The Road To CRISPR

17:10 minutes

These days, if there’s a conversation about gene editing, it often centers on the CRISPR technique. CRISPR allows researchers to quickly edit DNA more easily than any tool in the past. Labs worldwide are using CRISPR in a variety of research, including in efforts to improve crop breeding, and in the development of treatments for diseases like cancer and Parkinson’s.

But CRISPR as a gene-editing tool is still a new idea. In 2012, biochemist Jennifer Doudna and her colleagues first described the CRISPR-Cas9 technique in a study published in Nature.

[Just how easy is it to edit DNA?]

Doudna, co-author of “A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution,” discusses how her research into bacterial immune systems led to the revolutionary gene-editing technology. She also discusses the ethical questions that come up when using such a powerful tool.

[Read an excerpt from Jennifer Doudna’s book, A Crack in Creation.]

Segment Guests

Jennifer Doudna

Jennifer Doudna is co-author of A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution (Houghton Mifflin Harcourt, 2017). She’s an investigator with the Howard Hughes Medical Institute and a professor of Chemistry and Molecular and Cell Biology at the University of California, Berkeley.

Segment Transcript

IRA FLATOW: This is Science Friday. I’m Ira Flatow. These days if there’s a conversation about gene editing, it’s usually talking about CRISPR. The technique has become synonymous with gene editing. CRISPR allows scientists to easily cut and replace DNA sequences– a trick they learned from studying bacteria and how they fight off viruses.

Labs around the world are using CRISPR to investigate everything from creating better growing crops to developing treatments for diseases like cancer and Parkinson’s to editing out the genes for diseases in embryos. CRISPR as a tool has only been around since 2012. That’s like five years. And along with opening up the science, CRISPR has brought up questions about the ethics of how we should use such a powerful tool. Like how much hacking of the human genome would be wise? How is CRISPR developed? What therapeutic uses are the most promising? And how much do we really know about how it works? And where do we draw the ethical lines?

My next guest was one of the authors on that original study published in 2012 that described the CRISPR Cas9 system, as it’s known formally. And she’s one of the main pioneers of CRISPR. She’s here to give us her take. And here with a new book, Jennifer Doudna is professor of chemistry and molecular and cell biology, UC, Berkeley. She’s also co-author of A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. She joins us by Skype. Welcome to Science Friday.

JENNIFER DOUDNA: Hello, Ira. Great to be here.

IRA FLATOW: Nice to have you. Tell us why CRISPR is so much easier to use than the editing tools we’ve already had. Give us a quick idea– how it works. What makes it unique?

JENNIFER DOUDNA: Well, you can think about it almost like a pair of scissors for DNA in the cell. And the great thing about this tool is that it’s programmable. So scientists can directly tell the scissors where to go in the cell, which piece of DNA to cut, and can do that relatively inexpensively and quickly. So it’s become a very widespread technology for altering the DNA and virtually all types of cells.

IRA FLATOW: You’ve had sort of an evolving feeling about the use of CRISPR. Have you not?

JENNIFER DOUDNA: Very much so, yes. We discuss that in A Crack in Creation, our book. It’s a book co-written with a former graduate student of mine, Sam Sternberg. And we wanted to write about personal reflections on the developments of this field and my own evolving thoughts about this technology. Of course I’m an optimist. I’m very excited about the potential for this to do great things in the future. But I think it’s a powerful tool that really requires careful thought about its use in various settings.

IRA FLATOW: Now I want to get into that. Let me give out our number first– 844-724-8255– for people who would like to talk about this. You can also tweet us @scifri. let’s go back a little bit in time. The first time you heard about CRISPR, you heard it from a geomicrobiologist Jillian Banfield.

JENNIFER DOUDNA: That’s right.

IRA FLATOW: What was the overlap there that brought you two together?

JENNIFER DOUDNA: Well, this is one of the great things about being at a university like University of California, Berkeley, where I work. It’s a place that has a fantastic group of people working on all sorts of interesting problems.

And Jillian Banfield’s lab has long studied natural microbes in their environmental settings. And her research had uncovered many examples of the sequences in DNA that we refer to as CRISPRs. This was back before it was clear what they did biologically. But she had an inkling that they might be working as some sort of adaptive immune system– an idea that a few other scientists had been floating around in the scientific literature at the time. And so she contacted me as a biochemist to see if we might like to investigate this and figure out how these systems might work.

IRA FLATOW: So the CRISPR actually was sort of invented by bacteria to fend off viruses. And you guys figured out how to use it to edit genomes.

