Dr. Julian Nussbaum, an ophthalmologist, discussing eye health with a diabetes patient.CreditMichael Holahan/The Augusta Chronicle, via Associated Press
A lawsuit filed Monday accused three makers of insulin of conspiring to drive up the prices of their lifesaving drugs, harming patients who were being asked to pay for a growing share of their drug bills.
The price of insulin has skyrocketed in recent years, with the three manufacturers — Sanofi, Novo Nordisk and Eli Lilly — raising the list prices of their products in near lock step, prompting outcry from patient groups and doctors who have pointed out that the rising prices appear to have little to do with increased production costs.
The lawsuit, filed in federal court in Massachusetts, accuses the companies of exploiting the country’s opaque drug-pricing system in a way that benefits themselves and the intermediaries known as pharmacy benefit managers. It cites several examples of patients with diabetes who, unable to afford their insulin treatments, which can cost up to $900 a month, have resorted to injecting themselves with expired insulin or starving themselves to control their blood sugar. Some patients, the lawsuit said, intentionally allowed themselves to slip into diabetic ketoacidosis — a blood syndrome that can be fatal — to get insulin from hospital emergency rooms.
People protest against the US immigration ban at John F. Kennedy International Airport in New York City on 28 January.
Kaveh Daneshvar was thrilled when he was invited to speak at a molecular biology meeting next month in Banff, Canada. Daneshvar, a molecular geneticist, is finishing a postdoc at Harvard Medical School and Massachusetts General Hospital in Boston, and is preparing to go on the job market. He hoped that the conference talk would give him much-needed exposure to leaders in his field.
But that now seems impossible: if Daneshvar, an Iranian citizen, leaves the country, he may not be able to return. On 27 January, US President Donald Trump signed a sweeping executive order that blocks refugees from entering the United States for 120 days and stops Syrian refugees indefinitely. It also bans citizens of seven majority-Muslim countries “compromised by terrorism” — Iran, Iraq, Libya, Somalia, Sudan, Syria and Yemen — from entering the United States for 90 days. The US government has issued conflicting statements on whether the provisions apply to people such as Daneshvar who hold visas that would otherwise permit them to live, work or study in the United States — including those with the permanent resident visas known as green cards.
Nature spoke to more than 20 researchers affected by the new policy, who described their feelings of fear, shock and determination. Some asked to remain anonymous for fear of retaliation by the US government.
“I am really appreciative of what the US has given me and allowed me to achieve here, but at the same time this is really shocking,” says Ali Shourideh, an economist at Carnegie Mellon University in Pittsburgh, Pennsylvania. “I've always been under the assumption this is a free country, that once you immigrated they won't try to kick you out or make life hard for you.”
Shourideh, an Iranian citizen with a green card, has travelled to Iran several times recently to visit his mother, who has cancer. Now, if he leaves the United States, he may not be able to return. “You have to make a choice: do I want to see my mom or do I want to keep my job?” he says. “This is something that for sure will hurt us personally, but also the US, I think, because all these high-skilled-type professionals would not want to be here anymore.”
The team that made these chimaeras also reports the creation of mouse–rat and human–cow hybrids on 26 January in Cell1. Such modified animals could provide researchers with new models for testing drugs and understanding early human development.
To create chimaeras, scientists generally inject pluripotent stem cells — which can become any type of organ — from one species into the early embryo of a second species. In theory, the foreign cells should differentiate and spread throughout the body, but in practice, producing viable hybrid embryos has proven difficult.
To get around this, a team led by developmental biologist Juan Carlos Izpisua Belmonte of the Salk Institute for Biological Studies in La Jolla, California, used CRISPR gene-editing technology to create mouse embryos without the genes that cause organs to form. The scientists then injected rat stem cells into the mouse embryos and implanted the embryos into a mouse’s uterus.
Because the rat cells still contained genes for organ formation, the resulting chimaeras had organs that were composed largely of rat cells. The animals lived for up to two years, the normal lifespan of a mouse.
Mix and match
Next, the researchers attempted to hybridize two distantly related species: humans and pigs. The team injected more than 1,400 pig embryos with one of three types of human induced pluripotent stem cell — normal cells, cells that were primed to develop into tissue or "intermediate" cells that were neither normal nor fully primed. All of the human cells had been modified to produce a green fluorescent protein so that they could be identified within the newly created chimaeras.
The scientists allowed the pig–human chimaeras to develop for three to four weeks before destroying them, according to ethics regulations. Chimaeras injected with the intermediate stem cells grew to contain the largest proportion of human cells, suggesting that previous attempts to create chimaeras may have used stem cells at the wrong stage of development.
Even then, only about 1 in 100,000 of the cells in the pig–human chimaeras were human — at best, says study co-author Jun Wu, a biologist at the Salk Institute.
“I think it’s a very important, very exciting paper,” says Jacob Hanna, a developmental biologist at the Weizmann Institute of Science in Rehovot, Israel. Now, he says, researchers will want to see whether the human cells in the chimaeras have normal DNA structure and gene expression.
But Hiromitsu Nakauchi, a stem-cell researcher at Stanford University in California, says that the low number of human cells in the pig–human chimaeras means that the hybrids are still a long way from serving any useful purpose, such as organ donors. “It’s a good try, but the result seems like more a negative result,” he says.
Transplant hopes
Nakauchi’s group is using similar methods to create human–sheep chimaeras, in part because he suspects that sheep embryos may be better able to take up human cells than pig embryos can. But Wu, says that pigs will probably be the best organ donors, because their large litter sizes would allow quicker production of organs. Pig organs are also close to the same size as human ones.
Researchers are pursuing a number of strategies to make pigs into human-organ donors, such as using CRISPR to disable pig proteins that could cause an immune response in primates. The advantage of chimaeras, Izpisua Belmonte says, is that researchers could one day use a patient’s own cells to create a pig chimaera with a human organ that has been grown for that individual.
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.”
...
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.
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.”
Photo
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
