But did humans also favor certain wild plants for domestication because they were more easily “tamed”? Research from Washington University in St. Louis calls for a reappraisal of the process of plant domestication, based on almost a decade of observations and experiments. The behavior of erect knotweed, a buckwheat relative, has WashU paleoethnobotanists completely reassessing our understanding of plant domestication.

“We have no equivalent term for tameness in plants,” said Natalie Mueller, assistant professor of archaeology in Arts & Sciences at Washington University. “But plants are capable of responding to people. They have a developmental capacity to be tamed.”

Her work with early indigenous North American crops shows that some wild plants respond quickly to clearing, fertilizing, weeding or thinning. Plants that respond in ways that make cultivation easier or more productive could be considered more easily tamed than those that cannot.

“If plants responded rapidly in ways that were beneficial to early cultivators — for example by producing higher yields, larger seeds, seeds that were easier to sprout, or a second crop in a single growing season — this would have encouraged humans to continue investing in the co-evolutionary relationship,” she said.

This capacity to express different traits and characteristics in response to the environment is called plasticity, and not all species are equally plastic.

“Some plants respond quickly and obviously to cultivation and care,” Mueller said. “I think ancient people would have noticed that they could double their yields just by thinning out dense stands of plants. This is one of the simplest and most common gardening techniques, but it has many important effects on the development of plants.”

What would an early farmer do?

Mueller’s study, published April 7 in PLOS ONE, focuses on work with a plant called erect knotweed, a member of the buckwheat family that was domesticated by indigenous farmers in eastern North America. The domesticated sub-species is now extinct; humans don’t eat it anymore. But Mueller and others have previously uncovered caches of seeds stored in caves, charred plant remnants in ancient hearths, and even the seeds of erect knotweed in human feces, clear evidence that this species was once consumed as a staple food.

Mueller, who studies lost crops, has spent years growing erect knotweed and other crop progenitors in experimental gardens, including at Washington University’s environmental field station, Tyson Research Center. She hasn’t always been successful with growing the plants she collects in the wild. In that way, Mueller can relate to the early farmers who similarly experimented with plants to discover their potential.

Her efforts have often been stymied by seed dormancy, a common feature among wild plants.

Unlike seeds you buy at the garden store, the seeds of most wild plants will not germinate if you simply sprinkle some water on them. Their requirements for germination are diverse and shaped by their evolutionary history. For example, if a plant has evolved in a place with a winter, like the Midwest, its seeds may not germinate unless they experience a long cold period. This prevents them from germinating too soon in the wild — they are waiting for spring. Domesticated plants have lost their diverse germination requirements.

The loss of germination inhibitors has presented a paradox to theorists of domestication. Many of the selective pressures that could have favored the evolution of this trait derive from planting seeds. But why would ancient people have started planting seeds if none of them germinated?

With erect knotweed, Mueller experienced a breakthrough of sorts. Based on four seasons of observations, Mueller determined that growing wild plants in the low-density conditions typical of a cultivated garden (i.e. spaced out and weeded) triggers plants to produce seeds that germinate more easily. This makes the harvests easier to plant successfully the next time around, eliminating a key barrier to further selection.

“Our results show that erect knotweed grown in low-density agroecosystems spontaneously ‘act domesticated’ in a single growing season, before any selection has occurred,” Mueller said.

Think of it as the plant equivalent to that first wolf who, though still a wild animal, sat down with its human friend around the fire. This is a behavioral shift, rather than an evolutionary one, but it allows new evolutionary pathways to open up.

A role for plant behavior

Mueller believes there is a bias in domestication studies toward viewing this changeability, or plasticity, as noise that is getting in the way of attempts to explain evolutionary change. Instead, this paper argues that we need to understand the development and behavior of wild crop relatives in order to explain the evolutionary process of domestication.

“Because we lack the practical experience with crop progenitors that ancient people had, these effects of the environment on plant development have gone mostly unnoticed and understudied,” Mueller said.

Her findings could have applications for developing new food crops: there is no reason why we have to be limited to the plants that our ancestors domesticated thousands of years ago.

Some researchers have been calling for de novo domestication — selecting wild plants with desirable characteristics and intentionally domesticating them. It may make sense to start looking to wild plants that are easily tamed as potential crops that could be developed for the future, Mueller said.

