Researchers are puzzled by Calico’s stealthiness | Hacker News Reader

Researchers are puzzled by Calico’s stealthiness

vox.com

There are lots of good reasons for secrecy in these circumstances.

All the more extreme, imaginable interventions aging are going to be quite controversial - scientifically, socially and institutionally. The effects of anti-aging interventions would also be controversial.

Just as much, this is going to be chasing a lot of things that will turn out to be wrong. Being wrong and investing money "uselessly" isn't something that is presented very positively in the public eye these days.

Nah.. secrecy in a bioscience company is a bad idea. You have to have peer reviewed primary literature to support the engineering required.

...you have to have peer reviewed primary literature...

Maybe they are just not ready for that. This whole piece comes across as a situation where Calico wants to work in peace and quiet, and the rest of the world is literally dying (sorry) to know what they are working on. I can understand their idea of wanting to be left alone: Science is a field that by its' very nature is full of naysayers and sceptics. This isn't a bad thing: this is how new science is validated. However, release your ideas too early, and you have a good chance that a whole circus develops around the impossibilities of their ideas or direction, and possibly, Government oversight and regulations before anything is actually ready for any kind of scrutiny.

The overall tone of the article strikes me as "We are curious about what Calico is doing, and we are really annoyed they won't tell us". Remember, this is being done with private money, not Government grants, and Calico doesn't owe anything to anybody.

Still a bad idea.

Maybe I've read too many science fiction dystopias, but I think it will be interesting to see if any breakthroughs that this company makes are kept back to benefit the Google elite or shared with the rest of society.

I am sure they will be shared with as many people as can a) afford it and b) are of a similar mindset to the gate keepers.

Will it be: "Can afford it AND are of similar mindset" or would it be "OR".

Just much, the ultimate cost is big question. The only way to make a breakthrough imo is some combination of procedures that cut the Gordian knot of current health care processes and ways to automate these processes. Together, this may be cheaper than artisanal Cancer care and research - well especially if it could be done without royalty payments in Costa Rica.

So whether the knowledge gets out is a big question - cue the secrecy question again.

"Just much, the ultimate cost is big question."

There's a really interesting Radiolab episode that deals with this question.[1]

To quote from the episode:

"What do you do if you have a really expensive drug that's really, really good? ... Everyone that I know pointed me to this new drug, it's called Sovaldi... it is a drug that treats Hepatitis C, which is caused by a virus, and the disease itself goes to work on your liver, it inflames it, it scars it, it can cause liver cancer, cirrhosis, it can be fatal, and for the longest time the treatments that they had weren't that great or they just had wretched side effects, and along comes Sovaldi. It's one pill, twelve weeks, you take it with some other antiviral meds, it's a super simple treatment option, and the side effects are very minimal. It was kind of like the wonder drug. So a lot of doctors start to prescribe it. In the first half of 2013 70,000 people in the United States were treated, and it had a 95% rate of cure, in other words the virus was erradicated... but this drug costs $1000 dollars a pill, for one pill that I take one a day..."

Now imagine how much a cure for aging would cost.

[1] - http://www.radiolab.org/story/what-year-life-worth/

Sure, priced like a contemporary drug, the price of a life extender would infinite.

But then again, priced like a contemporary drug, the price of air or water would be infinite too. Fortunately, we have much of this around, so far, for nearly nothing (air more than water, so far again).

What about the Hep C drug makes it expensive? The research? The production process? The patents racket? If you knew the recipe could you make it in your basement with some ingredient of modest cost? Of expensive cost?

We're google, we love you! As long as you're not a gunowner. Or whatever other group we decide to label as undesirables in the future.

No elixir for you 65827!

Fortunately, over a long enough time scale, it doesn't matter, the technology will eventually leak out of their control. If they come up with incremental medical treatments, well, then they will be under patents and initially only available to the wealthy in first world nations, but over time patents will expire and countries that don't care about patents will find ways to replicate the science. At worst it won't be different than any other medical advancements. If they come up with an immortality serum or something equally fantastic, I can see governments and nations just ignoring Calico IP claims under a "public interest" argument, anyways... I think you are overestimating the risk that "they will solve ageing, but be evil about it" and underestimating the obvious risk of "they won't solve ageing" (which, honestly, still probably means we get a lot of interesting science done in the process, so it is still worthwhile to try)

"over a long enough time scale, it doesn't matter, the technology will eventually leak out of their control"

That long-term perspective may not be quite as comforting to someone whose loved ones are facing the miseries of old age and death while the elites hold the cure.

Sure, eventually, in a 100 years, or 200 years, or who knows how many centuries or millennia, we'll all be equal in a Star Trek utopia, and everyone will have equal access to advanced life-extension tech, but by then those of us who might not have won the startup lottery or otherwise managed to siphon up enough money to matter will be long dead.

As for patents, this tech might never be patented. It might be kept completely secret instead.

Sure, but, I mean, will we get it sooner if private companies are not working on it at the same time as public research institutions are? If we don't have access to the tech because it is being hoarded, or because it does not exist, the effect is the same. I also think it will be hard to hoard it for long, particularly if it really works the way people are assuming it will work ("immortality serum" style). I think that's wishful thinking for now, and that at the very best we will get the Xerox PARC of ageing research, which, honestly, would be victory enough.

> It might be kept completely secret instead.

