Anna Frebel digs a young universe

Anna Frebel can’t explain her fascination with the stars. It’d be like explaining why “berry purple-pink” is one of her favorite colors. “They are just a part of me,” says Frebel, an astronomer at MIT. “What’s going on with them and what they can tell us — there is something magical.”

Frebel’s fascination has led to the discovery of at least three record-breaking stars. Dating back roughly 13 billion years, the stars — all within the Milky Way galaxy — might be elders from the second generation of stars ever formed in the universe. She has also found that one of the tiny galaxies flitting around outside the Milky Way might be a fossil that has survived from not long after the Big Bang. The light from these ancient relics encodes stories about the birth of the first stars, the assembling of galaxies and the origin of elements essential to creating planets and life as we know i
“Anna has a really good track record of finding these amazing things,” says Alexander Ji, one of the three graduate students Frebel mentors at MIT. “She’s always finding things that change our understanding of the universe.”
As a young girl living in Germany, Frebel wanted to be an astronaut, but she passed on that dream when she learned about the centrifuge that whips trainees around to simulate launch acceleration. Not for her. She instead studied physics and astronomy, first at the University of Freiburg in Germany and then at the Australian National University in Canberra. Since then, Frebel, now 36, has earned a reputation as a “stellar archaeologist,” with the patience and perseverance to search through the universe’s most ancient debris.

Only someone with a galaxy’s worth of patience could sift through the tiny rainbows of light, the spectra, produced by thousands of stars, handpicking the specimens that might preserve clues to the conditions shortly after the first stars lit up the universe. And only a persistent person would spend more than two years pointing Australia’s 2.3-meter-wide Advanced Technology Telescope at 1,200 of the most promising candidates (“105 stars per night was my record,” she says) and eventually, with observations from other telescopes too, land on one star that was, for a while, among the oldest known.

She was first drawn to this research after hearing astronomer Norbert Christlieb, then a visiting researcher at the Australian National University, talk about his work on old stars. “It hit me: Oh my God, this project combines all my interests,” Frebel says. There were stars, chemistry, nuclear physics and the periodic table. “There are so many, for me, cool topics that come together.”

In combing through her stars, Frebel was looking for ones that contained hydrogen and helium — but little else. Most heavier elements up to iron are forged in the cores of stars, where atomic nuclei smash together. As the universe aged, its inventory of atoms such as carbon, silicon and iron steadily increased. The earliest stars, however, came on the scene when there were far fewer of these pollutants floating around.
Her efforts paid off in 2005 with a star branded HE 1327-2326, reported in

Nature

asthe most pristine star known at the time

. “She found one that took us closer back to the beginning of time as we know it,” says Frebel’s Ph.D. adviser, astronomer John Norris of Australian National. “It became clear to us early on that she was quite gifted.”

Her gifts netted her the Charlene Heisler Prize in 2007, given by the Astronomical Society of Australia for outstanding Ph.D. thesis. She has since won several recognitions, including the Annie Jump Cannon Award in 2010, given to notable young female researchers by the American Astronomical Society, for her “pioneering work in advancing our understanding of the earliest epochs of the Milky Way galaxy through the study of its oldest stars.”

Carbon seeding
The geriatric stars that Frebel finds are not perfectly pristine; they preserve in their atmospheres the chemical makeup of interstellar gas that had been seeded with a smidgen of heavy elements from the explosions of stars that came before. Chemical abundances in many of these stellar fossils are out of balance compared with modern stars. The fossil stars have much more carbon relative to iron, for example — carbon that had to have come from the debris of that very first crop of stars.

Frebel worked with theorists to show that excess carbon could have allowed successive generations of stars (and planets) to form, reporting the work in 2007 in Monthly Notices of the Royal Astronomical Society Letters. “I’ve always been interested in understanding the main message of the data,” she says, which leads her away from the telescope to computer simulations and theory. In this case, the message is that carbon “might have been the most important element in the universe.”

Gas needs to be cold, around –270° Celsius, just a few degrees above absolute zero, to clump and form stars. And carbon is an excellent coolant; its electrons are arranged in such a way to let it efficiently radiate energy. The first generation of stars didn’t have carbon’s help. They were probably slow to form and ended up as gargantuan fluffy orbs hundreds of times as massive as the sun. But once those stars exploded and seeded the cosmos with carbon, Frebel’s data suggest, subsequent generations of stars formed that would have looked more like the stars we see today.

