September 24, 2025 • 27 mins
Jennifer Doudna thought she had won the race. She thought she had beaten out all scientific competitors when she and her co-author had shocked the world with their groundbreaking technology for gene editing. But turned out, the race had just gotten fiercer.
Walter Isaacson sits down with Evan to talk about how one of the most cutthroat scientific competitions in biotech got started around one goal — making CRISPR work for humans, and getting the credit for it.
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Episode Transcript
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Speaker 1 (00:14):
Welcome back, everybody. My next guest is a Harvard medical professor,
a biologist, a geneticist, a chemist, and an engineer who's
worked with DNA is transforming our biology and our future.
Please welcome George Church. When it comes to geneting researchers,
George Church is the closest person in the field to
(00:35):
an actual, real world celebrity.
Speaker 2 (00:37):
George Church is a true gentleman scientist wrapped in the
cloak of being a madman scientist. He has a bushy beard.
He wants to bring the wooly mammoth back from extinction.
He talks in this very flamboyant way. He's just as
comfortable at the lab bench as he is on the
(00:58):
Colbert TV Show.
Speaker 1 (01:00):
For some he's known as the Godfather of synthetic biology
for his foundational work on gene editing technology, but for
most people today, he's best known as the co founder
of Colossal Biosciences, a company that's embarked on the ambitious
mission of de extincting species, most recently the dire Wolf.
And so when there's anything exciting happening in the field
of gene editing, you can bet George Church has been
(01:23):
involved with it in some way. Isaacson tells me that
the development of Crisper was no exception. He was one
of the researchers working on it and a close adviser
to Jennifer Dowdner at the time.
Speaker 2 (01:33):
He's become this mentor to a lot of people in
the biotech world, including Jennifer Dowdner, and I think he
started maybe three dozen companies. So he's not just a
great researcher. He applies it.
Speaker 1 (01:48):
He was twenty twelve and now that Dowdner and Charpentier
had successfully published their paper on how the Crisper CAST
nine mechanism worked, the next challenge for them was to
translate their findings from the test tube to the human cell.
Speaker 2 (02:01):
Well the end of the piece, they write they hint
that this could be used as a tool for editing genes.
But what they've done is only shown that it works
in a test tube. They haven't shown it can work
in a human cell. And so for the next six
to seven months you have a great race around the
(02:23):
world of scientists trying to show how this new combination
of RNA and enzyme a cast enzyme, a little manufactured
thing can edit human genes.
Speaker 1 (02:39):
And within this global race to figure out how crisper
could edit ourselves, one competitor came to the forefront, a
competitor who had also been mentored by George Church, a
Harvard scientist named Fungjong.
Speaker 2 (02:51):
Fung Jang is a great American story. His mother came
over from China on some fellowship to Iowa and just
saw how the labs and the universities and the schools
and the high schools in Iowa were so good that
she ends up bringing her young kid, Fung Jiang, to America,
(03:14):
and he becomes sort of a star in high school
in Iowa and eventually goes on studies with George Church
at Harvard and becomes a great biochemist and microbiologist.
Speaker 1 (03:26):
Fun Jong was working at the Broad Institute, a collaboration
between Harvard and MIT, when the race to apply crisper
and human cells was heating up, and so a triangle
of competition was born. George Church, Jennifer DOWDNA, and Fung Jong.
They were all racing towards the same goal, and Isaacson
says that Church, faced with competing with two of his protegees,
(03:47):
found himself in a tricky situation.
Speaker 2 (03:50):
It's complicated because he's very close to Jennifer Dowdner had
been an advisor and mentor, and he was close to
Fong Jiang who had worked in his lab, and so
he's conflicted a bit. He ends up wanting to help Jennifer.
Fung Jang is working behind his back, doesn't tell George
(04:10):
Church that he's trying to do this, and all three
of them at about the same time sort of circle
in on how do we prove it can work in
a human cell?
Speaker 1 (04:22):
What came next would feel one of the most disputed
questions around scientific discovery in the past decades. Who owns Crisper.
I'm Evan Ratliffe and this is on Crisper The Story
of Jennifer Dowdner Episode three, Patent Moore's So you have
(04:45):
these three labs who are chasing this question will this
work in a human cell? But again you have this
kind of competition cooperation because Fong Jiang has previously reached
out to Dowdna, been in contact with her because he
wants to understand her work.
Speaker 2 (05:03):
Phung Jong originally sends an email to Jennifer down to say,
I've read your piece. I want to figure out how
it's going to work, but they soon realize the stakes
are too high, and they all become more secretive and
more competitive. The question is, is that a bad thing. Suppose
(05:23):
there was no real competition thereby worked together, Well, that
would actually be friendlier and nicer. But maybe we wouldn't
have pushed science so far so fast if there weren't
an award forgetting their.
Speaker 1 (05:37):
First Isaacson tells me that if Dowdner and fun Jong
were racing on a track, Jong would have started in
the pole position. Even if Dowda might not have realized.
Speaker 2 (05:47):
It, she started off at a disadvantage. She had never
worked in living cells before, she had only done it
in a test to now you could have an argument,
as they did, about what is the more important way
to show something works. Is it best to be able
to show it in a living cell in the real world. Well,
(06:10):
that sounds logical, but actually to be able to show
it in a working in a test tube means that
you know the exact components. You know exactly which ingredients
are necessary or not which If you're doing it in
the human cell, there's also a messy other things happening.
