A doctor explains to a young couple that he has screened the pair’s in vitro fertilized embryos and selected those that had no major inheritable diseases. The couple had specified they want a son with hazel eyes, dark hair and fair skin. Then the doctor announces that he has also taken the liberty of eliminating the “burden” of genetic propensities for baldness, nearsightedness, alcoholism, obesity and domestic violence.
The prospective mother replies that they didn’t want those revisions. “I mean diseases, yes, but …” Her husband jumps in to say, “We were just wondering if it’s good to leave a few things to chance.” But the doctor reminds the would-be parents why they came to him in the first place. They want to give their child “the best possible start.”
That’s a scene from the movie Gattaca, which premiered 20 years ago in October. But thanks to recent advances in gene-editing tools such as CRISPR/Cas9, genetic manipulation of human embryos is becoming reality.
Soon, designer babies like those described in the film may even become morally mandatory, some ethicists say.
Gattaca’s narrator tells us that such genetic manipulation of in vitro fertilized embryos has become “the natural way of giving birth” in the near future portrayed in the film. It has also created an underclass of people whose parents didn’t buy those genetic advantages for their children. Until recently, that sort of fiddling with human DNA was only science fiction and allegory, a warning against a new kind of eugenics that could pit the genetic haves and have-nots against each other. At a symposium sponsored by the Hastings Center on October 26 before the World Conference of Science Journalists in San Francisco, ethicists and journalists explored the flip side of that discussion: whether parents have a moral obligation to make “better” babies through genetic engineering. Technology that can precisely change a baby’s genes is quickly becoming reality. This year, scientists reported using CRISPR/Cas9 in viable human embryos to fix mutations that cause heart and blood disorders. CRISPR/Cas9 acts as a molecular scissors that relatively easily and precisely manipulates DNA. Scientists have honed and developed the tool in the roughly five years it has been around, creating myriad “CRISPR” mice, fish, pigs, cows, plants and other creatures. Its use in human embryos has been hotly debated. Should we or shouldn’t we?
For many people, the fear of a class of genetically enhanced people is reason enough not to tinker with the DNA of the human germline — eggs, sperm, embryos and the cells that give rise to eggs and sperm. By all means, correct diseases, these folks say, but don’t add extras or meddle with characteristics that don’t have anything to do with health. A panel of ethicists convened by the U.S. National Academies of Medicine and Science also staked out that position in February, ruling that human germline engineering might someday be permissible for correcting diseases, but only if there are no alternatives and not for enhancements.
But the question “should we?” may not matter much longer, predicted the Hastings Center’s Josephine Johnston at the symposium. As science advances and people become more comfortable with gene editing, laws prohibiting tinkering with embryos will fall, she said, and it will be up to prospective moms and dads to decide for themselves. “Will editing a baby’s genes be mandatory, the kind of thing you’re supposed to do?”
For Julian Savulescu, an ethicist at the University of Oxford, the answer is yes. Parents are morally obligated to take steps to keep their children healthy, he says. That includes vaccinating them and giving them medicine when they’re ill. Genetic technologies are no different, he argues. If these techniques could make children resistant to infections, cancer or diabetes, then parents have an obligation to use them, he says.
For now, he cautions, CRISPR’s safety and efficacy haven’t been established, so parents shouldn’t subject their children to the risks. He also points out that this sort of editing would also require in vitro fertilization, which is prohibitively costly for many people. (And couples could pretty much forget about having the perfect baby through sexual intercourse. Designer darlings would have to be created in the lab.)
But someday, possibly soon, gene editing could become a viable medical intervention. “If CRISPR were safe and not excessively costly, we have a moral obligation to use it to prevent and treat disease,” Savulescu says.
Using gene editing to cure genetic diseases is something retired bioethicist Ronald Green of Dartmouth College can get behind. “I fully support the reproductive use of gene-editing technology for the prevention and elimination of serious genetic diseases,” Green said at the symposium. “If we could use gene editing to remove the sequences in an embryo that cause sickle cell disease or cystic fibrosis, I would say not only that we may do so, but in the case of such severe diseases, we have a moral obligation to do so.”
But that’s where a parent’s obligation stops, Green said. Parents and medical professionals aren’t required to enhance health “to make people who are better than well,” he said.
Savulescu, however, would extend the obligation to other nondisease conditions that could prevent a kid from having a full set of opportunities in life. For instance, children with poor impulse control may have difficulty succeeding in school and life. The drug Ritalin is sometimes prescribed to such kids. “If CRISPR could do what Ritalin does and improve impulse control and give a child a greater range of opportunities,” he says, “then I’d have to say we have the same moral obligation to use CRISPR as we do to provide education, to provide an adequate diet or to provide Ritalin.”
Green rejected the idea that parents should, or even could, secure a better life for their kids through genetic manipulation. Scientists haven’t identified all the genes that contribute to good lives — and there are plenty of factors beyond genetics that go into making someone happy and successful. Already, Green said, “the healthy natural human genome has enough variety in it to let any child successfully navigate the world and fulfill his or her own vision of happiness.” (A version of his remarks was posted on the Hastings Center’s Bioethics Forum.)
Many traits that would help a person make more money or have an easier life are associated with social prejudices and discrimination, says Marcy Darnovsky, the executive director of the Center for Genetics and Society in Berkeley, Calif. People who are taller and fair-skinned tend to make more money. If parents were to engineer their children to have such traits, “I think we would be inscribing those kinds of social prejudices in biology,” she says. “We get to very troubled waters very quickly as a society once we start down that road.”
Creating a class of “genobility,” as Green calls genetically enhanced people, would increase already staggering levels of inequality, Darnovsky says. That, says Savulescu, “is the Gattaca objection I often get.”
Yes, he acknowledges, “it could create even greater inequalities, there’s no doubt about that.” Whenever money is involved, people who have more of it can afford better treatments, diets and healthier lifestyles — and disparities will exist. “However, this is not inevitable,” Savulescu says. Countries with national health care systems could provide such services for free. Such measures could even correct natural inequalities, he argues.
Johnston worries that genetic manipulation could change family dynamics. Parents might be disappointed if their designer baby doesn’t turn out as desired. That’s a variation of the old problem of unfulfilled parental expectations, Savulescu says. “It’s a problem that deserves attention, but it’s not a problem that deserves banning CRISPR,” he says.
