Open Source Biotechnology

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URL = http://rsss.anu.edu.au/~janeth/

See also our entry on Open Biology


Contents

Definition

"Open Source licensing is a style of intellectual property management that has evolved in the past half-decade out of the Free Software movement, initiated in the early 1980s in response to restrictive copyright licensing practices adopted by commercial software developers. The Open Source approach seeks to preserve ongoing community access to proprietary software tools without precluding or discouraging commercial involvement in their development.

"Open Source Biotechnology" refers to the possibility of extending the principles of commerce-friendly, commons-based peer production exemplified by Open Source software development to the development of research tools in biomedical and agricultural biotechnology." (http://rsss.anu.edu.au/~janeth/)


Discussion: Janet Hope on Why It is Needed

Introduction

Janet Hope:

"Since the 1980’s, the life sciences have undergone a process of rapid commercialization. The legal mechanism for this process of commercialization has been the expansion of intellectual property (IP) protection to inventions that were previously regarded as unpatentable. The result has been a literally exponential increase in applications for biotechnology patents.

These patents not only protect inventions that are valuable as end products; they also protect early stage inventions and research tools. Advances in biotechnology require the use of many of the latter, for which researchers must obtain licenses from patent owners. A good example is “golden rice”, which utilized more than 70 different patented procedures and processes. To get permission to use all of these tools, scientists enter into multiple negotiations for each piece of IP. These mounting transaction costs can retard, and in some cases completely undermine, their scientific projects. Even if they are not prevented from pursuing research itself, institutions may find that the rights of other IP holders prevent them from commercializing the fruits of their labor.

In biomedicine, there are considerable social costs associated with working within this expensive proprietary system. These stem from the fact that such costs are beyond the resources of the smallest participants, or would-be participants, in the industry. Market forces will naturally tend to direct efforts by big private sector players to where there is the most substantial return on investment. This means research goals are inevitably being narrowed to those that will be most profitable, though not necessarily most useful. Thus, it is often not commercially worthwhile for the biomedical industry to devote significant resources to addressing medical or social needs, such as drugs for very common diseases like tuberculosis or malaria.

Similarly, in agriculture, breeding strategies will be oriented towards major crops in developed country markets, not towards finding genetic traits with characteristics that are useful to poor farmers. The last few years have also seen a series of mergers and acquisitions that have dramatically consolidated the industry, with a huge portion of fundamental research tools ending up in the hands of a tiny number of big multinationals. This level of industry concentration has inevitably led to the overpricing of technologies and the exclusion of innovative start-ups and public sector institutions. This, in turn, means that smaller firms can’t get a foot in the door.

This situation has been described as a “tragedy of the anticommons.” In contrast to the tragedy of the commons, when a public resource is overused because there is no one owner to regulate it, a tragedy of the anticommons occurs when a resource is underused because it has been divided up by a number of owners who may not be willing to agree or cooperate with one another."


Can Open Source Licensing Work With Biotechnology?

"When I spoke to Bruce Perens, who helped define the basis for open source development in his aptly titled document, The Open Source Definition, he took the view that the open source biotechnology movement does not aim to create a particular legal framework. Instead, it is a form of social engineering. There is no question that one could produce a legally binding open source license in biotechnology if one wanted to—the real question is whether anyone will use it.

The different proprietary regimes that prevail in the software and biotechnology contexts are important to consider in answering this question. Both software code and biotechnology innovations are protected under a mixture of licensing systems , but the primary one in software is copyright, whereas in biotechnology it is patents. The cost of patent protection can be substantial, whereas copyright protection arises automatically and without cost to the owner. Also, patent fees are usually at least partly recovered from licensees under the remuneration clauses in a proprietary license.

Second, standardized licenses appear to be important for keeping transaction costs low in open source software, but this approach may be less applicable outside a digital context. Biotechnology innovations are far more diverse in terms of composition than software, which is essentially non-physical and instantly reproducible. Defining rights in living biological materials, given their capacity for self-replication and mutation, is difficult. Determining what constitutes an improvement to a licensed biological technology is also challenging. This aspect would be especially critical in open source applications. As stated earlier, open source licenses generally require that improvements to the technology be made available to the other users. Naturally, this is far more difficult when the medium is biological matter, as opposed to digital information.

