For some people, snakes are exotic yet dangerous creatures of the wild; eerie but elusive, and not something to worry about in day-to-day life. For others, especially some farmers in India and Africa, they are a constant and terrifying threat to life. 

Venom from snake bites leads to more than 100,000 deaths every year, with around 400,000 people left permanently disabled The mortality burden is especially higher in low and middle-income countries in Africa and Asia, with India alone at a staggering average of 58,000 deaths in a year according to a 2020 report. However, considered a “poor man’s disease”, relatively less attention has been paid to the devastation caused by the bites. In some of these countries, snakebite incidence is distressingly high but inadequate access to proper healthcare prevents fast and efficient treatment, leading to disproportionately more deaths. 

Things were set to improve in 2017 when the World Health Organisation (WHO) finally stepped in to alert the world about one of its biggest hidden health crises. It officially classified snakebite envenoming as a highest priority neglected tropical disease.

Animals in the middle

A major issue is that the current process of producing antivenom is outdated: it involves injecting large animals like horses with snake venom and collecting the animals’ blood for the antibodies it produces against the venom.

But the horses’ blood could contain antibodies against other microorganisms as well, even against other components of the venom that are not harmful to humans. So only a fraction of the antibodies in the antivenoms is useful to humans, leading to more variability and the need for larger doses.

In addition, because these antibodies are produced in another animal, the chances of humans developing an adverse or allergic reaction to these antivenoms are also higher.

A variety of venoms

Driven by these concerns, a group of scientists — part of a consortium funded by the Wellcome Trust — decided to sidestep animals and use human antibodies instead. Using a type of toxin found in many kinds of snakes, they synthetically developed a broadly applicable human antibody against the toxin. Their results were recently published in the journal Science Translational Medicine.

“Venoms of snakes in India are so diverse that venoms of the same species across regions can’t be neutralised by the same antivenom,” Kartik Sunagar, head of the Evolutionary Venomics lab at the Indian Institute of Science, Bengaluru, and one of the lead authors of the study, said.

“Even in the same geographical location, if you look at individuals of the same species, antivenom can only neutralise some venoms and not others. There is a stark variation in venoms, so that’s why we wanted to figure out a solution that might work across regions and across species.”

Screening billions of antibodies

The scientists focused on three-finger toxins (3FTxs) — one of the most abundant and lethal ingredients in elapid venoms. Elapids are a major medically relevant family of snakes that include cobras, kraits, and mambas.

The scientists narrowed their focus on α-neurotoxins, a specific class of 3FTxs that target receptors in human nerve and muscle cells. These toxins prevent the receptors from responding to acetylcholine, a neurotransmitter involved in carrying messages from the neurons to the muscles, leading to paralysis, an inability to breathe, and eventually death.

Joseph Jardine, an antibody expert at Scripps Research Institute, in California, led the initial work of “finding the needle in the haystack” — i.e. finding the best antibody that could target the toxins among the billions of human antibodies available.

The scientists first synthesised variants of their toxin of interest, called long-chain 3FTxs (3FTx-L, a type of three-finger α-neurotoxins), in the lab. They then screened billions of human antibodies expressed on the surface of yeast cells for ones that bound best to the toxins in their study. This selection of antibodies far exceeds any number of antibodies that an animal’s immune system could cook up in response to a venom. After multiple rounds, they had a shortlist of antibodies that broadly reacted with most of the 3FTx variants they used.

All but king cobra

Nicholas Casewell’s group at the Liverpool School for Tropical Medicine in the U.K. then tested the antibodies in vitro in human cells, to see which of them could best neutralise the toxins. This step brought them to an antibody they dubbed 95Mat5.

Finally, Dr. Sunagar’s group tested 95Mat5 in vivo in mice, to see if this broadly neutralising antibody could help protect against lethal doses of α-bungarotoxin, the 3FTx-L in the highly venomous many-banded kraits. They also injected mice with whole venom from king cobras, black mambas, and monocled cobras — all different elapid snakes from Asia and Africa with venom containing 3FTx-L variants — and tested to check how their antibody worked against them.

They found 95Mat5 worked well against all the snake venoms, protecting the mice from death, with the only exception being the king cobras’ venom, where the antibody delayed but could not prevent death.

“We were surprised by the results of the black mamba, where the 3FTx-L is only 17% of the total venom composition. By knocking out that one toxin, we were able to protect mice fully from the other toxins in the venom in what may be a synergistic effect,” said Irene Khalek, a scientist at Scripps Research Institute and one of the authors of the study.

An ‘impossible’ find

“The study is really well-performed, and I would expect that the antibody could be used as an important component in future antivenoms against mambas and cobras in Africa and Asia,” Andreas Hougaard Laustsen-Kiel, head of the Tropical Pharmacology Lab at the Technical University of Denmark, said.

Dr. Laustsen-Kiel was involved in a different study, published in Nature Communications last year, where a group of scientists discovered a similar broadly neutralising antibody against long-chain α-neurotoxins from snakes.

“Because snake venoms are so complex, I would have thought it impossible to make an antibody that could knockout the whole venom,” Dr. Sunagar said.