Deep in the Bale Mountains of Ethiopia, wildlife workers trek up above 9,800 feet to save some of the world’s most rare carnivores, Ethiopian wolves.
“It’s cold, tough work,” says Eric Bedin, who leads the field monitoring team in its uphill battle.
In this sparse, sometimes snowy landscape, the lanky and ginger-colored wolves (Canis simensis) reign as the region’s apex predators. Yet the combined threats of rabies, canine distemper and habitat reduction have the animals cornered.
Bedin and his colleagues, traveling by horse and on foot through dramatically shifting temperatures and weather, track these solitary hunters for weeks at a time. Team members know every wolf in most packs in these mountains. The team has vaccinated some wolves against rabies, only to have hopes dashed when the animals died of distemper months later. “These guys work their asses off to protect these wolves,” says Claudio Sillero, a conservation biologist at the University of Oxford who heads up the Ethiopian Wolf Conservation Programme, of which the field monitoring team is an integral part. Down the line, humans stand to benefit from all this work too.
Sillero and his colleagues have been at this for 30 years. They’ve seen four major outbreaks of rabies alone, each leaving dozens of carcasses across the highlands and cutting some populations by as much as 75 percent.
Today, fewer than 500 Ethiopian wolves exist — around half of them in the Bale Mountains. A new oral rabies vaccine program aims to give the endangered animals a fighting chance. It may be their best hope for survival, Sillero says.
Later this year, if all goes well, oral vaccines hidden in hunks of goat meat will be scattered across wolf ranges and eaten by the animals. One dose every two years should bolster immunity against rabies among these iconic animals immortalized on several of their country’s postage stamps. One Health Vaccinating endangered animals en masse in the wild is rarely attempted. Making the case for vaccination takes years of testing. And even when the case is strong for stepping in, the tools needed to vaccinate wildlife aren’t often available, says Tonie Rocke, an epizootiologist with the U.S. Geological Survey in Madison, Wis. On the opposite side of the globe from Bale, on North America’s Great Plains, Rocke’s lab is testing an oral vaccine to protect prairie dogs and endangered ferrets from plague. A recent synergy has made these new oral vaccine efforts possible: improvements in vaccine technology (developed for humans and domesticated animals) and growing public and scientific interest in “One Health.” The conservation buzzword refers to efforts to help one species that also benefit others, including humans.
The researchers pushing for a green light in Ethiopia point to the one shining success in oral vaccines for wild animals, and to its One Health benefits. From 1978 to 2010, oral vaccines sprinkled across parts of Europe eliminated rabies in red foxes. Europe’s rabies cases in humans and other animals dropped by 80 percent from 1984 to 2014. But rabies is still common in certain parts of the world, including Ethiopia. Worldwide, more than 59,000 people die from the disease each year.
Successes on the plateaus of Bale and the prairies of North America could open the door for other vaccines to protect threatened species. Vaccines against Ebola in great apes and white-nose syndrome in bats are in the works.
But introducing vaccines into natural environments is a hard sell and can come with controversy and unexpected consequences. A last resort To the average U.S. vet or dog owner, vaccination is a no-brainer. But for endangered species, the stakes are high. Some conservationists are reluctant to intervene with disease-preventing vaccines in the wild, says Karen Laurenson, an epidemiologist and veterinarian with the Frankfurt Zoological Society.
Disease has its place in ecosystems. It can control population levels and put pressure on species to develop natural resistance, says Laurenson, who started working with the wolf project in the mid-1990s. Using a vaccine to take a disease out of the mix could leave a population vulnerable to future outbreaks should the vaccine become ineffective or stop being used. In an ecosystem with multiple power players, one vaccinated predator could gain an unnatural advantage over its competitors.
Some vaccines also bring direct risks. Injectable vaccines often require trapping the animal — a costly endeavor that’s stressful and dangerous for both wild animals and the humans doing the vaccinating. Oral vaccines could be scooped up and eaten by other animals. Plus, for an oral or injectable attenuated vaccine, which contains a living but harmless version of a virus, there’s a slim possibility that evolutionary pressure could eventually drive the virus, now distributed through the population, to become lethal again.
Because room for error is slim for a species on the brink of extinction, most instances of vaccine use have been limited to emergency responses during ongoing outbreaks.
Projects that don’t go well can have lasting repercussions. In 1990, researchers tried to vaccinate some packs of endangered African wild dogs (Lycaon pictus) in Tanzania and Kenya against rabies, assuming the disease was behind a recent dip in numbers. Every dog in the study died. The stress of getting vaccinated, shot by dart from a distance, may have made the dogs more susceptible to disease, though that theory was never proven. The incident increased skepticism about vaccines and caused some African countries to tighten vaccine regulations. “It left a terrible legacy,” says veterinarian Richard Kock of the University of London.
The long game The uphill battle faced by Sillero’s team involves more than the challenges of canvassing the Ethiopian highlands. Making a case to government officials that oral vaccines are necessary conservation tools took decades of fieldwork, genetic testing and meetings upon meetings. “The credit really goes to Claudio and the others for persisting,” Laurenson says. “Even when the doors have been shut, sometimes they’ve kept banging.”
Sillero arrived in Ethiopia in 1987 to study the wolves. A rabies outbreak hit in late 1989. Just as it does in dogs and humans, the disease attacks a wolf’s brain, causing aggressive behavior and, eventually, death. Canine distemper appeared in 1992. Marked by severe diarrhea, vomiting and coughing, the disease appears to hit wolves harder than dogs, Sillero says. The Ethiopian packs have faced four more major flare-ups of rabies and two of distemper. Two of the eight populations of wolves he came to study have gone extinct in that time.
“This is a human-caused problem, not a natural dynamic,” Laurenson says. Each year, shepherds and farmers move higher up into the wolves’ habitat, bringing grazing livestock. These people also bring domesticated dogs — the primary carriers of rabies and canine distemper (SN Online: 9/30/16). In one area of Ethiopia, wolf habitat shrunk by 34 percent from 1985 to 2003. Islands of wolf populations persist in remote highland areas surrounded by oceans of free-ranging dogs.
Vaccinating the wolves was plan B, after the lower-risk approach of vaccinating domestic dogs didn’t cut it. Because the dogs roam far and wide, dog vaccination programs didn’t reach enough animals to generate prolonged protection and prevent outbreaks in wolves. “I’m sure we were improving the situation and reducing the chance of spillovers in wild carnivores, but we weren’t preventing them altogether,” Sillero says.