Frebel likens her studies to watching her young son learn to walk and talk. “My overall interpretation is that the universe was still trialing things.”

Before she became a parent, she regularly went to one of the twin Magellan telescopes, 2,380 meters above sea level in the Chilean Atacama Desert. On long nights, while waiting for the telescope to soak up light from a star tens of thousands of light-years away, Frebel would feel the pull of the night sky. “I just lie on the ground and stare into the sky and get lost in the universe,” she says.

In recent years, Frebel has expanded her repertoire to include a horde of teeny galaxies that orbit the Milky Way and also serve as archaeological sites. “Now we can use not just one star,” she says. “We can use the entire galaxy as a fossil record.” One of these runts, called Segue 1, appears to be a remnant from the cosmic dawn and might be typical of the pieces that assembled into large galaxies like the Milky Way.

Frebel and her student Ji discovered that another dwarf galaxy, dubbed Reticulum II, contains clues about one of the mechanisms responsible for creating most of the elements heavier than iron. A long-ago smashup between two neutron stars once bombarded the gas in Reticulum II with neutrons, producing atoms, such as uranium, that can’t be formed in stellar cores. Similar run-ins in other galaxies might have helped build up the universe’s stockpile of heavy elements.

Frebel plans to continue her quest to understand the origin of atoms, stars and galaxies. Though the celestial bodies she studies are ancient, “my days never get old,” she says.

Barnacles track whale migration

DENVER — Barnacles can tell a whale of a tale. Chemical clues inside barnacles that hitched rides on baleen whales millions of years ago could divulge ancient whale migration routes, new research suggests.

Modern baleen whales migrate thousands of kilometers annually between breeding and feeding grounds, but almost nothing is known about how these epic journeys have changed over time. Scientists can glean where an aquatic animal has lived based on its teeth. The mix of oxygen isotopes embedded inside newly formed tooth material depends on the region and local temperature, with more oxygen-18 used near the poles than near the equator. That oxygen provides a timeline of the animal’s travels. Baleen whales don’t have teeth, though. So paleobiologists Larry Taylor and Seth Finnegan, both of the University of California, Berkeley, looked at something else growing on whales: barnacles. Like teeth, barnacle shells take in oxygen as they grow.
Patterns of oxygen isotopes in layers of barnacle shells collected from modern beached whales matched known whale migration routes, Taylor said September 25 at the Geological Society of America’s annual meeting. Roughly 2-million-year-old barnacle fossils have analogous oxygen isotope changes, preliminary results suggest. Converting those changes into migration maps, however, will require reconstructing how oxygen isotopes were distributed long ago, Taylor said.

DNA data offer evidence of unknown extinct human relative

VANCOUVER — Traces of long-lost human cousins may be hiding in modern people’s DNA, a new computer analysis suggests.

People from Melanesia, a region in the South Pacific encompassing Papua New Guinea and surrounding islands, may carry genetic evidence of a previously unknown extinct hominid species, Ryan Bohlender reported October 20 at the annual meeting of the American Society of Human Genetics. That species is probably not Neandertal or Denisovan, but a different, related hominid group, said Bohlender, a statistical geneticist at the University of Texas MD Anderson Cancer Center in Houston. “We’re missing a population or we’re misunderstanding something about the relationships,” he said.
This mysterious relative was probably from a third branch of the hominid family tree that produced Neandertals and Denisovans, an extinct distant cousin of Neandertals. While many Neandertal fossils have been found in Europe and Asia, Denisovans are known only from DNA from a finger bone and a couple of teeth found in a Siberian cave (SN: 12/12/15, p. 14).

Bohlender isn’t the first to suggest that remnants of archaic human relatives may have been preserved in human DNA even though no fossil remains have been found. In 2012, another group of researchers suggested that some people in Africa carry DNA heirlooms from an extinct hominid species (SN: 9/8/12, p. 9).

