“We have within our grasp the technology to change evolution. This could change the course of biological life.” — Paul Berg, Nobel Laureate and a pioneer of genetic engineering
In 2012, scientists in the U.S. and Sweden invented a technology as potentially life-altering as splitting the atom. One that you haven’t heard of—yet—called “CRISPR-Cas9”. This innovation with the cumbrous name allows biologists to edit DNA almost as easily as cutting and pasting words and letters on a laptop.
Scientists say that CRISPR-Cas9 may soon allow them to perform miraculous fixes to eliminate or alter mutations that cause everything from some cancers to Parkinson’s disease. More whimsically, the technology could be used to create, say, a unicorn, or a pig with wings; though it’s unlikely they could make swine fly. More nefariously, terrorists or the military might create pathogens that could harm far more people than splitting the atom has so far. Or, an accident could occur unintentionally.
The question is how to turn this seemingly earth-shattering technology from a yawn in the public perception into a topic that society is aware of, and one that is discussed, thereby preventing or making highly unlikely the bio-equivalent of a nuke exploding. This is not easy in a culture and political system that usually reacts only when disaster strikes, and often fails to act decisively even after careful deliberations and warnings. (Think climate change). Nor are stakeholders some scientists and companies, for instance, and even physicians eager to save people - always eager to dwell on what can go wrong.
This makes it all the more laudable that a group of 18 prominent scientists and experts in law and ethics—led by Nobel Laureate David Baltimore and a co-inventor of CRISPR-Cas9—published a letter a few days ago in Science calling for a moratorium on some uses of this technology. The group, which met in Napa, California, last January for a one-day summit, fretted about a possible “slippery slope” that might occur from using disease-curing applications that everyone wants, “toward uses with less compelling or even troubling implications.”
They call on scientists to impose a voluntary stoppage “while societal, environmental, and ethical implications of such activity are discussed among scientific and governmental organizations.”
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, a process that in nature allows bacteria to remember the DNA of viruses that have attacked them, so that next time the bacteria can identify and destroy theses viruses with the help of DNA-slicing enzymes. In 2012 Jennifer Doudna of the University of California at Berkeley and Emmanuelle Charpentier of Umea University in Sweden demonstrated in Science how to co-opt this process to intentionally edit DNA in any organism by using a slicer enzyme called Cas9—and improvement on past gene-editing techniques.
The Napa group is particularly concerned about the modification of the human germline, the DNA in cells that is passed down to our children and subsequent generations. Germline alterations are therefore permanent, as opposed to changes made to “somatic” cells—the cells in you and I that are generated after conception and are not passed on to our children.
“You don’t know in future generations how modifications will impact people, so we need to be careful,” said Stanford biochemist and Nobel Laureate Paul Berg, a signatory of the Napa group’s letter. In the 1970s Berg co-invented an earlier gene modification technique known as recombinant DNA.
In an email, CRISPR-Cas9 co-inventor Jennifer Douda told me: “My colleagues and I felt that it was critical to initiate a public discussion of the appropriate use of this technology, and to call for a voluntary ban on human germline editing for clinical applications at the present time.”
The Science letter, however, does not suggest which organizations or governmental or international agencies should take the lead. Nor what a response might look like. Most industrialized countries already have laws forbidding human germline modification and strict regulations on other forms of genetic manipulation. Many other nations have weak or nonexistent controls, which is why the authors appeal to scientists everywhere to avoid germline experiments with CRISPR-Cas9 on their own.
Even with tight regulations, suggests Stanford law professor and ethics expert Henry Greely, part of the Napa group, the U.S. needs to update rules developed mostly in the 1980s. “We were protected in a way by the science being so expensive and difficult,” he said. “Now some really bright high school student could conduct an experiment with CRISPR-Cas9. Let’s say he decides to modify a mosquito to do some good, and he accidently creates a super mosquito that gets in the environment and becomes like kudzu.”
(Kudzu, “the plant that ate the South,” was imported from Japan in the early 20th century to control erosion in the Southeastern U.S. and quickly took over, choking off native plants and driving everyone crazy even today.)
“Our current laws wouldn’t stop an ambitious scientist from using CRISPR to modify the germline,” added Berg. He and others tell of rumors that it’s already being tried in China. “You would be insane and criminally reckless to make a baby this way without 15 to 20 years of testing and proof it was safe,” said Greely.
The U.S. and the world could take cues from the United Nations in how they create consensus reports by scientists detailing the human impact on climate change. Or from the British system that formally consults with the public and stakeholders around new technologies, a process that began with the invention of in vitro fertilization—so-called test tube babies—in the late 1970s. The Brits also require a series of approvals by agencies and organizations that assess safety, ethics, and efficacy.
In February the British Parliament legalized a new method for combining the DNA of three people in a kind of genetic edit that went through this process. The fix prevents defects in the mitochondria—the part of a cell that converts fuel into energy—from being passed on to children who might then suffer brain damage or heart disease. This alteration is permanent in the child and his or her offspring.
In the U.S. such a consensus would be tough given our polarized politics and diffuse political system. You also have the likely opposition of the religious right, which still doesn’t recognize Darwinian natural evolution, never mind genetic tinkering by humans, even if it’s deemed safe.
Jennifer Doudna tells me she is working on setting up a meeting to move the CRISPR-Cas9 discussion forward, and Paul Berg suspects that in the U.S. the National Institutes of Health and the National Academies of Science, among others, will get involved. It might also be time to update the 2010 Obama administration report on synthetic biology—the broad field that CRISPR-Cas9 is a part of—issued by the Presidential Commission for the Study of Bioethical Issues.
Beyond this, the U.S. and the world should waste no time in getting creative with developing new processes for insuring that CRISPR-Cas9 and other powerful molecular technologies are allowed to move forward if safe, and restricted or shut down if they are not. But only after a careful and exhaustive process that includes all stakeholders, and is as de-politicized as much as possible—something that regrettably isn’t likely to happen anytime soon. (The need to get innovative about how our society makes decisions about new technologies is likely a subject for a future column.)
It’s worth noting that the last time life-science biologists issued a call for a similar moratorium was in the mid-1970s, when Paul Berg and others invented recombinant DNA. This allowed the insertion of DNA from one organism into another. Highly controversial at the time, some people feared that human-engineered organisms might run amuck, or that methods then used to combine DNA might create deadly, cancer-causing pathogens.
They didn’t, in part because a group of scientists led by Berg and others met at the Asilomar conference center south of San Francisco—150 miles from Napa—and issued their own call for a voluntary ban. This allowed a public dialogue to take place and safety measures to be implemented. Four decades later, recombinant DNA has led to dozens of life-saving drugs and is the basis of countless scientific discoveries—all accomplished without unleashing monsters.
The letter in Science is a modest step toward snatching the attention of the public and decision-makers about CRISPR-Cas9, although it’s not a flash in the pan. Hopefully it will launch a process that will push us toward cures rather than a catastrophe.