Why Drugs That Work In Mice Don't Work In Humans

LRI conducts experiments on animals; currently, in particular, mice. We believe that this is worthwhile -- that is, we believe that whether a drug makes mice live longer tells us something meaningful about whether it will make people live longer.

But is that a valid assumption? We know, after all, that most drugs that “work” in mouse experiments don’t go on to succeed in human clinical trials. Only 14% of drugs that are tested on humans succeed in demonstrating effectiveness[1], and all of these are drugs that have been found efficacious in animals, so successful animal studies are very far from a guarantee by themselves. Why do we trust them at all?

First of all, it should be noted that the overall clinical trial success rate is brought down by cancer drugs, which have only an 8% success rate in clinical trials. The success rate for trials of all non-oncology drugs is 20%.

Curing cancer in a laboratory mouse is very different from curing it in a person. In particular, these aren’t animals that got old and developed tumors spontaneously; they’re mice that have been made to get cancer, either by breeding a cancer-prone strain of mice, or by exposing the mice to a carcinogen, or by grafting a tumor into the mouse directly. None of these processes works exactly the same as developing spontaneous tumors, and in particular they may be easier to reverse than spontaneous tumors. Part of what makes humans get cancer is that, with age, we lose the ability to fight cancer off, through weakened immune systems and other dysfunctions; we’d expect it to be easier to eradicate tumors implanted in a young, healthy mouse than the ones acquired by an old, unhealthy one. Similarly, mutant tumor-prone mice may have genetically simpler forms of cancer than mice who develop cancer in old age, and their genetic defects may thus be easier to counteract with drugs. This means that the animal experiments are “playing on easy mode”, and many drugs that pass them would not pass the “hard mode” of a human study.

The same argument goes for many other so-called “animal models” of disease. We induce Parkinson’s-like symptoms in animals with a poison called MPTP -- but this produces only a narrowly targeted form of brain damage, while real Parkinson’s disease, naturally acquired in elderly humans, includes more types of damage to more areas of the brain. It is easier to reverse MPTP symptoms than Parkinson’s disease. Animal models of age-related disease generally do not wait for the diseases to be naturally acquired, but induce them artificially in young animals, which we’d expect to be overall more resilient than the elderly humans who normally get these diseases.

This flaw doesn’t apply to lifespan studies of mice -- we’re not simulating aging, we’re observing natural aging, and how drugs modify it.

by Sarah Constantin, LRI |  Read more:

Image: uncredited

Borsalino

Borsalino (NY Times)
via:

via:
[ed. Reminds me of my grandson.]

Ōhno Bakufu 大野麦風 (1888–1976)
via:

UC Terminates Subscriptions With World’s Largest Scientific Publisher

As a leader in the global movement toward open access to publicly funded research, the University of California is taking a firm stand by deciding not to renew its subscriptions with Elsevier. Despite months of contract negotiations, Elsevier was unwilling to meet UC’s key goal: securing universal open access to UC research while containing the rapidly escalating costs associated with for-profit journals.

In negotiating with Elsevier, UC aimed to accelerate the pace of scientific discovery by ensuring that research produced by UC’s 10 campuses — which accounts for nearly 10 percent of all U.S. publishing output — would be immediately available to the world, without cost to the reader. Under Elsevier’s proposed terms, the publisher would have charged UC authors large publishing fees on top of the university’s multi-million dollar subscription, resulting in much greater cost to the university and much higher profits for Elsevier.

“Knowledge should not be accessible only to those who can pay,” said Robert May, chair of UC’s faculty Academic Senate. “The quest for full open access is essential if we are to truly uphold the mission of this university.” The Academic Senate issued a statement today endorsing UC’s position.

Open access publishing, which makes research freely available to anyone, anywhere in the world, fulfills UC’s mission by transmitting knowledge more broadly and facilitating new discoveries that build on the university’s research and scholarly work. This follows UC’s faculty-driven principles on scholarly communication.

“I fully support our faculty, staff and students in breaking down paywalls that hinder the sharing of groundbreaking research,” said UC President Janet Napolitano. “This issue does not just impact UC, but also countless scholars, researchers and scientists across the globe — and we stand with them in their push for full, unfettered access.”

Elsevier is the largest scholarly publisher in the world, disseminating about 18 percent of journal articles produced by UC faculty. The transformative model that UC faculty and libraries are championing would make it easier and more affordable for UC authors to publish in an open access environment.

“Make no mistake: The prices of scientific journals now are so high that not a single university in the U.S. — not the University of California, not Harvard, no institution — can afford to subscribe to them all,” said Jeffrey MacKie-Mason, university librarian and economics professor at UC Berkeley, and co-chair of UC’s negotiation team. “Publishing our scholarship behind a paywall deprives people of the access to and benefits of publicly funded research. That is terrible for society.”

by UC Office of the President, Univ. of California |  Read more:
[ed. Elsevier = parasite.]

An Interview With Bob Costas

What do you think baseball needs to do for the next generation?

The most important thing is pace of play, and what’s best according to the analytics and the modern way of looking at the game, what’s best to give you a chance to win, is not what is best for the product. Baseball’s supposed to have a pleasing, leisurely pace. It’s not supposed to have a lethargic pace, and that’s what Manfred and company and the Players Association, if they’re enlightened about it, have to grapple with.

