Gordon Conference on Animal Microbe Symbioses: Hologenome Theory of Evolution

After almost 30 years of thinking and occasionally speaking about the hologenome  theory  I’m registered for the Gordon Conference in New Hampshire in June.  I hope I can meet some open minded and thoughtful people with whom to discuss these thoughts.

Since Gordon Conferences operate under what amounts to Chatham House Rule, and communications can’t be quoted (not that I am likely to publish much at this rate) I thought I’d at least post my abstract here in the dusty old blog.

RA Jefferson “Hologenome Theory” Abstract, Gordon Conference on Animal-Microbe Symbiosis, June 21-26 2015


The Hologenome Theory of Evolution: The origins, logic and implications of a ‘cloud genetics’.

Richard A. Jefferson, Professor of Biological Innovation, Queensland University of Technology (QUT), Brisbane, Australia & Cambia, GPO Box 3200, Canberra, Australia

The hologenome theory of evolution developed by Jefferson (1994, 2007) proposes that natural selection occurs at the level of a holobiont, comprising the population of microbial constituents together with a replication-competent macro-apobiont; in essence a populated scaffold. It asserts that the genetic composition of the holobiont comprises the genetic contributions of the micro- and macro-biota in a form called the hologenome and that this ‘hologenotype’ is optimized by natural selection for its performance and persistence over time, but also for its plasticity and responsiveness to change.

The origins of the theory hinge on studies of glucuronide metabolism by diverse vertebrate-associated microbes. The concentration and bio-availability of virtually all the steroid hormones that modulate, regulate or control reproductive performance, mate choice and ontogeny of vertebrates depends on the microbial processing of conjugated intermediaries, including steroid glucuronides. This occurs in microbially-rich complex ecosystems including intestine and surface epithelia, and is mediated by glucuronidases, arylsulfatases, permeases and other enzymes encoded by an extraordinary diversity of microbial constituents, and allows levels of these circulating hormones (and countless other metabolites) to be adjusted by action of a dynamic population of microbes that in turn are intrinsically sampled from and sampling the environment.

The implications from this premise are many, and in many ways, non-trivial. The ability to alter and modulate, amplify and suppress, disseminate and recruit new capabilities as microbially-encoded ‘traits’ means that sampling, sensing and responding to the environment become intrinsic features and emergent capabilities of the holobiont, with mechanisms that can provide rapid, sensitive, nuanced and persistent performance changes. Hologenome theory is essentially probabilistic. The population of microbes associated with the performant microbiome of a holobiont is neither fixed nor necessarily predictable, with the holobiont behaving as an indeterminate, temporally persistent standing wave.

Just as quantum theory (quantum field theory and quantum mechanics) allows a more accurate and generalizable description of physical phenomena at small and large scale both in time and space, so hologenome theory accommodates observations of the ubiquity and function of microbial populations, but also exposes observational and cognitive bias that has hitherto dominated our thinking about evolution and life sciences and their applications to society and the environment. This includes obvious impacts on health and agricultural improvement strategies, but curiously also economics and social institutions. The now classical ‘New Synthesis’ of evolution is by extension, basically a ‘Newtonian’ view of evolution and has fostered a scholarship of symbiosis that focuses on individual interactions rather than probabilistic, synergistic and dynamic populations and the complex and resilient systems these produce.

In this presentation I will review the biochemical and molecular genetic experimental work underlying the articulation of the theory, and describe some of the implications of its probabilistic nature that neither requires nor supports the intellectual construct and memes of ‘host’ and ‘symbiont’.

RA Jefferson (1994) The Hologenome in “’A Decade of PCR: Celebrating 10 Years of Amplification,’ Proceedings of a Symposium” Video released by Cold Spring Harbor Laboratory Press, 1994. ISBN 0-87969- 473-4.

RA Jefferson (2007) “The Hologenome & Hologenomics: a Different lens on evolution” in Science as Social Enterprise. http://blogs.cambia.org/raj/2007/09/06/the-hologenome-hologenomics/

The Illahee Talk: opening the innovation ecology

A few months ago, I had the opportunity to speak in Portland, Oregon on my thoughts of opening the innovation ecology.   The talk was sponsored by a non-profit, Illahee.org.

The talk was introduced by Illahee’s Director, Peter Schoonmaker.   In his  blog post, Peter described his summary of my presentation.

I used the occasion to wax lyrical about the congruence of the hologenome theory of evolution with our work on creating an open and transparent innovation cartography tool.

I tried to find a common thread of ‘biological innovation’ that can guide not only the practical realities of improving health, agriculture, environment and energy, but also the formation of productive and equitable economic and social structures and tools.

The full video of this presentation is available on Vimeo:   Enabling Innovation

van Linschoten: WikiLeaks WritLarge


Jan Huygens van Linschoten

The world’s greatest disruptive act of  Open Access Publishing.

The Dutch are pragmatists.   If there’s a more practical, hard-nosed, outcome-oriented culture that is steeped in business and trade, it might be the Chinese.  But the Dutch are (in so many ways) giants in the history of trade and commerce.

