We still need to find answers to many scientific questions on Covid-19: CCMB Director

We still need to find answers to many scientific questions on Covid-19: CCMB Director


There is still a need to find answers to many key scientific questions pertaining to the Covid-19 pandemic, which have not been addressed so far, according to Vinay K Nandicoori, Director, CSIR-Centre for Cellular and Molecular Biology (CCMB).

“Significant and rapid progress has been made primarily driven by our quest and need to tackle the pandemic. However, many unanswered scientific questions need to be investigated in depth,’‘ Nandicoori told BusinessLine.

He added that areas such as the nature of long Covid, nature of clinical response variations, microbiota, and its correlation with nutrition, among others, are yet to be studied. These are required to deepen our understanding.

“Science is not going to stop its work. HIV had come long ago; we still have research papers coming. Likewise, work on Covid needs to continue. Sequencing has become a huge tool in which India has done great work,’‘ the CCMB Director said.

About the continuation of Covid, the scientist said India still seems to be in the Omicron phase, and there is “nothing alarming’‘ as of now as most Indians appear to have developed hybrid immunity.

However, the immune system will not constantly produce antibodies- he added that there is a need for periodic booster doses.

CCMB’s Contribution

The CCMB has been contributing to the battle against the pandemic since its onset in 2020. It developed diagnostic tools and tested about 70 to 80 molecules besides developing an mRNA vaccine.

“We have done a lot of work on Covid, and we actually proved along with other CSIR Institutes that it can spread through aerosolic particles. We have sequenced a good number of samples. We continue to participate in sequencing efforts,’‘ Nandicoori said.

The premier research body is also engaged in key research beyond Covid.

“There is much to be done on other diseases like Tuberculosis (TB) and its pathogen, other viral diseases, the parasite that causes malaria, and antimicrobial resistance (AMR),’‘ the Director added.

In addition, CCMB continues to work on many other areas such as animal and plant conservation, structural, plant, genome, and infectious disease biology.

A team of scientists from the Centre had recently found eight novel genes which can impact male fertility.

Published on

September 10, 2022



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Sustained rise in antimicrobial resistance in India: ICMR study

Sustained rise in antimicrobial resistance in India: ICMR study


Many patients in India may no longer benefit from carbapenem, a powerful antibiotic administered mainly in ICU settings to treat pneumonia and septicemia, as they have developed antimicrobial resistance to it, an ICMR study has found.

The data analysis done between January 1 and December 31, 2021, pointed towards a sustained increase in drug-resistant pathogens, resulting in difficulty to treat certain infections with available medicines, senior Indian Council of Medical Research (ICMR) scientist Dr Kamini Walia, who led the study, said.

“Antibiotic resistance has the potential of taking the form of a pandemic in the near future if corrective measures are not taken immediately,” she said.

The ICMR study report was released on Friday.

Data compilation

The data collected from the network has enabled compilation of drug resistance data on six pathogenic groups on antimicrobial resistance from the country.

Data collected from the network is used to track resistance trends and to better understand mechanisms of resistance in the key priority pathogens using genotypic characterisation and whole genome sequencing (WGS).

According to the ICMR report, resistance to Imipenem, which is used to treat infections caused by bacteria E coli, has increased from 14 per cent in 2016 to 36 per cent in 2021.

The trend of decreasing susceptibility of bacteria to specific antibiotics was also observed with Klebsiella pneumoniae as it came down from 65 per cent in 2016 to 45 per cent in 2020 and 43 per cent in 2021.

Carbapenem resistance isolates of E coli and K pneumoniae are also resistant to other antimicrobials making it very challenging to treat carbapenem-resistant infections.

The resistance to broad-spectrum antibiotic carbapenem with respect to infections caused by Acinetobacter baumannii bacteria was recorded in 87.5 per cent of the patients who were part of the study, limiting the availability of treatment options, the report said.

Susceptibility of the same bacteria to minocycline is close to 50 per cent, making it the most susceptible antibiotic after colistin for Acinetobacter baumannii, it stated.

Rational use

In Pseudomonas aeruginosa, another bacteria which causes infections in the blood, lungs (pneumonia), or other parts of the body after surgery, there is a consistent increase in susceptibility to all the major antipseudomonal drugs in the last few years, Dr Walia said.