Less than a decade ago, scientists discovered that human ancestors mixed with Neandertals. People outside of Africa still carry a small amount of Neandertal DNA, some of which may cause health problems (SN: 3/5/16, p. 18). Bohlender and colleagues calculate that Europeans and Chinese people carry a similar amount of Neandertal ancestry: about 2.8 percent. Europeans have no hint of Denisovan ancestry, and people in China have a tiny amount — 0.1 percent, according to Bohlender’s calculations. But 2.74 percent of the DNA in people in Papua New Guinea comes from Neandertals. And Bohlender estimates the amount of Denisovan DNA in Melanesians is about 1.11 percent, not the 3 to 6 percent estimated by other researchers.

While investigating the Denisovan discrepancy, Bohlender and colleagues came to the conclusion that a third group of hominids may have bred with the ancestors of Melanesians. “Human history is a lot more complicated than we thought it was,” Bohlender said.

Another group of researchers, led by Eske Willerslev, an evolutionary geneticist at the Natural History Museum of Denmark in Copenhagen, recently came to a similar conclusion. Willerslev’s group examined DNA from 83 aboriginal Australians and 25 people from native populations in the Papua New Guinea highlands (SN: 10/15/16, p. 6). The researchers found Denisovan-like DNA in the study volunteers, the group reported October 13 in Nature. But the DNA is genetically distinct from Denisovans and may be from another extinct hominid. “Who this group is we don’t know,” Willerslev says. They could be Homo erectus or the extinct hominids found in Indonesia known as Hobbits (SN: 4/30/16, p. 7), he speculates.
But researchers don’t know how genetically diverse Denisovans were, says Mattias Jakobsson, an evolutionary geneticist at Uppsala University in Sweden. A different branch of Denisovans could be the group that mated with ancestors of Australians and Papuans.

Researchers know so little about the genetic makeup of extinct groups that it’s hard to say whether the extinct hominid DNA actually came from an undiscovered species, said statistical geneticist Elizabeth Blue of the University of Washington in Seattle. DNA has been examined from few Neandertal fossils, and Denisovan remains have been found only in that single cave in Siberia. Denisovans may have been widespread and genetically diverse. If that were the case, said Blue, the Papuan’s DNA could have come from a Denisovan population that had been separated from the Siberian Denisovans for long enough that they looked like distinct groups, much as Europeans and Asians today are genetically different from each other. But if Denisovans were not genetically diverse, the mysterious extinct ancestor could well be another species, she said.

Jakobsson says he wouldn’t be surprised if there were other groups of extinct hominids that mingled with humans. “Modern humans and archaic humans have met many times and had many children together,” he said.

Giggling rats help reveal how brain creates joy

Tickle a rat and it will jump for joy, gleefully squeak and beg for more. In addition to describing these delightful reactions to a tickling hand, a new study identifies nerve cells in the brain that help turn rats into squirmy puddles of giggles.

The results, published November 11 in Science, offer insight into how the brain creates glee, an understudied emotion. “People really underrate the positive things — fun, happiness, joy,” says study coauthor Shimpei Ishiyama of Humboldt University of Berlin.
Scientists knew that rats seemed to enjoy a good tickle from a human, but how the brain creates that emotion was a mystery. Although no protocol existed, the tickling part of the experiment turned out to be “surprisingly easy,” Ishiyama says. He simply stuck his hand in the cages and scribbled his fingers in the rats’ fur, to their apparent delight. Tickled rats laughed by emitting an ultrasonic 50-kilohertz giggle that humans can’t hear. They also jumped for joy, an acrobatic feat called “Freudensprünge,” and chased Ishiyama’s hand around the cage. Using laughter as a measurement, Ishiyama and colleagues found that the belly, not back or tail, is a rat’s most ticklish spot.

This joyful response may be created in part by nerve cells in the somatosensory cortex. In people, this brain region responds to tickles and is usually associated with touch perception. In tickled rats, many nerve cells in the part of the somatosensory cortex that corresponds to the rodents’ trunks grew active, electrodes revealed. A light stroke activated some of these nerve cells, but not as many.

