A Reddit AMA with the BioViva CEO
BioViva is a small group that recently announced they have moved ahead with a human test of telomerase and myostatin-related gene therapies as a potential method to modestly slow the effects of the aging process. Their initial goals are to get things moving in this part of the field by taking this step forward, observing the results, and raising funding for further development efforts to try to lower the costs of this sort of approach. The BioViva CEO Liz Parrish, who is also the initial test subject, recently hosted an AMA (ask me anything) event at Reddit's /r/futurology community. Her comments below are lightly edited for continuity, since they are pulled from numerous distinct answers to questions posted by the community:
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 FST nor hTERT have increased the risk of cancer. We expect to see the same result on myself, and to that effect we are measuring all known cancer biomarkers. The gene therapies on my body are to measure the effects on humans. There is plenty of animal research to support these gene therapies but no one was conducting human tests. We are using both visual biomarkers, MRI and a panel of blood and tissue testing including work on telomere length and epigenetic testing. We are collecting as much data as we can, but unfortunately we currently don't have the coverage rate for this therapy, how much of the tissue of the body is affected. Depending on the tissue and vector used we ultimately expect to see similar rates of transfection as seen in mice, which is somewhere between 5 to 60%.
We are working as hard as we can to bring it to the world as quickly and safely as possible. We will will evaluate monthly and within 12 months we will have more data. If the results are good we hope to have something to the general public, that is cost acceptable, in 3-5 years. Our goal is to build laboratories that will have the mission of a gene therapy product at a reduced cost. Gene therapy technology is much like computing technology. We had to build the super computer which cost $8 million in 1960. Now everyone has technologies that work predictably and at a cost the average person can afford. We need to do the same with these therapies. What you will get in 3-5 years will be vastly more predictable and effective that what we are doing today and at a cost you or your insurance can cover .
We need a lab that works solely to bringing those costs down. We would need about $1 - 1.5 million to build one lab to focus on this. We can expand as needed. I would love to crowdfund this project but I do not know how to get good results at that scale - I think the price tag is high for that modality. We are raising investment to do offshore clinical trials. Many USA companies do this. If we can cut costs we will be able to bring back a treatment that people can afford.
And only a few comments about overpopulation and only select people being able to get it. Shocking.
It is a pity that they are doing two gene therapies at once as it means that one having no effect cannot be ruled out.
I think the follistatin gene therapy has a better chance of having a positive effect, but then how much muscle loss is a fairly healthy 45 year old woman suffering at her age?
On the other hand, I like their gung ho approach of just doing the gene therapy overseas rather than trying to push it through the FDA. Although there is the corresponding risk that something goes wrong, but they don't have the data to prove that it was unrelated to the treatment.
It would be interesting to see one of the gene therapy based SENS treatments such as allotopic expression of mitochondrial genes being done via this route (once it has been shown to work in animal models).
I've always been moderately suspicious of BioViva, but the fact that the CEO has the gumption to actually do it to herself goes a long way in saying that they believe it's functional, if nothing else.
Really curious how this will actually help on the macro level.
Jim, I do wonder if it would of been more visibly effective (if it works at all) if she were a bit older, since she still looks fairly young as is. I like the fact that they're doing it away from the FDA as well, but if it does work, and tons of people start taking it, can other regulatory bodies eventually get involved?
Here's a snippet that didn't get answered really.. There was some arguing with him a bit as well, but the guy used cognitive bias as the reason why the other person was so for the treatments. /shrug
"When people live to be 200, do we require them to work for 50 years or 150?
When people reach retirement age and have money and property from the pre-BioViva days, where are the young going to live? Do we need to build giant urban dorms to house them, like Chinese factory workers? What prospects will the young have to achieve the lifestyles of the old? Do you think they will be happy to accept their lot?
How much can we expect the young to support the old?
Economics nowadays depends on continual growth. What is the link between economics and population age?
What is the carrying capacity of Earth? How many people can we feed? If the population doubled, will people starve?
Where is the water going to come from?
Will migration happen in much larger numbers? Would you like thousands of old people from a different culture on your doorstep?
Will people like being told not to have babies? Will there be riots? What effect will this tech have on the family?
