UC San Diego graduate students learn about what makes humans different than other great apes during a CARTA specialization track field course trip to East Africa (2017).

CARTA Maps Humanity’s Distinctive Evolution

For more than 20 years, the Center for Academic Research and Training in Anthropogeny has sought answers to big questions about where we came from, and what makes us uniquely human

In the summer of 2017, under the brightest stars she’d ever seen, Alison Caldwell sat around a fire singing songs with a small group of fellow UC San Diego graduate students and tribal members of Hadza people, an indigenous hunter-gatherer group in Tanzania.

“That night was a chance for us to all relax and connect in a very deep and human way,” said Caldwell, who earned her Ph.D. from UC San Diego in 2019 and is now a senior science writer in Chicago. “We all sing, dance and celebrate life's joys, whether we're hunter-gatherers in the Rift Valley or graduate students in southern California.”

Part of a recurring, monthlong field course in East Africa, the students spent three days with the Hadza, digging tubers, hunting and learning about their traditions.

The campfire was a long way from the Salk Institute lab where Caldwell was also in the middle of her graduate thesis research, studying how proteins secreted by brain cells called astrocytes influence how neurons develop. But the field course was also a degree requirement, part of an optional specialization track organized by the Center for Academic Research and Training in Anthropogeny (CARTA) to complement Caldwell’s graduate degree in neurosciences. The track is also available through seven other UC San Diego graduate degree programs.

CARTA, a collaboration led by UC San Diego and the Salk Institute, focuses on where humans came from and how we became what we are today. The center, which now includes almost 400 members around the world, started informally in the 1990s (as the Project for Explaining the Origin of Humans) and became an official UC San Diego organized research unit in 2008. CARTA was founded by co-directors Ajit Varki, M.D., of UC San Diego; Rusty Gage, Ph.D., of the Salk Institute; and Margaret Schoeninger, Ph.D., of UC San Diego.

While anthropology, broadly defined, is the study of humanity, anthropogeny focuses specifically on human origins and takes a particularly interdisciplinary look at such topics as bipedalism, stone tool technologies, diet, human development, molecular biology, evolutionary medicine and climate change.

“In short, anthropogeny is concerned with what made us such a strange ape,” said Pascal Gagneux, Ph.D., CARTA associate director and professor of pathology and anthropology at UC San Diego. “It’s both fascinating and humbling that we don’t have answers to some of the most basic questions about ourselves and how we differ from our closest evolutionary cousins, the great apes—questions that even kindergartners ask, like why do we walk on two legs instead of four? Why do we blush? When did we first develop language or use fire?”

Bringing together disparate experts

Varki says CARTA’s major strength is its ability to bring together the world’s leading experts on everything from neuroscience and genomics to archaeology, primatology and linguistics.

2017 CARTA specialization field course group on their last day of the trip to East Africa, during a pre-dawn hike to a cliff to watch the sun rise.

“Without CARTA, most of these experts would primarily be attending conferences in their own specialties—they might never be in the same room, tackling the same questions,” said Varki, who is also Distinguished Professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine. “It can be humbling sometimes to be a world-leading expert in particular field and suddenly find yourself out of your element, learning a new scientific language in order to talk to other world-leading experts—“sequencing,” for example, means something very different to a linguist than a geneticist.”

One of the group’s earliest accomplishments (before they were even called CARTA) was advocating for sequencing of the chimpanzee genome. In 2001, the first human genome sequence was nearly complete and many scientists were already arguing about which organisms should be next, after the mouse.

(Unlike today, each genome cost many millions of dollars to sequence at the time.)

The week of September 11, 2001, Varki and other scientists were in Bethesda, Md., for meetings at the National Institutes of Health when the terror attacks occurred. The airports were closed and the scientists found themselves stranded for several extra days.

Eric Green, M.D., Ph.D., who at the time was very involved in the Human Genome Project and currently leads the National Human Genome Research Institute, took pity on Varki and others and invited them out to dinner. Those discussions eventually led to white papers co-authored by that group and other scientists, which convinced Green and other NIH leaders that after human and mouse, the chimpanzee genome should be sequenced to help answer the many outstanding questions about human origins and evolution, as well as implications for human diseases.

Later, when the chimpanzee genome was being sequenced, there was a problem when it came to naming conventions because humans have one fewer chromosome than chimpanzees—two separate ancestral chromosomes fused together at some point in evolution to form the second largest human chromosome.

UC San Diego graduate students learn about what makes humans different than other great apes during a CARTA specialization track field course trip to East Africa (2017).

“So, there was controversy as to how to align the chimpanzee genome with the human genome in order to best look for similarities and differences,” Varki said. “We needed to get everyone on the same page, and that would have been much more difficult without a group like CARTA. But as with many such later examples, CARTA did not claim credit as an organization. Instead, we simply get transdisciplinary groups of experts together for scientific discussions and ask everyone to ‘check your ego at the door.’”

Shortly thereafter, the Mathers Foundation of New York provided funding for the group to hold a public symposium on the chimpanzee genome. That kicked off what has become a long-running series of public symposia held by CARTA several times each year since 2004. CARTA, with help from University of California Television (UCTV), Salk and the San Diego Supercomputer Center, has live-streamed and video-recorded each talk, long before the COVID-19 pandemic made this commonplace, making the information easily accessible to people all over the world.

