Think twice about buying ‘squashed-faced’ breeds, vets urge dog-lovers

British Veterinary Association launches #breedtobreathe campaign to highlight serious health issues breeds such as pugs and French bulldogs are prone to

Vets have urged dog-lovers to think twice about buying squashed-faced dogs such as pugs and French bulldogs, after many would-be owners were found to be unaware of the health problems such breeds often experience.

According to data from the Kennel Club, registrations of squashed-faced, or brachycephalic, breeds have shot up in recent years: while just 692 French bulldogs were registered in 2007, registrations reached 21,470 in 2016.

Certain DNA variations in dogs are linked to a short skull shape. The animals baby-like faces with large, round, wide-set eyes and flat noses are known to be a key factor in why owners choose such breeds: over time those traits have been bred for, and in some cases have been taken to extremes.

This selective breeding and prioritising appearance over health has left the breeds prone to skin disorders, eye ulcers and breathing difficulties among other problems.

Now the British Veterinary Association (BVA) has launched a campaign dubbed #breedtobreathe to draw attention to the issues, revealing that a new survey of 671 vets found 75% of owners were unaware of the health problems of brachycephalic breeds before they chose their squashed-faced dog. Moreover the vets said just 10% of owners could spot health problems related to such breeds, with many thinking that problems including snorting were normal for such dogs.

Brachycephalic dogs graph

The survey also revealed that 49% of vets thought advertising and social media were among the reasons behind the surge in ownership of these dogs, while 43% said celebrity ownership was one of the driving factors.

We find that our veterinary surgeons are finding increasing numbers of flat-faced dogs are coming into their practices with problems which are related to the way these animals are made, said John Fishwick, president of the BVA. One of the things that is causing this increase that we have seen over the last few years appears to be celebrity endorsements and their use in advertising.

Among those criticised by the BVA are pop star Lady Gaga, who is often photographed with her French bulldogs, and YouTube star Zoella, whose pug features in her videos. Big brands are also targeted; the organisation revealed that Heinz, Costa and Halifax have all agreed to avoid using squashed-faced dogs in future advertising.

Q&A

What sort of health problems do brachycephalic dogs have?

Breeds such as pugs, bulldogs, French bulldogs and boxers are prone to a range of health problems, many of which are related to their short skulls and other characteristic features.

Breathing problems

Brachycephalic breeds often have narrow nostrils, deformed windpipes and excess soft tissues inside their nose and throat all of which can lead to difficulties with breathing, which can also lead to heart problems. The dogs are also prone to overheating.

Dental problems

The shortened upper jaws of squashed-faced dogs means their teeth are crowded, increasing the risk of tooth decay and gum disease.

Skin disorders

The deep folds around the dogs faces, such as the characteristic wrinkles of a bulldog, also bring problems as they are prone to yeast and bacterial infections.

Eye conditions

The head shape and prominent eyes of brachycephalic breeds means the dogs are at risk of eye conditions including ulcers. Among the causes of eye ulcers is that brachycephalic dogs often cannot blink properly and have problems with tear production, while eyelashes or nasal folds can also rub the surface of their eyes.

Birth problems

Brachycephalic breeds can have difficulties giving birth naturally because of the disproportionate size of the puppies heads, meaning that caesarean sections are often necessary. According torecent researchmore than 80% of Boston terrier, bulldog and French bulldog puppies in the UK are born in this manner.

The BVA is urging people to send letters to brands asking them not to use such dogs in promotional material. The campaign also aims to raise awareness of potential health problems of squashed-face breeds, and stresses the need for vets, owners, dog-show judges, breeders, researchers and others to work together to make sure the breeds are healthy.

They are lovely breeds of dog, they are very friendly and they make good pets, said Fishwick. The problem is a lot of them are really struggling, and we really want to make sure people understand this and encourage them to think about either going for another breed or a healthier version of these breeds ones which have been bred to have a longer snout or possibly even cross breeds.

The BVA warned that without action, the number of corrective surgeries needed on such animals will soar.

Caroline Kisko, secretary of the Kennel Club urged owners to do their homework before buying a squashed-faced dog. As soon as you get a market drive then the puppy farms just say ooh well breed those now, she said.

But Dr Rowena Packer of the Royal Veterinary College (RVC) said the problem is not confined to new owners, with recent research from the RVC finding that more than 90% of pug, French bulldog and English bulldog owners said they would own another such dog in the future. It is not just going to be a flash in the pan that we see this huge surge and then it goes away, she said.

It has been suggested that vets may be unwilling to speak out for fear that owners will simply take their pets elsewhere, damaging business.

But Packer disagrees, saying: I dont think any vet went into [the job] hoping that their salary would be paid by the suffering of dogs who have been bred to effectively have problems.

Dr Crina Dragu, a London-based veterinary surgeon, noted that not all squashed-faced dogs have problems. You see the ones that have happy lives, normal lives, and you see the ones that the minute they are born they spend their entire lives as though [they are being smothered] with a pillow all day, every day, she said.

Packer said prospective owners should be aware squashed-faced dogs can be an expensive commitment: I think they need to be aware of both the emotional and financial hardship that they could be putting themselves and their dogs through for potentially five to 10 years.

Read more: https://www.theguardian.com/lifeandstyle/2018/jan/05/think-twice-about-buying-squashed-faced-breeds-vets-urge-dog-lovers

Excitement as trial shows Huntington’s drug could slow progress of disease

Hailed as enormously significant, results in groundbreaking trial are first time a drug has been shown to suppress effects of Huntingtons genetic mutation

A landmark trial for Huntingtons disease has announced positive results, suggesting that an experimental drug could become the first to slow the progression of the devastating genetic illness.

The results have been hailed as enormously significant because it is the first time any drug has been shown to suppress the effects of the Huntingtons mutation that causes irreversible damage to the brain. Current treatments only help with symptoms, rather than slowing the diseases progression.

Q&A

What is Huntington’s disease?

Huntingtons disease is a congenital degenerative condition caused by a single defective gene. Most patients are diagnosed in middle age, with symptoms including mood swings, irritability and depression. As the disease progresses, more serious symptoms can include involuntary jerky movements, cognitive difficulties and issues with speech and swallowing.

Currently there is no cure for Huntington’s, although drugs exist which help manage some of the symptoms. It is thought that about 12 people in 100,000 are affected by Huntington’s, and if a parent carries the faulty gene there is a 50% chance they will pass it on to their offspring.

Prof Sarah Tabrizi, director of University College Londons Huntingtons Disease Centre who led the phase 1 trial, said the results were beyond what Id ever hoped … The results of this trial are of ground-breaking importance for Huntingtons disease patients and families, she said.

The results have also caused ripples of excitement across the scientific world because the drug, which is a synthetic strand of DNA, could potentially be adapted to target other incurable brain disorders such as Alzheimers and Parkinsons. The Swiss pharmaceutical giant Roche has paid a $45m licence fee to take the drug forward to clinical use.

Huntingtons is an incurable degenerative disease caused by a single gene defect that is passed down through families.

The first symptoms, which typically appear in middle age, include mood swings, anger and depression. Later patients develop uncontrolled jerky movements, dementia and ultimately paralysis. Some people die within a decade of diagnosis.

Most of our patients know whats in their future, said Ed Wild, a UCL scientist and consultant neurologist at the National Hospital for Neurology and Neurosurgery in London, who administered the drug in the trial.

The mutant Huntingtons gene contains instructions for cells to make a toxic protein, called huntingtin. This code is copied by a messenger molecule and dispatched to the cells protein-making machinery. The drug, called Ionis-HTTRx, works by intercepting the messenger molecule and destroying it before the harmful protein can be made, effectively silencing the effects of the mutant gene.

How the drug works to slow the progress of Huntington’s disease

To deliver the drug to the brain, it has to be injected into the fluid around the spine using a four-inch needle.

Prof John Hardy, a neuroscientist at UCL who was not involved in the trial, said: If Id have been asked five years ago if this could work, I would have absolutely said no. The fact that it does work is really remarkable.

The trial involved 46 men and women with early stage Huntingtons disease in the UK, Germany and Canada. The patients were given four spinal injections one month apart and the drug dose was increased at each session; roughly a quarter of participants had a placebo injection.

After being given the drug, the concentration of harmful protein in the spinal cord fluid dropped significantly and in proportion with the strength of the dose. This kind of closely matched relationship normally indicates a drug is having a powerful effect.

