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The SENS Challenge - Calling all scientists


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#1 ag24

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Posted 28 July 2005 - 08:05 PM


I am told that something will appear at www.jasonpontin.com in about an hour from now....

Edit by kevin:

Please refer to the historical context of this thread here.


#2 eternaltraveler

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Posted 28 July 2005 - 10:13 PM

Wow, that's excellent.

#3 reason

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Posted 28 July 2005 - 11:01 PM

Permalinks:

http://pontin.trblog...ens_challe.html
http://www.fightagin...ives/000557.php

Are any of the Imminst SENS skeptics also molecular biologists in the field of aging research?

Reason
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#4 John Schloendorn

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Posted 28 July 2005 - 11:01 PM

omg you really did it ;-)

#5 Mark Hamalainen

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Posted 28 July 2005 - 11:03 PM

Amazing! This is really really BIG

#6 kevin

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Posted 28 July 2005 - 11:13 PM

Can you think of a better segue from which to hold SENS II in September?

NOT

#7 DJS

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Posted 28 July 2005 - 11:16 PM

What I still don't understand about this whole deal is that Pontin is against SENS, right?

If that's the case, then what is his motivation in funding this endeavor? Is he that confident that SENS is bunk?

#8 caliban

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Posted 28 July 2005 - 11:38 PM

well done! [thumb]

The Terms of the SENS Challenge

1. The Challenge is open to any molecular biologist with a Ph.D from a recognized academic institution who is now associated with a recognized research institution and who has published on biogerontology in peer-reviewed journals. Technology Review will rule on whether a given individual can enter the Challenge.
2. The purpose of the Challenge is to establish whether SENS is worthy of serious consideration. Submissions are sought that attempt to demonstrate that it is not.
3. Submissions will be judged by a review panel, entirely independent of Technology Review and the Methuselah Foundation, composed of recognized molecular biologists, clinicians, and engineers. The members of panel are to be announced.
4. De Grey will reply to all submissions. The biologist may respond. All three documents will be considered by the panel.
5. The initial Challenge prize fund of $20,000 will be paid by matching funds from Technology Review and the Methuselah Foundation.
6. Anyone who wishes to pledge to the Challenge prize fund may do so; they should contact jason.pontin@technologyreview.com, the Editor of Technology Review.
7. The form of the submission must be a core document of no more than 750 words, although additional footnotes, citations, and references can be of any length.
8. If the prize is won, the winning submission will be published as the “By Invitation” column in a forthcoming issue of Technology Review. The magazine will also print de Grey’s response.
9. Submissions should be sent to jason.pontin@technologyreview.com.

(my emphasis)

(3.) is taking the panel approach described above. By getting Pontin to do it, you have sidestepped most of the unpopularity trap that I was weary about. Now its all about "who" of course.

If I'm not missing something, (2.) and (7.) together mean, that it should be rather hard to loose. People might pick up on that.

#9 ag24

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Posted 28 July 2005 - 11:42 PM

Caliban - no in fact, I think the opposite is true. If the anti-SENS argument can't be stated in 750 words, it's probably not a particularly slam-dunk argument, and the challenge is to provide a slam-dunk, an argument that SENS is not just wrong but idiotic.

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Posted 29 July 2005 - 02:49 AM

This is excellent news. Congratulations to Aubrey, who is finally going to have an opportunity for a debate of substance in what will hopefully become a catalyst for greater SENS and MPrize recognition and for the reality of an impending solution to the aging problem.

Are any of the Imminst SENS skeptics also molecular biologists in the field of aging research?


I'm afraid I do not hold a doctorate (which is the first prerequisite), if you were meaning me Reason. Mind you I am a critic of implementation on a couple of points rather than the entire argument. So I'm more interested in improving rather than disproving which may end up being the choice of words that Pontin eventually has to use if he does not get any bites with his present challenge.

Jason Pontin writes:

I promised to find a working biogerontologist who would take on de Grey’s ideas. But while a number of biologists have criticized SENS to me privately, none have been willing to do so in public.

This silence is puzzling (de Grey, less charitably, calls it “catatonia”). If de Grey is so wrong, why won't any biogerontologists say why he is wrong? If he is totally nuts, it shouldn't be so hard to explain the faults in his science, surely?

One possible explanation for the silence of biogerontologists is that criticizing SENS would require time and effort—and that working scientists are too busy to waste time on something so silly. Another explanation (one obviously preferred by de Grey) is that biogerontologists reject SENS out of hand without examining its details.