“There is a need to strengthen and improve diagnostic labs to promote rational use of antibiotics. Antimicrobial prescriptions should be based on definitive diagnosis and not on presumptive diagnosis. Several broad-spectrum antimicrobials are being used for syndrome management,” she added.

“The resistance level is increasing to 5 to 10 per cent every year for broad-spectrum antimicrobials which are highly misused. With no new antimicrobials in the pipeline to treat drug-resistant infections, it is very important that we use judiciously what we have. There are also increasing levels of resistance to antifungals. Previously, not many labs were doing fungal cultures and antifungal susceptibility.

“The ICMR AMR network has developed this over the last few years and now many labs are reporting antifungal susceptibility rates giving an idea on antifungal resistance rates. The use of antifungals was particularly high during the Covid pandemic,” she said.

MRSA, MSSA and diarrhoea

In Staphylococcus aureus, which causes a wide variety of clinical diseases such as skin infections like abscesses and boils and sometimes pneumonia, susceptibility to erythromycin, clindamycin, ciprofloxacin, co-trimoxazole and high-level mupirocin was more evident in MSSA (Methicillin-Sensitive Staphylococcus Aureus) when compared to multi-drug resistant strains such as MRSA (Methicillin-Resistant Staphylococcus aureus).

MRSA rates are increasing each year from 2016 to 2021 (28.4 per cent to 42.6 per cent). Enterococci is another important pathogen which is quickly evolving and drug susceptibility has changed considerably in the last few years.

Among diarrheal pathogens like Diarrheagenic E. coli, Shigella spp. and Salmonella that cause large proportions of diarrhoea cases in India, norfloxacin susceptibility was very poor. Empirical use of norfloxacin for the treatment of bacterial diarrhoea is strongly discouraged, Dr Walia said.

There has been no significant change in the overall antimicrobial susceptibility pattern of Salmonella Typhi or S Paratyphi A from India with the pattern remaining uniform across all the participating centres in the AMR network.

Published on

September 10, 2022



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A breakthrough in solid-state battery tech

A breakthrough in solid-state battery tech


Due to safety and efficiency considerations, the world is turning to solid-state batteries (SSB), where the electrolyte — the material between the anode and cathode through which ions shuttle back and forth during charging and discharging — is solid, rather than liquid. As detailed in previous issues of  Quantum, SSBs have become the holy grail of battery technology.

Researchers are also working on all-lithium anodes. Negatively charged, the anode ‘donates’ electrons when the battery discharges. Lithium, a metal that has ‘spare’ electrons in the outermost ring of its atoms, is a good anode material but needs to be embedded (‘intercalated’) in some other material such as graphite. It would help to have an all-lithium anode because that would mean more electrons to be had on every charge-discharge cycle.

However, if you have an ‘embedded lithium’ anode and a solid electrolyte, it doesn’t give you the bang you want because the higher weight of the solid electrolyte (compared with liquid) nibbles away some efficiency.

So, the darling battery would be the one that has an all-lithium anode and a solid electrolyte. But there is one challenge yet.

As ions move from the anode to the cathode through the electrolyte (while discharging), the anode material (lithium) gets ‘pulled’ to form filaments called dendrites. If these dendrites touch the cathode, you have a short circuit and, likely, fire.

It was once believed that this dendrite formation would not happen if you use solid electrolytes instead of liquid, especially if the solid electrolyte’s rigidity (shear modulus) is twice that of lithium.

However, research revealed that dendrites grow even through solid electrolytes and, indeed, more than in liquid electrolytes. Researchers from Indian Institute of Science, Bengaluru, brought out a paper on the subject that says, “Lithium growth through solid electrolytes was observed at current densities as low as 100 microamperes per sq cm, much lower than current densities observed in liquid electrolytes.”

In essence, lithium cracking through the electrolyte, whether solid or liquid, is the biggest challenge in lithium-ion electrochemical batteries.

Prof Naga Phani Aetukuri at the solid state and structural chemistry unit of IISc and his student Vikalp Raj have delved into the problem of dendrite formation in solid-state Li-ion batteries and come up with a solution. In their research, they realised that microscopic ‘voids’ were developing in the lithium anode during discharge. The currents concentrated at the edges of these voids were about 10,000 times more than the average currents across the battery cell. This, they deduced, was creating stress on the solid electrolyte, leading to dendrite formation.

