I wrote briefly a few months ago about Altos Labs. It’s a new kind of biotech institute that is focused on cellular reprogramming.
Now we know much more and it’s clear this is a huge deal.
What’s in this article
What is Altos Labs? | Cellular rejuvenation | Reprogramming oldness | Challenges | Altos Strategies | Analysis of their paper | More insights | Locations | CIRM synergy? | Jobs | References
What is Altos Labs and does it have stock?
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.
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.
"cellular rejuvenation programming"
This was the little analyzed new technical coinage in the Altos Labs news and press release yesterday.
I expect they thought about it.
A thread 🧵
— Antonio Regalado (@antonioregalado) January 20, 2022
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.
Challenges for Altos Labs
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.
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.
Altos Labs focus: human cell aging & DNA methylation
It’s still early in their evolution as a biotech, but one day over lunch I took a look at what Altos researchers have published.
For this purpose, I did a simple PubMed search for papers that mentioned “Altos Labs.” I found 134 papers in mid-July 2023. Some of the published research was already ongoing before Altos existed but still that’s an impressive output. (By way of update now in early August around 3 weeks later the same Pubmed search yields 145 papers.)
Thankfully, the search, downloading the results, and making a word cloud from the paper titles (see above) took about 1 minute since I’ve done this kind of thing before on PubMed. It’s a quick but novel window into the institution’s priorities.
Note a limitation here is that the phrase “Altos Labs” may be in papers with only one or a few authors from Altos or even in papers that just mention Altos Labs. However, my impression from scanning through the papers is that mostly they are research papers from Altos teams. While manuscript titles don’t tell the whole story, they are the most important words of papers.
The most common title words are shown in bigger fonts. The top word was “aging” followed by “cell“/”cells“, and “methylation“. Another frequently used word in their paper titles is “human.”
That tells a story unto itself to me: Altos Labs papers have focused mostly on studying human cellular aging through DNA methylation analysis.
More insights on published papers
Note that Altos researchers, including especially Steve Horvath, have been defining biological clocks in cells and trying to relate that to aging for years prior to Altos being launched. I still found it surprising just how much the word “aging” is present in the paper titles. Same for “methylation.”
Based on the next tier of words in their paper titles, they are doing a lot of single-cell analysis, stem cell work, and epigenetic research.
We have “senescence”, “mice”, and “age” up next as common words in Altos paper titles. Other words pop up like “reprogramming”, “clock”, and “regeneration”. Another surprise to me was that “reprogramming” wasn’t more prominent.
It’s also interesting that the word “rejuvenation” mostly isn’t in the mix in the paper titles.
Overall, while Altos Labs may technically not be a longevity company (or at least not want to be viewed that way), their research is heavily focused on aging, cell biology, and DNA methylation, which are major areas of emphasis in the longevity space.
With all of this in mind, can Altos safely achieve rejuvenation in people by focusing on these areas? Within a decade? How will their research emphasis evolve?
It’s going to be fun to follow their work in coming years and track their research foci.
Altos locations
While the firm appears most bound to the Bay Area, it will be a broader and even international effort. From the website:
Altos will be initially based in the US in the San Francisco Bay Area and San Diego, and in the UK in Cambridge. The company will also have significant collaborations in Japan.
I’m curious how the other locations come together and grow.
It’ll be interesting to see if more of the great stem cell researchers in the San Diego/La Jolla area come on board for that Altos hub with the original group of four listed.
Altos Labs and CIRM?
One thing to consider is that given Altos’ mission related to regenerative medicine and regeneration as well as their Bay Area HQ in a sense, will they have some synergy with our California state stem cell agency, CIRM?
This kind of interaction would make good sense. CIRM, which stands for California Institute for Regenerative Medicine, is California’s largest funder of stem cell research. In fact, CIRM is one of the largest funders of stem cell research in the world. Possibly the largest now with its new round of state funding.
At the very least one might expect the PIs at Altos to start applying for CIRM grants to tap into that funding. This seems like a no-brainer even if Altos has around $3B in its own funding from investors.
However, I also wonder if the two entities might join forces on some initiatives.
Jobs at Altos Labs
A recent search on LinkedIn found 29 job openings at Altos Labs.
I have heard through the grapevine of quite a few people potentially gearing up to work there beyond those already announced.
Generally, it seems like Altos is going to be a major force in the regenerative medicine field in the U.S. and globally. I’m sure I’ll be posting much more about it over coming years.
Looking ahead, it’s going to be fun to watch this giant experiment unfold.
Focusing on therapies that involve transient introduction of reprogramming RNAs
I wonder if they know about MYMD-1 (MYMD bio), which is in stage 3 of very successful FDA trials. Its primary compound (patented) has already successfully provided real and significant anti-aging benefits. They are way ahead of Altos Labs. Too bad.