Richard Jefferson

Science as Social Enterprise
The CAMBIA BiOS Initiative

Nearly four billion people live on daily incomes lower than the price of a latté at
Starbucks. Most of them make dramatically less than that—and from that income,
they must acquire their food, their medicine, their shelter and clothing, their edu-
catione, and their recreation, and they must build their future and their dreams.
Their lives, and the quality of their lives, hinge on biological innovation.

Biological innovation is the ability to harness living systems for our social,
environmental and economic well-being. It is the oldest and most fundamental
form of human innovation, involving as it does the getting of food, the striving for
health, the making of homes, and the building of communities. The wealth creat-
ed over the millennia through the domestication and husbandry of plants and ani-
mals has powered human society.

Of all areas of biological innovation, agriculture is the most important, affect-
ing our environment, our health, our economies, and the fabric of our societies.
The world’s poorest nations depend largely on agriculture for their economic sur-
vival as well as their food, fuel and fiber. The challenges of innovation to create and
sustain productive and environmentally sound agriculture are even more pro-
nounced in these societies. Any failure to do so has enormous implications for the
global community, over and above the social, economic, and environmental
impacts.

For thousands of years biological innovation has been informed and guided by
keen observation and the accumulation and sharing of generations of empirical
knowledge. Farmers selected better crop varieties and livestock breeds, and devel-

Richard Jefferson is the founder and CEO of CAMBIA-BiOS. He earned his Ph.D. at
the University of Colorado, Boulder. In 1989 he joined the Food and Agriculture
Organization as their first senior staff Molecular Biologist. He left the UN System in
1991 in order to establish CAMBIA as an autonomous private research and develop-
ment institute. Richard was chosen as an Outstanding Social Entrepreneur by the
Schwab Foundation. In December 2003 he was named by Scientific American to the
List of World’s 50 most influential technologists, and cited as the World Research
Leader for 2003 for Economic Development. He was nominated as a finalist for Wired
Magazine’s Rave Awards for Scientist of the Year for 2005, and received the American
Society of Plant Biologists (ASPB) “Leadership in Science Public Service Award” In
Luglio 2005.

© 2007 Richard Jefferson
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Richard Jefferson

oped management strategies to maximize their performance. Seeds were shared as
a practical matter of survival and each improvement formed the basis for further
innovation. Because seeds of most crop plants breed true, the ease of sharing, E
the barriers to doing so were minimal. As with digital information, it is hard not to
condividere, and hard to impose limits on sharing, so norms evolve to maximize value
from this inevitability.

Extraordinary efficiencies
occur when the tools of
innovation are shared, are
dynamically enhanced, Avere
increased levels of confidence
(legal and otherwise)
associated with their use, E
are low or no-cost.

But the post-Enlightenment
explosion of possibility that began
when the unprecedented power of
science became focused on food,
agriculture, health, medicine and
environment seemed to dwarf all
previous attainments. And indeed
in the past hundred years, with the
advent of genetics, the pace has
been gathering; the last thirty
years has seen an unprecedented
dynamism in life sciences that is
being hailed as a “biotechnology
revolution.” But in this revolution,
is rarely being
biotechnology
applied to the critical issues of
alleviating poverty, eliminating
natural
stewarding
hunger,
resources, and preventing or curing the diseases of the disadvantaged. The margins
are small, the markets are modest, and the challenges are great. Are the paradigms
and practices that have emerged to harness science for society sufficient to engage,
and even solve, these seemingly intractable problems?

Today control over agricultural biotechnology is effectively limited to a few
multinational corporations who integrate seeds, agrichemicals, and biotechnology.
This disturbing consolidation of power is matched with a trend toward “me-too,"
big-ticket “innovations” of remarkable dullness. How many herbicide-tolerant big
acreage crops are enough? Similar trends are surfacing among the large pharma-
ceutical companies, collectively known as “big-pharma”: how many blockbuster
lifestyle drugs does society need?

Within the value system they respect, and according to their own success met-
rics of profitability, big agriculture and big pharma are not abject failures, but they
surely are not enough.

To address the myriad challenges of agriculture, environment and health that
are local in nature and modest in market or profit margins will require vigorous,
competitivo, local-scale small to medium enterprises creating a business and inno-
vation ecology. It will also require a biological innovation culture where the costs
of innovation are low, and the power and relevance of technology are high. It will
require leveraging the contributions of diverse people and institutions to create

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tools that better engage science into an integrated and economically sustainable
social agenda.

The mission of CAMBIA, of which I am the founder, is to advance this set of
required capabilities so that biological innovation can address the human chal-
lenges of the 21st century; the BiOS (Biological Open Source) Initiative is
CAMBIA’s mechanism for achieving its mission.

The term “open source” describes a paradigm for software development asso-
ciated with a set of innovation practices. The concept evolved out of the “free soft-
ware” movement, and is often merged into the expression “free and open source
software.” (See text box.) Several features together qualify a project as “open
source.”1 These include full disclosure of enabling information including docu-
mented source code and the use of legal instruments such as copyright licenses to
confer both permissive rights and responsibilities; they bind contributions into a
commons that is accessible to all who agree to share alike. Typically, certain prac-
tices and cultural norms are associated with distributive innovation, although this
is by no means required; some very successful free and open source software pro-
jects have only a few serious contributors, while others have thousands.

Extraordinary efficiencies occur when the tools of innovation are shared, are
dynamically enhanced, have increased levels of confidence (legal and otherwise)

How Do you Make Money in Open Source?

Free and open source software has rapidly engendered highly productive and
profitable business models that create value from the non-rivalrous2 use of
software components. Examples of such software include the famous Linux
operating system, the Apache web server, databases such as MySQL, myriad
programming languages such as Perl and Python, and the Firefox web brows-
er. These types of open source projects, co-developed by thousands of pro-
grammers, and shared through creative licensing which demands covenants of
behavior rather than financial consideration from the licit community of users,
have transformed the information and communications technology (ICT) sec-
tor.

Most of the high-profile free and open source software projects that have
affected both the sector and the public’s imagination have been “tools” and
platforms, rather than end-user applications. These allow users to build fully
commercial web applications, with high functionality, on robust, dynamic plat-
forme, with no reach-through financial obligations. The economic success sto-
ries of free and open source software thus are not Linux and Apache, but eBay
and Google. The business models that are shaking the ICT world are not the
modest ones selling support for open source products, such as Red Hat Linux.
The signal successes are commercial enterprises that create wealth by providing
new social value. Many ask, “How do you make money in open source?” The
answer: you make money not by selling open source, but by using open source.

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Richard Jefferson

associated with their use, and are low or no-cost. Rent extraction from the process
of innovation is reduced, transactions costs are minimized and developers focus
their resources on creating revenue by providing products and services and enlarg-
ing markets.

This concept is fully generalizable—although clearly the specifics are not—and
a large part of CAMBIA’s BiOS initiative explores and extends the software
metaphor. BiOS strives to create new norms and practices for dynamically design-
ing and creating the tools of biological innovation, with binding covenants to pro-
tect and preserve their usefulness, while allowing diverse business models for
wealth creation, using these tools.

In the first part of this paper I discuss the simultaneous burst of knowledge in
molecular biology and the precipitous decline of a commons of tools, using exam-
ples from plant biotechnology. I develop a practical model of innovation, high-
lighting how biological innovation is stymied or deflected to high margin applica-
tions if tools are not freely available, continuously improving and embodying the
permission to deliver work product into markets. I explore parallels, divergences
and resonance with open source paradigms in software engineering. The rest of the
paper focuses on CAMBIA BiOS Initiative activities: the BiOS Framework, IL
PatentLens, and the BioForge, and the creation of a “commons of capability”
through which new actors, including farmers and small-to-medium enterprise,
can use science to create viable innovations relevant to their needs.

POWER, TOOLS, AND THE COMMONS OF CAPABILITY

Twenty-eight years ago, I began a project to develop a set of tools—of tech-
niques—in molecular biology that could help researchers in that field visualize
how genes and cells functioned. Like virtually all scientific work, and most tech-
nology development, it was inspired and informed by what came before. And like
all tools and methods, it depends on the use of other tools and methods.

Some years earlier, Ethan Signer, Jonathan Beckwith, and others had made a
remarkable contribution to our toolkit for understanding how genes worked in
bacteria. They conceived of a single tool that would allow scientists to learn how
genes turn on and off in a bacterium. The tool “hooked up” the beta-galactosidase
gene (called lac) for which they had simple measurement tools and assays, A
another gene (called trp) for which measurement was difficult, but whose behav-
ior they were keen to understand. In so doing, they measured the trp gene by actu-
ally measuring lac. This tour de force of microbial genetics used publicly available
technologies and methods—in fact it was then unthinkable that there would be
any other kind. This occurred well before the advent of recombinant DNA, Quale
now allows apparently sophisticated genetic experiments to be done very simply.
And it occurred well before anyone had even contemplated patents on life sciences.
Years later, I thought, why not use the same concept to understand how cells in
animals and plants work? Why not have the organisms talk to us about their envi-
ronment, through their genes? I set out to develop a parallel system, using a differ-

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ent enzyme and gene that could function in these new organisms. The one I chose
was prosaically called GUS.

As I worked, I became increasingly aware that the availability of tools, and their
capabilities, completely dictated the science that was done, and who was doing it.
As an undergraduate at the University
of California and the University of
Edinburgh, I worked in some of the key
laboratories responsible for inventing
recombinant DNA methodology.
IO
watched, time and again, how an entire
field of
scientific endeavor would
almost instantly change course when a
new technique—tool—was provided.

