Sam Sternberg: How Will 'Cut And Paste' Technology Rewrite Our DNA? Biochemist Sam Sternberg describes how recent developments in gene editing technology may help end many diseases and even control our own evolution.
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How Will 'Cut And Paste' Technology Rewrite Our DNA?

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How Will 'Cut And Paste' Technology Rewrite Our DNA?

How Will 'Cut And Paste' Technology Rewrite Our DNA?

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GUY RAZ, HOST:

It's the TED Radio Hour from NPR. I'm Guy Raz. So imagine a big, thick book about the size of a dictionary. And inside that book, each and every page filled with just four letters...

SAM STERNBERG: Just four letters.

RAZ: ...Printed over and over - A, G, C and T.

STERNBERG: That's right - four letters of DNA.

RAZ: DNA...

STERNBERG: The same four letters that every species on the planet has.

RAZ: ...Is made up of four letters, each representing a chemical compound, arranged in just such a way to make you you.

STERNBERG: This is really where the information comes from - is not the four letters, but exactly how they're connected to each other. So is it AGCT or AAAG or AACT or AAAT?

RAZ: This, by the way, is Sam Sternberg.

STERNBERG: I study gene editing technology.

RAZ: And Sam says if you printed up all of the A's and G's and C's and T's it takes to complete your entire genetic code - which, by the way, is a lot of letters...

STERNBERG: The genome is 3.2 or so billion letters of DNA.

RAZ: ...You would have a lot of pages.

STERNBERG: If you had every page filled with A's, G's, C's and T's you'd have 800 dictionaries' worth of genetic code, something like that.

RAZ: For one person?

STERNBERG: For one person.

RAZ: So could you say that everything about us - our physical traits, the color of our eyes, our characteristics, our personality traits - come from four chemicals?

STERNBERG: I would say that.

RAZ: Wow.

STERNBERG: And essentially all the information to turn a single fertilized egg cell into an adult human is contained within that singular genome.

RAZ: Now, here's what's really crazy. Sixty years ago, we didn't even know what the genome was. The answer to the question what is life was a mystery.

(SOUNDBITE OF TED TALK)

JAMES WATSON: And that, of course, has been a question I wanted to know. You know, Darwin explained life after it got started, but what was the essence of life?

RAZ: What was the essence of life? That was the question answered by James Watson, who spoke about it on the TED stage.

(SOUNDBITE OF TED TALK)

WATSON: And...

RAZ: And Watson, along with his partner, Francis Crick, discovered the essence of who we are.

(SOUNDBITE OF TED TALK)

WATSON: Well, we got the answer on the 28th of February '53.

RAZ: That was when Watson and Crick discovered the hidden language of DNA.

(SOUNDBITE OF TED TALK)

WATSON: You know, if you just put A next to T and G next to C, you have a copying mechanism. So we saw how genetic information is carried, and it's the order of the four bases.

RAZ: Watson and Crick's discovery helped us eventually to figure out how those four letters added up to 800 dictionaries for one human, which led to another huge milestone on the journey to understanding who we are.

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED MAN: Earlier today at the White House, President Clinton announced the completion of the mapping of the human genome.

RAZ: This was in June of 2000.

(SOUNDBITE OF ARCHIVED RECORDING)

BILL CLINTON: More than a thousand researchers across six nations have revealed nearly all 3 billion letters of our miraculous genetic code. I congratulate all of you on this stunning and humbling achievement.

RAZ: And with the mapping of the human genome, we now had our greatest understanding yet of those 800 dictionaries and how all of the information in them adds up to a person.

(SOUNDBITE OF ARCHIVED RECORDING)

CLINTON: With this profound new knowledge, humankind is on the verge of gaining immense new power to heal. Genome science will have a real impact on all our lives and even more on the lives of our children.

RAZ: And so now years on, the next big thing is almost here.

STERNBERG: Back then, we - you know, the government spent $3 billion to get that first genome sequenced. And now we're talking about companies that are offering your complete genome for just $1,000.

RAZ: Wow.

STERNBERG: And so I think we're going to continue to see our knowledge relating those four letters back to various traits increase in the coming years.

RAZ: What this means is that scientists are now closing in on the day when they'll be able to easily access the 3 billion letters of code that make you you and then isolate, even change a particular chain of letters responsible for certain diseases or even certain physical or personality traits.

STERNBERG: There are many diseases whose genetic causes have been pinpointed precisely. The most common genetic diseases - cystic fibrosis, sickle cell anemia, Huntington's disease - we've known about those, you know, since the '80s and '90s.

RAZ: And presumably, we can pinpoint things that aren't diseases at all.

STERNBERG: Sure. To the shape of our noses...

RAZ: Yeah.

STERNBERG: ...There was a recent paper that was published, 23andMe just released a study defining the associations between gene variants and whether or not you're a morning person.

RAZ: Wow.

STERNBERG: So we're talking about the kinds of things that...

RAZ: Wow.