This paper also contributes to a growing awareness that plants are responsive and communicative beings. Though this idea is cutting-edge and hotly debated in biology and ecology, it is widespread in indigenous North American philosophies and probably would have been held by the people who domesticated erect knotweed and other plants thousands of years ago.

Recent research has shown how plants warn relatives about herbivores using chemical signaling, share resources through mycorrhizal networks and even emit noises when they are injured or stressed.

“You can’t explain plant domestication if you only consider the behaviors of humans, because domestication is the result of reciprocal relationships between multiple species that are all capable of responding to each other,” Mueller said.

In a clinical trial, 32 men with high-risk or very high-risk prostate cancers who were scheduled for prostate cancer surgery were treated with six weekly infusions of enoblituzumab prior to surgery, and were followed for an average of 30 months thereafter. Twenty-one patients, or 66%, had an undetectable prostate-specific antigen (PSA) level 12 months following surgery, suggesting that there was no sign of residual disease. Additionally, the drug was well-tolerated overall; no patients had any surgical delays or medical complications during or after the operation.

A description of the work was published April 3 in the journal Nature Medicine.

If enoblituzumab continues to perform well in further larger randomized studies, it could represent a new pathway for immunotherapy against multiple cancers, and the first one that may have a role for prostate cancer, says lead study author and cancer immunology researcher Eugene Shenderov, M.D., Ph.D., assistant professor of oncology at the Johns Hopkins University School of Medicine. Other existing antibody-based immunotherapy drugs have targeted immune checkpoints, natural on/off switches mediating immune responses, such as CTLA-4, PD-1 and LAG-3. Cancer cells hijack these checkpoints, turning off the immune response to cancer. “Drugs that block these checkpoints have had success in other types of cancers, including lung cancer and melanoma, but not in prostate cancer,” says Shenderov.

Enoblituzumab works by binding to a protein called B7-H3 that is overexpressed on prostate cancer cells and believed to impede the immune system’s ability to attack cancer cells. The new therapy could pack a one-two punch against cancer, Shenderov says, by blocking B7-H3’s inhibition of the immune system’s recognition and elimination of cancer cells, and also triggering a process called antibody-dependent cellular cytoxicity (ADCC), which leads to tumor cell destruction by activating additional immune cells such as macrophages and natural killer cells.

“Enoblituzumab appears safe and seems to activate the immune system in a way that involves both T-cells and myeloid cells,” Shenderov says. “What this means is if these results can be replicated in a larger, randomized study, it opens the possibility that combining this therapy with local, curative-intent therapies like surgical prostate removal or radiation therapy, would allow this drug to potentially kill micrometastatic disease hiding elsewhere in the body, and therefore prevent a significant number of men from experiencing recurring disease. That could be a paradigm shift in prostate cancer.”

The median age of study participants was 64 (age range 48-74). About half (47%) had a PSA greater than 10 ng/mL at diagnosis, which is abnormally high, and 50% had Gleason grade group 5 at biopsy, meaning they had highly aggressive disease. Patients were enrolled from February 2017 through June 2019. Enoblituzumab was confirmed to penetrate into prostate tumors and to bind to B7-H3 in the vast majority of participants, according to prostate samples studied after surgery.

Side effects of enoblituzumab were generally mild and included fatigue, neurological symptoms such as headache or dizziness, and flu-like or cold symptoms. One patient developed inflammation of the heart (myocarditis), which fully resolved with steroid treatment, and is a known side effect of other immune checkpoint drugs.

Beyond safety and anti-tumor activity based on PSA dropping to undetectable levels, investigators also looked for changes in the tumor microenvironment before and after enoblituzumab treatment. They found increased markers of cytotoxicity after treatment, consistent with the concept that the immune system was activated against tumor cells. The tumors showed increased infiltration with granulocytes, leukocytes and effector T-cells, and there was roughly a doubling of the density of cytotoxic T cells after treatment.

“The findings are exciting but exploratory, and need to be confirmed in larger study cohorts,” cautions senior study author Emmanuel S. Antonarakis, M.D., the Clark Endowed Professor of Medicine and director of GU Oncology for the University of Minnesota Masonic Cancer Center. Antonarakis was the senior investigator of the study while he was at the Johns Hopkins Kimmel Cancer Center.