So a Jennifer would say, being able to do with
(06:31):
the biochemistry in a test tube, that's actually the big deal,
and fong Jiang and others might say, no, no, test
tubes are easy. Doing it in a living cell is
the big leap.
Speaker 1 (06:46):
But they both knew that it would be a huge
discovery whoever got there first in terms of making it
work in the human cell.
Speaker 2 (06:53):
They both felt it would be a big discovery to
be able to do it first in the human cell.
Butjonniffer would argue, and did argue, that's not that big
of a leap once you know the ingredients that can
work and attest to. We've always had these things and
it's always been pretty ordinary in standard to then apply
(07:16):
them in the human cell. So she would argue the
big leap is figuring out the exact ingredients and that
every other gene editing tool. Once she had done that,
it wasn't that big of a leap to do it
in a cell. Now I think she's minimizing the importance
of doing it in a living cell. But that's why
there was a big dispute afterwards.
Speaker 1 (07:38):
But regardless of their starting positions, both Downa and Jung
knew that what mattered was who was first of the
finish line.
Speaker 2 (07:47):
The huge race is to actually be published first, because
that's the way you put a stamp on. I got
there first, and Jennifer knew that she was running behind that.
Jennifer for Dowbtne learns in a phone conversation from George
Church that not only is George Church trying to make
it work in human cells, which is logical, he had
(08:09):
done that his whole career, he had made other types
of technology work in human cells. But George Church also
says Pong Jang is doing a tiffic, so Jennifer tries
to speed up. She finds a publication that's online only
and that will rush it into publication, but she's still
She and Martin Yunick have to finish all the experiments
(08:32):
and show that it can be made to work, and
so over Christmas she's doing it, and then finally at
the very beginning of January twenty thirteen, when she's ready
to send it in Boom Science magazine, the grandest of all.
The magazine goes online and it has both George Church's
paper and Fong Jiang's paper showing how it works in humans.
(09:00):
Before Fong Jang and George church simultaneously a publishing Fong
Jang casually sends Jennifer an email saying, hey, my papers
about to be published. So her heart sinks. She knows
she's going to lose the race by about one or
two weeks because that's when her paper will be published.
(09:21):
And that may seem pretty you know, close in time,
but close doesn't count when it comes to patent surprises.
Speaker 1 (09:29):
Yeah, just the idea that it doesn't matter when you
knew it. It matters when that paper appears somewhere in
the world.
Speaker 2 (09:37):
One of the complexities is the winner of the race
is who published it as a paper first. But the
winner of a patent is a slightly more complicated task,
which is, even if you haven't published it, if you
can show you've made a certain discovery at a certain
(09:57):
point and you eventually get it on, it can count
in what's called a priority dispute. And so even now,
I mean we're ten years later, there's still a patent
war going on, and they're still showing pages in the
notebook where they show when they made each experiment.
Speaker 1 (10:18):
The notebook, a simple analog object would become a critical
piece of evidence in the timeline of Crisper's invention. Isaacson
tells me that Jennifer Downon knew that she could prove
that she had discovered the mechanism first just by looking
back at her notes each day.
Speaker 2 (10:34):
A great scientist who makes any discovery that day will
put it in a lab notebook and get two people
to witness it on the bottom of the page. And
early on with the first Crisper discoveries, Jennifer Dowdnan did
her husband, who's also a BIOCHEMISTY, that's important enough. You
got to go back to the lab, put it in
(10:55):
the notebook, and she got two of her graduate students
to witness set. So this is how important this claims
of priority can be.
Speaker 1 (11:06):
Now you've mentioned patents a couple of times, and I
feel like there was, of course a time when if
someone made this kind of breakthrough in a lab at university,
it wouldn't be patented necessarily. So what led to these
different university associated labs seeking patents on this type of discovery.
Speaker 2 (11:26):
In the early nineteen seventies, Herbert Bowyer and others working
at Stanford and universities in that area had come up
with genetic engineering advances how to do recombinant DNA. It
was called to make new types of organisms. And at
(11:49):
one point the Stanford lawyers helped some of them get
a patent, and the other scientists thought, hey, that's not
what we're doing here. We're doing research for the basic good.
But that patent ends up becoming the formation of this
multi billion dollar company, Genentech. So around then patents become
(12:12):
more important. America has a great system of allowing people
to patent the type of research they did at universities,
even if the government helped fund that research. And it
was two senators, Bob Dole and Birch Buy came up
(12:32):
with an act that said, how do we allocate it
if the federal government pays for research at the university.
And it's a slightly complicated formula, but the professor gets
a stake, the university gets a stake, the government has
a right to use the patented material. And it becomes
(12:52):
a great engine for commercializing basic science. And some people,
especially in the old days at Harvard or even in
the early seventies, soelth that's not good. You shouldn't be
trying to own this intellectual property. By the nineteen seventies
it was clear, we wanted research labs and research professors
(13:17):
to be able to make a buck if they made discoveries.
Speaker 1 (13:20):
In order to sort of drive that same competitive spirit.
