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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.”

Biologist Martin Dančák didn’t set out to find a plant species new to science. But on a hike through a rainforest in Borneo, he and colleagues stumbled on a subterranean surprise.

Hidden beneath the soil and inside dark, mossy pockets below tree roots, carnivorous pitcher plants dangled their deathtraps underground. The pitchers can look like hollow eggplants and probably lure unsuspecting prey into their sewer hole-like traps. Once an ant or a beetle steps in, the insect falls to its death, drowning in a stew of digestive juices (SN: 11/22/16). Until now, scientists had never observed pitcher plants with traps almost exclusively entombed in earth.
“We were, of course, astonished as nobody would expect that a pitcher plant with underground traps could exist,” says Dančák, of Palacký University in Olomouc, Czech Republic.

That’s because pitchers tend to be fragile. But the new species’ hidden traps have fleshy walls that may help them push against soil as they grow underground, Dančák and colleagues report June 23 in PhytoKeys. Because the buried pitchers stay concealed from sight, the team named the species Nepenthes pudica, a nod to the Latin word for bashful.

The work “highlights how much biodiversity still exists that we haven’t fully discovered,” says Leonora Bittleston, a biologist at Boise State University in Idaho who was not involved with the study. It’s possible that other pitcher plant species may have traps lurking underground and scientists just haven’t noticed yet, she says. “I think a lot of people don’t really dig down.”

The next generation of dark matter detectors has arrived.

A massive new effort to detect the elusive substance has reported its first results. Following a time-honored tradition of dark matter hunters, the experiment, called LZ, didn’t find dark matter. But it has done that better than ever before, physicists report July 7 in a virtual webinar and a paper posted on LZ’s website. And with several additional years of data-taking planned from LZ and other experiments like it, physicists are hopeful they’ll finally get a glimpse of dark matter.
“Dark matter remains one of the biggest mysteries in particle physics today,” LZ spokesperson Hugh Lippincott, a physicist at the University of California, Santa Barbara said during the webinar.

LZ, or LUX-ZEPLIN, aims to discover the unidentified particles that are thought to make up most of the universe’s matter. Although no one has ever conclusively detected a particle of dark matter, its influence on the universe can be seen in the motions of stars and galaxies, and via other cosmic observations (SN: 7/24/18).

Located about 1.5 kilometers underground at the Sanford Underground Research Facility in Lead, S.D., the detector is filled with 10 metric tons of liquid xenon. If dark matter particles crash into the nuclei of any of those xenon atoms, they would produce flashes of light that the detector would pick up.

The LZ experiment is one of a new generation of bigger, badder dark matter detectors based on liquid xenon, which also includes XENONnT in Gran Sasso National Laboratory in Italy and PandaX-4T in the China Jinping Underground Laboratory. The experiments aim to detect a theorized type of dark matter called Weakly Interacting Massive Particles, or WIMPs (SN: 12/13/16). Scientists scaled up the search to allow for a better chance of spying the particles, with each detector containing multiple tons of liquid xenon.

Using only about 60 days’ worth of data, LZ has already surpassed earlier efforts to pin down WIMPs (SN: 5/28/18). “It’s really impressive what they’ve been able to pull off; it’s a technological marvel,” says theoretical physicist Dan Hooper of Fermilab in Batavia, Ill, who was not involved with the study.

Although LZ’s search came up empty, “the way something’s going to be discovered is when you have multiple years in a row of running,” says LZ collaborator Matthew Szydagis, a physicist at the University at Albany in New York. LZ is expected to run for about five years, and data from that extended period may provide physicists’ best chance to find the particles.

Now that the detector has proven its potential, says LZ physicist Kevin Lesko of Lawrence Berkeley National Laboratory in California, “we’re excited about what we’re going to see.”

Tyrannosaurus rex’s tiny arms have launched a thousand sarcastic memes: I love you this much; can you pass the salt?; row, row, row your … oh.

But back off, snarky jokesters. A newfound species of big-headed carnivorous dinosaur with tiny forelimbs suggests those arms weren’t just an evolutionary punchline. Arm reduction — alongside giant heads — evolved independently in different dinosaur lineages, researchers report July 7 in Current Biology.