For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well-tolerated, said Tabrizi. This is probably the most significant moment in the history of Huntingtons since the gene [was isolated].

The trial was too small, and not long enough, to show whether patients clinical symptoms improved, but Roche is now expected to launch a major trial aimed at testing this.

If the future trial is successful, Tabrizi believes the drug could ultimately be used in people with the Huntingtons gene before they become ill, possibly stopping symptoms ever occurring. They may just need a pulse every three to four months, she said. One day we want to prevent the disease.

The drug, developed by the California biotech firm Ionis Pharmaceuticals, is a synthetic single strand of DNA customised to latch onto the huntingtin messenger molecule.

The unexpected success raises the tantalising possibility that a similar approach might work for other degenerative brain disorders. The drugs like Lego, said Wild. You can target [any protein].

For instance, a similar synthetic strand of DNA could be made to target the messenger that produces misshapen amyloid or tau proteins in Alzheimers.

Huntingtons alone is exciting enough, said Hardy, who first proposed that amyloid proteins play a central role in Alzheimers. I dont want to overstate this too much, but if it works for one, why cant it work for a lot of them? I am very, very excited.

Prof Giovanna Mallucci, associate director of UK Dementia Research Institute at the University of Cambridge, described the work as a tremendous step forward for individuals with Huntingtons disease and their families.

Clearly, there will be much interest into whether it can be applied to the treatment of other neurodegenerative diseases, like Alzheimers, she added. However, she said that in the case of most other disorders the genetic causes are complex and less well understood, making them potentially harder to target.

About 10,000 people in the UK have the condition and about 25,000 are at risk. Most people with Huntingtons inherited the gene from a parent, but about one in five patients have no known family history of the disease.

The full results of the trial are expected to be published in a scientific journal next year.

Read more: https://www.theguardian.com/science/2017/dec/11/excitement-as-huntingtons-drug-shown-to-slow-progress-of-devastating-disease

Ancestrys Genetic Testing Kits Are Heading for Your Stocking This Year

This holiday season, more people than ever before are giving the gift of spit. Well, what’s in your spit, to be precise. Want to know where your ancestors once walked or whether you’re at risk for a genetic disease? There’s a spit tube kit for that. And customers are buying them in record numbers.

Between Black Friday and Cyber Monday, leading personal genomics company AncestryDNA sold about 1.5 million testing kits designed to provide insights into your ethnicity and familial connections. That’s like 2,000 gallons of saliva—enough to fill a modest above-ground swimming pool with the genetic history of every person in the city of Philadelphia.

Ancestry says it’s equipped to deal with the impending deluge, but the flood of consumer interest has its executives eyeing the long-term prospects of their stretched supply chain. It also has some policymakers and public health officials concerned about the pace with which people are blindly giving away their genetic data to these types of companies, who can turn around and sell it to third parties.

At a press conference on Sunday, Senator Chuck Schumer (D–New York) called for increased federal scrutiny of the privacy practices of consumer DNA testing companies like Ancestry and its chief rival, 23andMe. The Food and Drug Administration regulates consumer DNA tests related to health, like the 23andMe panel it approved earlier this year. So what exactly does the congressman want? For the Federal Trade Commission to force the firms to extract all their buried fine print about how they might distribute your data, and broadcast it loud and clear. “I think if most people knew that this information could be sold to third parties they would think twice,” Schumer said. “The last gift any of us want to give away this holiday season is our most personal and sensitive information.”

While there’s no evidence that these companies have let anyone’s genetic data fall into the hands of hackers—or anything half that bad—their policies do grant them free rein to host, transfer, process, analyze, distribute, and communicate your genetic information. You still technically own your DNA, but they own the rights to what’s in it—after it’s been anonymized and de-identified, of course. Both companies say the primary way they use this genetic data is to improve their products and services. But both have research partnerships that involve exchanging data for money—23andMe with drug companies like Pfizer and Genentech, Ancestry with Alphabet longevity spinout Calico.

“This isn’t a videogame, it’s people’s genetic code and it’s a very valuable commodity,” says Peter Pitts, the president of the Center for Medicine in the Public Interest and former FDA associate commissioner. He’d like to see more transparency from Ancestry and 23andMe about how often they resell DNA data and how much they make from it. That’s the only way for people to know what it’s really worth. “To treat it like a toy and put it under the Christmas tree is incredibly irresponsible.”

But that’s exactly what millions of people are going to do. While Ancestry officials didn’t provide exact sales figures for this year’s Black Friday weekend, they did say they sold three times as many kits as the same time period in 2016, an amount they’d previously reported as 560,000. Going into the long weekend, the company had sold slightly more than 6 million tests since launching the product in 2012. 23andMe declined to give any financial details, but thanks in part to a big price cut, its health test was one of Amazon’s five best-selling items on Black Friday, behind the Amazon Echo Dot, two other Alexa add-ons, and a programmable pressure cooker.

Amazon has become an increasingly important sales channel for both Ancestry and 23andMe in the two years since they began selling in the "home tests" section of the two-click shopping platform. But it was particularly huge for Ancestry when the aforementioned pressure cooker sold out late in the day on Monday. “From that moment you could just see it take off like a hockey stick,” says Ancestry executive vice president and general manager Ken Chahine, still surprised.

But not as surprised, he says, as Amazon. “They didn’t expect us to sell that much, so they moved a bunch of inventory out of the distribution centers to cold storage, probably in the middle of nowhere, and then they had to go track it all down, and for a while nobody knew where it was,” he says. It’s since been sorted out. But if you ordered a kit and it hasn’t come yet, at least now you know why.

Both Ancestry and 23andMe have acknowledged the criticism that has come with more widespread use of their products. But the companies maintain that their customers understand the trade-offs and have the opportunity to opt out at any time. When I interviewed Ancestry’s chief scientific officer Catherine Ball at the Commonwealth Club in July, the majority questions from the audience focused on issues of privacy and third-party access. “We do not own or assert any ownership over your genetics,” she told the crowd of about 100. “We just see ourselves as stewards and only do that which our customers have consented us to do.”

On Sunday night, in response to Schumer’s remarks, Kate Black, 23andMe’s privacy officer and corporate counsel, told NBC News something similar: “We do not sell individual customer information, nor do we include any customer data in our research program without an individual’s voluntary and informed consent. 23andMe customers are in control of their data—customers can choose to consent, or not to, at any time.”

Critics like Pitts say that’s “true but not accurate,” if you dig into the fine print. Which, he fears, people will spend even less time doing if they get the tests from a friend or relative. “That comes with an implicit endorsement, so people are likely to pay even less attention to the potential risks,” he says. A genetic test won’t shoot your eye out, but it should be handled with care.

Read more: https://www.wired.com/story/ancestrys-genetic-testing-kits-are-heading-for-your-stocking-this-year/

Everything You Need to Know About the GOP Tax Bill

Here are key changes to U.S. tax law for individuals and businesses that have emerged from the final Republican bill that’s headed for votes in the House and Senate next week.

Individual Tax Rates

(Note: Individual rate cuts would expire after 2025.)

Current law:

  • Seven rates, starting at 10 percent and reaching 39.6 percent for incomes above $418,401 for singles and $470,701 for married, joint filers.

Proposed: 

  • Seven rates, starting at 10 percent and reaching 37 percent for incomes above $500,000 for singles and $600,000 for married, joint filers.
    For joint filers:
    • 10 percent: $0 to $19,050
    • 12 percent: $19,050 to $77,400
    • 22 percent: $77,400 to $165,000
    • 24 percent: $165,000 to $315,000
    • 32 percent: $315,000 to $400,000
    • 35 percent: $400,000 to $600,000
    • 37 percent: $600,000 and above

    For single filers:

    • 10 percent: $0 to $9,525
    • 12 percent: $9,525 to $38,700
    • 22 percent: $38,700 to $82,500
    • 24 percent: $82,500 to $157,500
    • 32 percent: $157,500 to $200,000
    • 35 percent: $200,000 to $500,000
    • 37 percent: $500,000 and above

Corporate Tax Rate

Current law: 35 percent

Proposed: 21 percent, beginning in 2018.

Corporate Alternative Minimum Tax

Current law: Applies a 20 percent rate as part of a parallel tax system that limits tax benefits to prevent large-scale tax avoidance. Companies must calculate their ordinary tax and AMT tax, and pay whichever is higher.