Going with oral vaccines was plan C. In 2003, the government approved use of an injectable vaccine only in response to outbreaks. Sillero’s team first had to collect samples and send them to international labs to confirm that an outbreak was happening. The researchers were always behind. An oral option that proactively protects the animals started to sound like a smart way to go.
Deliver the dose On paper, the wolves look like good candidates for an oral vaccine intervention. Few other animals brave the highlands habitat, so the odds are low that a vaccine distributed in bait would get eaten by the wrong creatures. And not vaccinating is arguably riskier than making the effort. Consecutive rabies and distemper outbreaks recently cut one of the smallest known wolf populations down to two individuals, Sillero’s team reported in December in Emerging Infectious Diseases.
The Ethiopian team chose to test an oral rabies vaccine, called SAG2, that had been used successfully in red foxes. Twenty million baits had been dropped across Europe with no vaccine-induced rabies cases or reported deaths. SAG2 also passed safety tests in a slew of different species, including African wild dogs. “That work was absolutely fundamental,” Laurenson says. Getting the vaccine into the animals is the trickiest part. Animals have to bite into the bait to puncture an internal packet that contains the vaccine, rather than swallow the bait whole. “You’ve got to make the bait such that the [wolf] would chew it,” says Anthony Fooks, a vaccine researcher who runs a U.K. government lab that handles sample tests for the wolf project.
So Sillero and his team launched a series of pilot studies of an oral SAG2. “We set up cafeteria-type experiments, with different baits and delivery methods,” Sillero says. The researchers dropped 445 baits in locations around Bale. Hiding the vaccine in goat meat and distributing the goods at night worked better than other options, the team reported in 2016 in Vaccine. Of 21 wolves trapped a couple of weeks later, 14, or 67 percent, carried a biomarker showing the vaccine was in the wolf’s system. Of those, 86 percent had developed immunity against rabies. The impact on other wildlife was low: Only a few raptors snatched up vaccines meant for the wolves.
With all that data in hand, Sillero’s team finally won over Ethiopia’s Wildlife Conservation Authority in December, receiving an official thumbs-up to move forward. This month, 4,000 vaccines arrived; the mass vaccination program could get off the ground this summer.
It’ll be the first mass oral vaccination program to target an endangered species in the wild. The basic plan: Distribute the oral vaccines at night once every two years, vaccinate at least 40 percent of a chosen wolf population and use motion-sensing cameras to see if each pack’s high-ranking males and females — the primary pup producers — take the bait. It’s important to keep the top producers healthy. Drones and peanut butter Having a readily available oral vaccine for the wolves was a lucky break for the researchers in Ethiopia. A research team in the United States had no such luck. Tonie Rocke and her colleagues had to develop their own oral plague vaccine for prairie dogs. The team devised a raccoon poxvirus that produces plague proteins once inside the prairie dog body. The proteins train the immune system to fight the plague-causing Yersinia bacteria.
Saving plague-ridden prairie dogs (Cynomys spp.) is an indirect way to protect the real target: an endangered predator, black-footed ferrets (Mustela nigripes) of the Great Plains. The ferrets survive on a diet of mostly prairie dogs and had nearly gone extinct in the 1970s due to centuries of habitat loss, prey declines and plague. On top of captive breeding and reintroduction programs to keep the ferret species afloat, the U.S. Fish and Wildlife Service traps and vaccinates wild ferrets directly. But it’s not enough.
Rocke and her colleagues went ahead and developed a peanut butter–flavored oral plague vaccine. They distributed it by drones and four-wheelers in small test plots in seven states to limit prairie dog carriers. (Plague can threaten prairie dog populations too, so everybody wins.)
Last June, the researchers published the results of these successful small-scale field trials in EcoHealth. A prairie dog’s odds of surviving in plague-ridden areas just about doubled. And the peanut butter pellets were as good at reducing plague levels as traditional insecticides that kill plague-carrying fleas. It’s unclear just how many prairie dogs in colonies need to be vaccinated to protect the ferrets from plague.
Getting the vaccine approved wasn’t as tortuous as it has been in Ethiopia. Collaborators at Colorado Parks and Wildlife already had a cheap way to make the baits, and in 2017, Colorado Serum Company licensed the product through the U.S. Department of Agriculture.
This year, Rocke hopes to conduct larger-scale field trials to determine the levels of immunity required for success in a mass vaccination. Ultimately, the application will be limited — just selected populations of prairie dogs that are either in ferret territory or endangered themselves, such as the Utah prairie dog (C. parvidens). Plague infects a handful of humans and domesticated animals each year as well, and the team is looking into using the vaccine in areas where humans spend time, like national parks. Encouraging others Success for one species could be good news for others. Similar preventative strategies might work in other threatened animals, including other members of the dog family dealing with rabies and ungulates like zebras at risk of catching anthrax while grazing. Researchers are testing preventative vaccines to protect wild Hawaiian monk seals from a seal-specific distemper virus.
Oral vaccines aren’t the only nontraditional delivery method. Rocke’s lab is working on a topical vaccine against white-nose syndrome, which threatens bats (SN Online: 3/31/16), and one to combat rabies in common vampire bats (Desmodus rotundus). Vampire bats in particular nuzzle each other during social grooming. “It’s an easy way to get the vaccine distributed amongst members of the colony,” Rocke says.
In October in PLOS Neglected Tropical Diseases, her lab reported that the vaccine works in captured big brown bats (Eptesicus fuscus), but it still hasn’t been tested in vampire bats, key rabies carriers in South America. Rocke and colleagues hope to start trials in vampire bats this year in Mexico and Peru.
Great apes can fall victim to some of the same pathogens as humans, such as measles and Ebola. In March 2017 in Scientific Reports, a research team published successful lab tests of an oral vaccine against Ebola in captive chimpanzees (Pan troglodytes). The vaccine relies on the rabies virus to deliver Ebola proteins that elicit an immune response in chimps, but it hasn’t been tested in the field yet.
Such a vaccine should be used selectively, Kock says. Vaccinating great apes against Ebola in preserves where the animals might encounter human carriers makes sense. But vaccinating gorillas across large forests in the Congo “is just silly,” he says.
Protecting isolated species on the brink of extinction is where vaccines could do the most good. Endangered Amur tigers (Panthera tigris altaica) have been hit hard by canine distemper, their numbers falling to around 500 individuals in their Siberian habitat. Vaccines have been debated as a potential option and injectables have been tested in captive tigers.
