By Kamal Pratap Singh and Seema Pavgi Upadhye
India is a country of around 1.3 billion living in as congested places like Dharavi in Mumbai to spacious lush green Lutyen’s zone of Delhi. Handling world’s second most population is not an easy task but the situation till now is under the control. However, there are few who speculate that we have just postponed the pandemic which will come after lifting up the lockdown or may recur like other viral infections.
There has been around two months (in India) since the lockdown which has led life to travel on road. The strategy has been proved successful till now, but we were not able to find rocket science behind this act, when it was asked for 21 days only as time window for scientific and other preparations and then extended for around 60 days.
Despite having complete Genome sequence(s) and biochemical information which can further help to prepare recombinant vaccine, unavailability of COV-2 vaccine anywhere is the most embarrassing situation for scientific fraternity in world when the institutions and companies of world declare themselves as world’s no.1 including in the field of biosciences. It is important to refer Remdesvir here because it has become first drug of emergency use in COVID-19 by FDA (not by WHO) but has failed to gain trust of market, it is in the market since 2004. According to a recent update of WHO, no Indian Vaccine has entered human trial as on 15th May. (Reference 1)
On the many occasions Biotech Express magazine has reported accomplishments of India’s scientific developments but we at this occasion have nothing great to show as there is still no ‘Make in India’ diagnostic method and/or treatment available from the country. In this COVID-19 pandemic too, we are lagging behind many nations when we could control whole attention through a vaccine or a cure. In this article we are discussing about current status of India in Virus research, what has been done by Indian science leaders and scientists to combat this virus and its transmission and what more is expected to become global leader in Biological sciences.
NOTE: Chinese research and products are not mainly included in this article.
Major decisions taken by global bodies
– World Health Organization is facilitating collaboration, accelerated research, and international communications with a goal to raise US$8 billion
– Coalition for Epidemic Preparedness Innovations (CEPI) is working with global health authorities and vaccine developers to raise US$8 billion. The United Kingdom, Canada, Belgium, Norway, Switzerland, Germany and the Netherlands had already donated US$915 million by early May.
– The Gates Foundation, a private charitable organization dedicated to vaccine research and distribution, is donating US$250 million for research and public educational support.
– Global Alliance for Vaccines and Immunisation (GAVI) is financing and organizing clinical groups in under-developed countries with COVID-19 vaccination preparedness.
– Global Research Collaboration for Infectious Disease Preparedness (GLoPID-R) is coordinating among the international funding and research organizations to maintain updated information on vaccine progress and avoid duplicate funding.
– The International Severe Acute Respiratory and Emerging Infection Consortium organizes and disseminates clinical information on COVID-19 research to inform public health policy on eventual vaccine distribution.
COVID-19- India’s Approach(es)
To start with Indian healthcare and medical science, health of a common man of this country is supported by Ministry of health and family welfare (MHFW) headed by Dr. Harsh Vardhan. MHFW supports health infrastructure required for medical treatment and/or research activities in this field. The budgetary allocation for the MHFW in 2019-20 was Rs 60,908.22 crore, with Rs 6,400 crore earmarked AB-PMJAY. Ministry of Health and Family Welfare has three Departments- Department of Health & Family Welfare, Department of Health Research (ICMR as its flagship organization) and recently added Department of AYUSH. Directorate General of Health Services (DGHS) is attached office of the Department of Health & Family Welfare.
The next important organization of Govt. which supports science activities is Ministry of science and technology, it mainly look up research activities in the country. The Ministry of Science and Technology (S&T) has three wings under it — the Department of Science and Technology (DST), Department of Biotechnology (DBT) and Council for Scientific and Industrial Research (CSIR). In 2019-20, the DST has been allocated Rs 5,321 crore, the DBT has been allocated Rs 2,580 crore and the CSIR has been allocated Rs 4,895 crore. (Reference 2)
To know the efforts of Indian science to this biological pandemic it is important to see and understand the activities of these two ministries MHFW and MST in current times, which together are premiere authorities for health infrastructure and research and are responsible to provide urgent plan for combating and curing this health hazard now and in recurrent future.
