Parabiosis seems to work because you're basically using the young mouse as a breathing dialysis unit for the older mouse, not because there's any secret sauce in their blood per se.
Your claim ("it doesn't work") requires evidence, which you haven't presented.
The evidence that it does work already exists:
"When Wyss-Coray’s team tried a simpler experiment than parabiosis—giving old mice injections of plasma from young mice—they saw similar effects on the hippocampal neurons. The old mice also performed significantly better than untreated animals on tests of learning and memory."
Science's default position -- the null hypothesis -- is that there is no relationship between two phenomena.
In this case, the phenomena are "administering treatment" and "seeing positive results".
If the null hypothesis is accurate, and there is no relationship between treatment and outcomes, then it doesn't work. So yes, that is indeed science's default position.
No, in this case, the phenomena are "administering treatment" and "seeing results" (not just positive). You start off with "we don't know if it makes humans better or worse or does absolutely nothing, let's do a bunch of tests". Also, when it comes to clinical tests, you almost never do simply control/placebo vs treatment. There are usually a few groups with various degrees of treatment.
No, you start off with "we assume it does nothing".
"Clinical tests" is a wide range of studies, and initially may indeed be 'simple' placebo controlled studies. If an effect is seen, then testing will be done with 'various degrees' to determine a dose response, etc.
No. In order to get permission to transport what you're testing and administer it to patients you need to file an Investigational New Drug application and approval stipulates that you don't market or charge for anything related to the clinical trials until the final New Drug Application is approved.
The problem is that "young blood" isn't some new drug it's just blood. Once the FDA approves something, they have almost no control over how a legally practicing doctor administers the treatment. Various ethics and medical boards, depending on the jurisdiction, have authority to ban the doctor from practicing medicine but blood transfusions are such a common thing and liability is always enforceable so it's hard to justify here. Done properly the risk of complications is small and there are proven treatments to many of the rare issues. I think this treatment is ridiculous but whether it is clearly unethical I think falls to a matter of opinion.
If it's found to work well, it will be great for the young people struggling with money. The bar to entry of such a business is very low - you just have to test the blood donors for disease, which can be outsourced to numerous labs.
Maybe there is a startup opportunity to sell spare kidneys, and even lungs and liver-halfs too! Maybe even a cash-for-corpses business, we need to get rid of these ridiculous self-serving medical regulations. DISRUPT!
You can sell plasma, can you still sell your blood in the US? I know you could on one point, but people with blood-borne illnesses shouldn't give blood, and with a financial incentive there were problems with people lying about it.
Yes. It ends up being unprofitable to buy from donors directly, but it is still legal. There is also a thriving secondary market in selling donated blood, the Red Cross for instance makes a large amount of money selling blood.
When you can grow back your kidneys, lungs, and livers, this will be a sensible extension of the idea.
I initially wanted to make this comment sarcastically, but really, if we become capable of regrowing organs within your body you could legitimately make a business case for it.
In a typical adult recipient LDLT, 55 to 70% of the liver (the right lobe) is removed from a healthy living donor. The donor's liver will regenerate approaching 100% function within 4–6 weeks, and will almost reach full volumetric size with recapitulation of the normal structure soon thereafter. It may be possible to remove up to 70% of the liver from a healthy living donor without harm in most cases. The transplanted portion will reach full function and the appropriate size in the recipient as well, although it will take longer than for the donor.
You know you make new blood, and people donate blood regularly? Apart from small slices of liver, your organs don't really regrow. You could donate/sell one of your kidneys, but we now know there are negative long-term effects of that.
Somewhat OT, but kidney donation is surprisingly low risk in the long term.
"Compared to the general public, most kidney donors have equivalent (or better) survival, excellent quality of life, and no increase in end-stage kidney disease"
I would suspect that there is a selection bias here, as a whole lot of the low end of the general health distribution would prevent you from donating a kidney, or at least make it less likely. So you'd expect them to do better than average if donation had no effect.
