More Signs that Calico Will Fund Broad Mainstream Drug Discovery and Genetic Research

Google is pouring a large amount of money into aging research via the Calico Labs initiative. Their declared aim is to produce treatments that impact the whole of age-related degeneration, and their open support of that goal is certainly going to make it easier for other initiatives to raise funding in the future - it adds that much more legitimacy to the space in the eyes of investors and philanthropists who have so far stayed away. That is the good part. However it has become increasingly clear that the Calico Labs approach, telegraphed pretty early on, is to broadly fund the central mainstream of research and development relating to aging, which at this time is the standard process of drug discovery and investigations of the genetics of longevity. In this they might be considered a second iteration of the Ellison Medical Foundation, a funding addendum to the present efforts of the NIA and pharmaceutical companies, but really introducing no fundamentally new and better strategy. So expect past performance to predict the next decade or so here.

The Ellison Medical Foundation achieved essentially nothing of great note over the course of its existence, a period when the same could be said of most NIA projects, because the mainstream approach to aging does not consist of strategies likely to produce any significant gains in healthy human life span. I've talked about why this is the case at length over the years, but in essence it boils down to the same reasons as to why I support the SENS programs for rejuvenation biotechnology development. The preponderance of evidence strongly suggests that aging is caused by an accumulation of damage to cells and tissues. The best approach, which is the SENS approach, is to repair that damage periodically but otherwise not tinker with the operation of our metabolism: it is complicated and we understand very little of it in comparison to our understanding of the damage that is linked to aging. This is not the mainstream approach, however. In the mainstream of aging research, where researchers are interested in treating aging at all that is, the focus is on finding ways to alter the operation of our metabolism so as to slow down damage accumulation.

It doesn't require a vast and detailed understanding of biology to grasp that slowing damage is a worse strategy than repairing damage in any system, complex or not. It cannot restore youthful function and is of limited utility to old people. Further, safely altering metabolism to achieve specific goals is much harder than repairing known and clearly demarcated forms of cellular damage. This is illustrated by the fact that a clear set of plans for damage repair exist with many different options for implementation, but at this time - and after decades of work and billions of dollars invested - researchers still don't have a clear understanding of how calorie restriction works or can be reproduced, and that is the simplest and most reliable altered state of metabolism known to extend life and improve health. Even if the calorie restriction response could be recreated with a drug, the outcome would be far less health and life gained than for even a partial implementation of repair treatments.

Here are some recent news reports on the Calico initiative that reinforce the point on the broad fundamental research strategy they are choosing to take, acting in essence as a supplemental fund for existing programs and approaches to drug development, with a heavy emphasis on genetics:

Broad Institute and Calico announce an extensive collaboration focused on the biology of aging and therapeutic approaches to diseases of aging

The Broad Institute of MIT and Harvard has entered into a partnership with Calico around the biology and genetics of aging and early-stage drug discovery. The partnership will 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. "This alliance is a key part of Calico's strategy to bring the best cutting-edge science to bear on problems of aging. The Broad Institute is one of the nation's preeminent research organizations whose outstanding research has repeatedly revealed fundamental mechanisms of the biology and genetics of disease," said Art Levinson, Chief Executive Officer of Calico.

Calico, QB3 Launch Longevity R&D Partnership

Google-back Calico said Tuesday it will partner with the University of California institute QB3 to study longevity and age-related diseases, as well as create and foster an interdisciplinary community of scientists in those fields. The four-year partnership is designed to generate discoveries that will translate into greater understanding of the biology of aging and potential therapies for age-related diseases. The partnership plans to identify, fund and support QB3 research projects focused on aging, using committed funding from Calico - which focuses on aging research and therapeutics. "We are all aging, and we will all benefit from the discoveries made in this program and the therapies that will result," QB3 director Regis Kelly said in a statement. "We are grateful to Calico for recognizing the deep expertise at the University of California that attracts so many scientists of exceptional ability."

For those of us who do support the SENS repair approach, the lesson to take home and remember is that we will see mainstream funding of SENS-related research and development when that work becomes mainstream. Not before. It is already the case for cancer and stem cell science, where there are strands of SENS-like work taking place in many laboratories, but for the other forms of tissue repair there must be demonstrations of effectiveness. We can learn from the growing interest in senescent cell clearance: that only emerged in earnest after the 2011 demonstration of improved health in accelerated aging mice. This year we are seeing the fruits of that interest in the form of new demonstrations of effectiveness in normal mice and the first company founded to commercialize an approach to clear senescent cells. More researchers, more results, more programs underway.

However frustrating it might be, funding follows success. This is why it is so important that we continue to raise funds for early stage SENS research in order to create the technology demonstrations that can pull in that attention and funding. We are, after all, winning at this game step by step. Five years ago senescent cell clearance was something that no research groups looked at in earnest, and now we have mice that are healthier as a result of treatments that remove senescent cells. Ten years from now there will be clinical trials underway in humans. Meanwhile there are four or five other important forms of damage repair that must make the same leap, and that is only going to happen with the support of you, I, and other philanthropists.

