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Gene editing pioneer and Harvard professor - Dr. George Church

harvard genetics podcast crspr nebula

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#1 onz

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Posted 07 February 2019 - 04:27 PM


Very excited to announce our next guest on the longecity podcast is Dr. George Church!

 

His upcoming gene editing research on dogs is aimed at reversing ageing with the goal of moving this to humans in approximately 8 years! :|o  :-D  You can read more about it in this article.

 

You can also watch this YouTube video where Dr. Church speaks about the delivery of 45 gene editing therapies, all targeted at reversing age-related disease. 

 

He's also the co-founder of Nebula Genomics, which empowers people to contribute to genetic research while dramatically reducing the cost of genome services to make it affordable for everyone:)

 

The interview is scheduled for next Friday the 15th February, let us know if you have any questions in the comment section below  :laugh:

Attached Files


Edited by Mind, 07 February 2019 - 06:56 PM.

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#2 Lothar

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Posted 12 February 2019 - 01:44 PM

If nobody wants to know something from Prof. Church I'll take the chance to ask five questions all at once:
 
1. I've seen that Prof. Church belongs to the advisory board of the SENS foundation:
 
 
So I want to know the relation between his work in the aging research field and the SENS approach: what have they in common, where are the main differences? Is it - for instance - the following:
 
„Church: By going straight to human cells, we won't get into the trap of spending years working on mice, which is rather expensive, only to find out that it doesn't work in humans. We can actually do a cheaper and more relevant study in human cells, confirm them in mice, then test them in larger animals, and then in humans. I think that going from human cells to mice and back to humans is likely to save us time and money."
 
 
2. Does his work aim only on some factors that cause aging or on all?
 
3. Every time someone is making a prediction about upcoming breakthroughs in anti-aging research for humans this has tremendous consequences for probably millions of people. Especially for the elder ones the question whether it will last less than ten or more than twenty or even thirty years etc. is a matter of life and death! So I want to know how solid this above quoted - in my opinion revolutionary - prediction* of just 8 years really is!?
 
- What are the relevant factors, that this will really come true? 
- What are nearer milestones or interim results to judge, whether the scientific development is in time, or slower or even faster? 
- How are the different experiments, the 65 gene therapies that are being tested in mice and larger animals*, working? 
- Are they already into phase one trails in humans?
- Latest results?
 
 
4. I've read that Prof. Church is involved in a lot of different scientific fields, for instance he is permanent portrayed in the media for the attempt of bringing back the mammoth by new genetic means. My question is what priority has the aging research in all of his works? And especially how many employees in how many teams work for him in the anti-aging field?  Has he enough scientists or is it a question of financing to even speed up the development?
 
5. What is his opinion about several other promising studies in the anti-aging field and are there overlaps to his own works like Senolytics, Metformin, Parabiosis, the Calico approach, or the work of Craig Venters Human Longevity Inc. ... to name only a few?

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#3 Mind

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Posted 12 February 2019 - 06:42 PM

I recall at one point that Dr. Church said he did not want to extend his own life or rejuvenate. I am not 100% sure this is an accurate assessment of his opinion, but I intend to find out. Being that he is so involved with the rejuvenation scene, I would suspect he would want to live a lot longer.



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#4 Lothar

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Posted 12 February 2019 - 07:08 PM

@ Mind: I suspect too. See the following quote from the Technology Review article, which is linked above by the thread starter:
 
„In a January presentation about his project at Harvard, Davidsohn closed by displaying a picture of a white-bearded Church as he is now and another as he was decades ago, hair still auburn. Yet the second image was labelled 2117 AD—100 years in the future.
 
The images reflect Church's aspirations for true age reversal. He says he'd sign up if a treatment proved safe, or even as a guinea pig in a study. Essentially, Church has said, the objective is to "have the body and mind of a 22-year-old but the experience of a 130-year-old.""
 

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#5 xEva

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Posted 13 February 2019 - 06:50 AM

In the lecture you linked, several times, he refers to CRISPR as "genome vandalism". Could he elaborate on this?

 

the other question has already come up on the forum, is about the immune response to the viruses used in the genetic therapy.  Like, is it true that it can be done only once, because the immune response will not allow it the second time? What if the person has been naturally exposed to the particular virus used  and already has antibodies to it?   


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#6 xEva

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Posted 13 February 2019 - 07:33 PM

And another question. In a lecture a year ago (on youtube) he mentions a study  where the endogenous viruses were edited out of a mouse genome. Q: What was the impact on the development, health and lifespan of those mice?   


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#7 xEva

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Posted 18 February 2019 - 05:47 PM

so where is the podcast itself?  Is there a link somewhere?


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#8 Mind

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Posted 18 February 2019 - 06:08 PM

The podcast is done. I got in most of the questions. We are working on the editing now. The was a little trouble in the recording, so we might have to transcribe this one.



#9 xEva

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Posted 10 March 2019 - 09:12 PM

So, is there a link to this podcast? thanks


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#10 Mind

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Posted 11 March 2019 - 03:53 PM

We will have a transcript soon. The audio did not record well.



#11 Mind

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Posted 18 March 2019 - 04:19 PM

I asked him about his current focus on research and he said most of his efforts are involved in Rejuvenate BIO:

 

 

We’ve been involved in making databases for (long-lived species) and the naked mole rat, but the most recent I would say is turning all that know-how from the databases, model organisms, and super-centenarians, into gene therapies. And then passing those … in combinations with a large number of age related diseases, so each of these diseases are thought to be multi-genetic and our hypothesis is that there a few proteins that are decreasing with age that we could boost back up with gene therapy....some very intriguing results from combination gene therapy in mice and is now (interested in) applying it to dogs and humans.

