January 17, 2005
Proposal For Open Source Drug Development
How about open source development of drugs for Third World tropical diseases?
Only about 1% of newly developed drugs are for tropical diseases, such as African sleeping sickness and dengue fever. While patent incentives have driven commercial pharmaceutical companies to make Western health care the envy of the world, the commercial model only works if companies can sell enough patented products to cover their R&D costs and produce profits for shareholders. The model thus fails in the developing world, where few patients can afford to pay patented prices for drugs. The solution to this devastating problem, say Stephen Maurer, Arti Rai, and Andrej Sali in the premier open-access medical journal PLoS Medicine, is to adopt an "open source" approach to discovering new drugs for neglected diseases.
They call their approach the Tropical Diseases Initiative (www.tropicaldisease.org), or TDI. "We envisage TDI as a decentralized, Web-based, community-wide effort where scientists from laboratories, universities, institutes, and corporations can work together for a common cause."
What would open-source drug discovery look like? "As with current software collaborations, we propose a website where volunteers could search and annotate shared databases. Individual pages would host tasks such as searching for new targets, finding chemicals to attack known targets, and posting data from related chemistry and biology experiments. Volunteers could use chat rooms and bulletin boards to announce discoveries and debate future research directions. Over time, the most dedicated and proficient volunteers would become leaders."
The key to TDI's success, they argue, is that any discovery would be off patent. An open-source license would keep all discoveries freely available to researchers and--eventually--manufacturers. The absence of patents, and the use of volunteer staff, would contain the costs of drug development.
Reflecting the range of issues that a proposal like this must address the three fellows making this proposal, Stephen Maurer, Arti Rai and Andrej Sali, are two lawyers and a computational biologist respectively.
You can read the full journal article for free. Note that open source drug development is becoming possible because of advances in computer and communications technology.
Ten years ago, TDI would not have been feasible. The difference today is the vastly greater size and variety of chemical, biological, and medical databases; new software; and more powerful computers. Researchers can now identify promising protein targets and small sets of chemicals, including good lead compounds, using computation alone. For example, a SARS protein similar to mRNA cap-1 methyltransferases—a class of proteins with available inhibitors—was recently identified by scanning proteins encoded by the SARS genome against proteins of known structure . This discovery provides an important new target for future experimental validation and iterative lead optimization. More generally, existing projects such as the University of California at San Francisco's Tropical Disease Research Unit (San Francisco, California, United States) show that even relatively modest computing, chemistry, and biology resources can deliver compounds suitable for clinical trials . Increases in computing power and improved computational tools will make these methods even more powerful in the future.
As computers and modelling software become steadily cheaper the rate of advance of biomedical research will accelerate. More work will be done in computer simulations. More collaborations across great distances will take place. Ideas and results will be shared far more rapidly.
However, I see at least one big problem with this approach: If patent royalties can not be earned off of drugs developed in this approach then there will be no company with the financial incentives to pay the hundreds of millions of dollars it would take to fund taking an open source drug through the drug approval processes of more industrialized countries. So the drug would never be developed for First World country uses. Whether the potential First World uses were identical or for a completely different purposes the financial incentive would be lacking to pay for getting a drug through First World clinical trials and regulatory hoops.
Take, for example, artemisinin. Henry Lai and Narendra Singh at the University of Washington Department of Bioengineering have found that artemisinin, a compound used in less developed countries to treat malaria, works against cancer cells. But while preliminary research has found anti-cancer effects in animals and there are desperate cancer patients taking it on their own (since it is from an herb it is available over the counter as an herbal extract) the problem with artemisinin's being unpatentable prevents it from attracting major investment from big pharma companies. It may be possible for companies to develop similar compounds that are patentable that work the same way or take artemisinin or one of its active forms and attach it to antibodies to target cancer cells and get a patentable treatment that way. But the fact that artemisinin and artemether (another form of the compound) are not patentable has slowed development of this therapy for cancer.
The real challenge to the open source for pharma products is how it will mobilize the resources necessary to complete a project. It will not be easy. Development, production and transaction costs are not marginal in pharma as they are in software. They are real and material.
