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LIFEMAG Original

Solving the mystery of Calico

by Published on 14th Aug 2015

by Published on 14th August 2015

The name 'calico' is given to many things: a type of cotton cloth, a multi-coloured cat, a ghost town in San Bernardino County, California, a type of gun, a rare species of lobster. It is also short for California Life Company, a Google-funded enterprise which conducts research into anti-ageing. However, due to its super-secretive nature, the latter is all too easily lost in a crowd of feline and fabric-related Google search results.   

Whilst Calico may be on a mission to ‘tackle one of life’s greatest mysteries’, we at LIFEMAG decided that it was time to tackle the mystery surrounding the company itself. What exactly are they doing? We’re going to don our detective hats and examine the evidence.

Surely, the easiest thing to do would be to approach Calico and ask them directly? Well, the following statement on the company’s website is basically just a polite way of telling nosy journalists that, whilst they’re welcome to try this method, they really ought to mind their own business:

“As we make early progress on our research and goals, our capacity for handling press inquiries is limited. We'll do our best to be in touch: press@calicolabs.com”

Having ruled out that option, all we can really do is analyse the information which has been made available to the public.    

Can we figure out what they are doing based on what was said about the company when it was announced?

Plans to launch Calico were announced by Google in September 2013 and Arthur Levinson was put in charge.  At the time, Google’s CEO, Larry Page stated that:

“Illness and aging affect all our families. With some longer term, moonshot thinking around healthcare and biotechnology, I believe we can improve millions of lives.”  

A few months later, Page said something quite similar about Calico in Google’s 2013 Founder’s Letter:

“we continue to invest for the long term, in our next generation of big bets. In healthcare we have Calico—a new company led by the former CEO of Genentech, Art Levinson, that’s focused on health, wellbeing and longevity”

Based on Page’s words, Calico was interpreted as being the embodiment of a grand vision borne by Google to extend the human lifespan. It seemed that Google, the master of internet search engines, was set on becoming the master of life and death. However, the phrases ‘longer term’ and ‘next generation’ also implied that progress towards this ambitious goal was likely to be slow. Some sceptics took this to mean that Calico didn’t really have much of an idea about how to achieve its aims.

Can we figure out what they are doing based on who works there?

Calico’s team is a constellation of scientific superstars. Its employees are experts from the fields of medicine, drug development, molecular biology, and genetics. Although Calico is reluctant to be more specific about its activities, the company certainly doesn’t shy away from lauding the achievements of its small but select team.  

Arthur D. Levinson, the Chairman and former CEO of Genentech and Chairman of Apple is Calico’s Chief Executive Officer. Notably, Levinson received the American Association for Cancer Research Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research in 2011. Therefore it wouldn’t be at all surprising if Calico produced innovations to combat cancer.

Another Calico employee who specialises in cancer research is Robert L. Cohen. After joining Genentech in 1994, he made important contributions to the research and development of several ground-breaking cancer drugs, before switching to the business development side of the company full-time in 2004. His role as a Calico Fellow is described as one which ‘spans R&D and business development.’ If Calico were to make any ground-breaking discoveries to improve the treatment of cancer, Cohen would be the one to take responsibility for making them commercially viable.   

In November 2013, Hal V. Barron, made a shocking move by leaving his post as Chief Medical Officer at Roche (the Swiss health care giant) in order to become Calico’s President of Research and Development.  Personal connections definitely played a role in Barron’s decision, since he served under Levinson for many years as a chief medical officer at Genentech. Barron specialises in cardiovascular research and speciality therapeutics. He has already been issued with several patents for his work in thrombosis and angiogenesis. In the future Calico could take advantage of its exclusive access to Barron’s expertise in these fields.   