I became increasingly
aware that the availability
of tools, and their
capabilities, completely
dictated the science that
was done, and who was
doing it.

When I first developed the GUS
technology, the scientific community I
was originally working within—which
studied animal embryo development—
was not very interested; the tool just
wasn’t needed much. My first paper on
this topic was received with an ill-sti-
fled yawn. But I moved my interests to
plants and agriculture, during the heady dawn of plant molecular genetics.

Efforts to transfer beneficial genes into key crops such as cotton, soybean,
maize, and rice were running into a brick wall. There was no way to visualize suc-
cess, nor to measure and improve on first steps. The GUS reporter system made
visualizing genes and their action in plants very easy and efficient—it was proving
to be a very powerful tool at the right time.

In 1985 I arrived for my postdoctoral research at the Plant Breeding Institute
(PBI) in Cambridge, England, a vigorous international group of colleagues who
were at the cutting edge of technology development and exploration in molecular
plant sciences. The Plant Breeding Institute was also one of the few sites in the
world that combined the patient and disciplined craft of successful agricultural
innovation, such as plant breeding and agronomy, with the impatient and fer-
menting world of molecular biology. As well, the Plant Breeding Institute was still
at that time an entity focused on the public good, a non-profit institute that earned
substantial income for the U.K. government through royalties on its own crop
varieties.

At Plant Breeding Institute, my colleagues3 and I designed and conducted the
first field test of a transgenic food crop. It was also the first BioSentinel experiment:
a gene we wished to study was fused to the GUS gene, to conduct a field trial ask-
ing a fundamental question about how genes act under field conditions. We used
public money, in the public sector, to ask a fundamental question for the public.
The field was planted on June 1, 1987—completely by chance one day before
Monsanto’s first field trial. The lessons of the field trial were fascinating. We found

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that gene activity in a field is extraordinarily variable, and our preconceived labo-
ratory-based notions of how genes worked would turn out to be very inadequate
when dealing with field populations. Our technology, though cutting-edge, era
not up to the questions that real-world agriculture presents.

The Plant Breeding Institute was an international institute, with students and
scientists from all over the world. The institute had a reputation for brilliant wheat
breeding and genetics, so most of the countries whose agriculture depended on
cereal production would send their scientists to us for training. Many of the stu-
dents and postdoctoral fellows in the Molecular Genetics department came from
India, Pakistan, Turkey, the Middle East, China, Africa, Latin America, and Eastern
Europe. Most of them indicated that this period in Cambridge was their one shot
at career establishment. If they published a paper or two in a good journal, Essi
had a reasonable chance of employment back home. And some of them confessed
that they likely would not be able to use the new biotechnologies to effect any
change in their home agriculture or economy. Not only did they lack the finances
and infrastructure to make use of these high-tech tools, but the tools were better
for science than for problem solving.

These people were exemplary of perhaps the most crucial but neglected
resource for social advancement through science: dedicated and capable people. IO
observed, Tuttavia, that instead of using their own experience to inform the sci-
ence that was being done and the technologies being developed, their own world-
views and self-images were rapidly aligning to the incentive and reward system of
the prevailing and fashionable science trends. And their energy to change the
options in their home countries was dissipating.

By early 1987, after intensive experimentation in-house, we had assembled
hundreds of copies of a GUS kit of dozens of DNA molecules and a comprehen-
sive “how-to” manual. I rewrote the big “GUS Manual” and sent it to a mass-mailed
newsletter called Plant Molecular Biology Reporter, which was distributed free to
thousands of scientists rather than initially publishing a peer-reviewed scientific
paper, which I eventually did.4 The grapevine is also a powerful communications
tool in science; soon many people were hearing about this new technology that
would let them see the cells and tissues where their gene was functioning. It would
also allow let them optimize gene delivery experiments; this was an urgent priori-
ty for both industry and academia. At that time no important commercial crop
had been genetically engineered, so requests started flooding in for the GUS sys-
tem. And I started sending out hundreds, even thousands of samples, and the
User’s Manual, all with no licenses, to scientists in dozens of countries, in both the
private and public sectors. I only included a letter saying that while I had filed for
a patent on the system, I wanted everyone to use it, and royalties—if any resulted
—would go back to creating the next generation of technology.

I sent the kit to scientists at Agracetus in Wisconsin who were working, con
little success, on transferring genes to soybeans. They had no idea if the genes they
were introducing with their new process were actually making it into the right
cells. One of those scientists, Paul Christou, told me of their thrill when they were

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able to immediately visualize gene transfer with the blue color of the GUS test, E
soon succeeded at introducing genes into soybeans for the first time. And they
could only do it with GUS, which also had no apparent restrictions. They were
delighted, Ovviamente, as was Monsanto, for whom they worked.5

That work with GUS
turned out to be the single
biggest money maker in plant
biotechnology, possibly ever in
agriculture. Monsanto devel-
oped its RoundUp ReadyTM soy-
bean line, which it ultimately
used to breed most of the trans-
genic soybean plants now cov-
ering the world, using GUS to
select plants.

Within a year after we began
widely distributing the GUS
technology, hundreds of new
avenues of plant science were
emerging. Within two years,
breakthroughs in maize,
soybean, cotton, and many
other crops occurred.

Within a year after we
began widely distributing the
GUS technology, hundreds of
new avenues of plant science
were emerging. Within two
years, breakthroughs in maize,
soybean, cotton, and many
other crops occurred. New technologies were invented that used the tool in its very
creation and optimization, such as particle bombardment (the tool that Agracetus
had been exploring) and critical improvements were made to core technologies
such as gene transfer by Agrobacterium. GUS demonstrated that one powerful new
tool, widely distributed, could rapidly change an entire field.

The idea of intentionally changing the directions of inquiry and the demo-
graphics and economics of problem-solving by designing and providing new tools
would shape the next thirty years of my professional life. With increasing exposure
to the realities of practical agriculture, intellectual property, policy and business,
my definition of “tool” matured. It came to include not just the technologies need-
ed for scientific investigation, but also the critical normative, economic, policy,
legal and business instruments to convert investigation into socially and econom-
ically sound innovations. A business model really can be a tool.

Enclosing the Toolkit: The Case of Agrobacterium

But while this period hinted at the vast potential for new tools emerging from
molecular biology to lead to rapid innovation, it also saw the rush to privatize the
kinds of tools that had always been seen as a commons, as exemplified by the
adventures of Agrobacterium. When I started to work at Plant Breeding Institute,
plant molecular genetics was in its infancy, and only three or four major institu-
tions had serious capability in this nascent field. All of them were using

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Agrobacterium-mediated transformation as their fundamental tool for transferring
genes to plants.

Several years earlier, several public research teams had discovered an astonish-
ing biological phenomenon.6 A soil bacterium long known to be the agent of a
familiar plant disease called crown gall was found to cause these tumors on plants
by a hitherto unforeseen mechanism. The bacterium—Agrobacterium—actually
inserted into the plant, by “natural” genetic engineering, a component of its own
genome, and in so doing reprogrammed the plant to produce a “gall” and new food
for the bacterium. This phenome-
non, a sort of biological Trojan
horse, was thought to be unique in
the biological realm. And everyone
in plant biology saw that it was to be
a critical tool in the development of
new options of biotechnology.

[T]he contents of many
patents were breathtakingly
obvious to all practitioners
in the field, but for small- A
medium-sized enterprises
these patents still served as a
real disincentive to innovate.

The groups that first made the
discoveries were all in the public sec-
tor, funded largely by public monies;
they could all see that Agrobacterium
would be a fundamental tool of the
field. In spite, or perhaps because of
all this, the gold rush for patenting
started. And not only did the pio-
neer groups in the field file patents;
over the next twenty years over a
thousand patents were filed—and granted in many nations—that covered various
aspects of Agrobacterium-mediated gene transfer. Some were so minor and trite as
to be laughable were they not presumed valid by law, but they still produced a
thicket of rights, nearly impenetrable even to the specialist.

And of course the pioneering patents were fought over viciously. To monetize
the patents, the rights were sold to the highest bidder. But the rights were not clear;
bitter wrangling over primacy with the fundamental patents continued for almost
twenty years before any legal clarity emerged. Of course the winning bidders ended
up being large multinational companies, notably Monsanto (either directly or by
acquisition); and in most cases the payments to universities and institutes were
negligible or even negative. But the effect of increasingly consolidating these
patents in a few hands was anything but negligible.

Soon, public and private sector scientists were patenting their developments as
a matter of course. Some of these findings became powerful patent estates that
potentially blocked most of the world’s agricultural enterprises from using these
tools without permission, often at any price. Per esempio, Japan Tobacco discov-
ered and patented a method to use Agrobacterium to transfer genes into rice and
other cereal crops.

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The case of Agrobacterium was repeated with many subsequent technologies,
ranging from genetic selections, to the wholesale patenting of promoters and
genes,7 to gene inactivation technologies (such as RNAi and co-supression). Again,
the contents of many patents were breathtakingly obvious to all practitioners in
the field, but for small- to medium-sized enterprises these patents still served as a
real disincentive to innovate. They also extracted huge rents from industry, E
raised transaction costs to an unbearable level, mostly because the patent land-
scapes were so opaque and complex. This trend has accelerated markedly and now
applies to medical as well as agricultural technologies. The consequences are clear-
ly that only the biggest-ticket targets are getting attention. But blockbusters alone
don’t make for good agriculture, good environmental management or good pub-
lic health.