Technology Review thinks it would be useful to determine which of the two explanations is correct. If SENS has some validity, then we should take it seriously. Because if we can significantly extend healthy life, we will have to ask—should we?


Jason was doing really well until that last sentence. Why on earth anyone, who is of sound mind and body, would choose not to extend their lifespan is beyond reason but I suppose he must continue to play this role for the sake of the perceived values of his constituency. One aspect of the pursuit of SENS type interventions which goes largely undereported are the multiple benefits to conventional pathologies such as cancer, organ disease, etc.

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Posted 29 July 2005 - 02:59 AM

I wonder if Jason may be a closet immortalist after all...

:)

#12 jaydfox

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Posted 29 July 2005 - 01:24 PM

Added my own commentary to the fray:
http://longevityfirs...technology.html

The problem is, the biogerontologists are ignoring SENS. Perhaps they think it won't work. Perhaps the idea that aging can be cured is so wild that, despite the rational scientific approach of SENS, these biogerontologists are just afraid of it, the way that Flat Earthers are afraid of the possibility that the earth is round.

"Sure, there's ‘evidence’, and sure, there's a valid ‘theory’, but are you stupid! The earth is flat! End of discussion! I will not consider this fairy tale that the earth is round. Total Rubbish!"

That's what the silence of the biogerontology community amounts to. Flat Earthers, afraid to acknowledge that biotechnology is moving at an amazingly rapid and accelerating rate, and while the complex biochemistry of metabolism might elude us for several more decades, the molecular and cellular causes of aging are already known, and in theory, treatable in the next two to three decades, if we would but dedicate the personnel and the funding and the research tools.

Perhaps a bit harsh, perhaps even a bit uncalled for, but their silence really has brought such types of criticism upon themselves.

#13 jaydfox

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Posted 29 July 2005 - 01:27 PM

but their silence really has brought such types of criticism upon themselves.

Hmm, I don't think that's grammatically correct. The silence didn't criticism upon the silence. Let me try again:

...but the biogerontologists, through their silence, have really brought such types of criticism upon themselves.

#14 kevin

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Posted 29 July 2005 - 07:48 PM

Here's a link to a bit of a discussion beginning on sci.life-extension

http://groups.google...a6176f5f875df74

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Posted 30 July 2005 - 01:24 AM

I am worried by this idea.

It specifically motivates to discredit SENS offering  $20,000,
including the Methuselah Foundation money ($10,000 dollars) !

I believe that this money could be much better spent on objective
evaluation of the SENS project, rather than for making direct
invitation to discredit it.


He has a point. A 750 word article for $30K is pretty smart takings. A few days of work for an astute biologist and the possibility of a backfire to this plan since a cleverly worded article that is strongly referenced could effectively hamstring SENS to the sceptical portion of the public. Of course, Aubrey, like a dedicated athlete, has been waiting a long time for this and has presumably prepared for all permutations of attack. There are some vulnerabilities, however, which could be exploited and should be buffered against. This would be a good time to look at such weaknesses and devise appropriate strategies of defence. Who can see any holes in SENS?

#16 DJS

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Posted 30 July 2005 - 01:45 AM

Yes Prometheus, this is also what concerns me. This Pontin character is obviously not a friend of the Immortalist ethos. He wants us dead and buried (literally [lol] ). So what's his strategy here? Is his goal to get some big name biologist to take a superficial swipe at SENS and then hold up the 750 word document as the ultimate proof that SENS is nonsense? I think that is what's worrying me here.

Edited by DonSpanton, 30 July 2005 - 02:23 PM.


#17 caliban

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Posted 30 July 2005 - 02:06 AM

Caliban - no in fact, I think the opposite is true. If the anti-SENS argument can't be stated in 750 words, it's probably not a particularly slam-dunk argument, and the challenge is to provide a slam-dunk, an argument that SENS is not just wrong but idiotic.


Sorry, I was not clear enough. My point is that people will say (probably not in writing mind you) that the deck is stacked, because 750wds, slam-dunk is 'not scientific'.

Given Popper, I have some sympathy with that argument. (You cannot prove scientifically that faeries don't exist. You can offer a slam dunk pamphlet on why it is 'idiotic' to think that faeries exist; but even with faeries you might actually need a surprising amount of those 750 words.)

We are now in the fortunate position that we can point towards a challenge, (and it is very important that the challenge is sponsored by the apparent opponent) but the 'slam dunk' will meet with criticism.

edit:
As the previous commentators seem to be worried that you could loose, and I am worried that you cannot loose... maybe you are doing everything right.

