I will definitely be keeping an eye on how this develops. Parrish is so enthusiastic about her work it is contagious. I hope this project turns out positively, for her sake and the sake of the research.
> Your cells dividing indefinitely is not the opposite of aging, it's cancer.
Look at it this way: the Hayflick Limit on cellular replication limits act as a fail-safe in case other growth inhibition mechanisms fail. If a liver cell decides that it wants to be its own immortal organism but doesn't express telomerase, it won't get very far in its enterprise. The replication limit makes it more likely that we'll survive to reproductive age.
On the other hand, the Hayflick Limit kills us. Evolution doesn't care much about this side effect, but we do. If we can suppress cancer other ways --- or hell, even if we can't --- NOPing out the Hayflick Limit safety code is worthwhile.
> Your cells dividing indefinitely is not the opposite of aging, it's cancer.
No. As long as they divide on schedule in the amount they're supposed to, they're not cancer.
Dividing indefinitely is the opposite of aging at the cell level; aging at the whole-organism level has some other stuff to it. I think there's so much emphasis on the cell division clock because we know what it is.
Probably not in the US. But the workaround is already in the article: do it in another more-favorable jurisdiction.
Medical tourism for price reasons is already a big thing. People are also traveling to Mexico or South Korea for stem-cell treatments unavailable in the US. Startups might also find US jurisdictions that want to carve out more experimental freedom than the FDA's defaults, as with stem cells in Texas:
How is this irresponsible? It's her body. Yeeesh. She is brave to believe in her work. I don't think the article author is aware of how the cause of ulcers was proved and shared the 2005 Nobel prize.
Some ways this is irresponsible, from the (much much better) Tech Review article:
>Fossell, the anti-aging entrepreneur, says even if Parrish were to somehow succeed in slowing the aging of her body, an outcome he rated as unlikely, the experiment would have no impact because of how it was carried out. “The problem is that no one is going to believe them,” he says. “The credibility will be zero even if they are right on the money.”
Also:
> “We as a company have our own ethics,” she says, referring to what she calls the need for inexpensive gene therapy treatments. “I am certainly not going to ask someone’s permission to potentially create new industries and cures.”
Anybody saying "we have our own ethics" is way way out there, it casts doubt on all of the rest of their endeavor.
So if it works, only the people who have adopted Liz Parrish's ethics and those who do not live under the rule of those who refuse to accept her ethics will be able to live forever. That's because, in the ethics of Fossell, some truths are not ethical to believe in, no matter what the evidence. They become ethical to believe in once the proper authorities have determined those truths to be ethical.
> Anybody saying "we have our own ethics" is way way out there, it casts doubt on all of the rest of their endeavor.
Everybody has slightly different ethics. She's just pointing out that she views the advancement in this field and the millions of people it could give longer life to if it comes about sooner as more important than the arguments against a human trial, and to make sure someone isn't being taken advantage of, she's doing it on herself. I'm not sure how to fault that.
>Fossell, the anti-aging entrepreneur, says even if Parrish were to somehow succeed in slowing the aging of her body, an outcome he rated as unlikely, the experiment would have no impact because of how it was carried out
That's not really true, is it? If she lives to 120, or she lives a normal life span with dramatically "younger" looks and energy, it will have a huge impact. Even if the treatment can't be replicated exactly they'll know where to start looking.
Her body is not the only thing that's affected. This kind of unscientific showmanship could make legitimate aging research look like a joke to the public, who can't tell the difference. It's hard enough to get funding already.
Helicobacter pylori was in many ways a well-understood entity just by virtue of being a bacterium, and was treatable with antibiotics.
Meddling with growth factors and chromosome structure systemically is hardly going to be reversible in anywhere near as controlled a way, and could well end up hurting her (and others who may decide to follow the example), potentially hurting her in a life threatening way by inducing cancer.
Then there's the abstract damage from reckless human experimentation on attitudes and community reactions. Early failures with gene therapy probably delayed the clinical use about a decade. We don't need more of that, and we don't need more excuses for people to dismiss life extension as a crackpot venture.
I hope she turns out at least unharmed. Got to admit the case study could prove to be interesting.
BioViva is one of the small groups interested in bringing telomerase therapies to humans sooner rather than later. It seems they have started in on their small long-term trial of human gene therapy for telomerase activation, and have treated the first volunteer.
I should say that at any given time there is a fairly large gap between what can be done in human medicine, the technology that actually exists and works, and what is being done in trials. Most of this gap is due to regulation, and the rest of it because development groups want to have a reasonable certainty that what they are doing actually works, does more good than harm, and so forth. The regulatory process might last a decade, while the actually useful part of that testing (does it basically work, and is the risk profile sufficiently defined and acceptable to patients) is only a few years. As the cost of research and development in the life sciences falls, it will become increasingly untenable that a huge ball and chain slows progress thanks to regulatory risk aversion, and a growing number of initiatives will forge ahead and build anyway. Some years ago I proposed the Vegas Group fable, something that I think will happen in the fullness of time: alternative roads that bypass official regulation in favor of faster progress, an inevitability in an environment of low-cost research. Also, I think, a necessity.
