Previous installment: Five Easy Pieces, Sage’s Federation
What motivates scientists, companies, and funders to develop bold new treatments? Of course, everybody enters the field out of a passion to save humanity. But back to our question–what motivates scientists, companies, and funders to develop bold new treatments?
The explanations vary not only for different parts of the industry (academics, pharma companies, biotech firms, government agencies such as NIH, foundations, patient advocacy groups) but for institutions at different levels in their field. And of course, individual scientists differ, some seeking only advancement in their departments and the rewards of publishing, whereas others jump whole-heartedly into the money pipeline.
The most illustrious and successful projects in open source and open culture have found ways to attract both funds and content. Sage, the Federation, and Arch2POCM will have to find their own sources of ammunition.
The fuse for this reaction may have to begin with funders in government and the major foundations. Currently they treat only a published paper as fulfillment of a contract. The journals also have to be brought into the game. All the other elements of the data chain that precede and follow publication need to get their due.
Sage is creating a format for citing data sets, which can be used in the same ways researchers cite papers. A researcher named Eric Shadt also announced a new journal Open Network Biology, with the commitment of publishing research papers along with the network models used, the software behind the results, and the underlying data.
Although researchers are competitive, they also recognize the importance of sharing information, so they are persuadable. If a researcher believes someone else may validate and help to improve her data, she has a strong incentive to make it open. Releasing her data can also raise her visibility in the field, independent of publications.
Arch2POCM has even more ticklish tasks. On the one hand, they want to direct researchers toward work that has a good chance of producing a treatment–and even this goal is muddled by the desire to encourage more risk-taking and a willingness to look beyond familiar genes. (Edwards ran statistics on studies in journals and found them severely clustered among a few genes that had already been thoroughly explored, mostly ignoring the other 80% or 90% of the human genome even though it is known to have characteristics of interest in the health field. His highly skewed graph drew a strong response of concern from the audience.)
According to Teri Melese, Director of Research Technologies and Alliances for UCSF School of Medicine, pharma companies already have programs aiming to promote research that uses their compounds by offering independent researchers the opportunity to submit their ideas for studies. But the company has to approve each project , and although the researcher can publish results, the data used in the experiment remains tightly under the control of the researcher or the company. This kind of program shows that nearly infinite degrees of compromise lie between totally closed research systems and a completely open commons–but to get the benefits of openness, companies and researchers will need to relinquish a lot more control than they have been willing to up till now.
The prospect of better research should attract funders, and Arch2POCM targets pharma companies in particular to pony up millions for research. The companies have a precedent for sharing data under the rubric of “pre-competitive research.” According to Sage staffer Lara Mangravite, eight pharma companies have donated some research data to Sage.
The big trick is to leave as much of the results in the commons as possible while finding the right point in the development process where companies can extract compounds or other information and commercialize them as drugs. Sage would like to keep the core genetic information free from patents, but is willing to let commercial results be patented. Stephen Friend told me, “It is important to maintain a freedom of interoperability for the data and the metadata found within the hosted models of disease. Individuals and companies can still reduce to practice some of the proposed functions for proteins and file patents on these findings without contaminating the freedom of the information hosted on the commons platform.”
The following diagram tries to show, in a necessarily over-simplified form, the elements that go into research and are produced by research. Naturally, results of some research are fed back in circular form to further research. Each input is represented as a circle, and is accompanied by a list of stake-holders who can assert ownership over it. Medicines, patents, and biological markers are listed at the bottom as obvious outputs that are not considered as part of the research inputs.
Inputs and outputs of research
The relationships ultimately worked out between the Sage commons and the pharma companies–which could be different for different classes of disease–will be crucial. The risk of being too strict is to drive away funds, while the risk of being too accommodating is to watch the commons collapse into just another consortium that divies up rewards among participants without giving the rest of the world open access.