To explore how open source might translate into the biotechnology context, it is necessary to characterize it in terms of generalized principles, as distinct from software-specific features. Although it is becoming a popular subject of study for people in many disciplines, no unifying principle has yet emerged as the dominant approach. I have chosen to view open source development through the lens of a relatively new theory from the field of innovation management, known as User Innovation Theory


User Innovation Theory and Open Source Biology

Read the full entry on User Innovation Theory


Conclusion: Will the Open Source Software model work for biology?

"Proprietary approaches to intellectual property in biotechnology have the effect of consolidating knowledge and research tools into a smaller number of hands, stifling the diversity of research and increasing costs to users. Open source approaches to technology licensing and development offer the possibility of a partial solution to these problems. Open source approaches won’t always be applicable to material media, but there are many areas where they could effectively work.

The biggest determinant of open source’s adoption is whether the balance of costs and benefits will make it more attractive to IP owners than the proprietary approach. Of course, this is less likely the more a manufacturer is entrenched in proprietary IP. Thus, it is important to note that even if there are only one or two adopters of open source in a given industry sector, the actions of those adopters can have a big impact. By undermining customers’ willingness to pay for access to tools from a proprietary source which they can get at a lower cost from an open one, a small number of open source adopters can shift the balance of competition in a sector away from proprietary technologies. In this sense, open source principles have the power to transform industries. This is why Microsoft is wary of Linux, and it is also why open source has the potential to break the IP logjam in biotechnology.

People often conflate the successes and failures of open source software with the possibility of open source biology. In this connection, people bring up the current copyright litigation surrounding Linux distributors and the overall non-profitability of such companies as illustrations that the future of open source software is uncertain. While it is true that there are not yet any stand-alone open source software businesses that are actually profitable, this is also largely the case for the traditional business model in biotech. Despite the hype and the high market valuations of the late 1990’s, biotechnology has not yet been a profitable industry overall. In any case, it is not necessary to see open source as a stand-alone business model. Instead, it should be viewed as a business strategy that may be used to complement other strategies.

In the end, the proof for the viability open source biotechnology is not tied to the ultimate success of open source software. Open source software is simply the basis for an analogy—the seed of an idea rather than a rigid formula for success." (http://www.gene-watch.org/genewatch/articles/18-1Hope.html)


By Janet Hope at http://rsss.anu.edu.au/~janeth/OSBiotech.html


How likely is it that pharmaceutical companies would go open source?

Janet Hope:

The obvious question for a for-profit company (eg a pharmaceutical company) is why give away the crown jewels? Why would I donate free access to my intellectual property, that I have generated through my private investment, to everyone -- including my competitors?

And the answer is that there are other ways for a firm to benefit from the adoption and use of its IP, eg:

1. free revealing of IP may establish an advantageous industry standard which may be useful to a company that hopes to commercialise complementary goods and services that sit on top of that technology platform. In other words, free revealing can lead to growth in a secondary market that may bring in more revenue than it loses.

2. free revealing may allow or facilitate improvements to the core technology. If the original innovator then gains access to those improvements, this represents a cost saving in R&D for that company.

3. by revealing its IP, a company may generate a favourable reputation that is useful in selling associated offerings, by enhancing brand value or enhancing the company's ability to attract and keep high quality employees.

As with any other strategy, there are costs as well as benefits associated with an open source approach. Opportunity costs are the gains that an innovator could have made by adopting an exclusive proprietary approach according to the traditional model in biotech and elsewhere. Actual costs include the costs of producing and then diffusing an innovation (if you choose to actively build a user community around your open source product, obviously maintaining and supporting that community will entail extra costs).

Whether the balance of costs and benefits of an open source approach make it more attractive to an IP owner than the traditional proprietary approach will depend on the circumstances. From what I've seen, the likelihood of pharmaceutical companies "open sourcing" their drugs - the actual therapeutic molecules - seems very low.

