📰 AlphaFold: A tour de force in science
How have our methods of predicting protein structures changed with AI-based tools? What does this development signify for structural biology?
•DeepMind, a company owned by Google, announced this week that it had predicted the three-dimensional structures of more than 200 million proteins using AlphaFold.
•AlphaFold is an AI-based protein structure prediction tool. It used processes based on “training, learning, retraining and relearning” to predict the structures of the entire 214 million unique protein sequences deposited in the Universal Protein Resource (UniProt) database.
•The Indian community of structural biology needs to take advantage of the AlphaFold database and learn how to use the structures to design better vaccines and drugs.
•The story so far: DeepMind, a company based in London and owned by Google, announced this week that it had predicted the three-dimensional structures of more than 200 million proteins using AlphaFold. This is the entire protein universe known to scientists today.
What is AlphaFold?
•AlphaFold is an AI-based protein structure prediction tool. It is based on a computer system called deep neural network. Inspired by the human brain, neural networks use a large amount of input data and provides the desired output exactly like how a human brain would. The real work is done by the black box between the input and the output layers, called the hidden networks. AlphaFold is fed with protein sequences as input. When protein sequences enter through one end, the predicted three-dimensional structures come out through the other. It is like a magician pulling a rabbit out of a hat.
How does AlphaFold work?
•It uses processes based on “training, learning, retraining and relearning.” The first step uses the available structures of 1,70,000 proteins in the Protein Data Bank (PDB) to train the computer model. Then, it uses the results of that training to learn the structural predictions of proteins not in the PDB. Once that is done, it uses the high-accuracy predictions from the first step to retrain and relearn to gain higher accuracy of the earlier predictions. By using this method, AlphaFold has now predicted the structures of the entire 214 million unique protein sequences deposited in the Universal Protein Resource (UniProt) database.
What are the implications of this development?
•Proteins are the business ends of biology, meaning proteins carry out all the functions inside a living cell. Therefore, knowing protein structure and function is essential to understanding human diseases. Scientists predict protein structures using x-ray crystallography, nuclear magnetic resonance spectroscopy, or cryogenic electron microscopy. These techniques are not just time-consuming, they often take years and are based mainly on trial-and-error methods. The development of AlphaFold changes all of that. It is a watershed movement in science and structural biology in particular.
•AlphaFold has already helped hundreds of scientists accelerate their discoveries in vaccine and drug development since the first public release of the database nearly a year back.
What does this development mean for India?
•From the seminal contribution of G. N. Ramachandran in understanding protein structures to the present day, India is no stranger to the field and has produced some fine structural biologists. The Indian community of structural biology is strong and skilled. It needs to quickly take advantage of the AlphaFold database and learn how to use the structures to design better vaccines and drugs. This is especially important in the present context. Understanding the accurate structures of COVID-19 virus proteins in days rather than years will accelerate vaccine and drug development against the virus.
•India will also need to speed up its implementation of public-private partnerships in the sciences.
•The public-private partnership between the European Molecular Biology Laboratory’s European Bioinformatics Institute and DeepMind made the 25-terabyte AlphaFold dataset accessible to everyone in the scientific community at no cost.
•Learning from this, India could facilitate joint collaborations with the prevalent hardware muscle and data science talent in the private sector and specialists in academic institutions to pave the way for data science innovations.
Is AlphaFold one-of-a-kind tool in predicting protein structures?
•Although a tour-de-force in structural biology, like any other method, AlphaFold is neither flawless nor the only AI-based protein structure prediction tool. RoseTTaFold, developed by David Baker at the University of Washington in Seattle, U.S., is another tool. Although less accurate than AlphaFold, it can predict the structure of protein complexes.
•The development of AlphaFold is sure to make many scientists feel vulnerable, especially when they compare their efforts from years of hard work in the lab to that of a computer system. However, this is the time to adjust and take advantage of the new reality.
📰 Working towards animal health
A collaboration is needed between veterinary science and human health experts to forge effective tools
•The developments unleashed by COVID-19 have once again put the spotlight on the pressing need to create greater collaborations and synergies between research on human health and animal health. India has a livestock population of 1.6 billion, that in turn translates into a scenario where approximately 280 million farmers rely on the livestock and related industries for livelihood.
•From the perspective of trade, the dairy industry in the country is valued at $160 billion, while the meat industry is valued at $50 billion. In addition, livestock and related activities have significant overlap with wildlife and humans. In the current atmosphere of climate change and unpredictable weather, animal husbandry assumes significance as a source of reliable income to farmers.