What about the science here? I've never been a big fan of telomere lengthening approaches, as average telomere length as it is measured today in immune cells looks very much like a marker of the progress of aging, an end stage consequence far removed from root causes. Telomeres shorten with cell division and new long-telomere cells are delivered into tissues by stem cell populations. Thus average telomere length in immune cells reflects some combination of immune health and stem cell activity, both of which are known to decline with age. You can't argue with the fact that telomerase gene therapy has been shown to extend life in mice, however, though you can certainly note that the size of the effect has been getting smaller as the research groups have refined their data and approaches.
How does this work to slow aging in mice? At this point I lump enhanced telomerase activity into the general category of approaches that either probably work or intend to work by boosting the activation of old stem cell populations, resulting in increased repair and tissue maintenance and thus a slower decline into frailty and organ failure. More telomerase doesn't seem to raise cancer risk in mice, but mice have very different telomere dynamics and cancer risk profiles than we humans. The fastest way to figure out what is going to happen in humans is of course to try it, and kudos to anyone volunteering at this stage, but I'd be waiting for a few more years of testing first in animal or tissue models closer to human telomere dynamics. In part that decision would be driven by the fact that I don't think that this is the best approach to move ahead with practical applications, to push ahead and get things done. I absolutely agree that pushing ahead to get things done needs to happen, but I'd rather see this sort of boldness for SENS treatments like senescent cell clearance.
I am patient zero. I will be 45 in January. I have aging as a disease. To take on this role myself was the only ethical choice. I am happy to step up. I do feel we can use these therapies in compassionate care scenarios now but we will have to work them back into healthier people as we see they work as preventive medicine.
The genes targeted are human telomerase reverse transcriptase (hTERT) and follistatin (FST). In animal models neither ...
One thing to be cognizant about is that cancer is really a disease caused by the reverse aging of particular cells. If you make a cell think it is too young it is going to become invasive. We don't normally think of embryonic development requiring invasive behavior of cells, but that is certainly the case. Take a look at the development of the cerebral cortex and how cells must travel through other layers to reach their destination. It appears that they are targeting telomerase which is very interesting and parallels cancer where its over-expression is used often as a marker. But then again telomerase under-expression can occur in early-stage cancer and is thought to contribute to genome instability/mutation to affect other genes before it is eventually over-expressed. So this kind of experiment is really exciting and will almost certainly give us insight into many different medical fields. I just hope that her experiment winds up on the preventative side of cancer rather than the causative one.
No, cancer is caused by DNA damage. The longer a cell lives, the more damage it gathers, so if you make a cell immortal and the mechanisms the body has for killing malfunctioning cells or repairing damage to damaged DNA is disabled, weakened, or overwhelmed, then you get cancer.
Well, cancer is complicated. There are types that behave like embryo cells (including one benign type which can create hair or toe nails randomly in the body).
The previous posters final comment is the critical one: let's hope she hasn't given herself cancer. Previous gene therapy trials were all stopped because of that risk. Current Crispr techniques (if that's what she used) aren't specific enough to avoid off target effects, those could easily cause cancer.
I tend to be quite pro DIY medicine, but this still seems quite rash to me because of those risks.
DNA damage can lead to the deregularization of various cell mechanisms, the ability of the cell to repair DNA being one of them. Only when several of those mechanisms go rogue you get cancer; having only one or two of them disabled is usually not sufficient.
In your example, an immortal cell who cannot repair DNA or even identify damaged DNA wouldn't be that dangerous, since it doesn't have the signal to reproduce wildly.
Yes those are all important parts in the development of cancer. But you have to take into account the tools that cancer has to take advantage of when it comes to invasiveness and proliferation. DNA instability is the root cause which results in incorrect signalling, cell cycle progression, cell morphology, and immune system evasion. But take angiogenesis, an extremely important tool for a developing embryo, and how ubiquitous it is for a growing tumor. But we can go farther and consider the factors that influence the guidance of a cell during development. Accutane or Isotretinoin is very similar in structure to retinoic acid, a guidance molecule in the posterior embryo. Consequently isotretinoin causes birth defects. Interestingly isoretinoin has also been implicated as an anti-cancer treatment. Thalidomide, which also interrupts proper development has also been used as an anti-cancer treatment. My point isn't to dispute the importance of DNA damage and gene expression profile changes, but rather to emphasize the importance of metastasis and its apparent parallels with embryonic development since metastasis is the main reason (sans leukemias) why cancer has such a high lethality.
I love how this mixes the "n=1" self-experimentation of Seth Roberts [1] with the "not just the President, but also a client" salesmanship of Sy Sperling [2].
Publicity stunt instead of scientific paper in reviewed journal, "we don't care about FDA approval" attitude, undisclosed location in latin America - sounds totally credible.
If governments and FDAs of the developed world were more cooperative it wouldn't happen this way.
