India needs more labs dealing with extremely dangerous pathogens as well as trained human resources, says SC Mande, director-general of Council of Scientific and Industrial Research
There has been a deluge of information as well as misinformation, leading to panic since the UK variant — VUI-202012/01 — hit the headlines. India has been among several countries who have stopped flights to and from the United Kingdom, fearing this strain of the novel coronavirus, SARS-CoV-2.
Questions have cropped up about how virulent this ‘mutant’ is and whether vaccines in the pipeline would be effective.
Down To Earth (DTE) spoke to SC Mande, director-general of the Council of Scientific and Industrial Research (CSIR) December 23, 2020.
CSIR is India’s apex research and development body that has a network of 38 national labs, besides over three dozen other centres and institutes scattered across the country.
Mande talked on a range of issues including, the basic science of mutation, the answers that are not yet so black-and-white, how India would be impacted and what lessons the COVID-19 pandemic had taught an institution as big as his. Edited excerpts:
Banjot Kaur: How does a virus mutate?
SC Mande: When viruses replicate in our body, a sort of battle ensues between them and the host. The host tries to get rid of the virus, which, in turn, tries to get established inside the host. This usually leads to mutations, some of which proliferate better than others.
BK: How many mutations of SARS-CoV-2 have there been? When should we be alarmed?
SCM: A large number of mutations have accumulated in this virus so far. Even in India, there are multiple variants of the virus, let us say, for example in Delhi and Tamil Nadu.
The most predominant variant in Delhi would be of one kind and the most predominant one in Tamil Nadu would be of another kind. Even within Delhi, we can’t say that all the mutations which lead to the evolution of one particular variant are exactly the same.
There may be a predominant set of mutations but we cannot say that all are one and the same. Therein lies the diversity.
BK: How many variants of the virus has India reported?
SCM: There are quite a few mutations in India as well. Some of them are unique to the country.
There are two different aspects of any virus, including SARS-CoV-2. They are transmissibility and lethality. At times, a virus can be very transmissible and not very lethal or vice-versa.
As of now, we really don’t have any evidence to suggest that one variant of SARS-CoV-2 is more lethal than the other.
In the case of the new UK variant, all we know is that it is 70 per cent more transmissible.
BK: The UK has sequenced thousands of positive samples and they got to know about the new variant. How many samples has India sequenced to rule out or find out the UK strain?
SCM: I can’t answer this right now, but I believe that we have sequenced more than 4,000 viral isolates. I am not sure whether this pool contains the sample of virus from anyone among those who have returned from the UK so far.
(A look at the international database suggests India has not submitted any sequence after October 3. The UK new variant was announced this week)
BK: Since we have not sequenced to find out the UK strain, how correct is it scientifically to say that there is no circulation of the particular variant here?
SCM: At this moment, I would like to believe that we don’t have the strain here. All of us will like to believe this till new evidence emerges. We have to wait and watch.
BK: You have been quoted as saying that the new variant will not have any impact on the development of vaccines. But the European Centre for Disease Control and Prevention has said the properties of the new strain are being studied and it may take three weeks. Shouldn’t we wait before saying anything about vaccine development?
SCM: Making a definitive statement on this is very difficult. I can make a more probable statement that is very unlikely that the vaccination would change.
It is more likely that vaccines would be as effective on this mutation as on other variants of this virus. The mRNA COVID-19 vaccines make spike protein (similar to what is actually present in the virus). Once the vaccine-induced spike protein goes inside our body, the antibodies against the virus generate as an immune response.
Our body generates a holistic immune response against the entire spike protein. The mutation has occurred in one part of the virus’ spike protein. Therefore, the antibodies which may have bound on one particular region of the spike protein in the absence of mutation, may not do so now. But they may bind on other portions of the spike protein and this will produce an immune response. Therefore, the hypothesis that the vaccine would be as effective with this mutation as well.
BK: How will diagnostics be impacted since the S gene-based RT-PCR Tests are still limited in India?