#18 jaydfox

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Posted 30 July 2005 - 02:26 AM

It's not enough to say that metabolism and aging are complicated. I think the only way that someone could win this would be to show that two or more of the seven points not even theoretically solvable with the knowledge we have at this time. Remember, de Grey's stance is that each of the seven is theoretically solvable with knowledge we have now, we just don't have the specifics worked out or the technology available.

For example, someone would have to show that WILT couldn't theoretically work, even if implemented flawlessly. In other words, they'd have to show that cancer could kill without the ability to lengthen telomeres.

One way might be to show that cancer cells could infect and turn on all necessary oncogenes and disable all necessary tumor suppressors, in at least 1 in a few million cells that come in contact with cancer cells. Not only would this have to be possible, but for it to be relevant, it would have to be the standard MO of cancer. I brought up this very argument with Aubrey several months ago in fact, since I could have sworn I'd heard of such cancer spreading methods, but de Grey seemed confident that it doesn't happen. He'd obviously thought of it as well, and found evidence to discount the possibility. If necessary, Aubrey'll have references, and at the least, any such argument will fall flat on its face without its own set of references.

As another example, one would have to show that, even protected within the relative safe harbor of the nucleus, the mitochondrial genome would still degrade in a normal lifespan. But the very fragility of the mitochondrial DNA is inherent to its structure and its hostile location. With both the location and the structure fixed, I don't think that argument could be made in 750 words or less, and like I said, I think someone would need to discredit at least two of de Grey's ideas. If only one is discredited, I don't think the panel will be impressed. Could I be wrong?

#19 DJS

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Posted 30 July 2005 - 02:33 AM

To clarify, I am not worried that Aubrey will lose in a fair fight. I am only concerned that Pontif and TR will not fight fair.

In other words, what is the motivation on the other side of the fence?

Is Pontin confident that SENS is absolute bunk, and therefore feels confortable going forward?

Or does he want to acquire some superficial ammunition that he can use against SENS for years to come?
--------------------------------------------------------------

Maybe I have a poor view of human motivations, but I can't imagine that Pontin is actually doing this to advance science -- that would make him a pure idealist. I'm assuming that he has to be looking to get something out of this.

#20 DJS

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Posted 30 July 2005 - 02:41 AM

Jay

One way might be to show that cancer cells could infect and turn on all necessary oncogenes and disable all necessary tumor suppressors, in at least 1 in a few million cells that come in contact with cancer cells. Not only would this have to be possible, but for it to be relevant, it would have to be the standard MO of cancer. I brought up this very argument with Aubrey several months ago in fact, since I could have sworn I'd heard of such cancer spreading methods, but de Grey seemed confident that it doesn't happen. He'd obviously thought of it as well, and found evidence to discount the possibility. If necessary, Aubrey'll have references, and at the least, any such argument will fall flat on its face without its own set of references.


Another line of attack would be to argue that that there are more than seven deadlies (I can't think of any, but who knows, maybe a brilliant theoretician could).

But these are all valid line of criticism that get the ball rolling (toward a more thorough debate of the issues). I'm more concerned with sleight of hand tricks by the other side.

#21 treonsverdery

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Posted 30 July 2005 - 03:12 AM

Idea: Immortality research benefits from publicity. A Lewis-Frasier "fight" is being staged. Build VIP viewership with this plan:

Put up 100 flyers each on the medical research corridors of the seven most relevant research campuses MIT, Cambridge UK,
Baylor, UC system, UW, ETH, n the like People willing to put up these flyers might be found at imminst.org or cheaply at volition.com volition.com where freelance temps abound at 7-11 $ per hour. SENS takes the meme positive space of the debate when it writes the flyers. 200 US $ is sufficient to cover the volition.com employees.

Edited by treonsverdery, 19 October 2006 - 04:45 AM.


#22 Mark Hamalainen

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Posted 30 July 2005 - 03:34 AM

Another line of attack would be to argue that that there are more than seven deadlies (I can't think of any, but who knows, maybe a brilliant theoretician could).


SENS is not meant to absolutely complete, its meant to get us to escape velocity.

I think jaydfox is right, the only 'slam dunk' that is possbile, is for somebody to explain how one of the 7 deadlies is theoretically impossible with our current understanding.

What happens to submissions that are struck down by the reviewers? Do we get to see them?

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Posted 30 July 2005 - 04:51 AM

To clarify, I am not worried that Aubrey will lose in a fair fight. I am only concerned that Pontin and TR will not fight fair.


