New U.S. Experiments Aim To Create Gene-Edited Human Embryos
New U.S. Experiments Aim To Create Gene-Edited Human
Embryos
A scientist in New York is conducting
experiments designed to modify DNA in human embryos as a step toward someday
preventing inherited diseases, NPR has learned.
For now, the work is confined to a
laboratory. But the research, if successful, would mark another step toward
turning CRISPR, a powerful form of gene editing, into a tool for medical
treatment.
A Chinese scientist sparked international outrage in November
when he announced that
he had used the same technique to create the world's first gene-edited human
babies. He said his goal was to protect them from infection with HIV, a claim
that was criticized because there are safe, effective and far less
controversial ways of achieving that goal.
In contrast, Dieter Egli, a
developmental biologist at Columbia University, says he is conducting his
experiments "for research purposes." He wants to determine whether CRISPR can safely
repair mutations in human embryos to prevent genetic diseases from being passed
down for generations.
So far, Egli has stopped any
modified embryos from developing beyond one day so he can study them.
But if the approach is successful,
Egli would likely allow edited embryos to develop further to continue his
research.
Egli hopes doctors will someday be able edit embryonic human DNA
to prevent many congenital illnesses, such as Tay-Sachs disease, cystic fibrosis and Huntington's disease.
In the lab, Egli is
trying to fix one of the genetic defects that cause retinitis pigmentosa, an
inherited form of blindness. If it works, the hope is that the approach could
help blind people carrying the mutation have genetically related children whose
vision is normal.
"Preventing inherited forms of blindness
would be wonderful — very important for affected families," Egli says.
But that is likely to take years
of additional research to demonstrate that the technique is both effective and
safe.
Nevertheless, even this kind of
basic research is controversial.
"This is really disturbing," says Fyodor Urnov,
associate director of the Altius Institute for
Biomedical Sciences in Seattle. He worries such experiments
could encourage more irresponsible scientists to misuse gene-editing
technologies.
"As we've learned from the
events in China, it is no longer a hypothetical that somebody will just go
ahead and go rogue and do something dangerous, reckless, unethical," Urnov
says.
Egli's research is reviewed in
advance and overseen by a panel of other scientists and bioethicists at
Columbia.
While the debate over research like Egli's continues, the U.S.
National Academies of Science, Engineering and Medicine, the World Health Organization and others are trying to
develop detailed standards for how scientists should safely and ethically edit
human embryos.
Some bioethicists and scientists
are calling for an explicit global moratorium on creating any more gene-edited
babies. Others, like Urnov, would like to see a hiatus in even basic research.
The U.S. government prohibits the
use of federal funding for research involving human embryos. But gene editing
of human embryos can be done using private funding. The Food and Drug
Administration is barred from considering any studies that would involve using
genetically modified human embryos to create a pregnancy. But laws that govern
the creation of genetically modified babies vary widely internationally.
Egli is well aware that his work
may be controversial to some people. To try to be completely transparent about
his experiments, Egli recently invited NPR to his laboratory for an exclusive
look at his research.
"We can't just do the editing
and then hope everything goes right and implant that into a womb. That's not
responsible," Egli says. "We have to first do the basic research
studies to see what happens. That's what we're doing here."
To show NPR what he is doing,
early one morning Egli pushes open the door of a tiny windowless room on the
sixth floor of one of Columbia's research towers in Upper Manhattan. The lab is
jammed with scientific equipment, including two microscopes.
Egli snaps on blue rubber gloves
and opens a frosty metal cylinder holding frozen human eggs.
"I'm going to wear gloves
because we want to keep things clean," he tells me.
To begin his experiment, Egli
starts the long, slow process of thawing the frozen human eggs that were
donated for research. After several hours of careful work and waiting, Egli has
readied 15 eggs for his experiment.
After setting up a large
microscope, Egli slides a round glass dish under the lens. The dish contains
sperm from a blind man who carries the mutation that Egli is trying to fix. It
also holds the CRISPR gene-editing tool.
"I'm starting with just one
egg," he says as he gently places the first thawed egg into the dish.
"It's a beautiful cell,"
Egli says, pointing to a magnified image of the egg on a computer monitor.
"I would say it's one of the most beautiful cells."
