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In The Hindu: Medicines in India, For India

I write in The Hindu on what it takes to get a drug from the lab to the market. Here is the full piece along with hyperlinked references.

January marked an important breakthrough in the fight against tropical diseases. Researchers at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Delhi found a drug candidate that prevented the TB and Malaria pathogens from infecting human blood cells.

This cutting edge research took place not just in India, but for Indian challenges — whose solutions have global implications. Further, Anand Ranganathan and his colleagues did not just find this drug candidate, but also helped develop processes to develop these drug leads. It also happened thanks to a combination of a UN facility set up decades ago, attracting top global research talent to come back to India and work here. And the research was funded not just through international sources, but also a ‘Grand Challenge Programme’ on vaccines set up by the Department of Biotechnology, Government of India. Much of this success is a delayed fruit of a biotechnology push in India that started in the mid 1980s, which has gained in strength over time.

However, the discovery of the drug candidate ‘M5 synthetic peptide’ is the beginning of a long road and not the end. The process of drug discovery here is not yet complete, and has to be succeeded by more research and a host of clinical trials. Here is a plausible set of intermediate steps before a new TB or Malaria drug enters the market from the work of Ranganathan and others.

The ICGEB researchers have attempted ‘rational drug design’, where they have not only found a drug candidate, but have done so while identifying what protein target it interacts with in the body, and the mechanism it uses to prevent disease. The first steps forward for all interested researchers in the field will likely be to study further how the peptide drug candidate works, what its structure is, what the key biochemical interactions are, and how its target proteins behave.

While the drug candidate might work well in a test tube or an agar plate, its efficacy in the human body is an entirely different story. At this stage, whether the peptide can be easily absorbed by the body or be happy in blood, whether it finds the right targets, has no side effects or toxicity, are all unknown. Researchers, including those in private pharmaceuticals, can start developing variants of the M5 peptide that might have more desirable properties and have higher efficacy, and a good number of promising drug candidates might be patented by public sector researchers or pharmaceutical companies, depending on who discovers their utility.

It is after this that pre-clinical trials start on promising compounds, from tests in mammals to finally humans. Phase I clinical trials are typically about testing safety among healthy people, moving to phase II which are small trials of efficacy among patients. The last and the most expensive — Phase III, involves large, double-blind tests to determine both safety and efficacy among large groups of people.

The entire process of drug development is one of attrition, where a hundred lead compounds might trickle down to one or two medicines. It can take a decade or more, and cost in the order of a billion dollars, or 6000+ crore rupees.

Science is often described in popular retelling in a triumphalist manner, when in reality research involves many misses by researchers, incremental progress, and the eventual success of someone who stands on the shoulders of many giants.

For this process to happen, you need to have a robust research ecosystem, adequate funding, and good pipelines that ensure minimum friction in the development of drug candidates and lead compounds into medicine that you can buy at the corner shop.

The challenge in India is that tropical diseases have often been neglected by big pharmaceuticals because the size of the drug market is lower, with people having lower incomes in tropical countries. Further, companies are uncertain about intellectual property rights on essential drugs, unsure about whether they can recover high sunk costs in this inherently risky proposition. It is no surprise that big Indian corporations have stayed away from pharmaceutical R&D, finding more secure avenues for a return on their investment.

Policymakers in India will need to strike the right balance between public funding, and the role and return on private investment on drug development. Greater clarity on India’s eminent domain and compulsory licensing positions could make foreign-patented drugs more costly for India, but might spur R&D on tropical and endemic diseases in the long run.

Further, the unwritten compact in developed countries on drug development is that a thick layer of public funds pay for the basic research up to and including drug candidate discovery. It is over and above this that private pharmaceuticals come in, patent drugs and develop them.

Indian funding on basic research and drug discovery remains minuscule in comparison, with the entire Department of Biotechnology budget being lesser than 1500 crore rupees in 2014-15, or about 250 million dollars. The Government of India’s spending on drug development is broadly of the same order of magnitude of what is spent by the Gates Foundation and others on drugs for tropical diseases, and both the quality and quantity of public spending has to dramatically improve if we want more drug candidates against TB, Malaria, Dengue, Cholera and other diseases.

One way to increase the funding is to redirect extensive funds that go towards large healthcare subsidies, so that future drugs can be both better and cheaper.

India also has the opportunity to re-examine how clinical trials are governed. While we want ethical and safe practices in clinical testing, American or European regulations have accumulated some extra bureaucracy and regulations along the way. India can also set new standards on transparency so that new research is easy to discover, verify and build on.

Getting 21st century medical solutions to India’s health concerns is a long slog. The new potential cure for TB and malaria gives us a chance to think through how to develop medicines in India, and for India.

Hindu_Feb14_PavanSrinath_MedicinesFromLabtoMarketRead the article in The Hindu on their website.

 

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In Mint: Let India’s urban poor pay for good water

I write in Mint this week on how thinking along the lines of micro finance principles can change how we approach water pricing. Instead of an ideological stand on keeping water free, it’s better to ask how we can make clean water cheaper and more affordable for urban India’s most deprived.