If one nation or ethnicity stops having babies but not another, what would people think about it? Might politics swing to hawkish and right-wing?
Will the perceived value of human life go down?
How will the treatments be allocated? Should it be on wealth? Who will decide? What will happen if, for example, governments try to limit access to the treatment for the reasons I've just laid out? Will the people riot? I imagine so.
These are just concerns I have tossed out. The point is not that it's bad to try and help people, but that there are secondary effects. No-one in this thread seems to be discussing this.
I suspect it was going to happen anyway, but Liz has really let the genie out of the bottle now. This is an extremely emotive topic and people will riot over it- to the point that I don't think anyone can control this thing for long.
So while I like the idea of science being pure investigation, people like the clever employees at BioViva have quite possibly done something very stupid, and the idea that scientists don't have to make moral choices about the technology they release is naive. And when you say "people have the right", I wonder how you think you can deliver it.
ITT, many people going "ooh shiny" and congratulating Liz, and no one playing the scenario forward."
I am very hopeful that they will be at least partially successful if not 100% and that they will garner alot of (positive) publicity and other companies plus new ones will be initiated by this. I'd love to think this is only the beginning, 3-5 years is not far off.
Someone will be first on the dance floor, then others will stop hanging around at the edge.
There are dozens of things that can be tried out in the BioViva model or similar, some of them even helpful from the SENS damage repair perspective, if you have a few hundred thousand dollars, connections with some scientists, and a willingness to say screw the FDA.
It is incredible what she is doing ! It should turn out fine, 45 years old at regular aging rate of telomeres attrition is down to 6-8 kb length (starting from 8-10 kb (8000-10000 TTAGGG repeat base pairs), she lost about 2 kb, unless she is biologically older or younger (looks 55-60 or 30-35 for her age) than her chronological 45 years, then she would have lost 2.5-2.75 kb or only 1.5 kb). Meaning, if she has no inflammatory illness of long date, cancer mutational burden is still low enough at that age to be safe from oxidative stress-caused tumor formation (high overall telomeres, high methylation means high genome stability by good transcription fidelity/integrity) but not in some inflammed over-stressed oxidized demethylated short telomeres. It is when at 50 to 55 years old that cancer can suddenly appear and telomeres attrition can accelerate because the 5th decade starts to show some damage and freaky scary weird stuff pops up (like my own mother who died of stomach cancer at 56 years old and went to the hospital because of a jaundice; only to find out a cancer). From two studies, she could see about the effect of TAT 65 cycloastragenol in Astragalus activating hTERT transcript. Roughly 15 to 25 years biorejuvenation. Or about 500 to 1000 basepairs elongation give or take. It will very unlikely rejuvenate her back to very adolescent age, that would be nearly 30 years rejuvenation and 1700 basepairs, nearly 2 kb. The study shows that hTERT transfection in cultured *Human* skin cells yields at max telomerase about 1kb rejuvenation (roughly 20 years back). About 25 % of median lifespan increase like in mice; and no extension beyond maximum lifespan of 122 years; telomerase can't seem to counter-act telomere attrition in high age and sooner or later, short telomeres appear from longlife oxidative stress.
This means the Redox is far important than telomerase magic, redox controls oxidative stress state
This is kind of big news, im really surprised there isn't any real coverage of this anywhere. Maybe in a year when some results are shown, perhaps?
Ham wrote: "people like the clever employees at BioViva have quite possibly done something very stupid, and the idea that scientists don't have to make moral choices about the technology they release is naive."
Something very stupid? Like letting 100,000 people die every day? That's it?
@CANanonymity I concur with you.
The Helen Blau experiment also found out that additional treatments yielded decreasingly impressive results, suggesting that there is some kind of natural buffer that prevents the telomeres simply growing non stop. This is good as it means in theory they will hit an ideal length and stop.
Also from testing with TA65 there is indication that whilst it was not powerful enough to lengthen telomeres per se it does seem to reduce the % of short telomeres. Now assuming as Dr Fossel and Andrews are saying TA65 is about ~5% of the strength needed and gene therapy is an order of magnitude more powerful then one could assume we would see both an decrease in % of short telomeres (implicated in diseases) as well as a general increase in average lengths as you describe. I think we will see both actions in play as well as telomerase interaction with the wnt pathway and P53-PCG-1-Mitochrondrial pathways leading to stem cell mobilization.