Because these nerve cells respond to touch, it’s not surprising that they grew active during a tickle, Ishiyama says. But additional experiments found active nerve cells when the rats were chasing a tickling hand without being touched — suggesting the cells are responding to something specific about a tickle, not just touch in general. What’s more, when the researchers used electrodes to stimulate the somatosensory cortex in untouched rats, the rats giggled.
It turns out that ticklishness is a flighty state, and not just because some rats like to be tickled more than others. Anxious rats on a platform and in bright lights emitted fewer laughlike vocalizations than calm rats, the researchers found. Nerve cells in the somatosensory cortex were less likely to fire off signals, too, results that highlight just how mood-dependent tickling is.

The new study shows for the first time that laughter can result from stimulation of the somatosensory cortex, says neuroscientist Elise Wattendorf of the University of Fribourg in Switzerland. The brain area’s involvement in both the sensory aspects of tickling and its social context is “unexpected, and constitutes an outstanding result,” she wrote in an e-mail. Using brain scans, Wattendorf and colleagues had previously found that the somatosensory cortex was active when people laughed as they were tickled.

Many brain studies focus on troubles such as depression, Ishiyama says. But by taking the opposite approach, he hopes to reveal new insights into how the brain creates and maintains happiness. Besides, he says, “it’s also fun to study fun.”

Chinese patient is first to be treated with CRISPR-edited cells

Chinese scientists have injected a person with CRISPR/Cas9-edited cells, marking the first time cells altered with the technique have been used in humans. Researchers used the powerful gene editor to alter immune cells to fight lung cancer, Nature reports November 15.

Immune cells called CAR-T cells have already been engineered using other gene-editing technologies. A baby’s leukemia was successfully treated in 2015 with CAR-T cells engineered with gene editors known as TALENs.

Chinese researchers led by oncologist Lu You of Sichuan University in Chengdu got approval to conduct the new trial this summer. U.S. researchers have gotten clearance to begin similar clinical trials.

You’s team removed immune cells from a patient with lung cancer. They then used CRISPR/Cas9 as molecular scissors to cut and inactivate the PD-1 gene in T cells. That gene’s protein usually holds immune cells back from attacking tumors. The hope is that the edited cells will now go on the offensive and help the patient fight cancer. Researchers plan to give the patient a second dose of engineered cells, Nature reports.

The researchers’ progress with the technique could spark a space race–style biomedical competition between the United States and China, Carl June, an immunotherapist at University of Pennsylvania in Philadelphia, told Nature. “I think this is going to trigger ‘Sputnik 2.0,’” he said, hopefully improving the end product.

‘The Glass Universe’ celebrates astronomy’s unsung heroines

In the early 1880s, Harvard Observatory director Edward Pickering put out a call for volunteers to help observe flickering stars. He welcomed women, in particular — and not just because he couldn’t afford to pay anything.

At the time, women’s colleges were producing graduates with “abundant training to make excellent observers,” Pickering wrote. His belief in women’s abilities carried over when he hired staff, even though critics of women’s higher education argued that women “originate almost nothing, so that human knowledge is not advanced by their work.”
Pickering and his “harem” sure proved the critics wrong.

In The Glass Universe, science writer Dava Sobel shines a light on the often-unheralded scientific contributions of the observatory’s beskirted “computers” who helped chart the heavens. By 1893, women made up nearly half of the observatory’s assistants, and dozens followed in their footsteps.

These women toiled tirelessly, marking times, coordinates and other notations for photographic images of the sky taken nightly and preserved on glass plates — the glass universe. These women’s routine mapping of the stars gave birth to novel ideas that advanced astronomy in ways still instrumental today — from how stars are classified to how galactic distances are measured.

Using diaries, letters, memoirs and scientific papers, Sobel recounts the accomplishments of these extraordinary women, going into enough scientific detail (glossary included) to satisfy curious readers and enough personal detail to bring these women’s stories to life.

Sobel traces the origin of the glass universe back to heiress Anna Palmer Draper. The book opens in 1882 with her exulting in hosting a party for the scientific glitterati under the glowing and novel Edison incandescent lights. Her husband, Henry Draper, a doctor and amateur astronomer, had pioneered a way to “fix” the stars on glass photographic plates. The resulting durable black-and-white images revealed spectral lines that could provide hints to a star’s elements — and eventually so much more. Henry’s premature death five days after the party launched Anna’s philanthropic support of the Harvard Observatory and the creation of the glass universe.
Other women featured in the book had a more hands-on impact on astronomy. For instance, Williamina Fleming came to the United States as a maid. But Pickering soon recognized her knack for mathematics. At the observatory, she read “the rune-like lines of the spectra,” Sobel writes, noticing patterns that led to the first iteration in 1890 of the Draper stellar classification system. That system, still used today, was later refined by the observations of other women.