In microfinance, people also acknowledge that it costs more to lend to the poor. When most people have to take a big loan from a bank, they have a steady income to show. They have a credit history. They also have assets they can pledge as surety, in case they default on the loan. The poorest of the poor don’t have salaries to showcase. They don’t have assets to pledge. The risk of defaulting on a loan is higher, and it is humane that they be allowed to default when the circumstances are dire. By allowing microfinance institutions to charge higher interest rates, the policies allow them to service these needs.

Similarly, the costs of supplying water for a city’s poor can be high. People often don’t have address proofs or any proofs of legal residence, making installing water connections harder. Getting even basic piping to reach the heart of a slum is not always cheap, given that there is hardly any road space to dig up. Maintaining pipes is even tougher. Installing and maintaining water meters is difficult, thereby making bill collection costlier.

It is highly disingenuous to ignore all these real issues and shout for a right to free water.The better approach is to ask, “how can we make water cheaper for the poorest?” And that line of thinking can birth an entirely new range of solutions.

Read the full article at Live Mint, February 13, 2015.

Live Mint e-Paper - Mint - 14 Feb 2015 - Page #11 Pavan Srinath

 

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The Unhistoric US-China Climate Deal

China and the United States of America inked a climate pact this month and this has been lauded by various corners as landmark and historic. Vasudevan Mukunth quoted me in his article for Scroll.

Here is the full text of my comments to Scroll.

The history of the global negotiations on climate change negotiations has so far shown two things:

One, big emitters have typically employed salami slicing tactics, where they inch up the emission levels they are willing to go down to. Changing the base years and letting the reduction targets slide are commonplace.

Two, any penalty measures used to enforce emission reduction targets have been repeatedly flouted – including by countries like Canada – with no direct consequences.

I remain skeptical of this deal because the size of the Chinese emissions ‘peak’ remains unknown. That gives a lot of wiggle room for China. Secondly, there is no tangible enforcement mechanism presented, nor does one seem feasible. At best, this is a gentlemen’s agreement between the United States and China, and there are no gentlemen in international relations.

Implications for India and other developing countries:

India has routinely done a poor job of defending its record in global climate change negotiations, though it has done far better in substance than the likes of China. There is a risk that India will be painted into a corner, in spite of being a low carbon emitter on a per capita basis, and in spite of significant efforts at home to promote renewables.

Further, India’s more immediate focus must be on climate adaptation, but international financing and promotion of mitigation efforts serve to distract domestic policy. For India to get back to high economic growth, India must be willing and able to use all forms of energy — from coal to natural gas to nuclear power and renewables, and use the growth to provide better public goods and build resilient infrastructure.

This deal and its seeming historicity makes it a harder challenge for India to make its case convincing for a global audience.

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A Long Overdue Hike in Bangalore’s Water Prices

The Bangalore Water Supply and Sewerage Board (BWSSB) recently hiked its water tariff, a move that was long overdue.  I am quoted in Citizen Matters on why this hike is a good move.

The hike in BWSSB’s water tariff is a welcome development that was long overdue. BWSBB has been a national leader in the professional delivery of water supply and sewerage services, and it is no accident that Bangalore has the largest number of metered water connections in the country.

Water is an increasingly scarce resource in the 21st century, and pricing it at its highest marginal cost is essential to conserving this vanishing resource. While we talk about excessive or misdirected LPG and petrol subsidies, the water subsidy that even the most prosperous Bangalore receives is much higher.

The higher price of water will also spur more people to do rainwater harvesting and efficient use of water. We must also recognise that people pay many times more for water tankers – a small increase in BWSSB tariffs could in fact reduce overall water cost for the city’s residents.
[Citizen Matters: Should Bengalureans be grateful for BWSSB’s water rates? 11 November 2014]

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In Business Standard: Setting our sights beyond Mars

On the day after India’s successful Mars orbiter insertion, I write in Business Standard that India and ISRO must now focus on achieving human spaceflight, and that we have to do things differently in order to achieve it:

The target of human spaceflight is necessary because successful space programmes need visible goals to orient themselves and not get lost along the way. They also need public confidence and steady government support since the development cycles are long.

Space exploration is primarily a pursuit of excellence: of exploring the unexplored, doing the impossible and pushing the frontiers of knowledge and human ability. As India has seen in the last decade, having ambitious plans to get to Mars and the moon inspired ISRO to step up its game.

Clear targets like human spaceflight breed innovation and spark creativity. For the Mars mission to succeed, various ISRO wings had to align their objectives and work at their best, as a complex mission requires flawless execution. ISRO needed to figure out deep space communication, precision orbital planning for such a long and complex journey, as well as mechanics and electronics that leave little room for error – and they had to do all of this within a tight deadline.