Meraxes gigas, named for a dragon in George R. R. Martin’s “A Song of Ice and Fire” book series, lived between 100 million and 90 million years ago in what’s now Argentina, says Juan Canale, a paleontologist with the country’s CONICET research network who is based in Buenos Aires. Despite the resemblance to T. rex, M. gigas wasn’t a tyrannosaur; it was a carcharodontosaur — a member of a distantly related, lesser-known group of predatory theropod dinosaurs. M. gigas went extinct nearly 20 million years before T. rex walked on Earth.
The M. gigas individual described by Canale and colleagues was about 45 years old and weighed more than four metric tons when it died, they estimate. The fossilized specimen is about 11 meters long, and its skull is heavily ornamented with crests and bumps and tiny hornlets, ornamentations that probably helped attract mates.

Why these dinosaurs had such tiny arms is an enduring mystery. They weren’t for hunting: Both T. rex and M. gigas used their massive heads to hunt prey (SN: 10/22/18). The arms may have shrunk so they were out of the way during the frenzy of group feeding on carcasses.

But, Canale says, M. gigas’ arms were surprisingly muscular, suggesting they were more than just an inconvenient limb. One possibility is that the arms helped lift the animal from a reclining to a standing position. Another is that they aided in mating — perhaps showing a mate some love.

Getting a COVID-19 test has become a regular part of many college students’ lives. That ritual may protect not just those students’ classmates and professors but also their municipal bus drivers, neighbors and other members of the local community, a new study suggests.

Counties where colleges and universities did COVID-19 testing saw fewer COVID-19 cases and deaths than ones with schools that did not do any testing in the fall of 2020, researchers report June 23 in PLOS Digital Health. While previous analyses have shown that counties with colleges that brought students back to campus had more COVID-19 cases than those that continued online instruction, this is the first look at the impact of campus testing on those communities on a national scale (SN: 2/23/21).
“It’s tough to think of universities as just silos within cities; it’s just much more permeable than that,” says Brennan Klein, a network scientist at Northeastern University in Boston.

Colleges that tested their students generally did not see significantly lower case counts than schools that didn’t do testing, Klein and his colleagues found. But the communities surrounding these schools did see fewer cases and deaths. That’s because towns with colleges conducting regular testing had a more accurate sense of how much COVID-19 was circulating in their communities, Klein says, which allowed those towns to understand the risk level and put masking policies and other mitigation strategies in place.

The results highlight the crucial role testing can continue to play as students return to campus this fall, says Sam Scarpino, vice president of pathogen surveillance at the Rockefeller Foundation’s Pandemic Prevention Institute in Washington, D.C. Testing “may not be optional in the fall if we want to keep colleges and universities open safely,” he says.
Finding a flight path
As SARS-CoV-2, the virus that causes COVID-19 rapidly spread around the world in the spring of 2020, it had a swift impact on U.S. college students. Most were abruptly sent home from their dorm rooms, lecture halls, study abroad programs and even spring break outings to spend what would be the remainder of the semester online. And with the start of the fall semester just months away, schools were “flying blind” as to how to bring students back to campus safely, Klein says.

That fall, Klein, Scarpino and their collaborators began to put together a potential flight path for schools by collecting data from COVID-19 dashboards created by universities and the counties surrounding those schools to track cases. The researchers classified schools based on whether they had opted for entirely online learning or in-person teaching. They then divided the schools with in-person learning based on whether they did any testing.

It’s not a perfect comparison, Klein says, because this method groups schools that did one round of testing with those that did consistent surveillance testing. But the team’s analyses still generally show how colleges’ pandemic response impacted their local communities.

Overall, counties with colleges saw more cases and deaths than counties without schools. However, testing helped minimize the increase in cases and deaths. During the fall semester, from August to December, counties with colleges that did testing saw on average 14 fewer deaths per 100,000 people than counties with colleges that brought students back with no testing — 56 deaths per 100,000 versus about 70.
The University of Massachusetts Amherst, with nearly 30,000 undergraduate and graduate students in 2020, is one case study of the value of the testing, Klein says. Throughout the fall semester, the school tested students twice a week. That meant that three times as many tests occurred in the city of Amherst than in neighboring cities, he says. For much of the fall and winter, Amherst had fewer COVID-19 cases per 1,000 residents than its neighboring counties and statewide averages.