Proposed: Repealed.

Individual Alternative Minimum Tax

Current law: Individual AMT can apply after exemption level of $54,300 for singles and $84,500 for married, joint filers, and the exemptions phase out at higher incomes.

Proposed: Increase the exemption to $70,300 for singles and $109,400 for joint filers. Increase the phase-out threshold to $500,000 for singles and $1 million for joint filers. The higher limits would expire on Jan. 1, 2026.

Expensing Equipment

Current law: Businesses must take depreciation, spreading the recognition of their equipment costs for tax purposes over several years.

Proposed: Businesses could fully and immediately deduct the cost of certain equipment purchased after Sept. 27, 2017 and before Jan. 1, 2023. After that, the percentage of cost that could be immediately deducted would gradually phase down.

Repatriation

Current law: The U.S. taxes multinationals on their global earnings at the corporate rate of 35 percent, but allows them to defer taxes on those foreign earnings until they bring them back to the U.S., or “repatriate” them.

Proposed: U.S. companies’ overseas income held as cash would be subject to a 15.5 percent rate, while non-cash holdings would face an 8 percent rate.

Pass-Through Deduction

Current law: Pass-through businesses, which include partnerships, limited liability companies, S corporations and sole proprietorships, pass their income to their owners, who pay tax at their individual rates.

Proposed: Owners could apply a 20 percent deduction to their business income, subject to limits that would begin at $315,000 for married couples (or half that for single taxpayers).

Obamacare Individual Mandate

Current law: An individual who fails to buy health insurance must pay penalties of $695 (higher for families) or 2.5 percent of their household income — whichever is higher, but capped at the national average cost of the most basic, low-premium, high-deductible plan.

Proposed: Repeal the penalties.

Standard Deduction and Personal Exemptions

Current law: $6,350 standard deduction for single taxpayers and $12,700 for married couples, filing jointly. Personal exemptions of $4,050 allowed for each family member.

Proposed: $12,000 standard deduction for single taxpayers and $24,000 for married couples, filing jointly. Personal exemptions repealed.

Individual State and Local Tax Deductions

Current law: Individuals can deduct the state and local taxes they pay, but the value is subject to certain limits for high earners.

Proposed: Individuals can deduct no more than $10,000 worth of the deductions, which could include a combination of property taxes and either sales or income taxes.

Mortgage Interest Deduction

Current law: Deductible mortgage interest is capped at loans of $1 million.

Proposed: Deductible mortgage interest for new purchases of first or second homes would be capped at loans of $750,000 starting on Jan. 1, 2018.

Medical Expense Deduction

Current law: Qualified medical expenses that exceed 10 percent of the taxpayer’s adjusted gross income are deductible.

Proposed: Reduce the threshold to 7.5 percent of AGI for 2017 and 2018.

Child Tax Credit

Current law: A $1,000 credit for each child under 17. The credit begins phasing out for couples earning more than $110,000. The credit is at least partially refundable to qualified taxpayers who earned more than $3,000.

Proposed: Double the credit to $2,000 and provide it for each child under 18 through 2024. Raise the phase-out amount to $500,000, and cap the refundable portion at $1,400 in 2018.

Estate Tax

Current law: Applies a 40 percent levy on estates worth more than $5.49 million for individuals and $10.98 million for couples.

Proposed: Double the thresholds so the levy applies to fewer estates. The higher thresholds would sunset in 2026.

    Read more: http://www.bloomberg.com/news/articles/2017-12-15/everything-you-need-to-know-about-the-gop-tax-overhaul-bill

    It’s Gonna Get a Lot Easier to Break Science Journal Paywalls

    Anurag Acharya’s problem was that the Google search bar is very smart, but also kind of dumb. As a Googler working on search 13 years ago, Acharya wanted to make search results encompass scholarly journal articles. A laudable goal, because unlike the open web, most of the raw output of scientific research was invisible—hidden behind paywalls. People might not even know it existed. “I grew up in India, and most of the time you didn’t even know if something existed. If you knew it existed, you could try to get it,” Acharya says. “‘How do I get access?’ is a second problem. If I don’t know about it, I won’t even try.”

    Acharya and a colleague named Alex Verstak decided that their corner of search would break with Google tradition and look behind paywalls—showing citations and abstracts even if it couldn’t cough up an actual PDF. “It was useful even if you did not have university access. That was a deliberate decision we made,” Acharya says.

    Then they hit that dumbness problem. The search bar doesn’t know what flavor of information you’re looking for. You type in “cancer;” do you want results that tell you your symptoms aren’t cancer (please), or do you want the Journal of the American Medical Association? The search bar doesn’t know.

    Acharya and Verstak didn't try to teach it. Instead, they built a spinoff, a search bar separate from Google-prime that would only look for journal articles, case law, patents—hardcore primary sources. And it worked. “We showed it to Larry [Page] and he said, ‘why is this not already out?’ That’s always a positive sign,” Acharya says.

    Today, even though you can’t access Scholar directly from the Google-prime page, it has become the internet’s default scientific search engine—even more than once-monopolistic Web of Science, the National Institutes of Health’s PubMed, and Scopus, owned by the giant scientific publisher Elsevier.

    But most science is still paywalled. More than three quarters of published journal articles—114 million on the World Wide Web alone, by one (lowball) estimate—are only available if you are affiliated with an institution that can afford pricey subscriptions or you can swing $40-per-article fees. In the last several years, though, scientists have made strides to loosen the grip of giant science publishers. They skip over the lengthy peer review process mediated by the big journals and just … post. Review comes after. The paywall isn’t crumbling, but it might be eroding. The open science movement, with its free distribution of articles before their official publication, is a big reason.

    Another reason, though, is stealthy improvement in scientific search engines like Google Scholar, Microsoft Academic, and Semantic Scholar—web tools increasingly able to see around paywalls or find articles that have jumped over. Scientific publishing ain’t like book publishing or journalism. In fact, it’s a little more like music, pre-iTunes, pre-Spotify. You know, right about when everyone started using Napster.

    Before World War II most scientific journals were published by small professional societies. But capitalism’s gonna capitalism. By the early 1970s the top five scientific publishers—Reed-Elsevier, Wiley-Blackwell, Springer, and Taylor & Francis—published about 20 percent of all journal articles. In 1996, when the transition to digital was underway and the PDF became the format of choice for journals, that number went up to 30 percent. Ten years later it was 50 percent.

    Those big-five publishers became the change they wanted to see in the publishing world—by buying it. Owning over 2,500 journals (including the powerhouse Cell) and 35,000 books and references (including Gray’s Anatomy) is big, right? Well, that’s Elsevier, the largest scientific publisher in the world, which also owns ScienceDirect, the online gateway to all those journals. It owns the (pre-Google Scholar) scientific search engine Scopus. It bought Mendeley, a reference manager with social and community functions. It even owns a company that monitors mentions of scientific work on social media. “Everywhere in the research ecosystem, from submission of papers to research evaluations made based on those papers and various acts associated with them online, Elsevier is present,” says Vincent Larivière, an information scientist at the University of Montreal and author of the paper with those stats about publishing I put one paragraph back.

    The company says all that is actually in the service of wider dissemination. “We are firmly in the open science space. We have tools, services, and partnerships that help create a more inclusive, more collaborative, more transparent world of research,” says Gemma Hersh,1 Elsevier’s vice president for open science. “Our mission is around improving research performance and working with the research community to do that.” Indeed, in addition to traditional, for-profit journals it also owns SSRN, a preprint server—one of those places that hosts unpaywalled, pre-publication articles—and publishes thousands of articles at various levels of openness.

    So Elsevier is science publishing’s version of Too Big to Fail. As such, it has faced various boycotts, slightly piratical workarounds, and general anger. (“The term ‘boycott’ comes up a lot, but I struggle with that. If I can be blunt, I think it’s a word that’s maybe misapplied,” Hersh says. “More researchers submit to us every year, and we publish more articles every year.”)

    If you’re not someone with “.edu” in your email, this might make you a little nuts. Not just because you might want to actually see some cool science, but because you already paid for that research. Your taxes (or maybe some zillionaire’s grant money) paid the scientists and funded the studies. The experts who reviewed and critiqued the results and conclusions before publication were volunteers. Then the journal that published it charged a university or a library—again, probably funded at least in part by your taxes—to subscribe. And then you gotta buy the article? Or the researcher had to pony up $2,0002 to make it open access?