Comments

Question for anyone:

Hypothetically, let's say SENS nails down the removal of senescent cells. Would they patent the method and sell/lease it? Would it be open source? Are there any commercial legal hangups being a non-profit?

Posted by: johnathan at March 24th, 2015 8:39 PM

@johnathan: The SENS Research Foundation funds work internally but also at established external laboratories. What happens to the intellectual property thereafter depends on the nature of the grant agreements, but it is unlikely to be open when other large establishments are involved (especially universities). One of the better futures ahead for the Foundation is to augment philanthropy with licensing revenues that can flow right back into more research, and I imagine that's been the goal for a while now.

The basic research itself of course will be open (or at least accessible for a journal fee), and any group in areas less respectful of intellectual property and with the necessary skills can work in parallel to develop their own implementations or make the leap to commercial venture from what has been published to date.

Posted by: Reason at March 24th, 2015 9:03 PM

Lets hope for some more breakthrougha soom because the biotech market is buoyant/bubbly right now. The people at Mayo/Scripps Institutes must be getting near to looking for some venture capital... it would be nice if this and a few other arms of the SENS program could go to the markets for capital. From reading fightaging.org the next likely breakout area is the removal of glucosepane.

Posted by: Jim at March 25th, 2015 12:57 AM

@johnathan: SENS is now developing a new mouse strain that they will patent. So yes, unfortunately, probably most of their practical research will be patented.

Posted by: Antonio at March 25th, 2015 2:12 AM

I just... don't get it. These guys are literally giving interviews to major publications where they talk about hundreds of years of life. Ray Kurzweil is a part of their organisation. What the hell am I missing here? Why are they seemingly only going after small gains, while trumpeting such a revolutionary worldview?

Posted by: Ben at March 25th, 2015 2:16 AM

You state that Calico wants to do nothing but fund others' research and claim that this will lead to unsatisfying results. You provide no arguments other than a comparison to Ellison.

Calico is not Ellison. This is a different time and place. For one, we can look forward to deep learning helping out in drug discovery, and Ido Bachelets DNA-nanobots to deliver said drugs precisely where they need to be.

Calico is no doubt aware of the SENS / Kurzweil mindset as well. It's quite a claim to say Calico won't lead to anything useful.

I am, however, of the opinion that Bill Maris needs to have a meetup with Aubrey de Grey.

Posted by: Jay at March 25th, 2015 3:41 AM

I'd like to think Calico will lead to something useful, especially with all the big names they have on board, along with the other competition in the field. Competition drives innovation, so anything that puts us into LEV or much closer to it (depending on your age) would be welcome. Also, about Larry Ellison... Is he funding anything in the field anymore? He clearly has an interest in aging research... It would be great if SENS could secure some funding from him, equivalent to what the Ellison foundation was getting, though I have a feeling SENS might need to show more in order to secure such funding.

Posted by: Ham at March 25th, 2015 5:11 AM

@Ham: Based on interviews and articles from past years, I believe that Ellison's interest was actually in molecular biology, not aging. It was somewhat a matter of happenstance that he happened to fund aging research.

Posted by: Reason at March 25th, 2015 6:13 AM

I see. Still, his comment about death and "not understanding how someone could exist one moment, then vanish" (I'm at work, don't have the exact quote) shows that he would probably have an interest in the field at the very least. Whether there's enough interest to provide funding is a different issue though.

Posted by: Ham at March 25th, 2015 6:53 AM

SENS is clearly high enough profile nowadays that Calico will be well aware of what they are trying to do. If I remember correctly Kurzweil even provided a small amount of funding to the Methuselah Foundation in its early years.

What I'd be really interested to know is the reasoning behind why organisations such as Calico aren't choosing to take the rejuvenation path. The "repair and maintain" process is pretty much the de facto standard in every branch of engineering out there so you'd expect it to be a slamdunk for biological engineering too. In fact, most of medicine works this way; you don't need to understand depression at a cellular level to prescribe some Prozac.

I believe Kurzweil is 67 right now, maybe his outlook may change over the next decade or so.

Posted by: steve695 at March 27th, 2015 3:25 AM

I'm sure calico is aware of SENS' approach, as are most everyone else in the field. However I wouldn't necessarily equate that to being high profile. Once they bring forth something meaningful (and in turn, secure substantial funding) then I think they'll be truly high profile. I do favor the SENS approach, but if other things come along as a stopgap until their therapies are realized then I can deal with that. I think once they produce meaningful results the rest of the field might switch directions to build on the SENS idea.

Posted by: Ham at March 27th, 2015 8:38 AM

@Ham:- If "meaningful results" are what it takes to be "high profile" then where are the "meaningful results" supporting pharmacological mimicry of longevity alleles? If you include preliminary findings in culture or in mice, this approach has far fewer "meaningful results" than SENS-like approaches.

