Using Google’s AlphaFold, researchers identified the bundle of three sperm proteins that seem to make sexual reproduction possible.They’re the original odd couple: One is massive, spherical and unmoving. The other is tiny, has a tail and never stops swimming. Yet the union of egg and sperm is critical for every sexually reproducing animal on Earth.Exactly how that union occurs has long been a mystery to scientists. A study published Thursday in the journal Cell that relied on Nobel Prize-honored artificial intelligence technology shows that an interlocked bundle of three proteins is the key that lets sperm and egg bind together. That crucial bundle is shared by animals as distantly related as fish and mammals, and most likely including humans.For nearly all animals on Earth, life begins with a sperm cell making its way to an egg’s cell membrane. Somehow, the two cells recognize each other and bind together. Then, in a flash, the sperm head passes into the egg, as if stepping through a door. Now the fused cell is a zygote and ready to grow into a new animal.In earlier research, scientists had found four proteins on mammal sperm that are also present on fish sperm and are needed for fertilization. But no one knew whether they might work as a team to enter an egg, or how.In the new study, Andrea Pauli, a molecular and developmental biologist at the Research Institute of Molecular Pathology in Vienna, and collaborators across several institutions asked how sperm proteins might team up during fertilization.The researchers relied on AlphaFold, a technology that shared the Nobel Prize in Chemistry last week. It uses A.I. to predict the shape of a protein. With AlphaFold, the team could compare the four sperm proteins shared across mammals and fish against a library of about 1,400 other proteins found on cell surfaces in zebrafish testes, looking for potential partners.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Nearly 50,000 preterm births may have been averted across a group of mostly high-income countries in one month alone.Elizabeth Decker had a stressful second pregnancy, plagued by daily vomiting and the worry that this baby, like her first, would drive her blood pressure dangerously high and need to be delivered preterm. Oddly, the most relaxing part was her final trimester, which overlapped with the world’s descent into Covid lockdown in spring 2020.Ms. Decker, who is 36 and lives in North Reading, Mass., decided to leave her high-pressure job as a lawyer and stay home. Her husband, a teacher, started working from home at that time, teaching online. He cared for their toddler and handled meals while Ms. Decker rested and slept. “I was able to really not do anything for the last three months of my pregnancy,” she said. The blood pressure spike that her doctor had expected didn’t arrive until late June, a week past Ms. Decker’s due date, at which point she delivered a healthy baby.An ambitious worldwide study of births suggests that Ms. Decker was not the only expectant parent who avoided the experience of a preterm delivery during the earliest months of lockdown. The study, published Monday in the journal Nature Human Behavior, showed that across a group of mostly high-income countries — such as the United States, Belgium, Canada, Chile, Denmark and Switzerland — in spring 2020, there were about 4 percent fewer preterm births than expected. At a global level, the study’s authors estimated, the change most likely added up to nearly 50,000 premature births averted in the first month of lockdown alone.The finding could help researchers better understand the causes of preterm birth, which remain frustratingly elusive to medical science.“This is a unique natural experiment, where the whole world experienced this pretty drastic lockdown at the same time,” said Meghan Azad, an associate professor of pediatrics and child health at the University of Manitoba and one of the study’s leaders. “So it was a neat opportunity to look at what that might mean for maternal-child health.”Around the time Ms. Decker was caring for her full-term infant, doctors in a variety of countries were also seeing fewer premature babies than they had expected. Some of their observations, shared before peer review but since formally published, were striking: Across Denmark, for instance, numbers of the smallest preemies were down by 90 percent. At a hospital in Ireland, very early births dropped by three-quarters or more.The Irish authors speculated that pregnant people who were locked down at home might be experiencing lower stress, less air pollution or fewer viral or bacterial infections, all of which might reduce their odds of delivering early.More on the Coronavirus PandemicLab Leak: New intelligence has prompted the Energy Department to conclude that an accidental laboratory leak in China most likely caused the pandemic, though U.S. spy agencies remain divided over Covid’s origins.New Drug’s Long Odds: A promising new treatment quashes all Covid variants, but regulatory hurdles and a lack of funding make it unlikely to reach the United States market anytime soon.Dangers Remain for Seniors: For older Americans, the Covid pandemic still poses significant threats. But they are increasingly left to protect themselves as the rest of the country abandons precautions.N.Y.C.’s Mandate: New York City will end its aggressive but contentious vaccine mandate for