Why CRISPR Gene Editing Gives Its Creator Nightmares
Has CRISPR co-creator Jennifer Doudna invented the Pandora's Box of genetic engineering, or can CRISPR be used for the forces of good?
Jennifer A. Doudna, Ph.D., Professor of Molecular and Cell Biology and Chemistry at the University of California, Berkeley, has devoted her scientific career to revealing the secret life of RNA. Using structural biology and biochemistry, Doudna's work deciphering the molecular structure of RNA enzymes (ribozymes) and other functional RNAs has shown how these seemingly simple molecules can carry out the complex functions of proteins.
Doudna is a pioneer of the revolutionary CRISPR/Cas9 gene-editing technology. Working with microbiologist Emmanuelle Charpentier, postdoctoral researcher Martin Jinek and graduate student Krysztof Chylinski, the team published their findings in Science in August 2012. Their paper immediately and dramatically transformed the field of molecular biology and genetics. Since then, Doudna and other scientists have shown that the CRISPR/Cas9 technique works in human cells, a finding with enormous implications for preventing and treating many intractable diseases, including viral illnesses, such as HIV, and genetic conditions, such as Down syndrome and sickle cell anemia.
Jennifer Doudna is the author of A Crack in Creation: Gene-Editing and the Unthinkable Power to Control Evolution.
JENNIFER DOUDNA: Well, CRISPR is an acronym that actually represents a sequence of DNA letters in the genomes themselves. It is found in bacteria and it was interesting to scientists originally because it's a bacterial immune system, a way that bacteria can fight viral infection. But the CRISPR acronym has now become widespread in the media as an indication of a new technology for gene editing. And the story of how an adaptive immune system and bacteria was harnessed as a technology for gene editing is really part of what A Crack in Creation is about.
So the CRISPR gene editing technology is a tool that scientists can use to change the letters of DNA in cells in precise ways. So I like to use the analogy of a word processor on our computer. So we have a document, you can think about the DNA in a cell like the text of a document that has the instructions to tell the cell how to grow and divide and become a brain cell or a liver cell or develop into an entire organism. And just like in a document the CRISPR technology gives scientists a way to go in and edit the letters of DNA just like we might cut and paste text in our document or replace whole sentences even whole paragraphs or chapters. We can now do that using the CRISPR technology in the DNA of cells.
So, we think about a technology that allows precise changes to DNA to be made, for scientists this is sort of really a gift that allows research to proceed very quickly in terms of understanding the genetics of cells and organisms, but also provides a very practical way to solve problems. There's many that we could discuss, but I'll mention a couple that I think are particularly exciting.
So in clinical medicine, the opportunity to make changes to blood cells that would cure diseases like Sickle Cell Anemia disease, where we've understood the genetic cause or for a long time but until now there hasn't been a way to actually think about treating patients. And now with this technology it's possible, in principle, to remove stem cells that give rise to blood cells in a person's body, make edits to those cells that would correct the mutation causing Sickle cell disease and then replace those cells to essentially give a patient a new set of cells that don't have the defect. So I think that's very exciting, and there are multiple research groups right now working on doing just that. So I think that's a future probably sometime in the next two to five years we will see clinical trials in that area, and we hope a real progress toward curing that disease.
But another example that I think is also potentially very impactful clinically—but it has a very different kind of strategy—is the idea of making edits to pigs to create animals that are going to be better organ donors for humans. And so pigs are already of interest for organ donation, but imagine that we could make edits to the DNA of pigs to make their organs more human like and also to remove any viruses from pig cells that might otherwise infect a patient and those are both things that are actively underway using the CRISPR technology.
And then a third area that I think is interesting to think about from the perspective of global impact in disease is thinking about using gene editing not to change the DNA in people, per se, but actually to effect the kinds of insects that transmit disease to people. And the idea here is that one could use a gene editor to create mosquitoes that would be unable to transmit viruses like a dengue virus or Zika virus by using a technique called gene drive that allows traits to be spread very quickly through a population using an efficient way of gene editing such as the CRISPR tool. And I think that's an opportunity that could have a very big impact in terms of global health but also requires obviously some very thorough vetting and discussion about potential environmental impact.
I think one of the aspects of this technology that's been very interesting to me personally is my own kind of personal growth through the last few years.
I think when I started this research project, which actually began now almost ten years ago in the lab, we were certainly not thinking about technology that would allow alteration of human evolution or anything of that nature. And over the last few years as this technology has begun to be deployed globally for different applications I found that I've gone from thinking about it initially just with sort of almost wide-eyed excitement thinking about all the opportunities that this offers to realizing that there was real risk and that we really needed—“we” meaning the scientific community and really frankly the human community—needed to be aware of this and discussing it.
And one of the things that sort of brought that to the forefront of my mind was a dream that I had fairly early on in which I walked into a room and a colleague of mine said to me, "Jennifer I'd like you to explain the CRISPR technology to a friend."
And he brought me into a room, and a person was sitting with their back to me and as they turned around I realized it was sort of a horror that it was Hitler, and it was actually Hitler with sort of a pig nose and it almost looked like a chimeric pig human sort of creature.
And it sounds funny in a way to relate that image, but in the dream it was a terrifying thing, and I really felt real just stone-cold fear in the dream and sort of woke up from that dream with a start and realized this initial feeling of “what have I done?!”
And that was really one of the things that motivated me to get out of the lab and start talking to people more broadly about the technology, about its capabilities, about the great things about it but also about things that really required really deep thought and careful consideration and regulation.
Jennifer Doudna was a pioneer of CRISPR, which is a gene-editing technology that is being increasingly studied and used across the world. Jennifer relates the genesis of CRISPR to us and explains the pros and cons of giving birth to such a potentially world changing process. On the positive side, she tells us how scientists are already combining her technology with stem cell research to potentially rid the world of sickle cell anemia. On the negative side, she describes a vivid nightmare she had early on in the process wherein she meets Hitler with a pig nose—a David Lynch-ian vision that represents the negative possibilities of what could happen if CRISPR falls into the wrong hands. While the Pig Hitler scenario is a lot less likely to actually happen, Jennifer understands the duality of her role in CRISPR's creation.
Jennifer Doudna's most recent book is A Crack in Creation Gene Editing and the Unthinkable Power to Control Evolution.
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