Germline editing dominates DNA summit

Author(s): John Travis

Source: Science, New Series, Vol. 350, No. 6266 (11 DECEMBER 2015), pp. 1299-1300
Published by: American Association for the Advancement of Science
Stable URL: https://www.jstor.org/stable/24740857
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 IN DEPTH

Scientists,
Scientists,physicians,
physicians,
ethicists.
ethicists.and
andothers
othersdebated
debated
human
human gene
geneediting
editingatat
the
the
Washington,
Washington,D.C.,
D.C.,summit.
summit.

GENETIC ENGINEERING

Germline
Germlineediting
editingdominates
dominates
DNADNA
summit
summit
Prospect of heritable changes sparks questions about safety, ethics, and rationa
By
/JohnTravis John Travis cations could be justified to prevent the the U.S. National Academy of Medicine,
inheritance of disease or, more contro the United Kingdom's Royal Society, and
versially, to produce "enhancements" suchthe Chinese Academy of Sciences rushed to
shadow of eugenics. Philosophi as higher IQ or a reduced need for sleep. In convene the summit.
cal, ethical, and moral debates. fact, the organizers called for an "ongoing By tweaking CRISPR's RNA or nuclease
Uncertain science and patchy regu international forum" to regularly revisit the components, researchers expect to make

» congressman's warning. The long issue of germline editing. "The unthinkable the tool, developed from an immune sys
lations. And a cast that included
scientists expected to share ahas become conceivable," declared biologist tem found in bacteria, still more precise.
Nobel
Prize for a new DNA-changing technology, David Baltimore of the California Institute And "there are likely more powerful sys
commonly called CRISPR. All was on dis of Technology in Pasadena, the chairperson tems still out there in nature," noted Feng
play last week at the International Summit of the organizing committee. Zhang of the Broad Institute in Cambridge,
on Human Gene Editing, held at the U.S. The new molecular toolkit motivating the Massachusetts, who at one point shared the
National Academy of Sciences (NAS) in summit, CRISPR, consists of a DNA-cutting stage with other CRISPR pioneers, Jennifer
Washington, D.C. enzyme called a nuclease and a piece of RNA Doudna of University of California, Berke
"CRISPR and related technologies have ley, and Emmanuelle Charpentier of the
the potential to revolutionize the treat Max Planck Institute for Infection Biology
ment of diseases but could be used in in Berlin. Many predict the trio will win a
many ways not beneficial to society," "The noted
unthinkable Nobel for developing the system.
Representative Bill Foster (D-IL), has the become
only conceivable Few at the summit had qualms about us
Ph.D. physicist in the U.S. Congress, as the ing CRISPR and its rivals in somatic cells to
David Baltimore. California Institute
summit opened. treat disease. By applying zinc finger nucle
of Technology
The gathering ended on a similar note: ases to immune cells in vitro, groups have
The organizing committee strongly en already deactivated the gene for CCR5, a pro
dorsed the use of CRISPR and similar meth that homes in on a DNA sequence, en tein that the AIDS virus uses to invade the
abling researchers to create precisely tar cells; the modified cells were then returned
z ods for basic research that involves altering
§ DNA of human sperm, eggs, and embryos, geted mutations, corrections to mutations, to HIV-infected people. And last month, a
I but concluded that producing a pregnancy or other alterations. Along with two earlier team reported on using TALENs to edit can
s from such modified cells or embryos genome is cur editors, zinc finger nucleases andcer-fighting immune cells that subsequently
I rently "irresponsible" because of ongoing TALENs, CRISPR is transforming basic arrested leukemia in a 1-year-old girl. Speak
£ safety concerns and a lack of societal con biology and aiding the development of newers also discussed plans to use CRISPR on
£ sensus. Yet the group—12 biologists, physi crops and farm animals. Earlier this year, blood
a stem cells to reverse disorders such as
S cians, and bioethicists—did not flatly rule Chinese team became the first to publicly sickle cell anemia and beta thalassemia by
< out future use of such "germline editing," report using CRISPR to alter the DNA of fixing hemoglobin gene mutations.
| in which the DNA changes would be passed human embryos—nonviable ones—from in Biologist Janet Rossant of The Hospi
| down from one generation to the next, vitro fertilization (IVF) clinics, and a U.K. tal for Sick Children in Toronto, Canada,
O
g Much of the summit's discussions re group said it wanted to do similar research among others, spoke of the need to go fur
PHOT:NATIONAL CADEMYOFSCIEN S/PJ
AMRISDON volved around whether germline modifi in the United Kingdom. In response, NAS, ther and use gene editing to do basic re

