LSD is famed for the hallucinations it often produces.
The acid tests of 1960s San Francisco have morphed into something quite different in today’s Silicon Valley. Mind-altering trips have given way to subtle productivity boosts purportedly caused by tiny amounts of LSD or other psychedelic drugs. Fans claim that this ‘microdosing’ boosts creativity and concentration, but sceptics doubt that ingesting or inhaling one-tenth of the normal dose could have an effect.
Science could soon help to settle the matter. Researchers have finally mapped the 3D structure of LSD in its active state — and the details, published today in Cell1, indicate the key to the chemical’s potency1. Another team reports today in Current Biology2 that it has pinpointed the molecular go-between that creates the perception of deep meaning experienced during acid trips — a feeling that the writer Aldous Huxley once described as “solidarity with the Universe”.
“This is what we dreamed of doing when I was a graduate student in the seventies,” says Gavril Pasternak, a pharmacologist at Memorial Sloan Kettering Cancer Center in New York City who has spent decades studying the receptor proteins in the brain that mediate the activity of opioids and psychedelic drugs. “Work like this expands our understanding of how these receptors work.”
In 1972, researchers revealed LSD’s shape by mapping the arrangement of atoms in its crystallized form3. But in the decades since, they’ve struggled to reveal the crystal structure of a receptor grasping a molecule of LSD or another psychedelic drug. This active configuration is key to understanding how drugs work, because their action depends on how they cling to molecules in the body.
Now, the team behind the Cell study has shown how LSD binds to the protein 5-HT2B, a receptor for the neurotransmitter serotonin, which helps regulate activities such as appetite and mood. “This is the first picture of a psychedelic drug in action,” says lead author Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill.
Roth was surprised to discover that the receptor includes a lid-shaped structure that hovers over the LSD molecule, and that the drug apparently triggers the lid to close, trapping the molecule inside the receptor. “Imagine a person crawling into a manhole and a cover sliding over them so they can’t get out,” he says.
The lid seems to explain why LSD’s effects can last for more than 20 hours, depending on the amount taken. It also supports the idea that microdosing can have an effect, even when people take doses that are less than one-tenth of the normal amount. “The fact that LSD gets trapped provides an explanation for why extremely small amounts of the drug can still be potent,” Roth says. “Before this, what I heard from Silicon Valley was purely anecdotal.”
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The sound of music
Preller’s team asked study participants to list songs that were personally meaningful to them. Then each person was randomly given LSD, a placebo or LSD with ketanserin, a drug that stops LSD from binding to a serotonin receptor similar to 5-HT2B. Importantly, ketanserin does not prevent LSD from connecting to other proteins, such as dopamine receptors or adrenoreceptors.
Soon after the dose, the participants heard clips from their chosen tunes, similar songs and free jazz, which almost none of them had previously considered meaningful. They rated each clip in terms of whether the song felt meaningful, pleasant and connected with them. Free jazz elicited substantial emotions only in those who had taken LSD without ketanserin.
A woman suffering from complications caused by an unsafe abortion at a hospital in Zongo, the Democratic Republic of Congo, in 2015. The so-called Mexico City policy prohibits organizations abroad from using American aid to discuss abortion as a method of family planning.CreditFederico Scoppa/Agence France-Presse — Getty Images
DAKAR, Senegal — The clinic, tucked discreetly inside the student health center on the University of Dakar campus, prescribes birth control pills, hands out condoms and answers questions about sex that young women are nervous about asking in this conservative Muslim country.
The clinic performs no abortions, nor does it discuss the procedure or give advice on where to get one. Senegal, by and large, outlaws abortion. But for other health services like getting contraceptives, said Anne Lancelot, the Sahel director at the organization that runs the clinic, “there is a very high demand.”
Now, under a Reagan-era policy revived by President Trump, the clinic may no longer be able to count on aid money from the United States Agency for International Development, part of a ban on providing abortion counseling overseas that could curtail a broad range of health services, including those that go well beyond abortion.
Known as the Mexico City policy — and by its critics as the global gag rule — the abortion policy prohibits organizations abroad from using American aid to talk about abortion as a method of family planning. Anti-abortion groups like the Family Research Council have welcomed Mr. Trump’s decision, saying it is consistent with “his campaign promise that he will protect taxpayers from having to pay for abortions.”
Direct American aid to carry out abortions was already prohibited, but the rule Mr. Trump revived goes further. It requires not only hospitals or clinics to refrain from providing advice or information on the benefits and availability of abortion. It also requires any international organizations supporting those clinics to stop promoting abortion or advocating abortion rights anywhere in the world — even if they use non-American money to do so.
Experts say the rule has cut American aid to groups offering a wide range of services, not just abortion, during previous Republican administrations that have adopted the policy.
But this time, they say, the impact could be much bigger.
The wording in the Trump order extends the restrictions to all American global health aid, an $8.5 billion pot of money, according to an analysis by the Kaiser Family Foundation, a research organization. More than half of that money goes to programs for H.I.V. and AIDS, including services for women of reproductive age, the analysis found. An additional 9 percent goes to maternal and child health care, which is partly aimed at promoting safe pregnancies.