Once students left for winter break, campus testing stopped – so overall local testing dropped. When students returned for spring semester in February 2021, area cases spiked — possibly driven by students bringing the coronavirus back from their travels and by being exposed to local residents whose cases may have been missed due to the drop in local testing. Students returned “to a town that has more COVID than they realize” Klein says.

Renewed campus testing not only picked up the spike but quickly prompted mitigation strategies. The university moved classes to Zoom and asked students to remain in their rooms, at one point even telling them that they should not go on walks outdoors. By mid-March, the university reduced the spread of cases on campus and the town once again had a lower COVID-19 case rate than its neighbors for the remainder of the semester, the team found.

The value of testing
It’s helpful to know that testing overall helped protect local communities, says David Paltiel, a public health researcher at the Yale School of Public Health who was not involved with the study. Paltiel was one of the first researchers to call for routine testing on college campuses, regardless of whether students had symptoms.

“I believe that testing and masking and all those things probably were really useful, because in the fall of 2020 we didn’t have a vaccine yet,” he says. Quickly identifying cases and isolating affected students, he adds, was key at the time.
But each school is unique, he says, and the benefit of testing probably varied between schools. And today, two and a half years into the pandemic, the cost-benefit calculation is different now that vaccines are widely available and schools are faced with newer variants of SARS-CoV-2. Some of those variants spread so quickly that even testing twice a week may not catch all cases on campus quickly enough to stop their spread, he says.

As colleges and universities prepare for the fall 2022 semester, he would recommend schools consider testing students as they return to campus with less frequent follow-up surveillance testing to “make sure things aren’t spinning crazy out of control.”

Still, the study shows that regular campus testing can benefit the broader community, Scarpino says. In fact, he hopes to capitalize on the interest in testing for COVID-19 to roll out more expansive public health testing for multiple respiratory viruses, including the flu, in places like college campuses. In addition to PCR tests — the kind that involve sticking a swab up your nose — such efforts might also analyze wastewater and air within buildings for pathogens (SN: 05/28/20).

Unchecked coronavirus transmission continues to disrupt lives — in the United States and globally — and new variants will continue to emerge, he says. “We need to be prepared for another surge of SARS-CoV-2 in the fall when the schools reopen, and we’re back in respiratory season.”

In the quest to measure the fundamental constant that governs the strength of gravity, scientists are getting a wiggle on.

Using a pair of meter-long, vibrating metal beams, scientists have made a new measurement of “Big G,” also known as Newton’s gravitational constant, researchers report July 11 in Nature Physics. The technique could help physicists get a better handle on the poorly measured constant.

Big G is notoriously difficult to determine (SN: 9/12/13). Previous estimates of the constant disagree with one another, leaving scientists in a muddle over its true value. It is the least precisely known of the fundamental constants, a group of numbers that commonly show up in equations, making them a prime target for precise measurements.
Because the vibrating beam test is a new type of experiment, “it might help to understand what’s really going on,” says engineer and physicist Jürg Dual of ETH Zurich.

The researchers repeatedly bent one of the beams back and forth and used lasers to measure how the second beam responded to the first beam’s varying gravitational pull. To help maintain a stable temperature and avoid external vibrations that could stymie the experiment, the researchers performed their work 80 meters underground, in what was once a military fortress in the Swiss Alps.

Big G, according to the new measurement, is approximately 6.82 x 10-11 meters cubed per kilogram per square second. But the estimate has an uncertainty of about 1.6 percent, which is large compared to other measurements (SN: 8/29/18). So the number is not yet precise enough to sway the debate over Big G’s value. But the team now plans to improve their measurement, for example by adding a modified version of the test with rotating bars. That might help cut down on Big G’s wiggle room.

No beast on Earth is tougher than the tiny tardigrade. It can survive being frozen at -272° Celsius, being exposed to the vacuum of outer space and even being blasted with 500 times the dose of X-rays that would kill a human.

In other words, the creature can endure conditions that don’t even exist on Earth. This otherworldly resilience, combined with their endearing looks, has made tardigrades a favorite of animal lovers. But beyond that, researchers are looking to the microscopic animals, about the size of a dust mite, to learn how to prepare humans and crops to handle the rigors of space travel.
The tardigrade’s indestructibility stems from its adaptations to its environment — which may seem surprising, since it lives in seemingly cushy places, like the cool, wet clumps of moss that dot a garden wall. In homage to such habitats, along with a pudgy appearance, some people call tardigrades water bears or, adorably, moss piglets.