The software open source movement in IT has been propelled by five major factors: production is performed on low cost machinery (PCs owned by individuals); factor inputs that are primarily digital (i.e., material marginal costs); highly modular problem decomposition; a relative free trial and error loop; and the ability of developers to utilize company resources (e.g., company time) for development. None of these are true in pharma. As an experienced veteran of the dotcom game I am comfortable asserting that programmers spend time developing open source code when they should be working for the company. In addition, drug development is not the process of scanning databases. Real lab work is required on the front end (I will not dwell on clinical trials). These costs are material even if on the margin for a running pharma. I suspect that rational pharma company will be and should be very leery to permit the use of resources on the margin. They will encounter a number of agency problems if they do.
Alternatively, factor inputs employed in the pharma industry are not as divisible as they are in the software industry. This makes it hard to secure all the resources necessary to develop drugs. In addition, ownership of the factor inputs is more clearly located within the firm.
Many people fail to appreciate that just because pharma products have high upfront costs and low production costs (marginal production costs), that they are not equivalent to to software. Software has relatively low development costs. It is the debug and update cycles that eat up massive amounts of dollars.
"millions of dollars it would take to fund taking [a] drug through the drug approval processes"
There's the problem that needs a fix. Perhaps "open source" drugs could prove a wedge for reform: change the rules so that if a new drug isn't patented, it is "grandfathered" past regulation.
The same people who insist on regulatory approval for patented drugs also insist on it for unpatented drugs. There is no way around the fact that the vast majority of the population are not libertarian or anywhere near it.
Bleh. 3rdworlders STILL BREED like roaches. No offense but it's SO TRUE. [Perhaps] Should their population decline then drugs will be cheaper for them. Hope their numbers would DECLINE for long. :SIGH:
We must make all diseases extinct,so we can choose how we evolve.The average newborn has three hundred mutations,that is detrimental to it`s health.We will probably always face the threat of pathogens jumping the species barrier,but we could remove them from our species.With our prompt global response to the tsumani disaster,we have averted a new strain of cholera from developing.This open source drug development will help in the eradication of tropical diseases.This would be good for the Indian pharmaceutical companies.
I refer you to December's Wired magazine. It is a little blurb about how CUBA (you know, the place off the coast of Florida we plan to reinvade some day) is the country working on tropical and other medicines. The future drugs in the US are developed by universities (with government money) and handed to companies to run the trials and profit from them.
Drug companies in the US market "lifestyle" drugs. Viagra, all those purple pills for people who won't, don't or can't cope with reality. They refuse to make drugs for saving lives. Or they play games with the "orphan drug" laws so that DrugX, which can be used to cure a million or so people each year for DiseaseY, is instead licensed for treating DiseaseZ, which affects a couple hundred people per year. As a result of abusing the tax breaks and credits for "orphan drugs" the taxpayers end up subsidizing the drug companies to the tunes of hundreds of millions of dollars each year.
Our future drugs won't be coming from domestic pharmaceutical companies. They will be licensed from offshore.
The next to last paragraph goes:
"It's like Castro said: They don't really like patents. They like medicine. Cuba's drug pipeline is most interesting for what it lacks: grand-slam moneymakers, cures for baldness or impotence or wrinkles. It's all cancer therapies, AIDS medications, and vaccines against tropical diseases."
Mike, we came up with the FDA about 100 years ago because any crackpot could put morphine and alcohol in a bottle and sell it as a "patent" medicine. We have the FDA to help the public decide what is safe and what isn't. It doesn't help when we have industries, like the tobacco industry, who have advertised for over 100 years that not only is smoking safe, it is good for you. Perhaps you might like to devote a weekend to reading "Trust Us, We're Experts." Most public libraries have a copy.
Over half the drugs now in big pharma development pipelines are for cancer. Over half. So the stereotype that drug companies just develop lifestyle drugs is obviously false.
Castro: Well, where is Cuba's equivalent of Gleevec? And how many of the AIDS medicines in use are from Cuba?
I expect most of our future drugs in the next 20 years will come from US drug companies followed by European drug companies. Though an increasing portion are going to come from biotech start-ups funded by venture capitalists.
Our future drugs won't be coming from domestic pharmaceutical companies. They will be licensed from offshore.
> What's wrong with that? If they can make it cheaper with the same high quality, we do it ourselves?