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Changing Human DNA Via Gene Editing: The New Nazi Eugenics?
The road to eugenics was paved with good intentions, says Siddhartha Mukherjee. So what questions are essential to ask now that we can change human DNA through gene editing technology?
Siddhartha Mukherjee is the author of The Emperor of All Maladies: A Biography of Cancer, winner of the 2011 Pulitzer Prize in general nonfiction, and The Laws of Medicine. He is the editor of Best Science Writing 2013. Mukherjee is an assistant professor of medicine at Columbia University and a cancer physician and researcher. A Rhodes scholar, he graduated from Stanford University, University of Oxford, and Harvard Medical School. He has published articles in Nature, The New England Journal of Medicine, The New Yorker, The New York Times, and Cell. He lives in New York with his wife and daughters.
Siddhartha Mukherjee: Gene editing technologies allow us, allow scientists to change the genetic code within cells including embryonic cells, including embryonic stem cells in an intentional manner. That means that, you know, you can have a gene and you can change that code. The process is inefficient. It looks like there’s some collateral damage. Other genes can be damaged. All of this is being worked out right now. But in principle gene editing means just like you can go into a word processor and erase a word from what you’ve written. And you can change that word for a different word. The technologies are beginning to allow us to go into a cell, change its internal code or vocabulary which would be its DNA and its genome and certainly too for a human cell. And you can switch out the word, change the word with certain caveats.
Prenatal genetic diagnosis on the other hand has to do with the idea that you can look at an egg or an early embryo, decipher what mutations it might have, what changes, what variations it might have and decide to implant that egg or embryo or not implant that egg or embryo. The ultimate goal of these technologies of course is to allow different or just to fundamentally change genes.
Who should we intervene on? What are the limits? Who gets to decide what normalcy versus abnormalcy is? Who gets to decide whether is someone, you know, what suffering is? You could give an example of for instance of let’s say a terrifying lethal disease which you could detect in an embryo before implanting it and decide that that’s not the embryo that you want to implant.
But that depends on you and I saying that’s a terrifying lethal disease. And that’s a decision that you and I need to make and I really mean society needs to make in consensus. So it’s a time to emphasize that idea that we’re making decisions like this.
Really this issue came to a head when researchers in China decided to take nonviable human embryos and decided to try to attempt changing a disease linked gene in that nonviable human embryo set. It’s important to note that they were nonviable in the long run but it’s also important to note that they were indeed human embryos or very early human embryos and that the proof of principle experiment was launched. So it’s created a worldwide set of questions about what we can and cannot do with the human genome.
The road to eugenics was paved with the best intentions. And it was a series of, you can almost see the world tipping towards horror step by step by step, you know. It seemed like one iterative step didn’t seem that much and yet as you accumulated all of these very soon you went from, you know, in Nazi Germany in particular starting with trying to eliminate or sterilize those who were somehow physically different from others all the way including folks who were deaf, folks who had various neurological diseases. And then sort of marched inexorably towards other forms of identity including obviously Jews, Gypsies, homosexuals and so forth.
So it’s worthwhile remembering that that progression that occurred in the 1930s was perceived by citizens at that time as part of a progression. It was not as if, you know, all of a sudden someone woke up. There was a kind of glacial silence to the progression of eugenics in Nazi Germany. And in fact there was a glacial silence from the United States about what was going on in Nazi Germany. If anything, you know, the folks in the United States applauded the eugenicists and applauded the efforts of Nazi scientists in their attempts to cleanse their populations of all sorts of evil and emancipate themselves.
It’s incredibly important to remember that history when we step as we are going to, as we’re stepping towards the genetic modification of human embryos. Or even to some extent the genetic modification of animals or plants. We have to remember that it seems as if there’s a progression but all of a sudden by the time from the beginning until the end you may land up in a very different place. It’s important also not to throw as we enter new genetic technologies, not to throw the baby out with the genetic bath water. I mean it’s important to remember that our ability to manipulate genes can be very powerful, it has been very powerful.
The road to eugenics was paved with good intentions, says Siddhartha Mukherjee. So what questions are essential to ask now that we can change human DNA through gene editing technology? Siddhartha Mukherjee's newest book is The Gene: An Intimate History.