SCM: This is very critical.
(The RNA is extracted from the collected sample swab. RT-PCR, with the help of primers, picks up small fragments of RNA and amplifies them)
If the fragment amplified from the sample has a fragment matching with the virus, we understand that it is a SARS-CoV-2 case.
There is a chance that a primer is designed to pick up that particular region of the virus in which the mutation has now occurred, ie the S-gene. Due to the mutation, that particular region may escape the test and not get amplified (and the test may come as false negative).
So, we will have to see if any of the primers are targeted towards only that region of the virus in which the mutation has occurred and if yes, we will have to change strategy and move the primer to that region of the virus which is less mutated.
BK: India has submitted, as you said, a little more than 4,000 genome sequences to the international database but other countries have submitted many more. Do you think it is enough for India, considering the caseload?
SCM: In psephology, a sample size of 16,000 is considered good enough to forecast a national election result if the samples are completely random.
What matters is not just the quantity but randomisation in sampling. And our genome sequencing has been random enough. But let me stress that we should increase our sequencing. We are actively considering doing so.
BK: How many labs in India can sequence genomes?
SCM: Ten. The ones in a leadership role are the Institute of Genomics and Integrative Biology, Delhi and the Centre for Cellular & Molecular Biology, Hyderabad, with others also chipping in.
BK: Do you think we need to ramp up this infrastructure or is this enough?
SCM: I truly believe the country needs to ramp up genome sequencing capabilities and not just for the COVID-19 pandemic. It has come and it will go.
But what about other infectious outbreaks? Besides, we have an increasing load of cancer patients. As of now, the standard of care does not dictate that you map the mutation in the cancer before you decide which therapy is to be given from the bouquet available. If we can do sequencing, we can easily choose.
Then, we have a huge burden of rare genetic disorders in this country. About seven crore people suffer from them. We must map them. For doing all of this, we need better sequencing capabilities.
BK: What should we do first to improve genome-sequencing capabilities?
SCM: We need to remain at the forefront for the new technologies that are coming in. We must be in a position to adopt them very quickly and implement them.
BK: CSIR has sponsored trials for many AYUSH drugs meant for COVID-19. What proofs of concepts were generated before embarking on them?
SCM: We are actually trying right now on five different AYUSH formulations like ashwagandha, etc. They are generally considered safe. From multiple evidences, we know that they have not shown any adverse effects. We have designed their clinical trials exactly on the lines of trials for drugs of modern medicine. The trials are going on.
BK: What evidence did you find, especially for the treatment part?
SCM: I did not say anything about treatment. I said these have been used by many people around the country. They have been regarded as safe. People are taking them under the belief that they have some curative properties. They have not been proven and that is what we are trying to do.
BK: In this pandemic, we got vaccines in just 10 months. The earlier record was four years. What, in your view, were the deciding factors to cut the very long timelines to such a short period?
SCM: It is a difficult question to answer … regulators across the world have been looking at the data very closely before giving emergency authorisation. Even after the administration of the vaccine, the beneficiaries would be observed for a long period to monitor for adverse events.
BK: What were the key challenges and lessons from the pandemic for CSIR?
SCM: Our scientific infrastructure must be up to the mark. We have a general lack of biosafety level-4 (BSL-4) facilities where we can handle extremely dangerous pathogens for research. We need at least 10 more BSL-4 labs. Even BSL-3 level facilities are not adequate.
We need to have trained human resources as well to work on important issues like this. This is not the last pandemic and we must be prepared for upcoming ones.
BK: What would be your suggestions to the Indian government?
SCM: Besides the need of improving overall pandemic preparedness, we have to be self-dependent on handling many things on our own. For instance, we are dependent on other countries for active pharmaceutical ingredients (for making drugs). India has done well in other sciences like those of weather but we have to take a 360-degree view of all possible kinds of calamities that may strike us in the future, including pandemics and be prepared with solutions.
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