How CRISPR lets us edit our DNA | Jennifer Doudna
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How CRISPR lets us edit our DNA | Jennifer Doudna

A few years ago, with my colleague, Emmanuelle Charpentier, I invented a new technology
for editing genomes. It’s called CRISPR-Cas9. The CRISPR technology allows
scientists to make changes to the DNA in cells that could allow us
to cure genetic disease. You might be interested to know that the CRISPR technology came about
through a basic research project that was aimed at discovering
how bacteria fight viral infections. Bacteria have to deal with viruses
in their environment, and we can think about a viral infection
like a ticking time bomb — a bacterium has only a few minutes
to defuse the bomb before it gets destroyed. So, many bacteria have in their cells
an adaptive immune system called CRISPR, that allows them to detect
viral DNA and destroy it. Part of the CRISPR system
is a protein called Cas9, that’s able to seek out, cut
and eventually degrade viral DNA in a specific way. And it was through our research to understand the activity
of this protein, Cas9, that we realized that we could
harness its function as a genetic engineering technology — a way for scientists to delete or insert
specific bits of DNA into cells with incredible precision — that would offer opportunities to do things that really haven’t
been possible in the past. The CRISPR technology
has already been used to change the DNA in the cells
of mice and monkeys, other organisms as well. Chinese scientists showed recently that they could even use
the CRISPR technology to change genes in human embryos. And scientists in Philadelphia showed
they could use CRISPR to remove the DNA
of an integrated HIV virus from infected human cells. The opportunity to do this kind
of genome editing also raises various ethical issues
that we have to consider, because this technology can be employed
not only in adult cells, but also in the embryos of organisms, including our own species. And so, together with my colleagues, I’ve called for a global conversation
about the technology that I co-invented, so that we can consider all of the ethical
and societal implications of a technology like this. What I want to do now is tell you
what the CRISPR technology is, what it can do, where we are today and why I think we need to take
a prudent path forward in the way that we employ this technology. When viruses infect a cell,
they inject their DNA. And in a bacterium, the CRISPR system allows that DNA
to be plucked out of the virus, and inserted in little bits
into the chromosome — the DNA of the bacterium. And these integrated bits of viral DNA
get inserted at a site called CRISPR. CRISPR stands for clustered regularly
interspaced short palindromic repeats. (Laughter) A big mouthful — you can see why
we use the acronym CRISPR. It’s a mechanism that allows cells
to record, over time, the viruses they have been exposed to. And importantly, those bits of DNA
are passed on to the cells’ progeny, so cells are protected from viruses
not only in one generation, but over many generations of cells. This allows the cells
to keep a record of infection, and as my colleague,
Blake Wiedenheft, likes to say, the CRISPR locus is effectively
a genetic vaccination card in cells. Once those bits of DNA have been inserted
into the bacterial chromosome, the cell then makes a little copy
of a molecule called RNA, which is orange in this picture, that is an exact replicate
of the viral DNA. RNA is a chemical cousin of DNA, and it allows interaction
with DNA molecules that have a matching sequence. So those little bits of RNA
from the CRISPR locus associate — they bind —
to protein called Cas9, which is white in the picture, and form a complex that functions
like a sentinel in the cell. It searches through all
of the DNA in the cell, to find sites that match
the sequences in the bound RNAs. And when those sites are found — as you can see here,
the blue molecule is DNA — this complex associates with that DNA and allows the Cas9 cleaver
to cut up the viral DNA. It makes a very precise break. So we can think of the Cas9 RNA
sentinel complex like a pair of scissors
that can cut DNA — it makes a double-stranded break
in the DNA helix. And importantly,
this complex is programmable, so it can be programmed to recognize
particular DNA sequences, and make a break in the DNA at that site. As I’m going to tell you now, we recognized that that activity
could be harnessed for genome engineering, to allow cells to make
a very precise change to the DNA at the site where
this break was introduced. That’s sort of analogous to the way that we use
a word-processing program to fix a typo in a document. The reason we envisioned using
the CRISPR system for genome engineering is because cells have the ability
to detect broken DNA and repair it. So when a plant or an animal cell detects
a double-stranded break in its DNA, it can fix that break, either by pasting together
the ends of the broken DNA with a little, tiny change
in the sequence of that position, or it can repair the break by integrating
a new piece of DNA at the site of the cut. So if we have a way to introduce
double-stranded breaks into DNA at precise places, we can trigger cells
to repair those breaks, by either the disruption or incorporation
of new genetic information. So if we were able to program
the CRISPR technology to make a break in DNA at the position at or near a mutation
causing cystic fibrosis, for example, we could trigger cells
to repair that mutation. Genome engineering is actually not new,
it’s been in development since the 1970s. We’ve had technologies for sequencing DNA, for copying DNA, and even for manipulating DNA. And these technologies
were very promising, but the problem was
that they were either inefficient, or they were difficult enough to use that most scientists had not adopted them
for use in their own laboratories, or certainly for many
clinical applications. So, the opportunity to take a technology
like CRISPR and utilize it has appeal, because of its relative simplicity. We can think of older
genome engineering technologies as similar to having
to rewire your computer each time you want to run
a new piece of software, whereas the CRISPR technology
is like software for the genome, we can program it easily,
using these little bits of RNA. So once a double-stranded
break is made in DNA, we can induce repair, and thereby potentially achieve
astounding things, like being able to correct mutations
that cause sickle cell anemia or cause Huntington’s Disease. I actually think that the first
applications of the CRISPR technology are going to happen in the blood, where it’s relatively easier
to deliver this tool into cells, compared to solid tissues. Right now, a lot of the work
that’s going on applies to animal models