“These meetings and symposia not only host expert discussions, but they do it in the presence of graduate students, whose brains are still developing even into their third decade of life—another unique thing about humans,” Gagneux said. Like CARTA itself, participants in the affiliated graduate specialization in anthropogeny represent a broad range of departments across the university from Visual Arts and Linguistics to Biomedical Sciences and Neurosciences. Regardless of a student’s background, Gagneux emphasized that CARTA symposia are “a valuable opportunity for them to ask questions, and meet their scientific heroes.”

Before the pandemic, the in-person symposia could draw up to 800 attendees. Now with more than 40 million views of recorded symposia to date, they’ve clearly proven popular.

“I think so many people attend or watch the symposia because they feature experts on topics every human is interested in for intellectual, scientific, philosophical or religious reasons, or just out of pure curiosity,” Varki said.

Enabling collaborative, comparative research

Dr. Berhane Asfaw from the National Museum of Ethiopia showing UC San Diego graduate students the original fossils of “Ardi” (Ardipithecus ramidus), a four-and-a-half million year old bipedal hominid from Ethiopia that he co-discovered.

In 1984, Varki was a physician-scientist at UC San Diego when he saw a patient have a reaction to horse serum, a therapy still used today for aplastic anemia. He read papers about this “serum sickness,” and discovered that it happens when the patient’s immune system generates antibodies against sugars called sialic acids in the serum. Varki wondered how that could possibly happen since every cell in the human body is already covered with sialic acid.

“That’s when I got interested in what makes humans different, on a molecular level,” Varki said.

It turns out that the chemical structure of human sialic acid differs from the sialic acid produced by most other mammals, including chimpanzees, by just one oxygen atom. In decades of sialic acid research since, Varki, Gagneux and Nissi Varki, M.D., professor of pathology, have discovered that this small difference may help explain many human-chimpanzee differences—for example, why some infectious diseases only affect humans and why people who eat a lot of red meat are at higher risk for cancer while other carnivorous animals are not.

CARTA’s interdisciplinary interactions have also inspired many other collaborative research projects and publications that illustrate human uniqueness. Examples include studies of Hadza microbiomes and dental health; explorations of when humans started standing upright and started running (long-distance running being another thing that humans do that chimpanzees don’t); how random genomic duplications might lead to evolutionary advantages; and how humans might have “self-domesticated” by collectively selecting against certain types of aggression.

To help spur further advancements, CARTA is developing an important resource for the field—the Matrix of Comparative Anthropogeny, a catalog of the many uniquely human features that set us apart from the great apes.

Training the next generation

UC San Diego graduate students like Alison Caldwell who select the anthropogeny specialization track take courses that cover topics ranging from human and primate genetics and evolution to language and cognition. In the elective field course to East Africa, not only do students learn from the Hadza about their way of life, but the Hadza also ask the students about the things that are unusual to them, such as gay marriage and nuclear weapons. The rest of the trip is packed with experiences that include a visit to the museum that houses “Lucy” and “Ardi,” two of the oldest known hominid fossils; safaris to the Ngorogoro Crater and Serengeti to experience African fauna and ecosystems; and talks with primatologists at Gombe National Park, where Jane Goodall famously conducted her chimpanzee research.

Many graduate students take the specialization track and the field course in part because it reminds them why they first became interested in science, and how their own research might fit into the bigger picture of what makes us human.

“What did the specialization track and field course have to do with neuroscience? Maybe it kinda doesn’t…but at same time, I think it does,” Caldwell said in a video she made about the experience. “One thing that’s tough about grad school is that you get deeply involved in your research project, which tends to be focused on a tiny, intricate corner of the field. Programs like CARTA and this field course gave me the opportunity to step back and reflect on why I was doing the work I did, and why I became interested in neuroscience in the first place.

UC San Diego graduate students learn about the daily life of the Hadza people, an indigenous hunter-gatherer group in Tanzania, during a CARTA specialization track field course trip to East Africa (2017).

“Science doesn’t exist in a vacuum. The experiences I have as a person influence the questions I ask, and the ways I try to answer them. So, while I didn’t do any brain research while overseas, I had time to refresh and reset my own brain, and pack it full of some new experiences to incorporate in my life and my work.”

For Gagneux, the field course also helps build valuable connections. For example, CARTA has helped bring awareness and funding to the Greater Mahale Ecosystem Research and Conservation, a group in Western Tanzania run by a UC San Diego alumnus and several Tanzanian biologists.

“It’s one of things I’m proudest of CARTA for—without it, this field project might not exist,” Gagneux said. “And now it’s a well-established wild chimpanzee research site, one of the few located in a savannah woodland ecosystem. Incidentally, the ecosystem is very similar to the one in which ‘Ardi,’ or Ardipithecus ramidus, inhabited in Ethiopia more 4 million years ago. You can go there and follow chimpanzees as they move through the tall grasses. They can’t see over the grass, but we can…another advantage of being bipedal!”

While the COVID-19 pandemic has put the field course on temporary hiatus, Gagneux hopes to return to East Africa in the summer of 2022. In the meantime, since the understanding of where we came from and how we got here is relevant to understanding where we are going as a species, CARTA is turning its attention toward the impact humans have on the planet. Beginning on March 5, CARTA’s next two public symposia will address these critical questions, as experts explore how a single species evolved the capacity to completely alter the surface of an entire planet.