In 1985 the sector was viewed as exhilarating, entrepreneurial and vibrant,
with almost unlimited possibility for doing good in world agriculture; within a
decade or so it had all but stalled into a corporate oligopoly, with vertical integra-
zione, ossified and oppressive business models, and massive patent portfolios tying
up almost every key technology and platform used in the field. And though near-
ly all the pioneering discoveries were made in the public sector, they were not
reserved for public use or for the small-to-medium enterprise sector that the pub-
lic trusts. It is no surprise then that the public now views the entire agricultural
biotechnology sector—as manifest in the outcry against GMOs—as being a tawdry
exercise in failed promises, industry consolidation, public sector abandonment
and simplistic agendas. Perhaps the greatest crisis that has emerged from this cor-
porate control of problem-solving in agriculture is that the public now seems to
have very little confidence in the use of any science in agriculture! This has indeed
been a case of throwing the baby out with the bathwater.8

Biotech Bazaar: Tools for Sale

At the Plant Breeding Institute, I was working with colleagues from scientific cul-
tures that had historically used the discoveries and technologies that came before
to grapple with the next generation of scientific challenges, with the tacit under-
standing that this process would naturally yield real-world solutions, such as plant
varieties and agronomic processes. After all, the Plant Breeding Institute paid its
way in the world by doing just this.

But that world was collapsing. The distinction between discovery and inven-
tion was being blurred as patents were filed on each component; that process
entirely altered the dynamic of translation into true innovation: delivering the
products of science and technology to the marketplace. It was now possible to con-
trol the tools and platform discoveries themselves, not just the products that they
created.

In the early 1980s with the passing of the Bayh-Dole Act, universities in the
United States were actively encouraged to patent their work products. The Act’s
fundamental policy goal was to see publicly- funded science and technology better

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used by society, by encouraging industry to adopt it. The trend of public agencies
using the patent system exploded internationally into a filing frenzy. No one fore-
saw then that the fragmentation of the platforms and tools would make it so com-
plex, so expensive and so intractable to assemble the “freedom to operate and free-
dom to innovate.” Nor did we see
that the resulting
innovazioni
themselves would be so few, so
stodgy, and so slow to reach the
marketplace.

Perhaps the greatest crisis
that has emerged from this
corporate control of
problem-solving in
agriculture is that the public
now seems to have very little
confidence in the use of any
science in agriculture.

At almost the same time, IL
advent of recombinant DNA and
the ability to determine DNA and
protein
sequences massively
A
increased scientists’ ability
explore, understand, and manipu-
late living systems, or at least living
organisms. So every new life sci-
ences discovery could be, and often
era, dressed up as an invention
and subject to patent; as the patent
claims were granted, they cast a
huge net over the possible options.
Public sector coalitions would frequently compete with private big-science, E
who usually won the plum of patent monopoly? The privatized efforts. Was this
right, or necessary?

I began my own foray into patents and their importance when I arrived in
Cambridge in 1986. I discovered close relationships between some large companies
and the public-sector institute where I was based, shaped by personal histories and
friendships. I didn’t view this as a bad thing. I shared all my ideas and technologies
with them from the outset. In fact, I shared with pretty much anyone who was
interested, thinking that—in economic terms—my ideas were non-rival; sharing
didn’t cost me the ability to use them myself. How wrong I would later prove to
be.9 And how times were changing.

One company, ICI,10 was keen to use GUS in its commercial development pro-
grams; like many companies it was mostly interested in having clear rights to do
so. ICI suggested that I patent my technology so it could be sure it would have
access to GUS in the future. I didn’t understand the logic at the time, but I took the
first steps and filed a patent in the United Kingdom and the United States, con un
filing date in 1986. The University of Colorado, where the first stages of the work
had been done, had waived its interest in patenting it.

Thus began a long and painful learning process of partnerships with powerful
attorneys in which I watched patent-craft by The Masters. It took almost seven
years for my first patent to issue in the USA, and nine years for the one with most
of the valuable claims. Even when it was issued, complex agendas and issues11 kept

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me from licensing the patents or even having a clear title for quite some time. Questo
delay wrought havoc with my ambitions to use patents to create and fund CAM-
BIA, and when revenue did come in, it was in sporadic bursts, and barely in time
to make payroll.

As a technology, GUS has had a surprisingly long shelf-life, and is unusual in
being a largely stand-alone technology. If one has the “right” to put a gene into a
plant, GUS remained a useful and legally usable tool to monitor that gene and its
activity. But it turned out that even that right, the legal permission to transfer a
gene to a plant, proved to be a critical and contentious issue because patents are
opaque and licensing rights even more so, and because advances in the life sciences
are so interdependent.

Wheels and Spokes: The Interdependency of Technologies

The patent system is so complex it is almost awe-inspiring. Single patent docu-
ments can run to hundreds of pages, with arcane language that few understand,
and rights that courts interpret and re-interpret on the fly. Thousands of these can
exist in a single field of innovation, with many thousands more latent in the sys-
tem. One or two—or none—may be, or may unexpectedly become, dominant.
Fundamental biological processes, such as the ubiquitous gene-regulation mecha-
nismo, RNAi, have been patented. Most of the important genes of many important
organisms—humans, rice, maize, mice- have been subject to patent applications
and sometimes grants, many of them contestable by many separate claimants. IL
platforms on which we must build are privatized and enclosed, but the owners and
their ambitions are completely unclear; the platform for future innovation is built
on shifting sand.

But worse, while the ownership of the “patent” itself is usually a matter of pub-
lic record, the ownership of the rights—the most important feature of a patent —
is completely obscured. Nowhere, in most jurisdictions, is there recorded or avail-
able the patterns of power: who owns what rights. A university may own hundreds
of patents, and may have sold off the rights to any of the useful ones, but who
bought them? The answer is rarely clear.

When a small company licenses a patent, or develops its own patent portfolio,
to whom has it licensed and on what terms? The patterns of power and ownership
are as important—and in the aggregate perhaps more important—than any other
feature of a patent grant. And yet we have no public information whatsoever,
except in piecemeal and scattered disclosures. Some jurisdictions, including Brazil
and France, do impose a responsibility on licensees to disclose—at least to the
patent office. But most do not. And none make it easy to find this information.
This makes it difficult, if not impossible, for a researcher in a small- or medium-
scale enterprise to assemble all the licenses or capabilities needed to refine and
adapt a tool and ultimately to create an innovation that will help meet basic needs.
And researchers need this information because few discoveries stand on their
own, and even fewer inventions. Not only do they each depend on the pre-existing

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knowledge base; they almost always incorporate components of many other tech-
nologies in their execution. This is particularly true of “meta-technologies,” tools
and technologies with broad effects used by communities of innovators quite dis-
tant from the tool’s original inventor.

Consider the wheel, perhaps a six-spoked wheel. In some ways, it is the most
fundamental and important tool in
society. It has countless uses unantici-
pated by its inventors; most were made
by people who are not wheel-builders.
The wheel is only useful when it is used
for something, such as moving a cart; its
economic value to society lies not in the
price of the wheel, but in the wealth cre-
ated through the use of the wheel.

Virtually all the practices
of academic scientists
promote the belief that
“good science” can, almost
by magic, transform itself
into public or private
goods. It can’t.

If it takes all six spokes for this
wheel to turn, and each of these spokes
is potentially different in some way, we
have a good metaphor for a modern
biological technology. Increasingly, bio-
logical technologies are not self-con-
tained; rather they are rather interde-
pendent technologies that require multiple key methods and components to func-
zione. If one spoke is withheld, no wheel is built. If one spoke is broken the wheel
will jam. And then the cart cannot move forward. By analogy, the most powerful
technologies can be considered as “wheels,” requiring a number of “spokes” to
function. For instance, the ability to transfer a gene to a crop plant may require
dozens of individually protected, discrete technologies. Denial of access to any one
of these “spokes” obstructs not only the use of the technology, but its improve-
ment. Only when the core technology is in place, with full functionality, can it be
subject to iterative and cooperative shaping to meet diverse users’ needs.

Unfortunately, even placing one or more key methods or components into the
public domain allows no leverage to bring other components into a collective
whole with broad access. Virtually all the practices of academic scientists promote
the belief that “good science” can, almost by magic, transform itself into public or
private goods. It can’t. Infatti, by failing to deliver such goods with broad and pre-
served access, the public sector science community is complicit by neglect, because
the true stranglehold rests where much less public sector effort is expended: in the
process of converting invention and discovery into innovation, by building and
using wheels.

But we can change this landscape, if we provide one or more of the spokes to
all the wheel-builders and users with covenants of behavior, rather than financial
consideration (outlined later as BiOS licenses). If a user can access a spoke only by
promising to share spokes, or improvements, then the whole logic can change.

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This is where we find the leverage: change the logic of copyright licenses in
software to allow free and open source software to exist, and do the same for patent
licenses or Materials Transfer Agreements (MTAs) in BiOS. Then we can regain a
full complement of spokes, and see the “wheels” of real innovation turn rapidly
and deploy on many roads, creating wealth through their use.

How Fear, Uncertainty, and Doubt Can Deter Innovation

Uncertainties over intellectual property rights undermine the long-term and sus-
tainable pursuit of innovation by making projects look more risky to potential
partners and investors. This risk combines with others characteristic of early stage
technology development: lack of a fully-specified business model, concerns over
potential technology effectiveness, and the absence of a well-established delivery
channel. Together they generate the fear, uncertainty and doubt (FUD, in the awk-
ward but widely used acronym) that is the core impediment to technology devel-
opment. Currently, every worldwide industry that depends intensively on science
and technology experiences FUD. Sometimes a competitor is the focus; sometimes
the bleak patent situation alone can lead an investor, client, customer and/or the
public to lose confidence in the prospects of creating a viable technology-driven
enterprise.

