The Alternate View
“Mitochondrial Doping” is Coming to Sports
by John G. Cramer
Competitive sports are already grappling with complex “doping” problems. If generic mitochondrial transplantation (see AV 233 in the Nov/Dec 2024 Analog) soon becomes a standard treatment widely used in hospital emergency rooms, its spillover effects in competitive sports may be far-reaching and profound. It will probably impact everything from levels of athletic performance to anti-doping regulations and detection methods. It may perturb the essential definition of just what “natural” athletic ability is.
Here’s my vision of what is to come. Dr. James McCully is a pioneering mitochondrial researcher at Boston Children’s Hospital, who participated in the first successful human mitochondrial transplantation to the heart of a dying baby girl. He recently reported that, due to news articles about his groundbreaking work with mitochondria, he has already been approached by athletes seeking mitochondrial infusions to boost their performance levels. Today, such mitochondrial therapy is very preliminary and experimental, but Dr. McCully says “It seems to have worked in every organ we’ve looked at.”
Amateur sports, including college and Olympic-class competitions, already have in place very strict anti-doping regulations and have created an agency to enforce them. On the other hand, professional sports make their own rules, which presently are rather more lenient than those that apply to amateur competitions. For example, the National Football League (NFL) presently imposes a 4-game suspension on any offending player for a first-offense doping violation involving banned stimulants or steroids. In contrast, an amateur athlete can be banned from their sport for two years for exactly the same violation. The professional leagues often focus on “drugging” substances relevant to their sport, and they often allow therapeutic use exemptions for medical substances, particularly those that are widely used in treating sports related injuries.
The World Anti-Doping Agency (WADA), which enforces anti-doping rules for amateur sports, has already put in place a framework that might classify mitochondrial transplantation as a prohibited method. The WADA Prohibited List includes “Gene and cell doping” (Category M3), which specifically bans the non-therapeutic use of cells, genes, genetic elements, or the modulation of gene expression to enhance performance. A court of law would probably have to decide if increasing one’s own mitochondria, which are not precisely a cell, a gene, a genetic element, or a gene expression modifier, would be banned under this prohibition. Therefore, it might or might not fall under this category and be prohibited.
Should mitochondrial transplantation be prohibited? By infusing healthy mitochondria into an athlete’s bloodstream or injecting them into specific sites (e.g., arm or leg muscles), it is expected that an athlete might significantly boost his or her strength and aerobic capacity, might delay the onset of fatigue, and might speed up the recovery time after tiring exertion. All of these improvements are highly sought-after advantages in competitive endurance-based and power-based sports. Thus, considering its likely effects, the mitochondrial transplant procedure might be considered to be a form of “cellular doping” that manipulates and enhances the body’s fundamental energy systems to obtain a huge competitive edge.
Assuming that mitochondrial transplantation was prohibited, one of the most significant challenges for anti-doping authorities would be enforcing the ban. They would have to establish valid testing that could unambiguously prove that mitochondrial transplantation had actually been done. This would be particularly difficult, if the athlete’s own (autologous) mitochondria were used in the transplantation process.
The transplant process begins by obtaining stem cells to be amplified in quantity. If the stem cells used in the production of mitochondria were taken from an athlete’s own body (e.g., muscle tissue, blood cells, bone marrow, . . .), amplified in a bioreactor, and then the extracted mitochondria were coated to suppress immune response and infused into the athlete’s bloodstream, there would be no foreign genetic material that could be detected.
The athlete’s average mitochondrial DNA copy number might be significantly increased. That is measurable, in principle, by using the new droplet digital PCR technique. However, establishing a baseline for that indicator and using it to conclusively prove that there had been illicit enhancement would be quite challenging.
Otherwise, there appears to be no testable indications that a mitochondrial transplant had ever taken place. Standard sports doping tests, which often look for synthetic substances or their metabolites, would be completely ineffective. Detecting such a subtle biological enhancement might be effectively impossible, or at best would require a new generation of sophisticated and potentially invasive testing methods, possibly involving repeating time-dependent short-cycle monitoring of an athlete’s biological status to look for subtle changes with time in cellular markers or metabolic byproducts.
Alternatively, transplanted mitochondria might have come from the stem cells of a random or selected donor, perhaps because these were more readily available for immediate use, for example from a hospital emergency department’s supply of “banked” generic mitochondria. Such transplantation would, in principle, produce a detectable condition. Mitochondria have their own DNA, a small ring of 16,569 base pairs that can be readily sequenced and its structure recorded. The sequencing of an athlete’s mitochondrial DNA after a donor-based transplant would be likely to show the presence of two distinctly different mitochondrial DNA haplogroups (inherited mutation patterns). To avoid such detection, determined athletes and their supporting team physicians might choose mitochondria with matching top levels or seek out a donor with a matching mitochondrial DNA haplotype, e.g., from a maternal-line relative, to minimize the chances of such detection.
