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.
It's just the current cycle that involves opiates, but methamphetamine, cocaine, and others have caused the trajectory of overdoses to head the same direction
- It appears that overdoses are increasing exponentially, no matter the drug itself
- If the study bears out, it means that even reducing opiates will not slow the trajectory.
- The causes of these trends remain obscure, but near the end of the write-up about the study, a hint might be apparent
Through computationally intensive computer simulations, researchers have discovered that "nuclear pasta," found in the crusts of neutron stars, is the strongest material in the universe.
- The strongest material in the universe may be the whimsically named "nuclear pasta."
- You can find this substance in the crust of neutron stars.
- This amazing material is super-dense, and is 10 billion times harder to break than steel.
Superman is known as the "Man of Steel" for his strength and indestructibility. But the discovery of a new material that's 10 billion times harder to break than steel begs the question—is it time for a new superhero known as "Nuclear Pasta"? That's the name of the substance that a team of researchers thinks is the strongest known material in the universe.
Unlike humans, when stars reach a certain age, they do not just wither and die, but they explode, collapsing into a mass of neurons. The resulting space entity, known as a neutron star, is incredibly dense. So much so that previous research showed that the surface of a such a star would feature amazingly strong material. The new research, which involved the largest-ever computer simulations of a neutron star's crust, proposes that "nuclear pasta," the material just under the surface, is actually stronger.
The competition between forces from protons and neutrons inside a neutron star create super-dense shapes that look like long cylinders or flat planes, referred to as "spaghetti" and "lasagna," respectively. That's also where we get the overall name of nuclear pasta.
Caplan & Horowitz/arXiv
Diagrams illustrating the different types of so-called nuclear pasta.
The researchers' computer simulations needed 2 million hours of processor time before completion, which would be, according to a press release from McGill University, "the equivalent of 250 years on a laptop with a single good GPU." Fortunately, the researchers had access to a supercomputer, although it still took a couple of years. The scientists' simulations consisted of stretching and deforming the nuclear pasta to see how it behaved and what it would take to break it.
While they were able to discover just how strong nuclear pasta seems to be, no one is holding their breath that we'll be sending out missions to mine this substance any time soon. Instead, the discovery has other significant applications.
One of the study's co-authors, Matthew Caplan, a postdoctoral research fellow at McGill University, said the neutron stars would be "a hundred trillion times denser than anything on earth." Understanding what's inside them would be valuable for astronomers because now only the outer layer of such starts can be observed.
"A lot of interesting physics is going on here under extreme conditions and so understanding the physical properties of a neutron star is a way for scientists to test their theories and models," Caplan added. "With this result, many problems need to be revisited. How large a mountain can you build on a neutron star before the crust breaks and it collapses? What will it look like? And most importantly, how can astronomers observe it?"
Another possibility worth studying is that, due to its instability, nuclear pasta might generate gravitational waves. It may be possible to observe them at some point here on Earth by utilizing very sensitive equipment.
The team of scientists also included A. S. Schneider from California Institute of Technology and C. J. Horowitz from Indiana University.
Check out the study "The elasticity of nuclear pasta," published in Physical Review Letters.
Scientists think constructing a miles-long wall along an ice shelf in Antarctica could help protect the world's largest glacier from melting.
- Rising ocean levels are a serious threat to coastal regions around the globe.
- Scientists have proposed large-scale geoengineering projects that would prevent ice shelves from melting.
- The most successful solution proposed would be a miles-long, incredibly tall underwater wall at the edge of the ice shelves.
The world's oceans will rise significantly over the next century if the massive ice shelves connected to Antarctica begin to fail as a result of global warming.
To prevent or hold off such a catastrophe, a team of scientists recently proposed a radical plan: build underwater walls that would either support the ice or protect it from warm waters.
In a paper published in The Cryosphere, Michael Wolovick and John Moore from Princeton and the Beijing Normal University, respectively, outlined several "targeted geoengineering" solutions that could help prevent the melting of western Antarctica's Florida-sized Thwaites Glacier, whose melting waters are projected to be the largest source of sea-level rise in the foreseeable future.
An "unthinkable" engineering project
"If [glacial geoengineering] works there then we would expect it to work on less challenging glaciers as well," the authors wrote in the study.
One approach involves using sand or gravel to build artificial mounds on the seafloor that would help support the glacier and hopefully allow it to regrow. In another strategy, an underwater wall would be built to prevent warm waters from eating away at the glacier's base.
The most effective design, according to the team's computer simulations, would be a miles-long and very tall wall, or "artificial sill," that serves as a "continuous barrier" across the length of the glacier, providing it both physical support and protection from warm waters. Although the study authors suggested this option is currently beyond any engineering feat humans have attempted, it was shown to be the most effective solution in preventing the glacier from collapsing.
Source: Wolovick et al.
An example of the proposed geoengineering project. By blocking off the warm water that would otherwise eat away at the glacier's base, further sea level rise might be preventable.
But other, more feasible options could also be effective. For example, building a smaller wall that blocks about 50% of warm water from reaching the glacier would have about a 70% chance of preventing a runaway collapse, while constructing a series of isolated, 1,000-foot-tall columns on the seafloor as supports had about a 30% chance of success.
Still, the authors note that the frigid waters of the Antarctica present unprecedently challenging conditions for such an ambitious geoengineering project. They were also sure to caution that their encouraging results shouldn't be seen as reasons to neglect other measures that would cut global emissions or otherwise combat climate change.
"There are dishonest elements of society that will try to use our research to argue against the necessity of emissions' reductions. Our research does not in any way support that interpretation," they wrote.
"The more carbon we emit, the less likely it becomes that the ice sheets will survive in the long term at anything close to their present volume."
A 2015 report from the National Academies of Sciences, Engineering, and Medicine illustrates the potentially devastating effects of ice-shelf melting in western Antarctica.
"As the oceans and atmosphere warm, melting of ice shelves in key areas around the edges of the Antarctic ice sheet could trigger a runaway collapse process known as Marine Ice Sheet Instability. If this were to occur, the collapse of the West Antarctic Ice Sheet (WAIS) could potentially contribute 2 to 4 meters (6.5 to 13 feet) of global sea level rise within just a few centuries."
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