municipal workers, Mayor Eric Adams announced, signaling a key moment in the city’s long battle against the pandemic.Responding to the Irish study on Twitter, Dr. Azad wondered aloud — morbidly, she admitted — if doctors were seeing drops in premature births that spring because some of those babies had been lost to stillbirth or miscarriage.Within two days, Dr. Azad was teaming up with other scientists to study this very question. “It was this kind of crazy time,” she said. “A bunch of researchers had a lot of time on their hands, because their projects were slowed down or their conferences were canceled.” They were free to dive into a large-scale side project.The collaboration ultimately grew to include over 100 scientists from across the world, and 52 million births. Using data from 2015 to 2020, the scientists modeled the expected numbers of preterm births and stillbirths in the first months of each country’s strict lockdown period.A pregnant woman in Lima, Peru, received an ultrasound in the first summer of the pandemic. The findings highlighted how much is still unknown about what causes preterm birth. “Even if there are 52 million births in the study, it is not going to immediately answer all the questions,” said one of its authors.Paolo Aguilar/EPA, via ShutterstockThey realized that data from smaller samples, such as a single hospital, might not tell a full story. For example, Dr. Azad said, what if that hospital had become a dedicated site for Covid treatment and had simply diverted its pregnant patients elsewhere?For that reason, the researchers focused their main analysis on high-quality data sets that covered an entire country, or a large region of a country. That included 18 high-income and upper-middle-income nations, as defined by the World Bank. Although the results varied across sites, the researchers concluded that preterm births had dropped by an average of 4 percent during both the first and second months of lockdown.In the third month, the statistical signal was weaker. By the fourth month of lockdown — as countries were most likely diverging in their guidelines and in how strictly people adhered to them, Dr. Azad said — the drop in preterm births was gone.The authors did find a slight uptick in stillbirths in Brazil during the second and third months, and in Canada during the first month. “But that certainly didn’t seem to explain the overall decrease in preterm births” across the data set, Dr. Azad said.The authors noted that Covid itself raises a person’s risk of both premature birth and stillbirth. But because infection with the virus was less widespread in spring 2020 than later periods, this probably didn’t affect the study’s results.“The causes of preterm birth have been so elusive, despite considerable efforts,” said Dr. Denise Jamieson, an obstetrician at Emory University’s School of Medicine in Atlanta who was not involved in the new study. Even though the global study found a dip of only about 4 percent, “I think any reduction in preterm birth is noteworthy and important,” she said.“The next step is to really look at the why,” Dr. Jamieson added.Dr. Azad and Dr. Roy Philip, a co-author of the new paper and also the Irish neonatologist at University Maternity Hospital Limerick who in 2020 found a striking drop in very early births at his hospital, both said it was possible that lockdowns had quite different effects on different groups of people. A pregnant person like Ms. Becker who was able to stay home in a low-stress environment, with good support, might have benefited. A frontline worker without health insurance might have had a different experience.In this way, the findings highlighted how much is still unknown about what causes preterm birth. “Even if there are 52 million births in the study, it is not going to immediately answer all the questions,” Dr. Philip said. “But at least this should trigger people to look more closely at what is ideal during pregnancy.”The study also highlighted the uneven preterm birthrates across different countries. Across the five years of data, the United States had the highest preterm birthrate of any high-income nation included — just shy of 10 percent. Finland’s rate, by contrast, was below 6 percent.The disparity isn’t surprising, Dr. Jamieson said. “Unfortunately, the United States is an outlier for a lot of important maternal and infant health outcomes when you compare it to other high-income countries.”Future research could use this global data set to investigate such variations in maternal health. Dr. Azad said she had originally hoped to dig into the drivers of preterm birth during lockdown, not just its frequency: Were changes in air pollution correlated with changes in early births? What about hygiene, or income, or access to health care? But she lacked funding to investigate further, Dr. Azad said, and now those other projects that were deferred early in the pandemic have caught up with her and her colleagues.Dr. Azad doubts one of her tweets today could launch a huge international research effort. People in spring 2020 had “this burning desire to do something, to either help the pandemic or make something of it,” she said. Some researchers even worked on the project without pay. “I’m a scientist; I don’t like using the word ‘magical,’” she said. “But it was kind of magical.”Now the mysteries of preterm birth will have to wait for other investigators, Dr. Azad said, adding, “We don’t all have that extra time anymore.”

