Powerful DNA 'Editing' Has Arrived, Are
We Ready for It?
Jeff Bessen, Harvard University
This article was originally published on
The Conversation . The publication
contributed this article to Live Science's
Expert Voices: Op-Ed & Insights.
CRISPR/Cas is a new technology that
allows unprecedented control over the
DNA code. It’s sparked a revolution in
the fields of genetics and cell biology,
becoming the scientific equivalent of a
household name by raising hopes about
new ways to cure diseases including
cancer and to unlock the remaining
mysteries of our cells.
The gene editing technique also raises
concerns. Could the new tools allow
parents to order “designer babies”?
Could premature use in patients lead to
unforeseen and potentially dangerous
consequences? This potential for abuse
or misuse led prominent scientists to call
for a halt on some types of new research
until ethical issues can be discussed – a
voluntary ban that was swiftly ignored in
some quarters.
The moratorium is a positive step toward
preserving the public’s trust and safety,
while the promising new technology can
be further studied.
Editing DNA to cure disease
While most human diseases are caused,
at least partially, by mutations in our
DNA, current therapies treat the
symptoms of these mutations but not the
genetic root cause. For example, cystic
fibrosis, which causes the lungs to fill
with excess mucus, is caused by a single
DNA mutation. However, cystic fibrosis
treatments focus on the symptoms –
working to reduce mucus in the lungs
and fight off infections – rather than
correcting the mutation itself. That’s
because making precise changes to the
three-billion-letter DNA code remains a
challenge even in a Petri dish, and it is
unprecedented in living patients. (The
only current example of gene therapy,
called Glybera , does not involve
modifying the patient’s DNA, and has
been approved for limited use in Europe
to treat patients with a digestive
disorder .)
That all changed in 2012, when several
research groups demonstrated that a
DNA-cutting technology called CRISPR/
Cas could operate on human DNA.
Compared to previous, inefficient
methods for editing DNA, CRISPR/Cas
offers a shortcut. It acts like a pair of
DNA scissors that cut where prompted
by a special strand of RNA (a close
chemical relative of DNA). Snipping DNA
turns on the cell’s DNA repair process,
which can be hijacked to either disable a
gene – say, one that allows tumor cells
to grow uncontrollably – or to fix a
broken gene, such as the mutation that
causes cystic fibrosis. The advantages of
the Cas9 system over its predecessor
genome-editing technologies – its high
specificity and the ease of navigating to
a specific DNA sequence with the “guide
RNA” – have contributed to its rapid
adoption in the scientific community.
The barrier to fixing the DNA of diseased
cells appears to have evaporated.
Playing with fire
With the advance of this technique, the
obstacles to altering genes in embryos
are falling away, opening the door to so-
called “designer babies” with altered
appearance or intelligence. Ethicists have
long feared the consequences of allowing
parents to choose the traits of their
babies. Further, there is a wide gap
between our understanding of disease
and the genes that might cause them.
Even if we were capable of performing
flawless genetic surgery, we don’t yet
know how specific changes to the DNA
will manifest in a living human. Finally,
the editing of germ line cells such as
embryos could permanently introduce
altered DNA into the gene pool to be
inherited by descendants.
And making cuts in one’s DNA is not
without risks. Cas9 – the scissor protein
– is known to cleave DNA at unintended
or “off-target” sites in the genome. Were
Cas9 to inappropriately chop an
important gene and inactivate it, the
therapy could cause cancer instead of
curing it.
Take it slow
All the concerns around Cas9 triggered a
very unusual event: a call from
prominent scientists to halt some of this
research. In March of 2015, a group of
researchers and lawyers called for a
voluntary pause on further using CRISPR
technology in germ line cells until ethical
guidelines could be decided.
Writing in the journal Science, the group
– including two Nobel laureates and the
inventors of the CRISPR technology –
noted that we don’t yet understand
enough about the link between our health
and our DNA sequence. Even if a
perfectly accurate DNA-editing system
existed – and Cas9 surely doesn’t yet
qualify – it would still be premature to
treat patients with genetic surgery. The
authors disavowed genome editing only
in specific cell types such as embryos,
while encouraging the basic research
that would put future therapeutic editing
on a firmer foundation of evidence.
Pushing ahead
Despite this call for CRISPR/Cas
research to be halted, a Chinese research
group reported on their attempts at
editing human embryos only two months
later. Described in the journal Protein &
Cell, the authors treated nonviable
embryos to fix a gene mutation that
causes a blood disease called β-
thalassemia.
The study results proved the concerns of
the Science group to be well-founded.
The treatment killed nearly one in five
embryos, and only half of the surviving
cells had their DNA modified. Of the cells
that were even modified, only a fraction
had the disease mutation repaired. The
study also revealed off-target DNA
cutting and incomplete editing among all
the cells of a single embryo. Obviously
these kinds of errors are problematic in
embryos meant to mature into fully
grown human beings.
George Daley, a Harvard biologist and
member of the group that called for the
moratorium, concluded that “their study
should be a stern warning to any
practitioner who thinks the technology is
ready for testing to eradicate disease
genes."
In the enthusiasm and hype surrounding
Cas9, it is easy to forget that the
technology has been in wide use for
barely three years.
Role of a moratorium
Despite the publication of the Protein &
Cell study – whose experiments likely
took place at least months earlier – the
Science plea for a moratorium can
already be considered a success. The
request from such a respected group has
brought visibility to the topic and put
pressure on universities, regulatory
boards and the editors of scientific
journals to discourage such research.
(As evidence of this pressure, the
Chinese authors were rejected from at
least two top science journals before
getting their paper accepted.) And the
response to the voluntary ban has thus
far not included accusations of “stifling
academic freedom,” possibly due to the
scientific credibility of the organizers.
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