The question is how long would it take assuming vector infection rate (currently unknown how well it has infected) has been good? They used an AAV2 vector with a broad target range so multiple cell types are effects.
I was quoting that Antonio, to be clear. But yeah that's part of people's argument about how people need to die, and if they didn't those 100,000 would still be alive On top of the new ones being born so we would become massivly overpopulated etc. Sad. Now I'm not suggesting that there wouldn't need to be something done about birthrates in the long term, but everyone freaks out about this so much. Ugh.
@CANanonymity any thoughts on the second therapy the Follistatin?
There are a number of interesting animal studies indicating it may be able to mitigate foam cells as well as the better known benefits to muscular tissue and even fibrotic tissue.
REASON SAID: "Someone will be first on the dance floor, then others will stop hanging around at the edge.
There are dozens of things that can be tried out in the BioViva model or similar, some of them even helpful from the SENS damage repair perspective, if you have a few hundred thousand dollars, connections with some scientists, and a willingness to say screw the FDA."
Really like the dance floor comparison and I think you are right. The more people join the dance means the more competition too which Liz has said will drive costs down further which is good.
I know bioviva has some targets on the SENS list too and is hoping to see plaque removal from this if their animal and anecdotal data pans out.
There seem to be a fair amount of people unhappy or unconvinced by the AMA the other day. Theres been criticism in a couple threads, but here is a link to one that popped up today:
I personally want to believe.
Ham, I believe it's not big news because it's self-reported, the organisation has a low profile, and the experiment has just started. So there's nothing to discuss, apart from the legal/ethical implications.
@Nico yes and no. It is worthy of discussion because as Reason points out "Someone will be first on the dance floor, then others will stop hanging around at the edge."
I think starting tests like this send a strong signal that longevity research is becoming more mainstream and that confidence is growing. Yes the data needs to come in and be positive but it is still exciting to hear that people are out there trying such things.
I hate to be a wet blanket, but I'm going to be a wet blanket.
Does anyone have any confirmation, other than the Reddit, that any of this has actually taken place, or is in the process of taking place, in terms of an actual human trial at this point?
Seeing someone speak on the possibility of something, and them actually *doing* what they believe is theoretically possible are two very different things.
I've personally been unable to confirm via any of my contacts in biotech that any of this is anything other than an elaborate troll.
@Steve: It is indeed an interesting announcement.. for us, followers of longevity initiatives. But for the mainstream outlets, and the scientific ones, this is of little value because of the complete absence of objective indicators to rely on whilst researching the veracity of the story.
@Terry: That's the issue. Self-reporting. No one should (yet?) get high hopes from this story.
@Terry Lambert: The presence of people such as George Church on the advisory board suggests it is an earnest initiative:
Nico, I get what you're saying. It's just that there is next to nothing that they can talk about about the specifics of the therapy (I get that though, for the most part) to quell people's concerns at this time. I definitely think if George Church or someone on their board could speak about them on their behalf, it would probably go a long way now... especially since people are saying its a scam and there are no real scientists involved.
This is something I want to believe happened, and will work to a somewhat meaningful extent. I'm looking forward to whatever data they decide to provide us.
I said it before and will say it again, Aubrey de Grey is aware of this ask him. You can also ask if George Church is aware of this assuming you can get hold of him. Both these people are on her SAB and whilst likely cannot or will not elaborate they will confirm it has gone ahead.
@Nico Yes agree with you. The big thing we are waiting on is obviously the initial data, I am sure given Liz she will soon publish the data as soon as it becomes available. Not much more to do bar waiting.