Here’s the kind of thing that just irks me, and it shows you football’s sway over everything. Baseball’s agreement with Fox allows league-championship games to be on Fox Sports 1. So Game Seven [of the Nation League championship] between the Brewers and the Dodgers is on FS1, which a lot of people can’t get or don’t know where to find. Game Seven.

But during the World Series, after Game Two, at Fenway Park, Joe Buck, by contract, has to go [announce] some dog-ass Thursday night [football] game, and then go to Dodger Stadium to do Game Three [of the World Series], which turns out to be an eighteen-inning classic. Game Three of the World Series. Now what does that say? That some soon-to-be-forgotten, regular-season football game in October should actually be important enough to divert the voice of the World Series from Boston to Houston before he goes to Los Angeles for Game Three. Now, I don’t care how many chartered planes are involved. I don’t care how capable Joe Buck is, and he’s very capable, and it’s amazing that he was able to do an excellent job on both and still be fresh in the eighteenth inning of a marathon game. What does this say? Subliminally—

It’s not even subliminal—

Forget about subliminally. What does it say about the power of the N.F.L. that its relatively meaningless Thursday-night game in October should get in the way of the World Series? That’s an affront to anyone’s intelligence.

Is football at a place now where its power to demand this stuff is unparalleled in the history of modern sports?

Yes. Absolutely. Absolutely. They’re unaccountable. They get their way on everything. They’re a sports juggernaut, an entertainment juggernaut, and, in some sense, a cultural juggernaut. (...)

The N.B.A. right now is in an interesting place. The ratings are obviously nowhere near football, but, generally, they’ve been really good. The impact in popular culture and the brands of these athletes seem to be through the roof. The sport has not had the scandals that football has had, and, politically, it’s got a lot of stars who seem to be outspoken without a ton of controversy, the way you see in the N.F.L. I don’t know how you feel about basketball as a sport now, but it just seems like the type of thing you’re interested in doing, which involves talking about sports but also bringing in cultural and political things sometimes. Would you fit well in the N.B.A. of 2019?

Eventually, sooner rather than later, I’ll go back to doing something that’s a hybrid of what I used to do on HBO and what I did on “Later.” And there’s always been an intersection of sports and society, sports and issues beyond the playing field. People who say otherwise are abjectly ignorant of history, going all the way back to Teddy Roosevelt and football, to Jack Johnson and the Great White Hope, to Jackie Robinson, Billie Jean King, [Tommie] Smith and [John] Carlos. You know the list. And so the idea that sports and politics do not intersect is insane. (...)

What did you think of Colin Kaepernick’s settling his lawsuit against the N.F.L.?

Some people may have misread what the settlement or the nondisclosure clause means. It does not mean that Kaepernick can’t speak out on social issues. It doesn’t mean that he can’t, if he should return to the field, take a knee if he feels like taking a knee. Unless there’s some secret clause that we as yet don’t know of, my read of it is that it’s a standard nondisclosure as to the terms of the settlement, but it certainly isn’t a gag order going forward.

Do you think it’s important that he keeps speaking out?

I think he should do whatever he feels comfortable doing, but I don’t think the following is a contradiction: you can recognize that he was interested in shining a light on an important issue, but many of his other proclamations made him a less than perfect messenger. Maybe that’s why it’s better that he’s essentially gone radio-silent, and there are images of him, and a notion of him that’s out there, that elevates him to hero status in some quarters.

But, when you look a little deeper, it doesn’t hold up as well when he says, I don’t vote, because the oppressor will never allow you to vote your way out of your oppression. So I guess it doesn’t matter to him that, when he first took a knee, Barack Obama was President, and now Donald Trump is President. If you praise Fidel Castro without reservation, or without nuance, if you wear socks that depict cops as pigs, I think you undermine your own credibility with reasonable people who are sympathetic to the issue that first brought you to public prominence. (...)

Do these things that you just brought up make you think that he should not be grouped with a number of other athletes throughout history whom you would probably think of as heroic political spokespeople?

Yeah. I was asked that when he first knelt. And I was asked about it by Michael Smerconish, going on two years ago.

Oh, God, I’m asking the same questions as Michael Smerconish.

No, it was just that one question. He asked me whether Kaepernick has gained that status, and it was in the same interview in which I said flatly it was clear that he was being blackballed. But, no, I would not put him with Muhammad Ali. I would not put him with Curt Flood. I wouldn’t put him with Arthur Ashe. I wouldn’t put him with Kareem Abdul-Jabbar. Did I say Billie Jean King?

No.

Yeah, I just think that, in the case of Ali or even Smith and Carlos, their impact was more profound, and I think if you talk about Ashe or Kareem or others, that they had a more sophisticated grasp of issues. And, in the case of Ali, he put so much more on the line.

Well, there’s no Vietnam War going on.

I think what Kaepernick did had a noble intent, and he deserves credit for that. I would just hesitate to elevate him into that pantheon. We have to see how this plays out, and we have to see whether he can articulate something that is more nuanced and more convincing than his original statement. If his original statement of kneeling and starting this movement is all he wants to do, then mission accomplished, and I applaud him for it. But that doesn’t mean that his every utterance is worthy of immediate agreement or everybody falling in line.

