Perspective: Graduation time | Nature

Universities should forego profits from tuberculosis, say David G. Russell and Carl F. Nathan. Tuberculosis (TB) is the single leading cause of death from bacterial infection. It is rapidly

becoming untreatable, and untreated TB has a fatality rate of about 70% after three years. The challenges in developing new drugs for TB are scientific, logistical, fiscal and societal. >

 The financial picture is particularly bleak for TB. Over the past decade many pharmaceutical firms have abandoned antibiotic research, having failed to discover effective candidates with

new mechanisms of action. A further disincentive is the lower return on investment that rapidly curative drugs offer compared with palliative medications for prevalent conditions. The

financial picture is particularly bleak for TB, which chiefly afflicts people in low- and middle-income countries. The prospect of even scantier profits makes it all the harder to entice

drug companies to work on TB rather than infections that are common in wealthy markets. The treatment of TB requires combination chemotherapy, because the use of a single agent virtually

guarantees the rapid emergence of resistance. When new TB drugs do reach the market, rampant drug-cutting and counterfeiting in poorer countries mean that one or more of the drugs in the

combination may be absent, or present at suboptimal concentrations, promoting the accelerated emergence of drug resistance, which is already prevalent to each of the widely used TB drugs.

Consequently, one new TB drug is unlikely to do the trick: we need sets of drugs that work together. The difficulty of finding a new combination is more than additive, as each drug must not

interfere with the others or with the antiretrovirals used to treat HIV infection (a common co-infection in sub-Saharan Africa). Thus, even if a pharmaceutical company discovers one

effective new TB drug (a big if), the chances are that such a drug would be rapidly lost to resistance unless it were used in combination with two or three other new drugs. Embarking on such

a search takes an unprecedented level of social consciousness and cross-industry cooperation. Despite these formidable challenges, a remarkable number of public–private partnerships (PPPs)

have been launched for TB drug discovery and development. Among them are the Global Alliance for TB Drug Development, headquartered in New York, the Bill & Melinda Gates

Foundation's TB Drug Accelerator (Seattle, Washington), the Lilly TB Drug Discovery Initiative (Seattle), the Tres Cantos Open Lab Foundation (Guildford, UK), and the Innovative

Medicines Initiative (Brussels). Many of these consortia pair academic researchers who have an up-to-date understanding of _Mycobacterium tuberculosis_ biology and TB pathogenesis with

pharmaceutical scientists who have access to chemical compound collections that are larger than those in universities, more suited to drug development, and more extensively curated. Even

more important, the pharmaceutical companies bring expertise in medicinal chemistry, chemoinformatics, pharmacology, pharmacokinetics and toxicology, along with the infrastructure to perform

clinical trials. Such partnerships provide outstanding opportunities for innovation and efficiency. Although these PPPs commonly have more open approaches to intellectual property (IP) than

are usual in drug development, several pharmaceutical companies have proved willing participants in the search for treatments for neglected diseases. Unfortunately, this enlightened attempt

to find a solution to the depleted TB drug pipeline has not been matched by all universities. Many academic institutions are struggling to fill a fiscal deficit. In the United States, as a

consequence of the Bayh–Dole Act of 1980, universities in receipt of federal funding are free to license IP as a source of income. Under this profit-driven model, some institutions prefer to

save precious patent-filing funds for IP with greater potential return. Some do not want to commit to the distribution of drugs on a non-profit basis in the public markets of low-income

countries, a condition required by many of the PPPs. There may also be concerns about sharing ownership of IP with a drug company, or universities may demand a share that is disproportionate

with their contribution. Few institutions have heeded the call of the student Universities Allied for Essential Medicines, a global group headquartered in Oakland, California, that

challenges universities to adopt IP policies that promote affordable access to medicines and medical technologies for the world's poor. Although the technology transfer offices in

universities may regard the potential income from the IP associated with the early stages of drug discovery as an attractive source of funds, this expectation is unrealistic for TB drug

development because of the limited commercial return. Moreover, any such income pales in comparison with the hundreds of millions of dollars that need to be invested to turn lead compounds

into drugs. Who will pay to develop the best candidates that emerge from the PPPs? To conduct the clinical trials? To deliver the drugs to those in need? Regrettably, both a penchant for

fiscal conservatism and a zeal for IP protectionism at some universities can obstruct the earliest stages of drug discovery. The world cannot afford to wait long for answers to these

questions, and universities need to play their part in finding solutions. For example, they will need to absorb some of the costs of IP protection and accept the potential for low fiscal

returns for IP related to drug discovery for diseases like TB. More broadly, universities should lobby for larger, lasting fixes to the broken antibiotic pipeline, such as those called for

by a recent panel of the Institute of Medicine of the US National Academies, based in Washington, DC. We need to examine ways of uncoupling the direct link between the rewards for antibiotic

development and income from selling the drugs. As an alternative solution, a global fund — perhaps capitalized by financial transaction taxes — could compensate participating drug

discoverers for their activities in proportion to their products' reduction of the burden of disease. This would encourage industry and academia to become partners, promote cooperation,

and render counterfeiting non-profitable. At this critical time it is imperative that universities re-evaluate their position and become activists for global health. AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * David G. Russell is the William Kaplan Professor of Infection Biology in the Department of Microbiology and Immunology at the College of Veterinary Medicine,

Cornell University, Ithaca, New York 14853, USA., David G. Russell * Carl F. Nathan is the R.A. Rees Pritchett Professor of Microbiology and Chair of the Department of Microbiology and

Immunology at the Weill Cornell Medical College, New York, New York 10065, USA., Carl F. Nathan Authors * David G. Russell View author publications You can also search for this author

inPubMed Google Scholar * Carl F. Nathan View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS

ARTICLE CITE THIS ARTICLE Russell, D., Nathan, C. Perspective: Graduation time. _Nature_ 502, S7 (2013). https://doi.org/10.1038/502S7a Download citation * Published: 09 October 2013 * Issue

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