Startups don't have a billion dollars for FDA trials.
It is a different way of going about bootstrapping funding for a new venture in medicine.
The gene therapies used are well exercised in animal studies. At some point you have to move to humans, but that costs money. This is one approach to raising the funding to perform small trials, you get the first trial member done first since that's what you have the funds for, and move on from there.
Parrish has been a member of the community interested in aging and biotech for some years. Look at the the advisory board of BioViva. You don't magically get George Church on your board without having paid your dues.
Meanwhile if you happen to be someone who disagrees with the existence and current practice of the FDA - and this may be a minority position, but it isn't a small minority position - then linking this all with regulatory arbitrage makes perfect sense. There is an enormous gap between what can be done safely (large set) and what the FDA permits (small set), and with the cost of biotechnology and medicine falling rapidly, sooner or later something has to give.
The FDA is all about maintaining the position of FDA bureaucrats. That's the only real way to interpret the 2.5x cost increase in trials over the past decade. They are willing to suppress as much medical progress as it takes in order to look like people who are doing a non-phony-baloney job. But medicine is inherently risky. There will always be people who die as a result of new therapies: it should be up to the patients to make informed decisions, not a matter of bureaucrats pushing the cost of development upwards to a point at which only a trickle of new treatments emerges on the other side. The public doesn't react to the invisible death toll of people who would have been saved by the medicines that are no longer cost-effective to develop.
After the FDA started pressuring 23andme in to not giving data relating to diseases to customers, I lost of respect for them in the genetic arena. Customers have a right to know what's in their bodies. At the moment 23andme is only cleared to give out data from a single disease, which is pathetic. Clearing the way for more genetic diseases will likely be a bureaucratic nightmare and would harm more people in the long run.
Given how conservative the FDA is in allowing companies to inform customers what's in their own bodies, it's unlikely companies will get any form of approval for modification.
I imagine the reasoning is that give people incorrect information about a disease they may have could be extremely damaging. Having models that predict the accuracy of each diagnosis to within a few percent and presenting this percentage would be better (maybe requiring it be over a certain percentage), but the FDA is conservative enough I can imagine them requiring 99% accuracy or better on everything.
I don't know the details of the particular case of FDA and 23andMe (I remember only the one when FDA asked 23andMe to fix their marketing, or else), but there is a known problem with giving medically-relevant information to people - that armed with such information, fully predictably, they go batshit insane.
Most people are not properly equipped to handle such information. I see this as a failure of education, that could probably be easily fixed if e.g. high-school curriculum taught basic statistics and probability theory as applied to interpreting medical results. It's the simple things, like "just because you got a positive test on X doesn't mean you have X", "think of horses before zebras" and "if you read 'X causes cancer' or 'X increases risk of cancer by 1000%' in the news, take note if anyone is providing the base level - an increase of 0.00001% probability to 0.0001% means you can ignore the news and keep enjoying X", and "if commonly-used-in-food-X was really dangerous, you'd see people dying like flies around you; if you don't, it means it's mostly safe so don't panic".
While I agree with your assessment of how people act, I really hope that's not a reason that the FDA really uses to keep information from people[1]. It would be troubling to find out that the government had decided that I should not be able to freely access personal information about myself, given that it exists. Whether as a society we can deal with that information currently or not, there's no hope for us dealing with it in the future if we aren't given a chance.
1: I don't doubt it's some people's underlying motivation, I just hope it's not overt enough that it's valid reasoning in official reports.
I'm not familiar with FDA that much (I live in EU) and I believe it isn't anywhere near perfect, but you want to be conservative when it comes to public health. Look at case of Thalidomide from 50s https://en.m.wikipedia.org/wiki/Thalidomide
In the United States, pharmacologist Frances Oldham Kelsey M.D.
withstood pressure from the Richardson-Merrell company
and refused Food and Drug Administration (FDA) approval
to market thalidomide, saying further studies were needed.
Then again, how many people would be lost if public confidence in drugs as being safe was lost? We can't get a sizable portion of people to even vaccinate their children anymore, and that was all sourced from a single fraudulent paper, which the author lost his license over[1].
You have to admit that FDA approval can be onerous, and that a "mad scientist" way of demonstrating technology can be an effective way to build public demand.
Consider another technology: safe, effective, and reversible male birth control [1]. It's been used in India for decades, but happens to be illegal in the US right now due to the slow and expensive nature of the approval process.
Just a note: I haven't seen it mentioned in article, but "gene therapy" was discovered in 70s and it's widely used https://en.wikipedia.org/wiki/Gene_therapy - what's new here is use for anti-aging and DIY nature of treatment.
I feel it's important to judge weight of this story.
Give her credit for taking a risk with her own health. Although of course the animal studies haven't shown cancer development. But still a brave thing to do, and obviously worth it given the existing animal studies.
I believe that regulations are holding back therapy development, especially in any area that is not already popular.
I think this is an issue with government in general, and we will need a totally new type of government if we are going to get a moral society that integrates with technology.