Speaker 2 (13:24):
If you look around the world at where the greatest
advance has come in biotech and genetic engineering and the Internet,
in searches like Google, which were done at a Stanford
university under a government grant, it tends to happen in
the US because you're able to get rewarded if you
(13:45):
make discoveries, but it also funds them. It costs a
lot of money to build that lab at Berkeley, with
all of the not just the benches, but the hoods
and the ventilation and the test tubes and the pipeds
and the the graduate students being paid to do things.
That's a huge investment.
Speaker 1 (14:07):
We'll be right back, coming back to our trio of
scientific racers, DAWNA, Young, and Church. They would all publish
their papers close together in twenty thirteen detailing how crisper
could work in human cells, and while the patent question
(14:27):
was still up in the air, Isaacson says, they began
to explore the possibility of linking arms and creating a
joint company to share the ownership.
Speaker 2 (14:35):
After they all figure out how to make it work
in a human cell in this great race, and in
January twenty thirteen each published their papers. Initially they start
to work together, with George Church being the Ben Franklin
type trying to bring everybody together and starting a company
(14:56):
in which all of their intellectual property, any patents they
get in anything in the future, will all be part
of one consortium and they'll be able to commercialize it
and make it work. And the venture capitalists in Boston
in particular, are investing in a big company that's going
to do it. And yet there was a lot of
(15:18):
bad feelings, and I think in particular in the book,
there's this Jennifer describing that she thought fong Jiang was
working with the venture capitalists behind her back, and it
turns out he had filed for an expedited patent application
without telling her and the group, and she just feels
(15:42):
the guys are ganging up on me, and I don't
want any part of this, and she pulls out. And
then she thought, well, maybe I'll do it with Emmanuel Sharpentay.
But Emmanuel Sharpentay, she's off in her own world. She
wanted her own thing. I think eventually they're going to
all have to cross license the patents. But it almost
(16:06):
worked at the beginning to have one consortium. But now
if you want to make a treatment for sickle cell
anemia for other you know, for type of blindness, and
you're using crisper, sometimes you got to figure out which
of these patents do I have to license them all?
The field would be better off if they could settle
(16:29):
their patent dispute.
Speaker 1 (16:30):
And you, as you're reporting the book, you're you are
moving as we discussed, you're moving across talking to all
the players involved. Where did you land in terms of
pong Jiang's actions pursuing the expedited patent, for example, being
machiavellian versus having, you know, purer motives around trying to
(16:50):
accelerate the discovery.
Speaker 2 (16:52):
I think Pong Jang is a decent, good person and
a great scientist. And what he was doing was in
the realm of regular ethical conduct, which is trying to
get the patent first, rushing the patent application, and many
other things. And what he also did was keeping it secret.
(17:15):
Well that's not against the ethics rules. But as George
Church said to me, yes, what he did was in
the bounds of all the rules of ethics. But it's
not the way I would have had him do it
if he had still been part of my lab. That's
not the way we work. There's a system of honor
(17:38):
that goes beyond the ethics of are you supposed to
tell the other side? Or how open do you have
to be? I don't think Fong Xiang is a manipulative
or deceitful person, but he did decide toss to his
(18:00):
own course a little bit secretively, and that rubbed George
Church the wrong way.
Speaker 1 (18:06):
And is part of it. The way that the incentives
change when you move from you know, when you're talking
about trying to understand bacteria in a salt pool somewhere,
there's discovery incentive and there's curiosity that's driving you. But
when you reach this point, you have possible financial incentives
that come into play. These are businesses that are being started.
(18:26):
Did you feel like that played a role in how
people responded to the situation.
Speaker 2 (18:33):
One of the things that happened at one of these
breakfasts in Cambridge or meetings where they're all trying to
figure out how to pool together their patents and maybe
have one big company is. Jennifer asked George Church, how
big of a deal do you think this is? This
editing genes using Crisper pet and he basically says, grace yourself.
(18:58):
This is one of the biggest things ever to come
down the pike. So when the stakes get to be
so big and you realize this may be the biggest
discovery of the decade and it may have huge financial implications,
and that's a little bit different than trying to share
(19:19):
research on exactly how the sequences of Crisper might work
in different bacteria.
Speaker 1 (19:26):
So let's try to help people understand why it is
such a world changing, potentially world changing development because people
may know, well, we could sort of edit genes before this,
and they've heard of gene editing, So what is the
fundamental breakthrough when it comes to human cells and gene
editing that Crisper allows that we couldn't do before.
Speaker 2 (19:48):
Before when you had to edit, you could do something
very tailored and complicated, but it wasn't like programming a microchip,
which we can, you know, do in forty second. If
we want to fiddle with a program with Crisper, you
can instantly program it to cut wherever you want. In
(20:10):
the gene and then if you decide, well there's some
other place you went up, you're just tap tap, tap
and you get a new one. So it's very easy,
and with the combined single RNA guide we talked about,
it becomes pretty easy to get it into the cell.
So this is the difference between being a monk doing
(20:33):
a scribe work on a great manuscript and being able
to edit it with a quill pen and having a
amazing cut and paste computer programming type thing where you
can cut and paste and change. So Crisper at its
foundation using Crisper cast nine, the enzyme and the tool
(20:54):
becomes a foundation for even more tools that will allow
us to rewrite our genetic code.
