CRISPR's Greatest Hurdle Isn't Biology, But Ethics
Jennifer Doudna, the CRISPR co-creator, says that the genie of genetic engineering might be hard to put back in the bottle.
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, when we think about designer humans or “CRISPR babies” as we've seen in the media, this sparks some people's imagination to think about what one might want to do with a technology like this, maybe not today and maybe not next year but in the future.
And it's one thing to talk about being able to remove mutations from the human population that cause genetic disease—and I think for many people that would be a desirable thing to do—On the other hand I think it's a very different discussion to think about using a technology like this to create enhanced human beings, people that are taller or have a certain eye color or other kinds of physical or intellectual traits that might be considered desirable.
And it sort of immediately brings up sort of the whole area of eugenics and sort of access to technology, who gets access, who pays for it, who decies? Who decides whether or not to do such a thing? Should companies be allowed to offer this as a service to parents who want to do this so should they be regulated in some way? There's a lot of very interesting and challenging questions I think that go along with that. And then there's the whole question of, since this is a technology that is widely available—I really call it a democratizing technology because it's not very expensive to use and labs worldwide have been able to easily deploy it in different systems—So then how do we think about a global regulation?
Is it even possible to come to some kind of consensus globally? I'm not sure, honestly, of the answer to that.
I think that it's certainly important to be having this discussion with our colleagues in other countries and fortunately that's happening.
But are we going to be able to control what people are doing in every jurisdiction? I think no way, and so I think it's one of those things that it's one of the aspects of this technology that we have to grapple with, is the fact that it's widely available and that people will start using it in different ways, potentially even in the future to create genetically altered humans.
Can genetic engineering be regulated? Better question: should it be regulated? Jennifer Doudna, the co-creator of genetic engineering tool CRISPR, thinks that the answer isn't easy. Corporate interests could change everything, as could the desires of a madman if CRISPR were to fall into the wrong hands. But Doudna is happy that people are talking about the best ways to regulate the technology this early in the game as it's the kind of thing that could truly reshape the human race. Should we be concerned? Frankly, no. But we should remain vigilant that CRISPR gets used correctly and not for a future Westworld-esque scenario.
Jennifer Doudna's most recent book is A Crack in Creation
Gene Editing and the Unthinkable Power to Control Evolution.
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Information may not seem like something physical, yet it has become a central concern for physicists. A wonderful new book explores the importance of the "dataome" for the physical, biological, and human worlds.
- The most important current topic in physics relates to a subject that hardly seems physical at all — information, which is central to thermodynamics and perhaps the universe itself.
- The "dataome" is the way human beings have been externalizing information about ourselves and the world since we first began making paintings on cave walls.
- The dataome is vast and growing everyday, sucking up an ever increasing share of the energy humans produce.
Physics is a field that is supposed to study real stuff. By real, I mean things like matter and energy. Matter is, of course, the kind of stuff you can hold in your hand. Energy may seem a little more abstract, but its reality is pretty apparent, appearing in the form of motion or gravity or electromagnetic fields.
What has become apparent recently, however, is the importance to physics of something that seems somewhat less real: information. From black holes to quantum mechanics to understanding the physics of life, information has risen to become a principal concern of many physicists in many domains. This new centrality of information is why you really need to read astrophysicist Caleb Scharf's new book The Ascent of Information: Books, Bits, Machines, and Life's Unending Algorithms.
Scharf is currently the director of the Astrobiology Program at Columbia University. He is also the author of four other books as well as a regular contributor to Scientific American.
(Full disclosure: Scharf and I have been collaborators on a scientific project involving the Fermi Paradox, so I was a big fan before I read this new book. Of course, the reason why I collaborated with him is because I really like the way he thinks, and his creativity in tackling tough problems is on full display in The Ascent of Information.)
What is the dataome?
In his new book, Scharf is seeking a deeper understanding of what he calls the "dataome." This is the way human beings have been externalizing information about ourselves and the world since we first began making paintings on cave walls. The book opens with a compelling exploration of how Shakespeare's works, which began as scribbles on a page, have gone on to have lives of their own in the dataome. Through reprintings in different languages, recordings of performances, movie adaptations, comic books, and so on, Shakespeare's works are now a permanent part of the vast swirling ensemble of information that constitutes the human dataome.
I found gems in these parts of the book that forced me to put the volume down and stare into space for a time to deal with their impact.
But the dataome does not just live in our heads. Scharf takes us on a proper physicist's journey through the dataome, showing us how information can never be divorced from energy. Your brain needs the chemical energy from food you ate this morning to read, process, and interpret these words. One of the most engaging parts of the book is when Scharf details just how much energy and real physical space our data-hungry world consumes as it adds to the dataome. For example, the Hohhot Data Center in the Inner Mongolia Autonomous Region of China is made of vast "farms" of data processing servers covering 245 acres of real estate. A single application like Bitcoin, Scharf tells us, consumes 7.7 gigawatts per year, equivalent to the output of half a dozen nuclear reactors!