“However, these results in high-risk prostate cancer patients, and the broader need for immunotherapeutic strategies with efficacy in prostate cancers, provide justification to further develop multipronged approaches that include targeting B7-H3 to optimize antitumor activity in prostate cancers and other solid malignancies,” he says.

Investigators are now planning a larger, randomized trial of enoblituzumab in newly diagnosed prostate cancer patients to assess clinical activity of the drug compared to current standards of care.

Coauthors of the current study were Angelo M. De Marzo, Tamara L. Lotan, Hao Wang, Sin Chan, Su Jin Lim, Hogkai Ji, Mohamad El Allaf, Carolyn Chapman, Samuel R. Denmeade, Kenneth J. Pienta, Christian P. Pavlovich, and Drew M. Pardoll of Johns Hopkins. Other study authors contributing to the paper were from MacroGenics Inc. of Rockville, Maryland (the maker of enoblituzumab); NanoString Technologies Inc. of Seattle; Adaptive Biotechnologies of Seattle; CDI Labs of Baltimore; the Northwestern University Feinberg School of Medicine in Chicago; and Charles G. Drake formerly at Johns Hopkins, who currently leads Immuno-Oncology at Janssen Research and Development.

The work was supported by the National Institutes of Health (Cancer Center Support Grant P30 CA006973), an NCI SPORE in Prostate Cancer (P50CA58236), a Prostate Cancer Foundation Young Investigator Award, the Department of Defense (grants W81XWH-16-PCRP-CCRSA and W81XWH-18-2-0015), and the Bloomberg~Kimmel Institute for Cancer Immunotherapy and by Macrogenics Inc, of Rockville, Maryland.

E. Shenderov is a paid consultant to GT Biopharma, Guidepoint Global, FirstThought, GLG, and receives institutional research funding from MacroGenics Inc., manufacturer of enoblituzumab. These relationships are managed by The Johns Hopkins University in accordance with its conflict of interest policies. E. Antonarakis has served as a paid consultant for Janssen, Astellas, Sanofi, Bayer, Bristol Myers Squibb, Amgen, Constellation, Blue Earth, Exact Sciences, Invitae, Curium, Pfizer, Merck, AstraZeneca, Clovis and Eli Lilly; and has received research support from MacroGenics, Janssen, Johnson & Johnson, Sanofi, Bristol Myers Squibb, Pfizer, AstraZeneca, Novartis, Curium, Constellation, Celgene, Merck, Bayer, Clovis and Orion. These relationships are managed by the University of Minnesota (Antonarakis’ current institution) in accordance with their conflict of interest policies.

Critically, they’ve shown how the production of these molecules can be efficiently managed so as not to hamper normal plant growth.

Pheromones are complex chemicals produced and released by an organism as a means of communication. They allow members of the same species to send signals, which includes letting others know they’re looking for love.

Farmers can hang pheromone dispersers among their crops to mimic the signals of female insects, trapping or distracting the males from finding a mate. Some of these molecules can be produced by chemical processes but chemical synthesis is often expensive and creates toxic byproducts.

Dr Nicola Patron, who led this new research and heads the Synthetic Biology Group at the Earlham Institute, uses cutting-edge science to get plants to produce these valuable natural products.

Synthetic biology applies engineering principles to the building blocks of life, DNA. By creating genetic modules with the instructions to build new molecules, Dr Patron and her group can turn a plant such as tobacco into a factory that only needs sunlight and water.

“Synthetic biology can allow us to engineer plants to make a lot more of something they already produced, or we can provide the genetic instructions that allow them to build new biological molecules, such as medicines or these pheromones,” said Dr Patron.

In this latest work, the team worked with scientists at the Plant Molecular and Cell Biology Institute in Valencia to engineer a species of tobacco, Nicotiana benthamiana, to produce moth sex pheromones. The same plant has previously been engineered to produce ebola antibodies and even coronavirus-like particles for use in Covid vaccines.

The Group built new sequences of DNA in the lab to mimic the moth genes and introduced a few molecular switches to precisely regulate their expression, which effectively turns the manufacturing process on and off.