On the other hand, if any team over the last two years had signed Colin Kaepernick, although many of us would have supported that, there would have been huge outcries: “I’m burning my season tickets in front of the stadium. I’ll never go to another game. This is it. I can’t stand this. Screw him.” Yet, when domestic abusers or people with long rap sheets bounce from one team to another, there aren’t picket lines, by and large, outside the stadium. People are evidently more comfortable with literal criminals than they are with someone who protests peacefully and in a dignified way.

by Isaac Chotiner, New Yorker | Read more:
Image:Rich Schultz/Getty

Tidying Up is Not Joyful

Inspired by an episode of Tidying Up with Marie Kondo on Netflix, I cleaned my dresser drawers this weekend. It was a generally satisfying way to shirk work duties (the reason I watched Netflix in the first place). Yet, despite my neater bureau, I find the popularity of Kondo’s ‘tidying’ unbearable. We are awash in stuff, and apparently so joyless that the promise of joy through house-cleaning appeals to us. The cultural fascination sparked by Kondo strikes me as deeply disordered.

As a scholar of East Asian philosophies, one pattern in the Kondo mania is all too familiar: the susceptibility of Americans to plain good sense if it can but be infused with a quasi-mystical ‘oriental’ aura. Kondo is, in several ways, a Mr Miyagi for the anxious, late-capitalist, consumerist age. Unlike the Karate Kid, we are bedevilled by our own belongings rather than by bullies – but just as Mr Miyagi could make waxing cars a way to find one’s strength and mettle, so too Marie Kondo can magically render folding T-shirts into a path toward personal contentment or even joy. The process by which mundane activities transmute into improved wellbeing is mysterious, but the mystery is much of the allure, part of what makes pedestrian wisdom palatable. Folding clothes as an organisational strategy is boring. But folding clothes as a mystically infused plan of life is alluring. It’s not about the clothes. It’s about everything, all at once.

Popular uses of East Asian philosophies often tend this way: toward making the circumscribed expansive, toward making small wisdoms carry water for all the wisdom. This is how the ancient military theorist Sun Tzu might end up guiding your retirement savings, coaching your kid’s football team, improving your marriage, or even raising your kids. Sun Tzu’s Art of War has been leveraged into self-help advice on all of these subjects and more. Superficially, and also for trained scholars of early Chinese military history, it might seem that Sun Tzu is in fact only really interested in managing violent conflict well. But at a deeper level – which is to say, at the level of what might be marketed to gullible Western consumers – he is actually addressing all of life’s mysteries. What reads like straightforward instruction on wartime espionage might yet have something to teach us about our children. To access this deeper meaning, we need to assume that ‘oriental’ wisdom is never about this or that, but always about everything. And importantly, at root, it is reassuring.

Worse than the bizarre uses of Sun Tzu are the seemingly endless heartwarming and encouraging things that Confucius is claimed to have said. Blandly inspirational Confucius memes are now so numerous and so detached from reality that they have spawned a meta-meme, one that reads: ‘Confucius: I never said all that shit.’ Most of the memes detailing what Confucius ‘said’ say little that is compelling or even mildly interesting. But that is exactly why it’s so important to append ‘Confucius said’ to them. Without this addendum, bracing us to receive a bit of ‘Eastern wisdom’, we might believe them to be yet more dull mini-homilies. Which, to be clear, they are. Poor old Confucius features in these memes as a mystical oriental kitten, telling us all to hang in there!

by Sally Davies, Aeon |  Read more:

Image: Netflix

The Super Salmon

The Super Salmon - A video documentary about the Susitna River in Alaska and proposals to dam it.

[ed. Beautiful video. Back in the early 80's when damming the Susitna River really gained traction, I had the task of coordinating and preparing the Alaska Department of Fish and Game's (ADF&G) comments to the Federal Energy Regulatory Commission (FERC) re: licensing for the project. That analysis (and associated mitigation requirements) required synthesizing years of intensive studies on fish and wildlife populations and their habitats, vegetation, hydrology, river morphology, and a host of other issues. Definitely one of the more complex projects of my career (which occurred simultaneously with another mega-project - a massive coal mine on the west side of Cook Inlet). A very busy time. Fortunately both projects were eventually shelved (until recently). In Alaska, bad ideas never die they just get recycled every 30 years or so (but hopefully not this one!). Addendum: to get a real sense of the issues involved read: this thread.]

Would Your Portfolio Survive a Nuclear Incident?

There hasn’t been a major nuclear incident, outside of accidental meltdowns, since World War II. This is no small miracle, and there’s reason to wonder when this string of good luck—because it has included many near-disasters—will end.

The U.S. recently formally announced that it will withdraw from the Intermediate-range Nuclear Forces (INF) Treaty with Russia if Russia doesn’t come into compliance, and at some point we could still face a showdown over nuclear disarmament on the Korean Peninsula. Further adding to the risks are the U.S. President’s authority to launch a first-use nuclear strike, without Congressional approval, and command and control infrastructures that are susceptible to false alarms. There are also the ever-present dangers of a regional Pakistan-India nuclear exchange or a nuclear or dirty bomb terrorist attack somewhere in the world.

Investors may be aware of some of these risks, yet most participants in the capital markets rarely discuss them. Banks, money managers, regulators, and the broader business community should do what they can to help with efforts at preventing a nuclear incident, while simultaneously helping to prepare for the economic shock if prevention efforts fail.