Precisely. This argument will likely be made in a heavily biased fashion against the validity of SENS, in an arena (TR) that has a track record of ridiculing Aubrey. Thankfully, the remarkably stupid ad hominem attack provided an advantage for Aubrey by enabling defenders to come to his aid without even needing to consider the merits of SENS. With this retrospective available, Pontin, who is nobody's fool will be infinitely better prepared in his mission to debunk SENS.

In Pontin's defence, however, I should say that he is not against aging interventions, he is against snake oil peddlers. At the time when I had a few email exchanges with him I perceived that he did not fully appreciate all aspects of the science involved and had formed a view that had the potential to evolve provided it was sufficiently informed.

Another line of attack would be to argue that that there are more than seven deadlies


There are more than seven deadlies, but the SENS solution set appears to theoretically deal with all instances of them*. This is its pivotal strength - that irrespective of the cause of pathology, SENS brings cellular/tissue physiology back to a level where it can function optimally.

At this stage my concern with SENS is WILT. I would prefer to see WILT scaffold and WILT proper separated since the rate of stem cell replenishment could be a lot less than Aubrey's suggesiton of 10 years. But it is too late for that. Now we must examine the literature for ways by which the date of 10 years can be supported.


* This does not mean it cannot be improved upon - but that is another matter.

#24 arrogantatheist

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Posted 30 July 2005 - 08:12 AM

Prometheus:  Jason was doing really well until that last sentence. Why on earth anyone, who is of sound mind and body, would choose not to extend their lifespan is beyond reason but I suppose he must continue to play this role for the sake of the perceived values of his constituency. One aspect of the pursuit of SENS type interventions which goes largely undereported are the multiple benefits to conventional pathologies such as cancer, organ disease, etc.


Excellent point. I have thought you know if your body was much younger even in some aspects, it would be much more capable of fighting off things like cancer. I wonder if we can push this way of thinking as a backdoor way to life extension?


Navigation: Quote tags corrected

Edited by DonSpanton, 30 July 2005 - 02:22 PM.


#25 ag24

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Posted 30 July 2005 - 11:52 AM

Thanks to everyone for your comments.

One thing to note is that the panel who will adjudicate on submissions has not yet been appointed. Pontin is going after very big names -- I can't say whom yet -- who are biologists but who also have a record of seminal technological breakthroughs, i.e. they are also engineers, at least in terms of how they think. I see no prospect of this ending up as "not a fair fight". I don't think Pete Estep's appeal to entropy would get far, for instance.

A challenge to SENS that identifies problems with one or two of the seven fixes would, as Jay says, have to be extremely damning in order to win. It would have to show that WILT, for example, is completely broken. My homework on that, of course, began with running the third SENS roundtable in December 2002 -- if the participants there were convinced enough of the plausibility (albeit long-term) of WILT to coauthor the paper, after discussing every facet of WILT for a whole day, the chance of there being a slam-dunk refutation of WILT is low.

A challenge on the basis that the seven strands are not exhaustive is much more likely to be attempted, because it's in line with mainstream thinking -- the whole idea that a piecemeal approach to postponing aging could possibly work is the main thing my colleagues balk at. But of course, when I ask them "OK, so supposing we implemented all these things, what WOULD people die of, and at what age?", they have no answer.

So this leads to the third and probably most likely type of challenge, which is that the seven strands are indeed adequately comprehensive, but that within each strand there are an absurdly impractical number of tissues to fix. It's indeed the case that doing numerous things at the same time to the same mice will be a leap into the unknown. But interestingly, when people try to make this argument to me, they always find themselves retreating to idiotic errors. Typically they either overlook that I'm talking about escape velocity rather than perfection, or they overlook that I'm only talking about mice in the first instance (and thus they say things about the feasibility of somatic gene therapy, for example, that are based on safety). The reason people are tempted into this sort of thinking is of course that interfering in multiple metabolic PROCESSES in the same mouse is indeed likely to blow up in one's face, just as Nuland wrote in the original article. SENS, of course (and as I wrote in my answer to Nuland's article), is precisely designed in acknowledgment of that,in that it interferes with the damage, not the processes that lay down the damage.

Osiris -- yes, all submissions and my replies will be public.

Don -- I think Pontin is now genuinely interested in the result of this -- he feels he has been badly taken advantage of by mainstream biogerontologists who effectively authorised him to ridicule me and have since failed to support him in writing. But also, he got such huge publicity from the original articles that he no doubt sees this (correctly, I would say) as a way to milk the SENS story for more publicity for TR. I see nothing wrong in that.