    Now, publishers like Elsevier will say that the process of editing, peer-reviewing, copy editing, and distribution are a major, necessary value add. And look at the flip side: so-called predatory journals that charge authors to publish nominally open-access articles with no real editing or review (that, yes, show up in search results). Still, the scientific publishing business is a $10 billion-a-year game. In 2010, Elsevier reported profits of $1 billion and a 35 percent margin. So, yeah.

    In that early-digital-music metaphor, the publishers are the record labels and the PDFs are MP3s. But you still need a Napster. That’s where open-science-powered search engines come in.

    A couple years after Acharya and Verstak built Scholar, a team at Microsoft built their own version, called Academic. It was at the time a much, let’s say, leaner experience, with far fewer papers available. But then in 2015, Microsoft released a 2.0, and it’s a killer.

    Microsoft’s communication team declined to make any of the people who run it available, but a paper from the team at Microsoft Research lays the specs out pretty well: It figures out the bibliographic data of papers and combines that with results from Bing. (A real search engine that exists!) And you know what? It’s pretty great. It sees 83 million papers, not so far from estimations of the size of Google’s universe, and does the same kind of natural-language queries. Unlike Scholar, people can hook into Microsoft Academic’s API and see its citation graph, too.

    Even as recently as 2015, scientific search engines weren’t much use to anyone outside universities and libraries. You could find a citation to a paper, sure—but good luck actually reading it. Even though more overt efforts to subvert copyright like Sci-Hub are falling to lawsuits from places like Elsevier and the American Chemical Society, the open science movement gaining is momentum. PDFs are falling off virtual trucks all over the internet—posted on university web sites or places like ResearchGate and Academia.edu, hosts for exactly this kind of thing—Scholar’s and Academic’s first sorties against the paywall have been joined by reinforcements. It’s starting to look like a siege.

    For example the Chan Zuckerberg Initative, philanthropic arm of the founder of Facebook, is working on something aimed at increasing access. The founders of Mendeley have a new, venture-backed PDF finder called Kopernio. A browser extension called Unpaywall roots around the web for free PDFs of articles.

    A particularly novel web crawler comes from the non-profit Allen Institute for Artificial Intelligence. Semantic Scholar pores over a corpus of 40 million citations in computer science and biomedicine, and extracts the tables and charts as well as using machine learning to infer meaningful cites as “highly influential citations,” a new metric. Almost a million people use it every month.

    “We use AI techniques, particularly natural language processing and machine vision, to process the PDF and extract information that helps readers decide if the paper is of interest,” says Oren Etzioni, CEO of the Allen Institute for AI. “The net effect of all this is that more and more is open, and a number of publishers … have said making content discoverable via these search engines is not a bad thing.”

    Even with all these increases in discoverability and access, the technical challenges of scientific search don’t stop with paywalls. When Acharya and Verstak started out, Google relied on PageRank, a way to model how important hyperlinks between two web pages were. That’s not how scientific citations work. “The linkage between articles is in text. There are references, and references are all approximate,” Acharya says. “In scholarship, all your citations are one way. Everybody cites older stuff, and papers never get modified.”

    Plus, unlike a URL, the location or citation for a journal article is not the actual journal article. In fact, there might be multiple copies of the article at various locations. From a perspective as much philosophical and bibliographical, a PDF online is really just a picture of knowledge, in a way. So the search result showing a citation might also attach to multiple versions of the actual article.

    That’s a special problem when researchers can post pre-print versions of their own work but might not have copyright to the publication of record, the peer-reviewed, copy-edited version in the journal. Sometimes the differences are small; sometimes they’re not.

    Why don’t the search engines just use metadata to understand what version belongs where? Like when you download music, your app of choice automatically populates with things like an image, the artist’s name, the song titles…the data about the thing.

    The answer: metadata LOL. It’s a big problem. “It varies by source,” Etzioni says. “A whole bunch of that information is not available as structured metadata.” Even when there is metadata, it’s in idiosyncratic formats from publisher to publisher and server to server. “In a surprising way, we’re kind of in the dark ages, and the problem just keeps getting worse,” he says. More papers get published; more are digital. Even specialists can’t keep up.

    Which is why scientific search and open science are so intertwined and so critical. The reputation of a journal and the number of times a specific paper in that journal gets cited are metrics for determining who gets grants and who gets tenure, and by extension who gets to do bigger and bigger science. “Where the for-profit publishers and academic presses sort of have us by the balls is that we are addicted to prestige,” says Guy Geltner, a historian at the University of Amsterdam, open science advocate, and founder of a new user-owned social site for scientists called Scholarly Hub.

    The thing is, as is typical for Google, Scholar is as opaque about how it works and what it finds. Acharya wouldn’t give me numbers of users or the number of papers it searches. (“It’s larger than the estimates that are out there,” he says, and “an order of magnitude bigger than when we started.) No one outside Google fully understands how the search engine applies its criteria for inclusion,3 and indeed Scholar hoovers up way more than just PDFs of published or pre-published articles. You get course syllabi, undergraduate coursework, PowerPoint presentations … actually, for a reporter, it’s kind of fun. But tricky.

    That means the citation data is also obscure, which makes it hard to know what Scholar’s findings mean for science as a whole. Scholar may be a low-priority side-project (please don’t kill it like you killed Reader!) but maybe that data is going to be valuable someday. Elsevier obviously thinks it’s useful.

    The scientific landscape is shifting. "If you took a group of academics right now and asked them to create a new system of publishing, nobody would suggest what we're currently doing," says David Barner, a psychologist at UC San Diego and open science advocate. But change, Barner says, is hard. The people who'd make those changes are already overworked, already volunteering their time.

    Even Elsevier knows that change is coming. “Rather than scrabble around in one of the many programs you’ve mentioned, anyone can come to our Science and Society page, which details a host of programs and organizations we work with to cater through every scenario where somebody wants access,” Hersh says. And that’d be to the final, published, peer-reviewed version—the archived, permanent version of record.

    Digital revolutions have a way of #disrupting no matter what. As journal articles get more open and more searchable, value will come from understanding what people search for—as Google long ago understood about the open web. “We’re a high quality publisher, but we’re also an information analytics company, evolving services that the research community can use,” Hersh says.

    Because reputation and citation are core currencies to scientists, scientists have to be educated about the possibilities of open publication at the same time as prestigious, reputable venues have to exist. Preprints are great, and the researchers maintain copyright to them, but it’s also possible that the final citation-of-record could be different after it goes through review. There has to be a place where primary scientific work is available to the people who funded it, and a way for them to find it.

    Because if there isn’t? “A huge part of research output is suffocating behind paywalls. Sixty-five of the 100 most cited articles in history are behind paywalls. That’s the opposite of what science is supposed to do,” Geltner says. “We’re not factories producing proprietary knowledge. We’re engaged in debates, and we want the public to learn from those debates.”

    I'm sensitive to the irony of a WIRED writer talking about the social risks of a paywall, though I'd draw a distinction between paying a journalistic outlet for its journalism and paying a scientific publisher for someone else's science.

    An even more critical difference, though, is that a science paywall does more than separate gown from town. When all the solid, good information is behind a paywall, what’s left outside in the wasteland will be crap—propaganda and marketing. Those are always free, because people with political agendas and financial interests underwrite them. Understanding that vaccines are critical to public health and human-driven carbon emissions are un-terraforming the planet cannot be the purview of the one percent. “Access to science is going to be a first-world privilege,” Geltner says. “That’s the opposite of what science is supposed to be about.”

    1 UPDATE 12/3/17 11:55 AM Corrected the spelling of this name. 2 UPDATE 12/4/17 1:25 PM Removed the word "another;" researchers sometimes pay to make their own articles open-access. 3 UPDATE 12/4/17 1:25 PM Clarified to show that Google publishes inclusion criteria.

    Read more: https://www.wired.com/story/its-gonna-get-a-lot-easier-to-break-science-journal-paywalls/

    The Most Promising Cancer Treatments In a Century Have ArrivedBut Not For Everyone

    In 1891, a New York doctor named William B. Coley injected a mixture of beef broth and Streptococcus bacteria into the arm of a 40-year-old Italian man with an inoperable neck tumor. The patient got terribly sick—developing a fever, chills, and vomiting. But a month later, his cancer had shrunk drastically. Coley would go on to repeat the procedure in more than a thousand patients, with wildly varying degrees of success, before the US Food and Drug Administration shut him down.