It looks like (science funding) politics is the only reason we are not testing how these genes work in large mammals and primates. The public is scared of genetic engineering.
And nuclear power, and geo-engineering. Public hysteria is placing us at great risk on numerous fronts. Ultimately, though, I'm optimistic. Not once in human history has anyone been able to suppress technology once it became both possible to make and profitable to produce. In this instance, the Chinese will probably beat us to gene therapy technology, and we'll desperately play catch-up once we see the difference it makes in life outcome.
If there had been a major war, you'd have seen them come right back. It's not as if the Japanese simply forgot how to make the things during the Edo period.
Do you have any idea how difficult it is to actually maintain a low-calorie diet? It's simply not a realistic option for most people. Yes, with sufficient willpower, it'd be possible in theory, but that's like saying that unaided human flight is possible with sufficient muscular power. Dietary restriction just isn't in us.
And the universal increase in obesity in the west doesn't matter? The idea that voluntary dietary restrictions might have any effect on public health is ludicrous. If that strategy could work, it would have already worked. Do you think many obese people _want_ to be obese?
Look, my point is that it's possible to eat fewer calories, but it's not necessarily easy to do it in a way that doesn't harm you. It's not suppressing appetite that is really complicated, it's reducing calories and staying on top in terms of nutrition.
I'm not sure willpower is the right word to use here. If there was proof that a certain diet had a significant positive effect on increasing my lifespan, I would almost definitely pursue it. It would be irresponsible not to.
On the other hand, I think it would be irresponsible to pursue it based purely on the fact it lengthened your lifespan. For example, I personally would not pursue caloric restriction if it yielded a single year of life on average. Quality of life matters.
"Dietary restriction just isn't in us." like ... unsure how to respond to this... Like its just so blatantly wrong. source: me, a person whos maintained substantially fasted states for long periods of time
Yes, that's you. Go outside. Look around. Do you think we _as_ _a_ _population_ can maintain diets? The existence of rare outliers (and anorexics) does not disprove the bloody obvious conclusion that at population scale telling people to eat less has no effect on how much they actually eat.
You don't need a low calorie diet. You need a lower calorie diet. The amount of food that people need to give up is sometimes quite small. Or they need to change a few items a day to a healthier alternative. This is slow, but maintainable, and it's what most modern evidence-based weight loss plans recommend.
That's true. These plans, properly followed, work as advertised. That's physics. The trouble is that most people do not follow this plans, and after 40 years of trying to show otherwise, we now know that this situation isn't going to change.
Why is it that so many people are completely oblivious to the limits of human psychology? Telling people to eat less doesn't work. We need to try other public health measures.
I just said that these modern plans are not about telling people to just eat less, perhaps I wasn't clear.
Modern weight loss plans focus on making sure people feel full, and have tricks to help people feel like nothing is forbidden (you could still eat cheese or chocolate, just controlled small amounts), while helping them make better choices.
There's not much evidence, and the evidence is about as good as all the other dietary stuff (not great) but they do seem to work and be maintainable.
Low-carbohydrate diets are supposed to decrease calorie intake without reducing satiation. They've been around for 50 years. They may work for individual people, but they do not work at scale as a public health measure.
Why is this concept so difficult to get across? There are _constant_ advertisements in every medium for weight loss programs of every sort. We've already explored the entire parameter space of dieting. Tweaking the food mix and saying, "No. This time we have the perfect mix to keep you health and full!" isn't science. It's quackery that belongs on the cover of Cosmo.
You know what works in reality?
* Amphetamines
* Nicotine
* 2,4-Dinitrophenol
* Gastric surgery of various sorts
* Cancer
Of course none of these things is an effective public health measure. (Although there's some evidence that e-cigarettes aren't quite as carcinogenic as regular cigarettes, but might still deliver all of nicotine's benefits.)
You know what might actually work?
* Pigovian taxes on high glycemic index food and drink
* A ban on food advertisement
* Portion size regulation
* Weight-based airfare
But these are all unpopular, because they contravene the pretty little dogma that we all have enough willpower within ourselves to accomplish our goals. Sometimes we need an external kick in the ass.
It's time we stop pretending that yelling at people about diet and exercise is going to make a bit of difference. We might as well yell at the sea and tell it to stop rising.
> Of course none of these things is an effective public health measure. (Although there's some evidence that e-cigarettes aren't quite as carcinogenic as regular cigarettes, but might still deliver all of nicotine's benefits.)
N=1 sample, not to prove anything but sharing an anecdote: I'm nicotine-taking non-smoker, consuming it in form of nicotine gums. I haven't noticed any effect of it on my weight over the period of last two years. I did respond to ketogenic diet however, but found it hard to maintain over long periods of time - basically it's a big time and cognitive investment to invent new foods that you won't puke on out of a limited set of ingredients. I do think that a lot of diets would work if they were the only thing people have to think about during the day. Alas, the cognitive demands of our fast-moving, competitive world are strong.