A. Indian COVID-19 Science Task forces and their assigned tasks
To address the COVID-19 pandemic, various task forces/committees/groups were made in these two ministries, their departments, councils and organizations each one with their own leaders and peers. Analysis of various task forces revealed lack of harmony among these groups which we will discuss later. The various groups made are as under:
1. Central Govt. Task forces
COVID-19 task force was set up on March 29, 2020 which directly operates under the Prime Minister. This task force, with handpicked bureaucrats and key officials, operates around the powerful Prime Minister’s Office. These include cabinet secretary Rajiv Gauba, health secretary Pritee Sudhan and home secretary Ajay Bhalla, three officers–principal secretary to the PM, P.K. Mishra; principal advisor to the PM, P.K. Sinha; and newly-appointed secretary to PM, Amarjeet Sinha. Reporting to the PM’s task force are V K Paul, NITI Aayog member for health, and Balram Bhargava, secretary, health research, and also director-general of the Indian Council of Medical Research (ICMR). Another key official in this grid is K. Vijay Raghavan, principal scientific advisor to the government. The government’s public interface includes the daily press briefing at the National Media Centre. The briefings are given by Lav Agarwal, joint secretary in the health ministry, ICMR DG Bhargava, ICMR chief scientist R. Gangakhedkar, home ministry spokesperson P.S. Srivastava and K.S. Dhatwalia, director-general of the Press Information Bureau. (Reference 3, 4)
On April 19, the centre has formed again a high-level task force to track and monitor the work being carried out to develop vaccine against COVID-19. The panel has been led by Member (Health), NITI Aayog and PSA to the PM. AYUSH, ICMR, DST, DBT, CSIR, DRDO, DG Health Services and Drug Controller are members of the task force. In this task force the Department of Biotechnology has been asked to become a central coordination agency to identify pathways for vaccine development. (Reference 5)
As per records, the first high-level technical committee of 21 scientists and Public Health Experts for COVID-19 was established on 18th March under the Chairmanship of Dr Vinod K Paul, Member, NITI Aayog, to guide the prevention and control activities in the country. (Reference 6)
On 6th April, National Task Force for COVID-I9 has constituted the following research groups to identify the research priorities and quickly initiate research studies. (Reference 7)
1. Clinical Research Group
2. Research on Diagnostics and bio-markers
3. Epidemiology and surveillance
4. Operations Research
5. Vaccines/Drug Research and Development
ICMR’s Rapid Response Team for COVID-19 appeared on 26th April (Reference 8).
CSIR has not constituted any formal task force but has been seen to coordinate with other science agencies on regular basis.
On April 29, CSIR and Cadila started clinical trial of Sepsivac’ drug in PGIMER Chandigarh to evaluate efficacy of an existing gram-negative sepsis drug, called Sepisvac for COVID-19 patients.
On 5th May, CSIR-IGIB and TATA Sons signed a MoU for licensing of KNOWHOW for FNCAS9 EDITOR LINKED UNIFORM DETECTION ASSAY (FELUDA) FOR RAPID DIAGNOSIS OF COVID-19. (Reference 9).
On 8th May, CSIR under its New Millennium Indian Technology Leadership Initiative (NMITLI) has sanctioned a project to develop human monoclonal antibodies as therapy for COVID-19 infections. National Centre for Cell Science (NCCS), IIT-Indore and a Gurgaon-based company, PredOmix Technologies will also collaborate with Bharat Biotech on the project. The cost of project has not been disclosed. (Reference 10)
More info about CSIR strategies and drugs being considered by CSIR for followup can be found herehttps://urdip.res.in/covid19/vertical2.jsp (Reference 11)
4. Department of Science and Technology
On March 27, the Department of Science and Technology (DST) said it has set up a Covid-19 task force for mapping of technologies to fund nearly market-ready solutions in the area of diagnostics, testing, healthcare delivery solutions and equipment supplies. The capacity mapping group consists of representatives from DST, DBT, ICMR, Ministry of Electronics and Information Technology, and CSIR. It also has representative from the Atal Innovation Mission (AIM), Ministry of Micro, Small and Medium Enterprises (MSME), Startup India and All India Council for Technical Education (AICTE). (Reference 12)