There are two main reasons for this:

1. Opportunity costs associated with open source. The major opportunity cost of adopting an open source exploitation strategy is the loss of profits you might have made if you had taken an exclusive proprietary approach. In most fields that opportunity cost is actually not all that high, because it turns out there are serious caps on the return you can realistically get from a limited number of licensees. The most important reason for this is that because the patent grant technically covers the means of achieving an end, not the end in itself, patents in most fields are quite easy to invent around, so in effect, the upper limit of the licensing fee you can charge is the estimated cost to potential licensee of coming up with an alternative way of achieving the same goal. Interestingly for our purposes, pharmaceuticals are one of only two exceptions to the rule that patent ownership is not all that profitable in practice (the other, not co-incidentally, is chemicals). The main reason for this is that over the years the pharmaceutical industry has successfully pushed for patent grants that are broad enough to effectively cover not just a particular molecule that happens to have value as a drug, but all the variations of that molecule that might be effective, and this means that pharmaceutical patents are actually almost impossible to invent around. So the opportunity costs for a pharmaceutical company in giving up an exclusive proprietary approach to drugs in favour of an open source approach are likely to be too high for pharma to be interested.

2. Established business practice: Pharmaceutical companies rely heavily on patent positions - whether or not they have a patent on a particular pharmaceutical product makes a big difference both to the results of their operations in terms of the economics of selling drugs, and to the company's valuation on the stock market; and this translates into a big emphasis on IP, to a degree even in areas that aren't really related to their proprietary position on their drug products. In other words, not sharing IP is deeply ingrained. To a large degree the biotech industry has inherited that culture of not sharing. The costs of changing established business practice are very real in terms of organisational structure and providing incentives for your employees to shift the way they look at things - and so there is plenty of inertia for large, established companies like the big pharma companies when it comes to adopting fundamentally new business models like open source.

But that doesn't mean open source has no application in relation to the pharmaceutical industry.

For example:

1. One established use of open source business strategies in the software context is to pre-empt the establishment of proprietary technological standards owned by your rivals. Even though pharmaceutical companies hate sharing, one thing they hate even more is being beholden to a single supplier for some critical value driver. This means they might be prepared to put money into an open source biotech company that planned to come up with a really critical tool -- say a toxicology tool that would help predict R&D failures before a drug hit the expensive clinical phase of development. This is a significant example because currently, exclusive patent positions are important to biotech start-ups largely as a way to attract capital. So this kind of support would provide a credible alternative story for biotech start-ups to tell potential investors and thus could promote the development of open source strategies in the biotechnology sector.

2. Using open source as a form of leverage to gain access to improvements to its technology that other people have made for their own purposes: this is of course a form of pre-competitive collaboration, well known in other industries despite high capital costs and time investments. Ironically, the closest to a true open source arrangement that I've come across in interviews was in the heart of exclusive IP territory - in the business model of a successful biotech firm that provides data to pharmaceutical companies. This biotech firm had a licensing arrangement where if any of their customers discovers and characterises a full length gene using the information in their database, the customer has to grant back to the biotech company AND to all of its other customers non-exclusive freedom to operate in drug discovery. Initially this clause was inserted in order to allow customers to use the data without fear of infringement suits from other customers, but it came to be seen as an additional source of value - customers aren't just getting access to the biotech firm's data, they're also getting access to information from all of their rivals. The most interesting part of this story is that this has been happening since the biotech firm set up shop in the early 1990s, some time before Linux took off.

It's also important to note that even if only one or two companies or institutions in a given industry sector choose to go open source, the actions of those companies have a big impact. By undermining customers' willingness to pay for access to tools from one company that they can get at a lower cost or even for free elsewhere, a couple of open source players can shift the basis of competition in the sector away from proprietary technologies. So in this sense, open source really has the power to transform industries. This is one reason why Maurer's proposal is quite exciting - but it also means you'd expect resistance from established firms to anything that looked like open source. We shouldn't underestimate the power of big pharma to influence how open source is perceived if they felt it would be to their disadvantage. Also note that it wouldn't have to be a company that provided open source technologies in order to have this industry-wide effect: it could be a non-profit organisation.