An important component of the new research was the ability to fine tune the production of the pheromones, as coercing plants to continuously build these molecules has its drawbacks.

“As we increase the efficiency, too much energy is diverted away from normal growth and development,” explained Dr Patron.

“The plants are producing a lot of pheromone but they’re not able to grow very large, which essentially reduces the capacity of our production line. Our new research provides a way to regulate gene expression with much more subtlety.”

In the lab, the team set about testing and refining the control of genes responsible for producing the mix of specific molecules that mimic the sex pheromones of moth species, including navel orangeworm and cotton bollworm moths.

They showed that copper sulphate could be used to finely tune the activity of the genes, allowing them to control both the timing and level of gene expression. This is particularly important as copper sulphate is a cheap and readily-available compound already approved for use in agriculture.

They were even able to carefully control the production of different pheromone components, allowing them to tweak the cocktail to better suit specific moth species.

“We’ve shown we can control the levels of expression of each gene relative to the others,” said Dr Patron. “This allows us to control the ratio of products that are made.

“Getting that recipe right is particularly important for moth pheromones as they’re often a blend of two or three molecules in specific ratios. Our collaborators in Spain are now extracting the plant-made pheromones and testing them in dispensers to see how well they compare to female moths.”

The team hope their work will pave the way to routinely using plants to produce a wide range of valuable natural products.

“A major advantage of using plants is that it can be far more expensive to build complex molecules using chemical processes,” said Dr Patron. “Plants produce an array of useful molecules already so we’re able to use the latest techniques to adapt and refine the existing machinery.

“In the future, we may see greenhouses full of plant factories — providing a greener, cheaper and more sustainable way to manufacture complex molecules.”

The research is part of the SUSPHIRE project, which received support from ERACoBiotech funded by the Horizon 2020 research and innovation program and the UKRI Biotechnology and Biological Sciences Research Council (BBSRC).

“Cas A represents our best opportunity to look at the debris field of an exploded star and run a kind of stellar autopsy to understand what type of star was there beforehand and how that star exploded,” said Danny Milisavljevic of Purdue University in West Lafayette, Indiana, principal investigator of the Webb program that captured these observations.

“Compared to previous infrared images, we see incredible detail that we haven’t been able to access before,” added Tea Temim of Princeton University in Princeton, New Jersey, a co-investigator on the program.

Cassiopeia A is a prototypical supernova remnant that has been widely studied by a number of ground-based and space-based observatories, including NASA’s Chandra X-ray Observatory. The multi-wavelength observations can be combined to provide scientists with a more comprehensive understanding of the remnant.

Dissecting the Image

The striking colors of the new Cas A image, in which infrared light is translated into visible-light wavelengths, hold a wealth of scientific information the team is just beginning to tease out. On the bubble’s exterior, particularly at the top and left, lie curtains of material appearing orange and red due to emission from warm dust. This marks where ejected material from the exploded star is ramming into surrounding circumstellar gas and dust.

Interior to this outer shell lie mottled filaments of bright pink studded with clumps and knots. This represents material from the star itself, which is shining due to a mix of various heavy elements, such as oxygen, argon, and neon, as well as dust emission.

“We’re still trying to disentangle all these sources of emission,” said Ilse De Looze of Ghent University in Belgium, another co-investigator on the program.

The stellar material can also be seen as fainter wisps near the cavity’s interior.

Perhaps most prominently, a loop represented in green extends across the right side of the central cavity. “We’ve nicknamed it the Green Monster in honor of Fenway Park in Boston. If you look closely, you’ll notice that it’s pockmarked with what look like mini-bubbles,” said Milisavljevic. “The shape and complexity are unexpected and challenging to understand.”

Origins of Cosmic Dust — and Us

Among the science questions that Cas A may help answer is: Where does cosmic dust come from? Observations have found that even very young galaxies in the early universe are suffused with massive quantities of dust. It’s difficult to explain the origins of this dust without invoking supernovae, which spew large quantities of heavy elements (the building blocks of dust) across space.

However, existing observations of supernovae have been unable to conclusively explain the amount of dust we see in those early galaxies. By studying Cas A with Webb, astronomers hope to gain a better understanding of its dust content, which can help inform our understanding of where the building blocks of planets and ourselves are created.