    Coley’s experiments were the first forays into a field of cancer research known today as immunotherapy. Since his first experiments, the oncology world has mostly moved on to radiation and chemo treatments. But for more than a century, immunotherapy—which encompasses a range of treatments designed to supercharge or reprogram a patient’s immune system to kill cancer cells—has persisted, mostly around the margins of medicine. In the last few years, though, an explosion of tantalizing clinical results have reinvigorated the field and plunged investors and pharma execs into a spending spree.

    Though he didn’t have the molecular tools to understand why it worked, Coley’s forced infections put the body’s immune system into overdrive, allowing it to take out cancer cells along the way. While the FDA doesn’t have a formal definition for more modern immunotherapies, in the last few years it has approved at least eight drugs that fit the bill, unleashing a flood of money to finance new clinical trials. (Patients had better come with floods of money too—prices can now routinely top six figures.)

    But while the drugs are dramatically improving the odds of survival for some patients, much of the basic science is still poorly understood. And a growing number of researchers worry that the sprint to the clinic offers cancer patients more hype than hope.

    When immunotherapy works, it really works. But not for every kind of cancer, and not for every patient—not even, it turns out, for the majority of them. “The reality is immunotherapy is incredibly valuable for the people who can actually benefit from it, but there are far more people out there who don’t benefit at all,” says Vinay Prasad, an Oregon Health and Science University oncologist.

    Prasad has come to be regarded as a professional cancer care critic, thanks to his bellicose Twitter style and John Arnold Foundation-backed crusade against medical practices he says are based on belief, not scientific evidence. Using national cancer statistics and FDA approval records, Prasad recently estimated the portion of all patients dying from all types of cancer in America this year who might actually benefit from immunotherapy. The results were disappointing: not even 10 percent.

    Now, that’s probably a bit of an understatement. Prasad was only looking at the most widely used class of immunotherapy drugs in a field that is rapidly expanding. Called checkpoint inhibitors, they work by disrupting the immune system’s natural mechanism for reining in T cells, blood-borne sentinels that bind and kill diseased cells throughout the body. The immune cells are turned off most of the time, thanks to proteins that latch on to a handful of receptors on their surface. But scientists designed antibodies to bind to those same receptors, knocking out the regulatory protein and keeping the cells permanently switched to attack mode.

    The first checkpoint inhibitors just turned T cells on. But some of the newer ones can work more selectively, using the same principle to jam a signal that tumors use to evade T cells. So far, checkpoint inhibitors have shown near-miraculous results for a few rare, previously incurable cancers like Hodgkin’s lymphoma, renal cell carcinoma, and non-small cell lung cancer. The drugs are only approved to treat those conditions, leaving about two-thirds of terminal cancer patients without an approved immunotherapy option.

    But Prasad says that isn’t stopping physicians from prescribing the drugs anyway.

    “Hype has encouraged rampant off-label use of checkpoint inhibitors as a last-ditch effort,” he says—even for patients with tumors that show no evidence they’ll respond to the drugs. The antibodies are available off the shelf, but at a list price near $150,000 per year, it’s an investment Prasad says doctors shouldn’t encourage lightly. Especially when there’s no reliable way of predicting who will respond and who won’t. “This thwarts one of the goals of cancer care," says Prasad. "When you run out of helpful responses, how do you help a patient navigate what it means to die well?”

    Merck and Bristol-Myers Squibb have dominated this first wave of immunotherapy, selling almost $9 billion worth of checkpoint inhibitors since they went on sale in 2015. Roche, AstraZeneca, Novartis, Eli Lilly, Abbvie, and Regeneron have all since jumped in the game, spending billions on acquiring biotech startups and beefing up in-house pipelines. And 800 clinical trials involving a checkpoint inhibitor are currently underway in the US, compared with about 200 in 2015. “This is not sustainable,” Genentech VP of cancer immunology Ira Mellman told the audience at last year’s annual meeting of the Society for Immunotherapy of Cancer. With so many trials, he said, the industry was throwing every checkpoint inhibitor combination at the wall just to see what would stick.

    After more than a decade stretching out the promise of checkpoint inhibitors, patients—and businesses—were ready for something new. And this year, they got it: CAR T cell therapy. The immunotherapy involves extracting a patient’s T cells and genetically rewiring them so they can more efficiently home in on tumors in the body—training a foot soldier as an assassin that can slip behind enemy lines.

    In September, the FDA cleared the first CAR-T therapy—a treatment for children with advanced leukemia, developed by Novartis—which made history as the first-ever gene therapy approved for market. A month later the agency approved another live cell treatment, developed by Kite Pharma, for a form of adult lymphoma. In trials for the lymphoma drug, 50 percent of patients saw their cancer disappear completely, and stay gone.

    Kite’s ascendance in particular is a stunning indicator of how much money CAR-T therapy has attracted, and how fast. The company staged a $128 million IPO in 2014—when it had only a single late-phase clinical trial to its name—and sold to Gilead Science in August for $11.9 billion. For some context, consider that when Pfizer bought cancer drugmaker Medivation for $14 billion last year—one of the biggest pharma deals of 2016—the company already had an FDA-approved blockbuster tumor-fighter on the market with $2 billion in annual sales, plus two late-stage candidates in the pipeline.

    While Kite and Novartis were the only companies to actually launch products in 2017, more than 40 other pharma firms and startups are currently building pipelines. Chief rival Juno Therapeutics went public with a massive $265 million initial offering—the largest biotech IPO of 2014—before forming a $1 billion partnership with Celgene in 2015. In the last few years, at least half a dozen other companies have made similar up-front deals worth hundreds of millions.

    These treatments will make up just a tiny slice of the $107 billion cancer drug market. Only about 600 people a year, for example, could benefit from Novartis’ flagship CAR-T therapy. But the company set the price for a full course of treatment at a whopping $475,000. So despite the small clientele, the potential payoff is huge—and the technology is attracting a lot of investor interest. “CAR-T venture financing is still a small piece of total venture funding in oncology, but given that these therapies are curative for a majority of patients that have received them in clinical trials, the investment would appear to be justified,” says Mandy Jackson, a managing editor for research firm Informa Pharma Intelligence.

    CAR-T, with its combination of gene and cell therapies, may be the most radical anticancer treatment ever to arrive in clinics. But the bleeding edge of biology can be a dangerous place for patients.

    Sometimes, the modified T cells go overboard, excreting huge quantities of molecules called cytokines that lead to severe fevers, low blood pressure, and difficulty breathing. In some patients it gets even worse. Sometimes the blood-brain barrier inexplicably breaks down—and the T cells and their cytokines get inside patients’ skulls. Last year, Juno pulled the plug on its lead clinical trial after five leukemia patients died from massive brain swelling. Other patients have died in CAR-T trials at the National Cancer Institute and the University of Pennsylvania.

    Scientists don’t fully understand why some CAR-T patients experience cytokine storms and neurotoxicity and others come out cured. “It’s kind of like the equivalent of getting on a Wright Brother’s airplane as opposed to walking on a 747 today,” says Wendell Lim, a biophysical chemist and director of the UC San Francisco Center for Systems and Synthetic Biology. To go from bumping along at a few hundred feet to cruise control at Mach 0.85 will mean equipping T cells with cancer-sensing receptors that are more specific than the current offerings.

    Take the two FDA-approved CAR-T cell therapies, he says. They both treat blood cancers in which immune responders called B cells become malignant and spread throughout the body. Doctors reprogram patients’ T cells to seek out a B cell receptor called CD-19. When they find it, they latch on and shoot it full of toxins. Thing is, the reprogrammed T cells can’t really tell the difference between cancerous B cells and normal ones. The therapy just takes them all out. Now, you can live without B cells if you receive antibody injections to compensate—so the treatment works out fine most of the time.

    But solid tumors are trickier—they’re made up of a mix of cells with different genetic profiles. Scientists have to figure out which tumor cells matter to the growth of the cancer and which ones don’t. Then they have to design T cells with antigens that can target just those ones and nothing else. An ideal signature would involve two to three antigens that your assassin T cells can use to pinpoint the target with a bullet instead of a grenade.

    Last year Lim launched a startup called Cell Design Labs to try to do just that, as well as creating a molecular on-off-switch to make treatments more controlled. Only if researchers can gain this type of precise command, says Lim, will CAR-T treatments become as safe and predictable as commercial airline flight.