Speaker 1 (21:04):
At this point in the story, the wider scientific community
in the public are becoming aware of the importance of Crisper.
The initial attempt at a consortium has devolved into separate,
competing companies, and it's also a point where Isaacson becomes
unexpectedly pulled into the dispute over who pioneered Crisper. It
all starts with a paper written by Eric Lander, founding
director of the Broad Institute where Fung Jung works.
Speaker 2 (21:27):
One of the things that Eric Lander Does, who ran
the Broad Institute where Fong Jang was working, decided he
wanted to make sure that Fung Jang and his team
got credit, and he wrote a scientific paper that got
published called The Heroes of Crisper. It's actually a very
(21:49):
good paper, and it takes you through every person involved
in the process, starting with Francesco Molika, the guy in
Spain who sees it in the original crobes in saltwater ponds,
but he minimizes what Jennifer Dowden, Emmanuel Sharpenjay does in
sort of a dismissive part of a paragraph saying a
(22:13):
good scientist say this, and then paragraph after paragraph on
how important it was that Phong Xiang was able to
make it work in the human cell. This causes only
the type of controversy that can happen when you combine
basic science with Twitter, in which Twitter mobs are accusing
(22:33):
Eric Lander are being sexist, and you know, doing to
Emmanuel Sharpentjay and Jennifer Dowdner what Jim Watson had done
to Rosalind Franklin and writing them out of history, and
also not disclosing when he wrote the piece that his
institute was in a patent battle with all of them,
(22:53):
so it becomes a mini scandal in the world of science.
Speaker 1 (22:59):
And then one of the people enlisted to help resolve
that scandal is you.
Speaker 2 (23:04):
At a certain point, the people at Harvard want to
restrain Eric Lander from going too far, and they know
it's gotten a bit unseemly. So I got a call
from somebody who said, can you host Eric Lander and
a group of science reporters and writers and technicians in
(23:26):
Washington and walk them through the Crispers story And we're
going to get him prepared to say nice things about
Jennifer Downer to try to resolve the controversy. And Eric
couldn't quite do it. I kept saying, all right, well
when the role of Jennifer, and he said, oh yeah,
they did okay. And I could see the person from
(23:47):
Harvard who was trying to orchesrate this kind of shrug
and roll their eyes. But I love Eric partly because
he's just so competitive.
Speaker 1 (23:57):
And was there a part of you that was this
did getting involved? Did you think, well, that's if I'm involved,
I'll just write it into the book. Or did you
say I'm trying to stay out of this.
Speaker 2 (24:09):
As a reporter. I was trained to stay out of it,
never to put yourself in a story. And over the years,
I realize you're more honest with the reader. Plus you
can make it a better understanding if you hold the
reader's hands and say, well, here's what I was doing
and how I got involved. And so with the Jennifer
(24:29):
Dowd in a book, I tried not to insert myself
in it unnecessarily. But at one point Jennifer Dowdn and
Emmanuel Sharp and Jay just are barely speaking to each
other even though that part, and Jennifer says, can you
call her up? And I had a joint session with
them on zoom, and I was just trying to see
(24:50):
if I could make sure that there was no misunderstandings
between them. And so what I was asked to do
this thing Ferick Landra, I said, if I'm upfront with
the reader and I plain exactly why I was doing it,
and it's actually truer to the situation than if I
pretend to have not been involved. Even when I'm at
(25:11):
a crisper conference like in Quebec City and I decide
to go out instead of with Jennifer Dowd newsgroup, I
decided to go to a restaurant with Fong Jang's group
and hear his side of the story. Instead of just
reporting his side of the story, I make it clear
they're competing debtors that night, and here's why I decided
to go to this one.
Speaker 1 (25:31):
You're like an enzyme. Maybe that's supercharging the competition just
by showing up and saying I'm going to write the
story about this.
Speaker 2 (25:38):
Yeah. I mean, enzymes are catalysts. They cause things to happen,
and you have to be careful that you're not distorting
the narrative by being there, that you're not too much
of a catalyst. On the other hand, when the story
is happening around you, when you're a part of it.
(25:59):
When I'm asked to moderate a panel at the Chris
Brook one of the later Christopher conferences at Cold Spring Arbor,
I want to do which best for the reader in
explaining how the tale unfolds.
Speaker 1 (26:16):
As of this recording, the dispute over who discovered Crisper
Cast nine is ongoing. In the next episode of On Crisper,
we delve into the ethical implications that gene editing technology
brings and how Jennifer Dowdner grappled with them, both professionally
and personally on Crisper. The Story of Jennifer DOWDNA is
a production of Kaleidoscope and iHeart. This show is based
(26:39):
on the writing and reporting of Walter Isaacson. It's hosted
by me Evan Ratliffe and produced by Adriana Tipia with
assistance from Alex Jandenveldt. He was mixed by Kyle Murdoch
and our studio engineer was Thomas Walsh. Our executive producers
are Kate Osborne and my Gaeshatikador from Kaleidoscope and Katrina
Dorvel from iHeart Podcasts. If you enjoy hearing stories about
visionaries and science and technology, check out our other seasons
(27:01):
based on the biographies that Walter Isaacson has written. On
Musk for an intimate dive into all facets of Elon
Musk and on Benjamin Franklin to understand how his scientific
curiosity shapes society as we know it.