Henrietta Leavitt, a promising Radcliffe College astronomy student slowly going deaf, joined the staff in 1895. While meticulously tracking the changing brightness of variable stars, she noticed a pattern: The brighter a star’s magnitude, the longer it took to cycle through all its variations. This period-luminosity law, published in 1912, became crucial in measuring the distance to stars. It underpinned Edwin Hubble’s law on cosmic expansion and led to discoveries about the shape of the Milky Way, our solar system’s place far from the galactic center and the existence of other galaxies.

The story belongs, too, to Pickering and his successor, Harlow Shapley. Perhaps partly motivated by economics at a time of shoestring budgets — in 1888, women computers earned just 25cents per hour — these men not only recognized, but also encouraged and heralded the women’s talent.

Sobel takes readers through World War II and a myriad of other moments starring women: first woman observatory head; first woman professor at Harvard (of astronomy, of course); discoveries of binary stars, the prevalence of hydrogen and helium in stars, and the existence of interstellar dust. In some cases, it took male astronomers to make those findings stick — the glass universe had a glass ceiling.

After World War II, radio astronomy emerged, and “the days of the human computer were numbered — by zeros and ones,” Sobel writes. Using film to photograph the stars ended in the 1970s. But the glass universe is far from obsolete. The roughly half-million plates hold the ghosts of pulsars, quasars and other stellar phenomena not even imagined when the plates were made. They also offer the promise of more discoveries to come, perhaps by the next generation of women astronomers.

Readers contemplate corals and more

Corals in crisis
Algae that provide nutrients to corals turn toxic and lead the corals to “bleach” and sometimes die when ocean temperatures spike. Researchers are seeding damaged reefs with baby corals and breeding heat-tolerant corals to help these imperiled marine animals, Amy McDermott reported in “Rebuilding reefs” (SN: 10/29/16, p. 18).

Ronald Swager wondered if researchers could use genetic engineering to make heat-stressed algae nontoxic.

Gene-editing tools may help corals survive, but the research is still quite preliminary, says Janelle Thompson, an environmental microbiologist at MIT. Among the difficulties: Scientists do not know how exactly the algae become toxic on a molecular level and they can only guess at the role of most algal genes. “One of the main challenges is the size of the [algae] genome, which … is on par with human genomes,” Thompson says. And there are many genetic variations of algae, some of which are only compatible with specific corals. Researchers would have to engineer more than one type of algae.
Heat-tolerant algae exist, but so far they don’t seem to perform well at normal temperatures, says Peter Harrison of Southern Cross University in Lismore, Australia. Assuming biologists work through the technical hurdles of genetic engineering, many people will be concerned about releasing genetically modified algae into the oceans, Harrison says.

Codex contention
Once regarded as fake by some scientists, a 10-page, bark-paper book called the Grolier Codex is authentic, according to a recent study by Yale archaeologist Michael Coe and colleagues. It may be the oldest known manuscript of ancient America, Bruce Bower wrote in “Maya codex real, analysis claims” (SN: 10/29/16, p. 16).
Physicist and astronomer John Carlson of the University of Maryland in College Park took issue with the study and Science News’ reporting. Carlson’s letter has been edited for brevity.

“I was dismayed to see my own published work establishing the authenticity of the Maya ‘Grolier Codex’ as likely the ‘oldest surviving book on paper from the ancient Americas,’ presented as ‘new analysis’ by Michael Coe and collaborators.

“There was no mention of the source of the most crucial evidence — the only radiocarbon dating of the codex’s bark paper — nor was I contacted for comments. My work, beginning in the late 1970s (and first published in 1983), determined that what had been known as ‘page 11’ was actually the lower portion of ‘page 10.’ That finding, with other primary sources, established a sequence of skeletal Evening Star manifestations of the planet Venus, something that could not have been known to any alleged faker in the mid-1960s when the codex was discovered. This work helped convince the majority of Mesoamericanist experts in Maya epigraphy and codex studies that the codex was genuine.