It is simply unrealistic to invest under the assumption that a nuclear incident will never happen during our lifetimes. As to the instinctive response some may have—“Hey, if there is a nuclear attack, my portfolio will be the least of my worries”—well, that may be true if talking about the type of mutual assured destruction that existed between the U.S. and U.S.S.R. for decades. However, that particular risk has receded. Much more likely is some type of limited nuclear incident that, even if it kills a few hundred thousand or a few million, would still leave 99.9% of the global population uninjured.

And any nuclear event, even a “small” one, could potentially instill widespread panic and disrupt the global capital markets. If this happens, most of us are going to care what’s happening to our portfolios, our companies, and the economy.

by David Epstein, Barron's | Read more:
Image: San Diego Air and Space Museum Archive

[ed. Not the Onion.]

Tech Industry Titans Suddenly Love Internet Privacy Rules

Analysis After years of fighting to prevent any form of legislation that would safeguard Americans' online privacy, this week Congress will have two hearings on the topic during which the tech industry will outline its newfound love for laws covering its business.

But, experts warn, there is one big goal behind the sudden willingness to engage: a set of nation-wide federal laws, strongly influenced by the industry itself, which override individual state laws, and in particular a California law that was passed last year in an extraordinary last-minute compromise.

"Here's a quiet fight that’s brewing in Washington that you should pay attention to," the newly appointed FTC Commissioner Rohit Chopra tweeted on Monday. "It's called preemption – that's the ability of Congress to hit delete on all state data protection laws."

The issue of federal versus states' rights is one of the United States' most enduring battles, and in the past year, the rules surrounding telecoms and the internet have been pulled firmly into its orbit, not least thanks to the FCC's controversial decision to tear up its own rules on net neutrality.

While Congress has failed miserably to deal with key issues in the digital era, and federal regulators have adopted a hands-off (or should that be hands-free?) approach to regulation, state legislators have stepped in and started making laws to protect their constituents from harm. But now Big Tech has realized that federal laws are all but inevitable, it has decided to see if it can use the process to get rid of the current laws it doesn't like. (...)

All eyes on the West Coast

But the foremost target is California's law that appeared out of nowhere, and was passed in record time last July.

The California Consumer Privacy Act of 2018 was the first such data privacy law passed in the US, despite years of legislative efforts in Washington DC, and while it didn't completely extend European-style GDPR protections, it did give the state's 40 million inhabitants the ability to view the data that companies hold on them and, critically, request that it be deleted and not sold to third parties.

Tech giants absolutely loathe the law, which threatens to undermine their fundamental business model of gathering, packaging, and selling user data while doing as much as possible to keep people as uninformed as possible about what information they actually have on them. Under the California law, any company with data on more than 50,000 people is covered, and each violation carries a hefty $7,500 fine.

How did online giants like Google and Facebook, which are based in Cali, ever allow such a law to pass? Why didn't they use their full lobbying might in Sacramento to kill it? Well, the fascinating answer behind that one is that they feared a worse alternative: a ballot measure. A chance for voters to directly give a thumbs up to new safeguards for their information.

In early 2016, a number of dedicated individuals with the funds and legislative know-how to make data privacy a reality worked together on a ballot initiative in order to give Californians the opportunity to give themselves their own privacy rights after every other effort in Sacramento and Washington DC has been shot down by lobbyists of Big Tech and Big Cable.

Such a law is enormously popular with voters and after real estate developer Alastair Mactaggart put about $2m of his own money into the initiative, it made its way through the somewhat complex procedure, and was just about to be placed onto the official ballot to voters.

It was almost certainly going to pass, and that meant that not only would Big Tech be forced to deal with a data privacy law but it would be far harder for it to change the legislation after the fact through Sacramento lobbying.

It came down to the wire: Mactaggart said that if California's governor signed into law a new privacy act before the ballot deadline, he would pull it. And so California's Congress scrambled, Governor Brown signed it, and literally the evening of the deadline, the ballot measure was pulled.

by Kieren McCarthy, The Register | Read more:
Image: Shutterstock
[ed. See also: The left needs to get radical on big tech – moderate solutions won't cut it (The Guardian)]

Hayley Richman

Love, love is a verb Love is a doing word Fearless on my breath Gentle impulsion Shakes me, makes me lighter Fearless on my breath Teardrop on the fire Fearless on my breath Night, night after day Black flowers blossom Fearless on my breath Black flowers blossom Fearless on my breath Teardrop on the fire Fearless on my Water is my eye Most faithful mirror Fearless on my breath Teardrop on the fire I've a confession Fearless on my breath Most faithful mirror Fearless on my breath Teardrop on the fire Fearless on my breath.

Joni Mitchell and David Hockney
via:

A World Without Clouds

On a 1987 voyage to the Antarctic, the paleoceanographer James Kennett and his crew dropped anchor in the Weddell Sea, drilled into the seabed, and extracted a vertical cylinder of sediment. In an inch-thick layer of plankton fossils and other detritus buried more than 500 feet deep, they found a disturbing clue about the planet’s past that could spell disaster for the future.

Lower in the sediment core, fossils abounded from 60 plankton species. But in that thin cross-section from about 56 million years ago, the number of species dropped to 17. And the planktons’ oxygen and carbon isotope compositions had dramatically changed. Kennett and his student Lowell Stott deduced from the anomalous isotopes that carbon dioxide had flooded the air, causing the ocean to rapidly acidify and heat up, in a process similar to what we are seeing today.

