Rice University bioengineer Omid Veiseh and collaborators identified new biomaterial formulations that could help turn the page on Type 1 diabetes treatment, opening the door to a more sustainable, long-term, self-regulating way to handle the disease.

To do so, they developed a new screening technique that involves tagging each biomaterial formulation in a library of hundreds with a unique “barcode” before implanting them in live subjects.

According to the study in Nature Biomedical Engineering, using one of the alginate formulations to encapsulate human insulin-secreting islet cells provided long-term blood sugar level control in diabetic mice. Catheters coated with two other high-performing materials did not clog up.

“This work was motivated by a major unmet need,” said Veiseh, a Rice assistant professor of bioengineering and Cancer Prevention and Research Institute of Texas scholar. “In Type 1 diabetes patients, the body’s immune system attacks the insulin-producing cells of the pancreas. As those cells are killed off, the patient loses the ability to regulate their blood glucose.”

For decades, scientists labored toward what Veiseh called a “‘holy grail’ goal of housing islet cells inside a porous matrix made out of a protective material that would allow the cells to access oxygen and nutrients without getting clobbered by the host’s immune system.”

However, materials with optimal biocompatibility proved very hard to find, due in part to screening constraints. On one hand, immune system response to a given implanted biomaterial can only be assessed in a live host.

“The problem is the immune response needs to be investigated inside the body of these diabetic mice, not in a test tube,” said Boram Kim, a graduate student in the Veiseh lab and co-lead author on the study. “That means that if you want to screen these hundreds of alginate molecules, then you need to have hundreds of animal test subjects. Our idea was to screen for hundreds of biomaterials at the same time, in the same test subject.”

On the other hand, different biomaterial formulations look the same, making it impossible to identify high-performing ones in the absence of some telltale trait. This made testing more than one biomaterial per host unfeasible.

“They are different materials but they look the same,” Veiseh said. “And once they are implanted in the body of a test subject and then taken out again, we cannot distinguish between the materials and we would be unable to identify which material formulation worked best.”

To overcome these constraints, Veiseh and collaborators came up with a way to tag each alginate formulation with a unique ‘barcode’ that allowed them to identify the ones that performed best.

“We paired each modified biomaterial with human umbilical vein endothelial cells (HUVEC) from a different donor,” Kim said.

“The HUVEC cells, because they come from unique donors, act as a barcode that allows us to tell what material was used initially,” Veiseh added. “The winners are the ones that have live cells in them. Once we found them, we sequenced the genome of those cells and figured out which material was paired with it. That’s how we uncovered the greatest hits.”

Trials are underway for stem cell-derived islet cell use in diabetic patients. However, current islet treatments require immunosuppression, making it a taxing way to treat Type 1 diabetes.

“Currently, in order to use implanted islet cells in diabetic patients, you have to suppress the entire immune system, just as if you were trying to do an organ transplant,” Veiseh said. “That comes with a lot of complications for the patient.

“They can develop cancer, they can’t fight infections, so, for the vast majority of patients, it’s better to actually do the insulin therapy where they inject themselves. With this biomaterial-encapsulation strategy, no immunosuppression is needed.”

Placing actual HUVEC cells inside the biomaterial capsules increased the likelihood that the host immune system would detect a foreign presence. This makes the experiment more robust than simply testing for immune response to the biomaterials alone.

“We wanted to test a library of these materials, with the selection pressure of having cells inside the beads that makes it harder for the material to not get noticed by the immune system,” Veiseh said. “There’s a lot of interest from all the islet cell manufacturers to be able to get rid of immunosuppression and instead use these alginate hydrogel matrices to protect the implanted cells.”

The new high-throughput “barcoding” approach can be deployed to screen for other medical applications using fewer live test subjects.

“That actually feeds into a lot of other projects in my lab where we’re doing biologic production from cells for other disease indications,” Veiseh said. “The same modifications can be applied to all types of materials that go into the body. This is not limited only to cell transplantation. The technology we developed can be paired with a lot of different device concepts.

“For instance, some diabetic patients use automated pump systems to self-administer insulin. The catheters on those pump systems have to be replaced every few days because they get clogged. We were able to show that coating the catheters with these new materials prevented clogging.”