of human disease, such as mice. The technology is being used to make
very precise changes that allow us to study the way
that these changes in the cell’s DNA affect either a tissue or,
in this case, an entire organism. Now in this example, the CRISPR technology
was used to disrupt a gene by making a tiny change in the DNA in a gene that is responsible
for the black coat color of these mice. Imagine that these white mice
differ from their pigmented litter-mates by just a tiny change at one gene
in the entire genome, and they’re otherwise completely normal. And when we sequence the DNA
from these animals, we find that the change in the DNA has occurred at exactly the place
where we induced it, using the CRISPR technology. Additional experiments
are going on in other animals that are useful for creating models
for human disease, such as monkeys. And here we find
that we can use these systems to test the application of this technology
in particular tissues, for example, figuring out how to deliver
the CRISPR tool into cells. We also want to understand better how to control the way
that DNA is repaired after it’s cut, and also to figure out how to control
and limit any kind of off-target, or unintended effects
of using the technology. I think that we will see
clinical application of this technology, certainly in adults, within the next 10 years. I think that it’s likely
that we will see clinical trials and possibly even approved
therapies within that time, which is a very exciting thing
to think about. And because of the excitement
around this technology, there’s a lot of interest
in start-up companies that have been founded
to commercialize the CRISPR technology, and lots of venture capitalists that have been investing
in these companies. But we have to also consider that the CRISPR technology can be used
for things like enhancement. Imagine that we could try
to engineer humans that have enhanced properties,
such as stronger bones, or less susceptibility
to cardiovascular disease or even to have properties that we would consider maybe
to be desirable, like a different eye color
or to be taller, things like that. “Designer humans,” if you will. Right now, the genetic information to understand what types of genes
would give rise to these traits is mostly not known. But it’s important to know that the CRISPR technology gives us a tool
to make such changes, once that knowledge becomes available. This raises a number of ethical questions
that we have to carefully consider, and this is why I and my colleagues
have called for a global pause in any clinical application
of the CRISPR technology in human embryos, to give us time to really consider all of the various
implications of doing so. And actually, there is an important
precedent for such a pause from the 1970s, when scientists got together to call for a moratorium
on the use of molecular cloning, until the safety of that technology
could be tested carefully and validated. So, genome-engineered humans
are not with us yet, but this is no longer science fiction. Genome-engineered animals and plants
are happening right now. And this puts in front of all of us
a huge responsibility, to consider carefully
both the unintended consequences as well as the intended impacts
of a scientific breakthrough. Thank you. (Applause) (Applause ends) Bruno Giussani: Jennifer, this is
a technology with huge consequences, as you pointed out. Your attitude about asking for a pause
or a moratorium or a quarantine is incredibly responsible. There are, of course,
the therapeutic results of this, but then there are the un-therapeutic ones and they seem to be the ones
gaining traction, particularly in the media. This is one of the latest issues
of The Economist — “Editing humanity.” It’s all about genetic enhancement,
it’s not about therapeutics. What kind of reactions
did you get back in March from your colleagues in the science world, when you asked or suggested that we should actually pause this
for a moment and think about it? Jennifer Doudna: My colleagues
were actually, I think, delighted to have the opportunity
to discuss this openly. It’s interesting that as I talk to people, my scientific colleagues
as well as others, there’s a wide variety
of viewpoints about this. So clearly it’s a topic that needs
careful consideration and discussion. BG: There’s a big meeting
happening in December that you and your colleagues are calling, together with the National Academy
of Sciences and others, what do you hope will come
out of the meeting, practically? JD: Well, I hope that we can air the views of many different individuals
and stakeholders who want to think about how to use
this technology responsibly. It may not be possible to come up with
a consensus point of view, but I think we should at least understand what all the issues are as we go forward. BG: Now, colleagues of yours, like George Church,
for example, at Harvard, they say, “Yeah, ethical issues basically
are just a question of safety. We test and test and test again,
in animals and in labs, and then once we feel it’s safe enough,
we move on to humans.” So that’s kind of the other
school of thought, that we should actually use
this opportunity and really go for it. Is there a possible split happening
in the science community about this? I mean, are we going to see
some people holding back because they have ethical concerns, and some others just going forward because some countries under-regulate
or don’t regulate at all? JD: Well, I think with any new technology,
especially something like this, there are going to be
a variety of viewpoints, and I think that’s
perfectly understandable. I think that in the end, this technology will be used
for human genome engineering, but I think to do that without careful
consideration and discussion of the risks and potential complications would not be responsible. BG: There are a lot of technologies
and other fields of science that are developing exponentially,
pretty much like yours. I’m thinking about artificial
intelligence, autonomous robots and so on. No one seems — aside from autonomous warfare robots — nobody seems to have launched
a similar discussion in those fields, in calling for a moratorium. Do you think that your discussion may
serve as a blueprint for other fields? JD: Well, I think it’s hard for scientists
to get out of the laboratory. Speaking for myself, it’s a little bit
uncomfortable to do that. But I do think that being involved
in the genesis of this really puts me and my colleagues
in a position of responsibility. And I would say that I certainly hope
that other technologies will be considered in the same way, just as we would want to consider
something that could have implications in other fields besides biology. BG: Jennifer, thanks for coming to TED. JD: Thank you. (Applause)