In the face of the uncertainties associated with the complex and opaque patent
situation, multinational private-sector firms have responded by acquiring large IP
portfolios and negotiating cross-licensing arrangements to obtain platforms of
enabling technologies. Even so, these companies still often find themselves with
constrained freedom to operate. Faced with the uncertainty of patent rights, Essi
seem to be involved in a sort of mutually assured destruction.

In contrast, the public-good sector, and small-to-medium enterprises have
only fragmentary portfolios, often made up of publicly-developed technology and
modest non-fixed capital pools that they believe can be expanded by their eager-
ness to license them out, but they are at a grave disadvantage; they face a monop-
sony.

Unfortunately, this approach not only destroys public value and confidence; Esso
is also ineffective in ensuring a sustainable private competitive advantage. Come il
expense of sequestering intellectual property outside the public domain in itera-
tive patents has increased, some leading technology firms have decided that an
open source model may yield higher private, as well as public, returns. A notable
example is IBM Corporation; in a bold recent move it is stimulating a universally
accessible “protected commons” of patents in a pool available for any open source
development. As the world’s largest patent holder, IBM could be viewed as a “rights
maximalist;” over 500 of its key software patents have been made available to all—
including competitors—who choose to use them under open source rules. Within
days, Sun Microsystems followed suit with another 1600 patents, and a myriad of
other companies are doing the same. The snowball effect continues, as companies

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realize that their sector makes progress when the standards and the toolkits are
clear, open, of high quality and consistently available.

Clearly, true wealth creation will come not through extracting rent from a tool,
but through using a continuously improving toolkit, with continuously decreasing
costs of innovation and a continuously expanding group of tool users. Diverse and
prosperous agriculture, robust public health and sustainable natural resource
management are the publicly valuable goals we must keep in clear sight. The tools
associated with their improvements must be plentiful, powerful and affordable.

As the ICT sector realized, we also need an open source movement in biologi-
cal innovation that can empower public and private sector innovators with the
tools, platforms and paradigms to allow rapid and efficient life-sciences innova-
tions for neglected priorities and new opportunities.

CREATING CAMBIA, MAKING CHANGE

In the mid-1980s, when I first formulated the ideas that became CAMBIA, I did
not intend to build an institution; I spent much time between 1987 E 1990 try-
ing unsuccessfully to convince universities or later the United Nations or the
CGIAR12 system to take on and host CAMBIA’s mission. But the complexity and
edgy nature of the mission, the need to integrate diverse skills and strategies, E
the entrepreneurial spirit, ultimately required an independent base.

Presto 1992 I moved to Canberra, Australia, to begin a project on behalf of
the Rockefeller Foundation, troubleshooting its rice biotechnology network in
Asia. At this point CAMBIA was not a legally incorporated body, but had reams of
letterhead and surprising credibility. Our job was to travel to virtually every labo-
ratory in the developing world that had Rockefeller Foundation support—and
over the next eight years this must have been hundreds—to help develop, improve,
and apply their biotechnology capabilities, especially as they pertained to rice
molecular biology. We developed and provided to many hundreds of labs—per-
haps over a thousand—the most effective and widely used “vectors” in plant
molecular biology, the pCAMBIA series, and provided courses and workshops in
the science and increasingly over time, in intellectual property management. In
hundreds of working visits to China, Indonesia, India, the Philippines, Thailand,
Vietnam and many other countries of Asia, Africa and Latin America, we forged a
sense of the possibilities if we had new types of technologies, and new communi-
ties to improve and share them.

During these years, as we became more sophisticated about licensing and
understanding the patent systems, we also became more aware of the yawning gulf
between biotechnology rhetoric and innovation realities in most of the world. On
the one hand we saw a large, untapped population of dedicated and knowledgeable
problem solvers, committed to solve problems of real substance to their countries
and peers—but they lacked the usable technologies that would improve their situ-
ation. We also saw that the science itself was not up to the job: the research being
conducted in the early days of plant molecular biology (and sadly still now) È

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intensely reductionist, whereas the problems of agriculture and society are inte-
grated into complex systems. D'altra parte, if we could design and provide
tools that fit the problem and the hand of the tool-user, we could rapidly and effec-
tively change the entire platform of problem solving, as long as the tools were
dynamic and could embody the permissions to integrate into real-world innova-
zione. CAMBIA was conceived to integrate and to address these issues.

Outlined in the earliest CAMBIA prospectus was the premise of using patent
revenues to create a sustainable funding base. We surmised that we would ask a
fair, tiered licensing fee of each company that was using the technology, propor-
tionate to their ability to pay. A big company pays a lot, mom-and-pop companies
pay peanuts, developing countries pay nothing. Then we would use the resulting
revenue stream to invent and distribute the next generation of technology. Al
time it looked like a logical and efficient way to move the sector forward with fair
and open competition, not for the capability to innovate, but for the innovations
themselves.

This worked to some extent, in that CAMBIA exists and might not have done
so without patent revenues. Companies that licensed the technology range from
giants like Monsanto, Dupont, Pioneer, Bayer, BASF, and Syngenta down to enti-
ties as small as the Hawaiian Papaya Growers Cooperative. But we also realized we
could not generalize or scale it as a business model in the current climate of frag-
mented rights and capabilities. The transaction costs of negotiating licenses, COME
more and more “spokes” were required to move forward, would simply be impos-
sible to bear for any but the highest-margin applications.

CAMBIA addresses these challenges through three interdependent activities:

1. The BiOS Framework creates, validates and promulgates licensing tools, along
with the norms and new business models to make use of strategies for “open
source” creation, improvement, and sharing of enabling technology.
2. The Patent Lens is a platform to focus, understand, and investigate the patent
rights and to inform practitioners and policy-makers.
3. CAMBIA’s own research into creating and distributing key “pump-priming”
enabling technologies is made available through our online interface, the BioForge.

The BiOS Framework

Biological Open Source is a nascent movement, evocative of the transformative
changes in information and communications technologies (ICTs) wrought by free
and open source software (FOSS). The two movements share some goals: seeing
transformational effects on a sector, and increasing the democratic involvement in
problem solving; we are learning many lessons from the software world, and will
continue to. But it would be a mistake to push the comparison too far. BiOS con-
cepts have emerged from twenty years within the life sciences and human develop-
ment culture, to address the needs and challenges of biological innovation.

The idea of using patent licenses not to extract a financial return from a user
of a technology, but rather to impose a covenant of behavior, is the single feature

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Patent Lens: A Platform for Understanding IP Landscapes

CAMBIA’s Patent Lens includes one of the world’s most comprehensive full-
text searchable databases of patents; cost-free and available to anyone, it has a
seven-year history of continued growth in features and power. It incorporates
the full text of applications and granted patents from the U.S. Patent and
Trademark Office, Patent Cooperation Treaty (PCV) database, European and
Australian jurisdictions, and their status and family relationships in many
dozens of countries. Its fast and user-friendly search engine has a nuanced
interface and presents common and harmonized data structures so that these
jurisdictions can be searched simultaneously.

The Patent Lens is becoming an increasingly important resource as the fee-
requiring “value-added” patent data providers continue to consolidate. Because
no national patent office has taken on the task of harmonizing collections over
many jurisdictions, the role of the “patent clergy’ remains central, and the gate-
keeper functions of the information providers remain onerous. National and
regional patent offices provide quite variable free patent searching; some are
appallingly primitive while others, like the European Patent Office, are quite
sophisticated. Patent offices, Tuttavia, have complex relationships with com-
mercial providers such as Thomson, which actually provide the patent offices
with integrated searching functions for their own in-house use. To further
complicate the situation, commercial providers have been calling for a reduc-
tion in the role of national patent offices as “value added” providers. The need
for a public good provider has never been greater.

Patent Lens focuses on user-adaptability, integration, annotation capabili-
ty and availability to the world community for free; these key features render it
particularly helpful in efforts to restore public good and transparency as the
raison d’etre of intellectual property systems.

Technology Intellectual Property (IP) Landscapes

IP Landscapes are analyses of key platform technologies, and the IP positions
associated with their development and use. They build on and use the patent
database, but include much more than a collection of relevant patents. Each
landscape is a searching and analysis effort involving many person-months, by
CAMBIA staff and soon others, who have particular knowledge of the science
and technology and of patent claims. Typically, patent “professionals” within
law firms accumulate billable hours by providing the same information over

of BiOS that is most resonant with Free and Open Source Software. We13 worked
with small companies, university offices of technology transfer, attorneys and large
multinational corporations to understand their concerns and experiences, E
then create a platform to share productive and sustainable technology.

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and over for different customers, and charging full fees again to update them
periodicamente. Increasingly we wish to do something no fee-requiring patent data
provider will ever do: turn the landscapes into living repositories of constantly
updated information, so no more updates will ever be required.

The goal is to use the harmonized datasets to create a facility where distrib-
uted and diverse users can generate, link, and dynamically annotate patent
landscape analyses through web interfaces. The landscapes will ultimately
become maps and decision support tools so users can distinguish greenfields
from minefields in the long path from discovery to practical delivery of an
innovation.

We have created a substantial number of such landscapes, in an early,
hypertext-linked but basically flat structure. But we aim to enable the prepara-
tion of many more, by many people, by leveraging informatics to create ready
frameworks and linkages between world patent literature and such resources as
PubMed Central, and Google Scholar whose relevance engines can enrich the
processi. Ultimately we see the navigation of technology landscapes as being a
critical feature in research and development decision making, but people will
only use them when their costs, in both time and money, are negligible and the
relevance and utility of the guided decisions are clear.