“I was able to study the codex itself carefully on three occasions and obtained the first carbon-14 dates from the actual codex, placing it in the 13th century. All of this was published in my article ‘The Twenty Masks of Venus’ in Archaeoastronomy in 2014 and presented at the Pre-Columbian Society of Washington, D.C., in November 2014. The scholarly details are available along with many other primary sources on my website: umd.academia.edu/JohnBCarlson.”

In an e-mail response to Science News, Michael Coe emphasizes that his team’s paper credits Carlson for his work on the Grolier Codex. Coe says that even by 1973, well before Carlson’s publications appeared, specialists in Maya writing were convinced that the codex was genuine. The new paper for the first time examines the full range of drawings and writings in the codex, Coe asserts, fitting them in with what’s now known about ancient Maya religion and gods.

‘Waterworld’ Earth preceded late rise of continents, scientist proposes

SAN FRANCISCO — Earth may have been a water world for much of its history, a new proposal contends. Just like in the Kevin Costner movie, the continents would have been mostly submerged below sea level. Previous proposals have suggested that Earth’s land area has remained comparatively unchanged throughout much of geologic time.

But geoscientist Cin-Ty Lee of Rice University in Houston proposes that Earth’s continents didn’t rise above the waves until around 700 million years ago, when the underlying mantle sufficiently cooled. Though many scientists are unconvinced, that continental rise may have contributed to the rapid diversification of life known as the Cambrian explosion. “The Earth is cooling and that actually has manifestations that dictate how life goes,” Lee said December 15 at the American Geophysical Union’s fall meeting.
Earth’s first continental crust formed billions of years ago. Slabs of this crust “float” above the underlying mantle like icebergs, with relatively cold roots than can extend tens of kilometers into the mantle. A continent’s elevation depends, in part, on the size of its root and the density of the mantle.

Earlier in Earth’s history when the mantle was hotter and less dense, the continents sat largely below sea level with only mountains peeking above the water’s surface, Lee proposed. The cooling of the mantle over time increased the relative buoyancy of the continents and lifted the landmasses above sea level. Considering mantle cooling rates and Earth’s topography, Lee proposes that this expansion of Earth’s dry land took place around 1 billion to 500 million years ago and lasted about 100 million years.

The new land would have altered carbon and nutrient cycles, Lee suggested. These effects could help explain large shifts in Earth’s climate around this time and might have nourished the Cambrian explosion. During that time, around 540 million to 500 million years ago, forerunners of the major groups of animals — from insects to mammals — first emerged.

This tale of rising continents may be overly simplistic, said Laurent Montési, a geodynamicist at the University of Maryland in College Park. Other factors such as the mass of the continents, the amount of water in the oceans and the rate of new crust formation on the seafloor could affect sea levels relative to the continents. The idea is worth considering, he said, “but the evidence is not completely there yet.”

‘Furry Logic’ showcases how animals exploit physics

Warning: Furry Logic is not, as the title might suggest, a detailed exploration of mammals’ reasoning skills. Instead, it’s a fun, informative chronicle of how myriad animals take advantage of the laws of physics.

Science writers Matin Durrani and Liz Kalaugher cite a trove of recent (and often surprising) research findings. They draw on their backgrounds — Durrani is a physicist, Kalaugher a materials scientist — to explain how animals exploit sound, light, electricity and magnetism, among other things, in pursuit of food, sex and survival. These creatures don’t consciously use physics the way that humans design and use tools, of course, but they are evolutionary marvels nonetheless.
Peacocks, for example, produce low-frequency sounds while shimmying their tail feathers (SN Online: 04/27/16). The birds use these sounds — and not just the sight of those colorful plumes — to impress females and fend off competing males. At the other end of the sonic spectrum, some bats use stealth echolocation to track down their preferred prey. Moths targeted by these bats have sensors that can pick up these ultrasonic calls, but the bats squeak so softly that a moth can’t hear its stalker until it is less than a half-second’s flight away.