Now, the task was simply to prevent the voids. Aetukuri and Raj introduced an ultra-thin layer of a refractory (heat-resistant) metal between the lithium anode and the solid electrolyte. This ‘lithium-phobic interlayer’ delayed dendrite growth.

That is the science. Now, it is up to engineers to adopt it into a battery.

Published on

September 04, 2022



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The rising spectre of bio-crimes

The rising spectre of bio-crimes


You cannot make a nuclear bomb in your garage lab, but you can make other things that are equally devastating. If a scientific criminal cannot use physics for his deviousness, there is biology at hand.

Some might remember the 2001 ‘anthrax attacks’ — people received letters laced with anthrax, a killer bacterium; five died and several fell sick, and it was not until years later that the letters were traced to Dr Bruce Ivins, an American microbiologist, who took his life just before he was about to be arrested.

Handling deadly pathogens called for (note the past tense) a large set-up, a lot of money and high levels of technical expertise. Not anymore. Today, we are in an era of do-it-yourself (DIY) and home-made drugs — stuff that can be beneficial and harmful. In the last few years, scientists have been red-flagging these dangers but, by all accounts, nobody is sure how to counter them.

In recent times, scientists have uncorked a genie called ‘synthetic biology’. There is no standard definition of synthetic biology, but it essentially refers to creating organisms that are not found in nature and designed to do a task that we desire.

However, synthetic biology could also mean “re-programming” natural organisms to perform a task or modifying them to have new abilities, in the same way that computers can be re-programmed for specific functions. For example, the chimeric antigen receptor (CAR) technology, where immune cells can be engineered to recognise and attack cancer cells.

Mariam Elgabry of University College London, who has produced quite a few papers on bio-crime, points out that “a traditional biological system could, for example, be modified to behave like a sensor that gets activated and emits a signal in the presence of a toxin or disease signature, which is useful for medical diagnostics or environmental solutions”.

Synthetic biology, often described as the biology equivalent of the internet, has many promising and useful applications. Every country is looking at it seriously. In February, the Department of Biotechnology, Government of India, brought out an insightful ‘Foresight Paper’ calling for a policy on synthetic biology. But much like how the internet has engendered cybercrimes, synthetic biology, too, could be misused.

Easy access

Now, synthetic biology is not exactly new. It has been around as a concept for decades. But scientists are generally agreed that two factors have helped make it rather commonplace.

One is ‘next-generation sequencing’ (NGS), which refers to ultra-quick genome sequencing. According to Illumina, a company that offers NGS services, the technology “is used to determine the order of nucleotides in entire genomes or targeted regions of DNA or RNA”. With NGS, the cost of genome sequencing has come down to a few hundred dollars from thousands earlier — the ‘sub-$100’ milestone is tantalisingly within reach.

The second is the gene editing tool CRISPR, a Nobel Prize winning technology that helps alter a DNA and modify gene functions. This technology has rather democratised genetic engineering. TALEN is another gene editing tool. These genome editing kits “are being made openly available for purchase over the internet”, says a publication of the UK Home Office on ‘Future trends in security’.

Skilled amateurs as well as professional scientists can experiment with gene editing technology.

Says the Government of India’s ‘Foresight Paper’: “Synthetic biology involves large-scale synthesis of DNA which can create new pathogens from scratch, recreate old pathogens, or engineer naturally occurring organisms to become a threat to biosafety. If a sequence coding for a toxin is made available on the Internet and anyone can print the gene or pathogen.”

Add to this deadly concoction yet another poison — cybercrime — and the potential for crime increases by orders of magnitude. Mariam Elgabry et al in a 2020 paper on ‘Criminogenic potential of synthetic biology’, published in  Frontiers in Bioengineering and Biotechnology, say: “Synthetic biology integrates a diverse set of technologies to enable various applications that have enormous potential. While these were once restricted to specialised institutions, they are now freely available online through kits, bioinformatics tools and data.”

Evil experiments

So, what all can a criminal possibly do? Systematic evidence quantifying the crime opportunities posed by synthetic biology has been limited, says the Elgabry paper, but it divides the universe of criminal activities into eight categories — illegal gene editing, home-made bad drugs, genetic blackmail, neuro-hacking, bio-hacking, bio-discrimination, cyber bio-crime and bio-malware.