100 thoughts on “How CRISPR lets us edit our DNA | Jennifer Doudna

  1. This changes evolution! This technology changes absolutely everything! Exciting and Terrifying all at the same time. It is mind blowing.

  2. While academia pauses, industry moves forward with it. I wonder now that Univ. of California won their patent on CRISPR/cas9 will it slow the adaption of the technology down?

  3. I may only be young but i am really intrested in the project. Im glad that y'all could touch this subject. People have been arguing about this cause most think it'll change the person. It may,but they will be happy that they could change their faults of their body.

  4. Like its gonna be used for healing people. like the system actually wants to heal people . Sickness is a business called PHARMA .

  5. "Designer humans if you will ?" God knows I despise the people . The lust for inventing without consideration for consequences. You opened Pandora's box . Those who play God are either naive or evil.

  6. I think everybody needs to check out Henrietta lacks chart and see that they've been messing around with DNA and crispr since the early 1900s Eugenics programs these Nazis I've been fucking around trying to play God for years and all of a sudden now we need to be prudent because there's people who don't look like us is tampering with a genome. You guys open Pandora's box it's going to be an interesting future superheroes supervillains comic book should come to life yay crispr morons

  7. Have you noticed does anybody notice how many designer babies are out there right now how many children that are working amongst us people that have gone through genetic manipulation?