So it may be surprising that what is arguably history’s most disruptive act of creating a ‘commons of knowledge’ that opened up global trade to competition and fair-play came from a Dutchman,   Jan Huygens van Linschoten.

van Linschoten managed in a single act of sharing – in his case the pilfered Portuguese portolans and charts – to open the world of maritime commerce up to free and open competition, stimulating an era of growth and innovation in technology – shipbuilding, sailing, logistics, cartography and navigation – and in business – insurance, investment tools, financial instruments – that changed civilization for ever.

In 1596 or thereabouts, van Linschoten published what had for over a century and a half, the state secrets of Portugal – the maritime cartography of the Indies – West and East.

The Lens I: What it’s all about

Since its inception twenty five years ago, Cambia has had one goal, even a passion:  to ‘democratize’ science-enabled innovation.

After over twenty years of laboratory work in CambiaLabs, creating, distributing and supporting openly available biological enabling technologies to the global research community –  some of which are amongst the most widely used in the field – we hung up our lab coats and put away our pipettes a few years back.

After over ten years of developing, improving and hosting the Patent Lens,  a hugely popular open web resource, we’re soon to be retiring the site per se.

After almost ten years designing, launching and supporting the BIOS Initiative (Biological Innovation for Open Society, aka Biological Open Source), its new ‘open source’ licensing strategies and its online collaboration platform Bioforge, we pretty much stopped about three years ago.  We turned off bioforge.net.

So we’re quitting?  We’ve run out of steam?    Is this the inevitable demise of the simplistic, science as social enterprise, sharing paradigm?

No bloody way, mate.

We have worked hard, contributed some and learnt much in these decades.   But progress through scientific method is based on having hypotheses *disproved*, not proved.     In the course of this – with careful design and with some grudging willingness be wrong – one gets closer to a truth.

So, doing all this stuff, we identified a common global, structural and systemic opportunity to change the system.

Biological Open Source won’t work without it.   Bioforge didn’t work without it. The Public Sector works very poorly without it.   Small enterprise desperately needs it.  Big business wastes billions to get it.

The biggest inefficiency in the history of post-enlightenment civilization is now entrenched, ubiquitous and feels inevitable.

And its pretty similar to the development of clergy, with their ecclesiastical literature, liturgy and their choke hold on society for the previous millenium.

Put simply,  we have to completely shift the demographics of problem solving by creating a global, open and dynamic resource for ‘innovation cartography’.

We must make it possible for virtually anyone to understand the landscapes of science, intellectual property, business, regulation and other innovation ‘intelligence’ that is necessary to make creative enterprise a possibility at all levels of society.

Creating and using credible dynamic landscapes showing the What, Who, Which, When, Where and Why of science-enabled innovation,  individuals and institutions in public and private sector can envision trajectories, partnerships, strategies, risks and opportunities.   We can engage untapped social, financial and intellectual capital to solve real and compelling problems.

These may be food, health, environment, energy or virtually any other productive economic activity.

The Lens

It would have been unthinkably hard ten years ago.  Five years ago, untenable and outrageously expensive.

Now, its manageable, affordable.  And essential.

The next posts will be about the ‘how’.

But it will *start* with  the world’s patents as the entry point to innovation intelligence.


Innovation cartography: Mapping and navigating the IP landscape

The Unknown

“As we know,
There are known knowns.
There are things we know we know.
We also know
There are known unknowns.
That is to say
We know there are some things
We do not know.
But there are also unknown unknowns,
The ones we don’t know
We don’t know.”

—Feb. 12, 2002, Department of Defense news briefing, Donald Rumsfeld
These now immortal words of the neo-bard Donald Rumsfeld, though often lampooned, actually provide a helpful insight into the nature of innovation and landscapes on which it occurs.
Innovation, like navigating the high seas, is as much a matter of not steering a wrong course as it is steering the right one.   This is particularly so for those whose resources are limited, and where the risk of failure courts disaster.
In innovation thinking – itself almost an oxymoron – talking about how to make right choices and fostering sparks of creativity seems the dominant discourse.
But the realities of innovation are that most of the innovation process is grueling hard work, and the hard yakka is in avoiding stuff ups: endeavouring mightily not to ‘run aground, or crash into continents’.

So what are these continents, the reefs, the shoals and the currents that could take our ship of creative product and service delivery down to Davy Jones?

In those sectors driven by science-and technology-enabled innovation (SEI),  much of the uncertainty, the obscurity, the buried bommies are in the world of intellectual property, and most of this in the patent literature.

Curiously however – much of the excitement and opportunity of future and futuristic problem solving also lies in this same byzantine, obscure, clergy-ridden literature.

So what is it and how do we navigate it?


The hologenome theory of evolution

I’d like to share an email exchange I had some months ago with Eugene Rosenberg, one of the authors of some extremely interesting papers outlining the hologenome theory of evolution.   He and his wife, Ilana Zilber-Rosenberg apparently completely independently from me articulated the hologenome theory from their experiences in microbiology and nutrition, and coral microbiology in particular.