Welcome back, everybody. My next guest is a Harvard medical professor,
a biologist, a geneticist, a chemist, and an engineer who's
worked with DNA is transforming our biology and our future.
Please welcome George Church. When it comes to geneting researchers,
George Church is the closest person in the field to
(00:35):
an actual, real world celebrity.
Speaker 2 (00:37):
George Church is a true gentleman scientist wrapped in the
cloak of being a madman scientist. He has a bushy beard.
He wants to bring the wooly mammoth back from extinction.
He talks in this very flamboyant way. He's just as
comfortable at the lab bench as he is on the
(00:58):
Colbert TV Show.
Speaker 1 (01:00):
For some he's known as the Godfather of synthetic biology
for his foundational work on gene editing technology, but for
most people today, he's best known as the co founder
of Colossal Biosciences, a company that's embarked on the ambitious
mission of de extincting species, most recently the dire Wolf.
And so when there's anything exciting happening in the field
of gene editing, you can bet George Church has been
(01:23):
involved with it in some way. Isaacson tells me that
the development of Crisper was no exception. He was one
of the researchers working on it and a close adviser
to Jennifer Dowdner at the time.
Speaker 2 (01:33):
He's become this mentor to a lot of people in
the biotech world, including Jennifer Dowdner, and I think he
started maybe three dozen companies. So he's not just a
great researcher. He applies it.
Speaker 1 (01:48):
He was twenty twelve and now that Dowdner and Charpentier
had successfully published their paper on how the Crisper CAST
nine mechanism worked, the next challenge for them was to
translate their findings from the test tube to the human cell.
Speaker 2 (02:01):
Well the end of the piece, they write they hint
that this could be used as a tool for editing genes.
But what they've done is only shown that it works
in a test tube. They haven't shown it can work
in a human cell. And so for the next six
to seven months you have a great race around the
(02:23):
world of scientists trying to show how this new combination
of RNA and enzyme a cast enzyme, a little manufactured
thing can edit human genes.
Speaker 1 (02:39):
And within this global race to figure out how crisper
could edit ourselves, one competitor came to the forefront, a
competitor who had also been mentored by George Church, a
Harvard scientist named Fungjong.
Speaker 2 (02:51):
Fung Jang is a great American story. His mother came
over from China on some fellowship to Iowa and just
saw how the labs and the universities and the schools
and the high schools in Iowa were so good that
she ends up bringing her young kid, Fung Jiang, to America,
(03:14):
and he becomes sort of a star in high school
in Iowa and eventually goes on studies with George Church
at Harvard and becomes a great biochemist and microbiologist.
Speaker 1 (03:26):
Fun Jong was working at the Broad Institute, a collaboration
between Harvard and MIT, when the race to apply crisper
and human cells was heating up, and so a triangle
of competition was born. George Church, Jennifer DOWDNA, and Fung Jong.
They were all racing towards the same goal, and Isaacson
says that Church, faced with competing with two of his protegees,
(03:47):
found himself in a tricky situation.
Speaker 2 (03:50):
It's complicated because he's very close to Jennifer Dowdner had
been an advisor and mentor, and he was close to
Fong Jiang who had worked in his lab, and so
he's conflicted a bit. He ends up wanting to help Jennifer.
Fung Jang is working behind his back, doesn't tell George
(04:10):
Church that he's trying to do this, and all three
of them at about the same time sort of circle
in on how do we prove it can work in
a human cell?
Speaker 1 (04:22):
What came next would feel one of the most disputed
questions around scientific discovery in the past decades. Who owns Crisper.
I'm Evan Ratliffe and this is on Crisper The Story
of Jennifer Dowdner Episode three, Patent Moore's So you have
(04:45):
these three labs who are chasing this question will this
work in a human cell? But again you have this
kind of competition cooperation because Fong Jiang has previously reached
out to Dowdna, been in contact with her because he
wants to understand her work.
Speaker 2 (05:03):
Phung Jong originally sends an email to Jennifer down to say,
I've read your piece. I want to figure out how
it's going to work, but they soon realize the stakes
are too high, and they all become more secretive and
more competitive. The question is, is that a bad thing. Suppose
(05:23):
there was no real competition thereby worked together, Well, that
would actually be friendlier and nicer. But maybe we wouldn't
have pushed science so far so fast if there weren't
an award forgetting their.
Speaker 1 (05:37):
First Isaacson tells me that if Dowdner and fun Jong
were racing on a track, Jong would have started in
the pole position. Even if Dowda might not have realized.
Speaker 2 (05:47):
It, she started off at a disadvantage. She had never
worked in living cells before, she had only done it
in a test to now you could have an argument,
as they did, about what is the more important way
to show something works. Is it best to be able
to show it in a living cell in the real world. Well,
(06:10):
that sounds logical, but actually to be able to show
it in a working in a test tube means that
you know the exact components. You know exactly which ingredients
are necessary or not which If you're doing it in
the human cell, there's also a messy other things happening.