Hi Steve, I believe the follistatin therapy has great potential. As you mention this naturally fabricated protein in the body is an inhibitor of various pathological changes due to excessive inflammatory processes, be it excessive fibrosis, fibrous plaque formation due to fat-saturated macrophage (foam cell) invasion and consumption/deposition of LDL particles (the LDL and endothelial cells signaling the entry of foam macrophages, cytokines, T-cells, NK cells, white corpuscles, neutrophils and other reactive immune cells in the atherosclerotic lesion to create this fibrous pouch' fatty LDLcholesterol filled plaque; that unstabilized by ROS excess from foamy macrophages can rupture and cause blood clot snowballing formation in a matter of minutes; and thus, a heart attack death), it will reverse this seedy silent and deadly process that steals so many's life; lower LDL in plaques, lower inflammatory immune cell activity (reduced C-reactive protein, NK, foam macros, IL-6, TNF-a, TGF-b, Plasminogen Activator and Fibrinogen), lower plaque size, increase pre-existing plaque stability from rupture and deadly arterial clot formation.
As for fibrotic tissue, same process as fibrous plaque formation, it will increase fibrinolysis by blocking fibrinogen and desintegrating fibrin fibers by increased proteolytic cleaving enzymes (serratio)peptidase, liguase, lipase, ..) activity.
Church comments here http://www.technologyreview.com/news/542371/a-tale-of-do-it-yourself-gene-therapy/ . Seems like he doesn't know much about the details of what happened either.
@ale: Much pearl-clutching on the part of the author of that article.
Ah, you beat me to posting that ale. I thought it was interesting that in the article Michael fossel said that the odds of the treatment working are slim, especially since he's into anti aging and telomerase himself.
And that's most appropriate given the context, Reason.
@Nico: Hardly. This is disruption: when something becomes cheap and fast, yet the establishment wants it done expensively and slowly, this is exactly what you'll see. Freedom of choice should win out, but the establishment will always fight it. If someone wants to undertake this sort of development activity as a way to push things along, then go for it I say.
We will be seeing much more of this going forward. Recall the early years of overseas stem cell clinics and single patient proof of concept work, ten to fifteen years ago. That will happen again for gene therapy, and I see it as a very necessary part of getting anything done in a world in which regulators would slow everything to a snail's pace.
I'm not personally in favor of the particular technological approach taken here; I don't think it likely to be useful. I am in favor of organizations carrying out regulatory arbitrage and setting out to get things done rather than going through the endless regulatory red tape. At some point all of the animal studies showing safety need to lead to human tests. Why not now, why not with people who choose to do it?
Reason, we read this article differently it seems.
You focused on the interviewees' reactions (i.e. the experiment should have gone through formal trials) whilst I focused on the author's approach (i.e. did that experiment really happen?).
And given that we have nothing to rely on but self-reporting, yes, I am of the opinion that the author wrote his article the right way. That's pretty much what I'd expect from serious journalists.
As for what irks you, which is the trials and the red tape surrounding them: I'm all for risk-taking persons being allowed to try whatever they want on their bodies, but the average lesser-informed person should be protected from risky experiments (which may occur without their full consent, that's the issue).
I agree with Reason but feel Parrish would have fared better by keeping her SAB informed, it seems to be vague. I do not doubt it has been done but I think some damage control is in order here.
I think the only way that could happen is with good sample analysis done by someone notable Eg, Church for example. She did mention in the AMA Lifelength and Spectracell are involved in data testing for the experiment so perhaps it can be salvaged.
I have to be honest I would not have done a double therapy at this point as it will be hard to tell which therapy is having an effect. I think being a bit more candid might have helped but then again I don't pretend to understand the fine line one has to walk to get work like this done.
I get a sort of pretentious vibe out of the article. Kind of off topic, maybe not. But in regards to the Technology review article, it would be nice to just once not see comments about overpopulation. Even the author left a comment saying less death from longer lifespans could be the biggest driving factor in population size. I swear, people screaming overpopulation are going to be the reason this kind of stuff gets held back. Or Fukuyama-esque bioethicists. Because I don't foresee people accepting something like a 1 child or no child rule, especially in the west.
Why didnt they interview Bill Andrews? He is on her board and works with telomerase and telomeres!
Steve, from what I gather, there is a lot of skepticism about Bill Andrews. There was an article about something he was doing a couple weeks ago on reddit that got mostly torn apart. I'll try and find it and link later. The comments by Fossel in the article were interesting to me though. Seems to be on the other end of George Church.
