mRNA

[TrekCyclist]

This year's Noble Prize in medicine was awarded to mRNA research. Of course, strogly related to the development of Covid-19 vaccines.
But what about mRNA Doping in sports?
There has been some general rumors from time to time. Together with some rough ideas, how that could work (e.g. to make the body increase erythropoetin production or improve the lactate breakdown).
But has there been any evidence or more substantial rumors, that mRNA doping is used in sports today?

 

[Sciatic]

This year's Noble Prize in medicine was awarded to mRNA research. Of course, strogly related to the development of Covid-19 vaccines.
But what about mRNA Doping in sports?
There has been some general rumors from time to time. Together with some rough ideas, how that could work (e.g. to make the body increase erythropoetin production or improve the lactate breakdown).
But has there been any evidence or more substantial rumors, that mRNA doping is used in sports today?

We can probably assume scientists are working on mRNA manipulation to increase healthy red blood cell production. There are many other severe anemia diseases that involve the red-blood making process, so there are probably coming development there. The problem is this, from an article describing their Nobel prize work:

“Cutting-edge experimental therapies for sickle cell are on the horizon, but they require patients’ own bone marrow cells to be removed, modified in a specialized laboratory and returned to them, a laborious and expensive process that isn’t practical to be administered in countries without vast medical resources.”

 

[Sciatic]

This year's Noble Prize in medicine was awarded to mRNA research. Of course, strogly related to the development of Covid-19 vaccines.
But what about mRNA Doping in sports?
There has been some general rumors from time to time. Together with some rough ideas, how that could work (e.g. to make the body increase erythropoetin production or improve the lactate breakdown).
But has there been any evidence or more substantial rumors, that mRNA doping is used in sports today?

You mentioned increasing erythropoetin production, which happens in the kidneys. I’m pretty darn sure there are no gene doping processes available (as a process dopers could adopt) at that end yet. I say that because folks who have severe anemia—the kind that must be treated— have only the same options as pro cyclists: taking EPO (and variants) or blood transfusions.

 

[Cookster15]

You mentioned increasing erythropoetin production, which happens in the kidneys. I’m pretty darn sure there are no gene doping processes available (as a process dopers could adopt) at that end yet. I say that because folks who have severe anemia—the kind that must be treated— have only the same options as pro cyclists: taking EPO (and variants) or blood transfusions.

And, if you are right, thank goodness for that. At least we know the likes of JV are unlikely to have utilized gene doping.

But I still think gene doping, should it be employed, has the potential to be caught by the biological passport.

 

[hrotha]

Isn't gene doping more of a theoretical thing that has never actually been documented? Since I can remember, the talk about gene doping has always been about a vague threat in the foreseeable future, like "if someone figures out how to do this all bets are off and there's no turning back", never anything more substantial than that. The rumours have always been more like "welp, I have no idea how to explain this, must be gene doping" where you could effectively replace "gene doping" with "the divine favour of Phoebus Apollo" and it would serve the exact same purpose.

I don't mean mRNA and gene doping in general shouldn't be kept in mind and protected against, just that the talk about them often gets way more specific than it has any right getting. We simply don't know.

It would be kinda funny if mRNA doping became the next big thing and Djokovič or whoever wouldn't touch it because of some antivaxxer crap though.

 

[Red Rick]

Isn't gene doping more of a theoretical thing that has never actually been documented? Since I can remember, the talk about gene doping has always been about a vague threat in the foreseeable future, like "if someone figures out how to do this all bets are off and there's no turning back", never anything more substantial than that. The rumours have always been more like "welp, I have no idea how to explain this, must be gene doping" where you could effectively replace "gene doping" with "the divine favour of Phoebus Apollo" and it would serve the exact same purpose.

I don't mean mRNA and gene doping in general shouldn't be kept in mind and protected against, just that the talk about them often gets way more specific than it has any right getting. We simply don't know.

It would be kinda funny if mRNA doping became the next big thing and Djokovič or whoever wouldn't touch it because of some antivaxxer crap though.

If current gene editing were so brilliant we'd see a lot more miracle cures for diseases I reckon unless it's so tunable you can literally black market and speedrun it perfectly while actual treatments take their years for FDA approval and stuff.

 

[fmk_RoI]

As I recall from when this was the Big Bad Bogeyman a few years ago - it usually ties in with the Olympic cycle, so we missed it in 2020-21 - one of the problems with this notion is the ability to turn off what you've turned on. You could theoretically turn on a gene to produce EPO but if you can't turn that gene off, the subject will probably die.