Increase in zoonotic diseases
•Statistics indicate that globally, we have witnessed around 9,580 instances of disease outbreaks from 2000 to 2010, of which 60% diseases were zoonotic in nature. Likewise, the incidences of disease outbreaks across the globe have been increasing at a compound annual growth rate (CAGR) of 6%. In India, we see that annual outbreak of zoonotic diseases translates into an estimated annual loss of $12 billion to the economy.
•Thus, even though these diseases do not affect human health directly, they are responsible for huge consequences to farmers, exports and gross domestic product (GDP) growth nationally. In this background, close collaboration is the need between veterinary science and human health experts to forge effective tools for pandemic preparedness. A major loophole in the context of pandemic preparedness can be attributed to the fact that it has largely been human centric, leaving a large unaddressed gap for diseases of pandemic potential in animals.
•The Department of Animal Husbandry in Government of India has been working towards increased investment in preparedness to protect health and building economic resilience so that India could become a world leader in animal pandemic preparedness. To this end, the Department of Animal Husbandry and Dairying (DAHD) has set up a dedicated ‘One Health Unit’ in collaboration with the Gates Foundation. One of the primary focus areas of the unit has been on coming up with an “animal pandemic preparedness” model by creating a mechanism for storage and seamless exchange of data and information on livestock health — this will be implemented through the National Digital Livestock Mission (NDLM).
•So far, synergies from advances in human vaccines have not been leveraged in animal vaccine development. Thus, to incentivise the growth of the animal health industry in India, companies can now avail incentives for setting up or expansion of animal vaccine and related infrastructure under the Animal Husbandry Infrastructure Fund.
•Additionally, DAHD in collaboration with the Office of the Principal Scientific Adviser, Central Drugs Standard Control Organisation (CDSCO), Indian Council of Agricultural Research (ICAR), and the Indian Pharmacopoeia Commission (IPC) has set up an Empowered Committee for Animal Health to streamline the animal health regulatory ecosystem in the country.
•To create a robust pandemic preparedness model, it is imperative to juxtapose the data on animal health with the available data on human health. Within the framework of the NDLM, so far, substantial progress has also been made by linking all the animal disease diagnostic labs involved in sero-surveillance through a single portal, and harmonisation of SOPs used by labs.
Creating a successful model
•A successful animal pandemic preparedness model template would entail seamless coordination with critical ecosystem partners to ensure timely and successful development of animal drugs and vaccines. The ecosystem partners would include entities carrying out pathogen prioritisation and aiding pharma companies in vaccine research, Indian pharma companies, and global organisations like World Organisation for Animal Health, Global Alliance for Vaccines and Immunisations, Bill and Melinda Gates Foundation, etc.
•This pandemic preparedness initiative would thus enable the linking and comparison of real-time information regarding diseases between wildlife and human systems — that would create a reliable mechanism for forecasting disease outbreaks. This India-focused initiative will also present a good starting point to lead global pandemic preparedness effort because this threat is faced by other countries as well, including developed economies.
•The dynamic model under preparation would further result in enhanced disease surveillance so that we are better prepared before the next outbreak hits.
India could take advantage of geopolitical developments to promote trade and gain better status for the rupee
•A number of countries, including India, are now considering the use of other currencies to avoid the U.S. dollar and its hegemonic role in settling international transactions. As for India, currency hierarchy goes back to colonial times when the Indian rupee was virtually linked to the British pound rather than to gold which it earned through exports. In the post-War period, the neo-colonial currency hierarchy has been clubbed with the continued use, primarily of the U.S. dollar, for the majority of international transactions. The current situation relates, in addition, to geopolitical developments, the Russia-Ukraine war in the forefront followed by the sanctions imposed on Russia by the West.
The present scenario
•In recent times, India has been taking an active interest in having the rupee used for trade and the settlement of payments with other countries, which include Russia, now facing sanctions. Even earlier, the annexation of Crimea in 2014 had resulted in the imposition of similar sanctions against Russia over a period of time. Settling payments with Russia by India, especially for mineral fuels and oil imports as well as for the S-400 Triumf air defence system has been continuing on a semi-informal basis through rupee payments by using the Vostro accounts maintained by Russian banks in India. The Reserve Bank of India has recently taken a proactive stand to have rupee settlement of trade (circular dated July 11, 2022). While options for invoicing in rupees were already legal in terms of Regulation 7(1) of the Foreign Exchange Management (Deposit) Regulations, 2016, the current circular aims to operationalise the special Vostro accounts with Russian banks in India, in a bid to promote trade and also gain a better status for the rupee as an international currency.
