This episode of SciShow is brought to you
by the American Society of Gene and Cell Therapy.
[♪ INTRO]
Gene therapy is probably one of the most mind-boggling
developments in the last few decades of medicine.
The fact that we can treat certain diseases
by changing someone’s genetic makeup seems
like it should be straight out of a sci-fi
book.
In fact, when I was a kid, it was.
But it can also be a little misunderstood.
One of the most common misconceptions about
gene therapy is the idea that it will someday
be used to create what people call “designer
babies” — essentially, kids who have their
traits chosen before birth.
Things like intelligence or eye color, or
even whether or not they’re gonna go bald
later in life.
The truth is, most gene therapy research
right now doesn’t involve modifying fetal
cells at all.
And even when it does, researchers are looking
to prevent or treat genetic disorders — not
customize DNA just because they can.
In some ways, it’s just like every other
kind of medicine.
And in others… it is very, very different.
But one way or another, fetal gene editing
could be a big part of the future of medicine
— a future that may be here faster than
you think.
There are a few different types of gene therapy,
but the best-studied ones involve viruses.
The basic idea is that scientists take a virus
— called a vector — and remove the parts
that cause disease.
Then, they insert bundles of information for
the vector to deliver instead.
That information usually takes the form of
instructions, telling the body to produce
something like a protein that it’s naturally
lacking.
For example, those with hemophilia don’t
have enough of a specific blood-clotting protein.
So the gene to treat it would tell their cells
to start making those protein molecules.
Over the last few years, there have been an
increasing number of successful gene therapy
tests in both lab animals and humans.
But treating a disease after someone is born
can still come with some complications.
Some treatments come with risks, others aren’t
thorough enough, and, for some conditions,
there just aren’t useful treatments at all.
So the idea behind fetal gene therapy is to
prevent these diseases before someone is born.
It might involve treating an embryo directly,
or treating a fetus by injecting vectors into
something like the amniotic fluid.
But whatever the method, most researchers
agree that these treatments shouldn’t be
used for just anything.
In the late 1990s, the UK’s Gene Therapy
Advisory Committee published two criteria
that any fetal treatments worth considering
should meet.
First, they should have a clear advantage
over other treatments, like transplants or
postnatal therapy.
And secondly, they should be used for life-threatening
diseases with no suitable treatment.
In other words, the heart behind this is to
help people to be as healthy as possible,
just like other types of medicine — not
to, say, genetically engineer an X-Man.
The general consensus of other ethics committees
has been along the same lines.
Still, even with guidelines in place, most
of these therapies are currently too risky
to try in human fetuses, so research has mostly
been confined to animal models.
Pregnant people can get blood and tissue tests
to determine if their child is likely to have
a genetic disease — including cystic fibrosis,
hemophilia, and sickle cell anemia.
But there are not many immediate options if
those tests are positive.
We are making progress, though.
In 2018, a promising study in Nature Medicine
showed how fetal gene therapy could treat
an illness in mice that is similar to Gaucher’s
disease in humans.
Gaucher’s is an inherited disorder that
causes an enzyme deficiency — specifically,
for an enzyme called glucocerebrosidase.
Without healthy levels of it, waste builds
up in the body, which can lead to all kinds
of trouble.
Often, this disease can be treated by getting
weekly enzyme injections, but a certain type
of Gaucher’s — type 2 — isn’t treatable.
In this type, there isn’t enough glucocerebrosidase
in the brain.
And because of the blood-brain barrier that
filters out most molecules, the enzyme injections
don’t work.
The disease is often fatal, and by the time
a baby is born, a lot of the damage has already
been done.
So researchers have been looking into how
to treat it using fetal gene therapy.
In the 2018 experiment, scientists injected
the brains of fetal mice with vectors full
of instructions to make that missing enzyme
— and it seemed to help!
The mice had relatively normal enzyme activity,
although they did tend to weigh less and didn’t
perform as well on movement tests.
A follow-up experiment seemed to be even more
encouraging.
In it, researchers injected the vectors into
the bloodstream instead of the brain.
The mice were only allowed to be kept alive
for 55 days for ethical reasons, but during
that time, they didn’t seem to be any different
from regular mice.
The team also showed that this vector-injecting
method worked on larger animal fetuses,
like macaques.
The study was so successful that some scientists
argue we are ready to start clinical trials
of this method in humans.
But others disagree, pointing out that success
in pre-clinical studies doesn’t always equal
success in clinical trials.
So they think we need to keep researching.
Because that’s the thing about fetal gene
therapy: It’s really complicated, both scientifically
and ethically.
After all, as soon as you start clinical trials
— treating human embryos or fetuses that
will develop into full-grown kids — you’re
dealing with a person’s life.
And that’s not something to be taken lightly.
We have done trials on fetuses before, but
only using methods that were heavily studied
and shown to be safe.
Like, in another 2018 study, published in
The New England Journal of Medicine, researchers
used fetal gene therapy to prevent XLHED — an
inherited disorder that impairs sweat glands
— in three babies.
The kids were around a year and a half old
when the paper was published, and seemed to
be doing okay.
The key was that the researchers were using
extensively tested methods, and also got permission
from their hospital’s ethics committee.
That’s very different from the news that
broke just a few months later, when it came
out that a Chinese researcher had altered
human embryos using CRISPR, a newer gene-editing
technique.
This trial violated most of the accepted ethical
guidelines.
For one, it was done to reduce the babies’
chances of contracting HIV, and there are
much less risky ways to do that.
The scientist also didn’t get permission
from a committee, and, most importantly, the
method he used isn’t established as safe.
CRISPR has done great in the lab, but it’s
also been shown to cause occasional,
accidental mutations.
Thankfully, the kids are healthy so far, but
that doesn’t mean they always will be.
So, let’s just say there’s a reason we
have these guidelines.
In the future, there will likely be a time
when we can safely edit an embryo’s genome
in all kinds of different ways.
But even when that day comes, there will be
other things to think about, too.
Like, what would the consequences be if someone’s
edited genes were passed to their offspring?
Or if the edited gene mutated over the course
of someone’s life?
And then there are even messier questions,
like how far is too far when it comes to gene
editing, and if this science is interfering
with evolution… or if it matters if it is.
The most we can say is that, right now, fetal
gene therapy is really only intended for
necessary  treatments.
The next steps are to continue the animal
tests scientists have already started,
to really understand how this science works and
what the risks are.
Because at the end of the day, when these
experiments are approved for more frequent
clinical trials in humans, we want to make
sure they are as safe as possible.
If you’re interested in keeping up with
the latest research, you should check out
the new patient education portal from the
American Society of Gene and Cell Therapy.
It’s a super comprehensive resource for
everything you’ve ever wanted to know about
the different types of gene therapy, how they
work, and both past and ongoing research into
all kinds of treatments.
And it is completely free.
To check it out for yourself, just head over
to asgct.org/education, or follow the link
in the description below.