So Noah and I started the company called Rejuvenate Bio which is now located in San Diego where Noah is (going) to do this is in dogs initially and then soon after in human trials.

The dog clinical trails go very quickly, typically 18 months while humans take 10 years. And it is possible we could start human clinical trials in 2 or 3 years but the dog trials will be done by then and hopefully either one will be proven in mice.

 

I asked him about gene editing approaches to rejuvenation vs. SENS damage repair approaches. He said he is supportive of "Many shots on goal", which is a reference to hockey (or soccer). Basically the idea is the more people working on different approaches to rejuvenation the more likely we will "score" with a winning therapeutic or other therapies.

 

 

 

I’m a big believer in diversity and diversity of ideas and lots of "shots on goal' …  Aubrey and I nicely represent … two extremes …(the basic idea is that) damage has to be repaired … is Aubrey’s representation, and I would represent that you could genetically reprogram cells to make them young, then they will take care of damage they way that young cells do, so most of the diseases of ageing do not kill 20-year-olds and it’s not just because there’s passages of time where you’re accumulating damage but they’re actually able to …  repair damage more effectively. So there are certain kinds of damage which (can be addressed) genetically just by making the cell think that it’s young but, there’s so many that can be addressed that way (so the SENS approach is) complimentary and hopefully we’ll have multiple solutions and that’s what we’re trying to do is … combinations of solutions because we think it’s a hard problem with potentially easy solutions.

 



#12 Mind

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Posted 31 March 2019 - 01:00 PM

About CRISPR and "genome vandalism", he wanted to point out the difference between adding things to the genome vs. "subtraction/deleting" which is CRISPR.

 

 

 

Right so not just CRSPR but most of the nuclease based therapies are best at subtraction … cutting DNA and then DNA repair in such a way that the gene is knocked out. Long before there was any editing methods in clinical trials there were classic gene therapies where you’re adding a missing protein, it could be missing because of disease or due to ageing. So replacing missing proteins is more nuanced than knocking them out, and genetic reprogramming also doesn’t involved covalent modification necessarily, there are a number of complimentary approaches to gene therapy … to all of them at some level.

 

About editing endogenous viruses and longevity effects, he says they haven't yet determined if there were any effects on aging.

 

 

 

So that was actually done in pigs, we wanted to do it in mice but we did it in pigs because those viruses are potentially hazardous to the immune suppressed transplant recipient patient … the virus could become a zonolotic disease like swine flu … so we felt it might be easier to knock out all of the pig (viruses)… and it was relatively easy and we’ve done it in multiple pig strains now … so it can be done, it’s interesting in the ageing context in that there’s some evidence (viruses)… can be associated with ageing, they are causing a kind of genetic damage … during development, so it might be preventative medicine to stop them

 

About Rejuvenate testing in dogs. He said they are focusing genetic approaches because it is easier to find effects, but they will try other things as well.

 

 

 

You know I think long-term it can address almost all of them, but short term there are limitations to the delivery, we’re using a and b viral delivery for the gene therapies, and so we’re focusing on therapies that are systemic or where a small number of cell getting the delivery does not affect a large number of cells by non-autonomous expression. I think the gene therapy tend to be easier to test the hypothesis, we can test dozens of hypothesis that are well established then we can move them into mouse and dog very quickly without doing these very difficult searches for small molecules where classic pharmaceutical companies would go. But in the lab we’re trying various other approaches … looking at old and young samples from the same person

 



#13 Mind

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Posted 31 March 2019 - 01:10 PM

I asked about current things in the marketplace, like "senolytics, NAD boosters, metformin, etc...) He said they all look kind-of promising based upon animal data.

 

 

 

Well I think those 3 that you just mentioned are promising, I personally think there’s probably going to be some combination therapy, you’ve got multiple system failure, a kind of planned obsolescence and you need to get a number of them back up to a youthful stage, and once you get a few of them … just like now you have several of them pushing you down you’ll have several pushing you back up. Most of the preliminary results on those 3 categories have a significant shift in the longevity (in animals)

 

When I asked him about human lifespan trials, he mentioned the difficulty of conducting traditional trials because humans live too long, but with better biomarker testing, we should be able to achieve progress in rejuvenation therapeutics.

 

I asked him about wanting rejuvenation for himself and the past impression (in error perhaps) that he wasn't interested in rejuvenation for himself.

 

 

 

No I think I’ve always been interested in it for myself but I don’t think I should go to the front of the queue necessarily, I’m not risk averse but I also don’t fell that I have to be guinea pig number 1, I am guinea pig no. 1 to the personal genome projects which is mostly analytic not therapeutic. I just feel that to be serious about this you have to have a strong multi-pronged effort and you have to have randomized clinical trails that involved animal models and humans, and I’ve always been willing to be part of that.

 

I asked if any of his colleagues are interested in rejuvenation and translational research and why not many researchers take that approach.

 

 

 

It’s hard to say, we have a world class team here, but it’s a tiny subset of the faculty, and I think other people feel our research isn’t as relevant, or maybe they think its’ a long shot, maybe they don’t want to try it on themselves because they think about being really old for a long time rather than being extra youthful. But I think like many fields it’s going to be changed by a small number of people who happen to have the right vision at the right time with the right tools.

 

Once again, I apologize for the audio trouble that plagued this podcast.



#14 samin

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Posted 12 April 2019 - 03:16 PM

Hi @Mind. Is there a transcript? Or is everything covered on this thread? Super thanks for the podcast and what you do. I'm loving them :)



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#15 Mind

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Posted 12 April 2019 - 04:06 PM

This is the best that could be recovered from the audio.







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