Andy Samberg and Cristin Milioti get stuck in an infinite wedding time loop.
- Two wedding guests discover they're trapped in an infinite time loop, waking up in Palm Springs over and over and over.
- As the reality of their situation sets in, Nyles and Sarah decide to enjoy the repetitive awakenings.
- The film is perfectly timed for a world sheltering at home during a pandemic.
The multifaceted cerebellum is large — it's just tightly folded.
- A powerful MRI combined with modeling software results in a totally new view of the human cerebellum.
- The so-called 'little brain' is nearly 80% the size of the cerebral cortex when it's unfolded.
- This part of the brain is associated with a lot of things, and a new virtual map is suitably chaotic and complex.
Just under our brain's cortex and close to our brain stem sits the cerebellum, also known as the "little brain." It's an organ many animals have, and we're still learning what it does in humans. It's long been thought to be involved in sensory input and motor control, but recent studies suggests it also plays a role in a lot of other things, including emotion, thought, and pain. After all, about half of the brain's neurons reside there. But it's so small. Except it's not, according to a new study from San Diego State University (SDSU) published in PNAS (Proceedings of the National Academy of Sciences).
A neural crêpe
A new imaging study led by psychology professor and cognitive neuroscientist Martin Sereno of the SDSU MRI Imaging Center reveals that the cerebellum is actually an intricately folded organ that has a surface area equal in size to 78 percent of the cerebral cortex. Sereno, a pioneer in MRI brain imaging, collaborated with other experts from the U.K., Canada, and the Netherlands.
So what does it look like? Unfolded, the cerebellum is reminiscent of a crêpe, according to Sereno, about four inches wide and three feet long.
The team didn't physically unfold a cerebellum in their research. Instead, they worked with brain scans from a 9.4 Tesla MRI machine, and virtually unfolded and mapped the organ. Custom software was developed for the project, based on the open-source FreeSurfer app developed by Sereno and others. Their model allowed the scientists to unpack the virtual cerebellum down to each individual fold, or "folia."
Study's cross-sections of a folded cerebellum
Image source: Sereno, et al.
A complicated map
Sereno tells SDSU NewsCenter that "Until now we only had crude models of what it looked like. We now have a complete map or surface representation of the cerebellum, much like cities, counties, and states."
That map is a bit surprising, too, in that regions associated with different functions are scattered across the organ in peculiar ways, unlike the cortex where it's all pretty orderly. "You get a little chunk of the lip, next to a chunk of the shoulder or face, like jumbled puzzle pieces," says Sereno. This may have to do with the fact that when the cerebellum is folded, its elements line up differently than they do when the organ is unfolded.
It seems the folded structure of the cerebellum is a configuration that facilitates access to information coming from places all over the body. Sereno says, "Now that we have the first high resolution base map of the human cerebellum, there are many possibilities for researchers to start filling in what is certain to be a complex quilt of inputs, from many different parts of the cerebral cortex in more detail than ever before."
This makes sense if the cerebellum is involved in highly complex, advanced cognitive functions, such as handling language or performing abstract reasoning as scientists suspect. "When you think of the cognition required to write a scientific paper or explain a concept," says Sereno, "you have to pull in information from many different sources. And that's just how the cerebellum is set up."
Bigger and bigger
The study also suggests that the large size of their virtual human cerebellum is likely to be related to the sheer number of tasks with which the organ is involved in the complex human brain. The macaque cerebellum that the team analyzed, for example, amounts to just 30 percent the size of the animal's cortex.
"The fact that [the cerebellum] has such a large surface area speaks to the evolution of distinctively human behaviors and cognition," says Sereno. "It has expanded so much that the folding patterns are very complex."
As the study says, "Rather than coordinating sensory signals to execute expert physical movements, parts of the cerebellum may have been extended in humans to help coordinate fictive 'conceptual movements,' such as rapidly mentally rearranging a movement plan — or, in the fullness of time, perhaps even a mathematical equation."
Sereno concludes, "The 'little brain' is quite the jack of all trades. Mapping the cerebellum will be an interesting new frontier for the next decade."
What happens if we consider welfare programs as investments?
- A recently published study suggests that some welfare programs more than pay for themselves.
- It is one of the first major reviews of welfare programs to measure so many by a single metric.