By contrast, the last time the rule was in place, under President George W. Bush, it applied only to family planning money, an amount that is currently around $520 million, the analysis found.
As health providers braced for cuts from Washington, the Netherlands lost no time in casting itself as a defender of reproductive rights. Its Foreign Ministry said Wednesday that it would start an international fund “to make up as much as possible for this financial blow.” It gave no specifics.
A spokesman for U.S.A.I.D. said the agency was still reviewing Mr. Trump’s presidential order to figure out how it would be enacted. But the language suggesting that it would be extended to all global health aid quickly sent a chill through the network of health providers that rely on American assistance to deliver a wide range of services in countries with fragile health care systems.
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A maternity ward at a clinic in Médina Yoro Foulah, Senegal, in 2011. The country, by and large, outlaws abortion, but there are clinics that prescribe birth control pills, hand out condoms and answer questions about sex.CreditLynsey Addario for The New York Times
In Swaziland, which has one of the world’s highest H.I.V. infection rates, one private health care provider said its staff members provide abortion information to H.I.V.-infected women when necessary. Swaziland allows abortion only in cases of rape and incest, but patients can be referred to neighboring South Africa, where abortion is legal.
“Our organization could definitely be affected, including our H.I.V. services, and you can imagine how detrimental that could be for a small country like Swaziland that’s been heavily affected by H.I.V.,” said Zelda Nhlabatsi, the executive director of the Family Life Association of Swaziland, which says it receives a quarter of its funding from the American government.
In Lesotho, a landlocked nation surrounded by South Africa, Lerotholi Pheko, the executive director of the Lesotho Planned Parenthood Association, said he feared a hit to his operating budget even though his clinic does not provide abortion counseling.
The reason: His clinic receives most of its funding from the International Planned Parenthood Federation, which has said that it will lose $100 million in American funding over the next four years under Mr. Trump’s order.
“If we are not able to increase the income we get locally,” Mr. Pheko said, “it would mean that we would have to downsize.”
Here in Senegal, the small waiting room at the clinic on the busy University of Dakar campus was crammed with young women this week. Some cradled smartphones and tablets with headphone cords dangling from their ears.
Students in their early 20s arrived with questions and confusion about options for pregnancy prevention in a nation where talking about contraception is still largely taboo. A box of condoms was on a shelf, and students can be tested for sexually transmitted diseases.
Ms. Lancelot said the clinic does not provide abortion services or counseling. But the organization that runs it, Marie Stopes International, based in London, provides abortions and abortion counseling in other countries where it is legal, though not with money from the United States.“We are your brothers and sisters who listen without judging,” read a banner at the center.
Marjorie Newman-Williams, director of operations for Marie Stopes International, which received $30 million in American funding 2016, said her group could not accept the Trump administration’s restrictions and would seek aid elsewhere.
“There will be a huge void in service delivery, and unless we can make up that money really fast, the funding won’t be there,” Ms. Newman-Williams said.
President Trump’s decision drew support from opponents of abortion in the United States. Jim DeMint, the president of the Heritage Foundation, issued his congratulations to Mr. Trump on Twitter “for reinstating Reagan’s #MexicoCityPolicy, preventing our tax dollars from funding abortion overseas.”
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A message reading “Stop Stigma. Let’s not drive them away. Let’s not discriminate them” in a slum in Nairobi, Kenya, on World AIDS Day, last month. The wording in the Trump order extends the restrictions to all American global health aid, and could affect H.I.V. services.CreditDai Kurokawa/European Pressphoto Agency
Senator Tom Cotton, Republican of Arkansas, echoed the sentiment, writing on Twitter, “Not one dime of taxpayer money should pay for abortion.”
The international groups affected by the prohibition usually provide a range of women’s health services, including pregnancy tests, H.I.V. tests and screenings for sexually transmitted diseases. To continue to receive American aid, the groups would have to certify that they do not offer abortion counseling, refer patients to abortion services or advocate legal abortions in the countries where they work. The policy spells out some exceptions, including cases of rape and treating women who have had botched abortions.
In Bogotá, Colombia, Marta Royo, who leads an organization called Profamilia, said she found the restrictions unacceptable.
Colombia legalized abortion in 2006, so to be barred from talking about it with patients, Ms. Royo said, would be “going against the country rules and the rights of the country that we have fought for.”
“It would be such a contradiction,” she said.
Her group, which is part of the International Planned Parenthood Federation, does not use American funding for abortion services, she said, only for family planning.
Research suggests that the policy has had a counterintuitive impact in the past. In countries that relied heavily on funding from the United States for reproductive health services, abortion rates rose when the Reagan-era policy was in place.
Researchers cite a possible reason: The aid spigot dries up for the organizations that provide contraceptive services to prevent unwanted pregnancies.
Avoiding such unintended pregnancies is what brought many of the young college students to the health clinic in Dakar. One 24-year-old student, Absa, who withheld her last name because her parents did not know she was sexually active, said she came to the clinic to ask about birth control after hearing a debate about contraception on television.