STERNBERG: ...You chat about at the water cooler or on your way to get a coffee. And we're beginning to understand the DNA sequences that can explain those behaviors. It's pretty mind-boggling.

RAZ: Who we are, what makes us us - it's one of the oldest questions out there. But new technology means we've never been closer to answering it in all kinds of ways that would've been unthinkable just a few years ago. So today on the show, ideas from science, psychology and philosophy about why we are who we are.

RAZ: So Sam Sternberg worked in the lab that developed one of the most groundbreaking innovations in gene editing. You may have heard of it. It's called CRISPR. And Sam described why it's such a big deal on the TED stage.

(SOUNDBITE OF TED TALK)

STERNBERG: We've known for over half a century that DNA contains the blueprints to make all living things. The genome can tell us a lot about ourselves, about our ancestry, our traits and our disease susceptibilities. But there are things in the genome that you might not want to find out. For example, with two misspelled versions of a gene called APOE4, your chance of developing Alzheimer's disease is more than 10 times above average. And with a single diseased copy of the Huntington gene, you're virtually guaranteed Huntington's disease, a devastating form of neurodegeneration. And in both of these cases, there aren't currently any effective prevention or treatment options.

And so this leaves many wondering, is this information even worth knowing? Well, what if we could do more than just learn that information by reading the genome but actually rewrite the genome to cure genetic diseases at their source? What if editing the letters of DNA were as simple and easy as fixing typos in Microsoft Word? This is no longer science fiction, thanks to a new tool called CRISPR-Cas9.

In the last three years, scientists have delivered CRISPR-Cas9 to human cells and precisely fixed the genetic mutations that cause cystic fibrosis, sickle cell anemia, muscular dystrophy and Huntington's disease. Genome editing in animals and cells is teaching us more about how cancers progress and revealing promising new drug targets. And companies have already raised almost a billion dollars to apply CRISPR-Cas9 as a therapy in patients.

The CRISPR-Cas9 technology was co-invented in my Ph.D. lab at the University of California, Berkeley. And many consider it to be one of the biggest breakthroughs of the last couple decades. But five years ago, when I started my Ph.D. with Jennifer Doudna, CRISPR wasn't a technology at all.

(SOUNDBITE OF MUSIC)

RAZ: I mean, so you're saying this technology didn't even exist five years ago. I mean, how fast has this become a huge deal?

STERNBERG: So when I started my Ph.D. in Jennifer's lab, that was 2010. You wouldn't find a single mention of CRISPR in, you know, the lay media unless it was talking about a vegetable crisper. But in the scientific literature, we're really talking a few dozen articles. So it was about maybe one a month was coming out. We now are at a point today where every day we have around five or 10 articles being published. I think you won't - will not find a biologist in the world that doesn't know about CRISPR. And you probably won't find many left that aren't actively using CRISPR...

RAZ: Wow.

STERNBERG: ...To study whatever biological question they go after in their laboratories because ultimately we're interested in understanding how life works. And if we know that DNA encodes life, then what better than a tool to rewrite that DNA and study what the effects are.

(SOUNDBITE OF MUSIC)

RAZ: OK. The technical details of how CRISPR-Cas9 works are complicated. CRISPR, for instance, is an acronym for clustered regularly interspaced short palindromic repeats. And Cas9 is the key protein that makes it all work. But what you need to know is that CRISPR/Cas9 makes it easy and relatively inexpensive to edit genes in precise ways - any genes in any living thing from bacteria to people.

STERNBERG: You know, coming back to the four letters of DNA, think about those 800 dictionaries filled with the same four letters. And now imagine that you have to search for a single page, and not just single page but a single letter on that page and mark that site for a change. And maybe not any change but an A to a T, not an A to a G or an A to a C. So for decades, this was the kind of pie-in-the-sky science fiction idea that we could dream about doing, but no one was going to be able to do it because it just seemed like it would never be possible.

RAZ: So - but now with CRISPR, basically you can just go into the body, find that chain of letters causing a disease or something and then just cut out one or two letters and replace it with the right letter?

STERNBERG: Absolutely. That's exactly what it does. And I'll just add one caveat. It's not been demonstrated yet in human patients. So if you had just said the same thing for human cells in a petri dish, absolutely. With human patients comes the additional challenge of getting to the right cells. And that's the same challenge that every drug has to contend with, this issue of delivery. And now it's just a matter of figuring out how to do that inside patients.

(SOUNDBITE OF TED TALK)

STERNBERG: Now, the next frontier will be really using this tool to improve human health. Can we achieve this ultimate goal of curing a genetic disease at its source at the level of DNA instead of just treating the downstream symptoms? Imagine a future in which we use stem cell technology together with CRISPR-Cas9 to remove diseased cells from a patient, repair them in the lab and then transplant those corrected cells back into the body. Clinical trials are already underway that offer a cure for HIV/AIDS by editing the DNA in blood cells taken from HIV positive patients. And I expect we're going to see more and more clinical trials with CRISPR entering the pipeline in the next few years.