But it turns out that a tardigrade’s damp, mossy home can dry out many times each year. Drying is pretty catastrophic for most living things. It damages cells in some of the same ways that freezing, vacuum and radiation do.

For one thing, drying leads to high levels of peroxides and other reactive oxygen species. These toxic molecules chisel a cell’s DNA into short fragments — just as radiation does. Drying also causes cell membranes to wrinkle and crack. And it can lead delicate proteins to unfold, rendering them as useless as crumpled paper airplanes. Tardigrades have evolved special strategies for dealing with these kinds of damage.
As a tardigrade dries out, its cells gush out several strange proteins that are unlike anything found in other animals. In water, the proteins are floppy and shapeless. But as water disappears, the proteins self-assemble into long, crisscrossing fibers that fill the cell’s interior. Like Styrofoam packing peanuts, the fibers support the cell’s membranes and proteins, preventing them from breaking or unfolding.

At least two species of tardigrade also produce another protein found in no other animal on Earth. This protein, dubbed Dsup, short for “damage suppressor,” binds to DNA and may physically shield it from reactive forms of oxygen.

Emulating tardigrades could one day help humans colonize outer space. Food crops, yeast and insects could be engineered to produce tardigrade proteins, allowing these organisms to grow more efficiently on spacecraft where levels of radiation are elevated compared with on Earth.

Scientists have already inserted the gene for the Dsup protein into human cells in the lab. Many of those modified cells survived levels of X-rays or peroxide chemicals that kill ordinary cells (SN: 11/9/19, p. 13). And when inserted into tobacco plants — an experimental model for food crops — the gene for Dsup seemed to protect the plants from exposure to a DNA-damaging chemical called ethyl methanesulfonate. Plants with the extra gene grew more quickly than those without it. Plants with Dsup also incurred less DNA damage when exposed to ultraviolet radiation.
Tardigrades’ “packing peanut” proteins show early signs of being protective for humans. When modified to produce those proteins, human cells became resistant to camptothecin, a cell-killing chemotherapy agent, researchers reported in the March 18 ACS Synthetic Biology. The tardigrade proteins did this by inhibiting apoptosis, a cellular self-destruct program that is often triggered by exposure to harmful chemicals or radiation.

So if humans ever succeed in reaching the stars, they may accomplish this feat, in part, by standing on the shoulders of the tiny eight-legged endurance specialists in your backyard.

Modern mammals are known for their big brains. But new analyses of mammal skulls from creatures that lived shortly after the dinosaur mass extinction show that those brains weren’t always a foregone conclusion. For at least 10 million years after the dinosaurs disappeared, mammals got a lot brawnier but not brainier, researchers report in the April 1 Science.

That bucks conventional wisdom, to put it mildly. “I thought, it’s not possible, there must be something that I did wrong,” says Ornella Bertrand, a mammal paleontologist at the University of Edinburgh. “It really threw me off. How am I going to explain that they were not smart?”

Modern mammals have the largest brains in the animal kingdom relative to their body size. How and when that brain evolution happened is a mystery. One idea has been that the disappearance of all nonbird dinosaurs following an asteroid impact at the end of the Mesozoic Era 66 million years ago left a vacuum for mammals to fill (SN: 1/25/17). Recent discoveries of fossils dating to the Paleocene — the immediately post-extinction epoch spanning 66 million to 56 million years ago — does reveal a flourishing menagerie of weird and wonderful mammal species, many much bigger than their Mesozoic predecessors (SN: 10/24/19). It was the dawn of the Age of Mammals.
Before those fossil finds, the prevailing wisdom was that in the wake of the mass dino extinction, mammals’ brains most likely grew apace with their bodies, everything increasing together like an expanding balloon, Bertrand says. But those discoveries of Paleocene fossil troves in Colorado and New Mexico, as well as reexaminations of fossils previously found in France, are now unraveling that story, by offering scientists the chance to actually measure the size of mammals’ brains over time.

Bertrand and her colleagues used CT scanning to create 3-D images of the skulls of different types of ancient mammals from both before and after the extinction event. Those specimens included mammals from 17 groups dating to the Paleocene and 17 to the Eocene, the epoch that spanned 56 million to 34 million years ago.