Another, Raicha, who was also worried about being condemned by her parents, came to the clinic after her boyfriend refused to use a condom. She worried she would get pregnant, so the couple agreed to look into using other contraceptives.
“I don’t want to get pregnant,” said Raicha, 22. “I want to finish my studies and be free to work.”9
Joaquín Guzmán Loera, known as El Chapo, was escorted off a plane at Long Island MacArthur Airport in Islip, N.Y., on Thursday. The decision to extradite Mr. Guzmán was an about-face for the Mexican government, which once claimed that he would serve his long sentence in Mexico first.CreditU.S. law enforcement, via Associated Press
MEXICO CITY — Joaquín Guzmán Loera, the notorious drug lord known as El Chapo who twice slipped out of high-security Mexican prisons and into criminal legend, was extradited to the United States on Thursday night, officials said, drawing to a close a decades-long quest to prosecute the head of one of the world’s largest narcotics organizations.
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The decision to extradite Mr. Guzmán was an about-face for the Mexican government, which once claimed that he would serve his long sentence in Mexico first. However, after his Houdini-like escape in 2015, when his associates tunneled him out of Mexico’s most secure prison, officials began to reconsider.
The fascination with Mr. Guzmán stemmed from the fact that one could never really count him out. He perfected the escape hatch, the underground tunnel and the trap door — all tools he used to evade law enforcement during his years on the run, which ended with an arrest in 2014. He sent his engineers to Germany for training, then dispatched them to his homes, where they would outfit closets, bathrooms and refrigerators with secret exits.
A pioneer of the cross-border tunnel, used to shuttle tens of thousands of tons of drugs into America, he ultimately adapted those feats of secret underground engineering for his escape from the Altiplano prison: a maximum-security facility in the State of Mexico where he lived in isolation, under 24-hour surveillance by a camera in his cell.
His escape was a stinging embarrassment for the government of President Enrique Peña Nieto, which had trumpeted his capture as a crucial victory in its bloody campaign against the narcotics trade.On the night of July 11, 2015, shortly before 9 p.m., Mr. Guzmán stepped into his shower and passed through a small hole in its floor, positioned in the camera’s one blind spot. From there, he descended into a mile-long tunnel, equipped with a motorcycle on rails, and raced to freedom.
Again a fugitive, Mr. Guzmán found the time to rendezvous with film stars, including Sean Penn, to discuss a biopic about his life. But his freedom was short-lived. After a manhunt that involved more than 2,500 people, he was seized in the town of Los Mochis in early 2016 after crawling out of a sewer.
In 2015 a MERS outbreak in South Korea took months to get under control. Now researchers want to develop and stockpile vaccines against this and other threats.
SARS, Zika, Ebola – when some of the world’s most terrifying disease outbreaks occur, health workers often find themselves powerless. A billion-dollar initiative launched on 18 January aims to change that situation by pre-emptively developing and stockpiling vaccines to combat potential epidemic threats.
“I'm thrilled. This is only the formal launch, and to have near $500 million — and likely more — to get started is great,” says Jeremy Farrar, director of biomedical charity the Wellcome Trust in London, one of the new project’s backers.
The Coalition for Epidemic Preparedness Innovations (CEPI) launched on 18 January at the World Economic Forum in Davos, Switzerland, with an initial US$460 million of backing from Norway, Germany, Japan, the Wellcome Trust and the Bill & Melinda Gates Foundation. The organization expects to raise the full $1 billion that it needs for the next 5 years by the end of 2017, says John-Arne Røttingen, CEPI's interim chief executive. It is by far the largest vaccine development initiative ever against viruses that are potential epidemic threats.
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Stocking the pipelines
The Ebola epidemic that began in December 2013 in West Africa shows the need to develop vaccines pre-emptively, says Farrar. No vaccine against Ebola was available when the outbreak started, but researchers were able to develop a safe and effective vaccine against the Zaire strain responsible in record time — just a year and a half. Making a vaccine from scratch usually takes years, or even decades.
They were able to move fast because US and Canadian researchers had already developed experimental Ebola vaccines. Researchers fighting Ebola lost valuable time, however, because the experimental vaccines, which had sat on the shelf for years, had been tested for safety in animals, but not humans.
Coalition for Epidemic Preparedness Innovations. Preliminary Business Plan 2017–2021 (CEPI, 2016).
“We had to spend what was 9–12 months getting safety data for those vaccines, and that was 9–12 months where ultimately many people lost their lives,” says Farrar.
By contrast, the CEPI's planned work on MERS, Nipah and Lassa vaccines will take experimental vaccine candidates — two for each disease — through testing in humans to establish that they are safe and produce an immune response that is likely to be protective. It would then create sufficient stockpiles of promising candidates to rapidly test for efficacy, and possible use, in the event of an outbreak. For the three diseases initially targeted, the CEPI aims to have stockpiles by 2021.
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The CEPI is particularly keen for the United States to join, but discussions will take time given the change in administration, adds Røttingen. “Irrespective of the government, it was a bad time to engage the United States on that."