Possible advantages
•The advantages India is currently seeking in these arrangements include avoidance of transactions in the highly priced dollar which has an exchange value of ₹80, impacting the Indian economy with inflation, capital flight (aggravated by interest rate hikes by the Fed and possible hikes in the European Union as well) and the drop in foreign exchange reserves by $70 billion since September 2021. Buying oil with a depreciated ruble, and at discounts, is not only cost-saving but also saves transport time with the use of multi-modal routes using land, sea and air routes. In addition, India is looking forward to trade expansion in sanctions-affected Russia (leading to recession and de-industrialisation there). As mentioned by Alexey Yusupov in the IPS Journal on July 20, the impact of sanctions on Russia includes L-shaped stagnation in GDP which has declined by 10% to 15%, with de-industrialisation and unemployment (largely on account of the retreat of most western companies from the country leading to sharp declines in the production of steel, wood and automobiles). With India having a trade deficit with Russia, which has been around $3.52 billion on average over the last two financial years, India’s opportunities include the possible use, by Russia, of the surpluses in the Vostro rupee account in Russian banks for additional purchases from India. Such purchases could include not only pharmaceutical products and electrical machinery (which are currently the major items of India’s exports to Russia) but also a range of products that Russia might need, particularly to redress the hardship faced with the sanctions.
Some hurdles
•There are quite a few problems that may prevail in implementing the desired rupee payments and avoiding dollar transactions. Apart from issues that concern an agreed exchange rate between the rupee and the ruble (R-R), two volatile currencies, there is also the question of the willingness of private parties (companies, banks) to accept the rupee for trade and settlements. Will they be ready to forego the greenback? Of course if Russia opens its door for exports from India, the ‘R-R’ route may prove attractive for Indian exporters. Finally, there are official concerns for reactions, particularly from the U.S., to deals, especially for purchase of the S-400 defence equipment. And the fear continues even after the recent Congressional approval of those purchases as a special case in the backdrop of Chinese aggression. Moreover, the deals between India and Russia, especially on oil, can be considered by the West as ‘indirect back door support’ — as India is importing Russian crude at 30% discount, processing at refineries in Gujarat which include Reliance, and then exporting those to the West. As reported by the Economic Times (June 13, 2021), such exports amounted to $1.5 billion per day in May 2021. These companies are exporting to the West with ‘robust refining margins’, as Alex Lawson mentions in The Guardian (June 22).
•There were attempts even before the novel coronavirus pandemic to initiate a clearing account on the BRICS platform. An analysis by the writer in the EPW on the quantitative implications indicate a skewed pattern of transactions — with China having most of the trade surplus. It is a pattern similar to what is happening in India-Russia trade at the moment.
Examples to note
•Attempts to use the rupee for invoicing and trading is, however, not new to India. A comprehensive bilateral trade and payments agreement was signed by India in 1953 with the Soviet bloc countries (it included those that later formed a part of the Commonwealth of Independent States.) Crucial aspects of the arrangement included: participation by state-trading units alone; fixed exchange rates as agreed upon by trade partners, and the offer of credit by countries that had a trade surplus to countries with a trade deficit. In general, most of the bilateral agreements were marked by scissor-like operations on a continuous basis, in effect clearing the imbalances as the surplus country was importing more from the deficit partner, or offering credit to the latter. The Soviet Union’s credit to India enabled the setting up of the Bhilai steel plant, other industrial units, oil refineries and pharmaceuticals — all controlled by India’s public sector. The agreement ended in 1991 following the dissolution of the Soviet Union, leaving behind some issues of a rupee surplus and the ‘R-R’ rate of exchange.
•However, history moves on. The market economies in most parts of the world today negate the possibility of having the state or the public sector at centre-stage. But still, the India-Soviet agreements of the past may provide a clue on how the current ‘R-R’ trade and the problems can be managed by initiating a push for Indian exports to Russia and, of course, avoiding all deals in dollars — benefiting both trade partners and countering, globally, the on-going currency hierarchy.
📰 Government’s own ‘gig workers’
Outsourcing jobs to contractors is far more inefficient than fixed term contracts
•When images of a langur appear on the walls of Vigyan Bhavan and nearby sites in New Delhi, the protagonist (Anjani Prasad) in the movie, Eeb Allay Ooo!, is summoned along with his thekedaar (contractor) to the office of the municipal corporation. A complaint about the images that were put up by Anjani to scare away the monkeys has reached the officer and he threatens to cancel the contract for shooing away the monkeys. The absurdity of the task, for which a thekedaar is appointed by floating a tender, may unsettle the viewers. However, for those engaged by the various levels of the government through such contracts, it is a lived reality.