“In Cas A, we can spatially resolve regions that have different gas compositions and look at what types of dust were formed in those regions,” explained Temim.

Supernovae like the one that formed Cas A are crucial for life as we know it. They spread elements like the calcium we find in our bones and the iron in our blood across interstellar space, seeding new generations of stars and planets.

“By understanding the process of exploding stars, we’re reading our own origin story,” said Milisavljevic. “I’m going to spend the rest of my career trying to understand what’s in this data set.”

The Cas A remnant spans about 10 light-years and is located 11,000 light-years away in the constellation Cassiopeia.

The answer: You see how it impacts things that you can see. In the case of dark matter, astronomers watch how light from distant galaxies bends around it.

An international team of astrophysicists and cosmologists have spent the past year teasing out the secrets of this elusive material, using sophisticated computer simulations and the observations from the one of the most powerful astronomical cameras in the world, the Hyper Suprime-Cam (HSC). The team is led by astronomers from Princeton University and the astronomical communities of Japan and Taiwan, using data from the first three years of the HSC sky survey, a wide-field imaging survey carried out with the 8.2-meter Subaru telescope on the summit of Maunakea in Hawai’i. Subaru is operated by the National Astronomical Observatory of Japan; its name is the Japanese word for the cluster of stars we call the Pleiades.

The team presented their findings at a webinar attended by more than 200 people, and they will share their work at the “Future Science with CMB x LSS” conference in Japan.

“Our overall goal is to measure some of the most fundamental properties of our universe,” said Roohi Dalal, a graduate student in astrophysics at Princeton. “We know that dark energy and dark matter make up 95% of our universe, but we understand very little about what they actually are and how they’ve evolved over the history of the universe. Clumps of dark matter distort the light of distant galaxies through weak gravitational lensing, a phenomenon predicted by Einstein’s General Theory of Relativity. This distortion is a really, really small effect; the shape of a single galaxy is distorted by an imperceptible amount. But when we make that measurement for 25 million galaxies, we’re able to measure the distortion with quite high precision.”

To jump to the punchline: The team has measured a value for the “clumpiness” of the universe’s dark matter (known to cosmologists as “S₈“) of 0.776, which aligns with values that other gravitational lensing surveys have found in looking at the relatively recent universe — but it does not align with the value of 0.83 derived from the Cosmic Microwave Background, which dates back to the universe’s origins.

The gap between these two values is small, but as more and more studies confirm each of the two values, it doesn’t appear to be accidental. The other possibilities are that there’s some as-yet unrecognized error or mistake in one of these two measurements or the standard cosmological model is incomplete in some interesting way.

“We’re still being fairly cautious here,” said Michael Strauss, chair of Princeton’s Department of Astrophysical Sciences and one of the leaders of the HSC team. “We’re not saying that we’ve just discovered that modern cosmology is all wrong, because, as Roohi has emphasized, the effect that we’re measuring is a very subtle one. Now, we think we’ve done the measurement right. And the statistics show that there’s only a one in 20 chance that it’s just due to chance, which is compelling but not completely definitive. But as we in the astronomy community come to the same conclusion over multiple experiments, as we keep on doing these measurements, perhaps we’re finding that it’s real.”

Hiding and uncovering the data

The idea that some change is needed in the standard cosmological model, that there is some fundamental piece of cosmology yet to be discovered, is a deliciously enticing one for some scientists.

“We are human beings, and we do have preferences. That’s why we do what we call a ‘blinded’ analysis,” Strauss said. “Scientists have become self-aware enough to know that we will bias ourselves, no matter how careful we are, unless we carry out our analysis without allowing ourselves to know the results until the end. For me, I would love to really find something fundamentally new. That would be truly exciting. But because I am prejudiced in that direction, we want to be very careful not to let that influence any analysis that we do.”

To protect their work from their biases, they quite literally hid their results from themselves and their colleagues — month after month after month.

“I worked on this analysis for a year and didn’t get to see the values that were coming out,” said Dalal.

The team even added an extra obfuscating layer: they ran their analyses on three different galaxy catalogs, one real and two with numerical values offset by random values.