Egli maneuvers a tiny glass needle
protruding into the side of the microscope dish toward one of the sperm.
"So you can see a moving sperm over here," he says. "Now I'm
picking it up. The sperm is in the needle. Now I'm dipping it in the CRISPR
tool."
Once the sperm is inside the
needle with the CRISPR gene-editing tool, Egli points the needle's tip at the
egg. "Oh no!" he exclaims with a sigh. "The sperm is swimming
away."
He searches the dish for the
errant sperm.
"Oh, here it is," he
says as he pulls the sperm back into the needle.
Next, Egli gently pierces the egg
with the needle. "The membrane is broken — breached. There we go,"
Egli says as he injects the sperm and CRISPR tool into the egg. He breathes a
sigh of relief.
The idea is that CRISPR will slice out the
mutation in the sperm, and the healthy DNA in the egg will serve as a template
to repair the genetic mutation.
"Hopefully the CRISPR tool
will cut the mutation and then the egg will replace that with a version that no
longer causes disease," Egli says. "The genome from the mother would
be rescuing the mutant genome from the father."
The approach was developed by scientists led by Shoukhrat Mitalipov of
the Oregon Health & Science University in Portland.
Egli was initially skeptical of the Oregon group's
claims that they had used CRISPR for the first time to repair a
mutation in human embryos this way. Egli's research is aimed at trying to
confirm that it works and how.
Mitalipov's group is also
continuing to study the technique to see whether it can safely fix several
genetic mutations in human embryos, including one of the breast cancer genes.
For the next two hours, Egli
painstakingly fertilizes and edits one egg after another. He has to overcome a
variety of technical complications. At one point, the tip of the fragile needle
unexpectedly breaks off at a crucial moment.
"There we go," he says later,
after the needle is replaced. "That one definitely worked.
Beautiful."
This work may be beautiful to
Egli, but it makes critics very nervous.
"Anyone with a connection to
the Internet will be able to download the recipe to make a designer baby,"
Urnov says. "And then the question becomes: 'What's to prevent them from
using it?' As we learned in the past year: apparently nothing."
So Urnov worries about any such
research proceeding.
"We need to hit the pause
button and keep it pressed until we understand how do we proceed in a way that
minimizes the risk of people going rogue," Urnov says.
Urnov and others argue society
needs a much broader debate about whether there is a truly a compelling reason
to ever try to make any more gene-edited babies. There are many other ways to
prevent genetic diseases, they note.
"If we've learned anything from what's happened in China,
it's that the urge to race ahead pushes science to shoot first and ask
questions later," says J. Benjamin Hurlbut,
an associate professor of biology and society at Arizona State University.
"But this is a domain where we should be asking questions first. And maybe
never shooting. What's the rush?"
That's especially true when the
prospect of creating gene-edited babies raises so many fraught ethical
questions, including fears that it could eventually lead to the creation of
"designer babies," critics say.
"We don't need to be mucking around with the genes of
future children," says Marcy Darnovsky, director
of the Center for Genetics and Society, a watchdog group. "This could open
the door to a world where people who were born genetically modified are thought
to be superior to others, and we would have a society of people who are
considered to be genetic haves and genetic have-nots."
But many other scientists and
bioethicists disagree.
"This is valid research, and I think it's important
research," says R. Alta Charo,
a bioethicist at the University of Wisconsin, Madison. "It has value not
only for the possible use in the future for some number of conditions that
would involve a live birth, but it has value for basic understanding of embryology,
basic understanding of development," Charo says. "Of course I think
we should be doing that research. Why wouldn't you be doing that
research?"
Many leading scientists agree.
"Is there value in doing that kind of research? I think
there is," agrees Jennifer Doudna, a
biochemist at the University of California, Berkeley, who helped invent CRISPR.
"Does it have to be carried out carefully and under the right regulatory
guidelines? Of course. But I think there's value in doing research like
that."
"I'd like to see the U.S. be
involved and show leadership on how to do that responsibly rather than say
we're not going to have a seat at the table," Doudna says.
Back in Egli's lab, it's now nearly 3 p.m., and he is wrapping up
the day's experiments.
"OK, that's it. That's the
last one," he says as he places back into storage the last of 14 eggs he
managed to fertilize and hopefully edit. He will stop their development the
next morning to see whether it worked.
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