Patents, Policies & Practices

This component includes tutorials that guide users in reading and interpreting
patents; the aim is to make novices more sophisticated about the nuanced real-
ities of intellectual property, particularly patents. It also includes Policy &
Practices papers that describe and advocate for informed and productive
changes in international, regional and national forums and laws.

The goal is to forge a learning resource that participants in innovation sys-
tems at all levels—scientists and engineers, business and legal professionals, cit-
izens and policy-makers—can use to learn of critical and timely issues relevant
to improving the public good and social and economic value by engaging with
the patent system.

The standards of modern patents are widely viewed as execrable; Anche se
many patents are presumed valid by law, they are at best frivolous and often
egregious. We aspire to provide the public with tools to recognize and overturn
such patents where they undermine progress or are being used without a long-
term and well-articulated stake in industry or society.

The basic premise underlying that license is that we would not charge any fee
for use of the “basket” of technologies with the patent estate being offered. By mak-
ing the license cost-free, we hoped to induce the most valuable contribution to the
license community: “freedom to innovate.” In exchange for full, unfettered com-

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mercial rights to our technologies, licensees are required to comply with three con-
ditions:
(cid:121) They will share with all BiOS licensees any improvements to the core technolo-

gies as defined, for which they seek any IP protection.

(cid:121) They agree not to assert over other BiOS licensees their own or third-party rights

that might dominate the defined technologies.

(cid:121) They agree to share with the public any and all information about the biosafety

of the defined technologies.

Several further features of BiOS Certified licenses are very important:

(cid:121) The definitions are critical. The core capabilities (enabling technologies, plat-
forme) and their scope must be carefully defined to allow confidence in the
development of viable business models that use these BiOS licensed technolo-
gies.

(cid:121) The BiOS License structure must be scalable, and it should be generalizable,
capable of development within these guidelines, and overseen by diverse institu-
zioni. We recognized that different technology sets have very different implica-
tions in the innovation chain, and that the agreement must accommodate differ-
ent sectors (per esempio., agricultural and medical) and different economic circum-
stances (industrialized and less-developed countries). Therefore we developed a
suite of licenses around several different enabling technologies CAMBIA devel-
oped. We created them around our own technologies to have first-hand learning
platforms from which we could generalize and help others create their own
BiOS-Certified programs.

As we have gained experience with our first-generation licenses through the
concerns and suggestions of many licensees and potential licensees, we have aimed
to create a “brand” of Biological Open Source (BiOS) that is independent of insti-
tution. The BiOS certification program will help ensure that core BiOS character-
istics are sculpted into forms that allow institutions to preserve their own cultures
and priorities. They may do this through the medium of patent licensing or
through materials transfer agreements (MTAs), a common form of bailment used
to provide materials for life sciences research, such as bacterial strains, plant lines,
cell cultures or DNA.

The certification approach has been particularly valuable in software develop-
ment, through the activities of the Open Source Initiative (opensource.org) Quale
overseas the branding of such licenses associated with copyright of free and open
source software. Tuttavia, life sciences are extremely sector-specific and technolo-
gy-specific, and it is impossible to forecast or fully anticipate the emerging patent
rights; these facts complicate BiOS certification and licensing. Of course these
same challenges also render patent-based BiOS licensing and MTAs even more
necessary.

Patent Lens: A Platform for Understanding IP Landscapes

With funding from the Rockefeller Foundation, In 1999 CAMBIA began to devel-
op an integrated, full-text database of patents in the agricultural sciences. Under

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the initial guidance of Dr. Carol Nottenburg, then CAMBIA’s Director of
Intellectual Property, the CAMBIA IP Resource became a prominent web-based
data tool to investigate patents in this field. Over the years, both the ambitions and
the capabilities of the CAMBIA Patent Lens team grew,14 and PatentLens has now
become one of the world’s foremost cost-free resources for full-text searching and
understanding patents in many jurisdictions and in all classifications. Patent Lens
(www.patentlens.net) harmonizes, parses and presents worldwide patent and tech-
nology data in a full-text searchable and highly integrated manner.

Tuttavia, it is much more than a patent database. PatentLens is an integrated
response to the massive complexity and opacity of the world of patents. It is
intended as a public platform to enable many actors to investigate and share analy-
sis of relevant IP issues, and to foster community involvement in overseeing and
guiding the patent system.

The patent system has grown so rapidly and become so complex and opaque
that even the most privileged and skilled clergy of patent law can only parse a tiny
area of specialized knowledge, and that tiny area changes daily. This fragmentation
has made it almost impossible to thoughtfully and factually assess the conse-
quences of action and inaction: How can the consequences of policy be modeled
or validated when patents are treated as fungibles? How can efficient progress in
sectors critical to social progress, such as health, ambiente, and agriculture, be
secured when the rights are tangled in a skein of patents?

The goal of the Patent Lens is to use the power of informatics and communi-
ty to harmonize and make transparent the world of patents, so that thoughtful
individuals, institutions and agencies can guide thoughtful and humane reform of
the innovation system and to spur efficient and socially relevant innovation. Questo
is an essential platform if we are to make use of the patent system itself to expand
and protect a technology commons, and to collectively target breakthrough inven-
zioni, work-arounds and “work-beyonds”15 and to make thoughtful and informed
partnerships.

BioForge: Field of Dreams?

BioForge was initially launched as a web-based collaboration platform to take
CAMBIA’s pump-priming technologies—including Transbacter (described later),
a new generation GUS called GUSPlus, and a novel genetic fingerprint technology
called DArT—and throw open the gates to enlightened self-interest. We wanted
scientists to try Transbacter in diverse bacteria and crops to create an open source
and effective toolkit. The first version of the web facility was based on a very cred-
ible collaborative software development platform created by Brian Behlendorf16
and his colleagues at Collabnet. We had hoped—in retrospect, perhaps naively—
to see a surge of interest: scientists from around the world, initially from the pub-
lic sector, would register, log on, and offer to collaborate to improve these tools,
and to share their thoughts and actions.

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BioForge: The Challenge of Aligning Incentives and Rewards

In initially designing BioForge, we had hoped that scientists in public sector
institutions would come to see the value of working together to build powerful
common toolkits to solve problems. Clearly most public entities endorse and
even encourage the notion of pulling together to solve intractable social and
economic problems: market failures. Infatti, this is the best justification for the
very existence of a public sector. But if the toolkit does not encourage scientists
to solve problems for their self interest, it will be irrelevant. And if such partic-
ipation carries a cost—in real time and resources—that is yet another disincen-
tive.

Inoltre, while discovery and occasionally invention are activities
within the public purview in universities and government agencies, innova-
tion—the delivery of new and tangible improvements to society—is not. Hence
it is not part of academic science culture to be aware of the challenges to inno-
vation. Nor does academia do much to reward sharing. The metrics for success
are almost always being “first” in a field of endeavor that is widely hailed as
being important and timely. The grind of innovation, with its need for long
timelines and the building of confidence at many stages of product or process
delivery, has little appeal and less relevance to academic advancement. Infatti,
the market increasingly rewards those who monetize or sequester the necessary
components of innovation—a perverse set of incentives if there ever was one.

The initial response was mildly enthusiastic, but within a few months we real-
ized that the actual engagement and contribution of scientific or personal
resources was miniscule. While the BioForge has almost a thousand registered
utenti, very few of them have substantially assisted the listed projects, technically or
scientifically. Tuttavia, many of the registered users are from India, China, E
other countries widely viewed as out of the mainstream of cutting-edge biological
research. This may reveal a latent need or desire for a better-crafted collaboration
culture. We also believe it reflects CAMBIA’s reputation as a provider of enabling
technology. Thousands of our pCAMBIA DNA vectors toolkits are in use in almost
every country, so this “market” knowledge and confidence could also be skewing
the numbers. Ancora, at this stage BioForge has yet to create a vibrant web-connected
community that actually does anything. We use it constantly, as a transparent and
inclusive “lab notebook” for our own work at CAMBIA.

To address the issue of enhancing contributors’ reputations (see BioForge text
box), CAMBIA has started a software development project called Karmeleon to
create open source, modular, software-mediated reputation metric tools. We hope
that people in many collaborative and distributive projects can use these tools, E
tune them to their diverse needs, ranging from online review of scientific publica-
tions through to research collaboration and product development. Our premise is

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Discoveries are routinely patented; while they are only part of the complex web
of capabilities that must be aggregated to create wealth, owners can game them
for short-term financial gain at the expense of sectoral progress.

Success with a BioForge project—or any cooperative project with long
timelines and complex feedback loops—requires aligning incentives and
ricompense. The most prominent metric for academic advance is reputation, Ma
the tools for recognizing and enhancing reputation are still very primitive,
including publication in high-impact peer-reviewed journals and serving on
committees and review panels to cement relationships.

BioForge lacks any mechanism to demonstrate its contributors’ influence
and success to the community at large, or to those entities and individuals that
have power over professional advancement. It takes an exceptional scientist to
work toward improving a technology if she or he has no personal stake in its
success.

The long timelines of agricultural and medical research and product devel-
opment all but forbid direct feedback when an innovation enters the market-
place. This is a key justification for vertically integrated companies: to ensure
that managerial oversight creates these links. If we wish to see alternative, dis-
tributive innovation in sectors with such challenges, we must create intermedi-
ate, interconnected and valuable feedback that enhances contributors’ reputa-
zioni, as well as new incentive pulls to participate.

that individuals should be rated on their contributions by accredited (rated) peers
in a transparent manner, but using sophisticated, multivariate metrics to reflect the
complex and diverse nature of the value of their contributions. Beyond their pro-
fessional value, these contributions can and often do have important community
and utility implications.