Sillero doesn’t expect to see any oral options developed against distemper in the future, because there’s not a big economic incentive. Unlike rabies, the disease doesn’t cause problems in humans. So he’s working with the shots available. Genetic analyses of locally circulating distemper strains published in July 2017 suggest the injectable distemper vaccines should work for the Ethiopian wolves, Fooks says. Sillero’s team is testing one in the field now. Preliminary data suggest the shot elicits a good immune response. What’s good for the wildlife Greater awareness about the overlap of human, livestock and wildlife health on shared lands underlies many of these projects. Ethiopia has one of the highest rabies death rates among humans in the world, and lowering the disease prevalence in any animals that humans come in contact with has benefit.
“This will have positive impacts for the threatened animals, for the welfare of domestic dogs and livestock, and for the health and finance of the human community,” Sillero argues. The One Health mind-set is also behind programs run in a few areas of Ethiopia’s northern highlands, to teach local farmers how to build more efficient stoves that require less firewood, and thus, less foraging in wolf territory.
“Vaccination and eradication of things like rabies … needs a whole of society approach,” Kock says. “It cannot be done piecemeal.”
For Ethiopia’s impending oral vaccine launch that has been so many years in the making, Sillero is optimistic. But he’s still holding his breath.
“I have to see the wolves taking up the baits before I can congratulate the team,” he says. “But I think we’re nearly there.”
When you’re stressed and anxious, you might feel your heart race. Is your heart racing because you’re afraid? Or does your speeding heart itself contribute to your anxiety? Both could be true, a new study in mice suggests.
By artificially increasing the heart rates of mice, scientists were able to increase anxiety-like behaviors — ones that the team then calmed by turning off a particular part of the brain. The study, published in the March 9 Nature, shows that in high-risk contexts, a racing heart could go to your head and increase anxiety. The findings could offer a new angle for studying and, potentially, treating anxiety disorders. The idea that body sensations might contribute to emotions in the brain goes back at least to one of the founders of psychology, William James, says Karl Deisseroth, a neuroscientist at Stanford University. In James’ 1890 book The Principles of Psychology, he put forward the idea that emotion follows what the body experiences. “We feel sorry because we cry, angry because we strike, afraid because we tremble,” James wrote.
The brain certainly can sense internal body signals, a phenomenon called interoception. But whether those sensations — like a racing heart — can contribute to emotion is difficult to prove, says Anna Beyeler, a neuroscientist at the French National Institute of Health and Medical Research in Bordeaux. She studies brain circuitry related to emotion and wrote a commentary on the new study but was not involved in the research. “I’m sure a lot of people have thought of doing these experiments, but no one really had the tools,” she says.
Deisseroth has spent his career developing those tools. He is one of the scientists who developed optogenetics — a technique that uses viruses to modify the genes of specific cells to respond to bursts of light (SN: 6/18/21; SN: 1/15/10). Scientists can use the flip of a light switch to activate or suppress the activity of those cells. In the new study, Deisseroth and his colleagues used a light attached to a tiny vest over a mouse’s genetically engineered heart to change the animal’s heart rate. When the light was off, a mouse’s heart pumped at about 600 beats per minute. But when the team turned on a light that flashed at 900 beats per minutes, the mouse’s heartbeat followed suit. “It’s a nice reasonable acceleration, [one a mouse] would encounter in a time of stress or fear,” Deisseroth explains.
When the mice felt their hearts racing, they showed anxiety-like behavior. In risky scenarios — like open areas where a little mouse might be someone’s lunch — the rodents slunk along the walls and lurked in darker corners. When pressing a lever for water that could sometimes be coupled with a mild shock, mice with normal heart rates still pressed without hesitation. But mice with racing hearts decided they’d rather go thirsty.
“Everybody was expecting that, but it’s the first time that it has been clearly demonstrated,” Beyeler says. The researchers also scanned the animals’ brains to find areas that might be processing the increased heart rate. One of the biggest signals, Deisseroth says, came from the posterior insula (SN: 4/25/16). “The insula was interesting because it’s highly connected with interoceptive circuitry,” he explains. “When we saw that signal, [our] interest was definitely piqued.”
Using more optogenetics, the team reduced activity in the posterior insula, which decreased the mice’s anxiety-like behaviors. The animals’ hearts still raced, but they behaved more normally, spending some time in open areas of mazes and pressing levers for water without fear. A lot of people are very excited about the work, says Wen Chen, the branch chief of basic medicine research for complementary and integrative health at the National Center for Complementary and Integrative Health in Bethesda, Md. “No matter what kind of meetings I go into, in the last two days, everybody brought up this paper,” says Chen, who wasn’t involved in the research.
The next step, Deisseroth says, is to look at other parts of the body that might affect anxiety. “We can feel it in our gut sometimes, or we can feel it in our neck or shoulders,” he says. Using optogenetics to tense a mouse’s muscles, or give them tummy butterflies, might reveal other pathways that produce fearful or anxiety-like behaviors.
Understanding the link between heart and head could eventually factor into how doctors treat panic and anxiety, Beyeler says. But the path between the lab and the clinic, she notes, is much more convoluted than that of the heart to the head.
An experimental treatment for endometriosis, a painful gynecological disease that affects some 190 million people worldwide, may one day offer new hope for easing symptoms.
Monthly antibody injections reversed telltale signs of endometriosis in monkeys, researchers report February 22 in Science Translational Medicine. The antibody targets IL-8, a molecule that whips up inflammation inside the scattered, sometimes bleeding lesions that mark the disease. After neutralizing IL-8, those hallmark lesions shrink, the team found.
The new treatment is “pretty potent,” says Philippa Saunders, a reproductive scientist at the University of Edinburgh who was not involved with work. The study’s authors haven’t reported a cure, she points out, but their antibody does seem to have an impact. “I think it’s really very promising,” she says.
Many scientists think endometriosis occurs when bits of the uterine lining — the endometrium — slough off during menstruation. Instead of exiting via the vagina, they voyage in the other direction: up through the fallopian tubes. Those bits of tissue then trespass through the body, sprouting lesions where they land. They’ll glom onto the ovaries, fallopian tubes, bladder and other spots outside of the uterus and take on a life of their own, Saunders says. The lesions can grow nerve cells, form tough nubs of tissue and even bleed during menstrual cycles. They can also kick off chronic bouts of pelvic pain. If you have endometriosis, you can experience “pain when you urinate, pain when you defecate, pain when you have sex, pain when you move around,” Saunders says. People with the disease can also struggle with infertility and depression, she adds. “It’s really nasty.” Once diagnosed, patients face a dearth of treatment options — there’s no cure, only therapies to alleviate symptoms. Surgery to remove lesions can help, but symptoms often come back.