•While the Agnipath scheme has ignited a debate on the nature of jobs in the government, ‘temporary’ jobs have comprised the vast majority of available government employment for quite some time. They may be classified into three categories; permanent, contractual and daily wagers.
Outsourcing: a dominant mode
•A commentator recently referred to it as “the caste system of permanent, contractual, and casual employees”. Outsourcing has become the dominant mode of working in the government, from highly specialised tasks to the most routine ones. It may be a safai karamchari (sanitation worker), a driver/conductor of your city bus service, a junior engineer or a highly paid consultant — all engagements are usually outsourced to an agency. The modalities of “contractual” jobs in the public sector, therefore, require a much deeper examination than it has been afforded in recent debates to understand its impact on various public services.
•There are two main methods to induct an ‘employee’ on contract in a government entity; first, directly on the payroll of the entity and, second, through a labour contractor or as part of any other contract entered into pursuant to a tender process. In both cases, the costs and liabilities of the government entity are significantly reduced compared to a “permanent” position. While the entity may remain the principal employer in both cases, the burden of responsibility is shifted to the contractor in the case of the latter, which is also the predominant mode of engaging contractual workers.
•Non-payment of salaries for extended periods, fudging of statutory deductions for the worker’s welfare such as provident fund (PF), employees’ state insurance (ESI), etc. by the labour contractor, and uneven distribution of work vis-à-vis “permanent” employees, are all common and well-known features of such contracts. This has serious repercussions for the quality of public service that is sought to be provided including sanitation, public transport, health, etc. Urban and rural local bodies are an important site to understand the implications of a large “contractual” workforce.
Shift of responsibility
•Arguably, for the managers or officers in the government, the shifting of responsibility to the contractor and the possibility of litigation seeking ‘regularisation’ for the workers predisposes them to such labour contracts. The overwhelming reliance on contractors, who almost function as the HR managers of the government, has undermined our institutions.
•It is often the case that the managers/officers in the government do not have the capability to draft or even review basic tender documents. Consequently, there is an endless chain of delegating tasks so much so that at any time there are more people to get things done than those who could actually do things. What is our solution then? We float another tender to appoint experts or consultants who would do things for us.
•I would argue that contractual recruitment has largely been a missed opportunity to augment the capacity of the government, particularly those wings of the state that cater various services to people, as well as to create a viable avenue of employment for India’s burgeoning working age population. This is subject to the appropriate mode of engagement and safeguards that add institutional capabilities rather than shifting the onus of management to an external agency.
•Due to fiscal constraints and a large workforce, contractual jobs will continue to eclipse ‘permanent’ ones at least in terms of numbers. Our local bodies, parastatals, special purpose vehicles and other public utilities stand to gain considerably if the modalities of engagement are diligently worked out.
•As an example, following the recent strike by the Maharashtra State Road Transport Corporation (MSRTC) staff in Maharashtra, Aurangabad’s City Bus Service, operated as a joint venture with the former, had to be suspended due to non-availability of drivers and conductors. Instead of outsourcing the service to a private agency, a decision was made to directly recruit the drivers and conductors from amongst ex-servicemen via fixed term contracts to be renewed periodically.
•In addition, a maintenance division was set up for daily maintenance from amongst the ex-servicemen retired from mechanical and engineering divisions of the Army. As a result, a significant improvement was seen in various service level parameters in a short span. The Ministry of Housing & Urban Affairs’ The Urban Learning Internship Program (TULIP), which enables city authorities to directly engage a young workforce for a fixed term, is another example of a step in the right direction.
Shaping realities
•Our critique of public employment, which is largely framed as the presence or absence of the security and benefits of a permanent job, may be disconnected from the predominant modes of recruitment shaping the realities of young people’s lives. Moreover, even though a permanent government job remains highly coveted, it may be important to also recognise that not everyone may aspire to ‘permanence’ due to various reasons.
•Fixed term contractual stints with the government with safeguards against sheer exploitation can be a major source of employment. However, such modes of recruitment will have to assimilate the principles of affirmative action, in line with the vision of social justice enshrined in our Constitution. This is key in order to avoid becoming a mechanism that will skirt provisions for reservation.
•As we seek to regulate the “gig economy”, it may be time for the government to take some concrete measures for its own “gig workers”.