Easier said than done. Very few technologies are kept secret in that way. Keep in mind that even for the fission bomb, the Soviets got it fully replicated after just 4 years, and other countries soon followed suit. These days we are all in panic because even marginalized states can afford to build the damn things. The only reason not every developed country has a nuclear arsenal is not secrecy, but legal arrangements and joint defense treaties. Now remember that is literally the strongest conspiracy for scientific secrecy in the history of mankind, with good reasons and everything, and it involves a device for which manufacture is insanely expensive, not just R&D. Medical research is even easier to replicate given even partial information about its workings.

There is an update at the bottom of the article which is relevant:

"Thanks to reader tips and additional searches in PubMed, we’ve located and linked to several Calico papers we weren’t aware of when we first published this story on Thursday. I flagged the papers with the researchers quoted in this story who said they did not change their assessment of Calico."

Stealth is a sign of weakness in a life sciences company.

How would you design a clinical trial for a life-extension drug? How long would it take, and how much investment would be required, to compile a compelling case to the FDA to approve your drug?

I want to know what Daphne Koller and her machine learning (probabilistic modeling?) team are doing. I want to know this badly.

In jest, you should just build a graphical model of likely states and then feed in some evidence to get a conclusion.

Couple ideas: mapping regulatory networks behind some phenotype or biological pathways. Building sensor networks based on some biological inputs. Encoding biological data into some kind of probabilistic database. Simulations. Applied neural networks of some kind.

In anti-aging research you would breed worms, mice, and fruit flies and look for anti-aging biomarkers in some set of conditions thought to promote life extension. You would also try to map known pathways between organisms to each other. You would sequence a ton of RNA... Also you would sequence genomes and RNA of people who are old and have lived a long time etc...

As a control sequence everyone else. Feed all of that into a NN and see what pops out.

It isn't news to the audience I usually talk to that the California Life Company, or Calico for short, Google's venture into aging research, is secretive. Outside of the staff, few people can do more than read the tea leaves regarding what exactly they are up to. The high level summary is that Google is channeling a large amount of funding into some sort of long-term development plan for therapeutics to treat aging as a medical condition. Over the past few years Calico has made sizable development deals with pharmaceutical and biotechnology companies, and hired some of the most noteworthy names in the aging research community. It is usual for biotechnology and drug development companies to be fairly secretive in their early stages, for reasons that largely relate to investment regulations. At some point they have to talk about what they are doing, however, given that the goal is clinical trials, customers, and revenue.

It may be the case that Calico is simply following the standard biotechnology startup game plan over a longer time frame and with more funding than is usually the case, including the secrecy portion of that plan, but by now most of those interested in faster progress and beneficial upheaval in the research community have written off Calico as a venture unlikely to make any meaningful difference [1] [2]. Given who has been hired to lead it, and given the deals made, the most likely scenario is that Calico is the second coming of the Ellison Medical Foundation. By that I mean an organization that is essentially running more of the same research funded at the National Institute on Aging, with a poor or absent focus on clinical translation, and constrained in goals to the paradigm of drug development to slightly slow the progression of aging. In this area you will find things like calorie restriction mimetics, pharmaceutical enhancement of autophagy, and so forth. The past twenty years of research have made it clear that it is very hard and very expensive to produce even marginally effective and reliable drugs capable of slowing aging through the adjustment of metabolic processes. Yet this is exactly what most research groups continue to try.

There is an alternative approach. Instead of altering the poorly understood intersection between metabolism and aging in an attempt to slow the damage of aging, instead periodically repair the quite well cataloged list of fundamental cell and tissue damage that causes aging. This approach is exemplified by senescent cell clearance - a way to extend healthy life and turn back symptoms of aging and age-related disease that is already showing itself more robust and useful than any of the present drug candidates aimed at altering the operation of metabolism to slow aging. Senescent cell clearance as a way to reverse aging has been pushed by the SENS rejuvenation research advocates for more than 15 years [3], with good evidence as support. Yet over that span of time the majority of the research community rejected damage repair in favor of focusing on efforts to slow aging, efforts that have not succeeded in producing useful therapeutics with sizable results on human health.

That rejection was clearly not sound. Once efforts started in earnest on development of methods of senescent cell clearance, it required only the past few years to robustly demonstrate its effectiveness as a rejuvenation therapy [4]. It is gathering ever more attention now - but not from Calico, so far as we know, and not from the majority of the research community that continues to work on slowing aging through adjustment of metabolism, an approach to aging as a medical condition that is demonstrably marginal and expensive. The funding used to bring senescent cell clearance up to its present point of proven success is a tiny fraction of what has been spent on so far futile efforts to produce calorie restriction mimetic drugs [5] that would, even if realized, be far less effective and far less useful to patients.

On the whole I think Calico is most likely a larger than usual example of the primary problem in aging research: the dominance of initiatives that put their funds towards complex, lengthy, and uncertain projects that even in the best of circumstances are only capable of producing poor outcomes for patients. In short, the problem is an unwillingness to pursue the repair and rejuvenation approach that is demonstrably more effective than the adjusting metabolism to slow aging approach. Excessive secrecy is a minor quibble in comparison.

[1]: https://www.technologyreview.com/s/603087/googles-long-stran...

[2]: http://mendelspod.com/podcasts/brian-kennedy-and-aubrey-de-g...

[3]: http://www.sens.org/research/introduction-to-sens-research

[4]: http://dx.doi.org/10.1038/nature16932

[5]: http://blogs.sciencemag.org/pipeline/archives/2008/04/24/720...

my summary of reasonattlm's post: Calico is going to fail like the Ellison Medical Foundation did. Everyone bet against SENS, and was wrong, as proven by senolytics. SENS is likely to be right about the other stuff as well, and people should put money into engineering instead of understanding.

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