- The findings will likely inform future welfare reform and encourage debate on how to grade success.
Welfare as an investment<p>The <a href="https://scholar.harvard.edu/files/hendren/files/welfare_vnber.pdf" target="_blank">study</a>, carried out by Nathaniel Hendren and Ben Sprung-Keyser of Harvard University, reviews 133 welfare programs through a single lens. The authors measured these programs' "Marginal Value of Public Funds" (MVPF), which is defined as the ratio of the recipients' willingness to pay for a program over its cost.</p><p>A program with an MVPF of one provides precisely as much in net benefits as it costs to deliver those benefits. For an illustration, imagine a program that hands someone a dollar. If getting that dollar doesn't alter their behavior, then the MVPF of that program is one. If it discourages them from working, then the program's cost goes up, as the program causes government tax revenues to fall in addition to costing money upfront. The MVPF goes below one in this case. <br> <br> Lastly, it is possible that getting the dollar causes the recipient to further their education and get a job that pays more taxes in the future, lowering the cost of the program in the long run and raising the MVPF. The value ratio can even hit infinity when a program fully "pays for itself."</p><p> While these are only a few examples, many others exist, and they do work to show you that a high MVPF means that a program "pays for itself," a value of one indicates a program "breaks even," and a value below one shows a program costs more money than the direct cost of the benefits would suggest.</p> After determining the programs' costs using existing literature and the willingness to pay through statistical analysis, 133 programs focusing on social insurance, education and job training, tax and cash transfers, and in-kind transfers were analyzed. The results show that some programs turn a "profit" for the government, mainly when they are focused on children:
This figure shows the MVPF for a variety of polices alongside the typical age of the beneficiaries. Clearly, programs targeted at children have a higher payoff.
Nathaniel Hendren and Ben Sprung-Keyser<p>Programs like child health services and K-12 education spending have infinite MVPF values. The authors argue this is because the programs allow children to live healthier, more productive lives and earn more money, which enables them to pay more taxes later. Programs like the preschool initiatives examined don't manage to do this as well and have a lower "profit" rate despite having decent MVPF ratios.</p><p>On the other hand, things like tuition deductions for older adults don't make back the money they cost. This is likely for several reasons, not the least of which is that there is less time for the benefactor to pay the government back in taxes. Disability insurance was likewise "unprofitable," as those collecting it have a reduced need to work and pay less back in taxes. </p>
What are the implications of all this?<div class="rm-shortcode" data-media_id="ceXv4XLv" data-player_id="FvQKszTI" data-rm-shortcode-id="3b407f5aa043eeb84f2b7ff82f97dc35"> <div id="botr_ceXv4XLv_FvQKszTI_div" class="jwplayer-media" data-jwplayer-video-src="https://content.jwplatform.com/players/ceXv4XLv-FvQKszTI.js"> <img src="https://cdn.jwplayer.com/thumbs/ceXv4XLv-1920.jpg" class="jwplayer-media-preview" /> </div> <script src="https://content.jwplatform.com/players/ceXv4XLv-FvQKszTI.js"></script> </div> <p>Firstly, it shows that direct investments in children in a variety of areas generate very high MVPFs. Likewise, the above chart shows that a large number of the programs considered pay for themselves, particularly ones that "invest in human capital" by promoting education, health, or similar things. While programs that focus on adults tend to have lower MVPF values, this isn't a hard and fast rule.</p><p>It also shows us that very many programs don't "pay for themselves" or even go below an MVPF of one. However, this study and its authors do not suggest that we abolish programs like disability payments just because they don't turn a profit.</p><p>Different motivations exist behind various programs, and just because something doesn't pay for itself isn't a definitive reason to abolish it. The returns on investment for a welfare program are diverse and often challenging to reckon in terms of money gained or lost. The point of this study was merely to provide a comprehensive review of a wide range of programs from a single perspective, one of dollars and cents. </p><p>The authors suggest that this study can be used as a starting point for further analysis of other programs not necessarily related to welfare. </p><p>It can be difficult to measure the success or failure of a government program with how many metrics you have to choose from and how many different stakeholders there are fighting for their metric to be used. This study provides us a comprehensive look through one possible lens at how some of our largest welfare programs are doing. </p><p>As America debates whether we should expand or contract our welfare state, the findings of this study offer an essential insight into how much we spend and how much we gain from these programs. </p>
Richard Feynman once asked a silly question. Two MIT students just answered it.