Caliban -- I see your point, but I don't think the analogy with a question about whether something exists is quite valid. A valid analogy would be with whether a given objective can be achieved in a given way, such as whether a particular design of perpetual motion machine would work. I actually don't know enough physics to be able to explain succinctly in 750 words to a non-physicist why perpetual motion machines are impossible, but I am confident that the average professional physicist could easily write such a thing.

#26 Da55id

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Posted 30 July 2005 - 06:03 PM

It would be very difficult for a physicist to prove perpetual motion to be impossible - when electrons and planets are already doing it - and the very lives of the physicists depend on this perpetual motion. Now of course in a few billions of years it could be proved that it wasn't actually perpetual - but then we'd have to be there to observe it wouldn't we ;-)

So this is why I have confidence in SENS. If strands of SENS turn out to be wrong, the PHILOSOPHY works - engineering...we already have proof of this. If you consider trauma to be accelerated degradation, then it is engineering that fixes it...surgery, splints, plasters, pins, sutures...SENS is a matter of scaling surgery down to the nano scale...so, just fix it faster than it degrades. then later improve the materials, means and methods to strengthen and prevent.

#27 outlawpoet

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Posted 30 July 2005 - 08:40 PM

any particular perpetual motion device can be debunked, and many have been.

Perpetual Motion in theory can be trivially shown to be impossible via thermodynamic arguments, at least in the long term. Electrons and planets, re: MethuselahMouse's comments, won't move forever, furthermore, if you try to use them to do any work, as perpetual motion scientist often intend, they degrade even faster. In fact, a serious problem for any immortalist is Entropy in the global sense, since we aren't sure where to get new protons when ours start breaking.

#28 Da55id

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Posted 30 July 2005 - 11:40 PM

any particular perpetual motion device can be debunked, and many have been.

Perpetual Motion in theory can be trivially shown to be impossible via thermodynamic arguments, at least in the long term. Electrons and planets, re: MethuselahMouse's comments, won't move forever, furthermore, if you try to use them to do any work, as perpetual motion scientist often intend, they degrade even faster. In fact, a serious problem for any immortalist is Entropy in the global sense, since we aren't sure where to get new protons when ours start breaking.


sigh - of course that's correct. I said it was perpetual in practical terms/time scales.

If we lived 1000 years, such a lifespan would be one five millionths of a stable yellow star system's lifespan. The practically perpetual weather/tidal systems do a really great job of offering up energy without the slightest danger of seriously slowing things down for millions of years. If oil was a product of degradation of living matter, then the practically perpetual rain, wind, sun and life cycles did/do a good job of putting lots of terawatts in the larder. We haven't even touched the unfathomable energy stored in the tides. So my point continues to be about the practical. Maybe it would be more ELEGANT to discover each and every cause of aging sometime over the next 200 years. But I think it preferable to go for the PRACTICAL goal of fixing the daggone machine in the meantime.

#29

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Posted 31 July 2005 - 03:05 PM

I'm only talking about mice


That's a worry. Up until now I was under the impression when we were talking about SENS it was in the context of human interventions.. Can you clarify this?

#30 ag24

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Posted 31 July 2005 - 04:08 PM

Prometheus wrote:

> Up until now I was under the impression when we were talking about SENS it was in the
> context of human interventions.. Can you clarify this?

The main clarification was my next four words -- "in the first instance". A singleminded focus on mice in the first instance is scientifically questionable, since we all know that there are quite a few important differences between mouse and human aging, so I am certainly keen to see work done that probably won't even be needed for the "robust mouse reuvenation" milestone (of which WILT is the most substantial). But as a sociopolitical strategy to achieve robust human rejuvenation (which I claim will equate to escape velocity) as soon as possible, it makes sense to prioritise a proof of concept (namely RMR) that will sweep away any doubts that aging of people who are already alive can probably be greatly postponed, and will sweep away any doubts that this would be a good thing about ten minutes later. Once that's happened, the consequent hike in funding and rate of progress towards RHR will (in my view) greatly outweigh any time that might have been lost in developing human therapies as a result of focusing on mice to a scientifically questionable degree. I mentioned this above in the context of somatic gene therapy because that's an extreme current example of this: the fact that gene therapy trials worldwide can be halted for over a year, leading perhaps to a delay of a month in the eventual development of safe gene therapy and thus to the loss of many thousands of lives at that time, as a result of the death of one guy who shouldn't have been in the trial in the first place, is a measure of our lack of sense of proportion on such matters, which will be recognised and abandoned in the aftermath of RMR.




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