5. ISRC (Non-Govt.)
Indian Scientists’ Response to CoViD-19 (ISRC) started as a group of Indian scientists who came together voluntarily in response to the COVID-19 pandemic. It has now grown to include more than 500 scientists, engineers, technologists, doctors, public health researchers, science communicators, journalists and a number of students; they hail from a range of disciplines but principally the physical and life sciences; they are affiliated to eminent research institutes of science and technology, universities, colleges, hospitals and private laboratories. The group also includes Indian scientists from laboratories all over the world. The few initiators of the group include S Krishnaswamy, Sandhya Koushika (TIFR, Mumbai), L S Shashidhara (Ashoka University), Rahul Siddharthan (IMSc, Chennai), Reeteka Sud (NIMHANS, Bengaluru) and many more. (Reference 13)
6. Principal Scientific Advisor’s Task forces
The first meeting of the Empowered Committee for COVID-19 response in India was held on March 21, 2020. The meeting was co-chaired by Dr. Vinod Paul, Member NITI-Aayog and Professor K. Vijay Raghavan, Principal Scientific Advisor (PSA) to Prime Minister, Government of India. The Committee was constituted to co-ordinate, amongst science agencies, scientists and regulatory bodies, and take speedy decisions on R&D implementation related to the SARS-Cov-2 virus and the COVID-19 disease.
According to an official release from PSA office, Indian research institutions and organizations were directed for speedy implementation of solutions related to COVID-19. “National research labs (defined as labs of DBT/DST/CSIR/DRDO/DAE for this directive were permitted to carry out clinical testing for COVID-19 based on self-assessment and willingness to follow established protocols and all applicable reporting regulations as defined by the DHR/ICMR,”. Also “Labs with BSL-3 or BSL-3+ facilities, with DBT/DST/CSIR/DRDO/DAE, were permitted to culture the virus and serve as additional testing and validation sites for research, based on self-assessment of BSL-3 facilities and willingness to follow established protocols as defined by the DHF2/ICMR. (Reference 14)
The Principal Scientific Advisor to the GoI, Dr K VijayRaghavan, has constituted a S&T Core Group ‘PSA Task Force on Repurposing of Drugs for COVID19’ on 16th March 2020 (in short “TFORD-COVID19“). The Task Force is being coordinated by: Dr V Premnath, Head, NCL Innovations at CSIR-NCL and Director, Venture Center and Dr Anurag Agarwal, Director, CSIR-IGIB. Key components planned for this task force are to Compile information on Drug Candidates, Reports by Nerve Center Team to PSA, Inter-disciplinary Advisory Group; Position/ Strategy Papers, Virtual Translation Network, Information on Path to Market/ Bedside, Requests to PSA etc. (Reference 15)
B. Vaccine Research and Manufacturing in India
The first two vaccines in India were developed by Dr Haffkine of British Government in 1893. The first recombinant vaccine made in India was Hepatitis-B made by Dr Ramareddy V Guntaka in 1996 for a company of first generation entrepreneur Varaprasad Reddy, Padma Bhushan who conceptualized the impossible task and fought against many odds. Since then Biotechnology has opened new avenues and interests for Indian Pharmaceutical sector. Now, India occupies a prominent position in Biologics drugs industry.