To know if there is an effect, you need to not compare to the general public, but to a subset similar in factors which are associated with the outcome measures to kidney donors.
This popular science piece is characteristic of a prevalent and hostile view of the growing practice of patient-funded clinical trials. In this model the patient pays a sizable portion of the costs, which certainly makes it a lot easier to gather larger amounts of data, as the trial organizers don't have to seek the funding themselves. On the other hand, it tends to rule out the ability to carry out a blind trial in which not everyone actually gets the treatment, as well as other similar refinements. That is a problem if the goal is to search for and quantify marginal effects, but if the point is to discover or rule out large effects, I'd argue that control groups are not necessary. The control in that case is the established progression for patients who do not get the treatment, or who undergo existing, marginal treatments. We are at the stage in the development of medicine to treat aging in which marginal effects, such as those resulting from the use of metformin as a calorie restriction mimetic, should be discarded as uninteresting. Once at the stage of trying things in human studies, the research community should be filtering for significant effects, such as those obtained by clearance of senescent cells. Given the poor state of funding for aging research in general, methods that can pull in more resources to obtain more data should be applauded.
In the case of the approach being trialed here by Ambrosia, I think our expectations should be low, and the outcome I expect is for there to be no significant benefit. The only ethical question worthy of consideration is whether those involved then do the right thing: publish the data, shut up shop, and move on to the next project - having done the good work of finding out that there is no large effect here. Transfusions of young blood to old individuals are not producing benefits in mice, and there is reason to think that the beneficial outcomes observed in old mice due to parabiosis, the linking of circulatory systems between an old and a young individual, are due to factors or circumstances not replicated by periodic transfusion. It isn't difficult to imagine that beneficial outcomes require the youthful system reacting in a dynamic way to the presence of aged signals, for example, or - as suggested by some researchers recently - that it is nothing more than a consistently maintained dilution of problem signals in the aged environment.
I wonder if you could run a paid study with a proper control group. Perhaps have everyone pay to participate, administer the treatment to half of them, and at the end of the study refund some amount of money (all? all + interest?) to the ones who received a placebo. That way they've only donated their time.
The prevalent and hostile view exists because this is a pretty dubious study design, and there's a ridiculous degree of financial entanglement in many of these "trials". Lots of bad data doesn't necessarily help anyone.
If the problem really is "This area doesn't have enough money", then the same money being used to buy into the trial could have funded a proper double-blind trial.
And this is from the perspective of someone who does support the use of non-randomized evidence in medicine.
reasonattlm, you're the man. I think lots of your good posts go unread because the paragraphs are too long. If you hit enter one more time than usual per paragraph, I think you'll 4x or better the posts read/understood.
The stories of her serial murders and brutality are verified by the testimony of more than 300 witnesses and survivors as well as physical evidence and the presence of horribly mutilated dead, dying and imprisoned girls found at the time of her arrest.
Stories which ascribe to her vampire-like tendencies (most famously the tale that she bathed in the blood of virgins to retain her youth) were generally recorded years after her death and are considered unreliable. Her story quickly became part of national folklore, and her infamy persists to this day.
She is often compared with Vlad III the Impaler of Wallachia, on whom the fictional Count Dracula is partly based, and has been nicknamed The Blood Countess and Countess Dracula.
Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan.
46 comments
[ 5.0 ms ] story [ 102 ms ] threadAlternatively, maybe the idea pitched to research institutions was knocked back as unethical or showed little scientific merit?
Parabiosis seems to work because you're basically using the young mouse as a breathing dialysis unit for the older mouse, not because there's any secret sauce in their blood per se.
The evidence that it does work already exists:
"When Wyss-Coray’s team tried a simpler experiment than parabiosis—giving old mice injections of plasma from young mice—they saw similar effects on the hippocampal neurons. The old mice also performed significantly better than untreated animals on tests of learning and memory."
http://www.sciencemag.org/news/2014/05/young-blood-renews-ol...
Science (natual ones) can't prove anything, only disprove the hypothesis.