So a Jennifer would say, being able to do with
(06:31):
the biochemistry in a test tube, that's actually the big deal,
and fong Jiang and others might say, no, no, test
tubes are easy. Doing it in a living cell is
the big leap.
Speaker 1 (06:46):
But they both knew that it would be a huge
discovery whoever got there first in terms of making it
work in the human cell.
Speaker 2 (06:53):
They both felt it would be a big discovery to
be able to do it first in the human cell.
Butjonniffer would argue, and did argue, that's not that big
of a leap once you know the ingredients that can
work and attest to. We've always had these things and
it's always been pretty ordinary in standard to then apply
(07:16):
them in the human cell. So she would argue the
big leap is figuring out the exact ingredients and that
every other gene editing tool. Once she had done that,
it wasn't that big of a leap to do it
in a cell. Now I think she's minimizing the importance
of doing it in a living cell. But that's why
there was a big dispute afterwards.
Speaker 1 (07:38):
But regardless of their starting positions, both Downa and Jung
knew that what mattered was who was first of the
finish line.
Speaker 2 (07:47):
The huge race is to actually be published first, because
that's the way you put a stamp on. I got
there first, and Jennifer knew that she was running behind that.
Jennifer for Dowbtne learns in a phone conversation from George
Church that not only is George Church trying to make
it work in human cells, which is logical, he had
(08:09):
done that his whole career, he had made other types
of technology work in human cells. But George Church also
says Pong Jang is doing a tiffic, so Jennifer tries
to speed up. She finds a publication that's online only
and that will rush it into publication, but she's still
She and Martin Yunick have to finish all the experiments
(08:32):
and show that it can be made to work, and
so over Christmas she's doing it, and then finally at
the very beginning of January twenty thirteen, when she's ready
to send it in Boom Science magazine, the grandest of all.
The magazine goes online and it has both George Church's
paper and Fong Jiang's paper showing how it works in humans.
(09:00):
Before Fong Jang and George church simultaneously a publishing Fong
Jang casually sends Jennifer an email saying, hey, my papers
about to be published. So her heart sinks. She knows
she's going to lose the race by about one or
two weeks because that's when her paper will be published.
(09:21):
And that may seem pretty you know, close in time,
but close doesn't count when it comes to patent surprises.
Speaker 1 (09:29):
Yeah, just the idea that it doesn't matter when you
knew it. It matters when that paper appears somewhere in
the world.
Speaker 2 (09:37):
One of the complexities is the winner of the race
is who published it as a paper first. But the
winner of a patent is a slightly more complicated task,
which is, even if you haven't published it, if you
can show you've made a certain discovery at a certain
(09:57):
point and you eventually get it on, it can count
in what's called a priority dispute. And so even now,
I mean we're ten years later, there's still a patent
war going on, and they're still showing pages in the
notebook where they show when they made each experiment.
Speaker 1 (10:18):
The notebook, a simple analog object would become a critical
piece of evidence in the timeline of Crisper's invention. Isaacson
tells me that Jennifer Downon knew that she could prove
that she had discovered the mechanism first just by looking
back at her notes each day.
Speaker 2 (10:34):
A great scientist who makes any discovery that day will
put it in a lab notebook and get two people
to witness it on the bottom of the page. And
early on with the first Crisper discoveries, Jennifer Dowdnan did
her husband, who's also a BIOCHEMISTY, that's important enough. You
got to go back to the lab, put it in
(10:55):
the notebook, and she got two of her graduate students
to witness set. So this is how important this claims
of priority can be.
Speaker 1 (11:06):
Now you've mentioned patents a couple of times, and I
feel like there was, of course a time when if
someone made this kind of breakthrough in a lab at university,
it wouldn't be patented necessarily. So what led to these
different university associated labs seeking patents on this type of discovery.
Speaker 2 (11:26):
In the early nineteen seventies, Herbert Bowyer and others working
at Stanford and universities in that area had come up
with genetic engineering advances how to do recombinant DNA. It
was called to make new types of organisms. And at
(11:49):
one point the Stanford lawyers helped some of them get
a patent, and the other scientists thought, hey, that's not
what we're doing here. We're doing research for the basic good.
But that patent ends up becoming the formation of this
multi billion dollar company, Genentech. So around then patents become
(12:12):
more important. America has a great system of allowing people
to patent the type of research they did at universities,
even if the government helped fund that research. And it
was two senators, Bob Dole and Birch Buy came up
(12:32):
with an act that said, how do we allocate it
if the federal government pays for research at the university.
And it's a slightly complicated formula, but the professor gets
a stake, the university gets a stake, the government has
a right to use the patented material. And it becomes
(12:52):
a great engine for commercializing basic science. And some people,
especially in the old days at Harvard or even in
the early seventies, soelth that's not good. You shouldn't be
trying to own this intellectual property. By the nineteen seventies
it was clear, we wanted research labs and research professors
(13:17):
to be able to make a buck if they made discoveries.
Speaker 1 (13:20):
In order to sort of drive that same competitive spirit.