1. Early Background & Development
In India, till 1850, the vaccine was imported from Great Britain. Anna Dusthall, a three year old child from Bombay (now Mumbai) became the first person in India to receive smallpox vaccine on June 14, 1802. In 1893, Dr Haffkine conducted vaccine trials in Agra, Uttar Pradesh, and showed the efficacy of Cholera vaccine in the effective control of the disease. Later he developed plague vaccine in 1897 and it is arguably, the first vaccine developed in India. This laboratory was called Plague Laboratory since 1899, renamed as Bombay Bacteriological Lab in 1905 and then finally named as Haffkine Institute in 1925, as it is known today.
In early twentieth century, four vaccines (smallpox, cholera, plague, and typhoid) were available in the country. Feeling growing demand, the Government of India decided to set up new vaccine institutes. The initial vaccine research unit was Haffkine Institute for plague vaccine. The smallpox vaccine lymph was being produced in Shillong since 1890. In 1904/1905, Central Research Institute was set up in Kasauli, Himachal Pradesh and then Pasteur Institute of Sothern India in Coonoor in 1907, in the same year the Pasteur Institute of India (PII) produced neural tissue Anti-rabies vaccine in 1907. The PII in due course of years, developed influenza vaccines, trivalent oral polio vaccines conducted landmark research and production of tissue culture and then Vero cell derived DNA purified rabies vaccine for human use.
Then many developments and reorganization of vaccine industry has taken place and can be found in the article published by IJMR in 2014. (Reference 16)
2. Current Landscape: Vaccine R&D and manufacturing infrastructure in India
What we have now and how to use it to fight this COVID-19 enemy is a question of the hour. In virology research, India’s position is not that much weak when compared to west, over the years the vaccine research and manufacturing infrastructure has developed into world class facility in the country.
Since we are discussing CoV2 here which require a specialized BSL-4 facility for handling, it is little sad to know that we have only three facilities with BSL-4 rating, in a country of 1.3 billion where viral infections are common thing. The three facilities are Microbial Containment Complex(MCC), ICMR- National Institute of Virology, Pune; High Security Animal Disease Laboratory, ICAR- National Institute of High Security Animal Diseases (NIHSAD), Bhopal; and CSIR-Centre for Cellular and Molecular Biology(CCMB), Telangana. Recently, DBT-RGCB announced to establish BSL 4 facility.
List of CDSCO Licensed Human Vaccine indigenous Manufacturing Facilities in India (Reference 17)
Biological E. Ltd.
Cadila Healthcare Limited
Dano Vaccine & Biological Pvt. Ltd.
Green signal BioPharma Ltd.
Serum Institute of India
Shantha Biotechnics Ltd.
GSK Asia Pvt. Ltd.
Sanofi Pasteur India Pvt Ltd.
Haffkine Bio Pharma Corporation
Human biological institute
HLL Biotech Ltd.
BCG vaccine, Guindy, Chennai.
CRI, Kasauli, District Solan, HP.