Information is everywhere
But the dataome is not just about energy. Entropy is central to the story as well. Scharf takes the reader through a beautifully crafted discussion of information and the science of thermodynamics. This is where the links between energy, entropy, the limits of useful work, and probability all become profoundly connected to the definition of information.
The second law of thermodynamics tells us that you cannot use all of a given amount of energy to do useful work. Some of that energy must be wasted by getting turned into heat. Entropy is the physicist's way of measuring that waste (which can also be thought of as disorder). Scharf takes the reader through the basic relations of thermodynamics and then shows how entropy became intimately linked with information. It was Claude Shannon's brilliant work in the 1940s that showed how information — bits — could be defined for communication and computation as an entropy associated with the redundancy of strings of symbols. That was the link tying the physical world of physics explicitly to the informational and computational world of the dataome.
The best parts of the book are where Scharf unpacks how information makes its appearance in biology. From the data storage and processing that occurs with every strand of DNA, to the tangled pathways that define evolutionary dynamics, Scharf demonstrates how life is what happens to physics and chemistry when information matters. I found gems in these parts of the book that forced me to put the volume down and stare into space for a time to deal with their impact.
The physics of information
There are a lot of popular physics books out there about black holes and exoplanets and other cool stuff. But right now, I feel like the most important topic in physics relates to a subject that hardly seems physical at all. Information is a relatively new addition to the physics bestiary, making it even more compelling. If you are looking for a good introduction to how that is so, The Ascent of Information is a good place to start.
A new study tested to what extent dogs can sense human deception.
Is humanity's best friend catching on to our shenanigans? Researchers at the University of Vienna discovered that dogs can in certain cases know when people are lying.
The scientists carried out a study with hundreds of dogs to determine to what extent dogs could spot deception. The team's new paper, published in Proceedings of the Royal Society B, outlined experiments that tested whether dogs, like humans, have some inner sense of how to assess truthfulness.
As the researchers wrote in their paper, "Among non-primates, dogs (Canis familiaris) constitute a particularly interesting case, as their social environment has been shared with humans for at least 14,000 years. For this reason, dogs have been considered as a model species for the comparative investigation of socio-cognitive abilities." The investigation focused specifically on understanding if dogs were "sensitive to some mental or psychological states of humans."
The experiments involved 260 dogs, which were made to listen to advice from a human "communicator" whom they did not know. The human told them which one of two bowls had a treat hidden inside by touching it and saying, "Look, this is very good!" If the dogs took the person's advice, they would get the treat.
Once they established the trust of the dogs, the researchers then complicated the experience by letting dogs watch another human that they did not know transfer the treat from one bowl to another. In some cases, the original communicator would also be present to watch but not always.
The findings revealed that half of the dogs did not follow the advice of the communicator if that person was not present when the food was switched to a different bowl. The dogs had a sense that this human could not have known the true location of the treat. Furthermore, two-thirds of the dogs ignored the human's suggestion if she did see the food switch but pointed to the wrong bowl. The dogs figured out the human was lying to them.
Photos of experiments showing the dog, human communicator, and person hiding the treat. Credit: Lucrezia Lonardo et al / Proceedings of the Royal Society B.
"We thought dogs would behave like children under age five and apes, but now we speculate that perhaps dogs can understand when someone is being deceitful," co-author Ludwig Huber from the University of Vienna told New Scientist. "Maybe they think, 'This person has the same knowledge as me, and is nevertheless giving me the wrong [information].' It's possible they could see that as intentionally misleading, which is lying."
This is not the first time such experiments have been carried out. Previously, children under age five, macaques, and chimps were tested in a similar way. It turned out that children and other animals were more likely than dogs to listen to the advice of the liars. Notably, among the dogs, terriers were found to be more like children and apes, more eagerly following false suggestions.
Evolution proves to be just about as ingenious as Nikola Tesla
- For the first time, scientists developed 3D scans of shark intestines to learn how they digest what they eat.
- The scans reveal an intestinal structure that looks awfully familiar — it looks like a Tesla valve.
- The structure may allow sharks to better survive long breaks between feasts.
Considering how much sharks are feared by humans, it is a bit of a surprise that scientists don't know much about the predators. For example, until recently, sharks were thought to be solitary creatures searching the seas for food on their own. Now it appears that some sharks are quite social.
