(phone rings) - [Bob] Jennifer.
- Bob, good morning. - [Bob] Good morning, congratulations. - Thank you so much. - [Bob] When did you find out about this? - About 2:53, I think, was the moment. The phone rang, and I
picked it up and she said, "Oh my gosh, you don't know,"
and I said, "Know, what?" And she said, "You won a Nobel Prize!" (Jennifer and Bob laugh) - [Bob] This is the first Nobel
Prize given only to women. - Is that true?
- [Bob] Yes. (bright music)
- Ever? - [Bob] Ever.
- Ever? (laughs) (people talking)
(cameras shooting) - This morning when I received the call from the General Secretary of the Royal Swedish Academy of Sciences, I was extremely emotional
and extremely moved, as a matter of fact. - [Jennifer] I'm so proud of the lab. I'm so proud of Berkeley. - [Observer] Should I get the sword? (crowd laughs)
- I might need the sword. (cork pops) - [Photographer] One, two, three! - [Everyone] CRISPR! (bright music continues) (birds chirping) - I remember having an actual physical, almost electrifying
feeling in Puerto Rico, in the spring of 2011,
when I met Emmanuelle. We were at a CRISPR meeting there, and we took a walk around Old San Juan. - We had a free afternoon, and
we went to a part of the city where we discussed different things. - And so we were walking around
these cobblestone streets, and we were just chatting about science And she said, "I've been
wanting to talk to you. "I'm glad to meet you in person,
because I've been thinking "that you might like to collaborate "with my lab on a project." - We thought we were
speaking the same language in principle and that we had the same way of approaching science. It was a very nice moment. - I love things that not a lot of people are paying attention to, which certainly CRISPR
was in its early days. It was an exciting time in the field, because although there was
a lot that wasn't known, it had the feeling of
something very interesting. - What was understood is CRISPR is a bacterial adaptive immune system. Experiments showed that the CRISPR system would allow bacteria to recognize
an infection with a virus and ultimately kill the virus. - It wasn't known how the molecules that participate in that
CRISPR pathway were working, but it was clear that the
CRISPR-associated proteins that are known as Cas somehow
seek and destroy viral DNA. We were talking about a
protein that at the time was known as Csn1, and
now is known as Cas9. (bright music continues) - And this mysterious Csn1 protein, surely, we were predicting the function, but no one could show up till
now how it was really working. - At the end of the
conversation, she said to me, "I think it's gonna be really
fun to work with your lab "on this mysterious Csn1,"
and just when she said that, "this mysterious Csn1," I
just felt this little chill going down my back. (bright music continues) What we do as scientists is we set up systems in the
laboratory and ask in isolation, "What does this particular molecule do? "What is its function?"
(bright music) - If you do the experiments
with the components purified, and you bring them
together in a test tube, and you show that it's working, then you know that it's self-sufficient. It's working like this. You don't need anything
else from the cell. - We said, "Well, let's see
if we can take that strategy "to answer the question,
'What does this protein, "'called Csn1, now known as Cas9, "'what does it actually do?'" - I was a post-doctoral fellow
in the lab of Jennifer Doudna when it kind of very
organically came together, and so I became the lead on
that project in Jennifer's lab. We had this idea that,
okay, the Cas9 protein was somehow going to be cutting DNA, but how exactly it was going to do it we didn't know at the time. - We knew that in nature, CRISPR systems have CRISPR RNA molecules, which are these little
copies of viral DNA. And it seemed like a reasonable hypothesis that the Cas9 protein could
use these working copies of RNA to find and destroy viral DNA. We made purified Cas9 protein, and we also made purified CRISPR RNA, and then combined them together to see can Cas9 use letters in the RNA to find a unique DNA sequence and cut it? And initially, the answer was,
no, no dice, nothing working. - (sighs) This is a
process of trial and error. You have some certain
ideas about what you need in order to cut the DNA, and
so you set up your reaction with a specific set of components, and you try to see what happens. - We thought maybe
there's something missing from the reaction. (gentle music) There was a second type of RNA that Emmanuelle's lab had
been studying, called tracr. - tracrRNA, it was an RNA molecule which we realized was very
abundant in the bacteria. - We started wondering
maybe it would be important to include the tracrRNA, and this was actually an experiment that was first done by