Science's default position is "we don't know" or "there's no evidence", not "it doesn't work".
In this case, the phenomena are "administering treatment" and "seeing positive results".
If the null hypothesis is accurate, and there is no relationship between treatment and outcomes, then it doesn't work. So yes, that is indeed science's default position.
"Clinical tests" is a wide range of studies, and initially may indeed be 'simple' placebo controlled studies. If an effect is seen, then testing will be done with 'various degrees' to determine a dose response, etc.
Sometimes people do the work to prove things wrong.
It seems like the clinical trial is just an excuse to get around medical regulations, so they can sell snake oil to gullible rich people.
OTOH, I'm not sure what medical regulations they'd be getting around.
The problem is that "young blood" isn't some new drug it's just blood. Once the FDA approves something, they have almost no control over how a legally practicing doctor administers the treatment. Various ethics and medical boards, depending on the jurisdiction, have authority to ban the doctor from practicing medicine but blood transfusions are such a common thing and liability is always enforceable so it's hard to justify here. Done properly the risk of complications is small and there are proven treatments to many of the rare issues. I think this treatment is ridiculous but whether it is clearly unethical I think falls to a matter of opinion.
http://newsok.com/article/4985779
I initially wanted to make this comment sarcastically, but really, if we become capable of regrowing organs within your body you could legitimately make a business case for it.
https://en.wikipedia.org/wiki/Liver_transplantation#Living_d...
In a typical adult recipient LDLT, 55 to 70% of the liver (the right lobe) is removed from a healthy living donor. The donor's liver will regenerate approaching 100% function within 4–6 weeks, and will almost reach full volumetric size with recapitulation of the normal structure soon thereafter. It may be possible to remove up to 70% of the liver from a healthy living donor without harm in most cases. The transplanted portion will reach full function and the appropriate size in the recipient as well, although it will take longer than for the donor.
"Compared to the general public, most kidney donors have equivalent (or better) survival, excellent quality of life, and no increase in end-stage kidney disease"
https://nhsbtdbe.blob.core.windows.net/umbraco-assets/1433/1... [PDF, page 7]
To know if there is an effect, you need to not compare to the general public, but to a subset similar in factors which are associated with the outcome measures to kidney donors.
In the case of the approach being trialed here by Ambrosia, I think our expectations should be low, and the outcome I expect is for there to be no significant benefit. The only ethical question worthy of consideration is whether those involved then do the right thing: publish the data, shut up shop, and move on to the next project - having done the good work of finding out that there is no large effect here. Transfusions of young blood to old individuals are not producing benefits in mice, and there is reason to think that the beneficial outcomes observed in old mice due to parabiosis, the linking of circulatory systems between an old and a young individual, are due to factors or circumstances not replicated by periodic transfusion. It isn't difficult to imagine that beneficial outcomes require the youthful system reacting in a dynamic way to the presence of aged signals, for example, or - as suggested by some researchers recently - that it is nothing more than a consistently maintained dilution of problem signals in the aged environment.
If the problem really is "This area doesn't have enough money", then the same money being used to buy into the trial could have funded a proper double-blind trial.
And this is from the perspective of someone who does support the use of non-randomized evidence in medicine.
People are vampires farming the remaining humans for their blood.
The stories of her serial murders and brutality are verified by the testimony of more than 300 witnesses and survivors as well as physical evidence and the presence of horribly mutilated dead, dying and imprisoned girls found at the time of her arrest.
Stories which ascribe to her vampire-like tendencies (most famously the tale that she bathed in the blood of virgins to retain her youth) were generally recorded years after her death and are considered unreliable. Her story quickly became part of national folklore, and her infamy persists to this day.
She is often compared with Vlad III the Impaler of Wallachia, on whom the fictional Count Dracula is partly based, and has been nicknamed The Blood Countess and Countess Dracula.
Telomeres, lifestyle, cancer, and aging:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/
Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan.
Or at least used it as a loofah.