BUILDING A BETTER BABY
UC-developed technology could allow us to customize embryos, perhaps even select our favorite traits. But is that an ethical line we should cross?
BERKELEY — The University of California has transformed biology by designing a cheap, fast, precise and powerful way to “edit” DNA, creating the prospects of a future with less sickness, more food — and perhaps perfect babies. But now it wants to hit the pause button. Alarmed that their new gene-editing tool recently was used by Chinese researchers to create the first genetically modified human embryos, scientists at UC’s Innovative Genomics Initiative are leading the call to urge only safe and ethical use of the tool. And they plan to hold a landmark conference to debate how to proceed.
“It is a really exciting thing and could have a potential impact on disease,” said Jacob Corn, the initiative’s scientific director. “But it is also something where we need to tread carefully.”
The ability to alter gene sequences was first proven at Stanford University in the 1970s, but genome editing has been slow to reach humans. The stunningly effective technology invented at UC Berkeley, however, portends a future with sci-fi-like implications. In merely three years, the tool has exploded in popularity in labs around the world — offering new opportunities but also ethical quandaries for scientists and society.
The technology could save the life of an individual patient. But it could
also change the genetic code of future generations, redirecting evolution in new, permanent and unimaginable ways.
“Is this what we want to do?” Corn asked. “Is this the right thing to do?”
Many biotechnology experts argue that the genie is out of the bottle and that a complete ban on the technology’s use in research and the clinic is a bad idea — and impractical. Instead, they say, it should be tightly regulated.
“Would it be unethical not to fix something if you could? If it were very safe, wouldn’t it be wrong not to?” asked biotech entrepreneur Juan Enriquez of Boston-based Excel Venture Management.
UC biologist Jennifer Doudna didn’t set out to revolutionize molecular biology. She was just studying the inner workings of bacteria in her lab at the Innovative Genomics Initiative, which has branch laboratories at UC San Francisco and UC Berkeley.
As a child, she loved decoding short pieces of encrypted text. And she suspected that bacteria’s CRISPR — an acronym for “clustered regularly interspaced short palindromic repeats,” those weird repetitive and mysterious sequences in genetic code — had a purpose.
She found that bacteria used CRISPR to recognize the genetic sequences of invading viruses so they could chop them up with the enzyme Cas9 — which acts like a pair of molecular scissors — and destroy them.
In 2012, Doudna and Emmanuelle Charpentier of Sweden’s Umea University created a way to engineer a CRISPR-based method that can identify any gene sequence in any cell and cut it out — and sometimes even repair it. While human cells don’t have CRISPRs, scientists
can deliver a custommade CRISPR into a cell to start the editing process.
It’s not the first time genes have been edited; other approaches have been used for decades. The gene therapy field, once full of excitement, took a big step backward in 1999 when Jesse Gelsinger, an Arizona teenager with a genetic liver disease, had a fatal reaction to the virus that scientists had used to insert a corrective gene.
But what distinguishes CRISPR is its accuracy, ease of use and low cost. In just the past year, it has been used to block HIV from entering human cells, alter genes in plants, destroy cancer cells and insert the genes of woolly mammoths into elephant cells.
But one particular application is setting off alarms: its ability to edit DNA in the cells that create sperm and eggs — which could alter the genes of future generations.
“The high school interns in my lab could, in fact, do it,” said Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla. “But we’re not doing it, even though we can. We won’t go beyond a certain line. It’s not appropriate.
“We could change genes in babies. Something as simple as getting a blue-eyed baby instead of a browneyed baby,” she said. “If we can do it, that means other labs can do it that aren’t as constrained. And that worries me.”
In January, the first primates to be born with their genomes engineered were reported by scientists in Nanjing, China. Three genes — governing metabolism, immune cell development and sex determination — were modified when macaque monkeys were still embryos.
Then, late last month, a different team of Chinese researchers, led by Junjiu Huang of Sun Yat-sen University in Guangzhou, announced that it had altered human embryos to try to fix the gene defect that causes beta thalassemia, a blood disease. Although the tool succeeded in some of the embryos, it failed in others, introducing unexpected mutations or only partially repairing genes. They used embryos from a local fertility clinic that were abnormal and could never grow into babies because they had been fertilized by two sperm.
“This is a wake-up call,” Corn said. “Human traits change naturally, over time. What we are talking about is the ability to do this to ourselves, faster than nature can do.”
Hank Greely, director of the Center for Law and the Biosciences at Stanford, predicts the transformative technology’s nonhuman uses — in the lab, on the farm and in the wild — could prove more valuable.
Want to end malaria? Alter mosquitoes.
Want to make a new biofuel? Alter algae.
Want to bring back the extinct passenger pigeon? Alter common band-tailed pigeons.
It “could let us reshape the biosphere,” Greely said.
Similarly, plant agriculture could be transformed, according to Daniel Voytas of Calyxt, a Minnesotabased biotechnology company that has licensed patent rights covering the use of the CRISPR technology in plants.
The tool makes it possible to precisely alter DNA sequences, providing unprecedented control over a plant’s nutritional value, resistance to pests and ability to grow on marginal lands, Voytas wrote in the journal PLOS Biology.
He predicts that crops created through CRISPR might be more accepted by the public than current genetically modified plants, which carry foreign DNA in their genomes.
But the technology is far from being proven safe, and it might accidentally induce changes in healthy strands of DNA, Greely said. And there are simpler ways to prevent transmission of almost all genetic diseases, such as selecting only healthy embryos during in vitro fertilization procedures, he added.
Most genetic diseases won’t be easily fixed because they’re not caused by one flaw but by a complex interaction of several bad mutations, said Jim Beck of the Parkinson’s Disease Foundation. And because the presence of a mutation doesn’t always trigger disease, he said, gene editing might be trying to solve a problem that doesn’t really exist.
Even in a disease such as Huntington’s, where the single mutation that kills brain cells is well known, “I wouldn’t advocate for it until more work done to prove its safety,” said George Yohrling, director of scientific affairs at the Huntington’s Disease Society of America. “You are messing with the genome in a way never done before.”
Sickle cell anemia patient Tosin Ola, of San Diego, has the same concerns. “I am really hesitant to say ‘It might cure this’ without knowing whether it could cause a something else,” such as another unwanted genetic mutation, she said.
Still, she can see how some people in her situation would take the risk. “Then your child would not have it,” she said. “Knowing how difficult it has been to live with sickle cell, I would never want to pass that on.”
Indeed, it’s that prospect of freeing future generations from deadly disease that many scientists find tantalizing.
While we work toward improved health of plants and animals, “should we deny this possibility for humans?” geneticist Robin Lovell-Badge, of London’s Francis Crick Institute, wrote in the British newsletter BioNews.
Faced with the growing use of the technology, the Berkeley scientists in January convened a closeddoor retreat of 18 experts in Napa Valley that resulted in a strongly worded commentary in the journal Science, urging more discussion about the technology’s potential and discouraging any use in human reproductive cells until the implications are discussed.
The UC scientists say they plan to soon hold a meeting modeled after the historic 1975 Asilomar conference on genetic engineering, where scientists created firm guidelines for their research for the military, pharmaceutical industry and agribusiness.
With CRISPR’s power comes tough questions: If the Huntington’s disease gene can be fixed, why not alter genes for dwarfism? Depression? Obesity? Shortness?
The questions both fascinate and haunt Enriquez, the Boston entrepreneur.
“When you have a technology, you have to take charge of it,” he said. “You’re responsible.”