“With this new cell-based barcoding technology, biomaterials research just got an unprecedented boost that will accelerate the translation to clinically applicable products, and make it more affordable,” said Dr. José Oberholzer, a transplant surgeon and bioengineer at the University of Virginia.

“This is a real paradigm shift. With this method, we can now screen hundreds of biomaterials at once and select those that the human body does not reject. We can protect cellular grafts from the assaults of the immune system, without the need for immunosuppressive medications,” Oberholzer added.

Former Rice bioengineering professor and current NuProbe U.S. CEO David Zhang noted that “high-throughput DNA sequencing has revolutionized many biomedical fields.”

“I am pleased to work with Omid to enable the development of improved biomaterials using my team’s expertise in DNA sequencing,” added Zhang, who was a co-investigator on the grant. “These improved biomaterials can enable durable implanted cell therapies to function as living drug factories, and can have a positively disruptive impact on patients with a variety of chronic diseases.”

The National Institutes of Health (R01 DK120459), JDRF (3-SRA-2021-1023-S-B), the National Science Foundation (CBET1626418), the Rice University Academy Fellowship and Rice’s Shared Equipment Authority supported the research.

As described April 28, 2023 in Science, they have now extended this research using synthetic biology to engineer a solution that keeps cells from reaching their normal levels of deterioration associated with aging. Cells, including those of yeast, plants, animals and humans, all contain gene regulatory circuits that are responsible for many physiological functions, including aging.

“These gene circuits can operate like our home electric circuits that control devices like appliances and automobiles,” said Professor Nan Hao of the School of Biological Sciences’ Department of Molecular Biology, the senior author of the study and co-director of UC San Diego’s Synthetic Biology Institute.

However, the UC San Diego group uncovered that, under the control of a central gene regulatory circuit, cells don’t necessarily age the same way. Imagine a car that ages either as the engine deteriorates or as the transmission wears out, but not both at the same time. The UC San Diego team envisioned a “smart aging process” that extends cellular longevity by cycling deterioration from one aging mechanism to another.

In the new study, the researchers genetically rewired the circuit that controls cell aging. From its normal role functioning like a toggle switch, they engineered a negative feedback loop to stall the aging process. The rewired circuit operates as a clock-like device, called a gene oscillator, that drives the cell to periodically switch between two detrimental “aged” states, avoiding prolonged commitment to either, and thereby slowing the cell’s degeneration.

These advances resulted in a dramatically extended cellular lifespan, setting a new record for life extension through genetic and chemical interventions.

As electrical engineers often do, the researchers in this study first used computer simulations of how the core aging circuit operates. This helped them design and test ideas before building or modifying the circuit in the cell. This approach has advantages in saving time and resources to identify effective pro-longevity strategies, compared to more traditional genetic strategies.

“This is the first time computationally guided synthetic biology and engineering principles were used to rationally redesign gene circuits and reprogram the aging process to effectively promote longevity,” said Hao.

Several years ago the multidisciplinary UC San Diego research team began studying the mechanisms behind cell aging, a complex biological process that underlies human longevity and many diseases. They discovered that cells follow a cascade of molecular changes through their entire lifespan until they eventually degenerate and die. But they noticed that cells of the same genetic material and within the same environment can travel along distinct aging routes. About half of the cells age through a gradual decline in the stability of DNA, where genetic information is stored. The other half ages along a path tied to the decline of mitochondria, the energy production units of cells.

The new synthetic biology achievement has the potential to reconfigure scientific approaches to age delay. Distinct from numerous chemical and genetic attempts to force cells into artificial states of “youth,” the new research provides evidence that slowing the ticks of the aging clock is possible by actively preventing cells from committing to a pre-destined path of decline and death, and the clock-like gene oscillators could be a universal system to achieve that.

“Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally-designed gene circuits that slow aging,” the researchers note in their study.

During their research, the team studied Saccharomyces cerevisiae yeast cells as a model for the aging of human cells. They developed and employed microfluidics and time-lapse microscopy to track the aging processes across the cell’s lifespan.

In the current study, yeast cells that were synthetically rewired and aged under the direction of the synthetic oscillator device resulted in an 82% increase in lifespan compared with control cells that aged under normal circumstances. The results revealed “the most pronounced lifespan extension in yeast that we have observed with genetic perturbations,” they noted.