While those 17 kinds of plankton were sinking through the warming waters and settling on the Antarctic seabed, a tapir-like creature died in what is now Wyoming, depositing a tooth in a bright-red layer of sedimentary rock coursing through the badlands of the Bighorn Basin. In 1992, the finder of the tooth fossil, Phil Gingerich, and collaborators Jim Zachos and Paul Koch reported the same isotope anomalies in its enamel that Kennett and Stott had presented in their ocean findings a year earlier. The prehistoric mammal had also been breathing CO2-flooded air.

More data points surfaced in China, then Europe, then all over. A picture emerged of a brief, cataclysmic hot spell 56 million years ago, now known as the Paleocene-Eocene Thermal Maximum (PETM). After heat-trapping carbon leaked into the sky from an unknown source, the planet, which was already several degrees Celsius hotter than it is today, gained an additional 6 degrees. The ocean turned jacuzzi-hot near the equator and experienced mass extinctions worldwide. On land, primitive monkeys, horses and other early mammals marched northward, following vegetation to higher latitudes. The mammals also miniaturized over generations, as leaves became less nutritious in the carbonaceous air. Violent storms ravaged the planet; the geologic record indicates flash floods and protracted droughts. As Kennett put it, “Earth was triggered, and all hell broke loose.”

The PETM doesn’t only provide a past example of CO2-driven climate change; scientists say it also points to an unknown factor that has an outsize influence on Earth’s climate. When the planet got hot, it got really hot. Ancient warming episodes like the PETM were always far more extreme than theoretical models of the climate suggest they should have been. Even after accounting for differences in geography, ocean currents and vegetation during these past episodes, paleoclimatologists find that something big appears to be missing from their models — an X-factor whose wild swings leave no trace in the fossil record.

Evidence is mounting in favor of the answer that experts have long suspected but have only recently been capable of exploring in detail. “It’s quite clear at this point that the answer is clouds,” said Matt Huber, a paleoclimate modeler at Purdue University.

Clouds currently cover about two-thirds of the planet at any moment. But computer simulations of clouds have begun to suggest that as the Earth warms, clouds become scarcer. With fewer white surfaces reflecting sunlight back to space, the Earth gets even warmer, leading to more cloud loss. This feedback loop causes warming to spiral out of control.

For decades, rough calculations have suggested that cloud loss could significantly impact climate, but this concern remained speculative until the last few years, when observations and simulations of clouds improved to the point where researchers could amass convincing evidence.

Now, new findings reported today in the journal Nature Geoscience make the case that the effects of cloud loss are dramatic enough to explain ancient warming episodes like the PETM — and to precipitate future disaster. Climate physicists at the California Institute of Technology performed a state-of-the-art simulation of stratocumulus clouds, the low-lying, blankety kind that have by far the largest cooling effect on the planet. The simulation revealed a tipping point: a level of warming at which stratocumulus clouds break up altogether. The disappearance occurs when the concentration of CO2 in the simulated atmosphere reaches 1,200 parts per million — a level that fossil fuel burning could push us past in about a century, under “business-as-usual” emissions scenarios. In the simulation, when the tipping point is breached, Earth’s temperature soars 8 degrees Celsius, in addition to the 4 degrees of warming or more caused by the CO2 directly.

Once clouds go away, the simulated climate “goes over a cliff,” said Kerry Emanuel, a climate scientist at the Massachusetts Institute of Technology. A leading authority on atmospheric physics, Emanuel called the new findings “very plausible,” though, as he noted, scientists must now make an effort to independently replicate the work.

To imagine 12 degrees of warming, think of crocodiles swimming in the Arctic and of the scorched, mostly lifeless equatorial regions during the PETM. If carbon emissions aren’t curbed quickly enough and the tipping point is breached, “that would be truly devastating climate change,” said Caltech’s Tapio Schneider, who performed the new simulation with Colleen Kaul and Kyle Pressel.

Huber said the stratocumulus tipping point helps explain the volatility that’s evident in the paleoclimate record. He thinks it might be one of many unknown instabilities in Earth’s climate. “Schneider and co-authors have cracked open Pandora’s box of potential climate surprises,” he said, adding that, as the mechanisms behind vanishing clouds become clear, “all of a sudden this enormous sensitivity that is apparent from past climates isn’t something that’s just in the past. It becomes a vision of the future.”

by Natalie Wolchover, Quanta |  Read more:

Image: Robert Wood

[ed. Not to mention melting permafrost and the massive amounts of CO2 such an event would release.]

Thinking about the Magical Elixir of MMT

I find that as often as not I agree with Matt Bruenig on policy matters. But those points of agreement can be obscured for me by differences of temperament and politics. Here though I find myself entirely in agreement with him on something called Modern Monetary Theory. You may not even have heard this phrase before. But you should and probably will soon. If you haven’t, you should familiarize yourself with it because it bulks very large in many current debates within the Democratic Party that you have heard about. It’s a big deal. Bruenig aptly describes it as “about using word games to make people believe that the US can have Northern European levels of government spending without Northern European levels of taxation.”

It’s not easy to simply explain what MMT is because it operates at several distinct and not always closely related levels.