Here's a fun experiment to try. Go to your pantry and see if you have a box of spaghetti. If you do, take out a noodle. Grab both ends of it and bend it until it breaks in half. How many pieces did it break into? If you got two large pieces and at least one small piece you're not alone.
But science loves a good challenge<p>The mystery remained unsolved until 2005, when French scientists <a href="http://www.lmm.jussieu.fr/~audoly/" target="_blank">Basile Audoly</a> and <a href="http://www.lmm.jussieu.fr/~neukirch/" target="_blank">Sebastien Neukirch </a>won an <a href="https://www.improbable.com/ig/" target="_blank">Ig Nobel Prize</a>, an award given to scientists for real work which is of a less serious nature than the discoveries that win Nobel prizes, for finally determining why this happens. <a href="http://www.lmm.jussieu.fr/spaghetti/audoly_neukirch_fragmentation.pdf" target="_blank">Their paper describing the effect is wonderfully funny to read</a>, as it takes such a banal issue so seriously. </p><p>They demonstrated that when a rod is bent past a certain point, such as when spaghetti is snapped in half by bending it at the ends, a "snapback effect" is created. This causes energy to reverberate from the initial break to other parts of the rod, often leading to a second break elsewhere.</p><p>While this settled the issue of <em>why </em>spaghetti noodles break into three or more pieces, it didn't establish if they always had to break this way. The question of if the snapback could be regulated remained unsettled.</p>
Physicists, being themselves, immediately wanted to try and break pasta into two pieces using this info<p><a href="https://roheiss.wordpress.com/fun/" target="_blank">Ronald Heisser</a> and <a href="https://math.mit.edu/directory/profile.php?pid=1787" target="_blank">Vishal Patil</a>, two graduate students currently at Cornell and MIT respectively, read about Feynman's night of noodle snapping in class and were inspired to try and find what could be done to make sure the pasta always broke in two.</p><p><a href="http://news.mit.edu/2018/mit-mathematicians-solve-age-old-spaghetti-mystery-0813" target="_blank">By placing the noodles in a special machine</a> built for the task and recording the bending with a high-powered camera, the young scientists were able to observe in extreme detail exactly what each change in their snapping method did to the pasta. After breaking more than 500 noodles, they found the solution.</p>
The apparatus the MIT researchers built specifically for the task of snapping hundreds of spaghetti sticks.
(Courtesy of the researchers)
What possible application could this have?<p>The snapback effect is not limited to uncooked pasta noodles and can be applied to rods of all sorts. The discovery of how to cleanly break them in two could be applied to future engineering projects.</p><p>Likewise, knowing how things fragment and fail is always handy to know when you're trying to build things. Carbon Nanotubes, <a href="https://bigthink.com/ideafeed/carbon-nanotube-space-elevator" target="_self">super strong cylinders often hailed as the building material of the future</a>, are also rods which can be better understood thanks to this odd experiment.</p><p>Sometimes big discoveries can be inspired by silly questions. If it hadn't been for Richard Feynman bending noodles seventy years ago, we wouldn't know what we know now about how energy is dispersed through rods and how to control their fracturing. While not all silly questions will lead to such a significant discovery, they can all help us learn.</p>
Finding a balance between job satisfaction, money, and lifestyle is not easy.
- When most of your life is spent doing one thing, it matters if that thing is unfulfilling or if it makes you unhappy. According to research, most people are not thrilled with their jobs. However, there are ways to find purpose in your work and to reduce the negative impact that the daily grind has on your mental health.
- "The evidence is that about 70 percent of people are not engaged in what they do all day long, and about 18 percent of people are repulsed," London Business School professor Dan Cable says, calling the current state of work unhappiness an epidemic. In this video, he and other big thinkers consider what it means to find meaning in your work, discuss the parts of the brain that fuel creativity, and share strategies for reassessing your relationship to your job.
- Author James Citrin offers a career triangle model that sees work as a balance of three forces: job satisfaction, money, and lifestyle. While it is possible to have all three, Citrin says that they are not always possible at the same time, especially not early on in your career.