We note that any detection of such a haplogroup mismatch is not likely to be accomplished rapidly. Mitochondrial DNA genetic analysis, currently available from genetic genealogy firms for a few hundred dollars, involves PCR amplification followed by full nanopore sequencing or biochip analysis. This process normally requires several weeks. Further, athletes whose parents had used (or can claim to have used) in vitro fertilization involving donor mitochondria to avoid genetic disease might already have two haplotypes of mitochondrial DNA in their systems and would certainly test positive. However, such a result would have nothing to do with any performance-enhancing doping. Thus, this mitochondrial doping scenario sets the stage for a new technological “arms race” between those seeking an illicit advantage in sports and the anti-doping establishment. This competition should push the boundaries of scientific detection and forensic analysis.
Thus, the expected widespread availability of mitochondrial transplantation in emergency medicine in a few years should create a significant ethical gray area in sports. An athlete who suffers a legitimate injury, e.g., a severe muscle tear or a brain concussion, might need to receive mitochondrial transplantation as standard medical treatment. This therapeutic intervention could, as a side effect, greatly enhance their baseline athletic capabilities upon their return to competition.
This scenario raises critical questions for anti-doping authorities:
How can a legitimate therapeutic use of mitochondrial transplantation be distinguished from a deliberate attempt to enhance performance?
Would athletes who received mitochondrial transplantation for a valid medical reason have an unfair advantage over their competitors?
Should there be a “stand-down” period after mitochondrial transplantation before an athlete can return to competition? If so, for how long?
The existing practice in sports has been to provide a Therapeutic Use Exemption that allows athletes to use certain prohibited substances for necessary medical reasons. This will become an incredibly complex territory to navigate.
A common occurrence in major professional sports these days is the aging “superstar” player who could greatly benefit professionally and financially from squeezing in just one more successful playing season. The advent of mitochondrial transplantation could profoundly reshape the landscape of the aging star players of major professional sports. For the senior superstars of the NFL, MLB, NHL, NBA, and international soccer, mitochondrial transplantation represents more than just a theoretical advantage. It offers the tantalizing prospect of extending their prime performance and high salary, rewriting the record books, and dramatically altering the economic and ethical fabric of their leagues.
So ultimately, the arrival of mitochondrial transplantation in the world of professional sports is very likely to be a matter of “when,” not “if.” It represents the next frontier in the ongoing competition between natural human ability and technological intervention. For injured players it offers fast recovery. For aging superstars, it promises a second wind, a chance to defy Father Time and Mother Nature. One can imagine the aging star quarterback employing his own longevity-medicine technical staff, who would set up a private bioreactor lab that operated secretly and continuously to amplify his own stem cells to supply his own mitochondria for his clandestine monthly mitochondrial transplant infusions, all at a net cost that was a rather small fraction of his large annual salary.
For the professional leagues that pay and play these star athletes, this promises to trigger a cascade of regulatory, ethical, and existential challenges that would force them to decide which option they value most: (1) the sanctity of their athletic records or (2) the spectacle of their greatest stars shining brighter and longer. The professional leagues all make their own rules, which have been known to bend with the wind of economic pressure. In the long run, spectacle and ticket sales and rising profits seem likely to prevail over ethics and records.
The potential for mitochondrial doping strikes at the heart of the “spirit of sport,” a core principle of the World Anti-Doping Code that emphasizes fair play, honesty, and the pursuit of human excellence without the aid of artificial enhancements in amateur sports.
The inevitable introduction of a technology that can fundamentally alter an athlete’s cellular physiology raises profound questions about the future of competitive sports. If success becomes increasingly dependent on access to cutting-edge and very expensive medical technologies, it could create a two-tiered system of “haves” and “have-nots,” in which financial resources rather than natural talent and dedication become a primary determinant of victory.
Thus, while mitochondrial transplantation holds immense promise for the field of medicine and particularly for longevity extension, its potential for becoming a standard emergency room procedure will cast a long shadow over the world of competitive sports. It will force a comprehensive re-evaluation of anti-doping strategies, ignite complex ethical debates, and potentially redefine what it means to be a twenty-first-century athlete.
Will sports governing bodies proactively address this emerging technology, or will aggressive sports teams “jump the gun” and buy into mitochondrial performance enhancement before it can be banned? Watch this column for further developments. n
References:
Mitochondrial transplantation: See https://mitrix.bio/; Mitrix Bio Inc., 4695 Chabot Dr. Suite 200, Pleasanton, CA 94588.
- Whipple, “Is mitochondrial therapy the next sports doping scandal?”, The Times (London) February 15 (2025).
- Geissler, “Athletes may be cheating with new ‘undetectable’ method, experts warn. The technique has been used to treat heart conditions and boost muscle function.,” Daily Express (London) Feb 14 (2025).
Hard SF Novels: John’s new hard SF novel, Fermi’s Question, and its prequel, his second hard SF novel Einstein’s Bridge, are available as eBooks from Baen Books at: https://www.baen.com/einstein-s-bridge.html.
His first hard SF novel Twistor is available online at: https://www.amazon.com/Twistor-John-Cramer/dp/048680450X.
Nonfiction QM Book: John’s 2016 nonfiction book describing his transactional interpretation of quantum mechanics, The Quantum Handshake—Entanglement, Nonlocality, and Transactions, (Springer, January 2016) is available online as a hardcover or eBook at: https://www.amazon.com/dp/3319246402.
Alternate View Columns Online: Electronic reprints of 236 or more of “The Alternate View” columns written by John G. Cramer and previously published in Analog are currently available online at: http://www.npl.washington.edu/av.