What the team found was a shock: Relative to their body sizes, Paleocene mammal brains were relatively smaller than those of Mesozoic mammals. It wasn’t until the Eocene that mammal brains began to grow, particularly in certain sensory regions, the team reports.

To assess how the sizes and shapes of those sensory regions also changed over time, Bertrand looked for the edges of different parts of the brains within the 3-D skull models, tracing them like a sculptor working with clay. The size of mammals’ olfactory bulbs, responsible for sense of smell, didn’t change over time, the researchers found — and that makes sense, because even Mesozoic mammals were good sniffers, she says.

The really big brain changes were to come in the neocortex, which is responsible for visual processing, memory and motor control, among other skills. But those kinds of changes are metabolically costly, Bertrand says. “To have a big brain, you need to sleep and eat, and if you don’t do that you get cranky, and your brain just doesn’t function.”
So, the team proposes, as the world shook off the dust of the mass extinction, brawn was the priority for mammals, helping them swiftly spread out into newly available ecological niches. But after 10 million years or so, the metabolic calculations had changed, and competition within those niches was ramping up. As a result, mammals began to develop new sets of skills that could help them snag hard-to-reach fruit from a branch, escape a predator or catch prey.

Other factors — such as social behavior or parental care — have been important to the overall evolution of mammals’ big brains. But these new finds suggest that, at least at the dawn of the Age of Mammals, ecology — and competition between species — gave a big push to brain evolution, wrote biologist Felisa Smith of the University of New Mexico in Albuquerque in a commentary in the same issue of Science.
“An exciting aspect of these findings is that they raise a new question: Why did large brains evolve independently and concurrently in many mammal groups?” says evolutionary biologist David Grossnickle of the University of Washington in Seattle.

Most modern mammals have relatively large brains, so studies that examine only modern species might conclude that large brains evolved once in mammal ancestors, Grossnickle says. But what this study uncovered is a “much more interesting and nuanced story,” that these brains evolved separately in many different groups, he says. And that shows just how important fossils can be to stitching together an accurate tapestry of evolutionary history.

Researchers have finally deciphered a complete human genetic instruction book from cover to cover.

The completion of the human genome has been announced a couple of times in the past, but those were actually incomplete drafts. “We really mean it this time,” says Evan Eichler, a human geneticist and Howard Hughes Medical Institute investigator at the University of Washington in Seattle.

The completed genome is presented in a series of papers published online March 31 in Science and Nature Methods.

An international team of researchers, including Eichler, used new DNA sequencing technology to untangle repetitive stretches of DNA that were redacted from an earlier version of the genome, widely used as a reference for guiding biomedical research.

Deciphering those tricky stretches adds about 200 million DNA bases, about 8 percent of the genome, to the instruction book, researchers report in Science. That’s essentially an entire chapter. And it’s a juicy one, containing the first-ever looks at the short arms of some chromosomes, long-lost genes and important parts of chromosomes called centromeres — where machinery responsible for divvying up DNA grips the chromosome.

“Some of the regions that were missing actually turn out to be the most interesting,” says Rajiv McCoy, a human geneticist at Johns Hopkins University, who was part of the team known as the Telomere-to-Telomere (T2T) Consortium assembling the complete genome. “It’s exciting because we get to take the first look inside these regions and see what we can find.” Telomeres are repetitive stretches of DNA found at the ends of chromosomes. Like aglets on shoelaces, they may help keep chromosomes from unraveling.

Data from the effort are already available for other researchers to explore. And some, like geneticist Ting Wang of Washington University School of Medicine in St. Louis, have already delved in. “Having a complete genome reference definitely improves biomedical studies.… It’s an extremely useful resource,” he says. “There’s no question that this is an important achievement.”

But, Wang says, “the human genome isn’t quite complete yet.”

To understand why and what this new volume of the human genetic encyclopedia tells us, here’s a closer look at the milestone.
What did the researchers do?
Eichler is careful to point out that “this is the completion of a human genome. There is no such thing as the human genome.” Any two people will have large portions of their genomes that range from very similar to virtually identical and “smaller portions that are wildly different.” A reference genome can help researchers see where people differ, which can point to genes that may be involved in diseases. Having a view of the entire genome, with no gaps or hidden DNA, may give scientists a better understanding of human health, disease and evolution.