The disease affects at least 10 percent of girls, women and transgender men in their reproductive years, Saunders says. And people typically suffer for years — about eight on average — before a diagnosis. “Doctors consider menstrual pelvic pain a very common thing,” says Ayako Nishimoto-Kakiuchi, a pharmacologist at Chugai Pharmaceutical Co. Ltd. in Tokyo. Endometriosis “is underestimated in the clinic,” she says. “I strongly believe that this disease has been understudied.”
Hormonal drugs that stop ovulation and menstruation can also offer relief, says Serdar Bulun, a reproductive endocrinologist at Northwestern University Feinberg School of Medicine in Chicago not involved with the new study. But those drugs come with side effects and aren’t ideal for people trying to become pregnant. “I see these patients day in and day out,” he says. “I see how much they suffer, and I feel like we are not doing enough.”
Nishimoto-Kakiuchi’s team engineered an antibody that grabs onto the inflammatory factor IL-8, a protein that scientists have previously fingered as one potential culprit in the disease. The antibody acts like a garbage collector, Nishimoto-Kakiuchi says. It grabs IL-8, delivers it to the cell’s waste disposal machinery, and then heads out to snare more IL-8.
The team tested the antibody in cynomolgus monkeys that were surgically modified to have the disease. (Endometriosis rarely shows up spontaneously in these monkeys, the scientists discovered previously after screening more than 600 females.) The team treated 11 monkeys with the antibody injection once a month for six months. In these animals, lesions shriveled and the adhesive tissue that glues them to the body thinned out, too. Before this study, Nishimoto-Kakiuchi says, the team didn’t think such signs of endometriosis were reversible. Her company has now started a Phase I clinical trial to test the safety of therapy in humans. The treatment is one of several endometriosis therapies scientists are testing (SN: 7/19/19) . Other trials will test new hormonal drugs, robot-assisted surgery and behavioral interventions.
Doctors need new options to help people with the disease, Saunders says. “There’s a huge unmet clinical need.”
SpaceX’s rapidly growing fleet of Starlink internet satellites now make up half of all active satellites in Earth orbit.
On February 27, the aerospace company launched 21 new satellites to join its broadband internet Starlink fleet. That brought the total number of active Starlink satellites to 3,660, or about 50 percent of the nearly 7,300 active satellites in orbit, according to analysis by astronomer Jonathan McDowell using data from SpaceX and the U.S. Space Force. “These big low-orbit internet constellations have come from nowhere in 2019, to dominating the space environment in 2023,” says McDowell, of the Harvard-Smithsonian Center for Astrophysics in Cambridge, Mass. “It really is a massive shift and a massive industrialization of low orbit.”
SpaceX has been launching Starlink satellites since 2019 with the goal of bringing broadband internet to remote parts of the globe. And for just as long, astronomers have been warning that the bright satellites could mess up their view of the cosmos by leaving streaks on telescope images as they glide past (SN: 3/12/20).
Even the Hubble Space Telescope, which orbits more than 500 kilometers above the Earth’s surface, is vulnerable to these satellite streaks, as well as those from other satellite constellations. From 2002 to 2021, the percentage of Hubble images affected by light from low-orbit satellites increased by about 50 percent, astronomer Sandor Kruk of the Max-Planck Institute for Extraterrestrial Physics in Garching, Germany, and colleagues report March 2 in Nature Astronomy.
The number of images partially blocked by satellites is still small, the team found, rising from nearly 3 percent of images taken between 2002 and 2005 to just over 4 percent between 2018 and 2021 for one of Hubble’s cameras. But there are already thousands more Starlink satellites now than there were in 2021.
“The fraction of [Hubble] images crossed by satellites is currently small with a negligible impact on science,” Kruk and colleagues write. “However, the number of satellites and space debris will only increase in the future.” The team predicts that by the 2030s, the probability of a satellite crossing Hubble’s field of view any time it takes an image will be between 20 and 50 percent. The sudden jump in Starlink satellites also poses a problem for space traffic, says astronomer Samantha Lawler of the University of Regina in Canada. Starlink satellites all orbit at a similar distance from Earth, just above 500 kilometers.
“Starlink is the densest patch of space that has ever existed,” Lawler says. The satellites are constantly navigating out of each other’s way to avoid collisions (SN: 2/12/09). And it’s a popular orbital altitude — Hubble is there, and so is the International Space Station and the Chinese space station. “If there is some kind of collision [between Starlinks], some kind of mishap, it could immediately affect human lives,” Lawler says.
SpaceX launches Starlink satellites roughly once per week — it launched 51 more on March 3. And they’re not the only company launching constellations of internet satellites. By the 2030s, there could be 100,000 satellites crowding low Earth orbit.
So far, there are no international regulations to curb the number of satellites a private company can launch or to limit which orbits they can occupy.
“The speed of commercial development is much faster than the speed of regulation change,” McDowell says. “There needs to be an overhaul of space traffic management and space regulation generally to cope with these massive commercial projects.”
The oldest known fossils of pollen-laden insects are of earwig-like ground-dwellers that lived in what is now Russia about 280 million years ago, researchers report. Their finding pushes back the fossil record of insects transporting pollen from one plant to another, a key aspect of modern-day pollination, by about 120 million years.
The insects — from a pollen-eating genus named Tillyardembia first described in 1937 — were typically about 1.5 centimeters long, says Alexander Khramov, a paleoentomologist at the Borissiak Paleontological Institute in Moscow. Flimsy wings probably kept the creatures mostly on the forest floor, he says, leaving them to climb trees to find and consume their pollen.
Recently, Khramov and his colleagues scrutinized 425 fossils of Tillyardembia in the institute’s collection. Six had clumps of pollen grains trapped on their heads, legs, thoraxes or abdomens, the team reports February 28 in Biology Letters. A proportion that small isn’t surprising, Khramov says, because the fossils were preserved in what started out as fine-grained sediments. The early stages of fossilization in such material would tend to wash away pollen from the insects’ remains. The pollen-laden insects had only a couple of types of pollen trapped on them, the team found, suggesting that the critters were very selective in the tree species they visited. “That sort of specialization is in line with potential pollinators,” says Michael Engel, a paleoentomologist at the University of Kansas in Lawrence who was not involved in the study. “There’s probably vast amounts of such specialization that occurred even before Tillyardembia, we just don’t have evidence of it yet.”