Aventis Pharma Limited
CPL Biologicals Limited
Eli Lilly India
Indian Immunologicals Limited
USV Biopharmaceuticals Limited
Venkateshwara Hatcheries Limited
Other Avenues of Indian science in Vaccinology
The Department of Health Research (DHR)/Indian Council of Medical Research (ICMR) took a far sighted decision of enhancing the country’s capacity for early identification and diagnosis of all viral infections of public health importance. This initiative of DHR/ICMR has been rolled out on approval of the VRDL Scheme by the Union Cabinet wherein it was envisaged to set up 160 Virus Research & Diagnostic Laboratories (VRDLs) in most of the Government Medical Colleges of the country in 12th Plan Period (2012-2017). (Reference 18)
A Multi Vaccine Development Program (Not For Profit Research Society) is committed to undertake, outsource, assist, promote and encourage scientific studies, epidemiology studies, product development, clinical studies & establish field sites with the object of advancing the development of vaccines against P. falciparum and P. vivax malaria identified by Research Institutes. Dr. Salunke current Director of the International Centre for Genetic Engineering and Biotechnology and Dr. T.S. Rao presently working as Adviser in the Department of Biotechnology, Ministry of Science & Technology, Govt. of India are among the governing board member of this initiative. (Reference 19)
C. Translational Research after COVID-19 pandemic
1. Diagnostic kits
Pune-based Mylab Discovery Solutions was the first Indian company to give Make in India diagnostic test. Mumbai-based Meril Diagnostics Pvt Ltd., Delhi based Medsource Ozone Biomedicals Pvt. Ltd., and others are among current manufacturers. (Reference 20)
On April 22, Indian scientists from the Institute of Genomics and Integrative Biology (IGIB) also declared to have successfully developed a low-cost, paper strip test which can detect the Coronavirus2 within an hour. It uses the cutting-edge, gene-editing tool – Crispr-Cas9 to target and identify the genomic sequences of the novel Coronavirus. The team led by Souvik Maiti and Debjyoti Chakraborty is currently testing the kit in a patient cohort for its accuracy and sensitivity and hope to seek validation from a regulatory body of the Indian Council of Medical Research (ICMR). (Reference 21)
However, with the accuracy in question there are questions on whether these kits can reliably help indicate the spread of the infection.
2. Vaccine or Treatment
There are no drugs or other therapeutics presently approved by the U.S. Food and Drug Administration (FDA) to prevent or treat COVID-19. Current clinical management includes infection prevention and control measures and supportive care, including supplementary oxygen and mechanical ventilatory support when indicated. (Reference 22)
– The National Institutes of Health, an agency within the Department of Health and Human Services, has been fast-tracking work with biotech company Moderna which is developing mRNA vaccine to prevent COVID-19. The company began the first phase 1 human trial on 45 volunteers testing a vaccine to prevent the disease in March and has been approved to soon start its phase 2, which would expand the testing to 600 people, by late May or June.
– Inovio began its early stage clinical trials for a potential vaccine on April 6, making it the second potential Covid-19 vaccine to undergo human testing after Moderna.
– Vaccine ChAdOx1 nCoV-19 (recombinant) developed by researchers at Oxford University began phase 1 human trials on April 23. British Health Minister Matt Hancock said that he would provide £20 million, ($24.5 million), to help fund the Oxford project.
Many others treatment options are in either preclinical, clinical stage or Midstage trial, some are BNT162, NVX-CoV2373, Remdesivir, Hydroxychloroquine, Favipiravir, Kevzara, Baricitinib etc. (Reference 23, accessed on 11 May 2020)
The FDA issued a warning against taking the drug outside a hospital or formal clinical trial setting after it became aware of reports of “serious heart rhythm problems” in patients. Similarly, even though remdesivir was granted FDA nod for emergency use, there are still several ongoing clinical trials testing whether it’s effective in stopping the coronavirus from replicating and The Lancet reported that Treatment with remdesivir did not speed up recovery or reduce deaths from COVID-19. (Reference 24)
More than 30 vaccines are in various stages of development in India, scientists informed Prime Minister Narendra Modi on May 5.
University of Oxford’s vaccine is also being developed with multiple partners including India’s Serum Institute of India. The WHO document says out of the 100 projects under pre-clinical stages,
Indian companies like Zydus Cadila, Codagenix-Serum Institute of India, Indian Immunologicals with Griffith University, Bharat Biotech in association with Thomas Jefferson University, Biological E Ltd, and the UW Madison-FluGen-Bharat Biotech combine are all working on potential vaccine candidates to cure the coronavirus infection. (Reference 25)
So far we discussed the organizational setup of Indian healthcare system and their working in COVID-19pandemic through science tasks forces for COVID-19, current research and manufacturing infrastructure and the output till now. It is imperative that India does not have any promising innovative product nor her scientists could utilize the time they were seeking for preparation by putting lockdown in place; She is using diagnostic kits of other nations and in treatment too she is not in the hit lists of COVID-19 Landscape drugs.