The newly complete genome doesn’t have gaps like the previous human reference genome. But it still has limitations, Wang says. The old reference genome is a conglomerate of more than 60 people’s DNA (SN: 3/4/21). “Not a single individual, or single cell on this planet, has that genome.” That goes for the new, complete genome, too. “It’s a quote-unquote fake genome,” says Wang, who was not involved with the project.

The new genome doesn’t come from a person either. It’s the genome of a complete hydatidiform mole, a sort of tumor that arises when a sperm fertilizes an empty egg and the father’s chromosomes are duplicated. The researchers chose to decipher the complete genome from a cell line called CHM13 made from one of these unusual tumors.

That decision was made for a technical reason, says geneticist Karen Miga of the University of California, Santa Cruz. Usually, people get one set of chromosomes from their mother and another set from their father. So “we all have two genomes in every cell.”

If putting together a genome is like assembling a puzzle, “you essentially have two puzzles in the same box that look very similar to each other,” says Miga, borrowing an analogy from a colleague. Researchers would have to sort the two puzzles before piecing them together. “Genomes from hydatidiform moles don’t present that same challenge. It’s just one puzzle in the box.”

The researchers did have to add the Y chromosome from another person, because the sperm that created the hydatidiform mole carried an X chromosome.

Even putting one puzzle together is a Herculean task. But new technologies that allow researchers to put DNA bases — represented by the letters A, T, C and G — in order, can spit out stretches up to more than 100,000 bases long. Just as children’s puzzles are easier to solve because of larger and fewer pieces, these “long reads” made assembling the bits of the genome easier, especially in repetitive parts where just a few bases might distinguish one copy from another. The bigger pieces also allowed researchers to correct some mistakes in the old reference genome.

What did they find?
For starters, the newly deciphered DNA contains the short arms of chromosomes 13, 14, 15, 21 and 22. These “acrocentric chromosomes” don’t resemble nice, neat X’s the way the rest of the chromosomes do. Instead, they have a set of long arms and one of nubby short arms.

The length of the short arms belies their importance. These arms are home to rDNA genes, which encode rRNAs, which are key components of complex molecular machines called ribosomes. Ribosomes read genetic instructions and build all the proteins needed to make cells and bodies work. There are hundreds of copies of these rDNA regions in every person’s genome, an average of 315, but some people have more and some fewer. They’re important for making sure cells have protein-building factories at the ready.

“We didn’t know what to expect in these regions,” Miga says. “We found that every acrocentric chromosome, and every rDNA on that acrocentric chromosome, had variants, changes to the repeat unit that was private to that particular chromosome.”

By using fluorescent tags, Eichler and colleagues discovered that repetitive DNA next to the rDNA regions — and perhaps the rDNA too — sometimes switches places to land on another chromosome, the team reports in Science. “It’s like musical chairs,” he says. Why and how that happens is still a mystery.

The complete genome also contains 3,604 genes, including 140 that encode proteins, that weren’t present in the old, incomplete genome. Many of those genes are slightly different copies of previously known genes, including some that have been implicated in brain evolution and development, autism, immune responses, cancer and cardiovascular disease. Having a map of where all these genes lie may lead to a better understanding of what they do, and perhaps even of what makes humans human.

One of the biggest finds may be the structure of all of the human centromeres. Centromeres, the pinched portions which give most chromosomes their characteristic X shape, are the assembly points for kinetochores, the cellular machinery that divvies up DNA during cell division. That’s one of the most important jobs in a cell. When it goes wrong, birth defects, cancer or death can result. Researchers had already deciphered the centromeres of fruit flies and the human 8, X and Y chromosomes (SN: 5/17/19), but this is the first time that researchers got a glimpse of the rest of the human centromeres.

The structures are mostly head-to-tail repeats of about 171 base pairs of DNA known as alpha satellites. But those repeats are nestled within other repeats, creating complex patterns that distinguish each chromosome’s individual centromere, Miga and colleagues describe in Science. Knowing the structures will help researchers learn more about how chromosomes are divvied up and what sometimes throws off the process.
Researchers also now have a more complete map of epigenetic marks — chemical tags on DNA or associated proteins that may change how genes are regulated. One type of epigenetic mark, known as DNA methylation, is fairly abundant across the centromeres, except for one spot in each chromosome called the centromeric dip region, Winston Timp, a biomedical engineer at Johns Hopkins University and colleagues report in Science.