Further study of these fossils might reveal if Tillyardembia had evolved special pollen-trapping hairs or other such structures on their bodies or heads, says Conrad Labandeira, a paleoecologist at the National Museum of Natural History in Washington, D.C., also not part of the study. It would also be interesting, he says, to see if something about the pollen helped it stick to the insects. If the pollen grains had structures that enabled them to clump more readily, for example, then those same features may have helped them grab Velcro-like onto any hairlike structures on the insects’ bodies.
Fungi may help some tree-killer beetles turn a tree’s natural defense system against itself.
The Eurasian spruce bark beetle (Ips typographus) has massacred millions of conifers in forests across Europe. Now, research suggests that fungi associated with these bark beetles are key players in the insect’s hostile takeovers. These fungi warp the chemical defenses of host trees to create an aroma that attracts beetles to burrow, researchers report February 21 in PLOS Biology.
This fungi-made perfume might explain why bark beetles tend to swarm the same tree. As climate change makes Europe’s forests more vulnerable to insect invasions, understanding this relationship could help scientists develop new countermeasures to ward off beetle attacks. Bark beetles are a type of insect found around the world that feed and breed inside trees (SN: 12/17/10). In recent years, several bark beetle species have aggressively attacked forests from North America to Australia, leaving ominous strands of dead trees in their wake.
But trees aren’t defenseless. Conifers — which include pine and fir trees — are veritable chemical weapons factories. The evergreen smell of Christmas trees and alpine forests comes from airborne varieties of these chemicals. But while they may smell delightful, these chemicals’ main purpose is to trap and poison invaders.
Or at least, that’s what they’re meant to do.
“Conifers are full of resin and other stuff that should do horrible things to insects,” says Jonathan Gershenzon, a chemical ecologist at the Max Planck Institute for Chemical Ecology in Jena, Germany. “But bark beetles don’t seem to mind at all.”
This ability of bark beetles to overcome the powerful defense system of conifers has led some scientists to wonder if fungi might be helping. Fungi break down compounds in their environment for food and protection (SN: 11/30/21). And some type of fungi — including some species in the genus Grosmannia — are always found in association with Eurasian spruce bark beetles. Gershenzon and his colleagues compared the chemicals released by spruce bark infested with Grosmannia and other fungi to the chemical profile of uninfected trees. The presence of the fungi fundamentally changed the chemical profile of spruce trees, the team found. More than half the airborne chemicals — made by fungi breaking down monoterpenes and other chemicals that are likely part of the tree defense system — were unique to infected trees after 12 days.
This is surprising because researchers had previously assumed that invading fungi hardly changed the chemical profile of trees, says Jonathan Cale, a fungal ecologist at the University of Northern British Columbia in Prince George, Canada, who was not involved with the research. Later experiments revealed that bark beetles can detect many of these fungi-made chemicals. The team tested this by attaching tiny electrodes on bark beetles’ heads and detecting electrical activity when the chemicals wafted passed their antennae. What’s more, the smell of these chemicals combined with beetle pheromones led the insects to burrow at higher rates than the smell of pheromones alone.
The study suggests that these fungi-made chemicals can help beetles tell where to feed and breed, possibly by advertising that the fungi has taken down some of the tree’s defenses. The attractive nature of the chemicals could also explain the beetle’s swarming behavior, which drives the death of healthy adult trees.
But while the fungi aroma might doom trees, it could also lead to the beetles’ demise. Beetle traps in Europe currently use only beetle pheromones to attract their victims. Combining pheromones with fungi-derived chemicals might be the secret to entice more beetles into traps, making them more effective.
The results present “an exciting direction for developing new tools to manage destructive bark beetle outbreaks” for other beetle species as well, Cale says. In North America, mild winters and drought have put conifer forests at greater risk from mountain pine beetle (Dendroctonus pendersoae) attacks. Finding and using fungi-derived chemicals might be one way to fend off the worst of the bark beetle invasions in years to come.
In August 2021 on a lonely crater floor, the newest Mars rover dug into one of its first rocks.
The percussive drill attached to the arm of the Perseverance rover scraped the dust and top several millimeters off a rocky outcrop in a 5-centimeter-wide circle. From just above, one of the rover’s cameras captured what looked like broken shards wedged against one another. The presence of interlocking crystal textures became obvious. Those textures were not what most of the scientists who had spent years preparing for the mission expected. Then the scientists watched on a video conference as the rover’s two spectrometers revealed the chemistry of those meshed textures. The visible shapes along with the chemical compositions showed that this rock, dubbed Rochette, was volcanic in origin. It was not made up of the layers of clay and silt that would be found at a former lake bed.
Nicknamed Percy, the rover arrived at the Jezero crater two years ago, on February 18, 2021, with its sidekick helicopter, Ingenuity. The most complex spacecraft to explore the Martian surface, Percy builds on the work of the Curiosity rover, which has been on Mars since 2012, the twin Spirit and Opportunity rovers, the Sojourner rover and other landers.
But Perseverance’s main purpose is different. While the earlier rovers focused on Martian geology and understanding the planet’s environment, Percy is looking for signs of past life. Jezero was picked for the Mars 2020 mission because it appears from orbit to be a former lake environment where microbes could have thrived, and its large delta would likely preserve any signs of them. Drilling, scraping and collecting pieces of the Red Planet, the rover is using its seven science instruments to analyze the bits for any hint of ancient life. It’s also collecting samples to return to Earth. Since landing, “we’ve been able to start putting together the story of what has happened in Jezero, and it’s pretty complex,” says Briony Horgan, a planetary scientist at Purdue University in West Lafayette, Ind., who helps plan Percy’s day-to-day and long-term operations.
Volcanic rock is just one of the surprises the rover has uncovered. Hundreds of researchers scouring the data Perseverance has sent back so far now have some clues to how the crater has evolved over time. This basin has witnessed flowing lava, at least one lake that lasted perhaps tens of thousands of years, running rivers that created a mud-and-sand delta and heavy flooding that brought rocks from faraway locales.