Durrani and Kalaugher let readers know when the science isn’t settled. Researchers aren’t quite sure how peahens pick up males’ infrasonic signals, for example. Scientists also haven’t figured out how the archerfish spits so precisely (SN: 10/4/14, p. 8), knocking prey off low-hanging branches above the water as often as 94 percent of the time. The submerged fish must somehow gauge the angle at which light bends as it enters the water and then accurately compensate for refraction while spewing a stream of water. Amazingly, this feat may be innate rather than learned via trial and error.

Readers need not understand the intricacies of polarized light, Earth’s magnetic field or surface tension to enjoy Furry Logic. Nor is this book an exhaustive account of the characteristics and behavior of every animal that uses such phenomena in interesting ways. There should be plenty of material for a sequel to this fascinating book.

Cancer studies get mixed grades on redo tests

An effort to reproduce findings of five prominent cancer studies has produced a mixed bag of results.

In a series of papers published January 19 in eLife, researchers from the Reproducibility Project: Cancer Biology report that none of five prominent cancer studies they sought to duplicate were completely reproducible. Replicators could not confirm any of the findings of one study. In other cases, replicators saw results similar to the original study’s, but statistical analyses could not rule out that the findings were a fluke. Problems with mice or cells used in two experiments prevented the replicators from confirming the findings.
“Reproducibility is hard,” says Brian Nosek, executive director of the Center for Open Science in Charlottesville, Va., an organization that aims to increase the reliability of science. It’s too early to draw any conclusions about the overall dependability of cancer studies, Nosek says, but he hopes redo experiments will be “a process of uncertainty reduction” that may ultimately help researchers increase confidence in their results.

The cancer reproducibility project is a collaboration between Nosek’s center and Science Exchange, a network of labs that conduct replication experiments for a fee. Replicators working on the project selected 50 highly cited and downloaded papers in cancer biology published from 2010 to 2012. Teams then attempted to copy each study’s methods, often consulting with the original researchers for tips and materials. The five published in eLife are just the first batch. Eventually, all of the studies will be evaluated as a group to determine the factors that lead to failed replications.
Critics charge that the first batch of replication studies did not accurately copy the originals, producing skewed results. “They didn’t do any troubleshooting. That’s my main complaint,” says cancer biologist Erkki Ruoslahti of Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Calif.

Ruoslahti and colleagues reported in 2010 in Science that a peptide called iRGD helps chemotherapy drugs penetrate tumors and increases the drugs’ efficacy. In the replication study, the researchers could not confirm those findings. “I felt that their experimental design was set up to make us look maximally bad,” Ruoslahti says.

Replicators aren’t out to make anyone look bad, says cancer biologist Tim Errington of the Center for Open Science. The teams published the experimental designs before they began the work and reported all of their findings. What Ruoslahti calls troubleshooting, Errington calls fishing for a particular result. Errington acknowledges that technical problems may have hampered replication efforts, but that’s valuable data to determine why independent researchers often can’t reproduce published results. Identifying weaknesses will enable scientists to design better experiments and conduct research more efficiently, he argues.

Other researchers took issue with the replicators’ statistical analyses. One study sought to reproduce results from a 2011 Science Translational Medicine report. In the original study, Atul Butte, a computational biologist at the University of California, San Francisco, and colleagues developed a computer program for predicting how existing drugs might be repurposed to treat other diseases. The program predicted that an ulcer-fighting drug called cimetidine could treat a type of lung cancer. Butte and colleagues tested the drug in mice and found that it reduced the size of lung tumors. The replication attempt got very similar results with the drug test. But after adjusting the statistical analysis to account for multiple variables, the replication study could no longer rule out a fluke result. “If they want a headline that says ‘It didn’t replicate,’ they just created one,” Butte says. Errington says the corrections were necessary and not designed to purposely invalidate the original result. And when replication researchers analyzed both the original and replication study together, the results once again appeared to be statistically sound.

A failure to replicate should not be viewed as an indication that the original finding wasn’t correct, says Oswald Steward, a neuroscientist at the University of California, Irvine, who has conducted replication studies of prominent neuroscience papers but was not involved in the cancer replication studies. “A failure to replicate is simply a call to attention,” Steward says. Especially when scientists are building a research program or trying to create new therapies, it is necessary to make sure that the original findings are rock solid, he says. “We scientists have to really own this problem.”

Editor’s note: This story was updated January 26, 2017, to correct the starting point of the x-axis in the first graph.