“Our oscillator cells live longer than any of the longest-lived strains previously identified by unbiased genetic screens,” said Hao.

“Our work represents a proof-of-concept example, demonstrating the successful application of synthetic biology to reprogram the cellular aging process,” the authors wrote, “and may lay the foundation for designing synthetic gene circuits to effectively promote longevity in more complex organisms.”

The team is currently expanding their research to the aging of diverse human cell types, including stem cells and neurons.

“In combination, the 11 articles we are now publishing in Science provide an enormous amount of information about the function and development of mammalian genomes,” says Kerstin Lindblad-Toh, Professor of Comparative Genomics at Uppsala University and one of two leaders of the international consortium of researchers. “Moreover, we have produced data that can be used for studies of evolution and medical research for many years to come.”

In a large international project jointly led by Uppsala University and the Broad Institute, more than 30 research teams have together surveyed and analysed the genomes of 240 mammal species. The results, now published in 11 articles in the journal Science, show how the genomes of humans and other mammals have developed in the course of evolution.

The human genome contains approximately 20,000 genes that constitute the code for manufacturing all the proteins in the body. The genome also contains instructions that direct where, when and how much of the proteins are produced. These parts of the genome, which are called regulatory elements, are much more difficult to identify than the parts that give rise to proteins. However, studying a great many mammals’ genomes makes it possible to figure out which parts of the genome are functionally important.

The hypothesis shared by the researchers behind the publications in Science has been that if a position in the genome has been preserved throughout 100 million years of evolution, it likely serves a function in all mammals. For the first time, they have been able to test this hypothesis on a large scale. By making a detailed survey and systematic comparison of the genomes of 240 mammals, the researchers have identified regions of the human genome with previously uncharacterised function. These regions are likely regulatory elements and are significant for the correct functioning of the genome. Mutations in these can play an important role in the origin of diseases or in the distinctive features of mammal species.

The researchers identified more than three million important regulatory elements in the human genome, about half of which were previously unknown. They were also able to ascertain that at least 10 per cent of the genome is functional, ten times as much as the approximately one per cent that codes for proteins.

The 240 different mammals in the study vary widely in their characteristics, such as the acuteness of their sense of smell or the size of their brain. The researchers were able to find regions in the genomes that lead to some species having a superior sense of smell or to certain species hibernating.

“It’s exciting to now have a picture of which mutations have steered the development of specific traits in these widely divergent mammals,” says Matthew Christmas, researcher and co-first author of one of the articles focusing on the function of the genome and how it affects distinctive features in different species.

One of the studies shows that mammals had begun to change and diverge ven before the Earth was hit by the asteroid that killed the dinosaurs, approximately 65 million years ago.

“Our results can also provide important information about whether mammals are at risk of extinction, depending on how much variation they have in their genome. This is information that can lay the foundation for understanding how to manage a species to help it survive,” says Professor Lindblad-Toh.

The new knowledge also helps researchers understand how diseases arise, by linking the positions in the genome conserved by evolution to known conditions. This can be done for all species and will also be usable with reference to human diseases.

“Our analyses of 240 mammals give us a better insight into the regulatory signals in the genome. We calibrated our results on positions that are known to contribute to disease, and then could use these to suggest additional positions which could be prioritised for neurological traits, such as schizophrenia or immune conditions including asthma or eczema,” says Jennifer Meadows, researcher and co-first author of the second article, which focuses on how the project’s data can contribute to knowledge about diseases.

The genome of healthy and sick people is compared to understand which mutations lead to disease. This produces a picture of the region in the genome that may be important, but does not yield an exact knowledge of which mutation causes the disease.

“A large proportion of the mutations that lead to common diseases, like diabetes or obsessive-compulsive disorder, lie outside the genes and have to do with gene regulation. Our studies make it easier to identify the mutations that lead to disease and to understand what goes wrong,” says Lindblad-Toh.

The researchers also studied the cancer medulloblastoma, which is the most common type of malignant brain tumour in children. Although modern treatments have improved the prognosis, not all children can be cured. Moreover, those that survive often experience lifelong side-effects from the aggressive treatment.