In 2009, I found some Rosenberg papers describing the hologenome theory from 2008 and 2009.  I was delighted at the clear and lucid writing and exposition, and that their observations leading to the hologenome concept came from such a different field to my own.

My  development of the hologenome theory in 1991-1994 came from two avenues of work I’d been pursuing for some years:

1)  vertebrate commensal microbes and their role in controlling critical hormones necessary for macro-organism fitness and

2) the role of endophytic and epiphytic microbes in plant performance in agriculture, including of course rhizobia and numerous other plant-associated bacteria.

Purging the backlog of thoughts

I’ve had an absurd number of people urge me to break my life-long writers’ block and start to put some of the lessons from the last couple of decades on (virtual) paper, so others can learn, criticize and comment, and so I can improve our strategies.

So I’ve undertaken that in the next year, I’ll write extensively on innovation systems, biological evolution, agriculture, patents, new technologies, social equity, biotechnology, environmental interventions, hologenomes, open stuff, and so on.

I haven’t decided if I’ll do it just on this blog, which seems one of the best-kept secrets on the internet, or publish in more conventional outlets, and mirror and discuss those pieces here.   Probably a bit of both.

USPTO Delivers big time: Free, fast, timely public access to the best patent data

At Cambia, to create the Patent Lens (www.patentlens.net) we’ve probably spent USD 300,000 or more over the years to acquire and serve to the public the full text and images of  US Patents and Applications.   This is a pretty heavy load for a small non-profit, but through commitment by our supporters, we’ve managed.

When the Open Government Directive was announced in the current administration, I was hopeful that the US Patent and Trademark Office would begin to make its bulk patent data available at no cost, and as well, create a way for the public to access the important ancillary data relating to status and prosecution history, called ‘PAIR’.

When USPTO announced the unusual partnership with Google to do just that, I was both pleased and a bit nervous that this was creating a cozy relationship with one big player in the information space, reminiscent of the relationships that EPO has had with ‘added value’ information gatekeepers.   I was also a bit skeptical that it would work and would deliver.

What happened in the last months since Jon Orwant at Google began hosting the bulk data was remarkable.    But it was incomplete.   The most valuable information (financially and often technically) is the most recent set of documents – the applications and grants published this year – and ideally this minute.      And these were lacking.    Until a couple of weeks ago, there was essentially no 2010 data on the Google bulk site.

I was concerned by this, and spent some serious time and bandwidth in conversations and emails with people in the Government and at Google, and in the last couple of weeks, the responsiveness of the USPTO, Google, the Commerce Department and the Office of Science & Technology Policy  has been nothing short of spectacular.   In fact, the whole experience made me realize that ‘Open Government’ is a passion and a mission to many of its practitioners in Washington and Virginia, and that there are some real heroes in the system who should get recognition.

In short, they made very courageous decision to provide to the public the highest margin data that they currently sell, at no cost, and on time.  And then they actually did it.  http://www.google.com/googlebooks/uspto-patents.html


The Hologenome: the Cold Spring Harbor 1994 presentation

I finally unearthed the old videos of my Cold Spring Harbor talk in 1994 in which I outlined the ideas and context of the ‘Hologenome’ as a new lens on evolution.  Cold Spring Harbor actually packaged and (briefly and presumably unsuccessfully) marketed these videos of the meeting.  Now out of print.

Cambia\’s Youtube Channel, including Cold Spring Harbor presentation

At that time (September, 1994)  I was trying to set the scene for why studying, understanding and manipulating complex systems with tools and approaches of reductionism would not be enough.

I started in part one with the concept of getting ‘Beyond the Model System’, and used real-world agriculture and environment as the entry point for that discussion.


Why should a multinational (e.g Monsanto) participate in an open source initiative?

A couple of years ago, a contributor to the BioForge forum, ‘Meredith’, asked me why Monsanto would ever participate in the BiOS Initiative or any other open source idea. I decided to repost an edited form of my reply here, since many others ask the same question. Well, Monsanto STILL hasn’t signed up. It has however published patent applications showing that our Transbacter technology – which is a core CAMBIA BiOS work product – works well in their key crops (soybean, corn, canola, cotton). It validates both our technology and more importantly, the premise that a dominant patent could be used to leverage community access to improvements.

Of course the only entity that can speak for Monsanto is Monsanto, so commentary by any of us about why or whether they’ll participate is only conjecture.

However, I would comment that ‘financial savvy’ is a great reason for them to participate on several fronts. By thinking of the different ‘levels’ at which technologies act, one can imagine different treatments of these technologies with regard to sharing or hoarding.

This is similar to considerations of the ‘stack’ in software, where such components as operating systems, programming languages, interoperability standards, middleware are generally shared tools required to move the sector forward. Then applications or suites of capabilities represent commercially viable products and services.

The same distinction works in biotechnology. (more…)