For some people, including President Joe Biden and National Institute of Allergy and Infectious Diseases director Anthony Fauci, the relief of vanishing COVID-19 symptoms and a negative test is fleeting. Biden, Fauci and many others have seen their tests turn positive again or have unwelcome symptoms return after taking a five-day course of the antiviral Paxlovid. Other people, including my husband, have had their infections rebound even without taking the drug.

Multiple studies have described cases of “Paxlovid rebound” after treatment. In one, seven Paxlovid-treated patients had the virus rebound to high levels after treatment ended, and symptoms returned for six of them, virologist Jonathan Li and colleagues reported in June in Clinical Infectious Diseases. Samples from three patients even carried infectious virus, a clue that some people who rebound might infect others. Another study that has yet to be peer-reviewed by other researchers found that fewer than 6 percent of people in the study who’d been prescribed Paxlovid had rebound infections in the month after finishing treatment.
It’s unclear why Paxlovid rebound happens, says Li, of Brigham and Women’s Hospital and Harvard Medical School. Studies show that people given the drug still develop a strong immune response to the virus after five days of treatment. “I think what’s happening in that situation is that you’ve got virus replication that’s been inhibited. All of a sudden, the drug has disappeared and the virus has a momentary opportunity to replicate. And it replicates to high levels,” Li says. But by then, the immune system has learned to fend off the coronavirus. If the recently trained immune cells encounter newly made viruses and set off alarm bells, symptoms may briefly come back.

Some people might not want to take the drug because they’re worried about rebound, Li says. But Paxlovid itself probably isn’t the cause. The drug’s not failing. It is still highly effective in preventing severe disease. “I would not hesitate to give my patients Paxlovid,” Li says. “I do tell them to be on the lookout for rebounding symptoms. But it doesn’t dissuade me in terms of prescribing it.”

Fauci took another course of Paxlovid in the wake of his rebound. The U.S. Food and Drug Administration says that there’s no evidence that 10 days of treatment is any more effective than five days, or that patients need a repeat. But, researchers are testing whether taking the drug for a longer period of time might prevent rebound.

Rebounding COVID-19 isn’t limited to patients who take Paxlovid. Li recalls that even in the early days of the pandemic, some patients would come to him in the hospital saying that they’d started to feel better but got worse again. It’s hard to know how to interpret such anecdotal reports, he says. Researchers are still learning what an untreated viral infection can look like in the body. While the virus’s (hopefully) brief invasion may appear straightforward on average — with virus levels in the body increasing to a peak before slowly declining as the person recovers — not everyone follows that pattern.
My husband got COVID-19 two months ago. His symptoms lasted about a week, and he was delighted to see the line on his antigen test getting fainter. Even so, despite feeling perfectly healthy, the line was suddenly back at full strength almost immediately after he added his sample to a new test days later. He was frustrated and, as a social person, lamented having to stay isolated.

Studies show he’s not alone. When Li and colleagues studied the course of disease in COVID-19 clinical trial participants who received a placebo treatment, 1 in 8 people experienced a rebound, with symptoms coming back for 1 in 4 people. That rebound, however, typically lasted about a day, and few had both high viral loads and returning symptoms, the team reports in a preliminary study posted August 2 at medRxiv.org that hasn’t yet been peer-reviewed by other scientists.

In this case, there’s no disappearing drug. Any returning symptoms without a positive test might be from something else such as allergies or a different respiratory virus, Li says. It’s also possible that the virus is replicating in different parts of the body at different times. Some tests might end up negative when the body eliminates virus from the throat, for example, but it’s still replicating at low levels in the nose.

That latter scenario may have happened with my husband. In a confusing twist, he tested negative on two saliva PCR tests while continuing to test positive on nasal antigen tests. A PCR test is far more sensitive, so we expected the opposite to happen. Since experts say to consider a positive antigen test as a sign you’re still contagious, he stayed isolated until he finally tested negative on an antigen test two weeks after his first symptoms appeared.

Luckily, he’s fully recovered now, and not at all eager for a repeat experience. That means we’re both still masking in public spaces and taking other precautions. We know we’re not done with this pandemic.

Potential hints of weird new particles in a dark matter detector have evaporated with new data.

Following up on a beguiling result from its predecessor experiment, the XENONnT experiment found no sign of extra blips that could point to new particles or another phenomenon, scientists report July 22 in Vienna at the International Conference on Identification of Dark Matter.

The XENONnT experiment (pronounced “xenon n ton”), at the Gran Sasso National Laboratory in Italy, uses 5.9 metric tons of liquid xenon to search for dark matter, an elusive substance that so far has been seen only via its gravitational effects in the cosmos (SN: 10/25/16). The detector is designed to look for dark matter particles crashing into xenon atoms’ nuclei, causing them to recoil. But the detector can also spot recoiling electrons.
In 2020, a smaller version of the experiment, called XENON1T, reported greater-than-expected numbers of those ricocheting electrons (SN: 6/17/20). “This caused a lot of stir when we published it,” says physicist Rafael Lang of Purdue University in West Lafayette, Ind.