JENNIFER DOUDNA: It’s a great story of how curiosity driven research aimed in one direction ended up uncovering something that could be employed in a completely different way. I think that the way that bacteria can program proteins to cut viral DNA and protect themselves from viral infection was the original work that we were doing. And this was a project– international collaboration with Emmanuelle Charpentier and her laboratory. And that uncovered the mechanism that we realized could be employed in a very different way, namely for gene editing.

IRA FLATOW: And it moved pretty quickly, this idea. It went right into the gene editing community, did it not?

JENNIFER DOUDNA: It did. And I think this really speaks to the way technology’s come along– and there’s a very important timing aspect to technologies. And I would say that’s true for gene editing. It was a tool that was very much– the scientific community was ready for. We needed a way to manipulate DNA and cells given all of the DNA sequencing that’s going on now, and whole genomes being sequenced, and more and more information about the content of genomes. And what was missing was a way to rewrite them, a way to manipulate that information. And when that tool became available, as you pointed out, it was very quickly adopted globally.

IRA FLATOW: In your book– in case you’ve just joined us, we’re talking with Jennifer Doudna about A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. The title itself– Unthinkable Power to Control Evolution– implies– and you say so as much in your book– is that we are now in a stage of human evolution when we can control human evolution. Is that not a fear and awe inspiring thought?

JENNIFER DOUDNA: Well, it certainly is for me. I think the understanding that we now as human beings can control the DNA that makes us who we are, and change it in the future, and change the DNA of other organisms in our environment in same way, it’s really a profound thing to think about. And I think it really opens up both opportunities and risks.

IRA FLATOW: Yeah, you say that– I’m going to quote from your book. “That we are unprepared for such colossal responsibility, I have no doubt. But we cannot avoid it. If controlling our genetic destiny is a terrifying thought then consider the consequences of having this power but not managing to control it. That would be truly terrifying, truly unthinkable.”


IRA FLATOW: So you’re basically saying– people talk about the ethical responsibilities of using it correctly or making sure we don’t use it incorrectly. But on the other hand, there’s also the ethical choice of having such a powerful tool to cure people with debilitating genetic diseases and not using it.

JENNIFER DOUDNA: That’s right. I think it’s an interesting situation where we have this tool and we as the scientific community can begin to see how it could be used for incredible things like curing what were previously incurable genetic diseases. This would be an amazing thing to be able to do. At the same time, it’s also a technology that enables making heritable changes to the human germline, that means making changes to DNA that could be inherited by future generations.

IRA FLATOW: In your book, you also talk about CRISPR– at least the original version of it– found that bacteria is not an entirely error free method of targeting and cutting DNA. And there was a study out last week in Nature Methods that found thousands of off target mutations in mice that seem to say, you know, wait a minute. CRISPR may not be as benign as we think it might be in creating these mutations. What’s your feeling about those studies?

JENNIFER DOUDNA: Well, I certainly think that the general question of how accurate is this technology is a very important one especially when we think about using it in human beings. I can say that from the large number of studies that have been done prior to this work that you just cited that appeared in the literature last week, there’s been a lot of evidence that this is actually quite a remarkably good technology in terms of accuracy. It’s not perfect, nothing is. But I think it’s really quite good at finding the correct DNA sequence– the desired sequence– and making a change.

Now, the study that you pointed out last week, I think has some serious issues associated with it. Anybody interested in this can Google this and you’ll find there’s a lot of blogging and tweeting going on about it because I think in the scientific community, there’s a feeling that first of all, if you look at the way the animals that they worked with were generated– they were generated using a very unconventional use of the CRISPR technology that might itself have been inclined to induce undesired DNA changes.

Also I think it’s interesting that they published the work in a non-peer reviewed fashion. So you have to ask yourself why would they want to do that especially with something potentially as explosive and important as this. And if you look at the statistics in the paper, I think there’s some serious questions about the way they did the study.

So I can’t really say we can draw any conclusions or maybe any conclusions from those data. I think it just is a reminder that we need to continue to evaluate this technology going forward.

IRA FLATOW: Chinese scientists have already conducted studies on embryos using CRISPR. Can we create a global consensus on where to draw the line? Or should we be doing that? Should we just let the scientists do what they think is right?

JENNIFER DOUDNA: I think we have to try to create a global consensus. I’ve been a very active proponent of this. We had a first meeting that was organized by a group I’m involved in in the Bay Area called the Innovative Genomics Institute that organized a meeting in early 2015 to discuss this question. And since then, there now have been multiple meetings, including in Washington at the end of 2015 sponsored by the National Academies of Science in the US, UK and China to really figure out can we come together as a scientific community and make some recommendations and also have some agreements about how we will and won’t use this technology?