Jezero has a more dynamic past than scientists had anticipated. That volatility has slowed the search for sedimentary rocks, but it has also pointed to new alcoves where ancient life could have taken hold.
Perseverance has turned up carbon-bearing materials — the basis of life on Earth — in every sample it has abraded, Horgan says. “We’re seeing that everywhere.” And the rover still has much more to explore. Perseverance finds unexpected rocks Jezero is a shallow impact crater about 45 kilometers in diameter just north of the planet’s equator. The crater formed sometime between 3.7 billion and 4.1 billion years ago, in the solar system’s first billion years. It sits in an older and much larger impact basin known as Isidis. At Jezero’s western curve, an etched ancient riverbed gives way to a dried-out, fan-shaped delta on the crater floor.
That delta “is like this flashing signpost beautifully visible from orbit that tells us there was a standing body of water here,” says astrobiologist Ken Williford of Blue Marble Space Institute of Science in Seattle.
Perseverance landed on the crater floor about two kilometers from the front of the delta. Scientists thought they’d find compacted layers of soil and sand there, at the base of what they dubbed Lake Jezero. But the landscape immediately looked different than expected, says planetary geologist Kathryn Stack Morgan of NASA’s Jet Propulsion Laboratory in Pasadena, Calif. Stack Morgan is deputy project scientist for Perseverance. For the first several months after the landing, the Mars 2020 mission team tested the rover’s movements and instruments, slowly, carefully. But from the first real science drilling near the landing location, researchers back on Earth realized what they had found. The texture of the rock, Stack Morgan says, was “a textbook igneous volcanic rock texture.” It looked like volcanic lava flows.
Over the next six months, several more rocks on the crater floor revealed igneous texture. Some of the most exciting rocks, including Rochette, showed olivine crystals throughout. “The crystal fabric was obviously cooled from a melt, not transported grains,” as would be the case if it were a sedimentary sample, says Abigail Allwood of the Jet Propulsion Lab. She leads the rover’s PIXL instrument, which uses an X-ray beam to identify each sample’s composition.
Mission scientists now think the crater floor is filled with igneous rocks from two separate events — both after the crater was created, so more recently than the 3.7 billion to 4.1 billion years ago time frame. In one, magma from deep within the planet pushed toward the surface, cooled and solidified, and was later exposed by erosion. In the other, smaller lava flows streamed at the surface. Sometime after these events, water flowed from the nearby highlands into the crater to form a lake tens of meters deep and lasting tens of thousands of years at least, according to some team members. Percy’s instruments have revealed the ways that water altered the igneous rocks: For example, scientists have found sulfates and other minerals that require water to form, and they’ve seen empty pits within the rocks’ cracks, where water would have washed away material. As that water flowed down the rivers into the lake, it deposited silt and mud, forming the delta. Flooding delivered 1.5-meter-wide boulders from that distant terrain. All of these events preceded the drying of the lake, which might have happened about 3 billion years ago.
Core samples, which Perseverance is collecting and storing on board for eventual return to Earth, could provide dates for when the igneous rocks formed, as well as when the Martian surface became parched. During the time between, Lake Jezero and other wet environments may have been stable enough for microbial life to start and survive.
“Nailing down the geologic time scale is of critical importance for us understanding Mars as a habitable world,” Stack Morgan says. “And we can’t do that without samples to date.”
About a year after landing on Mars, Perseverance rolled several kilometers across the crater floor to the delta front — where it encountered a very different geology.
The delta might hold signs of ancient life Deltas mark standing, lasting bodies of water — stable locales that could support life. Plus, as a delta grows over time, it traps and preserves organic matter.
Sand and silt deposited where a river hits a lake get layered into sedimentary material, building up a fan-shaped delta. “If you have any biological material that is trapped between that sediment, it gets buried very quickly,” says Mars geologist Eva Scheller of MIT, a researcher with the Percy team. “It creates this environment that is very, very good for preserving the organic matter.”
While exploring the delta front between April 2022 and December 2022, Perseverance found some of the sedimentary rocks it was after. Several of the rover’s instruments zoomed in on the textures and shapes of the rocks, while other instruments collected detailed spectral information, revealing the elements present in those rocks. By combining the data, researchers can piece together what the rocks are made of and what processes might have changed them over the eons. It’s this chemistry that could reveal signs of ancient Martian life — biosignatures. Scientists are still in the early stages of these analyses.
There won’t be one clear-cut sign of life, Allwood says. Instead, the rover would more likely reveal “an assemblage of characteristics,” with evidence slowly building that life once existed there.
Chemical characteristics suggestive of life are most likely to hide in sedimentary rocks, like those Perseverance has studied at the delta front. Especially interesting are rocks with extremely fine-grained mud. Such mud sediments, Horgan says, are where — in deltas on Earth, at least — organic matter is concentrated. So far, though, the rover hasn’t found those muddy materials.
But the sedimentary rocks studied have revealed carbonates, sulfates and unexpected salts — all materials indicating interaction with water and important for life as we know it. Percy has found carbon-based matter in every rock it has abraded, Horgan says.
“We’ve had some really interesting results that we’re pretty excited to share with the community,” Horgan says about the exploration of the delta front. Some of those details may be revealed in March at the Lunar and Planetary Science Conference.
Perseverance leaves samples for a future mission As of early February, Perseverance has collected 18 samples, including bits of Mars debris and cores from rocks, and stored them on board in sealed capsules for eventual return to Earth. The samples come from the crater floor, delta front rocks and even the thin Martian atmosphere.
In the final weeks of 2022 and the first weeks of 2023, the rover dropped — or rather, carefully set down — half of the collected samples, as well as a tube that would reveal whether samples contained any earthly contaminants. These captured pieces of Mars are now sitting at the front of the delta, at a predetermined spot called the Three Forks region. If Perseverance isn’t functioning well enough to hand over its onboard samples when a future sample-return spacecraft arrives, that mission will collect these samples from the drop site to bring back to Earth.
Researchers are currently working on designs for a joint Mars mission between NASA and the European Space Agency that could retrieve the samples. Launching in the late 2020s, it would land near the Perseverance rover. Percy would transfer the samples to a small rocket to be launched from Mars and returned to Earth in the 2030s. Lab tests could then confirm what Perseverance is already uncovering and discover much more.