@Ham its very interesting considering Fossel was singing her praises in interviews a few weeks ago. I appreciate to protect Telocyte he would distance himself but this went beyond that IMO.
George Church seems more supportive so let us hope he can add some credability to the situation. He could test samples with his lab and confirm any changes to biomarkers for example.
I do feel the article has some bias and it would have been better to talk to the whole SAB not just cherry pick.
@Ham Also yes Bill Andrews is a bit of a dark horse. On one hand he is has excellent industry knowledge and knows a lot about telomere biology (I recall Michael Fossel convinced him about telomeres years ago if the interview i saw is correct) but on the other hand his reputation is tarnished due to involvement in supplements. Yes proceeds from supplements he makes do go towards research and assaying telomerase activators at Sierra but he is involved in some good science. The supplements connection however does taint his credibility to some degree IMO.
It does somewhat colour his motives but nonetheless if he is on the SAB for Bioviva and I know for a fact he was interviewed why have all of his comments been disregarded? I suspect there is some bias to the article if other SAB members were interviewed and what they said was cherry picked or not included at all.
I get fossel wanting to protect telocyte. But doesn't he have some aging aspirations with that as well? I know it's being pursued for Alzheimer's though.
Assuming this works to some extent: I wonder if combining Bioviva's approach with senolytics from a hypothetical start-up, plus GDF-11 offered by another putative company willing to bypass the FDA, plus some cutting edge tissue engineering and ad-hoc stem-cell treatments like those currently available in various labs worldwide, plus a smattering of metformin pills and rapamycin for good measure, we would already be at a point where shaving a couple of decades off old people's biology is in fact reality.
@Barbara if telomerase mobilizes the stem cells you will not need GDF-11 in theory as the cell will produce it's own after being returned to more youthful function (assuming you agree with the Fossel theory ofc).
Stem cells (RepleniSENS) in artifical niche (eg hydrogel niche) combined with mobilized resident stem cells could potentially allow a "top up" to extend life.
Of course assuming Cancer does not occur and the final word on that is still debatable both ways.
"Claim of risky DIY gene therapy linked to unlicensed stem cell clinic"
I do wonder if this is going to cause more people to distance themselves from the anti-aging field and cause more to view it as pseudoscience? Will this only strengthen the FDA's view on aging? Even if she has successful data, will anyone really look at it, FDA included? There are multiple ways to look at this of course, such as the one view that the FDA is too slow, expensive, restrictive, and bureaucratic (which hopefully changes with 21st century cures act), which would cause things like this to intentionally circumvent them for a reason.
We've been seeing a bit of an uptick in support and funding in the field lately, and I would hate if more people distanced themselves due to claims of this potentially being snake oil.
If her self-experiment lead to somehow verifiable improvements, then at best this would usher funding for proper trials. A good outcome.
If the data she presents doesn't change the skeptic status quo, then it sure wouldn't help our cause.
Even if it does have a noticible effect, will it matter? It's one case, with a ton of people who are angsty about the way it went down. I hope there's a positive effect that leads to real promising trials but I'm not holding my breath. I wonder if the FDA would even be receptive if bioviva went to them with results? I think there's going to be skeptics until the day a working treatment is available. Skeptics, bioethicists, and normal people who will fight against it for various other reasons.
Yes, I'm not holding my breath either - regarding the treatment itself.
As to what would follow in case it does appear to work, there's no doubt that governmental and scientific authorities will remain skeptic. However it could convince biotech corporations and wealthy early adopters to finance (or at least campaign for) real trials, therefore giving traction to the rejuvenation field altogether.
I certainly hope there would be trials pursued. That being said, I don't think many people or companies even have an idea about what happened at Bioviva still. But as per FDA it would have to be in regards to a "real" disease or condition, so we'll see what happens.. Their response to the metformin trial has me slightly hopeful as they said they saw value in something that increases health and survival, even if aging is a target. I just wonder if Liz may have burned her bridges there. Interesting times ahead maybe.
New interview with Liz Parish:
Michael Fossel has made an official post about Bioviva in the wake of comments made about her work. I sense he has had time to consider what he said about her in technology review and has come back in her support! Good on Michael he is a nice guy at heart.