“In patients with medulloblastoma, we found many new mutations in evolutionarily conserved positions. We hope that analysis of these mutations will lay the ground for new diagnostics and therapies,” says Karin Forsberg-Nilsson, Professor of Stem Cell Research at Uppsala University, who led the cancer part of the study.

This work was supported in part by the National Institutes of Health (US), the Swedish Research Council (SWE), the Knut and Alice Wallenberg Foundation (SWE), and the National Science Foundation (US).

And now comes a major installment of that promise. In what Howard Hughes Medical Institute Investigator and HHMI Professor Beth Shapiro calls a treasure trove of research, more than 150 researchers from 50 institutions are publishing 11 different papers in the April 28, 2023, issue of Science. The research brings new insights from the Zoonomia Project, an unprecedented collaborative effort led by Elinor Karlsson, director of the Vertebrate Genomics Group at the Broad Institute of MIT and Harvard, that compares and analyzes the complete genomes of 240 different mammalian species, from aardvarks to zebus.

The findings from this enormous amount of genetic data include pinpointing genes that underlie the ability to hibernate or how brains grew larger, as well as identifying the small fraction of genes that makes humans unique. “These 11 papers are just a sampling of the type of science that can be done with the new genetic data,” says Shapiro, professor of ecology and evolutionary biology at the University of California, Santa Cruz. “They show how important these large consortia and foundational datasets really are.”

Two of the papers, co-authored by Shapiro and her Santa Cruz team, break new ground by showing how much valuable information can be found in genomes of a single species, such as endangered orcas, or even in the DNA of an individual. That individual is a sled dog named Balto, who has been immortalized in movies and a statue for helping to bring lifesaving diphtheria antitoxin to Nome, Alaska in an epic journey across the Alaskan wilderness in the winter of 1925. With just a snippet of the dog’s preserved skin and “these amazing new techniques we didn’t have before, we were able to do this cool scientific thing,” says HHMI postdoc Katie Moon, lead author of the Balto paper and a member of Shapiro’s team.

Mass extinctions

One of Shapiro’s new papers tackles a high-stakes, urgent question in conservation. Humans are now causing mass extinctions and a serious loss of biodiversity across the planet. But which species are most at risk? Traditionally, conservationists tackled the question by painstakingly counting how many individuals are in a population and estimating how much habitat remains. Such efforts show that some species, like pumas in California, which Shapiro’s team has also worked on, are seriously endangered.

But what if the animal in question is one of many thousands of species for which no good population or habitat data exist? For those, Shapiro’s team wondered, might it be possible instead to estimate the threat of extinction simply by looking through the creatures’ genomes for “bad” genes or genetic evidence of inbreeding — the tell-tale signs of trouble?

To answer the question, co-lead authors, HHMI scientist Megan Supple and Aryn Wilder of the San Diego Zoo Wildlife Alliance, used the International Union for Conservation of Nature’s “Red List of Threatened Species” to rank the 240 mammals in the Zoonomia Project along a continuum from “least concern” to “critically endangered.” Then they looked for the worrisome signals in each animal’s genome.

The results show that the genomes are remarkably revealing. “Information encoded within even a single genome can provide a risk assessment in the absence of adequate ecological or population census data,” the paper reports. No good data exist on numbers or habitats for the Upper Galilee Mountains blind mole rat, a small tunnel-digging rodent, for example. But its genome shows the species is doing just fine, thanks. In contrast, both the genomic and ecological data for orcas confirm that killer whales are in serious danger.

The genomes’ predictive power can be harnessed in the effort to identify and save endangered species, Shapiro suggests. “We know we’ll never have enough conservation dollars to go around, but by using even one genome, we can triage species,” she explains — quickly and inexpensively identifying those creatures most at risk.

Champion sled dog racer

The stakes were lower for the second paper from Shapiro’s team, the sled dog effort, but it was a lot more fun, the researchers say. “I hope people enjoy reading about Balto as much as I enjoyed working on the project,” says Moon.

The origins of the project actually go back a few years. Heather Huson, a champion sled dog racer turned Cornell University animal geneticist, was giving a talk at a meeting of sled dog veterinarians when one of the vets in the audience wondered if it would be possible to extract and analyze DNA from preserved hide. He even had a potential study subject in mind — Balto, whose taxidermied body is displayed in a glass case at the Cleveland Museum of Natural History.