As cephalopods become more important in neuroscience and other fields, scientists and welfare advocates seek to give the smart animals the same protections as mice and monkeys.Lab rats have rights. Before researchers in the United States can experiment on the animals, they need approval from committees that ensure they follow federal regulations for housing and handling the creatures humanely. The same is true of scientists working with mice, monkeys, fish or finches.These protected animals share one thing in common: a backbone.But invertebrates in research labs, including worms and bees or cephalopods like squid and octopuses, do not receive the same protections from the federal government. As researchers are more often working with cephalopods to answer questions in neuroscience and other fields, the matter of whether they’re treating the animals humanely is becoming more pressing.Governments in Europe and Australia have written these smart, spineless animals into their laws. But in the United States, “If you were in a research setting, and you wanted to buy some octopuses and do whatever you wanted to do with them, there is no regulatory oversight to stop you,” said Robyn Crook, a neuroscientist at San Francisco State University.That’s not to say cephalopod research is the wild west. American research institutions are increasingly opting to subject their cephalopod studies to the same approval process as experiments on mice or other vertebrates. But the lack of cephalopod care standards to guide their decisions, combined with the lack of federal oversight to back them up, reflects how rules and laws are lagging behind scientific understanding of these animals’ complex inner lives.🐙🔬🥼Like a lab rat, an octopus can learn to navigate a maze. Octopuses can also perform clever feats that rats can’t, such as disguising themselves as rocks and snakes, breaking out of their tanks or hiding inside coconut shells.In 2021, Alexandra Schnell, a biologist at the University of Cambridge, and others found that cuttlefish can pass a version of the marshmallow test, a famous measure of self-control in human psychology. The cephalopods resisted eating a piece of prawn for as long as two minutes to earn an even better snack (a live shrimp).Unlike humans — whose intelligence is, as it were, all in their heads — octopuses carry the bulk of their nervous system in their arms. Their suckers don’t just grab onto things, they feel and taste them, too. “It’s like if your hands were coated with tongues,” said Christine Huffard, a biologist at the Monterey Bay Aquarium Research InstIn one experiment, octopuses were found to stroke a wound with their beaks, and avoid chambers where they were placed after receiving a painful injection.Blickwinkel/AlamyIn a paper published in July, Dr. Huffard and Peter Morse, of James Cook University in Australia showed that male blue-ringed octopuses could use touch to recognize females they’d already mated with. After bumping into a former mate, the males fled, perhaps to avoid being eaten. Such research suggests that octopuses and other cephalopods are smart and sensitive.But do they feel pain like we do? It isn’t just a hypothetical concern. Some research with cephalopods involves potentially painful surgeries, such as amputating an octopus’s arm. We can’t simply ask them whether it hurts, though.“Whether or not pain experience exists in animals outside vertebrates is quite a controversial proposition,” Dr. Crook said. In a 2021 paper, she showed that octopuses that had received an injection of acetic acid had stroked the wound with their beaks and had avoided a chamber where they’d stayed after receiving the injection. But the octopuses had liked being in a chamber where they had experienced a numbing injection after the first one.Researchers use a similar test in rodents to judge whether drugs cause them pain. “We suggest that octopuses feel, and are capable of feeling, the same thing,” Dr. Crook said.In another 2021 paper, she and co-authors studied the nerve activity of octopuses and cuttlefish that had been anesthetized — or so the scientists thought. They’d dipped the animals in magnesium chloride to anesthetize them, a common lab procedure. When an animal stopped moving and turned white, scientists had assumed it couldn’t feel anything and wouldn’t be stressed by handling. But electrode recordings showed that for several minutes after becoming unresponsive, the cephalopod could still feel experimenters touching its body.Dr. Crook said the finding immediately changed how researchers in her lab anesthetized octopuses. Now, they wait as long as 20 extra minutes to make sure the animals won’t feel anything. She hopes other labs have changed their practices, too.🐙🔬🥼Who’s responsible for the well-being of captive animals? The answer, in the United States, is complicated.The Animal Welfare Act, passed in 1966, requires humane treatment of animals such as primates and pet dogs and cats. It doesn’t apply to farm animals, racehorses, invertebrates, fish, or lab rats or mice. Another law, the Health Research Extension Act of 1985, governs the treatment of all vertebrate animals in research funded by the U.S. government.Both laws require universities and other research institutions to have an Institutional Animal Care and Use Committee, or IACUC. Committees must include at least one veterinarian and one person unaffiliated with the institution. Before starting a research project, a scientist must submit a proposal to their institution’s committee, which, in turn, must make sure the scientist’s plan meets federal guidelines.