SCIENCE sciencemag.org 11 DECEMBER 2015 • VOL 350 ISSUE 6266 1299

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NEWS I IN DEPTH

search on human embryos—work that For example,

the if both parents have cystic MARINE fi MAMMALS
U.S. National Institutes of Health is cur brosis, an autosomal recessive disorder, any
rently prevented by law from funding offspring
and would carry double mutations.
that could get scientists imprisoned
many. Such studies, she explained, could
Similarly,
in Ger a person with two dominant mu
tations, such as those causing Huntington
A whale's life,
probe the causes of miscarriages, birth disease, would pass on one. Speakers raised
defects, and developmental disorders. "We other scenarios that might call for germline
inscribed in
baleen
still have a lot more to learn about the hu editing, including bids to reverse infertility
man embryo and preimplantation stages," and parents seeking a "savior sibling" to
Rossant said. Attendees largely agreed, provide but matched, healthy bone marrow for
differed about whether spare IVF embryos a sick older child.
are good enough for such work, or whether For now, few would say genome editing Fibrous
Fibrouskeratin keratin can can storestore
the door should be open to creating em is safe enough for such uses. In the human a
a chemical
chemicalrecord record ofof
bryos just for research. embryo experiment, CRISPR cut many non
Germline gene editing to produce babies targeted genes. And Rudolf Jaenisch of pregnancies pregnancies
the andand stress
stress
stirred deeper debate. The summit heard a Massachusetts Institute of Technology in
primer on the dark history of eugenics, but Cambridge noted that when CRISPR re By Rebecca Kessler
John Harris, a philosopher at the Universitypairs one copy of a disease gene, it some
of Manchester in the United Kingdom, later times mutates the healthy copy. Eric Lander n 2004, a collision with a ship cut short
argued that nothing is sacred about the of the Broad Institute pointed out that if the life of an endangered North Atlantic
germline. All forms of assisted reproduc editing is attempted in early-stage human right whale. Many lamented the death
tion affect future generations, he said, and embryos, rather than in sperm or eggs, it of Stumpy, as scientists called her—all
normal reproduction is might only reach some the more because she was pregnant. But
a "genetic lottery" that cells, not all, resulting Stumpy's demise could ultimately help
often produces birth de in a mosaic embryo with other whales. Researchers are using plates
fects and disease. some mutant tissues. of her tough, hairlike baleen to develop a
For now, the best ar Technology may not new method of reconstructing a whale's life
gument for germline be a showstopper, how story—much as scientists use growth rings
editing may be its po ever Zhang and others to reveal a tree's past. The nascent tech
tential to correct known at the summit were op nique could make it easier to study, and
genetic errors and al timistic about reducing perhaps protect, whales.
low parents to have CRISPR's worrisome off Deriving whale
whale biographies
biographies from
frombaleen
baleen
healthy children. That target edits. But Lander, is just one concept to be discussed next
did not sway Catholic who was on the summit's week at the 21st Biennial Conference on the
theologian Hille Haker organizing committee, Biology of Marine Mammals in San Fran
of Loyola University reminded attendees cisco, California. Some 3000 researchers
Chicago in Illinois, who that the issues go well will share insights into some of the world's
contended that no one beyond technical skill, most charismatic creatures, including first
has a right to have ge especially when it comes time audio recordings of rare species and
netically related chil to genetic enhancement. updates on struggling populations. They'll
dren and called for a We know far too little also discuss novel ways of assessing the
ban on all human germ about the human ge health and physiology of free-swimming
line editing research. Preimplantation genetic diagnosis of nome's role in cognitionmammals that can be hard to study in
Also stirring discus human embryos (shown here) offers an and other traits to try the wild.
sion was the question alternative to editing their DNA. to mess with it, he said. That's where the work involving
of whether germline "The conclusion is sim Stumpy—and a second right whale named
editing is actually the best way to prevent ply humility. Before we make permanent Staccato—will come in. Over the past de
the transmission of genetic diseases. Many changes to the human gene pool, we should cade or so, wildlife researchers have been
cited a potential alternative: preimplanta exercise considerable caution." figuring out how to pry life history informa
tion genetic diagnosis (PGD), a relatively Even if some parents and clinicians tion evenout of tissues based on keratin, the fi
new procedure in which cells removed from tually decide it's safe and sensible to do brous protein found in nails, hair, feathers,
IVF embryos are screened for inherited mu germline engineering, they face a pastiche horns, claws, hooves, and skin. Researchers
tations; only healthy embryos are then im of conflicting laws and regulations around have used hair, for example, to study past
planted. In most cases in which one or both the world. More than 40 countries outlaw drug use in humans and exposure to toxins
parents have a known inheritable disease, tampering with the germline in IVF efforts, in wildlife.
Mendelian genetics imply that some fraction although many others, including the United Keratin is also
also aa major
major component
component of of ba ba- §
of their embryos will be free of the respon States, do not. The U.S. government will leen,not
leen, the
the comblike
comblikestructures
structuresononthe theupper
upper §
sible mutation(s). With PGD, those healthy fund clinical trials of such work, but jaws
gives
jaws of
ofabout 14 whale
about species
14 whale that help
species that help |
embryos could be identified and implanted. free rein to private IVF clinics. Near the the
theend
animals
animals catch
catchfood.
food.The
Thetips
tipsofofbaleen
baleen «
Baltimore crystallized the issue, asking: "Is it of the summit, Barbara Evans of the plates—the Univer
plates—the comb's
comb'steeth—wear
teeth—wear awayawayoverover J
more ethical to edit embryos or screen a lot sity of Houston Law Center in Texastime, noted so
so whales
whales continuously
continuously grow
grownew new ,t
of embryos and throw many away?" that "the 'science' of regulation is more keratin
preto
keratin toreplace
replace what's lost.
what's TheThe
lost. newnew ba ba- |
In some cases, however, no IVF embryos carious and uncertain than the science of such as
leen stores chemicals, such as hormones
hormones or or s O

would be normal, rendering PGD useless. gene editing." ■ contaminants,

contaminants,which whichareare
circulating
circulating in in
the
PHOT :BENOfTRAJ U/the
SCIENCESOURCE J

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