That surplus, some scientists suggested, could have been explained by some unexpected new physics, such as hypothetical lightweight particles that may originate from the sun called solar axions. But the excess wasn’t large enough to be convincing, so more data were needed.

In the new analysis, which uses about 97 days of data, XENONnT spotted as many electron recoils as expected due to known particle interactions, the researchers also reported in a paper posted on the experiment’s website. Scientists don’t know what caused the extra detections in the previous experiment, but it’s possible it was merely a statistical fluke, Lang says. Or it may have been due to small amounts of tritium — hydrogen atoms with two neutrons in their nuclei — in the detector.

With the red herring out of the way, XENONnT researchers are now combing through their data for nuclear recoils, in hopes of detecting the real deal.

It may soon be too late to end the global monkeypox epidemic.

“We are losing the window to be able to contain this outbreak,” Boghuma Titanji, an infectious diseases doctor and virologist at Emory University in Atlanta said July 21 during a seminar sponsored by the Harvard Kennedy School’s Belfer Center for Science and International Affairs.

On July 23, Tedros Adhanom Ghebreyesus, director of the World Health Organization declared the global outbreak of monkeypox is a public health emergency of international concern, the organization’s highest state of alert. The WHO committee evaluating the matter was split on whether the outbreak constitutes an international emergency, but Ghebreyesus decided that enough conditions were met to warrant the designation.
Monkeypox has infected more than 15,700 people since the beginning of May, according to Global.health (SN: 5/26/22). More than 2,800 cases have been reported in the United States as of July 22, the U.S. Centers for Disease Control and Prevention report.

“Although I am declaring a public health emergency of international concern, for the moment this is an outbreak that is concentrated among men who have sex with men, especially those with multiple sexual partners,” Ghebreyesus said in a statement. “That means that this is an outbreak that can be stopped with the right strategies in the right groups.”

Monkeypox has caused outbreaks for decades in some parts of Africa, Anne Rimoin, an epidemiologist at the UCLA Fielding School of Public Health, said at the Harvard seminar. But the virus “has been neglected by the global health community.” Monkeypox “has been giving us warning signals” for years in Congo, Nigeria and other parts of West Africa, but has only gotten attention once it recently started causing cases outside of the continent, Rimoin said.

There has been no concerted global effort to contain the virus, which is related to smallpox, Titanji said. Each country has been left to set its own policies.

That has led to disparities. Well-resourced countries have had at least some access to testing, vaccines and medications, which may help limit the spread of the virus or the severity of the disease. Resource-poor nations often lack that access, leaving them with limited ability to track or control the virus. Continued spread of monkeypox in resource-poor countries could leave places that do manage to contain an initial outbreak vulnerable to reintroductions, Jay K. Varma, director of the Cornell Center for Pandemic Prevention and Response in New York City, said in the seminar. The WHO emergency declaration may lead to a more concerted international effort that could make more resources available to contain the spread of the virus.

Even for the wealthiest countries, containing the outbreak is a challenge. Questions abound about how the virus is transmitted, and whether vaccines and treatments — when people can get them — can halt its spread. Even diagnosing the disease can be tricky, with testing often hard to come by and missed diagnoses potentially leading to more cases.

The vast majority of monkeypox cases in the global outbreak have been among men who have sex with men. Of 528 people infected with monkeypox in 16 countries, 98 percent identified as gay or bisexual men, researchers report July 21 in the New England Journal of Medicine.

In some countries with outbreaks, “gay men are criminalized,” Kai Kupferschmidt, a correspondent for Science magazine, said during the seminar. In those countries, “people cannot access good information to help them keep from getting infected and cannot access health care if they do get infected. In these countries, it becomes really difficult to even see the problem,” he said.

Ghebreyesus urged all countries to “work closely with communities of men who have sex with men, to design and deliver effective information and services, and to adopt measures that protect the health, human rights and dignity of affected communities. Stigma and discrimination can be as dangerous as any virus,” he said in a statement.

Doctors might also miss cases of monkeypox because of the unusual presentation of the illness in this outbreak, compared with earlier outbreaks. For instance, in the NEJM study, only a quarter of patients had monkeypox lesions on their faces and only 10 percent had the sores on their palms or soles of their feet. Those body parts have been among some of the most affected in other outbreaks.

Instead, 73 percent of people in the study had lesions in the anal and genital regions and 55 percent on the trunk, arms or legs. Some people also had lesions in their mouths and throats. Most of the people in the study had fewer than 10 lesions, with 54 people having only a single lesion on their genitals, making confusion with herpes or syphilis possible, even easy.