Discussion 2: Conceptual clarification on the use of the Open Source concept

How Open Biology differs from Open Source Biology

Rob Carlson believes the concept of Open Source Biology or Open Source Biotechnology has no real meaning [1]:

"the analogy between software and biology just doesn't go far enough. Biology isn't software, and DNA isn't code. As I study the historical development of railroads, electricity, aviation, computer hardware, computer software, and of the availability of computation itself (distributed, to desktop, and back to distributed; or ARPANet to Microsoft Office to Google Apps), I am still trying to sort out what lessons can be applied to biological technologies. I have only limited conclusions about how any such lessons will help us plan for the future of biology.

When I first heard Drew Endy utter the phrase "Open Source Biology", it was within the broader context of living in Berkeley, trying to understand the future of biology as technology, and working in an environment (the then embryonic Molecular Sciences Institute) that encouraged thinking anything was possible. It was also within the context of Microsoft’s domination of the OS market, the general technology boom in the San Francisco Bay area, the skyrocketing cost of drug development coupled to a stagnation of investment return on those dollars, and the obvious gap in our capabilities in designing and building biological systems. OSB seemed the right strategy to get to where I thought we ought to be in the future, which is to create the ability to tinker effectively, perhaps someday even to engineer biology, and to employ biology as technology for solving some of the many problems humans face, and that humans have created.

As in 2000, I remain today most interested in maintaining, and enhancing, the ability to innovate. In particular, I feel that safe and secure innovation is likely to be best achieved through distributed research and through distributed biological manufacturing. By "Open Biology" I mean access to the tools and skills necessary to participate in that innovation and distributed economy.

"Open source biology" and "open source biotechnology" are catchy phrases, but they have little if any content for the moment. As various non-profits get up and running (e.g., CAMBIA and the BioBrick Foundation), some of the vagaries will be defined, and at least we will have some structure to talk about and test in the real world. When there is a real license a la the GPL, or the Lesser License, and when it is finally tested in court we will have some sense of how this will all work out.

I am by no means saying work should stop on OSB, or on figuring out the licenses, just that I don't understand how it fits into helping innovation at the moment. A great deal of the innovation we need to see will not come from academia or existing corporations, but from people noodling around in their garages or in start-ups yet to be founded. These are the customers for Biobricks, these are the people who want the ability to build biological systems without needing an NIH grant." (http://synthesis.typepad.com/synthesis/2007/03/thoughts_on_ope.html)

Examples

From a list compiled by Janet Hope at http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html

"Although open source biotechnology is at an early stage of development, several past and present biotechnology initiatives have adopted one or more aspects of the open source model.


General Public Licence for Plant Germplasm

"Proposed by plant scientist Tom Michaels in 1999, the General Public Licence for Plant Germplasm is a fairly straightforward adaptation of the archetypal share-alike software licence, the GPL, to germplasm (the indispensable raw material of plant breeding)." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)


Public Sector Human Genome Project

"Another proposal for open source-style licensing of biological information was privately floated in the context of the race between public and private sector scientists to complete a draft sequence of the human genome. Public sector researchers at the UK’s Sanger Institute were concerned that their commitment to publish their own sequence data with no strings attached gave their competitors an opportunity to free ride on their efforts. In 1999, the researchers explored the possibility of licensing the data on share-alike terms and went so far as to commission a draft licence before ultimately deciding that any constraint on data use, even constraints intended to promote public access, would likely be unacceptable to their collaborators." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)


HapMap Data Access Agreement

"The International HapMap Project was a private–public collaboration established to create a haplotype map of the human genome. Before December 2004, researchers wishing to access the Project’s online database had to agree to set of “click-wrap” conditions designed to discourage database users from filing patent applications that would block other users’ access to the data. According to a notice on the site, the software GPL directly inspired the terms of the click wrap agreement.Implementation was problematic, however, and the requirement was withdrawn before the Project was completed." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)

Tropical Disease Initiative and The Synaptic Leap

The Tropical Disease Initiative (TDI) is an open source-style drug discovery scheme proposed in 2004 by lawyers Stephen Maurer and Arti Rai and computational biologist Andrej Sali. Key to implementation of the TDI scheme is its partnership with the Synaptic Leap (TSL), a non-profit organisation founded in 2005 by a former commercial software industry executive. TSL’s goal is to extend the range of scientific collaborations beyond researchers’ personal networks by establishing a usable online open information and communications infrastructure. Recognising that the provision of a “seed” or “kernel” of usable technology is an important ingredient in successful open source collaborations, researchers associated with TDI/TSL have recently published results identifying potential drug targets in ten organisms that cause tropical disease."