Another mystery is how these prehistoric swimming and eating machines digest food. Although scientists have made 2D sketches of captured sharks' digestive systems based on dissections, there is a limit to what can be learned in this way. Professor Adam Summers at University of Washington's Friday Harbor Labs says:
"Intestines are so complex, with so many overlapping layers, that dissection destroys the context and connectivity of the tissue. It would be like trying to understand what was reported in a newspaper by taking scissors to a rolled-up copy. The story just won't hang together."
Summers is co-author of a new study that has produced the first 3D scans of a shark's intestines, which turns out to have a strange, corkscrew structure. What's even more bizarre is that it resembles the amazing one-way valve designed by inventor Nikola Tesla in 1920. The research is published in the journal Proceedings of the Royal Society B.
What a 3D model reveals
Video: Pacific spiny dogfish intestine youtu.be
According to the study's lead author Samantha Leigh, "It's high time that some modern technology was used to look at these really amazing spiral intestines of sharks. We developed a new method to digitally scan these tissues and now can look at the soft tissues in such great detail without having to slice into them."
"CT scanning is one of the only ways to understand the shape of shark intestines in three dimensions," adds Summers. The researchers scanned the intestines of nearly three dozen different shark species.
It is believed that sharks go for extended periods — days or even weeks — between big meals. The scans reveal that food passes slowly through the intestine, affording sharks' digestive system the time to fully extract its nutrient value. The researchers hypothesize that such a slow digestive process may also require less energy.
It could be that this slow digestion is more susceptible to back flow given that the momentum of digested food through the tract must be minimal. Perhaps that is why sharks evolved something so similar to a Tesla valve.
What is Tesla's valve doing there?
Above, a Tesla valve. Below, a shark intestine.Credit: Samantha Leigh / California State University, Domi
Tesla's "valvular conduit," or what the world now calls a "Tesla valve," is a one-way valve with no moving parts. Its brilliance is based in fluid dynamics and only now coming to be fully appreciated. Essentially, a series of teardrop-shaped loops arranged along the length of the valve allow water to flow easily in one direction but not in the other. Modern tests reveal that at low flow rates, water can travel through the valve either way, but at high flow rates, the design kicks in. According to mathematician Leif Ristroph:
"Crucially, this turn-on comes with the generation of turbulent flows in the reverse direction, which 'plug' the pipe with vortices and disrupting currents. Moreover, the turbulence appears at far lower flow rates than have ever previously been observed for pipes of more standard shapes — up to 20 times lower speed than conventional turbulence in a cylindrical pipe or tube. This shows the power it has to control flows, which could be used in many applications."
A deeper dive
Summers suggests the scans are just the beginning. "The vast majority of shark species, and the majority of their physiology, are completely unknown," says Summers, adding that "every single natural history observation, internal visualization, and anatomical investigation shows us things we could not have guessed at."
To this end, the researchers plan to use 3D printing to produce models through which they can observe the behavior of different substances passing through them — after all, sharks typically eat fish, invertebrates, mammals, and seagrass. They also plan to explore with engineers ways in which the shark intestine design could be used industrially, perhaps for the treatment of wastewater or for filtering microplastics.
It could fairly be said, though, that Nikola Tesla was 100 years ahead of them.
When we rely on the conscious mind alone, we lose; but when we listen to the body, we gain a winning edge.
- Our surroundings contain far more information than our conscious minds can process.
- Our non-conscious minds are constantly gathering information and identifying patterns.
- By being interoceptively attuned — that is, aware of the inner state of the body — we can tap into what our non-conscious mind is trying to tell us.
The following is an adapted excerpt from the book The Extended Mind. It is reprinted with permission of the author.
If you'd like to make smarter choices and sounder decisions — and who doesn't? — you might want to take advantage of a resource you already have close at hand: your interoception. Interoception is, simply stated, an awareness of the inner state of the body. Just as we have sensors that take in information from the outside world (retinas, cochleas, taste buds, olfactory bulbs), we have sensors inside our bodies that send our brains a constant flow of data from within. These sensations are generated in places all over the body — in our internal organs, in our muscles, even in our bones — and then travel via multiple pathways to a structure in the brain called the insula. Such internal reports are merged with several other streams of information — our active thoughts and memories, sensory inputs gathered from the external world — and integrated into a single snapshot of our present condition, a sense of "how I feel" in the moment, as well as a sense of the actions we must take to maintain a state of internal balance.
To understand the role interoception can play in smart decision-making, it's important to know that the world is full of far more information than our conscious minds can process. However, we are also able to collect and store the volumes of information we encounter on a non-conscious basis. As we proceed through each day, we are continuously apprehending and storing regularities in our experience, tagging them for future reference. Through this information-gathering and pattern-identifying process, we come to know things — but we're typically not able to articulate the content of such knowledge or to ascertain just how we came to know it. This trove of data remains mostly under the surface of consciousness, and that's usually a good thing. Its submerged status preserves our limited stores of attention and working memory for other uses.