Huson was hooked on the idea. “I grew up on the stories about Balto,” she recalls. But she had no experience working with old DNA, “and I wasn’t going to screw this up,” she says. So she reached out to the ancient DNA research community. The path quickly led to Beth Shapiro, a pioneer in revealing the genetic secrets of extinct creatures like mastodons and of ancient humans in the field called paleogenomics. “I reached out to Beth, and she said, ‘We can do this,'” says Huson.

The researchers got a sample of Balto’s skin from the Cleveland Museum and extracted the dog’s DNA from the sample. Moonthen did the heavy genetic lifting in UC Santa Cruz’s high-tech ancient DNA lab, reading the code of Balto’s snippets of DNA enough times to cover his entire genome 40 times over.

Normally, scientists would learn about the genetics of a species in part by looking at genetic variations among different individuals. Balto was just one individual, though, so “the challenge was how to make a research project out of one dog,” says Huson. But the team had an ace up their sleeve. In addition to being able to compare the sled dog’s genome to the 240 mammals in the Zoonomia Project, they also could tap a genetic repository created by the Broad Institute’s Karlsson that has complete genomes of 682 dogs from a wide variety of breeds. “It’s an incredible dataset,” says Moon. Because of the information it contains “we know so much about dogs — what parts of the genome make them look the way they do or perform the way they do,” Moon explains. Or as Shapiro adds, the Balto project “was an opportunity to bring these two datasets together.”

Exciting moment

Using just the information in Balto’s genes, Kathleen Morrill, then a PhD student in Karlsson’s lab at the University of Massachusetts Chan Medical School, was able to predict both the dog’s precise height and the fact that his black coat had tan highlights at the edges — which don’t even show up in most pictures. A talented artist, Morrill was able to draw a rendering, based on the genetics, that was more accurate than many pictures. “Her drawing was what Balto would have looked like,” says Moon. “It was the first time anyone has done this on an individual that’s been gone for almost 100 years — and it was a really exciting moment for me.” It also validates the idea that scientists can use genomics to accurately envision what long-extinct species — for which no pictures exist — really looked like. “It shows we can do a pretty good job predicting their physical appearance,” says Huson.

There were plenty of other scientific nuggets in Balto’s DNA as well. Born in the kennel of famous sled dog breeder Leonard Seppala in 1919, Balto was descended from dogs imported from Siberia. “But one of the coolest things is how close Balto is to modern Alaskan sled dogs as well as to the Siberian husky,” says Huson. His genome shows a mix of ancestors, with fewer deleterious genes compared to modern purebred breeds like Siberian huskies and Alaskan Malamutes. His DNA is also rich in so-called tissue development genes, which are involved in functions like muscle growth, metabolism, and oxygen consumption. “That’s exactly what you would need in a working dog,” says Moon.

Yet the genetics also reveal Balto’s limitations. Sled dogs were originally bred for great endurance, but since Balto’s time, breeders added in more speed. “Balto might have been a tough sled dog with a lot of endurance, but he wouldn’t have been very fast,” says Huson.

In fact, sled dog experts know that Balto wasn’t actually the real hero of the lifesaving 1925 journey. That honor belongs to a dog named Togo, who led Seppala’s team on the longest leg of the 674 mile trek, an astonishing 264 miles (compared to Balto’s 53 miles on the final segment). “Balto was the 2^nd string dog,” says Huson. Not being prime progenitor material, he was neutered, in contrast to Togo, “who is the dog — the foundation of a lot of sled dogs,” says Huson. So, the next step, she suggests, is getting a sample from Togo’s remains, now preserved in Nome, in order to reveal the next chapter in this canine genetic drama.

The new findings, published April 28 in the journal Science, fill an important gap in what is known about historical changes to the human genome. While a revolution in the capacity to collect data from genomes of different species has allowed scientists to identify additions that are specific to the human genome — such as a gene that was critical for humans to develop the ability to speak — less attention has been paid to what’s missing in the human genome.

