DNA editing takes a serious step forward -- for better and worse
DNA editing takes a serious step forward -- for better or
worse
By Eryn Brown
It's a scenario that has haunted biologists since the
dawn of the DNA age: the evil scientist custom-crafting a human being with test
tubes and Petri dishes..
So when a Chinese team revealed last month that it had
used a new laboratory technique to alter a gene in human embryos, it set off an
urgent debate over the ethics — and wisdom — of tinkering with the most basic
building blocks of life.
The technology makes genetic manipulations that were
theoretical in the past seem easy to achieve — and soon.
If scientists figure out how to do it in a way that's
safe for patients, gene editing could produce tremendously beneficial medical
treatments. The Chinese researchers, for instance, were trying to repair a
defect that causes beta thalassemia, a potentially fatal blood disorder.
But a simple way to alter DNA could open the door to more
frightening eugenic pursuits. That makes people nervous.
"The positive side is, it allows regular biologists
to change the DNA in any organism. The negative side is, it allows regular
biologists to change the DNA in any organism," said Harvard Medical School
geneticist George Church. "You can twist any technology into something
bad."
In the last few months, many researchers have come to
realize that the new gene editing tool, known as CRISPR/Cas9, might provide an
easy means for molding a person when he or she is just a single-celled embryo.
CRISPR/Cas9 makes it possible for nearly any scientist to
edit DNA in nearly any cell. In the last couple of years, scientists have used
it to edit genes in adult human cells, including bone marrow cells that may be
modified to make people resistant to HIV. Researchers have also used it on
animal embryos, including an experiment that proved it was possible to create
primates with customized versions of genes involved in immune function and
metabolism.
With thousands of labs using the technology, it seemed
inevitable that someone would try it on human embryos.
That's troubling to many scientists because, unlike edits
to a bone marrow cell, alterations in a single-celled embryo would be copied
into all the rest of the embryo's cells as it developed — and passed down via
sperm or egg to the embryo's children, grandchildren and generations beyond.
Before the Chinese study appeared in the journal Protein
& Cell, top scientists had already called for a high-level summit to hash
out the ethical issues raised by this sort of research. The goal is to make
sure gene editing in embryos isn't used prematurely in patients, or employed to
create genetically enhanced humans. Some experts say use of CRISPR/Cas9 on
human embryos should be put on hold until these hard questions can be
addressed.
"We've got to take this seriously," said
Caltech biologist David Baltimore, who won a Nobel Prize for his early work on
the genetics of viruses that cause cancer.
The potential to make permanent changes to DNA that are
passed from generation to generation has been recognized for decades. Although
the risks were clear, the urgency was lacking.
"It was logistically so complex that there was no
clear path forward, so we didn't worry about it a lot," Baltimore said.
"Now it's here."
Scientists have made steady progress in their ability to
edit DNA, but the CRISPR/Cas9 system marks a major advance in ease and
flexibility of use.
The system occurs naturally in bacteria and helps them
fight invading viruses. It uses strands of RNA called clustered regularly
interspaced short palindromic repeats, or CRISPRs, to direct DNA-chopping
enzymes from the Cas protein family to sever the viral genome.
About three years ago, microbiologists and bioengineers
realized the system could be deployed to edit DNA in many organisms. If there
was a specific spot in the genome they wanted to target, all they'd have to do
is design the right CRISPR machinery to get to that location, a relatively
straightforward task.
Once in place, a specially engineered Cas enzyme could
latch on and cut the DNA strand, allowing scientists to correct the mistake.
Some researchers have adapted the system to repress or activate genes; others,
to make insertions.
The CRISPR/Cas9 method is much simpler — and cheaper —
than earlier gene editing technologies in which scientists had to synthesize
complex proteins to carry out the same work. Some experts predict that the
scientists who figured out how to use CRISPR/Cas9 to edit genes will win a
Nobel Prize for their discovery.
The Chinese researchers, from Sun Yat-sen University in
Guangzhou, were attempting to modify a mutant form of a gene called HBB.
Certain mutations prevent people from producing enough hemoglobin to transport
oxygen through the bloodstream, resulting in beta thalassemia. The team wanted
to see whether they could delete the mutated portion of HBB and replace it with
the correct DNA.
To make sure their experiments wouldn't result in
genetically engineered babies, they used single-cell embryos rejected by
fertility clinics that weren't viable because they had been fertilized by two
sperm.
They are hardly the only ones attempting to edit genomes
for the sake of human health. Uptake in labs has been so enthusiastic that
CRISPR has become a verb, a la Google.
"People say, 'I'm going to CRISPR that,'" said
UC Davis stem cell biologist Paul Knoepfler.
Some of the enthusiasm turns to concern, though, when it
comes to making DNA changes that would be passed on to future generations.
A recent commentary in the journal Nature laid out a
variety of potential problems. Mistakes might occur in the editing process that
could result in severe birth defects. Successful edits could affect other parts
of the genome that were meant to be left alone. It's impossible to get consent
from future generations who might inherit an altered gene. People could use
gene editing for "non-therapeutic genetic enhancement" — making
designer babies with blue eyes and high IQs.
The authors, worried that problems with embryo editing
could derail work on gene therapies in general, called on scientists to cease
all experiments that would affect multiple generations until discussions about
safety and ethics were complete.
Those concerns were echoed a few weeks later in an essay
in the journal Science that said embryonic gene editing experiments should be
off-limits in clinical settings, such as fertility clinics.
The Chinese study bore out many people's fears. Though
the researchers were able to target the HBB gene, only rarely did the desired
correction occur. Sometimes they made changes in the wrong places. Summing up
their data, the team concluded that it was still too soon to use CRISPR/Cas9 to
edit embryos in clinical settings.
"They ran into all sorts of problems,"
Baltimore said. "It drives home that we're not ready to do this."
Most think that will change before long. With no
international rules governing this research, scientists are scrambling to get
guidelines in place. Dr. Francis Collins, director of the National Institutes
of Health, announced last week that his agency would not fund gene editing
experimentation involving embryos, which "has been viewed almost
universally as a line that should not be crossed," he said in a statement.
Baltimore, who is in favor of allowing the research, said
gene editing could be put to great use for medical treatments — perhaps even in
embryos, once it is proved safe and if there is no other way to circumvent
disease.
"I'm not a believer that you should limit scientific
capabilities," he said. "I'd rather scientists decide how they should
use it."
Church predicted that worries about the technology would
dissipate as people got more comfortable with gene editing.
He thought experiments using older DNA technologies —
including recent work that sought to alter highly pathogenic H5N1 bird flu
viruses to see whether they could become more contagious — were far scarier
than what was likely to emerge from CRISPR.
Others aren't so sure.
Knoepfler, who has been writing about the embryo editing
discussions on his blog, thinks CRISPR/Cas9 use is advancing so quickly that it
could render all the careful, considered ethical debates moot.
Someone might alter an embryo and implant it in a woman
for what seem like good reasons but with insufficient regard for the potential
risks. Or perhaps for glory — or money — someone will create what amounts to a
GMO uber baby.
"You can't disregard human ambition," he said.
Copyright © 2015, Los Angeles Times
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