At its simplest MMT states that government spending is not funded by taxing money or borrowing it. Taxes serve other purposes but getting money to pay for things is not actually one of them. As one of its top popularizing advocates put it, “Taxing the super rich at 70 or 80 percent is good in itself, because those people have too much money and are screwing up the world with it. But you don’t need it to fund an agenda.” In fact, all government spending, says MMT, is funded by printing money. At a very high level of abstraction there’s a way in which this redefinition of terms makes a certain sense. Indeed, there are elements of MMT that are similar to basic Keynesian economic theory – sort of Keynesianism on steroids or perhaps Keynesianism without a theory of inflation. For a more knowledgable and technical discussion see these two columns (one and two) Paul Krugman wrote on the question of MMT earlier this month. For pro-MMT arguments Stephanie Kelton is probably the most prominent advocate. You can see her arguments at her website.

To me, the discussions about MMT are very hard to pin down because it’s a bit hard to make sense of what level of practicality MMT advocates are trying to make their arguments. It can be a bit baffling like having a discussion about quantum physics and then hearing from the person you’re talking to that quantum physics makes some dramatic new things possible in the skyscraper you’re planning to build. That is quite likely completely untrue. So it is at a minimum quite unsettling. But again, to me the practical issues are not technical but political. And those I feel more comfortable speaking to.

If you look at the Green New Deal, you’ll see that it is actually a mix of two things. One is an extremely aggressive plan to address the climate crisis basically on all fronts: technology, infrastructure, regulation, etc. This is of course vastly expensive. But it’s not the biggest cost. But the really big spending isn’t for things that most of us would recognize as tied to climate or the environment at all. It’s basically the full social democratic policy package: universal health care, job guarantees, some version of a universal guaranteed income, free or no-debt higher education, etc.

Many of the things in the latter category are things that most Democrats believe in, others are quite controversial. Probably the bulk are things where the controversy comes down to matters of degree. The point I want to focus on here though is that these things are extremely expensive. (You can find a good discussion of these points in this and other columns by Noah Smith.)

If you look at the advocacy conversations surrounding the Green New Deal and various of these programs on the left and you get to how to pay for it … well, this is where MMT comes in. Setting aside the technical merits MMT increasingly serves as a placeholder to explain that the whole question is bogus. It’s not a matter of where do you get the money. The US government creates dollars and is in charge of how many dollars there are. So the whole question of where the government will get them is silly.

Here for example is The Intercept’s Ryan Grim this month in his email newsletter noting Alexandria Ocasio-Cortez flummoxing NPR’s Steve Inskeep with MMT.

Ocasio-Cortez was interviewed on Morning Edition today and when asked how to pay for a Green New Deal, talked about decoupling the concepts of tax revenue and government spending, which is the cornerstone of Modern Monetary Theory. Amazing to hear that on NPR. Not sure Steve Inskeep quite got it; it could take a little while to sink in.

A month earlier he made the same point on Twitter: “Here’s @AOC talking up Modern Monetary Theory as an answer to how the government can fund a progressive agenda. She’s right.”

One of the seductive things about this popularization of MMT is that it piggybacks on something most Democrats rightly and strongly believe: that deficit hawkery is a greatly overstated concern that is supposedly the biggest deal in the world when Democrats are trying to increase spending and becomes magically irrelevant when Republicans want to cut taxes. Remember that we spent the first four years of Obama’s presidency being told by Republicans that Obama’s fairly moderate post-crisis spending had us months away from an apocalyptic debt crisis.

Debt markets give us pretty accurate reads of impending debt crises and lenders spent years essentially paying the US to borrow their money. That was stupid and mendacious, scare-mongering in favor of austerity. The biggest problem the global economy faces at the moment and in some ways has for a couple decades isn’t inflation but lack of aggregate demand. But with MMT “deficits don’t matter” as perhaps a shorthand for ‘the danger of deficits is greatly overstated’ has become literally deficits don’t matter or more broadly that deficits don’t even exist.

I have no doubt that there are MMT advocates reading this now saying, no, you’re not getting what MMT says or you’re caricaturing it. Maybe. But what I’m able to speak to is how it is playing out in a political context. As Bruenig explains, if you want Northern European-style social democracy you’re going to need to have significantly or dramatically higher rates of taxation. And not only much higher rates on the uber wealthy but generally higher rates on a much broader range of the population. Whatever the theoretical merits of MMT, its political role is simply to say that core fiscal policy realities simply don’t exist. Or to put it more concretely, because taxing and spending and debt and money supply are all part of one equation, well, let’s not worry about it! How do you fund it? Well, MMT!

All of this might be notional and sort of irrelevant to our immediate political moment if it weren’t for the fact that MMT is actually central to the Green New Deal and thus at the center of political debate among Democrats without, seemingly, most people even realizing it. We’re seeing top presidential candidates signing on to it without seeming to realize what’s in it or the levels of taxation that are built into or that there’s no actual plan for where any of those revenues come from – even if they’re sort of hokum’d away with MMT finger-waving. You can wake up in mid-2020 having no idea what you’ve signed on to.

by Josh Marshall, TPM |  Read more:

Image: John Lamparski/Getty Images North America

Russia is Planning to Unplug From the Internet

Imagine the Internet shuts down. You turn your router off and on, to no avail. Cellular data too, seems to have disappeared—momentarily a blessing—but slowly it becomes clear that your entire city is disconnected. Soon, rumors begin to trickle in through phone calls and sidewalk chatter: It's the entire state; no, the whole country.