“I think it works well,” said Dr. Steve Niemi, a lab animal veterinarian and director of the Animal Science Center at Boston University. “This is both a highly contentious area and a highly scrutinized — and, I would argue, highly regulated — area” for vertebrates, Dr. Niemi said.Male blue-ringed octopuses were found to recognize females they’ve already mated with by their sense of touch, a sign of how sensitive their limbs are.Norbert Probst/AlamyDr. Niemi said critics have pointed out that animal care committees have rarely denied approval to researchers. But in his experience, this is because committees go back and forth with a scientist to revise the plan until it is acceptable. “To me, our mission is to enable responsible research,” he said.As scientists learn more about cephalopods’ intelligence and perception of pain, Dr. Niemi said, “It is incumbent upon us ethically to consider if, and how, to add them to our local oversight.”Already, many universities are voluntarily having their committees review research on cephalopods. Dr. Crook said that this trend has gained momentum in the past two years.However, she said, the job of these committees is to make sure researchers are following federal law, but when it comes to invertebrates, that law doesn’t exist. “They’re almost operating unanchored,” she said.There’s also no universal manual for cephalopod care because scientists are still learning about their biology. In the event that a researcher violated their agreement with the committee, for example, there could be no legal recourse to stop their experiment from happening.“In some ways, it’s regulation theater,” Dr. Crook said.🐙🔬🥼While universities and other research institutions try to apply a nonexistent law to their cephalopods, Katherine Meyer, who directs the Animal Law and Policy Clinic at Harvard Law School, is trying to pressure the National Institutes of Health, the main federal funder of biomedical research in the United States, into making a change.In 2020, Ms. Meyer’s clinic petitioned the institutes’ Office of Laboratory Animal Welfare to take action toward regulating cephalopod research. “I just had the idea that we should do something to protect octopuses,” she said.Ms. Meyer realized that while the 1985 Health Research Extension Act addressed the care of “animals in research,” it didn’t actually define an animal. The definition of animals as “live, vertebrate” creatures is in another N.I.H. document called the Public Health Service Policy on Humane Care and Use of Laboratory Animals.“That’s when I saw the opening,” Ms. Meyer said. She said the N.I.H.’s lab animal office could protect octopuses and their kin by simply changing the definition of “animals” in the policy to include cephalopods, rather than amending the underlying law.She received a response in July 2020 that said the agency was “aware of the standards in other countries that include cephalopods in animal welfare oversight and regulations” and was “currently considering options for providing guidance on humane care and use of invertebrates in N.I.H. funded research.”Beyond that, she said, “We have not gotten a substantive response from the agency.”“An unhealthy and overly stressed octopus isn’t going to yield useful data,” Dr. Huffard said. Terry Moore/Stocktrek Images, via AlamyIn response to a request for comment, a spokesperson for the N.I.H. Office of Extramural Research repeated the language from Ms. Meyer’s letter.Dr. Huffard said that in the absence of new federal guidance, many international scientific journals require U.S. researchers to show that they’ve passed cephalopod research through an IACUC or another institutional review process before their research can be published. An animal-welfare nonprofit called AAALAC International, which offers voluntary accreditation to research institutions, is also recommending that institutional committees approve cephalopod research.“I don’t know any cephalopod researcher that would just scoff at these rules,” Dr. Huffard said. Even if the U.S. government hasn’t determined that cephalopods deserve the same protections as other animals, scientists who study the many-armed creatures have made that determination for themselves.“An unhealthy and overly stressed octopus isn’t going to yield useful data,” Dr. Huffard said. Even aside from the data, she added, “I want the animals to be happy and healthy.”As long as we’re rethinking how our laws privilege animals with backbones, through, Dr. Huffard said it may not make sense to elevate cephalopods above the other spineless species. Octopuses “are very complex animals; nobody will doubt that,” she said. “Are they the most complex invertebrates? Depends on how you define that.”Bees, for instance, have remarkably intricate behaviors and social structures. Crabs and lobsters were recently declared sentient by the British government, and in Switzerland, it’s illegal to boil a lobster alive. “If people studied mantis shrimps the way they study octopuses, they would be really blown away at how smart they are,” Dr. Huffard said.“I feel like we should be treating all animals with that level of respect,” she said.