“We didn’t know which of them was real, so even if someone did accidentally see the values, we wouldn’t know if the results were based on the real catalog or not,” she said.

On February 16, the international team gathered together on Zoom — in the evening in Princeton, in the morning in Japan and Taiwan — for the “unblinding.”

“It felt like a ceremony, a ritual, that we went through,” Strauss said. “We unveiled the data, and ran our plots, immediately we saw it was great. Everyone went, ‘Oh, whew!’ and everyone was very happy.”

Dalal and her roommate popped a bottle of champagne that night.

A huge survey with the world’s largest telescope camera

HSC is the largest camera on a telescope of its size in the world, a mantle it will hold until the Vera C. Rubin Observatory currently under construction in the Chilean Andes, begins the Legacy Survey of Space and Time (LSST) in late 2024. In fact, the raw data from HSC is processed with the software designed for LSST. “It is fascinating to see that our software pipelines are able to handle such large quantities of data well ahead of LSST,” said Andrés Plazas, an associate research scholar at Princeton.

The survey that the research team used covers about 420 square degrees of the sky, about the equivalent of 2000 full moons. It’s not a single contiguous chunk of sky, but split among six different pieces, each about the size that you could cover with an outstretched fist. The 25 million galaxies they surveyed are so distant that instead of seeing these galaxies as they are today, the HSC recorded how they were billions of years ago.

Each of these galaxies glows with the fires of tens of billions of suns, but because they are so far away, they are extremely faint, as much as 25 million times fainter than the faintest stars we can see with the naked eye.

“It is extremely exciting to see these results from HSC collaboration, especially as this data is closest to what we expect from Rubin Observatory, which the community is working towards together,” said cosmologist Alexandra Amon, a Senior Kavli Fellow at Cambridge University and a senior researcher at Trinity College, who was not involved in this research. “Their deep survey makes for beautiful data. For me, it is intriguing that HSC, like the other independent weak lensing surveys, point to a low value for S₈ — it’s important validation, and exciting that these tensions and trends force us to pause and think about what that data is telling us about our Universe!”

The standard cosmological model

The standard model of cosmology is “astonishingly simple” in some ways, explained Andrina Nicola of the University of Bonn, who advised Dalal on this project when she was a postdoctoral scholar at Princeton. The model posits that the universe is made up of only four basic constituents: ordinary matter (atoms, mostly hydrogen and helium), dark matter, dark energy and photons.

According to the standard model, the universe has been expanding since the Big Bang 13.8 billion years ago: it started out almost perfectly smooth, but the pull of gravity on the subtle fluctuations in the universe has caused structure — galaxies enveloped in dark matter clumps — to form. In the present-day universe, the relative contributions of ordinary matter, dark matter, dark energy are about 5%, 25% and 70%, plus a tiny contribution from photons.

The standard model is defined by only a handful of numbers: the expansion rate of the universe; a measure of how clumpy the dark matter is (S₈); the relative contributions of the constituents of the universe (the 5%, 25%, 70% numbers above); the overall density of the universe; and a technical quantity describing how the clumpiness of the universe on large scales relates to that on small scales.

“And that’s basically it!” Strauss said. “We, the cosmological community, have converged on this model, which has been in place since the early 2000s.”

Cosmologists are eager to test this model by constraining these numbers in various ways, such as by observing the fluctuations in the Cosmic Microwave Background (which in essence is the universe’s baby picture, capturing how it looked after its first 400,000 years), modeling the expansion history of the universe, measuring the clumpiness of the universe in the relatively recent past, and others.

“We’re confirming a growing sense in the community that there is a real discrepancy between the measurement of clumping in the early universe (measured from the CMB) and that from the era of galaxies, ‘only’ 9 billion years ago,” said Arun Kannawadi, an associate research scholar at Princeton who was involved in the analysis.

Five lines of attack

Dalal’s work does a so-called Fourier-space analysis; a parallel real-space analysis was led by Xiangchong Li of Carnegie Mellon University, who worked in close collaboration with Rachel Mandelbaum, who completed her physics A.B. in 2000 and her Ph.D. in 2006, both from Princeton. A third analysis, a so-called 3×2-point analysis, takes a different approach of measuring the gravitational lensing signal around individual galaxies, to calibrate the amount of dark matter associated with each galaxy. That analysis was led by Sunao Sugiyama of the University of Tokyo, Hironao Miyatake (a former Princeton postdoctoral fellow) of Nagoya University and Surhud More of the Inter-University Centre for Astronomy and Astrophysics in Pune, India.