Speaker 2 (13:24):
If you look around the world at where the greatest
advance has come in biotech and genetic engineering and the Internet,
in searches like Google, which were done at a Stanford
university under a government grant, it tends to happen in
the US because you're able to get rewarded if you
(13:45):
make discoveries, but it also funds them. It costs a
lot of money to build that lab at Berkeley, with
all of the not just the benches, but the hoods
and the ventilation and the test tubes and the pipeds
and the the graduate students being paid to do things.
That's a huge investment.
Speaker 1 (14:07):
We'll be right back, coming back to our trio of
scientific racers, DAWNA, Young, and Church. They would all publish
their papers close together in twenty thirteen detailing how crisper
could work in human cells, and while the patent question
(14:27):
was still up in the air, Isaacson says, they began
to explore the possibility of linking arms and creating a
joint company to share the ownership.
Speaker 2 (14:35):
After they all figure out how to make it work
in a human cell in this great race, and in
January twenty thirteen each published their papers. Initially they start
to work together, with George Church being the Ben Franklin
type trying to bring everybody together and starting a company
(14:56):
in which all of their intellectual property, any patents they
get in anything in the future, will all be part
of one consortium and they'll be able to commercialize it
and make it work. And the venture capitalists in Boston
in particular, are investing in a big company that's going
to do it. And yet there was a lot of
(15:18):
bad feelings, and I think in particular in the book,
there's this Jennifer describing that she thought fong Jiang was
working with the venture capitalists behind her back, and it
turns out he had filed for an expedited patent application
without telling her and the group, and she just feels
(15:42):
the guys are ganging up on me, and I don't
want any part of this, and she pulls out. And
then she thought, well, maybe I'll do it with Emmanuel Sharpentay.
But Emmanuel Sharpentay, she's off in her own world. She
wanted her own thing. I think eventually they're going to
all have to cross license the patents. But it almost
(16:06):
worked at the beginning to have one consortium. But now
if you want to make a treatment for sickle cell
anemia for other you know, for type of blindness, and
you're using crisper, sometimes you got to figure out which
of these patents do I have to license them all?
The field would be better off if they could settle
(16:29):
their patent dispute.
Speaker 1 (16:30):
And you, as you're reporting the book, you're you are
moving as we discussed, you're moving across talking to all
the players involved. Where did you land in terms of
pong Jiang's actions pursuing the expedited patent, for example, being
machiavellian versus having, you know, purer motives around trying to
(16:50):
accelerate the discovery.
Speaker 2 (16:52):
I think Pong Jang is a decent, good person and
a great scientist. And what he was doing was in
the realm of regular ethical conduct, which is trying to
get the patent first, rushing the patent application, and many
other things. And what he also did was keeping it secret.
(17:15):
Well that's not against the ethics rules. But as George
Church said to me, yes, what he did was in
the bounds of all the rules of ethics. But it's
not the way I would have had him do it
if he had still been part of my lab. That's
not the way we work. There's a system of honor
(17:38):
that goes beyond the ethics of are you supposed to
tell the other side? Or how open do you have
to be? I don't think Fong Xiang is a manipulative
or deceitful person, but he did decide toss to his
(18:00):
own course a little bit secretively, and that rubbed George
Church the wrong way.
Speaker 1 (18:06):
And is part of it. The way that the incentives
change when you move from you know, when you're talking
about trying to understand bacteria in a salt pool somewhere,
there's discovery incentive and there's curiosity that's driving you. But
when you reach this point, you have possible financial incentives
that come into play. These are businesses that are being started.
(18:26):
Did you feel like that played a role in how
people responded to the situation.
Speaker 2 (18:33):
One of the things that happened at one of these
breakfasts in Cambridge or meetings where they're all trying to
figure out how to pool together their patents and maybe
have one big company is. Jennifer asked George Church, how
big of a deal do you think this is? This
editing genes using Crisper pet and he basically says, grace yourself.
(18:58):
This is one of the biggest things ever to come
down the pike. So when the stakes get to be
so big and you realize this may be the biggest
discovery of the decade and it may have huge financial implications,
and that's a little bit different than trying to share
(19:19):
research on exactly how the sequences of Crisper might work
in different bacteria.
Speaker 1 (19:26):
So let's try to help people understand why it is
such a world changing, potentially world changing development because people
may know, well, we could sort of edit genes before this,
and they've heard of gene editing, So what is the
fundamental breakthrough when it comes to human cells and gene
editing that Crisper allows that we couldn't do before.
Speaker 2 (19:48):
Before when you had to edit, you could do something
very tailored and complicated, but it wasn't like programming a microchip,
which we can, you know, do in forty second. If
we want to fiddle with a program with Crisper, you
can instantly program it to cut wherever you want. In
(20:10):
the gene and then if you decide, well there's some
other place you went up, you're just tap tap, tap
and you get a new one. So it's very easy,
and with the combined single RNA guide we talked about,
it becomes pretty easy to get it into the cell.
So this is the difference between being a monk doing
(20:33):
a scribe work on a great manuscript and being able
to edit it with a quill pen and having a
amazing cut and paste computer programming type thing where you
can cut and paste and change. So Crisper at its
foundation using Crisper cast nine, the enzyme and the tool
(20:54):
becomes a foundation for even more tools that will allow
us to rewrite our genetic code.
Speaker 1 (21:04):
At this point in the story, the wider scientific community
in the public are becoming aware of the importance of Crisper.