    The field has matured considerably since Coley first shot his dying patient full of a dangerous bacteria, crossed his fingers, and hoped for the best. Sure, the guy lived, even making a miraculous full recovery. But many after him didn’t. And that “fingers crossed” approach still lingers over immunotherapy today.

    All these years later, the immune system remains a fickle ally in the war on cancer. Keeping the good guys from going double-agent is going to take a lot more science. But at least the revolution will be well-financed.

    Read more: https://www.wired.com/story/cancer-immunotherapy-has-arrived-but-not-for-everyone/

    Americans Are Retiring Later, Dying Sooner and Sicker In-Between

    The U.S. retirement age is rising, as the government pushes it higher and workers stay in careers longer.

    But lifespans aren’t necessarily extending to offer equal time on the beach. Data released last week suggest Americans’ health is declining and millions of middle-age workers face the prospect of shorter, and less active, retirements than their parents enjoyed.

    Here are the stats: The U.S. age-adjusted mortality rate—a measure of the number of deaths per year—rose 1.2 percent from 2014 to 2015, according to the Society of Actuaries. That’s the first year-over-year increase since 2005, and only the second rise greater than 1 percent since 1980.

     

    At the same time that Americans’ life expectancy is stalling, public policy and career tracks mean millions of U.S. workers are waiting longer to call it quits. The age at which people can claim their full Social Security benefits is gradually moving up, from 65 for those retiring in 2002 to 67 in 2027.

    Almost one in three Americans age 65 to 69 is still working, along with almost one in five in their early 70s.

    Postponing retirement can make financial sense, because extended careers can make it possible to afford retirements that last past age 90 or even 100. But a study out this month adds some caution to that calculation.

    Americans in their late 50s already have more serious health problems than people at the same ages did 10 to 15 years ago, according to the journal Health Affairs.

    University of Michigan economists HwaJung Choi and Robert Schoeni used survey data to compare middle-age Americans’ health. A key measure is whether people have trouble with an “activity of daily living,” or ADL, such as walking across a room, dressing and bathing themselves, eating, or getting in or out of bed. The study showed the number of middle-age Americans with ADL limitations has jumped: 12.5 percent of Americans at the current retirement age of 66 had an ADL limitation in their late 50s, up from 8.8 percent for people with a retirement age of 65.

    At the current retirement age of 66, a quarter of Americans age 58 to 60 rated themselves in “poor” or “fair” health. That’s up 2.6 points from the group who could retire with full benefits at 65, the Michigan researchers found.

    Cognitive skills have also declined over time. For those with a retirement age of 66, 11 percent already had some kind of dementia or other cognitive decline at age 58 to 60, according to the study. That’s up from 9.5 percent of Americans just a few years older, with a retirement age between 65 and 66.

    While death rates can be volatile from year to year, Choi and Schoeni’s study is part of a raft of other research showing the health of Americans deteriorating.

    Researchers have offered many theories for why Americans’ health is getting worse. Princeton University economists Anne Case and Angus Deaton, a Nobel Prize winner, have argued that an epidemic of suicide, drug overdoses and alcohol abuse have caused a spike in death rates among middle-age whites.

    Higher rates of obesity may also be taking their toll. And Americans may have already seen most of the benefits from previous positive developments that cut the death rate, such as a decline in smoking and medical advances like statins that fight cardiovascular disease.

    Declining health and life expectancy are good news for one constituency: Pension plans, which must send a monthly check to retirees for as long as they live.

    According to the latest figures from the Society of Actuaries, life expectancy for pension participants has dropped since its last calculation by 0.2 years. A 65-year-old man can expect to live to 85.6 years, and a woman can expect to make it to 87.6. As a result, the group calculates a typical pension plan’s obligations could fall by 0.7 percent to 1 percent.

      Read more: http://www.bloomberg.com/news/articles/2017-10-23/americans-are-retiring-later-dying-sooner-and-sicker-in-between

      Trump Officials Dispute the Benefits of Birth Control to Justify Rules

      When the Trump administration elected to stop requiring many employers to offer birth-control coverage in their health plans, it devoted nine of its new rule’s 163 pages to questioning the links between contraception and preventing unplanned pregnancies.

      In the rule released Friday, officials attacked a 2011 report that recommended mandatory birth-control coverage to help women avoid unintended pregnancies. That report, requested by the Department of Health and Human Services, was done by the National Academies of Sciences, Engineering and Medicine — then the Institute of Medicine — an expert group that serves as the nation’s scientific adviser.

      “The rates of, and reasons for, unintended pregnancy are notoriously difficult to measure,” according to the Trump administration’s interim final rule. “In particular, association and causality can be hard to disentangle.”

      Multiple studies have found that access or use of contraception reduced unintended pregnancies. 

      Claims in the report that link increased contraceptive use by unmarried women and teens to decreases in unintended pregnancies “rely on association rather than causation,” according to the rule. The rule references another study that found increased access to contraception decreased teen pregnancies short-term but led to an increase in the long run.

      “We know that safe contraception — and contraception is incredibly safe — leads to a reduction in pregnancies,” said Michele Bratcher Goodwin, director of the Center for Biotechnology and Global Health Policy at the University of California, Irvine, School of Law. “This has been data that we’ve had for decades.”

      Riskier Behavior

      The rules were released as part of a broader package of protections for religious freedom that the administration announced Friday.

      The government also said imposing a coverage mandate could “affect risky sexual behavior in a negative way” though it didn’t point to any particular studies to support its point. A 2014 study by the Washington University School of Medicine in St. Louis found providing no-cost contraception did not lead to riskier sexual behavior.

      The rule asserts that positive health effects associated with birth control “might also be partially offset by an association with negative health effects.” The rule connects the claim of negative health effects to a call by the National Institutes of Health in 2013 for the development of new contraceptives that stated current options can have “many undesirable side effects.” 

      The rule also describes an Agency for Healthcare Research and Quality review that found oral contraceptives increased users’ risk of breast cancer and vascular events, making the drugs’ use in preventing ovarian cancer uncertain.

      Federal officials used all of these assertions to determine the government “need not take a position on these empirical questions.”

      “Our review is sufficient to lead us to conclude that significantly more uncertainty and ambiguity exists in the record than the Departments previously acknowledged.”

        Read more: http://www.bloomberg.com/news/articles/2017-10-06/trump-officials-dispute-birth-control-benefits-to-justify-rules

        Trump’s New Obamacare Killer to Cost Uncle Sam $194 Billion

        President Donald Trump is halting some Obamacare subsidies. A big money saver for taxpayers, right? Wrong. The move could actually force the government to dole out almost $200 billion more on health insurance over the next decade.

        Here’s why: The insurer payouts Trump cut off aren’t the only government funds financing the program. Consumers also can get help with their insurance premiums. When the insurer subsidies are discontinued, those premiums are pushed higher — and because the consumer subsidies are far bigger than those given to insurers, that’s a costly trade.

        More than eight in ten individuals who buy Obamacare plans get help paying their premiums directly from the federal government. Those subsidies effectively cap how much people have to pay for insurance as a percentage of their income. 

        Even if premiums climb, people who receive those benefits won’t pay more out of their own pockets. The subsidies are available to people making as much as four times the federal poverty level, or just over $97,000 for a family of four.

        That means that those most likely to be hurt by the president’s action aren’t low-income people who will still get help with their costs. Instead, consumers who make too much money to qualify for subsidies will now have to pay a much higher price for their health plans.

        It all adds up to a hefty bill for taxpayers for as long as the Affordable Care Act is the law of the land. The Congressional Budget Office estimated that ending the cost-sharing payments would increase the U.S. fiscal shortfall by $194 billion over the next decade as subsidy outlays jump.

          Read more: http://www.bloomberg.com/news/articles/2017-10-13/trump-s-latest-obamacare-killer-will-cost-uncle-sam-194-billion

          The shorter your sleep, the shorter your life: the new sleep science

          Leading neuroscientist Matthew Walker on why sleep deprivation is increasing our risk of cancer, heart attack and Alzheimers and what you can do about it

          Matthew Walker has learned to dread the question What do you do? At parties, it signals the end of his evening; thereafter, his new acquaintance will inevitably cling to him like ivy. On an aeroplane, it usually means that while everyone else watches movies or reads a thriller, he will find himself running an hours-long salon for the benefit of passengers and crew alike. Ive begun to lie, he says. Seriously. I just tell people Im a dolphin trainer. Its better for everyone.