Each category can spawn a class of criminals specialising in it. For example, banned psychoactive drugs can be made at home. Earlier, one might have needed, say, a camouflaged agricultural field to grow poppy, but today you only need to understand how the poppy plant makes the psychoactive drug (the biosynthesis pathway). You can mimic the process in a lab. “In the event that a single psychoactive constituent is desired by the consumer and isolation from the native host is costly, total synthesis may be one strategy to establish a robust supply chain,” says a 2021 paper on ‘Biosynthesis and synthetic biology of psychoactive natural products’, by Cooper Jamieson et al.

A blackmailer, for instance, could easily obtain saliva samples of a father and son and do a paternity test; if negative, he could resort to blackmail. A neuro-hacker can manipulate the gut biome of a person and control the person’s brain, because there is a connection between the activities of the bacteria in the gut and the brain.

The list is practically endless.

The unfortunate part is that the world seems ill-equipped to deal with this rising spectre of bio-crime. In a recent paper on ‘The future of biotechnology crime: A parallel Delphi study with non-traditional experts’, Elgabry et al note that “forecasting biotechnology crime trends remains a challenge as future misuses become more sophisticated”.

The Foresight paper recognises the inadequacy of regulatory tools to deal with the emerging situation. “Many of the existing regulatory frameworks were developed in the context of “traditional” fields such as biotechnology and genetic engineering,” it says, adding that these “may have to be revised in order to cope with fresh challenges raised by synthetic biology”.

Published on

September 04, 2022



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Strong and stable steel for power plants

Strong and stable steel for power plants


Scientists at the International Advanced Research Centre for Powdered Metallurgy and New Materials (ARCI), Hyderabad, have developed a new method for making alloys of high strength. Austenitic steel, a special alloy, is among the promising structural materials used in power plants and reactors owing to excellent creep, corrosion and oxidation resistance compared with ferritic or ferritic–martensitic steels. It can withstand high temperatures, large stress, chemically reactive environments and intense neutron radiation fields, but suffers from inferior tensile strength and stress corrosion resistance at higher temperatures. Besides, one of the major concerns over its use in advanced nuclear power reactors is severe swelling due to irradiation, which can be reduced by introducing stable nano-oxide particles into the austenite matrix. The high-energy ball milling method used to disperse oxide particles in metal matrix invariably leads to powder sticking to the milling media and thus decreasing the milled powder yield. Using carbon-containing process control agents (PCA) such as stearic acid results in carbon pickup, which will promote coarsening of oxide particles.

A two-stage ball milling without the addition of any carbon-based PCA was employed by the ARCI scientists. The first-stage milling is aimed at dispersing the oxide particles into the ferrite matrix, which is the starting powder microstructure, and the second-stage milling is to transform the oxide dispersion strengthened (ODS) ferritic steel into austenitic ODS (AODS) steel by the addition of nickel.

Nitrogen gas was used as the PCA in both stages of milling to improve the milled powder yield. The alloy developed in this method was found to have one of the best combinations of yield strength and fracture strain.

Copper for silver

The shining grid lines you see in a photovoltaic solar module is silver, a costly metal, which is only expected to become dearer because the e-mobility and 5G telecom sectors will also want it. Can you use a cheaper metal in place of silver in PV cells?

Yes, says Dr Markus Glatthaar of the Fraunhofer Institute, Germany. Glatthaar, an expert in metallisation and structuring, has developed an electroplating process for the promising heterojunction technology to replace silver with copper. Copper is many times cheaper and more readily available than silver.

“We developed a special electroplating process that makes it possible to use copper instead of silver for the busbars,” explains Glatthaar. This even improves conductivity — the copper contact lines are particularly narrow on account of their laser structuring. The light-absorbing silicon layer experiences less shading than with silver lines. This improves electricity yield.

The Fraunhofer team also used aluminium as a masking layer. “We were able to adapt the process parameters and develop a special type of electrolyte which ensures that the aluminium’s extremely thin, native oxide layer can reliably fulfil its insulating function. This was an important milestone for the success of our research project,” says a press release from Fraunhofer Institute quoting Glatthaar.

Published on

September 04, 2022



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