and one of the pioneers of CRISPR, has long argued that while the benefits of editing embryos seem small right now, they are compelling enough to expand research. Here’s what he told Stat in 2015:

We need only one compelling argument to initiate a new social norm — even when the market is small (as for orphan drugs). For germline modification, we have at least three compelling cases: 1) mitochondrial diseases; 2) families in which post-natal remedies are inadequate and both parents are fully afflicted (20 percent of the world’s marriages involve close relatives); and 3) scenarios in which treating (and possibly pre-screening) single germ cells is safer than treating millions of somatic cells, since each cell adds to the collective risk of developing cancer.

In that same piece, NIH director Francis Collins is much more worried about the potentially risky side effects of human germline editing; you should read their entire exchange.

This new report is hardly going to be the last word on this debate, but the NAS tends to be influential in guiding US government policy, and it’s nudged the discussion significantly in the direction of allowing designer babies — even in limited cases.