          Walker is a sleep scientist. To be specific, he is the director of the Center for Human Sleep Science at the University of California, Berkeley, a research institute whose goal possibly unachievable is to understand everything about sleeps impact on us, from birth to death, in sickness and health. No wonder, then, that people long for his counsel. As the line between work and leisure grows ever more blurred, rare is the person who doesnt worry about their sleep. But even as we contemplate the shadows beneath our eyes, most of us dont know the half of it and perhaps this is the real reason he has stopped telling strangers how he makes his living. When Walker talks about sleep he cant, in all conscience, limit himself to whispering comforting nothings about camomile tea and warm baths. Its his conviction that we are in the midst of a catastrophic sleep-loss epidemic, the consequences of which are far graver than any of us could imagine. This situation, he believes, is only likely to change if government gets involved.

          Walker has spent the last four and a half years writing Why We Sleep, a complex but urgent book that examines the effects of this epidemic close up, the idea being that once people know of the powerful links between sleep loss and, among other things, Alzheimers disease, cancer, diabetes, obesity and poor mental health, they will try harder to get the recommended eight hours a night (sleep deprivation, amazing as this may sound to Donald Trump types, constitutes anything less than seven hours). But, in the end, the individual can achieve only so much. Walker wants major institutions and law-makers to take up his ideas, too. No aspect of our biology is left unscathed by sleep deprivation, he says. It sinks down into every possible nook and cranny. And yet no one is doing anything about it. Things have to change: in the workplace and our communities, our homes and families. But when did you ever see an NHS poster urging sleep on people? When did a doctor prescribe, not sleeping pills, but sleep itself? It needs to be prioritised, even incentivised. Sleep loss costs the UK economy over 30bn a year in lost revenue, or 2% of GDP. I could double the NHS budget if only they would institute policies to mandate or powerfully encourage sleep.

          Why, exactly, are we so sleep-deprived? What has happened over the course of the last 75 years? In 1942, less than 8% of the population was trying to survive on six hours or less sleep a night; in 2017, almost one in two people is. The reasons are seemingly obvious. First, we electrified the night, Walker says. Light is a profound degrader of our sleep. Second, there is the issue of work: not only the porous borders between when you start and finish, but longer commuter times, too. No one wants to give up time with their family or entertainment, so they give up sleep instead. And anxiety plays a part. Were a lonelier, more depressed society. Alcohol and caffeine are more widely available. All these are the enemies of sleep.

          But Walker believes, too, that in the developed world sleep is strongly associated with weakness, even shame. We have stigmatised sleep with the label of laziness. We want to seem busy, and one way we express that is by proclaiming how little sleep were getting. Its a badge of honour. When I give lectures, people will wait behind until there is no one around and then tell me quietly: I seem to be one of those people who need eight or nine hours sleep. Its embarrassing to say it in public. They would rather wait 45 minutes for the confessional. Theyre convinced that theyre abnormal, and why wouldnt they be? We chastise people for sleeping what are, after all, only sufficient amounts. We think of them as slothful. No one would look at an infant baby asleep, and say What a lazy baby! We know sleeping is non-negotiable for a baby. But that notion is quickly abandoned [as we grow up]. Humans are the only species that deliberately deprive themselves of sleep for no apparent reason. In case youre wondering, the number of people who can survive on five hours of sleep or less without any impairment, expressed as a percent of the population and rounded to a whole number, is zero.

          The world of sleep science is still relatively small. But it is growing exponentially, thanks both to demand (the multifarious and growing pressures caused by the epidemic) and to new technology (such as electrical and magnetic brain stimulators), which enables researchers to have what Walker describes as VIP access to the sleeping brain. Walker, who is 44 and was born in Liverpool, has been in the field for more than 20 years, having published his first research paper at the age of just 21. I would love to tell you that I was fascinated by conscious states from childhood, he says. But in truth, it was accidental. He started out studying for a medical degree in Nottingham. But having discovered that doctoring wasnt for him he was more enthralled by questions than by answers he switched to neuroscience, and after graduation, began a PhD in neurophysiology supported by the Medical Research Council. It was while working on this that he stumbled into the realm of sleep.

          Matthew
          Matthew Walker photographed in his sleep lab. Photograph: Saroyan Humphrey for the Observer

          I was looking at the brainwave patterns of people with different forms of dementia, but I was failing miserably at finding any difference between them, he recalls now. One night, however, he read a scientific paper that changed everything. It described which parts of the brain were being attacked by these different types of dementia: Some were attacking parts of the brain that had to do with controlled sleep, while other types left those sleep centres unaffected. I realised my mistake. I had been measuring the brainwave activity of my patients while they were awake, when I should have been doing so while they were asleep. Over the next six months, Walker taught himself how to set up a sleep laboratory and, sure enough, the recordings he made in it subsequently spoke loudly of a clear difference between patients. Sleep, it seemed, could be a new early diagnostic litmus test for different subtypes of dementia.

          After this, sleep became his obsession. Only then did I ask: what is this thing called sleep, and what does it do? I was always curious, annoyingly so, but when I started to read about sleep, I would look up and hours would have gone by. No one could answer the simple question: why do we sleep? That seemed to me to be the greatest scientific mystery. I was going to attack it, and I was going to do that in two years. But I was naive. I didnt realise that some of the greatest scientific minds had been trying to do the same thing for their entire careers. That was two decades ago, and Im still cracking away. After gaining his doctorate, he moved to the US. Formerly a professor of psychiatry at Harvard Medical School, he is now professor of neuroscience and psychology at the University of California.

          Does his obsession extend to the bedroom? Does he take his own advice when it comes to sleep? Yes. I give myself a non-negotiable eight-hour sleep opportunity every night, and I keep very regular hours: if there is one thing I tell people, its to go to bed and to wake up at the same time every day, no matter what. I take my sleep incredibly seriously because I have seen the evidence. Once you know that after just one night of only four or five hours sleep, your natural killer cells the ones that attack the cancer cells that appear in your body every day drop by 70%, or that a lack of sleep is linked to cancer of the bowel, prostate and breast, or even just that the World Health Organisation has classed any form of night-time shift work as a probable carcinogen, how could you do anything else?

          There is, however, a sting in the tale. Should his eyelids fail to close, Walker admits that he can be a touch Woody Allen-neurotic. When, for instance, he came to London over the summer, he found himself jet-lagged and wide awake in his hotel room at two oclock in the morning. His problem then, as always in these situations, was that he knew too much. His brain began to race. I thought: my orexin isnt being turned off, the sensory gate of my thalamus is wedged open, my dorsolateral prefrontal cortex wont shut down, and my melatonin surge wont happen for another seven hours. What did he do? In the end, it seems, even world experts in sleep act just like the rest of us when struck by the curse of insomnia. He turned on a light and read for a while.

          Will Why We Sleep have the impact its author hopes? Im not sure: the science bits, it must be said, require some concentration. But what I can tell you is that it had a powerful effect on me. After reading it, I was absolutely determined to go to bed earlier a regime to which I am sticking determinedly. In a way, I was prepared for this. I first encountered Walker some months ago, when he spoke at an event at Somerset House in London, and he struck me then as both passionate and convincing (our later interview takes place via Skype from the basement of his sleep centre, a spot which, with its bedrooms off a long corridor, apparently resembles the ward of a private hospital). But in another way, it was unexpected. I am mostly immune to health advice. Inside my head, there is always a voice that says just enjoy life while it lasts.

          The evidence Walker presents, however, is enough to send anyone early to bed. Its no kind of choice at all. Without sleep, there is low energy and disease. With sleep, there is vitality and health. More than 20 large scale epidemiological studies all report the same clear relationship: the shorter your sleep, the shorter your life. To take just one example, adults aged 45 years or older who sleep less than six hours a night are 200% more likely to have a heart attack or stroke in their lifetime, as compared with those sleeping seven or eight hours a night (part of the reason for this has to do with blood pressure: even just one night of modest sleep reduction will speed the rate of a persons heart, hour upon hour, and significantly increase their blood pressure).