Between them, two members of Calico’s team have got the genetics research area covered. David Botstein, Chief Scientific Officer, was involved in establishing one of the founding theories of the science of genomics, namely a way to map human disease genes with DNA polymorphisms called restriction fragment length polymorphisms (RFLPs). Cynthia Kenyon, Vice President of Ageing Research, has undertaken equally pioneering work in the field of genetics, but with more of a focus on the molecular biology of aging. In 1993, she discovered that a single-gene mutation could double the lifespan of healthy, fertile C. elegans roundworms. This proved that the rate of ageing was subject to genetic control, both in humans and animals.

Jonathan W. Lewis, Vice President of Business Development, is responsible for supporting Calico’s growth through partnerships and collaborations (more details about those later). Take a wild guess as to which company he worked at for nearly 10 years! It’s possible to see how he would have become acquainted with some of his fellow Calico team members during his time at Genentech, since he was the Head of Oncology Business Development. Immediately before joining Calico’s ranks, however, he was employed as the Vice President of Global Business Development for UCB Pharma in Brussels.

The final member of the Calico crew is Senior Staff Scientist Nick van Bruggen. By now, it’s probably self-evident that he worked for Genentech; as a Director and Staff Scientist. During his time there he established a world renowned biomedical imaging department that pioneered the use of novel technologies, from magnetic resonance to positron emission and optical imaging. These techniques provided unique insight into the pharmacological treatment of disease. Throw the fact that he holds multiple patents into the bargain, and he’s another prize catch for Calico.
So apart from Genentech, another common theme in Calico’s recruitment strategy seems to have been to secure exclusive rights to the knowledge and expertise held by renowned anti-ageing scientists.   

Can we figure out what they are doing based on the deals they are making?

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.”

Can we figure out what they might do in the future based on the announcement of Alphabet?

This week, Google reorganized itself into a new conglomerate called Alphabet. The companies forming this conglomerate include Google Inc., YouTube, Android, Google Ventures, Google Capital, Google X and, importantly, Calico. Such a move has generated a great deal of speculation over the future of Calico. The opinions are divided into two camps.

On the one hand, one of the main reasons which the big-shots at Google gave for the creation of Alphabet was the need for greater clarity in how the mothership is choosing to invest in its various ventures, thus enabling its investors to better see how their money is being spent. On Alphabet’s website, Larry Page promised to “rigorously handle capital allocation and work to make sure each business is executing well.”

Yet, as mentioned above, back in 2013, Page implied that Calico was not something designed to make a quick buck; it was a longer-term project. Up until now, the company has also benefitted from an undisclosed research budget. Under the Alphabet conglomerate, Calico could come under pressure to stop daydreaming about ‘moonshot goals’ and start generating profits. More importantly, obligations of greater transparency could mean that Calico is finally forced to spill the beans on what it is doing in order to justify the funding of its research.  

On the other hand, Larry Page also stated: “fundamentally, we believe this allows us more management scale, as we can run things independently that aren’t very related.” This could imply that Calico will be given the freedom to pursue its ‘moonshot goals’ in even greater privacy. Levinson certainly seems to think that this will be the case. In an email to Matthew Herper at Forbes magazine, he wrote: “we expect no change to Calico’s mission, directions or goals (either near or long-term) as a result of today’s developments. Everyone involved understands the long-term nature of this business, as I know you too appreciate.”

So can the mystery be solved?

Whilst we don’t know exactly what is happening down at Calico HQ, we know that something is happening. And that it’s something big. Why else would Calico be so secretive?

Those whose curiosity remains unsatisfied, and who have the relevant qualifications, could apply for a job at Calico. Based on the considerable number of job adverts on the careers section of the company’s website, it looks like its super-skilled, superstar team is in need of some extra pairs of hands. This suggests that, with the funding, core team and research collaborations in place, Calico is now settling down to some serious work. What’s more, the Alphabet announcement means that the company will be able to carry out this work on its own terms; safe from the prying eyes of Wall Street.   

All in all, if there are going to be any scientific breakthroughs in the field of anti-ageing, then Calico is likely to be the one making them. Watch this space.