What about making researchers who use the commons return the results of their research to the commons? This is another ticklish issue that was endlessly discussed in (and long after) a break-out session I attended. The Sage commons was compared repeatedly to software, with references to well-known licenses such as the GNU GPL, but analogies were ultimately unhelpful. A genetic commons represents a unique relationship among data related to particular patients, information of use in various stages of research, and commercially valuable products (to the tune of billions of dollars).
Sage and its supporters naturally want to draw as much research in to the commons as they can. It would be easy to draw up a reciprocal terms of service along the lines of, “If you use our data, give back your research results”–easy to draw up but hard to enforce. John Wilbanks, a staff person at Creative Commons who has worked heavily with Sage, said such a stipulation would be a suggestion rather than a requirement. If someone uses data without returning the resulting research, members of the community around the commons could express their disapproval by not citing the research.
But all this bothers me. Every open system recognizes that it has to co-exist with a proprietary outer world, and provide resources to that world. Even the GNU GPL doesn’t require you to make your application free software if you compile it with the GNU compiler or run it on Linux. Furthermore, the legal basis for strict reciprocity is dubious, because data is not protected by copyright or any other intellectual property regime. (See my article on collections of information.)
I think that outsiders attending the Congress lacked a fundamental appreciation of the purpose of an information commons. One has to think long-term–not “what am I going to get from this particular contribution?” but “what might I be able to do in 10 years that I can’t do today once a huge collection of tools and data is in the public domain?” Nobody knows, when they put something into the commons, what the benefits will be. The whole idea is that people will pop up out of nowhere and use the information in ways that the original donors could not imagine. That was the case for Linux and is starting to come true for Android. It’s the driving motivation behind the open government movement. You have to have a certain faith to create a commons.
At regular points during the Congress, attendees pointed out that no legitimate motivation exists in health care unless it is aimed ultimately toward improving life for the patients. The medical field refers to the experiences of patients–the ways they react to drugs and other treatments–as “post-market effects,” which gives you a hint where the field’s priorities currently lie.
Patients were placed front and center in the opening keynote by Peter Kapitein, a middle-aged Dutch banker who suffered a series of wrenching (but successful) treatments for lymphoma. I’ll focus in on one of his statements later.
It was even more impressive to hear a central concern for the patient’s experience expressed by Vicki Seyfert-Margolis, Senior Science Advisor to the FDA’s Chief Scientist. Speaking for herself, not as a representative of the FDA, she chastised industry, academia, and government alike for not moving fast enough to collaborate and crowdsource their work, then suggested that in the end the patients will force change upon us all. While suggesting that the long approval times for drugs and (especially) medical devices lie in factors outside the FDA’s control, she also said the FDA is taking complaints about its process seriously and has launched a holistic view of the situation under its current director.
Vicki Seyfert-Margolis keynoting at Sage Commons Congress
The real problem is not slow approval, but a lack of drug candidates. Submissions by pharmaceutical companies have been declining over the years. The problem returns to the old-fashioned ways the industry works: walled off into individual labs that repeat each other’s work over and over and can’t learn from each other.
One of the Congress’s break-out groups was tasked with outreach and building bonds with the public. Not only could Sage benefit if the public understood its mission and accomplishments (one reason I’m writing this blog) but patients are key sources for the information needed in the commons.
There was some discussion about whether Sage should take on the area served by PatientsLikeMe and DIYgenomics, accepting individual donations of information. I’m also a bit dubious about far a Facebook page will reach. The connection between patient input and useful genetic information is attenuated and greatly segmented. It may be better to partner with the organizations that interact directly with individuals among the public.
It’s more promising to form relationships with patient advocacy groups, as a staff person from the Genetic Alliance pointed out. Advocacy groups can find patients for drug trials (many trials are canceled for lack of appropriate patients) and turn over genetic and phenotypal information collected from those patients. (A “phenotype” basically refers to everything interesting about you that expresses your state of health. It could include aspects of your body and mental state, vital statistics, a history of diseases and syndromes you’ve had, and more.)