Where Indian Science is lagging? Why even after these many organizational set-ups and efforts Indian scientists could not make a single entity of great scientists who would find drug/vaccine for this disease. We tried to find out more reasons why it is taking this much time to make a vaccine by Indian scientist when around 10,000 crore is going to DST, DBT and CSIR alone, where top most scientists are working. We could not figure out how much is going to DHR’s medical research from 62,000 crore but believing it must be having significant contribution in figures.
How the chaos is creating problem can understand by taking excerpts from one article – “Everything is fine as long as you take action,” Naveet Wig, head of the department of medicine at the All India Institute of Medical Sciences told other members of the government’s task force of public health experts on COVID-19 on 29 March 2020. “This discussion has gone on for too long and no action has been taken. No. No. We will have to tell the truth.” (Reference 26)
The records also show, while imposing the lockdown, the government had ignored recommendations from its top scientists. Instead of the current coercive lockdown, these scientists had advised “community and civil-society led self-quarantine and self-monitoring,” through their research in February 2020. However later concerned Indian organization denied the claims.
This can be the problem over fight for leadership, the next problem that holds a place here is leaders’ ignorance of national as well as internationally skilled scientists who have played with the viruses. According to a survey by Biotech Express magazine many senior scientists of concern field were not contacted to see their views.
Lack of infrastructure is also a concern here because not all virologists can use same facility in single time, we have 24 hours only. In this situation, which warrant future preparation there is need of establishing most advanced multiple scientific infrastructure for translational research.
Lack of appropriate choice of expertise was revealed as an important factor which was seen while formations of task forces. It mainly revolve around current employees irrespective of their specialization whereas many famous Indian Microbiology and Biotechnology researchers like Jacob John, G Padmanabhan, Madhavi, Rajeev Bhargava, N K Ganguly, Satyajit Rath and many more have not been appearing in any of the task forces.
Concept of domination by misinformation in science came from an observation of a video of Prof K Vijayraghavan where he was seen ignoring his expertise when News anchor called him a Microbiologist. Our observation found that he is not a Microbiologist but a Drosophila Developmental Geneticist who have never experienced virus research, at least not in his published research studies. (Reference 27)
Lack of manpower and its positioning is another concern that needs to be addressed in times of such pandemics. Working Chair has his own duties but professionalism should come first in emergency situations like this. We saw that how many task forces were made for each and every task but these forces have different leaders and soldiers and one of the main leader has not come to front at a single location or time till now i.e. Dr V K Paul, the first Member of the various committees, which shows either of his incapability(which seems illogical here) or inconsistency of science fraternity toward combating this science problem.
Indian Govt has not tried the Brain Drain of the Indian scientists who otherwise are doing great in other nations. Indian Human Resources for Health supported Sustainable Development Goal (SDG) 3, which ‘ensures healthy lives and promotes well-being for all at all ages’, the US order prioritised SDG 8, which states: ‘Promote sustained, inclusive and sustainable economic growth, full and productive employment and decent work for all’. Notably, the US order exempted foreign doctors, nurses, researchers and other healthcare workers and their dependents from the ban. (Reference 28)
We apologize that despite our duty we cannot spell more on Indian sciences as everyone is waiting for some working results but they are yet to come.
As Romila Thapar said somewhere, ‘’History is not written by committees but by individuals’’. Whenever a major activity like combating this ‘public Health crisis’ is undertaken by very intelligent and competent human beings, you will not always hear beautiful symphony music. Some jarring notes are bound to appear. Team work is very difficult to execute without discipline, commitment and command structure.
Authors’ Note: These are observations and views of authors’ only, communicating their personal views.
A brief history of vaccines & vaccination in India, http://www.ijmr.org.in/temp/IndianJMedRes1394491-7933325_220213.pdf
https://www.who.int/who-documents-detail/draft-landscape-of-covid-19-candidate-vaccines Accessed on 15th May 2020)