> Suicide attempts increase substantially in morbidly obese patients in the years following bariatric surgery, when the "honeymoon" period of substantial weight loss comes to an end, new research shows.
I agree that death does have a slimming effect.
> yelling at people about diet and exercise
Nothing in my posts can be seen as advocating for yelling at people. Please don't bring your bickering with other people into your replies to me.
What I'm talking about is an "Every Contact Counts"[1] style approach of supporting people to access a modern weight loss programme[2], for free if they can't afford it. This will be "prescribed" by their GP, paid for by Public Health[3] or perhaps their Clinical Commissioning Group. I've accepted that the evidence is not great, but if you want to find what's wrong with the evidence[2] used by NICE I'd be interested to hear it.
I haven't said anything in this thread about exercise, but I have said in other threads that exercise does not help weight loss. We should be recommending that people do exercise because it has other undeniable health benefits.
As Scott Alexander puts it, "society is fixed, biology is mutable"[0]. Dieting is only one of many things in which we're shooting ourselves in the foot as civilization by pushing for social solutions and discarding the technical ones because "willpower" and stuff.
A quote from the beginning that captures the gist of the article:
"[L]ecture on ADHD suggested several reasons for the increasing prevalence of the disease. Of these I remember two: the spiritual desert of modern adolescence, and insufficient iron in the diet. And I remember thinking “Man, I hope it’s the iron one, because that seems a lot easier to fix.”"
The same author also wrote an article about when it's better from a practical standpoint to treat something as a disease instead of a failure of character[1].
True. For many people issue lies, I feel, not with changing things, but with knowing what to change and how. Most people - myself included - have pretty streamlined diet: they know what they like, where to buy ingredients for that cheap and how to prepare them. Even starting on a stable, maintainable diet requires you to think through what exactly to change, what new components are needed, where to source them and how to alter your preparation routines. You want to do it in such a way as not to deprive yourself of important nutrients, or else your body will say "fuck it" and force you to break the diet (or if you're particularly strong willed, you'll feel like crap all the time). If you do this, it's easy to keep on diet, but you have to do a big investment up front. I've personally done this once; procrastinated months on it, but after I sit down and made the necessary time investment, my weight reacted to changes pretty much instantly.
But I can see how most people simply don't have time for diet. It's kind of like being poor - you could get a lot more for the same amount of money if you have enough capital available to do bulk purchases. But if you're living paycheck-to-paycheck, you don't have enough money to buy cheap.
Also that's why some people are willing to pay for someone else to figure it out for them. I personally know someone struggling with weight for almost two decades, for whom the solution for instant weight loss was to pay someone else to micromanage their food - she got a list of allowed choices and amounts for all meals a given week and - what I think was a key trick - a protein powder alternative to use if she didn't like a particular meal. It had pretty much no taste, but it was a line of retreat that let you skip something you don't like without breaking the diet.
Modern weight loss programmes are not that rigid and work by asking people to make small changes, maintain those changes, and then keep making more until target weight is reached, and then to keep going.
For most people it doesn't need that much thinking. 1) Stop drinking regular soda and switch to zero calories sodas, or water, or teas and coffee, or sugar-free squash. 2) When using something like cheese don't use 300 g in a sandwich - use 30 g of a stronger flavoured cheese and grate it finely.
These small simple steps are achievable and maintainable - and with diets the lifestyle changes you can stick to are the ones that work.
It's a good business model. People need to keep going to the groups once they've reached their target weight; people have the chance to keep buying the books and magazines and snack products.
There are lots of approaches to eliminating excess CO2 that we could talk about if people like you didn't reflexively smear technology as some great devil. Voluntary CO2 emission reduction looks so far like a doomed effort that goes against every incentive built into human nature.
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[ 2.4 ms ] story [ 138 ms ] thread> Telomerase ... is present in cells that can continue to divide indefinitely, like stem cells and tumors.
Your cells dividing indefinitely is not the opposite of aging, it's cancer. This is completely quackery.
Look at it this way: the Hayflick Limit on cellular replication limits act as a fail-safe in case other growth inhibition mechanisms fail. If a liver cell decides that it wants to be its own immortal organism but doesn't express telomerase, it won't get very far in its enterprise. The replication limit makes it more likely that we'll survive to reproductive age.
On the other hand, the Hayflick Limit kills us. Evolution doesn't care much about this side effect, but we do. If we can suppress cancer other ways --- or hell, even if we can't --- NOPing out the Hayflick Limit safety code is worthwhile.
No. As long as they divide on schedule in the amount they're supposed to, they're not cancer.
Dividing indefinitely is the opposite of aging at the cell level; aging at the whole-organism level has some other stuff to it. I think there's so much emphasis on the cell division clock because we know what it is.
Showmanship is not how we should evaluate clinical therapies.
Is it legal to offer a product that hasn't gone through FDA as long as consumers sign their acknowledgement?
It might be necessary to be a little careful with what entity is promoting the treatment and so on.
