Perspectives on Altos Labs and its $3B cellular rejuvenation push

I wrote briefly a few months ago about Altos Labs. It’s a new kind of biotech institute that is focused on cellular reprogramming.

My original piece was sparked in part by an article around the same time by Antonio Regalado over at MIT Tech Review. He provided some tantalizing details on Altos.

Also, I had heard some rumblings about it before.

Now we know much more and it’s clear this is a huge deal.

Altos Labs PIs
Some of the Altos Labs PIs listed on the website including my soon-to-be former UC Davis colleague Jodi Nunnari.

Altos Labs: big money + great scientists = serious potential

A new press release (PR) tells us quite a bit about Altos but leaves some interesting open questions too.

First off, they’ve got $3 billion in funds to get started.

Where did all that money come from? We’ll probably learn more about that soon. Earlier reports suggest Jeff Bezos is a major investor. Update: As best as I can tell so far I don’t see any plan to go public so it’s probably too early to talk about possible Altos Labs stock.

You can check out the new Altos Labs website too for more info including the list of their PIs.

The Altos Labs PR also reiterates some of the earlier hints including key people involved. These include Shinya Yamanaka and Juan Carlos Izpisúa Belmonte. Both are stem cell researchers doing pioneering work in the area of cellular reprogramming.

Yamanaka won the Nobel Prize for his transformative work reprogramming everyday cells to a pluripotent state yielding so-called iPS cells. These cells are the inspiration for the URL for The Niche website right here. Belmonte has produced some major firsts including in the embryo chimera space and with in vivo reprogramming work.

There are several other notable scientists involved in leadership. Rick Klausner, Wolf Reik, Peter Walter, Thore Graepel,  and on the Board three more Nobel laureates in Frances Arnold, Jennifer Doudna and David Baltimore.

The executive team seems outstanding as well with amazing experience.

What does Altos mean by “cellular rejuvenation programming”?

So what will Altos do exactly?

What are the big picture goals?

Antonio picked up on Twitter on a catchphrase from Altos: cellular rejuvenation programming.

What does this catchphrase mean?

Frankly, my first reaction was it feels a bit overly processed in a PR kind of way. However, I think I get what they mean by it and why they choose it.

Antonio’s thread of Tweets is an interesting read as he tries to answer that by dissecting the origin and possible main point of the phrase. Check it out. Many of his impressions ring true including the tie-in of the word “programming” in the phrase to the world of computers and coding, which should appeal to investors.

The origin of the overall Altos corporate catchphrase seems to arise from the core invention of Yamanaka with his cellular reprogramming method to make iPS cells. The new phrase reads like a mash-up of “cellular reprogramming” with the anti-aging buzzword “rejuvenation.”

It seems that the main goal of the firm will be to fight aging (and disease) with some kind of cellular programming technology.

Can they do it?

Reprogramming oldness in people

It’s clear that cellular reprogramming can reverse the oldness or agedness of cells to take them back to a youthful cellular state in the form of iPS cells. However, it’s much less clear whether this or similar technologies could reverse the aging of organisms like mice or especially people.

The new firm brings to mind past biotech efforts aimed at aging like Google’s Calico, which hasn’t done much so far it seems in almost a decade. That experience highlights the hurdles here and how slow this kind of research can be when done right.

Getting translational science into clinical trials can also take a really long time.

Still, Altos has a dream team to tackle these very difficult but exciting challenges.

Whatever rejuvenation methods they develop, the approaches will have to be both effective and safe.

Waddington Lanscape Knoepfler
Waddington Landscape Model highlighting the risk of cancer formation from reprogramming, Knoepfler & Seamount.

Challenges

What are the safety considerations?

One of the challenges with applying the idea of reprogramming to try to “anti-age” a person or stymie aging is that there can be a fine line between reprogramming and tumor formation.

For instance, in vivo reprogramming studies in animals have yielded tumors at times.

Older work by our team here in the Knoepfler lab found that some of the earlier and admittedly more basic reprogramming methods to make iPS cells bore some notable similarities to the tumor formation process. This overlap included the types of genes being induced as the processes unfolded.

While reprogramming methods have come a long way (e.g., no longer requiring the MYC oncogene or retroviruses), turning back the clock on cells is inherently going to risk invoking some of the same pathways that also can come into play in cancer. Why?

Conceptually, one of the main reasons that trying to tackle aging with cellular therapies brings possible risk is that the core stem cell machinery overlaps with some of the key genes and pathways that get mutated or otherwise induced during tumor formation.

There are probably ways around this.

Possible strategies and targets

For instance, it’s possible that a fully chemical reprogramming process or one that involves transient introduction of reprogramming RNAs could be safe and effective in making some cells or even tissues younger inside the body.

Reprogramming research could also indirectly yield cocktails of proteins that might have anti-aging properties.

If you look at the research foci of the Altos PI’s you can get some idea of the overall institute’s strategies and diseases of interest.

I see a heavy neuroscience and brain disease focus, for instance.

There’s also substantial research focus on senescence, mitochondria, metabolism, epigenetics, and protein folding and function. All make sense.

Will AI come into play? Probably.

Looking ahead, it’s going to be fun to watch this giant experiment unfold.

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