If we make valid, less “game-able” metrics available, users can develop confi-
dence in the value of one another’s contributions, and provide rewards as their
community norms dictate: career advancement, peer reputation, funding and so
SU. But the reputation metrics must be adaptable to the culture where the contrib-
utor is working and being evaluated. Our initial drafts of Karmeleon use three
metrics: Community value, Utility value, and Professional value. Scores in each
category in turn impact the “gravitas” of a user; we hope this will encourage more
sensible ratings to emerge.

The first generation of BioForge taught us something fairly obvious: that the
cultures of software engineering and the life sciences overlap very little. Software
developers live online. Their tool—the computer – is their window to the Internet.
Their product, software code, can be tested almost instantly and can be evaluated,
rejected or accepted almost as quickly. The engineer can build on tested code, E
be fairly confident of a secure base. In the life sciences, experiments can take

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An “Apollo Project” for Biological Innovation?

Several months after we published our TransBacter paper in Nature, Nature
Biotechnology—the most prominent scientific journal in the commercial
biotechnology sector—published an editorial expressing skepticism that a true
open source movement could happen in biotechnology, given the extent of
entrenched norms and interests.19 The title of the editorial, “Open Sesame,"
implied that a vision as clearly utopian and impractical as that of open source
for biotechnology would need a magic incantation in order to become reality.20
The article did conclude, Tuttavia, that an open source movement in biotech-
nology might just take root if, in an “Apollo Project” of some type could be
used to forge a common ground to develop new collaboration norms, tools,
business models and science around some mutually agreeable and highly desir-
able goal.21

While we at CAMBIA do not agree with the editors of Nature Biotechnology
that the only way forward for open source in biotechnology is a grand-scale
“Apollo project” of the type they suggested, we do agree that it may be an
attractive option

What would a 21st century Apollo project to spur biological innovation
look like? If the BiOS Initiative and the movement need such a platform from
which to explore, create and coordinate new modes of problem solving using
life sciences, what will that platform be? Primo, the project would require a
socially and economically highly desired goal for which a technological inter-
vention of great promise can be articulated. The project would need to focus
on catalyzing new opportunities for problem solving, not just on creating an

months or years; validation, scaling and quality assurance take even longer. E
the process can be so expensive or so specific to circumstances that it may never be
replicated by another entity.

We are cautiously optimistic that as we introduce new, recognized and respect-
ed “reputational” tools, if we nurture high profile and energetic champions for par-
ticular projects, and if we create new incentive and reward systems, we will be able
to move the BioForge from a field of dreams into a productive and focused mech-
anism for distributive innovation.

Beyond the Thicket: Transbacter

By about 2000, my colleagues at CAMBIA and I had seen so much “me-too” sci-
ence going on around the world and the vast increases in patenting and vertical
industry integration. We also saw public support eroding for genetic modification
and then for all scientific interventions in agriculture. So we decided it was time to
act more aggressively.

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imposed “solution.” It would not have a linear impact, nor would it merely
improve the cost effectiveness of conventional paradigms.

To engage both the scientific and the business community, such a coordi-
nated effort would offer an intellectually exciting proving ground for new col-
laborative approaches and new science and must require interdisciplinary
skills. The imagination and creative energy of science would be harnessed, Ma
much of science is intensely self-absorbed. An interesting problem will attract
much more attention than a mundane one.

The platform activities would afford opportunities for “spin off ” value for
other initiatives and activities, and would have impacts beyond its target goals.
A broad constituency must see some merit in various components of the proj-
ect—so that diverse, even divergent interests would build coalitions.

The project would also have a credible promise, or proof of principle.22 It
would not be too risky—or too safe. While it may be somewhat encumbered
by intellectual property, it would not yet be completely constrained. If the tar-
get has a suite of challenging IP thickets, that would be a platform for new
strategies—of decision support, collaboration and invention—to emerge,
allowing us to hone these capabilities. It would be in a field with few
entrenched interests, or those interests must be diffuse or distracted. If major
economic interests push back too early, they could slow or stall the effort.

Finally—and critically—it would also be in an arena where civil society,
industry and academia can engage constructively towards a détente, and where
they can explore and validate new models of social enterprise and business, COME
well as new economic and innovation strategies.

We decided to attack the first and most prominent thicket of patent rights—
that around Agrobacterium— which represented the beginning of the patent rush
in agricultural biotechnology. We chose this technology not because we believe
that it presents a unique or critical bottleneck to many new entrants into the sec-
tor, or because anyone has called for these patents to be revoked or broadly
licensed. Infatti, these tools have little market pull now. The “scorched earth” pol-
icy in the agricultural biotechnology sector has left virtually no inventive entities
queuing up to develop products, and no public desire for such products.

Piuttosto, we wanted to show the potential for a new combination: what if we
combined patent informatics and transparency with creative, targeted scientific
research, and new normative and licensing tools? What if we used it to build a true
public commons of technology—or rather “rebuild” a public commons of capabil-
ità. We sought not a silver bullet, but rather a platform to test and explore our
hypothesis that in alternate universes of innovation, tools and foundational dis-
coveries could be constantly improving common goods, and that prosperous
industries and business could be built on them.

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Assessing the Patent Landscape

In about 2000, we began a comprehensive analysis of the patent situation sur-
rounding Agrobacterium-mediated gene-transfer (AMGT), the process I discussed
earlier. We intended to publish a simple white paper describing this key thicket of
rights. But the task proved much more complex. Ultimately we published the first
analysis online; almost 400 pagine, and covering the top few hundred patents,17 Esso
has since seen two major updates. Over 1000 users downloaded it. But as we began
to realize the extent of the problem, we also realized that it could not be attacked
piece by piece. As we analyzed the “patent landscape,” we noted that all of the
patents used a common language and set of definitions that dated to the original
filings: that the inter-kingdom gene transfer was achieved as a unique event medi-
ated by a particular bacterial species, Agrobacterium tumefaciens.

Definitions are the key to a patent; they are critical in a patent prosecution to
establish the metes and bounds of the claimed invention, and to guide courts in the
event of a dispute. And the pioneering inventions typically establish precedent that
persists. In the case of Agrobacterium-mediated gene transfer, it was widely
believed and promoted that Agrobacterium was a one-off; a unique situation in
biologia. To this day most scientific papers baldly state that it is the only such situ-
ation.

The Strategy

My logic, and that of most biologists trained in evolution, is that if something hap-
pens once in life, it probably happens many times—maybe ubiquitously. We think
of a “one-off ” because we can rarely see other instances. So I began looking for
hints in the literature that other bacterial species could transfer genes to plants,
either natively or with a bit of convincing. And I found hints aplenty. So we set
out—again with support from the Rockefeller Foundation—to find or generate
the capacity for benign plant-associated bacteria to conduct gene transfer, and thus
to develop a system that would be competent to transfer genes to plants, which was
not infringing any Agrobacterium patents. If we could do this, the toolkit would
clearly fall outside all the patents over AMGT, rendering hundreds, even thousands
of patents irrelevant as blocking tools, but useful as “background science and tech-
nology.”

We further speculated that we would be able to develop a system that was not
only free and clear of the onerous Agrobacterium thicket, but would ultimately be
superior to Agrobacterium as a technology. Agrobacterium is a plant pathogen,
which normally causes disease in susceptible plants. Plants—even non-susceptible
ones—seem to know this, and become stressed. We reasoned that by using totally
benign symbionts, we’d eliminate the stress on the plant, and open new opportu-
nities for genetic enhancement. If we could make the technology more efficient
and wide-acting than Agrobacterium, a wholesale migration to the use would
occur, even by academics. This would infiltrate the new open source norms into
that most conservative of communities.

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The R&D

The process turned out to be more straightforward than most anyone expected,
and we published our results, which described a new system called “Transbacter,"
in Nature18 on February 10, 2005. After nearly two years of hard work by a skilled
laboratory staff, we described in that paper how we had induced three different
genera of benign plant bacteria to transfer genes to three different genera of plants.
These plants included the world’s most important crop, rice, over which Japan
Tobacco held dominant rights, and broadleaf plants, over which Monsanto held
dominant rights.

The capability of Agrobacterium to transfer genes to plants is virtually identi-
cal at a molecular level to the ubiquitous system by which virtually all bacteria
exchange genetic material, and even by which proteins and other molecules are
secreted. This similarity allowed us to excise and move this capability on a fairly
well-defined DNA construct into the benign symbionts. We were able to test the
system with the most sensitive tools in the sector: the open-sourced GUSPlus
reporter system.

The paper received exceptional coverage in the press, ranging from the New
York Times and Science to Nature Biotechnology and the Economist, but not just for
its scientific contributions.

The BiOS Licensing Framework

To share this technology, perhaps counter-intuitively, we filed patents on it. At first
glance, this is anathema to open sharing. But we were learning the lessons of pos-
itive selection and the ugliness of patent gaming and trolling (for an example, Vedere
appendix). As we developed the new technology we also developed, in parallel,
draft licensing templates for a prototype “BiOS” license, as I described earlier. Two
years later, we have over fifty licensees, including large multinational corporations,
small companies, and diverse public sector institutions. We have recently stream-
lined this technology to be more universal and easily disseminated, and have dis-
tributed over 300 kits of the new materials. Traction is building as the technology
is improving.

But this is not really transformative, merely illustrative and instructive. Real
transformation occurs when completely new actors are brought into innovation
systems, and when radically new options for problem solving emerge.

This is our next ambition.