Medical tourism for price reasons is already a big thing. People are also traveling to Mexico or South Korea for stem-cell treatments unavailable in the US. Startups might also find US jurisdictions that want to carve out more experimental freedom than the FDA's defaults, as with stem cells in Texas:
http://www.bloomberg.com/bw/articles/2013-01-03/stem-cell-sh...
http://discovermagazine.com/2010/mar/07-dr-drank-broth-gave-...
>Fossell, the anti-aging entrepreneur, says even if Parrish were to somehow succeed in slowing the aging of her body, an outcome he rated as unlikely, the experiment would have no impact because of how it was carried out. “The problem is that no one is going to believe them,” he says. “The credibility will be zero even if they are right on the money.”
Also:
> “We as a company have our own ethics,” she says, referring to what she calls the need for inexpensive gene therapy treatments. “I am certainly not going to ask someone’s permission to potentially create new industries and cures.”
Anybody saying "we have our own ethics" is way way out there, it casts doubt on all of the rest of their endeavor.
Everybody has slightly different ethics. She's just pointing out that she views the advancement in this field and the millions of people it could give longer life to if it comes about sooner as more important than the arguments against a human trial, and to make sure someone isn't being taken advantage of, she's doing it on herself. I'm not sure how to fault that.
That's not really true, is it? If she lives to 120, or she lives a normal life span with dramatically "younger" looks and energy, it will have a huge impact. Even if the treatment can't be replicated exactly they'll know where to start looking.
Meddling with growth factors and chromosome structure systemically is hardly going to be reversible in anywhere near as controlled a way, and could well end up hurting her (and others who may decide to follow the example), potentially hurting her in a life threatening way by inducing cancer.
Then there's the abstract damage from reckless human experimentation on attitudes and community reactions. Early failures with gene therapy probably delayed the clinical use about a decade. We don't need more of that, and we don't need more excuses for people to dismiss life extension as a crackpot venture.
I hope she turns out at least unharmed. Got to admit the case study could prove to be interesting.
http://ocp.hul.harvard.edu/contagion/vonpettenkofer.html
I should say that at any given time there is a fairly large gap between what can be done in human medicine, the technology that actually exists and works, and what is being done in trials. Most of this gap is due to regulation, and the rest of it because development groups want to have a reasonable certainty that what they are doing actually works, does more good than harm, and so forth. The regulatory process might last a decade, while the actually useful part of that testing (does it basically work, and is the risk profile sufficiently defined and acceptable to patients) is only a few years. As the cost of research and development in the life sciences falls, it will become increasingly untenable that a huge ball and chain slows progress thanks to regulatory risk aversion, and a growing number of initiatives will forge ahead and build anyway. Some years ago I proposed the Vegas Group fable, something that I think will happen in the fullness of time: alternative roads that bypass official regulation in favor of faster progress, an inevitability in an environment of low-cost research. Also, I think, a necessity.
What about the science here? I've never been a big fan of telomere lengthening approaches, as average telomere length as it is measured today in immune cells looks very much like a marker of the progress of aging, an end stage consequence far removed from root causes. Telomeres shorten with cell division and new long-telomere cells are delivered into tissues by stem cell populations. Thus average telomere length in immune cells reflects some combination of immune health and stem cell activity, both of which are known to decline with age. You can't argue with the fact that telomerase gene therapy has been shown to extend life in mice, however, though you can certainly note that the size of the effect has been getting smaller as the research groups have refined their data and approaches.
How does this work to slow aging in mice? At this point I lump enhanced telomerase activity into the general category of approaches that either probably work or intend to work by boosting the activation of old stem cell populations, resulting in increased repair and tissue maintenance and thus a slower decline into frailty and organ failure. More telomerase doesn't seem to raise cancer risk in mice, but mice have very different telomere dynamics and cancer risk profiles than we humans. The fastest way to figure out what is going to happen in humans is of course to try it, and kudos to anyone volunteering at this stage, but I'd be waiting for a few more years of testing first in animal or tissue models closer to human telomere dynamics. In part that decision would be driven by the fact that I don't think that this is the best approach to move ahead with practical applications, to push ahead and get things done. I absolutely agree that pushing ahead to get things done needs to happen, but I'd rather see this sort of boldness for SENS treatments like senescent cell clearance.
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Digest of the Reddit AMA with the BioViva CEO: https://www.reddit.com/r/Futurology/comments/3ocsbi/ama_my_n...
I am patient zero. I will be 45 in January. I have aging as a disease. To take on this role myself was the only ethical choice. I am happy to step up. I do feel we can use these therapies in compassionate care scenarios now but we will have to work them back into healthier people as we see they work as preventive medicine.
The genes targeted are human telomerase reverse transcriptase (hTERT) and follistatin (FST). In animal models neither ...
http://www.technologyreview.com/news/542371/a-tale-of-do-it-...