Meanwhile, Percy is climbing up the delta to explore its top, where muddy sedimentary rocks may still be found. The next target is the edge of the once-lake, where shallow water long ago stood. This is the site Williford is most excited about. Much of what we know about the history of how life has evolved on Earth comes from environments with shallow water, he says. “That’s where really rich, underwater ecosystems start to form,” he says. “There’s so much going on there chemically.”
Scientists have finally figured out how those arches, loops and whorls formed on your fingertips.
While in the womb, fingerprint-defining ridges expand outward in waves starting from three different points on each fingertip. The raised skin arises in a striped pattern thanks to interactions between three molecules that follow what’s known as a Turing pattern, researchers report February 9 in Cell. How those ridges spread from their starting sites — and merge — determines the overarching fingerprint shape. Fingerprints are unique and last for a lifetime. They’ve been used to identify individuals since the 1800s. Several theories have been put forth to explain how fingerprints form, including spontaneous skin folding, molecular signaling and the idea that ridge pattern may follow blood vessel arrangements.
Scientists knew that the ridges that characterize fingerprints begin to form as downward growths into the skin, like trenches. Over the few weeks that follow, the quickly multiplying cells in the trenches start growing upward, resulting in thickened bands of skin.
Since budding fingerprint ridges and developing hair follicles have similar downward structures, researchers in the new study compared cells from the two locations. The team found that both sites share some types of signaling molecules — messengers that transfer information between cells — including three known as WNT, EDAR and BMP. Further experiments revealed that WNT tells cells to multiply, forming ridges in the skin, and to produce EDAR, which in turn further boosts WNT activity. BMP thwarts these actions.
To examine how these signaling molecules might interact to form patterns, the team adjusted the molecules’ levels in mice. Mice don’t have fingerprints, but their toes have striped ridges in the skin comparable to human prints. “We turn a dial — or molecule — up and down, and we see the way the pattern changes,” says developmental biologist Denis Headon of the University of Edinburgh.
Increasing EDAR resulted in thicker, more spaced-out ridges, while decreasing it led to spots rather than stripes. The opposite occurred with BMP, since it hinders EDAR production.
That switch between stripes and spots is a signature change seen in systems governed by Turing reaction-diffusion, Headon says. This mathematical theory, proposed in the 1950s by British mathematician Alan Turing, describes how chemicals interact and spread to create patterns seen in nature (SN: 7/2/10). Though, when tested, it explains only some patterns (SN: 1/21/14).
Mouse digits, however, are too tiny to give rise to the elaborate shapes seen in human fingerprints. So, the researchers used computer models to simulate a Turing pattern spreading from the three previously known ridge initiation sites on the fingertip: the center of the finger pad, under the nail and at the joint’s crease nearest the fingertip. By altering the relative timing, location and angle of these starting points, the team could create each of the three most common fingerprint patterns — arches, loops and whorls — and even rarer ones. Arches, for instance, can form when finger pad ridges get a slow start, allowing ridges originating from the crease and under the nail to occupy more space.
“It’s a very well-done study,” says developmental and stem cell biologist Sarah Millar, director of the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai in New York City.
Controlled competition between molecules also determines hair follicle distribution, says Millar, who was not involved in the work. The new study, she says, “shows that the formation of fingerprints follows along some basic themes that have already been worked out for other types of patterns that we see in the skin.”
Millar notes that people with gene mutations that affect WNT and EDAR have skin abnormalities. “The idea that those molecules might be involved in fingerprint formation was floating around,” she says.
Overall, Headon says, the team aims to aid formation of skin structures, like sweat glands, when they’re not developing properly in the womb, and maybe even after birth.
“What we want to do, in broader terms, is understand how the skin matures.”
A mysterious new disease may be to blame for severe, unexplained inflammation in older men. Now, researchers have their first good look at who the disease strikes, and how often.
VEXAS syndrome, an illness discovered just two years ago, affects nearly 1 in 4,000 men over 50 years old, scientists estimate January 24 in JAMA. The disease also occurs in older women, though less frequently. Altogether, more than 15,000 people in the United States may be suffering from the syndrome, says study coauthor David Beck, a clinical geneticist at NYU Langone Health in New York City. Those numbers indicate that physicians should be on the lookout for VEXAS, Beck says. “It’s underrecognized and underdiagnosed. A lot of physicians aren’t yet aware of it.” Beck’s team reported discovering VEXAS syndrome in 2020, linking mutations in a gene called UBA1 to a suite of symptoms including fever, low blood cell count and inflammation. His team’s new study is the first to estimate how often VEXAS occurs in the general population — and the results are surprising. “It’s more prevalent than we suspected,” says Emma Groarke, a hematologist at the National Institutes of Health in Bethesda, Md., who was not involved with the study. VEXAS tends to show up later in life — after people somehow acquire UBA1 mutations in their blood cells. Patients may feel overwhelming fatigue, lethargy and have skin rashes, Beck says. “The disease is progressive, and it’s severe.” VEXAS can also be deadly. Once a person’s symptoms begin, the median survival time is about 10 years, his team has found.
Until late 2020, no one knew that there was a genetic thread connecting VEXAS syndrome’s otherwise unexplained symptoms. In fact, individuals may be diagnosed with other conditions, including polyarteritis nodosa, an inflammatory blood disease, and relapsing polychondritis, a connective tissue disorder, before being diagnosed with VEXAS.
To ballpark the number of VEXAS-affected individuals, Beck’s team combed through electronic health records of more than 160,000 people in Pennsylvania, in a collaboration with the NIH and Geisinger Health. In people over 50, the disease-causing UBA1 mutations showed up in roughly 1 in 4,000 men. Among women in that age bracket, about 1 in 26,000 had the mutations.
A genetic test of the blood can help doctors diagnose VEXAS, and treatments like steroids and other immunosuppressive drugs, which tamp down inflammation, can ease symptoms. Groarke and her NIH colleagues have also started a small phase II clinical trial testing bone marrow transplants as a way to swap patients’ diseased blood cells for healthy ones.
Beck says he hopes to raise awareness about the disease, though he recognizes that there’s much more work to do. In his team’s study, for instance, the vast majority of participants were white Pennsylvanians, so scientists don’t know how the disease affects other populations. Researchers also don’t know what spurs the blood cell mutations, nor how they spark an inflammatory frenzy in the body.
“The more patients that are diagnosed, the more we’ll learn about the disease,” Beck says. “This is just one step in the process of finding more effective therapies.”