Krzysztof Chylinski, the student in Emmanuelle's lab. - And we had set up an experiment. We did a lot of combinations of different types of
RNAs, of Cas9 mutated, and right away, we saw,
yes, actually tracrRNA can form a duplex with CRISPR RNA, and then guide this Cas9 protein to target the DNA to be cleaved. You just need those three
components, it will work. When one thinks of a genetic tool, one always wants to have a very
minimal small genetic tool. - I did a set of experiments that would allow us to
fuse the two RNAs together and reduce the complexity of the system. (upbeat music) This then led to these experiments with these single molecules,
single RNA guide fusions. - Martin had made several versions of these single guide RNAs that differed just in the letters of the sequence that would allow Cas9 to find and cut a different piece of DNA. We assumed that Cas9
would be cutting the DNA at five different places. We had an experimental way of looking for the cuts
that we call a gel. You can apply an electric field across it, and the pieces of DNA will
separate according to their size. - You get the image kind of line by line, so it forms in front of you
on the screen in real time, and so you're kind of expecting things to show up in certain places. (upbeat music continues) As soon as that part of
the image came through on the scanner, okay, I
knew, okay, we have it. It is working exactly as
we predicted it would. It was a great moment. - We had been able to engineer this thing to be different from how it is in nature and much simpler in a sense. - This was a programmable system that you could repurpose for other things, including genome editing. We realized that we
were sitting on a story that was going to shake things up. (bright music) The final weeks in this process were really very, yeah, very intense. - Finishing up the last few experiments and writing up a manuscript... - I was living in the Umeå
in the north of Sweden. Spring was coming, and so you switch to
the fuller bright days. It's very disturbing
physiologically speaking, because you never see darkness,
you just see a gray sky. (laughs) I would have a tendency to work a little bit around the
clock and to not sleep a lot. - We used to call it
collaboration by Skype and FedEx. We'd work on a draft during the day. At the end of it, we
would send it to Europe, playing ping pong, basically,
with the manuscript. - Maybe there weren't lots of people working on CRISPR biology,
but there were others. It was clearly gonna be a race. We published our paper
in "Science" magazine in June of that year. (gentle music) (gentle music continues) - We showed that CRISPR
Cas9 brings a simplicity, yet it is a sophisticated system. - The field was ready for a
transformative tool like Cas9. - It was neat. It was
minimal and unexpected. (audience clapping) - For harnessing an ancient
bacterial immune system as a powerful gene editing technology with wide ranging
possibilities for medicine. - The Breakthrough Prize is awarded to Emmanuelle Charpentier
and Jennifer Doudna. (audience clapping) - Here was something that
was truly fascinating, first of all, just
fundamentally about nature, and then thinking about how
you might be able to use that in other settings, in other kinds of cells was also incredibly fun. - Very fast, we saw publications showing that the technology was working in plant cells and human cells and different model organisms. - Emmanuelle Charpentier
and Jennifer Doudna are bringing a great benefit
to humankind in many ways. With the discovery of the
CRISPR Cas9 genetic system, it is easy to introduce
new genetic information and thereby rewrite the code of life. - We've never had in the past the ability to change the fundamental chemical nature of who we are in this way, and now we do. And what do we do with that? Different cultures think
about it differently. Even my scientist colleagues
thought about it differently. Frankly, many of them didn't wanna think about these big picture things, I feel. It made me think a lot about my father, 'cause my father was a very
deeply spiritual kind of person, and he loved to think
about these big questions. Who are we and why are we here, and what's the purpose of life? I would often challenge him and say, "Well, who defines what's
right and what's wrong?" If my dad were alive now
and knew about CRISPR, and I could imagine the
kinds of conversations that we might get into of that nature. I mean, this is a tool that
fundamentally allows us to change our relationship with nature. It actually allows us to change human evolution if we want to. It's that profound. (gentle music continues) (gentle music continues) (gentle music continues) (gentle music continues) (gentle music continues)