A study led by cognitive scientist Pawel Lewicki demonstrates this process in microcosm. Participants in Lewicki's experiment were directed to watch a computer screen on which a cross-shaped target would appear, then disappear, then reappear in a new location; periodically they were asked to predict where the target would show up next. Over the course of several hours of exposure to the target's movements, the participants' predictions grew more and more accurate. They had figured out the pattern behind the target's peregrinations. But they could not put this knowledge into words, even when the experimenters offered them money to do so. The subjects were not able to describe "anything even close to the real nature" of the pattern, Lewicki observes. The movements of the target operated according to a pattern too complex for the conscious mind to accommodate — but the capacious realm that lies below consciousness was more than roomy enough to contain it.
"Nonconscious information acquisition," as Lewicki calls it, along with the ensuing application of such information, is happening in our lives all the time. As we navigate a new situation, we're scrolling through our mental archive of stored patterns from the past, checking for ones that apply to our current circumstances. We're not aware that these searches are under way; as Lewicki observes, "The human cognitive system is not equipped to handle such tasks on the consciously controlled level." He adds, "Our conscious thinking needs to rely on notes and flowcharts and lists of 'if-then' statements — or on computers — to do the same job which our non-consciously operating processing algorithms can do without external help, and instantly."
But — if our knowledge of these patterns is not conscious, how then can we make use of it? The answer is that, when a potentially relevant pattern is detected, it's our interoceptive faculty that tips us off: with a shiver or a sigh, a quickening of the breath or a tensing of the muscles. The body is rung like a bell to alert us to this useful and otherwise inaccessible information. Though we typically think of the brain as telling the body what to do, just as much does the body guide the brain with an array of subtle nudges and prods. (One psychologist has called this guide our "somatic rudder.") Researchers have even captured the body in mid-nudge, as it alerts its inhabitant to the appearance of a pattern that she may not have known she was looking for.
Such interoceptive prodding was visible during a gambling game that formed the basis of an experiment led by neuroscientist Antonio Damasio, a professor at the University of Southern California. In the game, presented on a computer screen, players were given a starting purse of two thousand "dollars" and were shown four decks of digital cards. Their task, they were told, was to turn the cards in the decks face-up, choosing which decks to draw from such that they would lose the least amount of money and win the most. As they started clicking to turn over cards, players began encountering rewards — bonuses of $50 here, $100 there — and also penalties, in which small or large amounts of money were taken away. What the experimenters had arranged, but the players were not told, was that decks A and B were "bad" — they held lots of large penalties in store — and decks C and D were "good," bestowing more rewards than penalties over time.
How Our Brains Feel Emotion | Antonio Damasio | Big Think www.youtube.com
As they played the game, the participants' state of physiological arousal was monitored via electrodes attached to their fingers; these electrodes kept track of their level of "skin conductance." When our nervous systems are stimulated by an awareness of potential threat, we start to perspire in a barely perceptible way. This slight sheen of sweat momentarily turns our skin into a better conductor of electricity. Researchers can thus use skin conductance as a measure of nervous system arousal. Looking over the data collected by the skin sensors, Damasio and his colleagues noticed something interesting: after the participants had been playing for a short while, their skin conductance began to spike when they contemplated clicking on the bad decks of cards. Even more striking, the players started avoiding the bad decks, gravitating increasingly to the good decks. As in the Lewicki study, subjects got better at the task over time, losing less and winning more.
Yet interviews with the participants showed that they had no awareness of why they had begun choosing some decks over others until late in the game, long after their skin conductance had started flaring. By card 10 (about forty-five seconds into the game), measures of skin conductance showed that their bodies were wise to the way the game was rigged. But even ten turns later — on card 20 — "all indicated that they did not have a clue about what was going on," the researchers noted. It took until card 50 was turned, and several minutes had elapsed, for all the participants to express a conscious hunch that decks A and B were riskier. Their bodies figured it out long before their brains did. Subsequent studies supplied an additional, and crucial, finding: players who were more interoceptively aware were more apt to make smart choices within the game. For them, the body's wise counsel came through loud and clear.
Damasio's fast-paced game shows us something important. The body not only grants us access to information that is more complex than what our conscious minds can accommodate. It also marshals this information at a pace that is far quicker than our conscious minds can handle. The benefits of the body's intervention extend well beyond winning a card game; the real world, after all, is full of dynamic and uncertain situations, in which there is no time to ponder all the pros and cons. When we rely on the conscious mind alone, we lose — but when we listen to the body, we gain a winning edge.
Annie Murphy Paul is a science writer who covers research on learning and cognition. She is the author of The Extended Mind: The Power of Thinking Outside the Brain, from which this article is adapted.