With credit cards and ATMs unable to connect, arguments erupt in the mounting lines at corner stores and pizzerias down the block. Brighter minds run to the bank to stock up on cash, where even longer and more chaotic lines culminate in several inhibited computer terminals and a diminishing supply of physical cash.

The frantic shouting of the lines is joined by the interminable honking harmonies of the horrific car traffic appearing on many streets now that the traffic-light infrastructure cannot receive its usual optimized updates through the Web. With a stranglehold on communication, public transit delays are eternal, and all flights are grounded. Will the Internet-dependent energy grid work properly through such a shutdown? You'll soon find out. All the most hare-brained Y2K fears from the cable news of yore are realized in this scenario.

Russians, though, won't have to imagine; they'll be living out a version of it sometime in the next month, Kremlin's orders.

Russia is planning to temporarily disconnect itself from the Internet in order to satisfy a bill in its parliament requiring that the country and its Internet service providers take steps to give Russia greater sovereignty over its Internet, named Runet, according to the RBK news agency. As part of the information-gathering process for the bill, Russia's public and private Internet authorities have agreed to voluntarily unplug the country for a period of time.

Russia's long-term goal is reportedly to keep all Web traffic involving interactions between Russian users from traveling outside Russian borders. Currently, some communications between Russian neighbors may involve, say, the intermediary of a server located in another country. The location of Internet infrastructure determines which government's laws apply to it (a lesson LiveJournal users learned when political speech was banned on the platform in 2017 after the social network moved its servers to Russia).

But the more immediate goal of the Great Unplugging—a formal accounting of the ins and outs of Russia's Internet infrastructure intricacies—isn't all that different from similar projects undertaken in the United States, like the Department of Homeland Security's Internet Atlas. The Atlas was an attempt to create a detailed map of all the fiberoptic cable and other connective infrastructure that allows the U.S.'s Internet to run, in order to anticipate and bolster the elements most vulnerable to attack. (One big takeaway from the project is that all of the U.S.'s Internet infrastructure is privately owned.)

According to Paul Barford, an Internet topology expert at the University of Wisconsin who worked on the Internet Atlas, Russia's plan is almost certainly part of an attempt to defend itself against what he calls a "cyber cold war." To build a cyber-wall at its border, Russia needs to fully understand how its local traffic works. And one way to get a handle on that, Russia believes, is to declare a moratorium on its Internet. (...)

As far as Barford is concerned, Russia's goals of Internet isolation seem to be a turn against the Internet itself. "The Internet was not designed with an 'off switch' in mind," he says. "Furthermore, the idea of country-level isolation is antithetical to the goals of the Internet such as I understand them."

But Russia's push toward Internet isolation highlights a broader truth about the Internet, or, rather, Internets: that there are, and always have been, many of them. The Web's history is one of competing governments attempting to extend their ideology and interests through technology.

"The mistaken notion that the Internet is the one network of networks that will unite the world is the exception to the rule in the history of computer networks," Peters says. "It is no surprise now that the Internet first became popular as the one network of networks for a globalized world economy in the 1990s, the only decade in recent history in which geopolitics also appeared monopolar. The simple fact is that networks have been operating independently of one another for decades."

by Jack Denton, Pacific Standard |  Read more:

Image: Michael Bocchieri/Getty Images
[ed. See also: China bars millions from travel for ‘social credit’ offenses (AP)]

Netflix Is the Most Intoxicating Portal to Planet Earth

Netflix Is the Most Intoxicating Portal to Planet Earth (NY Times)

Image: Max Gunther

Four New DNA Letters Double Life’s Alphabet

The DNA of life on Earth naturally stores its information in just four key chemicals — guanine, cytosine, adenine and thymine, commonly referred to as G, C, A and T, respectively.

Now scientists have doubled this number of life’s building blocks, creating for the first time a synthetic, eight-letter genetic language that seems to store and transcribe information just like natural DNA.

In a study published on 22 February in Science, a consortium of researchers led by Steven Benner, founder of the Foundation for Applied Molecular Evolution in Alachua, Florida, suggests that an expanded genetic alphabet could, in theory, also support life.

“It’s a real landmark,” says Floyd Romesberg, a chemical biologist at the Scripps Research Institute in La Jolla, California. The study implies that there is nothing particularly “magic” or special about those four chemicals that evolved on Earth, says Romesberg. “That’s a conceptual breakthrough,” he adds.

Normally, as a pair of DNA strands twist around each other in a double helix, the chemicals on each strand pair up: A bonds to T, and C bonds with G.

For a long time, scientists have tried to add more pairs of these chemicals, also known as bases, to this genetic code. For example, Benner first created ‘unnatural’ bases in the 1980s. Other groups have followed, with Romesberg’s lab making headlines in 2014 after inserting a pair of unnatural bases into a living cell.

But the latest study is the first to systematically demonstrate that the complementary unnatural bases recognise and bind to each other, and that the double helix that they form holds its structure.

Benner’s team, which includes researchers from various US companies and institutions, created the synthetic letters by tweaking the molecular structure of the regular bases. The letters of DNA pair up because they form hydrogen bonds: each contains hydrogen atoms, which are attracted to nitrogen or oxygen atoms in their partner. Benner explains that it’s a bit like Lego bricks that snap together when the holes and prongs line up.