And I think that’s been a productive thing. I think it’s very hard to think about putting regulations in place globally. How would you enforce such things? I think it’s very hard. But I think having a group of scientists who are highly respected, who have deeply evaluated this technology and come together to make a statement is powerful.

IRA FLATOW: Let me go to the phones– 844-724-8255. Let’s go to Jim in Decatur, Georgia. Hi, Jim.

JIM: Hi. I have a son who has a chromosome gap on “chrom” 10. For your research, what is the likelihood of effective treatment for those specific, that have gaps in chromosome sequences?

JENNIFER DOUDNA: Well, hi, Jim. Thanks for calling in. I think what we’re finding right now with the technology is that it’s a lot easier to remove DNA sequences than to replace them or insert new ones. That’s very much at the cutting edge of the technology. And I’m very optimistic in the future about the potential to do that. But I think right now that’s still an area of very active development in the field.

IRA FLATOW: And in your book, you write about the possibilities of gene editing through the story of a patient named Kim who had hereditary disease just disappear. It’s interesting.

JENNIFER DOUDNA: Yeah, that’s right. That’s right. I mean, there’s some incredible stories clinically about changes that can happen in DNA. And wouldn’t it be great if someday we could do that in a very directed way?

IRA FLATOW: You actually talk about– I was very struck by you making a specific point– you talk about scientists as poor communicators to the public of the consequences and details of your work. Tell me more about this and your own evolution of your thought and understanding that scientists like yourself, if they’re going to inform– the public is going to be informed about new research– they need to get out and talk with people.

JENNIFER DOUDNA: I think it’s critical. I really speak from my own personal experience. I mean, I think it’s been very much a process for me to figure out how to talk about science and talk about the technical aspects of work that we’re doing and that other people are doing in a way that is not off putting or completely just unintelligible to non-scientists.

And I think that in general, in my own experience both as a student going through the educational system and then now as an educator, that we don’t really train our students and our colleagues to talk about our work outside of the scientific community. This needs to change because I think it’s really critical, especially now with the pace of new technologies coming along, for there to be active engagement between scientists and the rest of the world.

IRA FLATOW: I’m Ira Flatow. This is Science Friday from PRI, Public Radio International, talking with the author Jennifer A. Doudna. She was co-writer with Samuel Sternberg of A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. And I must say as you talk about communicating to the public, this is an incredibly well written and understandable book on CRISPR and just a great little reference. And you get into all the issues about CRISPR. And we get tweets– we have a couple tweets in. From Bruce Kaufman, please define the acronym CRISPR-Cas9. What does it mean?

JENNIFER DOUDNA: OK, it stands for– get ready– clusters of regularly interspaced short palindromic repeats. A big mouthful. And what does it mean? It really refers to a sequence pattern, a pattern of DNA sequences in the chromosome of that bacteria that is the hallmark of a bacterial immune system.

IRA FLATOW: Incredible. I mentioned before, the Chinese have already conducted studies on embryos. Do you doubt that there will soon be a baby born somewhere with CRISPR?

JENNIFER DOUDNA: I think it’s coming. I can’t tell you when, but I think this is something that– it’s in our future. And this is why it’s so critical right now to be grappling with all the various issues around such a thing.

IRA FLATOW: You write that the overarching takeaway from the book is quote “humans need to keep exploring through open ended scientific research.” But obviously you’re saying there should be some limits on the open mindedness of that.

JENNIFER DOUDNA: Well or at least the applications of it. I think to forge ahead without thought about the consequences of one’s work is just irresponsible.

IRA FLATOW: I remember, back at the Asilomar Conference– I remember covering that back in the 70s with Paul Berg. And you do feel like we’re at that moment now?

JENNIFER DOUDNA: Absolutely. And Paul Berg and David Baltimore, two of the scientists who were involved in those early discussions around the ethics of molecular cloning, have been incredibly helpful in thinking through the ethical challenges with gene editing.

IRA FLATOW: And so what would you like to see happen now?

JENNIFER DOUDNA: Well, of course I think that encouraging scientists and the rest of the world to embrace this technology for what it can do and to move ahead with the opportunities to use it to solve real human problems is great and should be encouraged. At the same time, I think we have to continue to have a very active discussion about appropriate use of this technology and encourage responsible activities around the world.

IRA FLATOW: Because you can get to your own home kit now– CRISPR kit, can’t you?


IRA FLATOW: All right. Well, we’ll leave it there with Jennifer Doudna, the professor of chemistry and molecular and cell biology, UC, Berkeley, co-author of a really good book– if you want some summer reading, it’s a quick read even though it’s got some nice technical stuff in it– A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. Thank you, Dr. Doudna for taking time to be with us today.

JENNIFER DOUDNA: Great to talk to you, Ira.

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