BIOSENTINELS: A 3D VISION FOR EQUITABLE INNOVATION

The most powerful impact of the scientific method has been to help us understand
what had been incomprehensible; it has also helped us visualize and measure the
parameters of the natural world. The importance of measurement cannot be over-
stated. Without the ability to measure—to see the consequences of an experiment
or intervention—we cannot understand it, or improve or build upon it. The future

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The Role of Measurement in the Next Green Revolution

It is often said—and it is true—that the Green Revolution, which so trans-
formed the agricultural and economic fabric of Asia and much of the rest of the
mondo, passed Africa by. The Green Revolution is not largely about plant breed-
ing, although the short-stature varieties garner great attention. Rather the great
advances were in the availability and management of inputs in agriculture.
Water, nitrogen, phosphorus, potassium, acidity and countless micro-nutrient
and abiotic stresses can each separately and together constitute major produc-
tion constraints, as well as input costs, to an agricultural system. Combine this
complexity with the countless impacts of biotic challenges such as pests and
diseases, especially cryptic or latent soil-borne diseases, and creating any kind
of profitable and ecologically sustainable farming becomes horrifically com-
plex in the best of circumstances. Little wonder that industrial agriculture’s
greatest successes—with their concomitant problems—come from homoge-
nizing these environments with massive inputs and then breeding and manag-
ing these artificial and unstable conditions to get maximum yields.

These options are not available for transforming low-input, low-output
agriculture into a prosperous enterprise. When capital, infrastructure and com-
munications are precarious, it becomes even more crucial to accurately and
judiciously source and apply suitable nutrition, and to guide management
decisions well.

The management of natural resources, whether endogenous or enhanced
by inputs, is the most critical and challenging bottleneck in agriculture. It will
be the lynchpin of the next Green Revolution. It is also the component most
amenable to measurement. But here is the conundrum: to have a sustainable
and scalable impact, such management decisions must be made by local prob-
lem solvers, and many such people are extraordinarily poor. They cannot afford
to measure, and they cannot afford not to.

of biological innovation will similarly hinge on turning the unseen into the seen,
and to sensibly report on the world around us so we can better respond.

Most critically, we must democratize these abilities, both to measure and to
respond, in order to diversify agro-ecosystems and environments and decentralize
the problem-solving capability. We will achieve this by fostering scientific method
and harnessing local knowledge and commitment in communities that have pre-
viously been ignored or treated as passive recipients of help. This is our 3D vision,
and the BioSentinel project will be the platform for exploring and realizing this
vision.

In many vineyards around the world, rosebushes are attractively located at the
end of each row. This curious planting regime does not reflect some shared aes-
thetic among winemakers or grape-growers. Rosebushes are sensitive to certain

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fungal diseases that affect grapevines more than the grapes themselves. If they
plant and observe roses, growers can easily see the early stages of fungal infection
on the roses, and can take measures to prevent disease in the grapes. The rose is a
natural BioSentinel.

For the last 15 years CAMBIA has been working on the components necessary
to generalize this phenomenon.23 Now, with the advent of new scientific under-
standing, new proofs of principle, E
the BiOS Framework, this work can now
be brought to scale. With initial support
from the Lemelson Foundation, we are
beginning to create an open source plat-
form to use plants as versatile living
BioSentinels to measure and report on
the status of their environment.

Imagine a plant—not necessarily a
food plant—that has been engineered as
an instrument to produce a colour, UN
smell, or a shape that indicates the level
of nitrogen or another essential nutrient
in the soil. This plant will be developed
in a collaborative, open sourced environ-
ment with components that are BiOS
licensed and held in public trust. It will
be a cost-free instrument that allows any farmer to better judge the condition of
her cropping system, and to create wealth by making careful decisions, informed
by measurements of the unseen parameters that influence her crop and its envi-
ronment.

[W]e are beginning to
create an open source
platform to use plants as
versatile living
BioSentinels to measure
and report on the status
of their environment.

But the BioSentinel project involves much more than engineering one plant to
make one color in a glasshouse. It is no mere academic curiosity. We intend to
develop the platform to create a modular toolkit for the public and private sectors
alike. We envision mixing and matching components to sense virtually any param-
eter (nutrient, water, pathogen), transmission of this signal via open standards,
and reporting on this parameter with any of several different detection systems
(colore, fluorescence, smell, form). We also intend to consider all the quality assur-
ance, regulatory and other parameters necessary for diverse collaborators to create
practical and deliverable innovations. The BioSentinels will cost nothing to man-
ufacture, once developed. They will cost nothing to use. But they will add value
through the information they make available.

This platform will be built using technologies developed under BiOS license,
guided by sophisticated patent informatics to ensure permissive use, and will pio-
neer new collaborative research methods that enshrine and perpetuate permissive
use by all parties. The platform need not create GMO foods, but will create new
communities of informed decision makers who are empowered to evaluate and
improve their own ecologies and economies.

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Richard Jefferson

CONCLUSION

At the start of the twenty-first century, science is at a critical juncture. Four cen-
turies of inquiry, discovery, and invention have created a base of knowledge that
has the potential to provide people everywhere, in all circumstances, with nourish-
ment, improved health, and longer life. But the institutional mechanisms that
ostensibly exist to encourage the application of science to practical problems are
today hindering that very process. The norms that have evolved around gate-keep-
ing have created new clergy, new impediments and new inefficiencies. Without a
systemic change, science’s promise will not be available for those who most need
Esso, and the promise of a truly diverse, robust and fair innovation culture may elude
us.

Patents are at the heart of the system of institutions that convert basic scientif-
ic knowledge into practical applications. The modern patent system was intended
to advance the public good by balancing the disclosure of ideas and the transpar-
ent definition of limited property rights. Today, it has degenerated into an instru-
ment that is often misused to obstruct the public good through enclosure of ideas
and obscure assertion of property rights that have no concomitant social benefit.
To the shared dismay of both scientists and thoughtful citizens, patent systems and
the myriad gaming practices they have spawned today are impeding innovation as
a social enterprise, and continuing to deprive most of the world’s population of
such fundamentals as adequate nutrition, access to health care services, and clean
water. This does not have to be. It is up to us to reclaim the beauty of science as a
democratized tool for social advancement and wealth creation. It is up to us to
write the terms of the compact. It is up to us to move beyond rhetoric and into
constructive engagement in reforming our innovation systems for economic
robustness and social justice.

We invite reader comments. E-mail .

APPENDIX. CO-OPTING THE COMMONS:
A NEGATIVE EXPERIENCE OF POSITIVE SELECTION

For nearly seven years, with expenditures of over $100,000, CAMBIA has battled
Syngenta, the large Swiss agribusiness, in European Patent Office opposition pro-
ceedings and appeals over the validity and scope of Syngenta’s patents on “Positive
Selection.” These broad patents (e.g. EP 601092, but with counterparts in the USA)
were granted with sweeping claims that conferred on Syngenta an absolute
monopoly on “positive selection” in plants.

Positive selection is the provision of a benign compound—such as a sugar—
that an organism cannot use without the action of a new gene; thus it “selects” for
those organisms that have acquired that gene. Positive Selection is one of the most
basic tools in genetics, used since the beginning of microbial genetics; all the bac-

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terial genetics in the 1950’s and 60’s was based on one bacterial strain gaining the
ability to grow on new sources of carbon and energy. When I started working with
plants, it was thus immediately obvious to me (and presumably to anyone not
employed at the patent office) that we could easily adapt this concept to plant
genetics, to determine when a new gene had been added to a crop plant, and that
a good first use would be my GUS gene.

So I began adapting GUS for this purpose, around the time I started sending
out GUS kits and information, and giving hundreds of lectures on its use. While
this mode of distribution was to dramatically change the field, it also allowed some
aspects of the system to be co-opted. Our ideas and hard work were basically
turned from “non-rival” goods that were available for all as we intended, into a pri-
vate monopoly that could, and did, suppress innovation by competitors.

Scientists at a Danish sugar company, DANISCO, filed a patent well after I had
given them the GUS gene, and after I had given public lectures on the use of GUS
for such purposes. In this patent, they were granted broad claims to all uses of pos-
itive selection, with any compound and any gene in any plant. This breathtaking
scope of claims was based solely on experiments described in the applications that
used the GUS gene to activate a biological compound that would allow plant cul-
tures that had GUS to stay green and be “selected.” This was fundamentally what I
had already reported at international meetings, with data showing that it worked.
Like many scientists, when I reported it at international congresses, I intended to
see it shared with everyone. DANISCO’s intention clearly was not.

The potential value of this patent estate caught the eye of Heinz Imhof, Poi
chairman of Novartis, who intervened personally to buy the patent applications
from DANISCO outright. These patents then served as powerful ammunition in
the patent war chest of Novartis, which went on to merge with other companies in
the vertical integration frenzy of agricultural biotech, to become Syngenta. IL
evolving strategy of Mutually Assured Destruction by Patent Estate between the
large multinationals required just such weapons.

The breadth of the claims as granted in Europe—together with their counter-
parts in the USA—ensures that any entity using the approach of conferring a
growth advantage on a cell or plant to obtain transgenic plants would be infring-
ing. This left only the use of antibiotic resistance and herbicide resistance as the
means of selecting transformed plants. The adverse public response to such antibi-
otic gene use is well documented.

Thus the environmentally attractive and benign technology of cleaving a sugar
and growing preferentially, with no antibiotics, was denied to the world’s agricul-
ture community by one group of patents, whose entire rationale was derived from
work that I had intended to make public. But with the patent, it was “enclosed.”

I had several meetings with Imhof and others at Syngenta; I attempted to make
the case that using GUS to garner such a powerful and oppressive patent position
was unjust and inappropriate and would ultimately be a pyrrhic victory for the
sector. The discussions went nowhere.