For the new study researchers used an even deeper genomic dive into primate DNA to show that the loss of about 10,000 bits of genetic information — most as small as a few base pairs of DNA — over the course of our evolutionary history differentiate humans from chimpanzees, our closest primate relative. Some of those “deleted” pieces of genetic information are closely related to genes involved in neuronal and cognitive functions, including one associated with the formation of cells in the developing brain.

These 10,000 missing pieces of DNA — which are present in the genomes of other mammals — are common to all humans, the Yale team found.

The fact that these genetic deletions became conserved in all humans, the authors say, attests to their evolutionary importance, suggesting that they conferred some biological advantage.

“Often we think new biological functions must require new pieces of DNA, but this work shows us that deleting genetic code can result in profound consequences for traits make us unique as a species,” said Steven Reilly, an assistant professor of genetics at Yale School of Medicine and senior author of the paper.

The paper was one of several published in Science from the Zoonomia Project, an international research collaboration that is cataloging the diversity in mammalian genomes by comparing DNA sequences from 240 species of mammals that exist today.

In their study, the Yale team found that some genetic sequences found in the genomes of most other mammal species, from mice to whales, vanished in humans. But rather than disrupt human biology, they say, some of these deletions created new genetic encodings that eliminated elements that would normally turn genes off.

The deletion of this genetic information, Reilly said, had an effect that was the equivalent of removing three characters — “n’t” — from the word “isn’t” to create a new word, “is.”

“[Such deletions] can tweak the meaning of the instructions of how to make a human slightly, helping explain our bigger brains and complex cognition,” he said.

The researchers used a technology called Massively Parallel Reporter Assays (MPRA), which can simultaneously screen and measure the function of thousands of genetic changes among species.

“These tools have the capability to allow us to start to identify the many small molecular building blocks that make us unique as a species,” Reilly said.

James Xue of the Broad Institute is lead author of the study.

Researchers found that first-person photos (capturing the scene as it looks from one’s own eyes) best represent the physical experience of an event for people.

But third-person photos like selfies (documenting a moment with themselves in it) better depict the deeper meaning of the event in their lives.

“We found that people have a natural intuition about which perspective to take to capture what they want out of the photo,” said lead author Zachary Niese, a PhD graduate of The Ohio State University, now a postdoctoral scholar at the University of Tübingen in Germany.

The results also provide a counter to the view that people post selfies on sites like Instagram just to promote themselves, said study co-author Lisa Libby, professor of psychology at Ohio State.

“These photos with you in it can document the bigger meaning of a moment,” she said. “It doesn’t have to be vanity.”

The study was published today (April 27, 2023) in the journal Social Psychological and Personality Science.

Previous research suggested that capturing the physical experience of an event or its broader meaning may be two important motivations for taking personal photos.

For example, someone at the beach with a friend may take a photo of the ocean to capture the physical experience of the beautiful and relaxing day. Or they could take a photo with themselves in it to capture the bigger meaning of spending time with a friend.

In a series of six studies involving 2,113 participants, the researchers explored the impact of perspective in personal photography.

In one online study, participants read a scenario in which they might want to take a photo, such as spending the day at a beach with a close friend. They were asked to rate how important the experience itself would be for them, and how important the bigger meaning would be. Results showed that the higher participants rated the meaning of the event to them, the more likely they said they would take a photo with themselves in it.

Another study demonstrated the truth of people’s intuitions about whether each perspective better captures the experience or meaning of events. This study asked people to examine photos they posted to their Instagram accounts.

Participants opened their most recent post featuring their own photo and were asked: “What does this photo make you think about more?” with the response options being “The physical experience of the moment” or “The bigger meaning of the moment.”

Results showed that if the photo featured the participant in the shot, they were more likely to say the photo made them think of the bigger meaning of the moment, while photos featuring how the scene looked from their own visual perspective made them think of the physical experience.

But sometimes people may not take the photo that captures their goal — and the result is that they don’t like the photo as much.

In another experiment, the researchers again asked participants to open their most recent Instagram post featuring one of their photos. They were asked whether they were trying to capture the bigger meaning or the physical experience of the moment.

Participants then rated how they felt about the photo on a scale of 1 (not at all positive) to 5 (extremely positive).

“We found that people didn’t like their photo as much if there was a mismatch between the photo perspective and their goal in taking the photo,” Libby said.

For example, if they said their goal was to capture the meaning of the moment, they liked the photo more if it was taken in third person, with themselves in the image.