From the guidelines: "Please submit the original source. If a post reports on something found on another site, submit the latter."
https://news.ycombinator.com/newsguidelines.html
The previous posters final comment is the critical one: let's hope she hasn't given herself cancer. Previous gene therapy trials were all stopped because of that risk. Current Crispr techniques (if that's what she used) aren't specific enough to avoid off target effects, those could easily cause cancer.
I tend to be quite pro DIY medicine, but this still seems quite rash to me because of those risks.
In your example, an immortal cell who cannot repair DNA or even identify damaged DNA wouldn't be that dangerous, since it doesn't have the signal to reproduce wildly.
See D. Hanahan and R. Weinberg "Hallmarks of Cancer: The Next Generation" for a scholarly (and quite readable) review http://www.sciencedirect.com/science/article/pii/S0092867411...
[1] https://en.wikipedia.org/wiki/Seth_Roberts
[2] https://youtu.be/IuRLGdGnqSU?t=47s https://en.wikipedia.org/wiki/Hair_Club
The gene therapies used are well exercised in animal studies. At some point you have to move to humans, but that costs money. This is one approach to raising the funding to perform small trials, you get the first trial member done first since that's what you have the funds for, and move on from there.
Parrish has been a member of the community interested in aging and biotech for some years. Look at the the advisory board of BioViva. You don't magically get George Church on your board without having paid your dues.
Meanwhile if you happen to be someone who disagrees with the existence and current practice of the FDA - and this may be a minority position, but it isn't a small minority position - then linking this all with regulatory arbitrage makes perfect sense. There is an enormous gap between what can be done safely (large set) and what the FDA permits (small set), and with the cost of biotechnology and medicine falling rapidly, sooner or later something has to give.
The FDA is all about maintaining the position of FDA bureaucrats. That's the only real way to interpret the 2.5x cost increase in trials over the past decade. They are willing to suppress as much medical progress as it takes in order to look like people who are doing a non-phony-baloney job. But medicine is inherently risky. There will always be people who die as a result of new therapies: it should be up to the patients to make informed decisions, not a matter of bureaucrats pushing the cost of development upwards to a point at which only a trickle of new treatments emerges on the other side. The public doesn't react to the invisible death toll of people who would have been saved by the medicines that are no longer cost-effective to develop.
It's a sad situation.
Given how conservative the FDA is in allowing companies to inform customers what's in their own bodies, it's unlikely companies will get any form of approval for modification.
Most people are not properly equipped to handle such information. I see this as a failure of education, that could probably be easily fixed if e.g. high-school curriculum taught basic statistics and probability theory as applied to interpreting medical results. It's the simple things, like "just because you got a positive test on X doesn't mean you have X", "think of horses before zebras" and "if you read 'X causes cancer' or 'X increases risk of cancer by 1000%' in the news, take note if anyone is providing the base level - an increase of 0.00001% probability to 0.0001% means you can ignore the news and keep enjoying X", and "if commonly-used-in-food-X was really dangerous, you'd see people dying like flies around you; if you don't, it means it's mostly safe so don't panic".
1: I don't doubt it's some people's underlying motivation, I just hope it's not overt enough that it's valid reasoning in official reports.
1: https://en.wikipedia.org/wiki/Andrew_Wakefield
Consider another technology: safe, effective, and reversible male birth control [1]. It's been used in India for decades, but happens to be illegal in the US right now due to the slow and expensive nature of the approval process.
[1] https://en.wikipedia.org/wiki/Reversible_inhibition_of_sperm...
I feel it's important to judge weight of this story.
I believe that regulations are holding back therapy development, especially in any area that is not already popular.
I think this is an issue with government in general, and we will need a totally new type of government if we are going to get a moral society that integrates with technology.
It looks like (science funding) politics is the only reason we are not testing how these genes work in large mammals and primates. The public is scared of genetic engineering.
And nuclear power, and geo-engineering. Public hysteria is placing us at great risk on numerous fronts. Ultimately, though, I'm optimistic. Not once in human history has anyone been able to suppress technology once it became both possible to make and profitable to produce. In this instance, the Chinese will probably beat us to gene therapy technology, and we'll desperately play catch-up once we see the difference it makes in life outcome.
How do you feel about Japanese suppression of firearms?
http://www.nature.com/tp/journal/v4/n10/full/tp201498a.html
Also, it's a mental illness so it's not a fucking choice.
Look, my point is that it's possible to eat fewer calories, but it's not necessarily easy to do it in a way that doesn't harm you. It's not suppressing appetite that is really complicated, it's reducing calories and staying on top in terms of nutrition.
Why is it that so many people are completely oblivious to the limits of human psychology? Telling people to eat less doesn't work. We need to try other public health measures.
Modern weight loss plans focus on making sure people feel full, and have tricks to help people feel like nothing is forbidden (you could still eat cheese or chocolate, just controlled small amounts), while helping them make better choices.
There's not much evidence, and the evidence is about as good as all the other dietary stuff (not great) but they do seem to work and be maintainable.