By adjusting these holes and prongs, the team has come up with several new pairs of bases, including a pair named S and B, and another called P and Z. In the latest paper, they describe how they combine these four synthetic bases with the natural ones. The researchers call the resulting eight-letter language ‘hachimoji’ after the Japanese words for ‘eight’ and ‘letter’. The additional bases are each similar in shape to one of the natural four, but have variations in their bonding patterns.

The researchers then conducted a series of experiments that showed that their synthetic sequences shares properties with natural DNA that are essential for supporting life.

by Matthew Warren, Nature |  Read more:

Image: Science Source/Science Photo Library

Yumiko Kayukawa
via:

Workism Is Making Americans Miserable

The decline of traditional faith in America has coincided with an explosion of new atheisms. Some people worship beauty, some worship political identities, and others worship their children. But everybody worships something. And workism is among the most potent of the new religions competing for congregants.

What is workism? It is the belief that work is not only necessary to economic production, but also the centerpiece of one’s identity and life’s purpose; and the belief that any policy to promote human welfare must always encourage more work.

Homo industrious is not new to the American landscape. The American dream—that hoary mythology that hard work always guarantees upward mobility—has for more than a century made the U.S. obsessed with material success and the exhaustive striving required to earn it.

No large country in the world as productive as the United States averages more hours of work a year. And the gap between the U.S. and other countries is growing. Between 1950 and 2012, annual hours worked per employee fell by about 40 percent in Germany and the Netherlands—but by only 10 percent in the United States. Americans “work longer hours, have shorter vacations, get less in unemployment, disability, and retirement benefits, and retire later, than people in comparably rich societies,” wrote Samuel P. Huntington in his 2005 book Who Are We?: The Challenges to America’s National Identity.

One group has led the widening of the workist gap: rich men.

In 1980, the highest-earning men actually worked fewer hours per week than middle-class and low-income men, according to a survey by the Minneapolis Fed. But that’s changed. By 2005, the richest 10 percent of married men had the longest average workweek. In that same time, college-educated men reduced their leisure time more than any other group. Today, it is fair to say that elite American men have transformed themselves into the world’s premier workaholics, toiling longer hours than both poorer men in the U.S. and rich men in similarly rich countries.

This shift defies economic logic—and economic history. The rich have always worked less than the poor, because they could afford to. The landed gentry of preindustrial Europe dined, danced, and gossiped, while serfs toiled without end. In the early 20th century, rich Americans used their ample downtime to buy weekly movie tickets and dabble in sports. Today’s rich American men can afford vastly more downtime. But they have used their wealth to buy the strangest of prizes: more work!

Perhaps long hours are part of an arms race for status and income among the moneyed elite. Or maybe the logic here isn’t economic at all. It’s emotional—even spiritual. The best-educated and highest-earning Americans, who can have whatever they want, have chosen the office for the same reason that devout Christians attend church on Sundays: It’s where they feel most themselves. “For many of today’s rich there is no such thing as ‘leisure’; in the classic sense—work is their play,” the economist Robert Frank wrote in The Wall Street Journal. “Building wealth to them is a creative process, and the closest thing they have to fun.”

Workism may have started with rich men, but the ethos is spreading—across gender and age. In a 2018 paper on elite universities, researchers found that for women, the most important benefit of attending a selective college isn’t higher wages, but more hours at the office. In other words, our elite institutions are minting coed workists. What’s more, in a recent Pew Research report on the epidemic of youth anxiety, 95 percent of teens said “having a job or career they enjoy” would be “extremely or very important” to them as an adult. This ranked higher than any other priority, including “helping other people who are in need” (81 percent) or getting married (47 percent). Finding meaning at work beats family and kindness as the top ambition of today’s young people. (...)

Here’s a fair question: Is there anything wrong with hard, even obsessive, work?

Humankind has not yet invented itself out of labor. Machine intelligence isn’t ready to run the world’s factories, or care for the sick. In every advanced economy, most prime-age people who can work do—and in poorer countries, the average workweek is even longer than in the United States. Without work, including nonsalaried labor like raising a child, most people tend to feel miserable. Some evidence suggests that long-term unemployment is even more wrenching than losing a loved one, since the absence of an engaging distraction removes the very thing that tends to provide solace to mourners in the first place.

There is nothing wrong with work, when work must be done. And there is no question that an elite obsession with meaningful work will produce a handful of winners who hit the workist lottery: busy, rich, and deeply fulfilled. But a culture that funnels its dreams of self-actualization into salaried jobs is setting itself up for collective anxiety, mass disappointment, and inevitable burnout.

In the past century, the American conception of work has shifted from jobs to careers to callings—from necessity to status to meaning. In an agrarian or early-manufacturing economy, where tens of millions of people perform similar routinized tasks, there are no delusions about the higher purpose of, say, planting corn or screwing bolts: It’s just a job.

The rise of the professional class and corporate bureaucracies in the early 20th century created the modern journey of a career, a narrative arc bending toward a set of precious initials: VP, SVP, CEO. The upshot is that for today’s workists, anything short of finding one’s vocational soul mate means a wasted life.

by Derek Thompson, The Atlantic |  Read more:

Image: Nicky Loh/Reuters

Japanese Probe Makes Asteroid Touchdown

Japanese Probe Makes Asteroid Touchdown After 4-Year Space Chase (Bloomberg)

Image: JAXA