Seventy people in the study were admitted to the hospital. Of those, 21 were hospitalized because of pain, mostly severe rectal pain. Others had eye lesions, kidney damage, inflammation of the heart or throat swelling that prevented them from taking in liquids.

Those complications fit with what health officials across the United States have been seeing. “While mortality appears very low, which is great, morbidity has been much higher than any of us expected,” Mary Foote, the medical director of the New York City Department of Health and Mental Hygiene, said July 14 in a news briefing sponsored by the Infectious Diseases Society of America.

“A lot of people with this infection are really suffering, and some may be at risk of permanent damage and scarring. We see many people with symptoms so severe that they are unable to go to the bathroom, urinate or eat without excruciating pain,” Foote said.

A small number of women and children have also gotten monkeypox in the outbreak. Two children in the United States have been diagnosed with monkeypox, CDC director Rochelle Walensky said July 22 in an interview with the Washington Post. Both children were social contacts of men that have sex with men, she said.

A child in the Netherlands who had no contact with anyone known to be infected with the virus also got monkeypox, researchers report July 21 in Eurosurveillance. His case raises the possibility that monkeypox may be spreading undetected more broadly in communities than realized.

“I don’t think it’s surprising that we are occasionally going to see cases in individuals who are not gay, bisexual or other men who have sex with men. The social networks we have as humans mean we have contact with a lot of different people,” Jennifer McQuiston, deputy director of the CDC’s Division of High Consequence Pathogens and Pathology said July 22 during a White House news briefing.

Exactly how the child in the Netherlands became infected is a matter of speculation. Monkeypox typically spreads among people through close contact with infected people or with clothing, bedding or towels used by people with the disease. Examination of viral DNA showed that the boy isn’t connected to any of the known cases in the Netherlands. He traveled to Turkey in June and may have gotten infected there or while traveling.

The boy has very low levels of IgA antibodies, which patrol mucous membranes and help prevent infections there. Low levels of the antibodies could make him vulnerable to respiratory infections. People can get infected with monkeypox through droplets given off by infected people during close face-to-face interactions, such as close conversation, kissing or during medical exams. But patterns of infection clearly indicate that monkeypox isn’t airborne the way COVID-19 or other respiratory viruses are, Kupferschmidt said.

Details of how monkeypox spreads are still unknown. For instance, researchers don’t know whether the virus can be transmitted through semen as a sexually transmitted disease. Researchers have found evidence of viral DNA in semen, saliva, urine and feces, but that may just be inactive remnants of the virus. So far, no researchers have reported finding infectious virus in genital body fluids that might be exchanged during sex. Also unknown is whether getting infected through mucous membranes during sexual contact would shield against catching the virus later, Rimoin said.

Scientists are questioning whether the monkeypox virus has changed or whether it has simply found a niche social-sexual network among gay and bisexual men that may enable the virus to spread more efficiently, Titanji said. It may be that there are different transmission patterns in historically affected countries and newly affected countries that require different strategies to stop the spread, she said.

Researchers also need to do good studies to figure out how well vaccines and therapeutics work and under what circumstances, Rimoin said. WHO’s emergency declaration includes recommendations for increasing testing and surveillance and for seeding up research on vaccines, treatments and other virus containment measures.

One thing is clear, Rimoin said. “We’re giving this virus room to run like it never has before.” People have passed the buck, leaving others to work out the problem of monkeypox, she said. But now, “it’s everybody’s problem to solve.”

How descendants of cannibals evolved abilities to share a home mostly without killing each other — never mind the rare oopsie snack — resonates after several pandemic years.

Among the many kinds of velvety Delena huntsman spiders, four species from Australia show what for their kind is a downright freaky tolerance between a mom and her live-in offspring. “Cannibalism might happen occasionally, but with Delena cancerides, it’s almost never,” says behavioral ecologist Linda Rayor of Cornell University, who has studied them in the wild and in her lab for 20 years.
Not eating their own kind isn’t really the oddity here: Cannibalism varies a lot among spider species, Rayor says, but overall, it’s mostly a move of solitary kinds of spiders if they meet outside of flirting or baby-guarding demands (SN: 4/25/22).

A small number of Delena species, however, generally tolerate their own kind. The only exception Rayor sees in D. cancerides are a wild-caught female’s takedown of a full-grown male still in her cage after she lays eggs. “Wild-caught females are very intolerant of males who stick around too long,” she says.

What’s really strange, at least in the arachnid world, is these spiders’ shared family life. Out of the more than 50,000-plus known spider species, biologists classify fewer than 80 as truly social. In the most complex, hundreds or even thousands of females spin a great airy silken city, where some stay their entire lives. However, Rayor says, “my huntsman don’t do that.”