Biobricks Foundation

"The BioBricks Foundation (BBF) is a non-profit organisation dedicated to promoting and coordinating the production of standardized modules or “biobricks” that can be assembled into functional synthetic biological systems. Some of the earliest writings on open source biology were triggered by synthetic biologists’ desire to ensure the viability of the enormous collaborative effort needed to realize their engineering goals. As of 2009, efforts are underway to develop a set of open source-style guidelines to encourage resource and data sharing in this growing field." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)


Private companies and Commercial Open Source Biotechnology

"A number of for-profit biotechnology companies have been inspired by the success of open source software enterprises to pursue business models that differ from the more conventional monopoly-based approach.

One example is Diversity Arrays Technology (DArT), a privately held Australian company established in 2001 to commercialize a patented molecular marker technology invented by its founder and director, Andrzej Kilian. The company’s non-proprietary, service-based business model has been inspired by that of Red Hat, the successful Linux distribution company whose initial public offering made Wall Street history in August 1999. DArT offers a concrete illustration of the distinctive commercial logic underpinning open source biotechnology. Instead of relying on injections of funds from capital markets supplemented by licensing revenue, the company’s business model is designed to exploit the synergy between service provision and ongoing technology development." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)

Biological Innovation for Open Society

"Biological Innovation for Open Society (“BIOS”) was an initiative of CAMBIA (Center for Application of Molecular Biology in International Agriculture), an independent non-profit research institute formerly based in Canberra, Australia.


The BIOS initiative, launched in 2005, incorporated:

1. the “Patent Lens,” a searchable patent database containing ancillary information and tutorials;

2. “BioForge,” a portal modelled on the open source software collaboration site Sourceforge.net; and

3. “Biological Open Source” (“BiOS”) licensing of some elements of CAMBIA’s own patent portfolio.


Under the BiOS licences, products derived from the licensed technology could be patented and commercialized subject to a number of constraints. These included a requirement that a broadly defined class of improvements be non-exclusively granted back to CAMBIA.

CAMBIA’s BiOS licenses explicitly invoked the language of open source, and for a time the initiative was widely regarded as the world’s first working prototype of open source biotechnology R&D. However, CAMBIA’s own website cautioned against treating open source as anything more than a metaphor in this case - and in fact, the terms of the BiOS licences diverged in key respects from the institutional logic of open source. In particular, they gave CAMBIA much more control over the actions of follow-on innovators than would have been compatible with established standards for open source software licensing. These standards are designed, in part, to protect contributors to an open source collaboration from exploitation by the project leader (in this case, CAMBIA). Perhaps for this reason, BiOS licences do not appear to have enjoyed significant uptake. As of early 2009, CAMBIA is relocating to the Queensland Institute of Technology." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)


Network for Open Scientific Innovation

"The Network for Open Scientific Innovation (NOSI) seeks to bring together experts from multiple disciplines to develop and analyse licences that comply with open source and other sharing principles for use in the life sciences." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)


Equitable Access Licensing ; Neglected Disease Licensing

“Equitable Access” and “Neglected Disease” licensing are twin elements of an open source-inspired proposal for improving access to essential medicines, put forward by Amy Kapczynski and colleagues at Yale University. These licensing models explicitly envisage universities as licensors but could be adopted, for example, by other researchers and institutions operating within the TDI framework described above. Equitable Access licensing aims to improve access to biomedical innovations in low-and middle-income countries. Neglected Disease licensing aims to facilitate research on orphan or neglected diseases." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)

