Pondering the California Life Company

The sad truth about Google's Calico initiative is that, for all the hype at the outset, what is going on under the hood looks very much like building a standard issue Big Pharma institution to work on commercializing drug discovery programs that won't make much of a difference to aging. The charitable view of that picture is that they are setting up a sustainable revenue stream in order to later investigate more relevant and interesting things. The more realistic view is that they intend to invest in what is currently the mainstream of aging research, a matter of trying to slightly alter the operation of metabolism to slightly slow down the aging process, and will never go beyond that. There are scores of larger companies capable of doing relevant and interesting things in aging, but they never go beyond tinkering with drug discovery to produce marginal therapies; once a revenue stream and mode of operation is established there is little incentive to do more.

This all suggests that the way in which disruptive ventures working on methods of rejuvenation gain traction with Calico is no different than the methods of gaining traction with the rest of Big Pharma: bootstrap the production of technology demonstrations that work. Gain support through the slow process of networking and incremental progress in research. Become the mainstream. Large scale funding is unimaginative and almost never backs radical new directions until all the excitement is done and the new new thing is obviously taking over. That is simply the way things are, and it is why our grassroots efforts to raise research funding and gain greater attention to the cause continue to be very important.

For the first year of its existence, all we knew about Calico was that the company had 'moonshot goals' and a team of scientific superstars. However, in September 2014 it finally sprang into action by announcing two research collaborations. The first was with AbbVie (a global, research-based biopharmaceutical company) and aimed to 'accelerate the discovery, development and commercialization of new therapies.' The two companies then immediately invested in the creation of a new research and development facility in San Francisco focused on aging and age-related diseases. Initially, AbbVie and Calico provided $250 million each to fund this project, and it was agreed that both sides would potentially contribute an additional $500 million in the future. The two also agreed to share the costs and profits equally.

The second collaboration was with the UT Southwestern Medical Center and 2M, to advance research and drug development for neurodegenerative disorders caused by the aging and death of nerve cells. Basically, Calico managed to muscle in on a deal which already been made between UT Southwestern and 2M concerning the licensing of P7C3 compounds (which had the potential to combat neurodegeneration). 2M and Calico entered into a new license agreement under which Calico took chief responsibility for developing and commercializing the compounds resulting from the research program. Calico no doubt persuaded 2M to agree to the new deal by promising to fund research laboratories in the Dallas area (where 2M is based) and elsewhere to support the program.

All went quiet again until March 2015, when The Broad Institute of MIT and Harvard entered into a partnership with Calico, concerning the genetics of aging and early-stage drug discovery. The partnership aimed to support several efforts at the Broad to advance the understanding of age-related diseases and to propel the translation of these findings into new therapeutics. The Institute agreed to use its genetics expertise and novel drug-discovery tools in pursuit of goals shared with Calico.

In the same month Calico formed a partnership with QB3, a University of California institute specialising in the advancement of biotechnological innovation. The purpose of this partnership was to conduct research into longevity and age-related diseases and, in the process of doing so, foster an interdisciplinary community of scientists in the relevant fields. Funding from Calico was to support QB3 research projects focused on aging; some in collaboration with Calico, others led solely by QB3. In exchange for providing the funds, Calico acquired the option to claim exclusive rights to discoveries made under the sponsored research agreement.

The third partnership made in March was with UC San Francisco (UCSF) (a University of California health sciences campus), on a project to develop potential therapies for cognitive decline. Under the agreement, Calico received an exclusive license to technology discovered in the laboratory of Peter Walter, Professor of Biochemistry and Biophysics at UCSF. This technology could potentially address the damage to cells caused by the Integrated Stress Response (ISR) mechanism. For an an undisclosed up-front fee, UCSF allowed Calico to take responsibility for further research, development and commercialization of the resulting therapeutics.

By April 2015 it was clear that Calico was splashing the cash in order to facilitate the formation of partnerships. For this reason, Calico started to become more tight-lipped about the financial aspect of its deals. In fact, they categorically refused to disclose the financial terms of a new partnership with the Buck Institute for Research on Aging. This partnership was to support research into longevity and age-related diseases. Calico was permitted to cherry-pick innovative research projects at the Institute and, in exchange for funding, obtain exclusive rights to the discoveries made.

Calico's most recent partnership was announced in July 2015 with AncestryDNA (an industry leader in consumer genetics). This partnership aimed to investigate the heredity of human lifespan. The two companies planned to evaluate anonymized data from millions of public family trees, as well as AncestryDNA's database of over one million genetic samples. Calico would then use the findings from the analysis to develop and commercialize potential therapeutics. Again, Calico refused to disclose just how much it had parted with in order to get its hands on AncestryDNA's data.

Looking at Calico's impressive array of employees and collaborations, it would seem, at the moment, that Calico is merely trying to make money using other people's knowledge. However, Chief Science Officer at SENS, Aubrey de Grey, claims that this is just a facade: "they are doing a bunch of highly lucrative irrelevant short-term stuff that lets them get on with unlucrative critical long-term stuff without distraction."

Link: http://lifemag.org/article/solving-the-mystery-of-calico

Comments

Please consider that even if they did revolutionary long-term research, they would probably not talk much about it at this point.