Some other biologists wouldn’t consider the Delena spiders Rayor studies as fully social — no spun-silk Sydney. Yet these spiders are not truly solitary either. A female doesn’t spin a web but shelters in a crevice, perhaps behind peeling bark on an acacia tree or under a slab of rock. These crevice-dwellers’ bodies look unusually flattened in profile: “a credit-card spider,” one scientist called the species, with some poetic license.

When a female triumphs in finding real estate, the kids can linger for months in her splendid mom cave — the kids with no sex life yet, that is. Never mind that older offspring already go out hunting on their own at night, or that often one or two later clutches of little ones hatch before the older ones leave. Spider moms guarding poppyseed-tiny hatchlings are common. Living with capable, nearly grown offspring, is strange in the arachnid world.
The most sociable of these sort-of tolerant moms, D. cancerides, lets a cohort of youngsters hang around the home for about a year after hatching. That’s a good portion of life for spiders that live only two and a half years. One of the reasons for doing so may sound familiar: Suitable housing can be hard to find.

Rayor once thought hanging with mom was an Australian thing, but she has now learned about tolerant moms from Madagascar in a Damastes species. To study the evolution of traits that add up to family life in the five species, Jacob Gorneau, now at the California Academy of Sciences in San Francisco, and his Cornell colleagues used four genes from spiders in 37 huntsman genera to create the most ambitious genealogical tree yet of the family. Then Rayor turned to her decades of data to see what behaviors appeared on branches leading to lingering kids.

For instance, a form of egg sac called “plastered” — not drunk but spun like a firmly anchored splat on a surface of spider retreats — shows up in branches with the family-tolerant behavior, the researchers report in the September issue of Molecular Phylogenetics and Evolution.

Spiders spin various shapes of outer sacs that discourage egg raiders. Spiders in a fixed retreat can conveniently anchor a sac, unlike some other moms that carry eggs with them. Also the more spread-out, plastered form might — Rayor emphasizes this is speculation — fit better in tight crevices than the puffier throw-pillow styles of egg sacs would.

Delena spiderlings still carry abundant egg yolk with them when they clamber out of the egg sac. They don’t eat until after their first molt. “They’ve got these big, fat, green abdomens,” Rayor says. “They don’t have long legs, so they waddle.”

Once they molt, one benefit of this family lifestyle could be table scraps for the littles. Very young spiderlings are “ridiculously small,” Rayor says, and can handle food only about the size of a fruit fly. The chance to sneak extra shreds of meat from an older sib could greatly boost nutrition. Older sibs probably would rather not share, but Rayor sees “tolerated theft.”

Cute babies may not matter to a spider mom, but maybe they should to humans. Gorneau, once “very afraid of spiders,” wants to fight the stereotype of spiders as aggressive dangers. Rayor’s spiders strike him as “stoic,” mostly sitting quietly. Rayor’s lab full of spiders in their homes, he now finds, is a “calming environment.”

Dinosaurs might have been endothermic, or warm-blooded…. The combination of large size, endothermy and naked skin may explain the extinction of dinosaurs. About 65 million years ago there was a sharp drop in temperature…. Dinosaurs, lacking skin insulation and too large to burrow underground … could not survive. Meanwhile, evidence has come that … the shells [of their eggs] became progressively thinner … too fragile to support the growing embryo.

Update
Some dinosaurs may have been warm-blooded and some could have laid soft-shelled eggs (SN: 7/12/14, p. 6). But neither trait led to the reptiles’ demise. In the late 1970s, geologists proposed that an asteroid strike triggered a mass extinction (1/25/92, p. 56), killing more than 75 percent of life on Earth. That theory is now widely accepted. Scientists have even found the killer’s calling card: a crater about 180 kilometers wide on the coast of the Yucatán Peninsula in Mexico. The asteroid probably crash landed there in the springtime 66 million years ago, fossils hint (SN: 3/26/22, p. 8).

A century from now, when biologists are playing games of clones and engineers are playing games of drones, physicists will still pledge their loyalty to the Kingdoms of Substance and Force.

Physicists know the subjects of these kingdoms as fermions and bosons. Fermions are the fundamental particles of matter; bosons transmit forces that govern the behavior of the matter particles. The math describing these particles and their relationships forms the “standard model” of particle physics. Or as Nobel laureate Frank Wilczek calls it, “The Core Theory.”
Wilczek’s core theory differs from the usual notion of standard model. His core includes gravity, as described by Einstein’s general theory of relativity. General relativity is an exquisite theory of gravity, but it doesn’t fit in with the math for the standard model’s three forces (the strong and weak nuclear forces and electromagnetism). But maybe someday it will. Perhaps even by 100 years from now.

At least, that’s among the many predictions that Wilczek has made for the century ahead. In a recent paper titled “Physics in 100 Years,” he offers a forecast for future discoveries and inventions that science writers of the future will be salivating over. (The paper is based on a talk celebrating the 250th anniversary of Brown University. He was asked to make predictions for 250 years from now, but regarded 100 as more reasonable.)