Similarly, human spaceflight will require ISRO to develop technologies for more powerful launch vehicles capable of transporting larger capsules to space. It will need the ability to re-enter the atmosphere and reach back to earth safely. It will also need all the trappings necessary for humans to survive and thrive while in space, and more. These skills and technologies are transferable, and will eventually aid ISRO’s other efforts and the economy at large.
[Full Article: Setting our Sights Beyond Mars, September 24, 2014]

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In Business Standard: Indian Cities, New and Improved

I write in Business Standard today on the 100 smart cities plan announced by Venkaiah Naidu and the lessons they must learn from JNNURM almost a decade of centrally-sponsored urban development schemes:

JNNURM had a tantalising premise when it was first launched: the Union government will give cities money for infrastructure as an incentive for states to devolve power to cities, and for these cities to reform. The Union government was a third party in the state-city equation, hoping to tip the scales in favour of cities and true decentralisation.

The promise of JNNURM was lost for two broad reasons. One, the ministry of urban development had to perform two conflicting functions: it had to spend money by disbursing it to states, but it also had to audit and verify the reforms process. The outlays were conditional on meeting reform targets. Though the ministry did a lot in checking whether cities had completed enough reforms, the spending mandate usually won through, and poor reformers were rarely punished. This made it a weak incentive for genuine urban reform. Some cities like New Delhi also received large infrastructure funds from sources such as the Commonwealth Games, making JNNURM irrelevant as an impetus for reform.

Two, the Union ministries demanded an extraordinary amount of scrutiny and control for the projects approved. For example, if a town in Karnataka wanted to finance a water supply project under JNNURM that improved the lives of its residents, often the project had to meet extremely trying norms such as 24/7 water supply or complete metering of connections, which were enforced by Union ministries and attached bodies. While these are desirable, the lack of state-level decision-making led to the projects losing local relevance, apart from being subjected to an excruciatingly long and difficult process of approval. If the intent of the Union government was to incentivise reform, then perhaps it should not have controlled the type of infrastructure projects beyond setting broad norms.
[Full Article: Building Blocks to Smart Indian Cities, June 3, 2014]

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NDTV’s We The People – On the Uttarakhand floods

Last Sunday, I appeared on NDTV’s We The People hosted by Barkha Dutt, to talk about the recent floods in Uttarakhand and on the “eco-insensitive” nature of politics in India. Here’s a clip of the comments I made during the show. You can watch the full recording at the NDTV website.

I also had the opportunity to underscore the same points during an interview by Maseeh Rahman of The Guardian.

But most analysts believe restricting the number of pilgrims would be political suicide. “The desire to worship at Kedarnath is almost like an irresistible force,” said Pavan Srinath, of the Chennai-based thinktank Takshashila Foundation. “Despite the tragedy, people are already talking about when they will undertake the sacred journey. No government can bar the devout from the Himalayas.”

Not all experts are in agreement. Srinath maintains that the devastation would have been even more widespread if the reservoir of the region’s biggest dam at Tehri had not contained a significant volume of the deluge. “Dams can also prevent disasters,” he said. “The critical issue is not dams, but proper dam management. In India, we just don’t have a culture of public safety.”
[The Guardian, June 28, 2013]

The comment the regulation of pilgrims, however, isn’t just about political feasibility – but about policy realism. In all likelihood, a strict regulation of official pilgrims to the holy sites will lead to a large number of illegal traffic of tourists and pilgrims, with much less safety.

Also, this blogger thinks that it’s more likely that the Tehri dam was empty and capable of receiving flood waters more by circumstance than by intent – nevertheless, it demonstrates the positive role well-managed dams can play in disaster risk reduction.

Related posts: Not every disaster is man-made | We are still vulnerable to climate variability

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We are still vulnerable to climate variability

Samanth Subramaniam writes in UAE’s The National on the floods in Uttarakhand and quotes me on the link between flooding and climate change.

But Pavan Srinath, a policy researcher at the Chennai-based Takshashila Institution, who has written extensively about climate change, told The National that cause and effect were difficult to establish in such situations.

“Theoretically, if you mess around in mountain systems, you can increase chances of landslides or floods, yes,” Mr Srinath said. “The question is: How much does the risk go up? We don’t know that yet.”

Similarly, Mr Srinath hesitated to draw a link between global climate change patterns and the early monsoon rain that triggered Uttarakhand’s floods.

“One of the theories is that global warming increases the intensity of the monsoon rains,” Mr Srinath said. He acknowledged that climate change was causing “extreme weather events” but argued that it was difficult to conclusively prove that these floods were one such event.

“I would say, instead, that our towns haven’t even adapted to regular variations in climates, let alone climate change-induced ones,” Mr Srinath said. “Really, that’s the conversation we should be having.”
[Samanth Subramaniam, The National]

I cannot stress the last point enough. The sad truth is, even without climate change, our towns, cities and villages are deeply vulnerable to the natural variability in climate. Be it droughts that hit parts of India like clockwork every few years, or how Assam or Orissa get inundated by floods regularly – we see constant evidence that we aren’t even resilient to what we ought to be. We should be talking about adapting to local climes, to variability and finally to climate change. Talking excessively of climate change alone shifts the focus instead to mitigation, to cutting greenhouse gas emissions and a host of other issues that serve as distractions.

For a nation that is one-sixth of the world’s population, we have but contributed to 3% of greenhouse gases emitted globally since the industrial revolution. Our most important goals need to be of climate adaptation, and building disaster resilience and good emergency services.

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