The Collateral Benefits of India's Open Source Drug Discovery Programme
Image: Mallikarjun Katakol for Forbes India
n a computer screen, UC Jaleel, a pharmaceutical researcher, shows me a complicated blue structure suspended against a black background. It looks like the outline of a giant lump of quartz. Jaleel informs me that this structure is actually a tiny protein called beta lactamase, secreted by the infamous mycobacterium tuberculosis, the germ that causes tuberculosis. Beta lactamase is one of the foes in our war against tuberculosis, because it makes tuberculosis resistant to a range of powerful antibiotics called beta lactams, leaving us with a smaller arsenal of drugs to fight the disease with. Pharmaceutical researchers are therefore searching for new drugs to block beta lactamase.
Jaleel and his team, a part of India’s ambitious Open Source Drug Discovery programme (OSDD), are among these researchers. Each day, they evaluate almost five lakh chemical compounds, in an attempt to find those that can paralyse targets such as beta lactamase. When they do manage to find such ‘hits’, as they are called in pharmaceutical parlance, it is only a prelude to a long and painstaking process of drug development. Several years of lab work, pre-clinical and clinical trials later, there is a small chance that one of these molecules will turn into a much-awaited new drug against tuberculosis.
But for that to happen, OSDD must train its own phalanx of drug discovery experts, who are currently scarce in India.
When India’s Council for Scientific and Industrial Research (CSIR) launched OSDD in 2008, the idea promised to disrupt the current drug-discovery paradigm, which is failing in diseases of the developing world. No pharmaceutical company wants to develop drugs for tuberculosis, malaria, or leishmaniasis, because the patients, typically poor, cannot afford to pay.
So, instead of investing their hopes in profit-driven corporations, OSDD threw the doors open to academic, government and private-sector researchers all over India and the world. The collaborative process of drug discovery meant an almost unlimited talent pool. Theoretically, the potential was immense.
But six years later, the challenges of this model are becoming apparent. As OSDD progresses beyond early stage discovery to late stage development, the lack of a critical mass of drug-discovery professionals in the Indian academic world is hampering progress. Also, the academic world does not have the system of training and incentives that make pharmaceutical companies tick.
“Typically the discovery timeline should be about two or two-and-a-half years. After that you should be talking a different language,” says Ram Vishwakarma, director of the Indian Institute of Integrative Medicine, a CSIR lab that partners with OSDD. “Now, we need to bring international-level expertise, and some of it will cost money.”
Addressing the Talent Crunch
One area of expertise that is missing in the Indian research landscape is cheminformatics.
Cheminformatics experts have a role to play at the crucial hit-identification stage of drug discovery. They use software to screen lakhs of compounds for tell-tale signs of effectiveness against a particular disease. For example, Jaleel’s team uses a training database of molecules known to be effective against tuberculosis to glean out structural properties common to all of them. Jaleel compares the process to the spam filter of Gmail. “How does Gmail know that certain emails, promotions are spam? It uses artificial intelligence. Cheminformatics is also like that,” he explains. Next, Jaleel’s team combs through an open database of 166 billion drug-like compounds, known as GDB-17, to find those that have properties similar to the training database.
But the lack of enough good cheminformatics experts in India is slowing things down for OSDD. In 2013, the Sir Dorabji Tata Trust gave OSDD a Rs 2.85 crore grant to create fellowships for PhD students. These students are now being trained in the discipline, even as they screen molecules. Jaleel says that while the enthusiasm and youth of these students is a distinct advantage, there are conceptual gaps in their understanding, and it will take time to turn them into experts.
OSDD is doing everything it can to address the gap. In February, it conducted a cheminformatics workshop in Pune where its 95 principal investigators got together with members of the UK’s Royal Society of Chemistry and developed their own cheminformatics algorithms for hit identification. Such in-house tools are necessary for OSDD, because the private sector does not make its proprietary tools available to others. Also, these proprietary tools are not designed with neglected diseases in mind.
The second talent gap is medicinal chemistry. When scientists identify a promising molecule after virtually screening compound databases, the hit they are left with is something of a blunt weapon. While it is capable of attacking the disease-causing bacteria, it often has too many side effects to become a viable drug.
For example, OSDD currently has a molecule developed in Lucknow’s Central Drug Research Institute (CDRI), known as the CDRI 830. “From a perspective of TB activity, this molecule is ready to go. But the chemical groups on it have been seen to cause cardiac problems,” says Tanjore S Balganesh, who heads OSDD. “So we have to detoxify it.”