Closer to a universal solution

In the current study, the scientists found one reason why their antibody worked so well against their toxins of interest: the crystal structures of their antibody 96Mat5 and 3FTx-L variants revealed that the antibody bound the toxin exactly where the toxin would have bound its target receptor in human nerve and muscle cells. By mimicking the receptor-toxin interaction, the antibody could whisk the toxins away from the receptors and prevent them from exerting their deadly effects.

The current antibody works well against a specific kind of toxin present in the venom of many dangerous snakes, but it is also a small first step towards a universal antivenom. The scientists said they are keen on discovering specific antibodies like these against toxins in other snake venoms as well, like in vipers.

“We need to discover antibodies for a couple of other toxins, then we can have a universal solution for the majority of snakes in the world,” Dr. Sunagar said.

Rohini Subrahmanyam is a freelance journalist.

Scientists at the Indian Institute of Science (IISc) in Bengaluru have created a promising new material that can replace natural sand in construction. This development comes as a response to the growing scarcity of sand, a crucial component in building materials.

The team at IISc’s Centre for Sustainable Technologies (CST) is exploring methods to utilise carbon dioxide (CO2) captured from industrial waste gases. They treat excavated soil and construction waste with this CO2, transforming it into a viable sand alternative.

“These materials can then be used to partially replace natural sand. This would not only reduce the environmental impact of construction materials but also impart properties that can enhance their use for construction,” stated IISc in a press release.

Led by Assistant Professor Souradeep Gupta, the research demonstrates that using CO2-treated construction waste in mortar, followed by curing in a CO2-rich environment, significantly accelerates the development of the material’s strength.

“CO2 utilisation and sequestration can be a scalable and feasible technology for manufacturing low-carbon prefabricated building products while being aligned with the nation’s decarbonisation targets,” explains Dr Souradeep Gupta, whose lab is carrying out these studies.

This innovative process boasts a 20-22% increase in the material’s compressive strength. Additionally, injecting CO2 into clay soil, commonly found at construction sites, improves its interaction with cement and lime. This not only stabilises the clay but also enhances its overall engineering performance.

Dr Gupta’s team’s research extends further. They’ve explored incorporating captured CO2 into excavated soil to create cement-lime-soil composites, potentially replacing up to half of the fine aggregates typically used in mortar. This technique promotes the formation of calcium carbonate crystals, leading to improved strength and reduced pore space. Exposing these materials to CO2 further accelerates curing and increases early-age strength by 30%.

The researchers have also developed 3D-printable materials using stabilised excavated soil combined with binders like cement, slag, and fly ash. These materials offer superior printability, potentially reducing the need for cement and sand by up to 50% each.

Future research will focus on the impact of industrial flue gas on these materials’ properties, paving the way for industrial applications and potentially revising standards for cement-based construction materials.

Indian Institute of Science, Bengaluru.

Two new studies from the Centre for Neuroscience, Indian Institute of Science, explore how closely attention and eye movements are linked and unveil how the brain coordinates the two processes.

According to IISc, attention is a unique phenomenon that allows us to focus on a specific object in our visual world and ignore distractions.

“When we pay attention to an object, we tend to gaze towards it. Therefore, scientists have long suspected that attention is tightly coupled to rapid eye movements, called saccades. In fact, even before our eyes move towards an object, our attention focuses on it, allowing us to perceive it more clearly – a well-known phenomenon called pre-saccadic attention,” IISc said.

However, in a new study published in PLOS Biology, the researchers at CNS show that this perceptual advantage is lost when the object changes suddenly, a split second before our gaze falls upon it, making it harder for us to process what changed.

“Our study provides an interesting counterpoint to many previous studies which suggested that pre-saccadic attention is always beneficial,” said Devarajan Sridharan, Associate Professor at CNS and corresponding author of the study.

In the PLOS Biology study, Priyanka Gupta, a PhD student in Prof. Sridharan’s lab, trained human volunteers to covertly monitor gratings (line patterns) presented on a screen without directly looking at them and to report when one tilted slightly.

“Importantly, the participants did this task just before their eyes moved in the pre-saccadic window. So, we were able to study the relationship between pre-saccadic attention and the detection of changes in the visual environment,” said Ms. Gupta.

A tracker was used to monitor their eye movements before, during and after their gaze fell on the object. “To our surprise, participants found it harder to detect the changes in the pre-saccadic window,” Ms Gupta said.

In the other study published in Science Advances, carried out with collaborators at Stanford University, the researchers used an unusual experiment – this time, to decouple attention from eye movements – in monkeys. Their goal was to tease out what is happening in the brain while these processes play out.

The monkeys had been trained on a counter-intuitive task called an “anti-saccade” task. Like the human study, the monkeys covertly monitored several gratings on a computer screen without directly looking at them. But when anyone grating tilted slightly, the monkeys had to look away from it instead of focusing more sharply on it. This helped the researchers delink the location of the monkey’s attention from the location where its gaze ultimately fell.

