In a loudly bubbling laboratory at Brigham and Women’s Hospital in Boston, about 2,800 of the salamanders called axolotls drift in tanks and cups, filling floor-to-ceiling shelves. Up close, axolotls are just on the cute side of alien. They have fleshy pink bodies and guileless, wall-eyed faces. Unlike most salamanders, which metamorphose into land-dwellers as they grow up, axolotls usually keep their youthful aquatic form for their whole lives. They wear their gills on the outside, a set of three feathery horns on each side of the head. Their four-fingered hands with black nails are delicate and vaguely human — but perhaps it’s best not to dwell on that, given the work that goes on here.

One of the animals in view is missing a limb that was amputated 11 days earlier. The stump has a reddish bull’s-eye visible at its center. It’s the bud of a new arm.

Salamanders are champions at regenerating lost body parts. A flatworm called a planarian can grow back its entire body from a speck of tissue, but it is a very small, simple creature. Zebra fish can regrow their tails throughout their lives. Humans, along with other mammals, can regenerate lost limb buds as embryos. As young children, we can regrow our fingertips; mice can still do this as adults. But salamanders stand out as the only vertebrates that can replace complex body parts that are lost at any age, which is why researchers seeking answers about regeneration have so often turned to them.

While researchers studying animals like mice and flies progressed into the genomic age, however, those working on axolotls were left behind. One obstacle was that axolotls live longer and mature more slowly than most lab animals, which makes them cumbersome subjects for genetics experiments. Worse, the axolotl’s enormous and repetitive genome stubbornly resisted sequencing.

Then a European research team overcame the hurdles and finally published a full genetic sequence for the laboratory axolotl earlier this year. That accomplishment could change everything.

“The genome was a huge problem that had been lingering over the heads of everyone working in axolotl,” said Jessica Whited, the assistant professor and researcher who supervises this laboratory at Harvard Medical School and Brigham and Women’s Hospital. Now that she and other researchers have the whole axolotl genome, they’re hoping to unlock secrets of regeneration and perhaps even to learn how humans could harness this power for ourselves. But they still have more questions than answers, and some of those questions have persisted since the first documented observation of these animals’ strange talent more than 250 years ago.

The Italian Priest and the Mexican Salamanders

The simplicity of the Italian priest’s diagrams belied the miraculousness of what he had seen. Lazzaro Spallanzani’s first sketch resembled three sides of a square, like a little table in profile; it was the stump of a salamander’s severed tail. The next showed a triangle sitting atop that table; the tail was somehow regrowing.

Spallanzani had been experimenting on salamanders, tadpoles, snails and earthworms and found that they could regenerate lost body parts. He shared that discovery and his drawings in a letter to the naturalist Charles Bonnet in 1766. Two years later, Spallanzani published his observations more widely in a brief collection of essays on reproduction and regeneration. The title of that 1768 collection, the Prodromo (meaning “an early indication”), hinted that a longer work on the subject would follow from him — but it never did.

Other scientists did take up those investigations, however, and researchers’ salamander of choice became the axolotl. Its scientific name is Ambystoma mexicanum; its common name rhymes with “packs a bottle.” Axolotls lent themselves well to study in part because they breed and survive so well in captivity. Warren Vieira, a postdoc in Catherine McCusker’s regeneration lab at the University of Massachusetts Boston, told me that axolotls sometimes wag their flat, eellike tails when a person comes into the room. Researchers who care for the animals generally agree that axolotls are inquisitive and alert to the presence of humans, who might be bringing food, although in general the axolotls are not too bright.

They are extremely inbred, after all. Most of the world’s laboratory axolotls are descended from 34 animals that came to Paris from Mexico in the 1860s. (Most wild axolotls are a mottled mud color rather than pale pink, but the lab animals are not albinos — true albino axolotls are yellowish, with golden eyes rather than black.) Since those animals were removed, their native waterways around Mexico City have been polluted, invaded by introduced species that altered the ecosystem and dramatically depleted by urbanization. Axolotls are also a traditional food for locals. Ironically, for animals that can survive so many horrible injuries, axolotls haven’t been able to withstand these combined assaults and are now nearly extinct in the wild. But the laboratory population has thrived.

In 1935, some of those European axolotls came back to North America and eventually became a collection at Indiana University under the direction of the biologist George Malacinski. When he retired in 2005, the University of Kentucky inherited his colony of 500 or so animals. Malacinski “just loaded them all up and drove them down one night,” said Randal Voss, who now directs the university’s Ambystoma Genetic Stock Center. Although the drive lasted only about three hours, the stress made some of the salamanders metamorphose. “Maybe 10 percent or so decided they didn’t want to be aquatic anymore because of the ride from Indianapolis,” Voss said.