Brave New World?

Not Even Close

Scientists have edited a human embryo, but were not
in scary scifi territory by a long shot
By James Kath, Noam Prywes on August 2, 2017

Credit: Natali_Mis Getty Images

When asked why he wanted to climb Mount Everest, George Mallory famously
quipped, Because its there. Today, a group of scientists, led by Shoukhrat
Mitalipov at the Oregon Health & Science University, report in the
journal Nature the successful use of a gene editing technology to correct a disease-
causing mutation in viable human embryos. As biologists early in our career, we are
skeptical that their motivation is any better than Mallorysand their endeavor
comes with greater ethical concerns.
The focus of this study is a single mutation in the gene MYBPC3. This error is
dominanta child that inherits just one copy of the mutant gene is at high risk
for a serious disease called hypertrophic cardiomyopathy, which can cause sudden
cardiac death. Since each person has two gene copies and receives one randomly
from each parent, a child with an affected father or mother has a 50 percent chance
of inheriting the disease.
Using a gene editing technology called CRISPR/Cas9, Mitalipov and colleagues
repaired the mutations in embryos created through in vitrofertilization (IVF) using
sperm from a patient with the mutation and eggs from healthy donors. The key
innovation of this study was simultaneously injecting the CRISPR machinery and a
single sperm into an egg using an established IVF technique. Out of 58 embryos
tested, 72 percent were mutation-free, compared with 50 percent of embryos in the
control group. The edited embryos also appeared to develop normally until they
were destroyed three days later. Importantly, the researchers did not detect any
mosaic embryos, containing corrections in some but not all of their cells, or
unintended mutations in other parts of the genomechallenges highlighted by a
controversial 2015 studythat attempted similar edits of nonviable embryos.
Since details of this study were leaked last week in the MIT Technology Review,
there have been renewed calls to carefully consider the ethics of making heritable
gene edits to embryos, eggs, and sperm. Concerns range from off-target effects and
the inability of future generations to consent to genetic editing to the potential for
Gattaca-style designer babies. In response, it has been correctly pointed out that
the simplest clinical application is at least a decade off, and using CRISPR on
embryos, eggs, and sperm, in contrast to other types of cells, is opposed by much of
the scientific community.
There is an additional reason, seldom discussed, that this study and CRISPR
research will not usher in a brave new world of eugenics: the genetics of most
traits is too complex. For example, height is a simple trait that is easily measured
and strongly determined by genetic factors. However, unlike in the case of
hypertrophic cardiomyopathy, there is not a single gene determining height, but
hundreds. A 2010 study found at least 180 genes that are associated with the
differences in height between people, each contributing a small effect. Even if we
could efficiently and safely edit individual genes using CRISPR, it will not be
feasible to simultaneously edit hundreds of poorly understood genes in the
foreseeable future. A recent study revealed that using CRISPR to edit just two genes
can lead to disastrous chromosomal rearrangements. These fundamental
stumbling blocks prohibit engineering more complex traits such as IQ, lifespan,
and athletic ability.
Does this study at least mean that CRISPR may be used in the not-too-distant
future to eliminate simple genetic disorders at the embryonic stage? Even this
application has no clear utility, as inheritance of a mutant gene can be avoided with
a simpler approach: pre-implantation genetic diagnosis (PGD). PGD is a procedure,
in use since the 1980s, in which an in vitro fertilized embryo is tested for disease-
causing mutations; mutation-free embryos are then selected for implantation. In
the scenario explored here, in which one parent carries a dominant disease trait, 50
percent of embryos will lack the mutation; if both parents carried the mutation, 25
percent of embryos would still be healthy. Although discarding viable embryos
carries its own ethical concerns for some, CRISPR will still require embryos to be
tested and potentially discarded, even if the success rate is improved beyond the 72
percent reported in the Mitalipov study.
The use of CRISPR, as explored in this study, has no clear advantage over PGD.
Mitalipov and colleagues claim that their approach could increase the number of
embryos available for transfer and ultimately improve pregnancy rates. Even if
CRISPR increases the percentage of mutation-free embryos during IVF, this
marginal benefit is outweighed by the risks and ethical concerns it introduces.
A recent National Academies of Sciences report on gene editing additionally
considers a scenario where one parent carries two copies of a dominant genetic
mutation, ensuring 100 percent inheritance of the mutation without gene editing.
However, this motivation is also not compelling. Since the chance of having one
mutant gene is rare, carrying two mutant copies, when not lethal, is vanishingly
rare and typically limited to small, isolated communities.
If engineering human embryos with CRISPR has no clear application, why is it
being pursued? At minimum, scientists conducting this research should confront
its ethical dilemmas and offer sufficient justification for studies that may draw
widespread opposition and fear. Such controversial uses of CRISPR may jeopardize
the success of its less fraught applications. For example, CRISPR makes it easy to
edit the genomes of many organisms that serve as new disease models.
Additionally, ongoing work to apply CRISPR to adult cells may generate new
treatments for diseases such as cancer and diabetes without the ethical concerns of
embryo modification. Weve only seen the beginning of the development of this
transformative technology. While we cant predict how CRISPR will develop, we
can say that engineered babies are not around the corner.
The views expressed are those of the author(s) and are not necessarily those of Scientific American.
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