Wilczek does not claim that his forecast will be accurate. He considers it more an exercise in imagination, anchored in thorough knowledge of today’s major questions and the latest advances in scientific techniques and capabilities. Where those two factors meet, Wilczek sees the potential for premonition. His ruminations result in a vision of the future suitable for a trilogy or two of science fiction films. They would involve the unification of the kingdoms of physics and a more intimate relationship between them and the human mind.

Among Wilczek’s prognostications is the discovery of supersymmetric particles, heavyweight partners to the matter and force particles of the Core Theory. Such partner particles would reveal a deep symmetry underlying matter and force, thereby combining the kingdoms and further promoting the idea of unification as a key path to truth about nature. Wilczek also foresees the discovery of proton decay, even though exhaustive searches for it have so far failed to find it. If protons disintegrate (after, on average, trillions upon trillions of years), matter as we know it has a limited lease on life. On the other hand, lack of finding proton decay has been a barrier to figuring out a theory that successfully unifies the math for all of nature’s particles and forces. And Wilczek predicts that:

The unification of gravity with the other forces will become more intimate, and have observable consequences.

He also anticipates that gravity waves will be observed and used to probe the physics of the distant (and early) universe; that the laws of physics, rather than emphasizing energy, will someday be rewritten in terms of “information and its transformations”; and that “biological memory, cognitive processing, motivation, and emotion will be understood at the molecular level.”

And all that’s just the beginning. He then assesses the implications of future advances in computing. Part of the coming computation revolution, he foresees, will focus on its use for doing science:

Calculation will increasingly replace experimentation in design of useful materials, catalysts, and drugs, leading to much greater efficiency and new opportunities for creativity.

Advanced calculational power will also be applied to understanding the atomic nucleus more precisely, conferring the ability…

to manipulate atomic nuclei dexterously … enabling (for example) ultradense energy storage and ultrahigh energy lasers.

Even more dramatically, computing power will be employed to enhance itself:

Capable three-dimensional, fault-tolerant, self-repairing computers will be developed.… Self-assembling, self-reproducing, and autonomously creative machines will be developed.

And those achievements will imply that:

Bootstrap engineering projects wherein machines, starting from crude raw materials, and with minimal human supervision, build other sophisticated machines (notably including titanic computers) will be underway.

Ultimately, such sophisticated computing machines will enable artificial intelligence that would even impress Harold Finch on Person of Interest (which is probably Edward Snowden’s favorite TV show).

Imagine, for instance, the ways that superpowerful computing could enhance the human senses. Aided by electronic prosthetics, people could experience the full continuous range of colors in the visible part of the electromagnetic spectrum, not just those accessible to the tricolor-sensitive human eye. Perhaps the beauty that physicists and mathematicians “see” in their equations can be transformed into works of art beamed directly into the brain.

Artificial intelligence endowed with such power would enable many other futuristic fantasies. As Wilczek notes, the “life of mind” could be altered in strange new ways. For one thing, computationally precise knowledge of a state of mind would permit new possibilities for manipulating it. “An entity capable of accurately recording its state could purposefully enter loops, to re-live especially enjoyable episodes,” Wilczek points out.

And if all that doesn’t sound weird enough, we haven’t even invoked quantum mechanics yet. Wilczek forecasts that large-scale quantum computers will be realized, in turn leading to “quantum artificial intelligence.”

“A quantum mind could experience a superposition of ‘mutually contradictory’ states, or allow different parts of its wave function to explore vastly different scenarios in parallel,” Wilczek points out. “Being based on reversible computation, such a mind could revisit the past at will, and could be equipped to superpose past and present.”

And with quantum artificial intelligence at its disposal, the human mind’s sensory tentacles will not merely be enhanced but also dispersed. With quantum communication, humans can be linked by quantum messaging to sensory devices at vast distances from their bodies. “An immersive experience of ‘being there’ will not necessarily involve being there, physically,” Wilczek writes. “This will be an important element of the expansion of human culture beyond Earth.”

In other words, it will be a web of intelligence, rather than a network of physical settlements, that will expand human culture throughout the cosmos. Such “expanded identities” will be able to comprehend the kingdoms of substance and force on their own quantum terms, as the mind itself merges with space and time.

Wilczek’s visions imply a future existence in which nature is viewed from a vastly different perspective, conditioned by a radical reorientation of the human mind to its world. And perhaps messing with the mind so drastically should be worrisome. But let’s not forget that the century gone by has also messed with the mind and its perspectives in profound ways — with television, for instance, talk radio, the Internet, smartphones and blogs. A little quantum computer mind manipulation is unlikely to make things any worse.

With delicate hues of purple and pink, a lab technique called gram staining has reliably characterized bacteria for more than a century. Yet many scientists are mistaken about why the vivid method works, new research finds.