Free and open source software programs for use in biotechnology settings

"In the post-genomic age, software programs have become key research tools in biotechnology and related industries. Some of the most powerful and widely used software tools for handling the large and complex data sets produced by molecular biologists are open source in the software sense. Why is the open source approach particularly suitable for bioinformatics software? The reason is that bioinformatics applications generally incorporate similar fundamental features, but often require extensive customisation before they can be applied to specific data sets. Unlike proprietary programs, open source bioinformatics tools can be re-used in other contexts but also freely modified to suit unique use environments. In the long term, open source bioinformatics may turn out to be significant as a non-proprietary wedge driven into the culture of an industry that has historically been strongly committed to proprietary strategies. If biotechnology industry participants are already willing to embrace non-proprietary tools in specific contexts, that willingness may gradually extend to other contexts. This is especially true as biotechnology research and development comes to rely more and more heavily on computer modelling and data analysis and the industry continues to experience an influx of researchers with “hard” science backgrounds who are familiar with open source." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)


==Open Source Drug Discovery initiative]]

Open Source Drug Discovery (OSDD) is an initiative led by the Council of Scientific and Industrial Research (CSIR) of India. The goal of the initiative is to “provide affordable healthcare to the developing world by providing a global platform where the best minds can collaborate” to develop new therapies for diseases that disproportionately affect poorer countries. OSDD is supported by the Indian government, which has committed US$38 million to the project. It seeks to raise an equivalent amount of funding from international agencies and private philanthropies.


The first phase of the initiative entails promoting Internet-mediated sharing of data and techniques among independent biologists working on developing drugs against tuberculosis." (http://opensourcebiotech.anu.edu.au/Open_Source_Biotechnology/Practice.html)


==Other sectoral examples--

Open Source Biotechnology in Agriculture

"Researchers in Australia have devised a method of creating genetically modified crops that does not infringe on patents held by big biotechnology companies. The technique will be made available free to others to use and improve, as long as any improvements are also available free." (http://business-times.asia1.com.sg/sub/views/story/0,4574,144880,00.html)

Internal Links

  1. International HapMap Project
  2. Patent Lens
  3. BiOS
  4. Cambia


Status

The Economist on What is already happening

Open Source Biotechnology, from The Economist

“open-source approaches have emerged in biotechnology already. The international effort to sequence the human genome, for instance, resembled an open-source initiative. It placed all the resulting data into the public domain rather than allow any participant to patent any of the results. Open source is also flourishing in bioinformatics, the field in which biology meets information technology. This involves performing biological research using supercomputers rather than test-tubes. Within the bioinformatics community, software code and databases are often swapped on “you share, I share" terms, for the greater good of all. Evidently the open-source approach works in biological-research tools and pre-competitive platform technologies. The question now is whether it will work further downstream, closer to the patient, where the development costs are greater and the potential benefits more direct. Open-source research could indeed, it seems, open up two areas in particular. The first is that of non-patentable compounds and drugs whose patents have expired. These receive very little attention from researchers, because there would be no way to protect (and so profit from) any discovery that was made about their effectiveness. To give an oft-quoted example, if aspirin cured cancer, no company would bother to do the trials to prove it, or go through the rigmarole of regulatory approval, since it could not patent the discovery. (In fact, it might be possible to apply for a process patent that covers a new method of treatment, but the broader point still stands.) Lots of potentially useful drugs could be sitting under researchers' noses.

The second area where open source might be able to help would be in developing treatments for diseases that afflict small numbers of people, such as Parkinson's disease, or are found mainly in poor countries, such as malaria. In such cases, there simply is not a large enough market of paying customers to justify the enormous expense of developing a new drug. America's Orphan Drug Act, which provides financial incentives to develop drugs for small numbers of patients, is one approach. But there is still plenty of room for improvement—which is where the open-source approach might have a valuable role to play." (http://www.economist.com/displaystory.cfm?story_id=2724420)

More Information

See the entry on Open Biology

PhD thesis by Janet Hope dowloadable at http://rsss.anu.edu.au/~janeth/OpenSourceBiotechnology27July2005.pdf

Chapter on OS biology is at http://rsss.anu.edu.au/~janeth/OSBiotech.html

Bryan Bishop on What's all this about "open", anyway? (bibliography (of sorts))