The initial attempt at a consortium has devolved into separate,
competing companies, and it's also a point where Isaacson becomes
unexpectedly pulled into the dispute over who pioneered Crisper. It
all starts with a paper written by Eric Lander, founding
director of the Broad Institute where Fung Jung works.
Speaker 2 (21:27):
One of the things that Eric Lander Does, who ran
the Broad Institute where Fong Jang was working, decided he
wanted to make sure that Fung Jang and his team
got credit, and he wrote a scientific paper that got
published called The Heroes of Crisper. It's actually a very
(21:49):
good paper, and it takes you through every person involved
in the process, starting with Francesco Molika, the guy in
Spain who sees it in the original crobes in saltwater ponds,
but he minimizes what Jennifer Dowden, Emmanuel Sharpenjay does in
sort of a dismissive part of a paragraph saying a
(22:13):
good scientist say this, and then paragraph after paragraph on
how important it was that Phong Xiang was able to
make it work in the human cell. This causes only
the type of controversy that can happen when you combine
basic science with Twitter, in which Twitter mobs are accusing
(22:33):
Eric Lander are being sexist, and you know, doing to
Emmanuel Sharpentjay and Jennifer Dowdner what Jim Watson had done
to Rosalind Franklin and writing them out of history, and
also not disclosing when he wrote the piece that his
institute was in a patent battle with all of them,
(22:53):
so it becomes a mini scandal in the world of science.
Speaker 1 (22:59):
And then one of the people enlisted to help resolve
that scandal is you.
Speaker 2 (23:04):
At a certain point, the people at Harvard want to
restrain Eric Lander from going too far, and they know
it's gotten a bit unseemly. So I got a call
from somebody who said, can you host Eric Lander and
a group of science reporters and writers and technicians in
(23:26):
Washington and walk them through the Crispers story And we're
going to get him prepared to say nice things about
Jennifer Downer to try to resolve the controversy. And Eric
couldn't quite do it. I kept saying, all right, well
when the role of Jennifer, and he said, oh yeah,
they did okay. And I could see the person from
(23:47):
Harvard who was trying to orchesrate this kind of shrug
and roll their eyes. But I love Eric partly because
he's just so competitive.
Speaker 1 (23:57):
And was there a part of you that was this
did getting involved? Did you think, well, that's if I'm involved,
I'll just write it into the book. Or did you
say I'm trying to stay out of this.
Speaker 2 (24:09):
As a reporter. I was trained to stay out of it,
never to put yourself in a story. And over the years,
I realize you're more honest with the reader. Plus you
can make it a better understanding if you hold the
reader's hands and say, well, here's what I was doing
and how I got involved. And so with the Jennifer
(24:29):
Dowd in a book, I tried not to insert myself
in it unnecessarily. But at one point Jennifer Dowdn and
Emmanuel Sharp and Jay just are barely speaking to each
other even though that part, and Jennifer says, can you
call her up? And I had a joint session with
them on zoom, and I was just trying to see
(24:50):
if I could make sure that there was no misunderstandings
between them. And so what I was asked to do
this thing Ferick Landra, I said, if I'm upfront with
the reader and I plain exactly why I was doing it,
and it's actually truer to the situation than if I
pretend to have not been involved. Even when I'm at
(25:11):
a crisper conference like in Quebec City and I decide
to go out instead of with Jennifer Dowd newsgroup, I
decided to go to a restaurant with Fong Jang's group
and hear his side of the story. Instead of just
reporting his side of the story, I make it clear
they're competing debtors that night, and here's why I decided
to go to this one.
Speaker 1 (25:31):
You're like an enzyme. Maybe that's supercharging the competition just
by showing up and saying I'm going to write the
story about this.
Speaker 2 (25:38):
Yeah. I mean, enzymes are catalysts. They cause things to happen,
and you have to be careful that you're not distorting
the narrative by being there, that you're not too much
of a catalyst. On the other hand, when the story
is happening around you, when you're a part of it.
(25:59):
When I'm asked to moderate a panel at the Chris
Brook one of the later Christopher conferences at Cold Spring Arbor,
I want to do which best for the reader in
explaining how the tale unfolds.
Speaker 1 (26:16):
As of this recording, the dispute over who discovered Crisper
Cast nine is ongoing. In the next episode of On Crisper,
we delve into the ethical implications that gene editing technology
brings and how Jennifer Dowdner grappled with them, both professionally
and personally on Crisper. The Story of Jennifer DOWDNA is
a production of Kaleidoscope and iHeart. This show is based
(26:39):
on the writing and reporting of Walter Isaacson. It's hosted
by me Evan Ratliffe and produced by Adriana Tipia with
assistance from Alex Jandenveldt. He was mixed by Kyle Murdoch
and our studio engineer was Thomas Walsh. Our executive producers
are Kate Osborne and my Gaeshatikador from Kaleidoscope and Katrina
Dorvel from iHeart Podcasts. If you enjoy hearing stories about
visionaries and science and technology, check out our other seasons
(27:01):
based on the biographies that Walter Isaacson has written. On
Musk for an intimate dive into all facets of Elon
Musk and on Benjamin Franklin to understand how his scientific
curiosity shapes society as we know it.
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