Contrary to standard scientific texts, the purple dye called crystal violet, a main ingredient in gram staining, does not actually enter bacterial cells, researchers report April 27 in ACS Chemical Biology. Instead, the dye gets trapped in a tight package of sugar-filled polymers, called peptidoglycan, which envelops bacterial cells. The thickness and integrity of the sweet bacterial armor determines whether crystal violet leaves a cell purple or not. That royal shade, or lack of it, reveals a cell’s type of outer structure.
Published by Hans Christian Gram in 1884, gram staining distinguishes gram-positive bacteria (purple) from gram-negative bacteria (pink). Gram-positive critters, such as staph, have a thick peptidoglycan layer that shields an inner cellular membrane. Gram-negative cells, such as E. coli, have a thin peptidoglycan layer sandwiched between a porous outer membrane and an inner membrane.
Microbiologists thought that crystal violet could easily pass through membranes and into both cell types, says microbiologist Moselio Schaechter, an emeritus professor at Tufts University School of Medicine in Boston. A subsequent harsh shower of alcohol could then corrode both cell types’ membranes. This particularly clobbers gram-negative cells’ outer structures, including the thin layer of peptidoglycan which is bound to the outer membrane, allowing the purple dye to flush away. Meanwhile, gram-positive cells’ sturdier layer of peptidoglycan warps a bit but stays largely intact, keeping the microbes purple. The colorless gram-negative cells can then be stained with another dye, such as safranine, tinting the cells pink.

But that explanation is incorrect, says physical chemist Michael Wilhelm of Temple University in Philadelphia. Using a recently developed spectroscopy technique that monitors molecules as they traverse membranes, Wilhelm and colleagues found that crystal violet doesn’t cross the inner membrane of either cell type.

Instead, crystal violet seeps into the cracks of peptidoglycan, which acts like a “brick wall of sugar,” Wilhelm says. A gram-negative cell’s thin wall crumbles in the alcohol wash and releases the dye, he explains. In gram-positive cells, crystal violet slowly drains from the thick peptidoglycan barrier, but not quickly enough to leave the cell colorless during the protocol.

The study is fascinating, says microbiologist Rita Moyes of Texas A&M University in College Station. Scientists should continue to use new technologies to study old techniques, she says.

“Who’d have thought gram stain lecture material needed an update?” says microbiologist Mark Forsyth of the College of William & Mary in Williamsburg, Va. But, he says, “it may take a while to convince old professors like me to actually change their shtick about how this historic stain works.”

Sci-fi novels and films like Gattaca no longer have a monopoly on genetically engineered humans. Real research scripts about editing the human genome are now appearing in scientific and medical journals. But the reviews are mixed.

In Gattaca, nearly everyone was genetically altered, their DNA adjusted to prevent disease, enhance intelligence and make them look good. Today, only people treated with gene therapy have genetically engineered DNA. But powerful new gene editing tools could expand the scope of DNA alteration, forever changing humans’ genetic destiny.

Not everyone thinks scientists should wield that power. Kindling the debate is a report by scientists from Sun Yat-sen University in Guangzhou, China, who have edited a gene in fertilized human eggs, called zygotes. The team used new gene editing technology known as the CRISPR/Cas9 system. That technology can precisely snip out a disease-causing mutation and replace it with healthy DNA. CRISPR/Cas9 has edited DNA in stem cells and cancer cells in humans. Researchers have also deployed the molecules to engineer other animals, including mice and monkeys (SN Online: 3/31/14; SN: 3/8/14, p. 7). But it had never before been used to alter human embryos.
The team’s results, reported April 18 in Protein & Cell, sparked a flurry of headlines because their experiment modified human germline tissue (SN Online: 4/23/15). While most people think it is all right to fix faulty genes in mature body, or somatic, cells, tinkering with the germ line — eggs, sperm or tissues that produce those reproductive cells — crosses an ethical line for many. Germline changes can be passed on to future generations, and critics worry that allowing genetic engineering to correct diseases in germline tissues could pave the way for creating designer babies or other abuses that will persist forever.

“How do you draw a clear, meaningful line between therapy and enhancement?” ponders Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, Calif. About 40 countries ban or restrict such inherited DNA modifications.

Rumors about human germline editing experiments prompted scientists to gather in January in Napa, Calif. Discussions there led two groups to publish recommendations. One group, reporting March 26 in Nature, called for scientists to “agree not to modify the DNA of human reproductive cells,” including the nonviable zygotes used in the Chinese study. A second group, writing in Science April 3, called for a moratorium on the clinical use of human germline engineering, but stopped short of saying the technology shouldn’t be used in research. Those researchers say that while CRISPR technology is still too primitive for safe use in patients, further research is needed to improve it. But those publishing in Nature disagreed.