Why is this concept so difficult to get across? There are _constant_ advertisements in every medium for weight loss programs of every sort. We've already explored the entire parameter space of dieting. Tweaking the food mix and saying, "No. This time we have the perfect mix to keep you health and full!" isn't science. It's quackery that belongs on the cover of Cosmo.
You know what works in reality?
Of course none of these things is an effective public health measure. (Although there's some evidence that e-cigarettes aren't quite as carcinogenic as regular cigarettes, but might still deliver all of nicotine's benefits.)You know what might actually work?
But these are all unpopular, because they contravene the pretty little dogma that we all have enough willpower within ourselves to accomplish our goals. Sometimes we need an external kick in the ass.It's time we stop pretending that yelling at people about diet and exercise is going to make a bit of difference. We might as well yell at the sea and tell it to stop rising.
N=1 sample, not to prove anything but sharing an anecdote: I'm nicotine-taking non-smoker, consuming it in form of nicotine gums. I haven't noticed any effect of it on my weight over the period of last two years. I did respond to ketogenic diet however, but found it hard to maintain over long periods of time - basically it's a big time and cognitive investment to invent new foods that you won't puke on out of a limited set of ingredients. I do think that a lot of diets would work if they were the only thing people have to think about during the day. Alas, the cognitive demands of our fast-moving, competitive world are strong.
http://www.medscape.com/viewarticle/852616?nlid=89075_2052&s...
> Suicide attempts increase substantially in morbidly obese patients in the years following bariatric surgery, when the "honeymoon" period of substantial weight loss comes to an end, new research shows.
I agree that death does have a slimming effect.
> yelling at people about diet and exercise
Nothing in my posts can be seen as advocating for yelling at people. Please don't bring your bickering with other people into your replies to me.
What I'm talking about is an "Every Contact Counts"[1] style approach of supporting people to access a modern weight loss programme[2], for free if they can't afford it. This will be "prescribed" by their GP, paid for by Public Health[3] or perhaps their Clinical Commissioning Group. I've accepted that the evidence is not great, but if you want to find what's wrong with the evidence[2] used by NICE I'd be interested to hear it.
I haven't said anything in this thread about exercise, but I have said in other threads that exercise does not help weight loss. We should be recommending that people do exercise because it has other undeniable health benefits.
[1] http://www.makingeverycontactcount.co.uk/
[2] http://www.nice.org.uk/guidance/ph53
[3] https://www.gov.uk/government/organisations/public-health-en... England's use of generic names is nice, but feels a bit weird sometimes.
A quote from the beginning that captures the gist of the article:
"[L]ecture on ADHD suggested several reasons for the increasing prevalence of the disease. Of these I remember two: the spiritual desert of modern adolescence, and insufficient iron in the diet. And I remember thinking “Man, I hope it’s the iron one, because that seems a lot easier to fix.”"
The same author also wrote an article about when it's better from a practical standpoint to treat something as a disease instead of a failure of character[1].
[0] - http://slatestarcodex.com/2014/09/10/society-is-fixed-biolog...
[1] - http://lesswrong.com/lw/2as/diseased_thinking_dissolving_que...
True. For many people issue lies, I feel, not with changing things, but with knowing what to change and how. Most people - myself included - have pretty streamlined diet: they know what they like, where to buy ingredients for that cheap and how to prepare them. Even starting on a stable, maintainable diet requires you to think through what exactly to change, what new components are needed, where to source them and how to alter your preparation routines. You want to do it in such a way as not to deprive yourself of important nutrients, or else your body will say "fuck it" and force you to break the diet (or if you're particularly strong willed, you'll feel like crap all the time). If you do this, it's easy to keep on diet, but you have to do a big investment up front. I've personally done this once; procrastinated months on it, but after I sit down and made the necessary time investment, my weight reacted to changes pretty much instantly.
But I can see how most people simply don't have time for diet. It's kind of like being poor - you could get a lot more for the same amount of money if you have enough capital available to do bulk purchases. But if you're living paycheck-to-paycheck, you don't have enough money to buy cheap.
Also that's why some people are willing to pay for someone else to figure it out for them. I personally know someone struggling with weight for almost two decades, for whom the solution for instant weight loss was to pay someone else to micromanage their food - she got a list of allowed choices and amounts for all meals a given week and - what I think was a key trick - a protein powder alternative to use if she didn't like a particular meal. It had pretty much no taste, but it was a line of retreat that let you skip something you don't like without breaking the diet.
For most people it doesn't need that much thinking. 1) Stop drinking regular soda and switch to zero calories sodas, or water, or teas and coffee, or sugar-free squash. 2) When using something like cheese don't use 300 g in a sandwich - use 30 g of a stronger flavoured cheese and grate it finely.
These small simple steps are achievable and maintainable - and with diets the lifestyle changes you can stick to are the ones that work. It's a good business model. People need to keep going to the groups once they've reached their target weight; people have the chance to keep buying the books and magazines and snack products.
Yay, thank god. Otherwise it might take us whole aeons to heat the planet beyond the point we can live on it.
Personal rudeness is not ok on HN, even when you think someone's view is wrong.