  8. you explained it FARRRR better than ALL the other people on YouTube who tried to "simplify" it, i know there is a possibility that your way of laying it out just so happens to coincidentally match my way of comprehending things, and that someone out here might STILL BE LOST in the woods after listening to everything you've said herein. But I must say, after trying 20 other videos, you actually explained it FARRRR better and clearer (crystal-clearer) than ALL the other people on YouTube who claimed to "simplify" it. i am NOT worried about the ethical questions, because if you're some evil scientist from North Korea (forgive me my Korean friends) and you use this innovation in BAD FAITH to deliberately introduce BAD sequences of DNA into otherwise healthy people, certainly this EXACT same technology can be used to REVERSE your beastly acts of malice ! i say this with confidence because if we take a step back and think about it . . . the ORIGIN and ESSENCE of this Cas9 and CRISPR innovation is based on dealing with EVIL sequences of of DNA that are ALREADY an evil element in innocent people's bodies/blood/tissue, i mean come on . . . this technology is originally created to SPECIFICALLY DEAL with the EVIL stuff, such that trying to use it in a malicious way to introduce EVIL stuff is going to be nothing but a FUTILE, REDUNDANT and complete WASTE of time and effort for the EVIL guy, trying to do EVIL things with this technology is a futile exercise because the technology is created specifically to DEAL with that sort of evil ! it would be like trying to keep an inflated balloon under the water, as soon as you leave it, that balloon will pop right BACK up to the surface of the water, unless you take other unrelated physical measures such as to now keep the balloon tied down and you lock it into a cage under the water or you physically burst it (kill it) ! i DON'T mind Cas9/CRISPR being used for "enhancement and cosmetic/aesthetic" purposes because in medicine nowadays we're already so deep into cosmetic and aesthetic procedures plastic surgery is now commonplace in medicine ! but for the EVIL guy/scientist out there, this innovation is specifically created TO DEFEAT YOUR evil acts of malice ! this technology is CREATED specifically to DEAL with evil and malicious things in the first place (bad genes/viruses/bad DNA sequences/etc) !! so i wouldNT obsess so much about it being used in malicious ways, in the same way that we certainly do NOT obsess about "guns" being used to commit crime, because the fate of a gun criminal is that he will sooner or later die of a GUN bullet himself if he does NOT hand in his "evil gun" ! I am also NOT worried about it producing undesirable long-term effects becuz as long as the initial gene editing was put on record, that initial editing can CERTAINLY be reversed at a later stage such that the DNA is restored back to its original sequence or FURTHER editing can be done to disturb/modify the long-term adverse effects of earlier poor editing

  9. Cut away lady.. we will have to evolve in order to reach the stars and keep up with the AI advancements no matter what. Unregulated the AI will however most likely wipe us out because we will slow down its evolution… A ticking evolutionary Pandora's Box is about to be opened by most likely naive and savage members of our species. Roll the dice and hope for the best.

  10. STOP developing the diseases and putting these diseases in our food air water, and stop F#%@&ing with GODS creation it has only been a little over 100 years since we have been getting these diseases invented by men and women like you….WARNING STOP GETTING VAXINES because this is how were are getting these diseases…May GOD have mercy on your souls…

  11. Asking for a global pause on this technology is like loaning money to that relative, when you know deep down they will not pay it back.

  12. This is the next step in artificially creating and evolving life. When you combine the organic advancement with an advanced three dimensional quontum computer, you set the stage for simulating a universe: maybe THE EXACT ONE we are in!

  13. Sorry , people are soooo corrupt these days I find it hard to trust what I hear , it sounds like a great idea to me to improve and prevent human defects etc. but It could be that the big corporations want a pause to give them time to take it away from the little companies and get patens and to control the market or to close it down and hide it away if they can't own it. Like they did with Tesla etc.

  14. So theoretically, if we had some of Hitler’s DNA we could make a clone of him but the clone wouldn’t be exactly like him depending on how he would be raised and where

  15. Sorry, Mrs. Doudna, but this train, which you have played no small part in accelerating, does not stop; it only gets faster and more perilous.

  16. Sounds like a potential plan to rid the world of the virus called humans?… I feel a train wreck coming on.
    " I am Legend " ?

  17. Chinese Dr?? does she mean the fraud who claimed to make the two babies immune to HIV? I certainly hope not. If so, Ted needs to take this embarrassment down straight away.