“Are there ever any therapeutic uses that would demand … modification of the human germ line? We don’t think there are any,” says Edward Lanphier, president of Sangamo BioSciences in Richmond, Calif. “Modifying the germ line is crossing the line that most countries on our planet have said is never appropriate to cross.”

If germline editing is never going to be allowed, there is no reason to conduct research using human embryos or reproductive cells, he says. Sangamo BioSciences is developing gene editing tools for use in somatic cells, an approach that germline editing might render unneeded. Lanphier denies that financial interests play a role in his objection to germline editing.

Other researchers, including Harvard University geneticist George Church, think germline editing may well be the only solution for some people with rare, inherited diseases. “What people want is safety and efficacy,” says Church. “If you ban experiments aimed at improving safety and efficacy, we’ll never get there.”

The zygote experiments certainly demonstrate that CRISPR technology is not ready for daily use yet. The researchers attempted to edit the beta globin, or HBB, gene. Mutations in that gene cause the inherited blood disorder beta-thalassemia. CRISPR/Cas9 molecules were engineered to seek out HBB and cut it where a piece of single-stranded DNA could heal the breach, creating a copy of the gene without mutations. That strategy succeeded in only four of the 86 embryos that the researchers attempted to edit. Those edited embryos contained a mix of cells, some with the gene edited and some without.

In an additional seven embryos, the HBB gene cut was repaired using the nearby HBD gene instead of the single-stranded DNA. The researchers also found that the molecular scissors snipped other genes that the researchers never intended to touch.

“Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications,” the researchers wrote.

The Chinese researchers crossed no ethical lines, Church contends. “They tried to dot i’s and cross t’s on the ethical questions.” The zygotes could not develop into a person, for instance: They had three sets of chromosomes, having been fertilized by two sperm in lab dishes.

Viable or not, germline cells should be off limits, says Darnovsky. She opposes all types of human germline modification, including a procedure approved in the United Kingdom in February for preventing mitochondrial diseases. The U.K. prohibits all other germline editing.

Mitochondria, the power plants that churn out energy in a cell, each carry a circle of DNA containing genes necessary for the organelle’s function. Mothers pass mitochondria on to their offspring through the egg. About one in 5,000 babies worldwide are born with mitochondrial DNA mutations that cause disease, particularly in energy-greedy organs such as the muscles, heart and brain.

Such diseases could be circumvented with a germline editing method known as mitochondrial replacement therapy (SN: 11/17/12, p. 5). In a procedure pioneered by scientists at Oregon Health & Science University, researchers first pluck the nucleus, where the bulk of genetic instructions for making a person are stored, out of the egg of a woman who carries mutant mitochondria. That nucleus is then inserted into a donor egg containing healthy mitochondria. The transfer would produce a person with three parents; most of their genes inherited from the mother and father, with mitochondrial DNA from the anonymous donor. The first babies produced through that technology could be born in the U.K. next year.

Yet another new gene-editing technique could eliminate the need to use donor eggs by specifically destroying only disease-carrying mitochondria, researchers from the Salk Institute for Biological Studies in La Jolla, Calif., reported April 23 in Cell (SN Online: 4/23/15).

Such unproven technologies shouldn’t be attempted when alternatives already exist, Darnovsky says, such as screening embryos created through in vitro fertilization and discarding those likely to develop the disease.

But banning genome-altering technology could leave people with genetic diseases, and society in general, in the lurch, says molecular biologist Matthew Porteus of Stanford University.

“There is no benefit in my mind of having a child born with a devastating genetic disease,” he says.

Alternatives to germline editing come with their own ethical quandaries, he says. Gene testing of embryos may require creating a dozen or more embryos before finding one that doesn’t carry the disease. The rest of the embryos would be destroyed. Many people find that prospect ethically questionable.

But that doesn’t argue for sliding into Gattaca territory, where genetic modification becomes mandatory. “If we get there,” says Porteus, “we’ve really screwed up.”

An unusual blast of radio waves from deep space had a sense of rhythm. Over the few seconds in December 2019 when the burst was detected, it kept a steady beat. That tempo holds clues to the potential origin of the mysterious outburst, one of a class of flares called fast radio bursts.

Of the hundreds of previously detected fast radio bursts, most last for mere milliseconds. But this one persisted for roughly three seconds, Daniele Michilli and colleagues report in the July 14 Nature. The burst consisted of multiple brief pulses, repeating about every two-tenths of a second.
Scientists have previously observed fast radio bursts that repeat with a delay of minutes or days (SN: 3/2/16). “With this one it was a train of [pulses] one after the other, a heartbeat, like, ‘boom boom boom boom,’” says Michilli, an astronomer at MIT.

That makes this fast radio burst very special, says astrophysicist Bing Zhang of the University of Nevada, Las Vegas, who was not involved with the research. Compared with other fast radio bursts, “this is a different animal.”

