The Hamilton Spectator

Elephant Stem Cells Created in the Lab

- By CARL ZIMMER

When the biotech firm Colossal started in 2021, it set a goal: to geneticall­y engineer elephants with hair found on extinct woolly mammoths.

Three years later, researcher­s with the company have now reported that they have created elephant stem cells that could be developed into any tissue in the body.

Eriona Hysolli, the head of biological sciences at Colossal, said the company’s work could lead to creating elephant eggs for breeding programs.

The method is known as induced pluripoten­t stem cells, or iPSCs. Vincent Lynch, a biologist at the University at Buffalo in New York State who was not involved in the research, said iPSCs could help scientists learn why elephants so rarely develop cancer.

George Church, a biologist at Harvard Medical School, reasoned that if he could alter an elephant embryo’s DNA, it would develop traits that allowed woolly mammoths to survive in cold climates.

Dr. Church, who was working with Dr. Hysolli’s team, struggled with a limited supply of elephant cells. So they set out to make their own supply. The Japanese biologist Shinya Yamanaka had figured out how to turn back the clock in adult mouse cells so that they were like the cells in an embryo. With the right combinatio­n of chemicals, these iPSCs could then develop into many different tissues, even eggs.

But elephant cells are harder to reprogram. Dr. Lynch suspected that the trouble had to do with the fact that elephants rarely get cancer. Elephants have evolved a number of extra defenses against cancer.

All mammals carry a gene for the protein called TP53, which causes a cell to self-destruct if it starts showing signs of uncontroll­ed growth. Elephants have 29 genes for TP53, which may kill cancerous cells.

These anticancer adaptation­s may have been what stopped adult elephant cells from being reprogramm­ed into iPSCs. The changes happening in the cell may resemble the first steps toward cancer, causing the cells to self-destruct.

Dr. Church’s team obtained fresh supplies of cells from Asian elephants, which are endangered. They were able to extract tissue samples of the umbilical cords of baby elephants. The researcher­s then created molecules to block the production of all p53 proteins in the cells. They succeeded in making elephant iPSCs, and coaxed these cells to grow into an embryolike cluster of cells.

Dr. Hysolli and her colleagues plan to change genes in the stem cells from elephant sequences to woolly mammoth sequences, which may lead to changes in the cells.

Dr. Lynch is skeptical about the company’s ultimate goal.

“We know almost nothing about the genetics of complex behavior,” Dr. Lynch said. “So do we end up with a hairy Asian elephant that doesn’t know how to survive in the Arctic?”

 ?? VIA COLOSSAL BIOSCIENCE­S ?? Scientists hope to use elephant stem cells to study some of the traits that were used by mammoths to survive in cold climates. Far left, a micrograph of elephant stem cells. The blue dots are DNA.
VIA COLOSSAL BIOSCIENCE­S Scientists hope to use elephant stem cells to study some of the traits that were used by mammoths to survive in cold climates. Far left, a micrograph of elephant stem cells. The blue dots are DNA.
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