Posted by: José at March 27th, 2015 1:16 PM

Why do you think SENS has comparatively little funding? Despite their promising premise, they haven't really provided any breakthroughs that have captured people's attention. Calico is high profile because it's backed by Google, and their vast amount of wealth. So no, I don't think they are quite as high profile as we all would like them to be. Could they potentially be? Yes of course, especially if they even had half the money that a company like Calico does at their disposal. It's kind of a catch22, since they need to produce results to get funding, and results generally take a decent amount of money. Also, where are the real meaningful results from SENS-like approaches so far? Do you mean the Senolytic drugs found by Scripps/Mayo Clinic that seems promising, but still need to be clinically tested? Or Rapamycin in yeast, fruit flies and mice?

Like I said earlier, I favor the SENS approach, but I don't think the first generation of therapies are going to come solely from that approach... probably more of a combination of SENS and metabolic approach. I hope SENS finds something and everyone switches toward that type of research, but until then, I don't expect most companies to divert from the slow road.

Posted by: Ham at March 27th, 2015 2:18 PM

Drug discovery might not be as useless as the author believes it to be.

I have here a link where Aubrey de Grey praises Insilico Med.

http://globenewswire.com/news-release/2015/03/27/719718/10126673/en/InSilico-Medicine-Inc-Stands-Out-from-High-Tech-Startups-at-2015-GPU-Conference.html

Quote: "To analyze how cancer cells respond to certain treatments, you must run drug scoring algorithms on high-end big data computer systems," said Zhavoronkov. "And no one can manage this work more effectively than our team of experts in both computer science and bioscience."

Posted by: Jay at March 27th, 2015 5:08 PM

We are missing something here, for sure. Why is that? because in real business world if an entity (SENS in this case) holds a technology that is disruptive/cutting edge, and is looking to team up, there is no way that a larger entity will not show up interest in a decent time frame (1 maybe 2 years) and partner. Or here we see SENS looking for funding and Google sitting on large amounts of money, yet they decide not to "acquire" SENS technology, but go their own way? Why is that? Isn't SENS rejuvenation technology convincing? Yes, most part of it is still “on paper”, but yet, analyze that information and can tell you if it is what pretends or not. So I believe, we are missing something, somewhere.

On the other hand, if SENS technology is "working for sure”, why aren't they "taking it to the bank"? Let's do some numbers. From what we know so far, SENS is talking about a need of 1 billion / year, to "make it happen". US/Canada + EU and couple other countries around the world, have about 1 billion people. Let's say 30% from these people, are in need to use rejuvenation to get back to their 30s. That is approx. 300 million people that for sure wants to pay for rejuvenation. In a dream world, a rejuvenation treatment would cost about 30k. So we are talking about a “sure” revenue of 9,000 billions.

Now, you tell me that if you go to couple large financial institutions and tell them that you have a technology that rejuvenate humans (and mammals), but to fully develop that technology requires an investment of 1 billion/year for next 10 years (and yes, might bump to twenty billions to be safe...) but in return they get a 9,000 billions (minus SENS percentage, that is negotiated at the beginning) … they will say NO to this? I don't think so!

How about this for a funding solution for SENS?

@ Michael Rae – would be nice, when you have the time, to comment on this suggestion. Thanks!

Posted by: Adrian Crisan at March 27th, 2015 5:23 PM

In my previous post, I accidentally provided the wrong quote. The right one is:

"Aging is humanity's most complex and daunting medical problem and it has defeated us for too long," said Dr. Aubrey de Grey, a gerontology expert and the Chief Science Officer of the SENS Research Foundation. "We will overcome it with a trifecta of new technologies, new insights - and new data analysis tools, an area at which Insilico Medicine promises to be at the forefront."

Posted by: Jay at March 28th, 2015 2:45 PM

I've thought two ways to better get the SENS agenda into the public eye might be:
1) Rejuventaion work on dogs or even rats/mice which conclusively shows they can live for an expanded time. Youthful, 5-year old mice would probably make headlines. Then, in the media spotlight, the involved scientists could say: "this is wonderful! *sigh* Too bad mainstream science and health authorities don't care to replicate this in humans, especially given the health costs of an aging population...."
2) At a more shallow yet effective(?) level, if it could be more widely known that glucosepane research would have a positive impact on delaying/reversing skin wrinkling it might cause an uptick in research funding. Certainly many members of the public, worried about their visibly aging skin, might be very interested in knowing the effects of AGEs like glucosepane on wrinkles, especially given how vain many people are (I consider myself among the latter). So this would be a shallow approach to a more serious issue but it might be effective, too. Imagine an advertising campaign like this: "we CAN do something about those wrinkles!!" Again, an approach that works on vanity but it might be useful.

Posted by: Chris at March 31st, 2015 7:48 AM

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