Posted by: Daniel Lemire at August 14th, 2015 8:02 AM

I hope you're wrong about the path you think Calico is going to take. I've been really hopeful about them. To just go ahead and take the slow typical method isn't really in line with Google and their typical "moonshot" thinking. Sure, some of ther partnerships are with places that have been pursuing conventional slowing aging methods, but maybe that's just to have a wider swath of research in all aspects of aging? Google has seemingly limitless funds, so it wouldn't surprise me to see all methods being addressed... But who knows. The brain behind the Calico idea has talked about greatly extended lives publicly before, and this certainly wouldn't really be in line with that. I'm hoping for the best, but expecting the worst I guess.

Posted by: Ham at August 14th, 2015 8:37 AM

Calico's real problem is the secrecy. They could be using published papers from SENS-funded universities, these secretive partnerships, in-house stuff they're not telling us about, anything.

However, if they actually want to release anything in the United States, they can't keep that a secret!

The real problem with secrecy, in general, is that it's too often used to mask incompetence and waste. I'm not worried that Google's working on the secrets to indefinite longevity behind closed doors; I'm worried that they're not, while thinking they are.

Posted by: Slicer at August 14th, 2015 12:19 PM

I think maybe they'll be a bit more forthcoming once they finalize all their planned partnerships... hopefully. It just doesn't seem like a big Google type move if they're simply going to get into the pharmaceutical world to essentially just mimic all the other existing pharmaceutical companies. Aubrey said in his AMA that he has aspirations for SENS to have some kind of partnership with Calico. the fact that they currently aren't at least collaborating together leads me to think a few potential thoughts (outside of the obvious fact that they're separate companies)...

1. Some type of collaboration might actually be be in the works, just working out details. It would be interesting to imagine if Calico brought in SENS to do the research on the regenerative medicine portion of their aging agenda.

2. Calico is going to be working on things in a similar fashion to the SENS approach and they feel they might not need SENS (all their acquisitions and partnerships are being used to approach aging in all directions, not just one or another).

3. They simply don't think the regenerative medicine path is the right one, or feasible, and they're actually going to pursue the traditional slow road.

Any way you slice it, more attention and progress towards this field is always a good thing, even if we don't like the method they're using.

Posted by: Ham at August 14th, 2015 12:47 PM

From their partnerships, it seems that they are following the slow way:

- Attacking cancer the traditional way.
- Attacking cardiovascular diseases the traditional way.
- Comparing genomes of long-lived people to genomes of normal-lived people to find ways to slightly slow aging.

Posted by: Antonio at August 15th, 2015 1:45 AM

Calico obviously see some merit in regenerative medicine as they teamed up with QB3 and the conboy lab very recently

http://bioeng.berkeley.edu/news/conboy-lab-wins-qb3-calico-longevity-fellowship

"July 30, 2015
Yan Liu, postdoctoral researcher in Professor Irina Conboy’s lab, is one of only three inaugural members of the QB3-Calico Fellows program. Liu is now a Longevity Fellow, receiving funding for a longevity-based research project.
The partnership between research company Calico and the California institute for Quantitative Bioscience aims to make discoveries that will translate into a better understanding of the biology of aging and potential therapies for age-related diseases."

Considering that Michael and Irina are involved in regenerative medicine as is their lab and has been for decades it is probably fair to think Calico is very interesting in the regenerative approach via stem cell mobilization and signalling.

Truth is we do not know what Calico is up to but they have a freer hand since Alphabet was created. I sincerely hope they fund the Conboys as they have viable regenerative technology.

Posted by: Steve H at August 15th, 2015 4:55 AM

Larry Ellison Medical Foundation 2.0

Posted by: Jim at August 15th, 2015 6:49 AM

I sincerely hope they're more successful than the Larry Ellison medical foundation.

Posted by: Ham at August 15th, 2015 8:39 AM

Thank you for that find, Steve. A confirmed link between SENS and Calico. Things might actually start getting done now. I can't even express my relief.

Posted by: Slicer at August 15th, 2015 3:21 PM

To be fair QB3 which Calico is part of and the Conboy lab which is supported by SENS is only a small link, I would not read too much into it tbh.

Its probably a case of Calico hedging it's bets. I can try to find out more but I suspect Irina and Michael will not know what Calico is up to.

Posted by: Steve H at August 15th, 2015 3:40 PM

Wow! If it works in humans, it would be awesome!

Posted by: Antonio at August 15th, 2015 4:12 PM

Well lets hope so because that would remove a big source of mortality right there and covers one of the seven deadly SENS.

Posted by: Steve H at August 15th, 2015 5:55 PM

I'll get excited about the misfolded protein attacker after the clinical trials. Broad-spectrum anything has a bad habit of hitting "Oh, yeah, people need that one, don't they..." targets.

Posted by: Slicer at August 15th, 2015 6:13 PM

It would be nice to see executives from Calico attend and speak at the Rejuvenation conference put on by SENS this week in SF. Calico should become a part of the community. It would be good for everyone.

Posted by: Deleo at August 16th, 2015 4:29 PM

Deleo, that's not a bad idea. I'd love to see that happen. Reason, what do you think the odds of that happening are going forward (maybe not this year, but next if more details about calico come out)?

Posted by: Ham at August 16th, 2015 5:59 PM

Dear California Life Company:

I like you to write me about clinical trials relevant to longevity. I have a set of facts about myself that are good for this. I have 4 science degrees and did much that is rare for my own health care and longevity. Also, when's is a pharmaceutical drug going to be available for longevity?

Thank you.

Sincerely,

Dr. Stephen Naghdi, MD-MA

Posted by: stephen naghdi at November 6th, 2016 6:16 AM

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