  18. If the CRISPR bacterial system is incorporating selective bits of foreign DNA, does this mean this mechanism won't work on RNA viruses? Without a RT enzyme in the bacterial cytoplasm how would it incorporate RNA genomic sequences?

  19. Thank you for your amazing work and super presentation.. I will be following this new technology.. this is such an amazing leap.

  20. My daughter has a als 2 gene. I would love to enroll her in human trials for crysper. Is there any in the usa?

  21. Literally

  22. Jennifer Doudna is A ROCK STAR!!!
    It’s amazing to me that sports and anti-trump politics is more NEWS WORTHY than CRISPR. Jennifer, you’re incredible! I’m a fan! Please don’t let politicians, the News Media, and CNN, meddle in what you’re doing by politicizing your work! They wont be thinking about humanity, all they care about is VOTES!!!!!! “WE” offer you “FREE” endless life, “FREE” of ALL deceases! (Even though they know the technology isn’t ready). They’ll protest… It’s the Republicans!!!! who are keeping this salvation from you!!!! VOTE FOR US, WE ARE THE ONLY ONES WHO WANT TO SAVE YOU. WE ARE YOUR SAVIOR! They wont even hesitate to think about the Frankenstein implications… they just want that limo and expensive trips to luxurious “world saving” events.

  23. In 2016 IPO, I asked my friend to invest 2k of my money into CRISPR Therapeutics on his Robinhood account since I didn't have one. He thought I was an idiot and so did my dad. They said, "you see something on YouTube and think you're a genius." Well, I'm still watching YouTube, now the stock is at $40.00 something dollars. If I sold now, I would've made 4k+. Thanks a lot…

  24. Such an elegant system. This is what the workflow looks like currently in the lab:

  25. I don't care about losing my hair (that ship has sailed) but I would like to see this used to alter cancer cells to stop doing what they are doing or alter T-cells to recognize the cancer cells and eliminate them.

  26. Scientists wasting time with AIDS when everybody knows that you Can't just get Aids out of nowhere , they should focus on Cancer and stuff like that

  27. I love how she tripped up when she mentioned Enhancement and how we've had things like this since the 1970s… shes lying. The elite have been making their kids this way for decades… google margot robbie and Jamie lee Presley

  28. wasn't 'invented' it was discovered – big difference… "I discovered a new species of crab in deep-water trenches – hence I own all this species of crabs and any uses that they may have" – see what I mean?

  29. Interrogator: Officer K-D-six-dash-three-dot-seven, let's begin. Ready?
    K: Yes, sir.
    Interrogator: Recite your baseline.
    K: "And blood-black nothingness began to spin… A system of cells interlinked within cells interlinked within cells interlinked within one stem… And dreadfully distinct against the dark, a tall white fountain played."
    Interrogator: Cells.
    K: Cells.
    Interrogator: Have you ever been in an institution? Cells.
    K: Cells.
    Interrogator: Do they keep you in a cell? Cells.
    K: Cells.
    Interrogator: When you're not performing your duties do they keep you in a little box? Cells.
    K: Cells.
    Interrogator: Interlinked.
    K: Interlinked.
    Interrogator: What's it like to hold the hand of someone you love? Interlinked.
    K: Interlinked.
    Interrogator: Did they teach you how to feel finger to finger? Interlinked.
    K: Interlinked.
    Interrogator: Do you long for having your heart interlinked? Interlinked.
    K: Interlinked.
    Interrogator: Do you dream about being interlinked… ?
    K: Interlinked.
    Interrogator: What's it like to hold your child in your arms? Interlinked.
    K: Interlinked.
    Interrogator: Do you feel that there's a part of you that's missing? Interlinked.
    K: Interlinked.
    Interrogator: Within cells interlinked.
    K: Within cells interlinked.
    Interrogator: Why don't you say that three times: Within cells interlinked.
    K: Within cells interlinked. Within cells interlinked. Within cells interlinked.
    Interrogator: We're done. "Constant K"… you can pick up your bonus.
    K: Thank you, sir.