Those dips are where kinetochores grab the DNA, the researchers discovered. But it’s not yet clear whether the dip in methylation causes the cellular machinery to assemble in that spot or if assembly of the machinery leads to lower levels of methylation.

Examining DNA methylation patterns in multiple people’s DNA and comparing them with the new reference revealed that the dips occur at different spots in each person’s centromeres, though the consequences of that aren’t known.

About half of genes implicated in the evolution of humans’ large, wrinkly brains are found in multiple copies in the newly uncovered repetitive parts of the genome (SN: 2/26/15). Overlaying the epigenetic maps on the reference allowed researchers to figure out which of many copies of those genes were turned on and off, says Ariel Gershman, a geneticist at Johns Hopkins University School of Medicine.

“That gives us a little bit more insight into which of them are actually important and playing a functional role in the development of the human brain,” Gershman says. “That was exciting for us, because there’s never been a reference that was accurate enough in these [repetitive] regions to tell which gene was which, and which ones are turned on or off.”

What is next?
One criticism of genetics research is that it has relied too heavily on DNA from people of European descent. CHM13 also has European heritage. But researchers have used the new reference to discover new patterns of genetic diversity. Using DNA data collected from thousands of people of diverse backgrounds who participated in earlier research projects compared with the T2T reference, researchers more easily and accurately found places where people differ, McCoy and colleagues report in Science.

The Telomere-to-Telomere Consortium has now teamed up with Wang and his colleagues to make complete genomes of 350 people from diverse backgrounds (SN: 2/22/21). That effort, known as the pangenome project, is poised to reveal some of its first findings later this year, Wang says.

McCoy and Timp say that it may take some time, but eventually, researchers may switch from using the old reference genome to the more complete and accurate T2T reference. “It’s like upgrading to a new version of software,” Timp says. “Not everyone is going to want to do it right away.”

The completed human genome will also be useful for researchers studying other organisms, says Amanda Larracuente, an evolutionary geneticist at the University of Rochester in New York who was not involved in the project. “What I’m excited about is the techniques and tools this team has developed, and being able to apply those to study other species.”

Eichler and others already have plans to make complete genomes of chimpanzees, bonobos and other great apes to learn more about how humans evolved differently than apes did. “No one should see this as the end,” Eichler says, “but a transformation, not only for genomic research but for clinical medicine, though that will take years to achieve.”

A chance alignment may have revealed a star from the universe’s first billion years.

If confirmed, this star would be the most distant one ever seen, obliterating the previous record (SN: 7/11/17). Light from the star traveled for about 12.9 billion years on its journey toward Earth, about 4 billion years longer than the former record holder, researchers report in the March 30 Nature. Studying the object could help researchers learn more about the universe’s composition during that early, mysterious time.

“These are the sorts of things that you only hope you could discover,” says astronomer Katherine Whitaker of the University of Massachusetts Amherst, who was not part of the new study.
The researchers found the object while analyzing Hubble Space Telescope images of dozens of clusters of galaxies nearer to Earth. These clusters are so massive that they bend and focus the light from more distant background objects, what’s known as gravitational lensing (SN: 10/6/15).

In images of one cluster, astronomer Brian Welch of Johns Hopkins University and colleagues noticed a long, thin, red arc. The team realized that the arc was a background galaxy whose light the cluster had warped and amplified.

Atop that red arc is a bright spot that is too small to be a small galaxy or a star cluster, the researchers say. “We stumbled into finding that this was a lensed star,” Welch says.

The researchers estimate that the star’s light originates from only 900 million years after the Big Bang, which took place about 13.8 billion years ago.

Welch and his colleagues think that the object, which they poetically nicknamed “Earendel” from the old English word meaning “morning star” or “rising light,” is a behemoth with at least 50 times the mass of the sun. But the researchers can’t pin down that value, or learn more about the star or even confirm that it is a star, without more detailed observations.

The researchers plan to use the recently launched James Webb Space Telescope to examine Earendel (SN: 10/6/21). The telescope, also known as JWST, will begin studying the distant universe this summer.

JWST may uncover objects from even earlier times in the universe’s history than what Hubble can see because the new telescope will be sensitive to light from more distant objects. Welch hopes that the telescope will find many more of these gravitationally lensed stars. “I’m hoping that this record won’t last very long.”