These five sets of analyses each use the HSC data to come to the same conclusion about S₈.

Doing both the real-space analysis and the Fourier-space analysis “was sort of a sanity check,” said Dalal. She and Li worked closely to coordinate their analyses, using blinded data. Any discrepancies between those two would say that the researchers’ methodology was wrong. “It would tell us less about astrophysics and more about how we might have screwed up,” Dalal said.

“We didn’t know until the unblinding that two results were bang-on identical,” she said. “It felt miraculous.”

Sunao added: “Our 3×2-point analysis combines the weak lensing analysis with the clustering of galaxies. Only after unblinding did we know that our results were in beautiful agreement with those of Roohi and Xiangchong. The fact that all these analyses are giving the same answer gives us confidence that we’re doing something right!”

The Johns Hopkins University team reports for the first time the mechanisms by which a protein known as histone H3 controls when and how worm embryos produce both highly specific cells and pluripotent cells, cells that can turn certain genes on and off to produce varying kinds of body tissue. The details are published today in Science Advances.

The new research could shed light on how mutations associated with these proteins influence various diseases. In children and young adults, for example, histone H3 is closely associated with various cancers.

“These mutations are highly prevalent in different cancers, so understanding their normal role in regulating cell fate and potentially differentiation of tissues may help us understand why some of them are more prevalent in certain diseases,” said lead author Ryan J. Gleason, a postdoctoral fellow in biology at Johns Hopkins. “The histones that we’re looking at are some of the most mutated proteins in cancer and other diseases.”

Histones are the building blocks of chromatin, the structural support of chromosomes within a cell’s nucleus. While histone H3 is particularly abundant in multicellular organisms such as plants and animals, unicellular organisms teem with a nearly identical variant of H3. That’s why scientists think the difference in rations of H3 and its variant hold crucial clues in the mystery of why pluripotent cells are so versatile during early development.

The researchers revealed that as C. elegans roundworm embryos grew, increasing H3 levels in their systems restricted the potential or “plasticity” of their pluripotent cells. When the team changed the worm’s genome to lower the amount of H3, they successfully prolonged the window of time for pluripotency that is normally lost in older embryos.

“As cells differentiate, you start to get a hundredfold histone H3 being expressed at that time period, which coincides with that lineage-specific regulation,” Gleason said. “When you lower the amount of H3 during embryogenesis, we were able to change the normal path of development to adopt alternative paths of cell fate.”

In pluripotent cells, histones help switch certain genes on and off to commit to specific cell types, be they neurons, muscles, or other tissue. Highly regulated by histones, genes act as a voice that tell cells how to develop. How quiet or loud a gene is determines a cell’s fate.

The new findings come from the gene-editing technique CRISPR, which helped the team track the role the two histones played as the worm’s offspring developed. CRISPR has made it much easier for scientists in the last decade to study the nuts and bolts of changing genetic material and spot what that does to animal, plant, and microbe traits, Gleason said.

Even though the C. elegans roundworm gives finer insights into how these pluripotent cells evolve, further research is needed to zero in on how histones might also underpin embryogenesis in humans and animals composed of hundreds of types of cells, said Xin Chen, a Johns Hopkins biology professor and co-investigator.

“Even though we are using this small worm to make these discoveries, really this finding should not be specific to one animal,” Chen said. “It’s hard to imagine the findings are only going to be applicable to one histone or one animal but, of course, more research needs to be done.”

The team includes Yanrui Guo of Johns Hopkins, Christopher S. Semancik of Tufts University, Cindy Ow of University of California, San Francisco, and Gitanjali Lakshminarayanan of Dana-Farber Cancer Institute.

The research is supported by grants NIGMS/NIH F32GM119347, NICHD/NIH K99HD09605, NIGMS/NIH R35GM127075, and a Faculty Scholarship and Investigator program from Howard Hughes Medical Institute.