[Ip-health] Lunch with the FT: Jennifer Doudna, Crispr scientist, on the ethics of editing humansHer gene-editing tool could cure disease and change the human race. But what happens if it falls into the wrong hands?

Thiru Balasubramaniam thiru at keionline.org
Sun Feb 2 10:01:26 PST 2020


Lunch with the FT
Life & Arts
Jennifer Doudna, Crispr scientist, on the ethics of editing humans Her
gene-editing tool could cure disease and change the human race. But what
happens if it falls into the wrong hands?
Hannah Kuchler

JANUARY 31 2020

Jennifer Doudna wears her responsibility lightly. The scientist who
co-discovered Crispr does not appear to be weighed down by the burden of
her creation: the revolutionary gene-editing technology that promises to
empower humans to control our own genome.


She has also found herself at the heart of a maelstrom. Crispr is now the
simplest, cheapest and most accurate way to edit our DNA, but its
development raises a multitude of moral questions. Fine-tuning our immune
systems to fight cancer is one thing — but given how much we have still to
discover about the genome, what might be the unintended consequences of
altering it? These are not merely speculative questions. In the years since
Doudna’s discovery, a Chinese scientist sent shockwaves through the
international scientific community when he announced the birth of the first
Crispr-modified babies.

 “One of the big challenges with gene editing is to think about how we take
a very powerful technology that has a lot of potential and make it more
widely available,” says Doudna, as we settle down at a small table in the
light-filled room. “I don’t want it to be something that is only available
to a few. That’s a big push, a big challenge.

 “But also we need to be thinking about these broader implications of a
powerful technology and how to develop them responsibly.”

A molecular biologist had noticed the presence of mysterious sequences —
Clustered Regularly Interspaced Short Palindromic Repeats — in bacteria’s
immune systems in the late 1980s, but hadn’t been able to figure out what
purpose they served. When Doudna first started studying these sequences in
the mid-2000s, it seemed highly unlikely that the work could lead to
patents that could be worth billions. At that time she was a leading
specialist in RNA, an essential molecule in the production of proteins.

In collaboration with French microbiologist Emmanuelle Charpentier, she
homed in on an enzyme called Cas9. The pair discovered that Crispr segments
could be used to guide Cas9 to locations on the genome, where it would then
cut like scissors. Together, Crispr and Cas9 could snip out genes or change
their function far more precisely than the clunky existing tools. This
technology has become known as Crispr.

The years since have seen a frenzy of Crispr-ing. Scientists are developing
Crispr-modified tomatoes that are more resistant to disease and Crispr-ed
beer that tastes more hoppy. Meanwhile researchers are using Crispr to
learn more about the human genome, experimenting with what happens when you
snip certain genes out. Patients with cancer and blood diseases have been
treated by having their blood cells taken out, Crispr-edited and put back
in. This year, the first Crispr gene-edits will be done in human cells
while they are still in the body, in trials to treat rare diseases in the
eye and the liver.


Feeling less than enlightened, I move the conversation back to Crispr.
Anyone with basic scientific knowledge and materials bought online can
experiment with Crispr in their own garage. Some so-called biohackers are
already injecting themselves with genetic material: for example, trying
(and thus far failing) to engineer more muscle.

Doudna agrees that there are dangers with these home-brew experiments but —
perhaps surprisingly for a professional scientist — welcomes them as part
of the democratisation of science.

“It’s a little bit analogous to the internet, where you have people working
around the world. They don’t have to have lots of special resources to
contribute to the content of the internet, or to develop the software that
has become widely available,” she says. “It’s kind of the same thing with
Crispr. It’s interesting that it’s being adopted widely and globally and
now we see really impactful work coming from all sorts of avenues.”

But I worry that we have failed to create robust international rules for
the internet — and that regulating Crispr will be even harder. Many
governments, including those in the EU and China, have made moves to ban
the editing of egg and sperm cells — “germline editing” — and in the US,
this in effect is the case as the FDA is not allowed to approve germline
editing studies. However, there are few rules specific to Crispr and, as
with online hackers, it will be challenging to enforce laws on people who
use gene editing dangerously.


Existing gene therapies can cost more than $2m for a one-time use. Crispr
could allow for new cures that senators feared would place an impossible
burden on the healthcare system. Although the first targets of trials in
humans are serious diseases that we know are caused by a single gene, such
as sickle cell or Huntingdon’s, as we understand more about combinations of
genes increasing risk factors for other diseases, Crispr could be used more

“They said, ‘Oh my gosh, if we’re on the verge of a cure for sickle cell
disease, and we have 100,000 people in the US [affected by the disease] . .
. how do we cater to that? How do we make sure they all have access to it
and they don’t bankrupt the government?’,” she says.


Crispr is already luring investors: Doudna has co-founded several Crispr
start-ups including Caribou Biosciences, which is working on editing the
immune system’s T-cells for therapies, and Mammoth Biosciences, programming
other Cas proteins to detect disease in patients or contamination in food
or the environment. She has also joined the board of Johnson & Johnson, a
sign that while large pharmaceutical companies appear to be waiting before
they invest heavily in Crispr, they are watching closely.

“I think they see the writing on the wall. I think they appreciate the
importance and the power of the technology for research,” she says. “We’re
going to have to rethink how we even define a drug.”

How can she make sure Crispr is not prohibitively expensive? Her answer is
simple: with more innovation. “The more efficiently you can do the editing,
the more effectively you can deliver editors into cells, whether plant
cells or the human brain or anything else, the better it will work, and the
more you can control cost,” she says.

“I guess I’ve grown up in a capitalist society where you believe that as
technologies become more capable, that it enables more companies to do
interesting things and then it drives down cost and we’ve seen this over
and over.”

She points to the iPhone as an example of a technology that was once the
stuff of sci-fi and is now widely available. Yet it seems wishful thinking
to imagine the same will happen for the drug market, with its web of
entrenched interests and government-granted monopolies.


As the market begins to take off, lawyers are battling over who owns which
Crispr patents. UC Berkeley, where Doudna is based, and the Broad Institute
of MIT and Harvard, home of scientist Feng Zhang, are in a drawn-out
dispute over when the scientists filed and over the use of the technology
in human cells. UC Berkeley is currently ahead with 20 US patents and the
European patent office recently cancelled a Crispr patent from the Broad.
The Broad has said it wants to reach a resolution with UC Berkeley.

 Doudna says the disagreement has been “very disappointing for me, as a
scientist and as a person” — whether because of an earnest sense of dismay
over the dispute between fellow scientists, or the potentially billions of
dollars in licensing fees that are at issue for the discoverers and their
universities. “When I get frustrated I try to take the long view,” she
says. “I try to imagine how I would feel 50 or 100 years from now, if I
came back and I was looking at this whole story. This will be one piece of
the story.” Hannah Kuchler is the FT’s US pharma and biotech correspondent

Thiru Balasubramaniam
Geneva Representative
Knowledge Ecology International
41 22 791 6727
thiru at keionline.org

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