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genes, the embryos actually have one normal gene and one
missing gene, caused by what’s called a large deletion. This
phenomenon has been documented in a handful of other
CRISPR studies and could explain why the researchers didn’t
detect any disease-causing genes when they examined the
edited embryos. If critics are right, these embryos would be
far from healthy.
Paul Thomas, leader of the Genome Editing Laboratory
and director of the South Australia Genome Editing Facility
at the University of Adelaide and South Australian Health
and Medical Research Institute, sought to directly answer the
large-deletion question. His team tested Mitalipov’s methods
in mouse embryos, and found these suspected large deletions
were common.
In response, Mitalipov’s group did a follow-up experiment
to show that their embryos didn’t have the deletions. But the
critics, including Dieter Egli, a cell biologist at Columbia
University, weren’t terribly satisfied. “Conclusive evidence for
the proposed repair mechanism is still missing,” he says.
Thomas had a similar reaction. “The reason for this dif-
ference [between the two studies] remains unclear,” he says.
“It will be interesting to see if the results from [Mitalipov’s
group] are replicated in studies using human embryos from
independent laboratories.”
LEGAL HURDLES
Science aside, human embryo research is a logistically tricky
business. The work is not eligible for financial support by the
National Institutes of Health, the main source of biomedical
research funding in the U.S.
The OHSU team has worked around this with private fund-
ing, but it will face a big obstacle when it’s ready to take the
gene repair treatment — that’s how they refer to their disease-
removing embryo edits — to clinical trial. To do that, the team
needs FDA approval. In 2015, however, Congress removed the
FDA’s funding to review “research in which a human embryo is
intentionally created or modified to include a heritable genetic
modification.”
This doesn’t stop Mitalipov from moving his work forward;
it just doesn’t allow him to seek official approval in the U.S. So
Mitalipov says that when embryonic gene repair is ready for
clinical trials, he’ll take it to a country that allows it but also has
strong legal and ethical oversight, such as the U.K.
He believes it’s actually irresponsible not to continue to study
and test the embryo repair techniques coming out of the lab.
That’s because once research is published, the ideas are out
there, with instructions in each study’s methods section. He
worries researchers or clinicians in other countries with dif-
ferent regulations would run with them before they’ve been
properly vetted.
“Of course, we will do [clinical trials overseas] in a respon-
sible way, with proper oversight,” says Mitalipov. “We have no
choice — we have to do it. We already started, and we cannot
leave it to [in vitro fertilization] clinics to do this job.”
When parents want to avoid passing their genetic condition
to their children, Amato says, a viable option is to undergo KRISTYN
A^ WEN
TZ- GR
AFF/OHSU
(^3 )Left: Researcher Nuria Marti-Gutierrez uses precision tools to corral human sperm and eggs in Mitalipov’s lab at Oregon Health and Science University. Center:
Marti-Gutierrez does her work by microscope, while a computer screen shows the human egg as it’s punctured by a needle that will deliver sperm and a dose of
CRISPR-Cas9. Right: After the eggs are fertilized, they’re kept in a warmer in the lab.