IISc said the researchers believe that uncovering such brain signatures can eventually point to what fails in attention disorders. “Discovering such mechanisms is vital for developing therapies for disorders like ADHD,” Prof. Sridharan said.

A view of the Indian Institute of Science building in Bengaluru. file photo
| Photo Credit: PTI

Indian Space Research Organisation (ISRO) Chairman S Somanath is among the five outstanding scientists and engineers who have been selected to receive the distinguished alumni awards of the Indian Institute of Science (IISc) for the year 2023.

The annual awards recognise exceptional contributions made by IISc alumni to their profession, society and the Institute. The nominations received are evaluated by a committee chaired by the Director of IISc.

Apart Mr. Somanath, this year’s awardees include D.N. Prahlad, Prof. K.K. Ramakrishnan, Prof. Mrinalini Chatta Rao and Dr. Dheepa Srinivasan. The awardees will be honoured at a ceremony to be held in December 2023.

Glory of Chandrayaan-3

Under Mr. Somanath’s leadership, ISRO carried out the third Indian lunar exploration mission named Chandrayaan-3, making India the first country to successfully land a spacecraft near the lunar south pole and the fourth country to demonstrate a soft landing on the moon.

He previously served as the Director of the Vikram Sarabhai Space Centre as well as the Liquid Propulsion Systems Centre, both in Thiruvananthapuram.

Pioneering development of hardware and software products

Mr. D.N. Prahlad is the founder of Surya Software Systems Private Limited, Bengaluru. Prior to founding Surya, he played a key role in the growth of Infosys Technologies.

He is currently the Non-Executive Chairman of Surya Software Systems Private Limited, Surya Financial Technologies Private Limited and Surya Digitech Private Limited. He pioneered the development of indigenous hardware and software products for global markets in the pre-liberalisation era of the country.

Building the internet

Prof. K.K. Ramakrishnan is currently Distinguished Professor at the Department of Computer Science and Engineering, University of California, Riverside, USA. He has published over 250 papers and has 173 patents in his name.

He has made immense contributions to solving fundamental problems in building the internet, specifically in network interface design, congestion control, network virtualisation, and operating system support, impacting nearly all network adapters and operating system designs in the world today.

Researching molecular basis of cell signalling

Prof. Mrinalini Chatta Rao is Professor Emerita at the Department of Physiology and Biophysics, University of Illinois at Chicago, USA.

She has pioneered research on elucidating the molecular basis of cell signalling, specifically on intestinal epithelial ion transport in health and diseases such as cystic fibrosis. She has also contributed to the most definitive textbook in the field of gastroenterology.

35 patents, 50 technologies

Dr. Dheepa Srinivasan is Chief Engineer at the Pratt & Whitney R&D Center on the IISc campus. She has over 35 patents in her name, and has developed more than 50 technologies and process applications that are now running in several gas turbines and steam turbines.

She is a pioneer in the area of metal 3D printing or additive manufacturing, and has developed several applications for metal laser additive manufacturing.

“We are extremely proud of the exemplary and meaningful contributions that these distinguished alumni have made to science and technology, as well as society. We hope that the stories of these alumni resonate as a source of inspiration for the entire IISc community,” Prof G Rangarajan, director, IISc said.

Indian Institute of Science, Bengaluru.

A team of researchers from the Indian Institute of Science and the University of Wisconsin-Madison, USA, have developed machine learning models for designing next generation nuclear reactor materials.

According to IISc, advanced nuclear reactors offer enhanced efficiency and safety compared to the long-standing conventional reactors in use, which is achieved by changing either the type or the rate of nuclear reactions within the reactor core.

However, it said that these changes could lead to increased radiation exposure for core materials, like austenitic stainless steels, which were not originally designed to endure such conditions, and an alternative is a special type of steel called Ferritic-Martensitic (FM) steel, which is more resistant to damage caused by nuclear radiation.

“But a variety of FM steels can be made by changing the composition and processing conditions, and they behave differently under different levels of radiation exposures at different temperatures. Only a small subset of these steels has been experimentally studied so far, mostly because conducting experiments in extreme environments brings its own challenges – scarcity of nuclear testing facilities, large expenses, and safety issues,” IISc said.

It added that it is, therefore, important to thoroughly investigate the effects of neutron irradiation on FM steels to identify the most suitable option for a specific irradiation level in a given reactor.

“One approach is to use physics-based models, but they require extensive defect characterisation data as input, which is missing in most experiments reported in the literature. As an alternative, a collaborative team from IISc and the University of Wisconsin-Madison has developed ML models. These models forecast the impact of neutron irradiation on the strength of FM steels, employing input parameters such as composition, processing conditions, and testing variables such as radiation dose and temperature,” IISc added.

The team used an algorithm called SHAP to pinpoint the most important input parameters/variables influencing the strength of FM steels upon irradiation. Using these variables, they deployed four ML algorithms to predict the strength of different FM steels subjected to varied radiation levels and temperatures.

IISc further said that this research demonstrates that these predictive models can significantly reduce the time and cost needed for conducting experiments in challenging conditions and accelerate the development of materials for advanced nuclear reactors.