          A lack of sleep also appears to hijack the bodys effective control of blood sugar, the cells of the sleep-deprived appearing, in experiments, to become less responsive to insulin, and thus to cause a prediabetic state of hyperglycaemia. When your sleep becomes short, moreover, you are susceptible to weight gain. Among the reasons for this are the fact that inadequate sleep decreases levels of the satiety-signalling hormone, leptin, and increases levels of the hunger-signalling hormone, ghrelin. Im not going to say that the obesity crisis is caused by the sleep-loss epidemic alone, says Walker. Its not. However, processed food and sedentary lifestyles do not adequately explain its rise. Something is missing. Its now clear that sleep is that third ingredient. Tiredness, of course, also affects motivation.

          Sleep has a powerful effect on the immune system, which is why, when we have flu, our first instinct is to go to bed: our body is trying to sleep itself well. Reduce sleep even for a single night, and your resilience is drastically reduced. If you are tired, you are more likely to catch a cold. The well-rested also respond better to the flu vaccine. As Walker has already said, more gravely, studies show that short sleep can affect our cancer-fighting immune cells. A number of epidemiological studies have reported that night-time shift work and the disruption to circadian sleep and rhythms that it causes increase the odds of developing cancers including breast, prostate, endometrium and colon.

          Getting too little sleep across the adult lifespan will significantly raise your risk of developing Alzheimers disease. The reasons for this are difficult to summarise, but in essence it has to do with the amyloid deposits (a toxin protein) that accumulate in the brains of those suffering from the disease, killing the surrounding cells. During deep sleep, such deposits are effectively cleaned from the brain. What occurs in an Alzheimers patient is a kind of vicious circle. Without sufficient sleep, these plaques build up, especially in the brains deep-sleep-generating regions, attacking and degrading them. The loss of deep sleep caused by this assault therefore lessens our ability to remove them from the brain at night. More amyloid, less deep sleep; less deep sleep, more amyloid, and so on. (In his book, Walker notes unscientifically that he has always found it curious that Margaret Thatcher and Ronald Reagan, both of whom were vocal about how little sleep they needed, both went on to develop the disease; it is, moreover, a myth that older adults need less sleep.) Away from dementia, sleep aids our ability to make new memories, and restores our capacity for learning.

          And then there is sleeps effect on mental health. When your mother told you that everything would look better in the morning, she was wise. Walkers book includes a long section on dreams (which, says Walker, contrary to Dr Freud, cannot be analysed). Here he details the various ways in which the dream state connects to creativity. He also suggests that dreaming is a soothing balm. If we sleep to remember (see above), then we also sleep to forget. Deep sleep the part when we begin to dream is a therapeutic state during which we cast off the emotional charge of our experiences, making them easier to bear. Sleep, or a lack of it, also affects our mood more generally. Brain scans carried out by Walker revealed a 60% amplification in the reactivity of the amygdala a key spot for triggering anger and rage in those who were sleep-deprived. In children, sleeplessness has been linked to aggression and bullying; in adolescents, to suicidal thoughts. Insufficient sleep is also associated with relapse in addiction disorders. A prevailing view in psychiatry is that mental disorders cause sleep disruption. But Walker believes it is, in fact, a two-way street. Regulated sleep can improve the health of, for instance, those with bipolar disorder.

          Ive mentioned deep sleep in this (too brief) summary several times. What is it, exactly? We sleep in 90-minute cycles, and its only towards the end of each one of these that we go into deep sleep. Each cycle comprises two kinds of sleep. First, there is NREM sleep (non-rapid eye movement sleep); this is then followed by REM (rapid eye movement) sleep. When Walker talks about these cycles, which still have their mysteries, his voice changes. He sounds bewitched, almost dazed.

          During NREM sleep, your brain goes into this incredible synchronised pattern of rhythmic chanting, he says. Theres a remarkable unity across the surface of the brain, like a deep, slow mantra. Researchers were once fooled that this state was similar to a coma. But nothing could be further from the truth. Vast amounts of memory processing is going on. To produce these brainwaves, hundreds of thousands of cells all sing together, and then go silent, and on and on. Meanwhile, your body settles into this lovely low state of energy, the best blood-pressure medicine you could ever hope for. REM sleep, on the other hand, is sometimes known as paradoxical sleep, because the brain patterns are identical to when youre awake. Its an incredibly active brain state. Your heart and nervous system go through spurts of activity: were still not exactly sure why.

          Does the 90-minute cycle mean that so-called power naps are worthless? They can take the edge off basic sleepiness. But you need 90 minutes to get to deep sleep, and one cycle isnt enough to do all the work. You need four or five cycles to get all the benefit. Is it possible to have too much sleep? This is unclear. There is no good evidence at the moment. But I do think 14 hours is too much. Too much water can kill you, and too much food, and I think ultimately the same will prove to be true for sleep. How is it possible to tell if a person is sleep-deprived? Walker thinks we should trust our instincts. Those who would sleep on if their alarm clock was turned off are simply not getting enough. Ditto those who need caffeine in the afternoon to stay awake. I see it all the time, he says. I get on a flight at 10am when people should be at peak alert, and I look around, and half of the plane has immediately fallen asleep.

          So what can the individual do? First, they should avoid pulling all-nighters, at their desks or on the dancefloor. After being awake for 19 hours, youre as cognitively impaired as someone who is drunk. Second, they should start thinking about sleep as a kind of work, like going to the gym (with the key difference that it is both free and, if youre me, enjoyable). People use alarms to wake up, Walker says. So why dont we have a bedtime alarm to tell us weve got half an hour, that we should start cycling down? We should start thinking of midnight more in terms of its original meaning: as the middle of the night. Schools should consider later starts for students; such delays correlate with improved IQs. Companies should think about rewarding sleep. Productivity will rise, and motivation, creativity and even levels of honesty will be improved. Sleep can be measured using tracking devices, and some far-sighted companies in the US already give employees time off if they clock enough of it. Sleeping pills, by the way, are to be avoided. Among other things, they can have a deleterious effect on memory.

          Those who are focused on so-called clean sleep are determined to outlaw mobiles and computers from the bedroom and quite right, too, given the effect of LED-emitting devices on melatonin, the sleep-inducing hormone. Ultimately, though, Walker believes that technology will be sleeps saviour. There is going to be a revolution in the quantified self in industrial nations, he says. We will know everything about our bodies from one day to the next in high fidelity. That will be a seismic shift, and we will then start to develop methods by which we can amplify different components of human sleep, and do that from the bedside. Sleep will come to be seen as a preventive medicine.

          What questions does Walker still most want to answer? For a while, he is quiet. Its so difficult, he says, with a sigh. There are so many. I would still like to know where we go, psychologically and physiologically, when we dream. Dreaming is the second state of human consciousness, and we have only scratched the surface so far. But I would also like to find out when sleep emerged. I like to posit a ridiculous theory, which is: perhaps sleep did not evolve. Perhaps it was the thing from which wakefulness emerged. He laughs. If I could have some kind of medical Tardis and go back in time to look at that, well, I would sleep better at night.

          Why We Sleep: The New Science of Sleep and Dreamsby Matthew Walker is published by Allen Lane (20). To order a copy for 17 go toguardianbookshop.com or call 0330 333 6846. Free UK p&p over 10, online orders only. Phone orders min p&p of 1.99

          Sleep in numbers

          Two-thirds of adults in developed nations fail to obtain the nightly eight hours of sleep recommended by the World Health Organisation.

          An adult sleeping only 6.75 hours a night would be predicted to live only to their early 60s without medical intervention.

          A 2013 study reported that men who slept too little had a sperm count 29% lower than those who regularly get a full and restful nights sleep.

          If you drive a car when you have had less than five hours sleep, you are 4.3 times more likely to be involved in a crash. If you drive having had four hours, you are 11.5 times more likely to be involved in an accident.

          A hot bath aids sleep not because it makes you warm, but because your dilated blood vessels radiate inner heat, and your core body temperature drops. To successfully initiate sleep, your core temperature needs to drop about 1C.

          The time taken to reach physical exhaustion by athletes who obtain anything less than eight hours of sleep, and especially less than six hours, drops by 10-30%.

          There are now more than 100 diagnosed sleep disorders, of which insomnia is the mostcommon.

          Morning types, who prefer to awake at or around dawn, make up about 40% of the population. Evening types, who prefer to go to bed late and wake up late, account for about 30%. The remaining 30% lie somewhere in between.

          Read more: https://www.theguardian.com/lifeandstyle/2017/sep/24/why-lack-of-sleep-health-worst-enemy-matthew-walker-why-we-sleep