Scientists still don’t know how fast radio bursts are generated, but evidence has been building that they are associated with ultradense, spinning dead stars called neutron stars and, in particular, highly magnetic neutron stars called magnetars (SN: 6/4/20).

The steady repetition rate hints at what may have caused this particular blast, discovered by the Canadian Hydrogen Intensity Mapping Experiment, a radio telescope in British Columbia.

Only certain types of cosmic processes produce such metronome-like signals. Neutron stars, for example, can appear to pulse as they spin, because they emit beams of radio waves that can sweep past Earth at regular intervals. Neutron stars tend to have tempos similar to that of the pulsating fast radio burst. But that burst was much more luminous than normal neutron star pulses, suggesting some unknown process would need to have amped up the emission.

Another idea is that large outbursts on magnetars could cause starquakes that jostle those stars’ solid crusts, generating regular barrages of radio waves. The rhythmic burst’s pulsing “is sort of consistent with a frequency with which we expect that magnetars could be shaking,” says astrophysicist Cecilia Chirenti of the University of Maryland in College Park, who was not involved with the new study.

Or the pulsing might result from two neutron stars that orbit one another. Outbursts could occur at regular points in that orbit, when the magnetic regions that surround each neutron star interact.

Scientists don’t know if all fast radio bursts are generated in the same way. An outlier like this one might have a different origin story than a more standard, one-off blast. That means it’s hard to make conclusions about other fast radio bursts, Zhang says. “Whatever we can derive from this one, I would not easily extrapolate to the other guys.”

Pocket gophers certainly don’t qualify as card-carrying 4-H members, but the rodents might be farming roots in the open air of their moist, nutrient-rich tunnels.

The gophers subsist mostly on roots encountered in the tunnels that the rodents excavate. But the local terrain doesn’t always provide enough roots to sustain gophers, two researchers report in the July 11 Current Biology. To make up the deficit, the gophers practice a simple type of agriculture by creating conditions that promote more root growth, suggest ecologist Jack Putz of the University of Florida in Gainesville and his former zoology undergraduate student Veronica Selden.
But some scientists think it’s a stretch to call the rodents’ activity farming. Gophers aren’t actively working the soil, these researchers say, but inadvertently altering the environment as the rodents eat and poop their way around — much like all animals do.

Tunnel digging takes a lot of energy — up to 3,400 times as much as walking along the surface for gophers. To see how the critters were getting all this energy, Selden and Putz in 2021 began investigating the tunnels of southeastern pocket gophers (Geomys pinetis) in an area being restored to longleaf pine savanna in Florida that Putz partially owns.

The pair took root samples from soil adjacent to 12 gopher tunnels and extrapolated how much root mass a gopher would encounter as it excavated a meter of tunnel. Then the researchers calculated the amount of energy that those roots would provide.

“We were able to compare energy cost versus gain, and found that on average there is a deficit, with about half the cost of digging being unaccounted for,” Selden says.

Upon examining some tunnels, Selden and Putz saw gopher feces spread through the interior along with signs of little bites taken out of roots and churning of the soil.

The gophers, the researchers conclude, provide conditions that favor root growth by spreading their own waste as fertilizer, aerating the soil and repeatedly nibbling on roots to encourage new sprouting.
“All of these activities encourage root growth, and once the roots grow into the tunnels, the gophers crop the roots,” Selden says. She and Putz say that this amounts to a rudimentary form of farming. If so, gophers would be the first nonhuman mammals to be recognized as farmers, Putz says. Other organisms, such as some insects, also farm food and started doing so much earlier than humans (SN: 4/23/20).

But the study has its skeptics. “I don’t really think you can call it farming per the human definition. All herbivores eat plants, and everybody poops,” says J.T. Pynne, a wildlife biologist at the Georgia Wildlife Federation in Covington who studies southeastern pocket gophers. So the root nibbling and tunnel feces might not be signs of agriculture, just gophers doing what all animals do.

Evolutionary biologist Ulrich Mueller agrees. “If we accept the tenuous evidence presented in the Selden article as evidence for farming … then most mammals and most birds are farmers because each of them accidentally have also some beneficial effects on some plants that these mammals or birds also feed on,” he says.

Not only that, but the study is also dangerous, says Mueller, of the University of Texas at Austin. The public will see through “the shallowness of the data,” he says, and will conclude that science is “just a bunch of storytelling, eroding general trust in science.”

For her part, Selden says she understands that because gophers don’t plant their crops, not everyone is comfortable calling them farmers. Still, she argues that “what qualifies the gophers as farmers and sets them apart from, say, cattle, which incidentally fertilize the grass they eat with their wastes, is that gophers cultivate and maintain this ideal environment for roots to grow into.”

At the very least, Putz says, he hopes their research makes people kinder toward the rodents. “If you go to the web and put in ‘pocket gopher,’ you’ll see more ways to kill them than you can count.”