What really got folks speaking this past year was the report in May that, for the first time ever, scientists used CRISPR-Cas9 to edit the DNA in human embryos. And unlike therapy in adult patients, this would introduce heritable changes that could be passed on to subsequent generations. You can imagine the controversy that this has provoked. And many fear that this technology could be abused, that it would usher in an era of eugenics where designer babies where a select few could pick and choose the best genes for their offspring.

Others would say if we deny unborn children a technology that could ease human suffering or eradicate a disease, it would be immoral. CRISPR-Cas9 is forcing us to rethink what kind of world we want to live in. And there are weighty ethical issues to discuss about how we should use this technology and how it should be regulated.

(SOUNDBITE OF MUSIC)

RAZ: That's Sam Sternberg. When we come back in just a minute, a little more about how gene editing could change who we are and how we should feel about that. On the show today, ideas about what makes us us. I'm Guy Raz. And you're listening to the TED RADIO HOUR from NPR.

It's the TED Radio Hour from NPR. I'm Guy Raz. And on the show today - ideas about who we are, what makes us us. And we've been talking to biochemist Sam Sternberg, who's been explaining how a new gene editing technology called CRISPR-Cas9 could make it cheap and easy to create humans who are - you're basically talking, like, superheroes - right? - like, perfect vision, superhuman strength, perfect SAT scores...

STERNBERG: That's the...

RAZ: ...Right? Sorry.

STERNBERG: That's the - yeah, yeah. I think that's the science fictionalization of what CRISPR could allow. We have long lists of gene variants associated with certain traits. And some of those are silly, like whether or not you're a morning person.

But we also have long lists of gene variants that are associated with things that might be desirable, like having extra-strong bones or leaner muscles or lower sensitivity to pain or lower risk of coronary heart disease. And as those lists continue to grow, we now have a technology that could, in theory, allow an individual to upgrade their genome.

RAZ: But why would that be the science fiction version, if it seems like the technology is so promising? Like, if there was a, you know, way to make a child more resilient to pain or give us all higher IQs, you can imagine that people would want to take advantage of all those things, right?

STERNBERG: I think they will. I think the challenge, then, is to think about how we can ensure that that technology, if it becomes available, is used safely - because we're certainly not there yet - but also, I think, equitably. There's a great example in the world of HIV/AIDS.

So it turns out 1 to 2 percent of all humans have a specific genetic mutation that is associated with HIV immunity because this gene variant they have essentially masks their cells. And the HIV virus can't get inside. So what if you now delivered it into a fertilized egg cell - into a human embryo - so that that future child, even though neither of his or her parents have that mutation, will still have HIV immunity?

We might assume - of course they would want that. But it's still a game-changing idea that we would be able to make those decisions and not just select the traits they'll inherit from the parents - something we can already do with IVF and genetic testing - but kind of installing new variants into their genome that they would never have gotten from their parents.

RAZ: It's like a pre-emptive solution for something that may never come to fruition. Like, we are just saying, hey, just in case, we're going to give you immunity against this thing that you may or may not ever need.

STERNBERG: Absolutely. So do you consider that an enhancement? Or is that disease prevention? - 'cause, you know, many people see - they divide DNA rewriting or gene editing into kind of two different categories, one being disease prevention and one being genetic enhancement. But I think there are many that fall right smack dab in the middle.

So yeah, with this HIV immunity gene, CCR5, that's disease prevention. But it's preventing a disease that you may never get. So in a way, it's kind of conferring a genetic advantage. And I'll just state again - that's a gene variant that exists naturally but only 1 to 2 percent of humans have.

RAZ: Yeah.

STERNBERG: So it's clearly giving you an advantage above what we might call normal human species functioning.

RAZ: Right. But I mean, a part of me wonders. Should we be doing that? You know what I mean? Like, there's a process that just kind of has sort of happened since the beginning of human evolution. And we would completely be upending that.

STERNBERG: That's certainly one way of looking at it. And yet, evolution is inherently cruel. For someone that has a genetic disease, that's kind of a crummy hand that they've been dealt. So I think this comes down to the question of - how sacred is the genome? And is it something that should remain untouched, untainted, left alone?

Of course, what we do in any one patient - that's a lifesaver for that patient. But when you think about human evolution over the course of hundreds or thousands of years, now we're talking about a technology that will not only affect that individual but that individual's children and their children and their children and their children.

And so that's where I think you have this very weighty issue of directing future evolution. You know, even saying that sounds hyperbolic - it sounds like science fiction. But I think the technology will get to a point where you could use it in embryos to install things like HIV immunity or stronger muscles and maybe someday, gene variants associated with higher IQ or being a morning person, if that's what you'd like to be. That's where things really take off.

(SOUNDBITE OF MUSIC)

RAZ: Sam Sternberg is working on a book about all this. It's called "A Crack In Creation: Gene Editing And The Unthinkable Power To Control Evolution." You can check out his TED Talk at ted.com.

(SOUNDBITE OF MUSIC)

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