  30. How transposons improve CRISPR efficiency (Cómo los transposones mejoran la eficiencia del CRISPR):

  31. I only support this if it is for therapeutic reasons such as treating diseases in children and adults. What I don't support is to genetically engineer a human being to have certain traits they were not naturally born with. Yes we have the power, from GOD to achieve many wonders but we should not forget that GOD still remains the Creator of human life…we should only improve lives not genetically alter them cos we want kids with high IQ, or beautiful children. Thank you

  32. myNotes:
    -bacteria fights virus, I want examples!
    -protein, cas9, is the tool we can modify DNA with
    -RNA is a copy of DNA at a particular moment, this reminds me of a "back-up"
    -Genome engineering, like a word processing program
    -What is the difference between genes and chromosomes? (the black/white mice example made me ask this)

  33. Last year, I was in her biology class at UC Berkeley, went to ask her a very simple question about isotopes. Had no idea who she was. She’s amazing! But I’m glad I didn’t know who she was, because I may not have gone to ask that simple question because I was too “shy.”

  34. The US is going to cripple itself with ethic and regulations, while the Chinese and the Russians are moving forward rapidly. We are doomed to lose the race !

  35. Does anyone have any idea as to how badly this could go wrong what it's not like we can kill off the screw up experiments because of Human Rights we're playing God too much this could be a big step in weakening mankind for the rest of our existence

  36. They have native to the body REDOX signaling molecules that are doing that with out your scary machine and crazy splicing and tearing of dna

  37. Concerned with the quality of the food products you eat daily? Meet the independent companies and people who are changing the entire agricultural paradigm by creating a first of its kind platform for food consumers to directly communicate with independent food producers, we are working on naturally breeding higher nutritional value, healthier crops as many of these crops are key ingredients for many of the food supplies you eat every day! its an exiting time in agriculture, come join the discussion and let the next generation of farmers and food producers know what food products and what labels you want on your food products on the shelf at the grocery store. These people are committed to providing you, the food consumers, with exactly what you want, through transparent production practices traceable from "farm to table" and every step in between! Imagine eating with confidence that you are feeding your family with only the very best quality. The first real discussion on a standardized food labeling program that is in its infancy of being put together by a group of independent companies and people right now, we need your input and feedback. The next generation of farmers and those involved in AG are waking up to the realization that it is out job to provide the customer (food consumers) with what products they want! tell us what you want, how you want it grown and we will customize a food production portfolio or plan for you no matter how big or small the request we are fulfilling the next evolution in true "farm to table" sourced foods, complete with a totally transparent food label, Come check this out! CRISPR is the proliferation of a better, simpler technology for gene editing, available to everyone CRISPR will render the large GMO companies obsolete! we have seen first hand the corrosive effective allowing large corporations to own and patent genomes to living organisms

  38. This is the smart girl from your group project for science class in 8th grade. I would take a moment to think about where this could lead. Just an fyi, the actual, i guess per "treatment" cost is like 0.02 cents (U.S.). This will be all over the dark web shipped all around the world, and could make us loose the chance to type "F" when it really matters.

  39. this manipulation is great only if they can remove the DNA errors to cure diseases. But not to try to create a perfect human

  40. Oh please…..stop with the Ethics BULLSHIT…..If I cannot get cancer-cured in the UK because CRISPR is totally outlawed in the EU, I will then fly to the US to get it done……If in the USA I cannot genetically alter my sperm and the wife's oocytes to prevent the child from having breast cancer (if she's a girl) which has killed many women in her family or Parkinson's, which has done the same to all the elderly on my side of the Family, I'll go to Russia to have this done…..If I cannot choose the type of child I want to have, tall, smart, strong, good looking…..I'LL GO TO CHINA! DUH!
    Because somebody, somewhere will do what can be done, when others don't. And then a Government like China could make it a law that all children will be 'CRISPRized', giving China full dominion over the World, which will mean that the rest of the World will be "F###ED"…..The other side of the equation is Quantum Computing, which China is currently investing the most as a Government.

  41. Its well known that plants help take air pollution out of the atmosphere. What if they created a super tree that is genetically engineered to absorb 10x more air pollution? Thar can help take care of global warming.

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