If such a gene edit had been fixed in the years since this story was last around, the dialysis industry would have probably collapsed.

 

[Netserk]

Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic ...

www.ncbi.nlm.nih.gov

However, it is important to note that gene therapy is still an emerging field and is not yet widely available for clinical use. Clinical trials are currently underway to evaluate the safety and efficacy of gene therapy with respect to various genetic conditions, including EPO deficiency caused by mutations in the EPO gene.

 

[Cookster15]

If current gene editing were so brilliant we'd see a lot more miracle cures for diseases I reckon unless it's so tunable you can literally black market and speedrun it perfectly while actual treatments take their years for FDA approval and stuff.

This is an excellent point. I guess per Netserk's linked paper "designer" genes are a work in progress. Relevant to cycling, the researchers are zeroing in on genetically boosting the EPO genes. I'd say it will take many years to perfect the research regardless of the black market.

But the way I figure any genetic doping would still risk an adverse finding under the Bio passport. The only way to circumvent would be to gene dope at the time they measured your baseline as a neo pro or young rider (to boost the baseline).

Bio passport irregularities . Dopeology

Product identification page for Bio passport irregularities (Programme) on Dopeology.org

www.dopeology.org

 

[proffate]

This is an excellent point. I guess per Netserk's linked paper "designer" genes are a work in progress. Relevant to cycling, the researchers are zeroing in on genetically boosting the EPO genes. I'd say it will take many years to perfect the research regardless of the black market.

But the way I figure any genetic doping would still risk an adverse finding under the Bio passport. The only way to circumvent would be to gene dope at the time they measured your baseline as a neo pro or young rider (to boost the baseline).

Bio passport irregularities . Dopeology

Product identification page for Bio passport irregularities (Programme) on Dopeology.org

www.dopeology.org

That is the promise of the bio passport, but does it actually work as well as that?

 

[Red Rick]

mRNA for EPO upregulation is pointless, if it doesn't violate the BP you can do it with normal methods anyway. The best candidate usage I can think of is probably upregulating the development of mitochondria.

 

[fmk_RoI]

The best candidate usage I can think of is probably upregulating the development of mitochondria.

Genetically modified Jedi. Crikey.

 

[Krzysztof_O]

mRNA for EPO upregulation is pointless, if it doesn't violate the BP you can do it with normal methods anyway. The best candidate usage I can think of is probably upregulating the development of mitochondria.

Yup, metabolism & muscles structure are candidates for some manipulation.

 

[Sciatic]

EPO, whether our native EPO or injected, initiates red blood cell development in bone marrow. It’s like Step 1 in the erythropoiesis (red blood cell production) process. As RR indicated, there’s not much point to gene manipulation there b/c it’s easy to reach 50 HCT just thru EPO or blood bags. There’s a fairly new med, luspatercept, that assists RBC development at the other end of the growth process, by keeping the cells that are produced healthier. Perhaps that could be a potential place for gene editing if it’s possible to make each red blood cell more efficient & healthier, if that could work without raising hematocrit. Seems like a lot of work for not a huge jump in oxygen carting capacity.

I think the 1st gene doping project should be one that builds stronger collarbones

 

[Netserk]

I don't think the passport is the only binding constraint on the use of EPO currently. So the equivalence of a new long-acting and undetectable drug would probably be of use.

 

[Unchained]

I will probably spend lots of time thinking and daydreaming about what athletes, including some of my historical favorites that I would want as part of my gene splicing recipe. There were stories about wattage outputs from Cancellara, non existing resting heart rate of Miguel Indurain..
and tons of others w qualities I would want.. but don't you need a baseline to understand bike racer makeup? Is it just something? VO2 max or a muscle tissue composition? This all sounds like you can make something in a lab that won't work on the road, and it sounds a little too science fiction for a racer..won't say a name, but let's say for a fake name Julian.. and this fictional racer kept coming up a tiny bit short.. they would do a gene modification on an adult and the results would be immediate enough to change let's say a race outcome ..within a short turn around.. Like I said it is a fictional racer but has genetic research shown if there is a specific gene about crashing because that would be super useful, again it's all just make believe.. Does Dr. Ferrari have a designated parking spot?
I should post my email in the event that scientists find the gene for getting dropped on @6-7% ten kilometer climbs because I have that genetic defect.. Will get the procedure tomorrow if it's available..

