Marveling at the size of the elephants or squealing at the cuteness of the meerkats, visitors come regularly to the Houston Zoo for the chance to observe exotic animals up-close. Meanwhile, just a few blocks away, a laboratory houses a markedly different sort of zoo. Instead of furry and feathered creatures in enclosures, there are thousands of blood samples in a pair of freezers surrounded by dozens of white boards covered by mathematical equations.
This is the DNA Zoo, where a team of thirty-plus scientists use cutting-edge genomic technology in service of boosting the survival chances for countless endangered species—work that could contribute to human health as well. The lab has acquired genetic samples of 4,234 animals representing 1,105 species, largely obtained from zoos and parks including the Houston Zoo, San Antonio Zoo, Sea World, and the Texas State Aquarium. In 2019, they opened a counterpart lab in Australia to focus on species unique to that continent.
“Humans are essentially one of nature’s experiments,” says Erez Lieberman Aiden, founder of the Aiden Lab at the Center for Genome Architecture at Baylor College of Medicine, which runs the DNA Zoo. “Nature has performed many, many, many experiments, and we can learn from the experiments that nature has performed on other species.”
Over the course of five years, beginning in 2011, Aiden and his team developed technology that allows them to sequence DNA in days, instead of the usual weeks, and at a cost of hundreds of dollars, rather than hundreds of thousands.
It took thirteen years to sequence the human genome and another four years for the corn genome, “but you ended up with a similar quality of work to what the DNA Zoo is doing now in a matter of days,” says Blake Hanson, an associate director of microbial genomics at the University of Texas Health Science Center in Houston.
Aiden, who built a scale model of DNA for a science fair in high school, remembers becoming truly fascinated during graduate school—he holds doctorates from Harvard and MIT—with how a DNA strand as long as six feet could fold inside a single cell. His studies led to genome mapping technology he dubbed Hi-C (after the fruity drink, a favorite of his) and Juicebox, software that facilitates the three-dimensional assembly of a DNA strand.
Genome sequencing requires disassembling and reassembling strands of DNA in order to fully understand how each of those segments relate to one another. Some segments—known as repeats or regions of low complexity—are nearly impossible to distinguish from others. “If you have a jigsaw puzzle that’s like pure black, it becomes really hard because a piece can go anywhere,” Aiden says. The algorithms built into Hi-C and Juicebox allow his team to solve that puzzle by ferreting out subtle patterns in the DNA that are otherwise extremely difficult to detect.
The DNA Zoo’s work assists zoos and other wildlife parks in their conservation efforts. For instance, Aiden’s team has sequenced the genes of all the elephants at the Houston Zoo, which helps in determining which of the animals should be bred with one another to keep the gene pool diverse, preventing the animals that mate from being too closely related. “The DNA Zoo won’t be the only piece we need to preserve the genomes of these animals to push forward the idea of conservation, but it is a huge piece in that puzzle,” Hanson says.
Furthermore, by making its collection of sequenced genomes publicly available, the DNA Zoo provides vital data to researchers looking to combat diseases, both in animals and humans. In 2015, Aiden and his team helped scientists map the DNA of the mosquito species that carried the Zika virus, an epidemic at the time. Aiden is enthusiastic in his explanation of how genomic technology is already changing the face of health care. “It’s literally a very straight line from the release of the genome of the SARS-CoV-2 virus to the vaccine,” he says of how similar knowledge has been deployed by others in the COVID-19 pandemic.
The DNA Zoo is hardly the first program to sample and store animal blood for scientific study. The Cryo-Zoo at the MD Anderson Cancer Center, which collaborates with the DNA Zoo, was founded by biologist T.C. Hsu in the 1970s. Hsu was a pioneer in studying animal chromosomes and collected them from thousands of species. Forty years ago, most zoos were much smaller and less involved in conservation efforts than they are today. As a result, many animal samples had to be acquired in the wild, which could be rather difficult.
“They would go places, like classical adventure-type stories,” says Olga Dudchenko, co-founder of the DNA Zoo. “Somebody would get stranded on a boat for several days without water and food trying to get some cells from some rodent in South Africa.”
Even today, it’s not always as simple as drawing blood from animals at zoos. Scientists sometimes have to get creative. In the case of the southern right whale—so named because whalers considered it a good target (i.e. the “right” whale to hunt), nearly hunting it to extinction in the twentieth century—there are none in captivity. So how do you get a DNA sample from a sixty-foot, ninety-ton animal swimming through the ocean? Out of the blowhole. Just as humans expel DNA when we sneeze, whales expel it when they breathe, and that can be collected by nearby scientists.
The highly technical efforts of the DNA Zoo are sometimes difficult to explain to the layperson, so the lab has employed more down-to-earth approaches in reaching out to both the scientific community and the world at large. Lab members write regular blog posts about the new sequences they have completed, which contain the complex language of scientists, but also fun facts about the species. A typical post, in February, featured an adorable photo of a mouse. “Weighing about as much as six paper clips,” the text explained, “the endangered Pacific pocket mouse (PPM) aka Perognathus longimembris pacificus is the among the smallest rodents in the world.”
The DNA Zoo has even produced a comic strip called ChromoGnomes, drawn by Adam Fotos, a comic book artist in Chicago. It tells of a pair of gnomes attempting to create various animals from their genetic code with varying degrees of success. The lab hopes it will make what they do more accessible to those without advanced degrees in biology and computer science.
“Similar to what we do with blog posts, we can do this in a more fun and visual way,” Dudchenko says. So far, they’ve only published four installments of the strip, though more are promised. “It turns out that writing comics is more difficult right now for us then creating genome assemblies.”
Fortunately, the Aiden team appears quite skilled at assembling DNA sequences. They convey excitement about where it all might lead, perhaps even into the realm of what sounds like science fiction. “The ultimate goal is that if we read through the genomes really, really well, and probably in a few years, we’ll be able to not just read but also generate DNA,” Dudchenko says. “In theory, you can re-create just from the seed, re-create species just from the sequence.”
This notion conjures images from Jurassic Park, the Michael Crichton novel that envisioned a world where dinosaurs could be replicated from the DNA of long-dead mosquitoes trapped in amber. It might someday not be quite as far-fetched as when the book came out.
Recently, in fact, a group of scientists who are collaborators with the DNA Zoo set a record by reading the DNA from a sample that was estimated to be a million years old. “It’s not like we would say no to Jurassic Park-level DNA,” Dudchenko says. “It’s too juicy a topic.”