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  • 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)

A few years ago,

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