He won ski races around the world—and rigorous training was only one reason why

The Takeaway:  Many elite athletes are born with traits that help them excel in their sports. In the future, CRISPR might be able to recreate those traits—but at what cost?

Cross country skier Eero Antero Mäntyranta became a legend in the 1960s in his homeland Finland when he won his first Olympic gold medal at the 1960 Games in Squaw Valley, Calif. (now Palisades Tahoe) in the 4 x 10 km relay race. In the 1964 Olympics in Innsbruck, Austria, he won two additional gold medals in the 10 km and 30 km races and a silver medal as the anchor in the 4 x 10 km relay race. His success continued in the 1968 Games in Grenoble, France, where he took the silver medal in the 15 km race and a bronze in the 30 km race. His team edged out the Soviet team to win the bronze medal, adding a seventh medal to Mäntyranta’s collection.

Unfortunately, accusations of drug use followed him. The fact that Eero did not look physically impressive despite his achievements may have played a role in the rumors. Yet he maintained his innocence and steadfast in his claim that his success was not due to illicit substances but because of his arduous training. Moreover, blood tests failed to detect any doping reagents in his circulation. However, the same blood tests uncovered something unusual about him: Eero had 15% more red blood cells (RBCs) than most males his age. The extra red blood cells carried additional oxygen to his muscles, providing him more energy and endurance in races. But why his blood contained more than the usual number of red blood cells remained a mystery for almost three decades.

High red blood cell count and EPOR mutation boost athlete performance—could CRISPR replace evolutionary benefits?

Eero’s mystery was solved by Albert de la Chapelle and his research team. de la Chapelle was a Finnish physician-scientist and human geneticist who led Finland’s first Department of Medical Genetics at the University of Helsinki and later served as the professor of cancer genetics at The Ohio State University. He and his team discovered a mutation in one of Eero’s genes called EPOR, which stands for erythropoietin receptor. The binding of the hormone erythropoietin to EPOR stimulates the production of new red blood cells. Eero’s mutation created a truncated region in the EPOR gene that is responsible for downregulation of the EPOR signaling. As a result, his hematopoietic stem cells became hyper-sensitive to EPO-producing more red blood cells, which increased oxygen-carrying capacity.

Interestingly, the same biological pathway is triggered for endurance athletes purposefully training at high altitudes, where the oxygen level is lower than sea level. Our bodies naturally produce extra red blood cells in low oxygen environments as compensation. EPO has been used as a performance enhancer by athletes, but it was banned in the early 1990s and that ban has been enforced since the 2000 Olympics.

This discovery, while clearing Eero’s name from the doping allegations, raises a fundamental question. As we enter the new era of rewriting the script of our DNA with the revolutionary CRISPR technology, should we use it for enhancement? Imagine a future where the genetic lottery is no longer left to chance, where traits like Eero’s could be engineered, not inherited. CRISPR technology offers us the ability to edit our genome with unprecedented precision like the scalpel of a skilled surgeon. We witnessed a historic event in December 2023 when the very first CRISPR-mediates genome engineering was approved in Europe and in the US for the treatment of sickle cell disease, a debilitating blood disorder affecting millions around the world. This was a first, but several other CRISPR-based therapies are currently in development. Thus, unlike Eero whose mutation was by nature, we now face the prospect of making these decisions ourselves.

Understanding the ‘Mäntyranta variant’

Eero’s mutation was the subject of a recent study in which researchers used CRISPR-Cas9 to recreate Eero’s mutation causing a truncation in the erythropoietin receptor and studied the effect of genotype variations on red blood cell development. They then combined the truncated EPOR (tEPOR) with a correction strategy developed for beta thalassemia and showed how combining the two genome editing events gave red blood cells a significant selective advantage, in the process demonstrating the potential of combining human genetics and genome editing to produce safer and more effective genome editing therapies for patients with genetic diseases.

“While insights from clinical genetics have typically implicated novel genes and pathways in disease, here we sought to use human genetics to develop novel strategies to treat disease.” the authors wrote. “While many efforts are underway to improve editing and engraftment frequencies, we hypothesized that we could develop a strategy to increase production of the clinically relevant cell type—the red blood cell—from edited hematopoietic stem and progenitor cells (HSPCs). If successful, then lower editing and engraftment frequencies could yield sufficient production of RBCs to achieve therapeutic benefit, and thus be curative for patients.”

CRISPR genome editing and ethical concerns

The case of Eero Mäntyranta is an interesting story and part of a larger debate that CRISPR genome editing poses. It prompts us to consider whether we should actively seek to replicate such anomalies. Where do we draw the line between therapeutic use and enhancement? More crucially, who decides what constitutes an enhancement?

Jennifer Doudna, pioneering biochemist and Nobel Prize winner for discovering CRISPR technology along with Emmanuelle Charpentier, has been a vocal advocate for ethical and responsible development and use of CRISPR technology. “Imagine that we could try to engineer humans that have enhanced properties, such as stronger bones, or less susceptibility to cardiovascular disease or even to have properties that we would consider maybe to be desirable, like a different eye color or to be taller, things like that—designer humans—if you will,” said Doudna in an influential TED talk watched by millions and sparked a global debate about CRISPR’s potential and ethical considerations. “This raises a number of ethical questions that we have to carefully consider” said Doudna. “This is why I and my colleagues have called for a global pause in any clinical application of the CRISPR technology in human embryos, to give us time to really consider all of the various implications of doing so.”

As we grapple with questions around gene editing and gene editing ethics, it is important to engage in a global dialogue, including the scientific community, ethicists, regulatory bodies, policymakers, and the public. The decisions we make today will shape the future of our species, especially when genome editing applications start involving germline.

What role IDT plays

As a leader in providing CRISPR genome editing solutions to researchers, IDT boasts a complete workflow solution. IDT’s Alt-R™ CRISPR Systems were developed through comprehensive research on each component of the CRISPR-driven technology that generates a double-stranded break critical for gene disruption and DNA insertion by homologous recombination. IDT’s CRISPR tools for research include:

• Alt-R CRISPR Cas-9 System
• Alt-R CRISPR-Cas12a (Cpf1) System
• Alt-R CRISPR Custom Guide RNAs
• cGMP gRNA Manufacturing
• rhAmpSeq™ CRISPR Analysis System and more

About the Author

Bahri Karacay, PhD, serves as the Senior Manager of Product Marketing for Gene Writing and Editing products. He is also an accomplished author with two bestsellers, "The Secret of Life DNA" and "Happy Brain" (both in Turkish) and more than hundred scientific publications. When he's not at work, Bahri enjoys practicing music and performing with his band TURKANA.