 

[jmdirt]

My understanding of mRNA doesn't open the doors that you are wondering about.

Side notes:
Its funny that many people avoided the 'new' technology...that has been in developement for about 50 years.

The end of October is the 'due date' for those who got mRNA vaccines to meet their fate...we're getting close.

 

[Krzysztof_O]

I will probably spend lots of time thinking and daydreaming about what athletes, including some of my historical favorites that I would want as part of my gene splicing recipe. There were stories about wattage outputs from Cancellara, non existing resting heart rate of Miguel Indurain..
and tons of others w qualities I would want.. but don't you need a baseline to understand bike racer makeup? Is it just something? VO2 max or a muscle tissue composition?

Cardiac output is the basis of all. How much blood can your heart pump per unit of time? The bigger the pump output (relatively to body mass), the better. This brings us to another aspect, which is mass (low body fat percentage needed here). Those two are primary ingredients for superb endurance. Then we have good blood parameters, which will enable to transport as much oxygen per unit of blood volume as possible (yup, EPO and other stuff) also . And then obviously oxygen utilization: lots of slow-twitch muscle fibres and efficient metabolism (thresholds) to take full advantage of one's big cardiac output.

 

[jmdirt]

Cardiac output is the basis of all. How much blood can your heart pump per unit of time? The bigger the pump output (relatively to body mass), the better. This brings us to another aspect, which is mass (low body fat percentage needed here). Those two are primary ingredients for superb endurance. Then we have good blood parameters, which will enable to transport as much oxygen per unit of blood volume as possible (yup, EPO and other stuff). And then obviously oxygen utilization: lots of slow-twitch muscle fibres, efficient metabolism (improving thresholds).

Take in, transport, utilize, and expel.

Is cardiac 'output' the basis? What if you can push a huge volume of blood, but not be transporting any more oxygen and/or getting the waste out?

 

[Krzysztof_O]

Take in, transport, utilize, and expel.

Is cardiac 'output' the basis? What if you can push a huge volume of blood, but not be transporting any more oxygen and/or getting the waste out?

Cardiac output is kinda ceilling here: one can't go beyond this (obviously training can improve it to some extent as well). The higher the ceilling, the bigger the potential to perform. Usually lungs have higher absorbing capacity (at least near sea level) than transporting capacity of heart so the latter is most important. It's normal that you don't use part of the oxygen that you breath in. It depends on how many muscles are engaged - i.e. cross country competitors can have VO2max even bigger than cyclists due to more muscles engaged. That's why they train a lot - to utilize as much of this oxygen as possible, improving muscles and metabolism (so that all parts of this oxygen "chain" are strong enough). Imagine two people: one is well trained and the other isn't. They perform medium-intensity 30-minute effort - the trained person still has a comfortable breath while the other is gasping for air and can barely keep going - even though he breaths in more oxygen than the trained person (due to a feedback that occurs at a high enough intensity in his body) he can't maintain the same level (worse utilization, maybe also smaller heart power).

 

[jmdirt]

Cardiac output is kinda ceilling here: one can't go beyond this (obviously training can improve it to some extent as well). The higher the ceilling, the bigger the potential to perform. Usually lungs have higher absorbing capacity (at least near sea level) than transporting capacity of heart so the latter is most important. It's normal that you don't use part of the oxygen that you breath in. It depends on how many muscles are engaged - i.e. cross country competitors can have VO2max even bigger than cyclists due to more muscles engaged. That's why they train a lot - to utilize as much of this oxygen as possible, improving muscles and metabolism (so that all parts of this oxygen "chain" are strong enough). Imagine two people: one is well trained and the other isn't. They perform medium-intensity 30-minute effort - the trained person still has a comfortable breath while the other is gasping for air and can barely keep going - even though he breaths in more oxygen than the trained person (due to a feedback that occurs at a high enough intensity in his body) he can't maintain the same level (worse utilization, maybe also smaller heart power).

Comparing trained to untrained isn't what were are talking about though, we are talking about two world tour racers.

My point is that that too many people focus on the heart but ignore the entire process.

 

[Sciatic]

Comparing trained to untrained isn't what were are talking about though, we are talking about two world tour racers.

My point is that that too many people focus on the heart but ignore the entire process.

Yes, it’s a complete system that has to function effectively. Pumping out more blood volume from the heart won’t help if it can’t be transported effectively and then utilized efficiently at the key muscle or organ end of the chain.