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So we made use of one of the few remedies afforded in the patent system to
small players: the opposition process. Once patents are granted in Europe, they can
immediately be challenged if one submits to the European Patent Office (EPO)
prior art that had not been considered. Our contention in the EPO was that much
public work, as well as my own work, including my public disclosure of the basic
idea, pre-dated the filings and would thus invalidate the novelty requirement for
the patent. We also argued that the patent was obvious in light of the pervasive use
of positive selection in every other biological system for many years. We also
asserted that the patent did not sufficiently enable one to practice the invention,
and in particular, did not merit the breadth of claims granted.

The opposition process is widely touted as much more affordable than litiga-
zione. No doubt this is true. Instead of paying several million dollars to lawyers so
we could be screwed by a multinational corporation in front of a judge, we only
had to pay a hundred thousand or so for the same privilege, but in front of a panel
of patent professionals. Of course reconsiderations of patent validity are conduct-
ed by the very same entity—the administrative machine of the patent office – Quello
made the initial patent grant. So even in the face of what we felt to be compelling
prior art, and convincing case law, the deck was stacked in favor of the status quo.
Watching the process, and the craft and gaming skills involved, was an eye-
opener for me. Until one has actually endured the multi-year posturing, arguing,
heartache and expense, there can be no clear way to convey the dysfunction of the
system, or its debilitating effect on inventors. We achieved only modest inroads in
restricting the breadth of their claims. But we did consume years of time and huge
amounts of money, in a failed bid to restore for public use a key application of a
technology that I had developed and had inadvertently let a multinational pull into
its private fiefdom. The opposition process is not available in the United States, so
the opportunity to lose extravagant sums of money there was denied to us.

What did Syngenta do with this technology? With the example they claimed
using GUS, nothing. They never made a single product using that tool, nor did
they develop it further. But they used the broad claims, granted by both the
European and U.S. patent offices, to ensure that no other player—large or small—
attempted positive selection without becoming beholden to them. Later, from
DANISCO, they acquired other examples of positive selection protocols which
worked pretty well and were protected under the umbrella of the broad claims,
they made them “available” under a research license to unsuspecting scientists in
the public sector. This “research license” strategy is one of the most pernicious co-
opting approaches used by large private-sector companies. Once a tool is used
under such a license, the only way to then release a product is through after-the-
fact negotiations for a “commercial license.” Several friends have gone through this
process and reported a bare-knuckled strategy that gives the licensee almost no
share in the benefit of the product they developed. Few takers, Ovviamente.

What are the lessons. Don’t share? This is not a lesson I cleave to, nor a recipe
for social progress. Could it have happened otherwise? Absolutely. This example
was a case study of how “open source” licenses could be crafted and protect the

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public commons, yet allow the private sector to build prosperous businesses using
that commons of technology. Perhaps I should have only sent the GUS gene and
disclosed the information to those who agreed to terms by which they would share
improvements that specifically used GUS; then the entire broad positive selection
concept would likely have stayed available to all entities—public and private, large
and small—that wished to explore its use. As would the many modifications on
which others had filed patents. Just imagine: what would happen if the public sec-
tor technology transfer professionals had access to such a leverage tool to further
the power of the commons toolkit and advance their mission?

1. Per esempio .
2. In economics, a good is considered either rivalrous (rivale) or nonrival. Rival goods are goods
whose consumption by one consumer prevents simultaneous consumption by other consumers.
In contrasto, nonrival goods may be consumed by one consumer without preventing simultaneous
consumption by others. Most examples of nonrival goods are intangible goods. (from Wikipedia,
2007).

3. Mike Bevan, my principal collaborator, went on to play a key role in coordinating the public sec-
tor sequencing of the Arabidopsis genome . Arabidopsis is the workhorse model plant of biotech-
nology, and was the first plant to have its entire DNA sequence described in the literature. IL
public efforts to create a public good, like some of mine, were likely co-opted by the secretive
wholesale filing of patents on the Arabidopsis genome by Mendel Biotechnology, an affiliate of
Monsanto. These patents have only recently surfaced () but pre-dated the
public effort by as much as two years, thus potentially capturing or hijacking much publicly-fund-
ed work, through a legal, though unpalatable practice called ‘after-claiming’.

4. R.A. Jefferson, T. UN. Kavanagh, and M. W. Bevan (1987), “GUS fusions: beta-glucuronidase as a
sensitive and versatile gene fusion marker in higher plants.” European Molecular Biology
Organization Journal, Dicembre 20; 6(13): 3901–3907. Apparently it has been read often, as it has
been cited in the scientific literature thousands of times. To our delight, Tuttavia, the user’s man-
ual in Plant Molecular Biology Reporter has been similarly cited, and likely more influential, In
the precursor to the Open Access publishing movement.

5. Monsanto later engaged Agracetus in a heated patent battle for the right to do genetic manipula-
tions in soybeans, and ultimately purchased Agracetus and its patents. At this point the patents
owned by Agracetus ceased being seen as reprehensible and unfair, and were defended as pillars
of rectitude.

6. These scientists included groups led by Mary Dell Chilton, Marc van Montagu, Eugene Nester, Jeff
Schell, Pat Zambryski and others, at the University of Washington, the University of Ghent, IL
Max Planck Institute, and elsewhere.

7 See forthcoming “Patent Landscape on Plant Genomes.”
8. Jefferson, R.A. (2001). “Transcending Transgenics: Is there a baby in that bathwater, or is it a dor-
sal fin?,” in The Future of Food,” edited by Phil Pardey (International Food Policy Research
Institute with Johns Hopkins Press), pp75-91.

9. See Appendix on positive selection.
10. Imperial Chemical Industries; its plant work was later absorbed into Zeneca and then into

Syngenta.

11. More details on the complexities of this period can be found in Richard Poynder’s online inter-
Fonte,

view

Biological

Basement

Interview:

Open

IL

me:

Di

12. The Consultative Group on International Agricultural Research, , a consortium
Di 15 agricultural research institutes and many governments, is the principal non-profit entity
engaged in agricultural development through science for poverty reduction.

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13. Dr Marie Connett, CAMBIA’s Deputy CEO, a scientist, patent agent, and IP Manager, jumped
into the deep end when she joined in 2005, and found herself working round the clock on cre-
ating the license, consulting with dozens of technology transfer professionals, lawyers, industry
colleagues and scientists.

14. The Patent Lens was featured in an editorial in Nature Biotechnology (2006, 24:474), called
“Patently Transparent” which was disarmingly positive about our PatentLens activity providing
a critical breath of transparent fresh air to the patent frenzy that is creating a crisis in biotech-
nology. The PatentLens team, led for the last two years by Dr. Marie Connett, still has its origi-
nal three software informatics specialists, Greg Quinn, Doug Ashton and Nick Dos Remedios,
and has been strengthened by additional talent, including Paul Freeland, Neil Bacon and Josh
Cole.

15. A work-beyond refers to a created technology which both bypasses and transcends the propri-
etary technology it seeks to replace. Transbacter, described later, is an example of a ‘work
around’, which will become a work-beyond when its efficacy and uptake increases.

16. Brian Behlendorf is the Chairman of the Apache Software Foundation, and a driving force in the
creation of the Apache Web server, one of the most widely used open source software tools in the
mondo, with nearly 70% of the world wide web making use of it.

17. Vedere . The first version was mostly a tour de force by Carolina Roa

Rodiguez with guidance from Carol Nottenburg. –

18. Nature, 2005, 433:629-633. “Gene Transfer to Plants by Diverse Species of Bacteria.”
19 An outstanding article by Kenneth Cukier appeared about a year later: “Navigating the Future(S)
of Biotech Intellectual Property,” Nature Biotechnology (2006) 24:249-251. It articulately
described the increasing impasse in biotechnology caused by misuse of the IP system, and fea-
tured CAMBIA’s BiOS Initiative very prominently and favorably. The metaphor Kenn used in
this paper-that of maritime navigation and commerce – is extremely apt and informative. His
paper is strongly recommended.

20. “Open Sesame,” Nature Biotechnology (2005), 23:633. Clearly the authors did not have a young
child to remind them that “Open Sesame” was the incantation that would open the cave in which
thieves had already sequestered stolen riches, a suitable parable for the misuse of the patent sys-
tem.

21. The Apollo project was the concerted effort by the United States government to reach the moon
before the Soviet Union did. The long-term focus may have been to reach the moon, but the pro-
ject’s real purpose was to coordinate massive scientific, engineering and technological progress
with industrial development, while building and preserving a societal and political confidence
associated with success. It wasn’t really about reaching the moon, it was about being able to reach
the moon.

22 In the absence of jet aircraft, rocket propulsion and supersonic flight, the idea of space flight

would have seemed ludicrous to many.

23. This work has benefited particularly from early contributions of Kate Wilson and Steve Hughes,
both Members of CAMBIA, now with CSIRO and Exeter University, rispettivamente. Summarized
In, e.g. R. UN. Jefferson (1993), “Beyond Model Systems: New Strategies, Methods, E
Mechanisms for Agricultural Research,” Biotechnology R & D Trends, Volume 700 of the Annals
of the New York Academy of Sciences, Dicembre 21, 1993. pag 53-73; Wilson, K. J, UN. Sessitsch, J.
C. Corbo, K. E. Giller, UN. D. l. Akkermans, and R. UN. Jefferson (1995), “(cid:31)-Glucuronidase (GUS)
transposons for ecological and genetic studies of rhizobia and other Gram-negative bacteria.”
Microbiology 141: 1691-1705.

44

innovazioni / autunno 2006

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