Academic research institutions and drug companies alike have been criticized for the high prices of their patent-protected drugs–particularly when these high prices are maintained in poor countries, where patients can least afford them.  Yale was the site of a conference last week where it and five other universities signed on to a statement of principles governing technology licensing in developing countries.  While this document is primarily a statement of shared philosophy, does it provide a good model for improving access to medicine in the poor nations–and perhaps even here at home?

Many would agree that universities should automatically subscribe to the principle of removing barriers to medication in developing countries; few but the most cynical would expect academic institutions to desire profits over the advancement of global health.  Unfortunately, it is unclear whether universities have the legal or practical potential to ensure that fruits of their researchers are equitably available–mostly because universities are not in the business of actually making the drugs.

The new licensing principles are crafted to address that disconnect between academic (and mostly publicly funded) research and the patient end-user.  In the context of academic biomedical patents, licenses are the contracts that the university (which reserves the right to patent anything invented within its facilities) signs with companies that agree to develop and market the innovation.  These licenses can contain anything mutually agreeable to both parties, but the main thing at stake is money: the university wants to get as large a percentage as possible in royalties, while still providing sufficient incentive to the company taking the risk of developing the drug.  The right of universities to profit, financially, from publicly funded research was codified by Congress almost thirty years ago, and major research universities have offices dedicated to working out license agreements.  What several universities, including Yale, have now agreed to in principle, is to exercise their rights as patent holders, to ensure licenses are written in such a way that, at the very least, they won’t be barriers to distributing discounted drugs in poor countries.

From an extremely idealistic vantage, it is appealing to compare these activist, principled licenses to the copyright licenses that have enabled the open-source software revolution, where creators invoke their intellectual property rights to ensure their creations are openly available.  Such a philosophy lies behind Creative Commons licenses, covering the words you’re reading right now, as well as the GPL, which has enabled a software revolution.

Of course, the comparison is completely metaphorical.  The major problem is that a license can be as activist and idealistic as anyone wants it to be, reserving rights to free distribution across Africa, Asia, Detroit and the Mississippi Delta, but it will have no impact unless the terms are acceptable to a drug company.

Furthermore, like many high-tech products, drugs are often born of quite complicated intellectual-property parenthood.  A company might license a research patent from a university, but then make several more patentable innovations, perhaps related to the process of actually manufacturing the drug, before the medication enters the marketplace.   Those who negotiate licenses on behalf of universities will have to be exquisitely shrewd to anticipate such complexities, and ensure that they can retract licenses if drug companies don’t follow through with equitable drug distribution.

The proposal enshrining the new guiding principles recognizes the pitfalls in ensuring access to medicines.  Time will tell whether universities can, within the current patent regime, exert a measurable influence over drug distribution, or whether their new principles are merely P.R. posturing.

Finally, by stating the principle of equitable access should be embodied in license agreements, how long can universities ignore patients here at home, in the U.S., that can’t afford medicine?  Drug companies are afraid that cheap drugs distributed even across the ocean in Africa will make it back to rich countries, diluting their market share and profits.  However, poverty is as globalized as ever, global warming threatens to bring tropical diseases to the temperate homeland, and meaningful health-care reform remains elusive.  Is it possible for Yale and other institutions to remain true to their goal of “implementing technology transfer strategies that promote the availability of health-related technologies”, without doing the same at home as in poor countries?

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More reading:

• Universities Allied for Essential Medicines: detailed proposals for Equitable Access Licenses.
• Yale press release.

It’s a familiar story, told in elementary school science lessons.  In 1867, Alfred Nobel patented Dynamite–a ground-breaking technology if there ever was one–which exploded into uses in rock quarries, road projects and the on the battlefield.  The wealth yielded by the sale of dynamite allowed the famous Swede to finance the Prize, which today was awarded for the beautiful research that led to 3-D structural models of the ribosome.

It could be argued that the word “fundamental” could be applied to any number of molecular machines that are essential to the livelihood of practically every cell in our bodies.  But ribosomes are in the very middle of the dogmatic process of turning genes to proteins, and they are extremely well-conserved throughout evolution.  And, as I’ve written before, these revealing biological discoveries will be protected by patents for years.

The New York Times news update described ribosomes this way:

If the sequence of lettered nucleic acids in the DNA form the blueprint for life, ribosomes are the factory floor.

It was a kind of reverse-engineering of this “factory floor” that constitutes the Nobel-winning work.  The laureates first had to crystallize various parts of ribosomes, an extremely complicated task given the size and complexity of these molecular complexes.  These crystals were analyzed with a very sensitive X-ray device, yielding information that, when reconstructed by a computer, can be modeled into a three-dimensional diagram of the molecular structures.

Other than being extremely beautiful, these structures are vital for determining how ribosomes interact physically with other molecules.  These other molecules include ones that  ribosomes would normally commingle with in the cells, like RNA.  More usefully, perhaps, this information can be used to design small, artificial molecules–drugs–that could bind to a part of the ribosome to alter its function in some way, or perhaps to disrupt it completely.

Tetracycline, designed and manufactured by bacteria. (Wikimedia)

A particular bacteria, Streptomyces, has been doing this kind of “drug-design” work for a very, very long time.  Streptomyces evolved various small molecules that bind to ribosomes and disrupt their function. These natural, bacterial molecules–tetracycline, neomycin and others–are now found in pills and over-the counter ointments.  As antibiotics, they kill other cells by attaching to and rendering their ribosomes useless.

Using the Nobel-winning structures to design the types of molecules that these bacteria have long been producing is a practice now protected by a number of patents.  Some of these patents, held by Yale in the name of the prize-winner Thomas Steitz and others, cover not only the process for determining the structure of the molecules, but also the computation used to design new antibiotics.  The Yale patents are currently licensed to Rib-X pharmaceuticals, a Yale-spinoff biotech company based in the New Haven area.

As always, there is an argument that intellectual property must be fully patent-protected before major investments can be made towards developing commercial products.  The patent holders and licensees surely believe that these products will be life-saving, and profitable, and I hate to rain on the Nobel Prize parade.  But should research so fundamental to life, such as the ribosome structure, be locked up for commercial gain–like Dynamite?  Should a private institution, such as Yale, have the only say over how ribosomes may be developed into new biomedical technologies?