Overall, the results suggest that people have an intuition about what perspective they should use in photos to fulfill what they want the photo to do, Niese said.

“I hope this study increases people’s knowledge about how photo perspective affects how they react to photos,” he said. “That way they can make sure they consciously choose the perspective that will meet their goal.”

The results also suggest people may be posting photos on Instagram and elsewhere for more than just their audience, Niese said.

“This work suggests people also have very personal motives for taking photos. Even on social media, it appears that people are curating images for themselves to look back on to capture the experience or the meaning of the event,” he said.

“Body size reduction is not the universal response to population increase in marine predators,” says lead author Ana Valenzuela-Toro, a paleoecologist at the University of California Santa Cruz and the Smithsonian Institution. “California sea lions were very resilient over the decades that we sampled and were able to overcome increasing competition thanks to prey availability. They’re like the raccoons of the sea: they can consume almost everything, and they can compensate if something is lacking.”

While many marine mammal species have rebounded to some extent since the Marine Mammal Protection Act was passed in 1972, California sea lions are notable for the size and duration of their population increase: the number of breeding females, who have been most consistently counted, has more than tripled in the US since the 1970’s — from around 50,000 to nearly 170,000 — and their population growth is only now beginning to plateau.

To explore how California sea lion ecology has changed as their population has grown, the researchers analyzed museum specimens of adult male and female California sea lions collected in central and northern California between 1962 and 2008. To estimate changes in body size, they compared the overall size of more than 300 sea lion skulls collected over the years. They also measured other skull features, such as the size of muscle attachment points, which allowed them to assess changes in sea lion neck flexibility and biting force.

The team additionally took tiny bone samples from some of the skulls and measured their stable carbon and nitrogen isotope composition, which allowed them to make inferences about where the sea lions were foraging and what they were consuming. “Carbon provides information about habitat use — whether they’re foraging along the coast or offshore — and nitrogen provides insights about the trophic level of their prey, for example if they’re consuming smaller or larger fish,” says Valenzuela-Toro.

Overall, the researchers found that male sea lions have increased in size, while female sea lion size has remained stable. This sex difference is probably due to the fact that size matters for male, but not female, mating success. “One male can breed with many females, and males in the breeding colony fight with each other to establish their territory,” says Valenzuela-Toro. “Bigger males are more competitive during physical fights, and they can go longer without eating, so they can stay and defend their territory for longer.”

Male sea lions also increased their biting force and neck flexibility over this same time period. “The neck muscles are really important because they allow them to move their head and neck more agilely, bite harder, and, eventually, win when they are fighting other males in the breeding colony,” says Valenzuela-Toro.

The isotopic analyses indicated that both male and female sea lions managed to meet their nutritional needs by diversifying their diet and feeding on a broader range of prey. Male sea lions also foraged further afield. “Over time, some male sea lions were foraging further north,” says Valenzuela-Toro. “This is consistent with some anecdotal records that they’ve even been seen in Alaska, where they were not known to go in the past.”

Female sea lions consistently had a more diverse diet compared to male sea lions. The authors suggest that this flexibility in food choice is what allowed females to maintain their average body size without foraging further away.

“They remain in a narrow zone around their breeding colony, but they still show a lot of flexibility in what they eat,” says Valenzuela-Toro. “We believe that skull morphology in the rostrum — which is related to the size and shape of the mouth — probably has something to do with this flexible foraging behavior. We found that the size and shape of the mouth of females is related to the size of the prey that they consume.”

However, this flexibility in diet can only take the sea lions so far, and the authors warn that the sea lions’ future may not be so rosy.

“All these dynamics occurred in an environment that was rich in prey: full of anchovies and sardines, two species that are super important for their diet,” says Valenzuela-Toro. “But over the last few years, the populations of these two fish have collapsed, so California sea lions are diversifying their diet to compensate, and apparently they are not doing so well.”

“As climate change progresses, prey availability of sardines and anchovies will decrease even more, and eventually we will have more permanent El Niño-like warming conditions, reducing the size and causing a poleward shift of these and other pelagic fishes,” she says. “It will be a really hostile environment for California sea lions, and eventually we expect that their population size will stop growing and actually decline.”