“I think Nepal handled the pandemic relatively well,” says Dr. Digbijay Raja Mahat

Dr. Digbijay Mahat, a research scientist at MIT, has developed and patented a novel methodology for single cell nascent RNA sequencing. His technology is used in blood biopsy, which helps to identify cancers before they metastasize to other organs. During the current pandemic, Dr. Mahat helped develop a new RT-PCR  test of SARS-CoV-2, which is currently licensed by a U.S. and a Japanese company. Born and raised in Tanahun, Nepal, he aims to return here after completing his postdoctoral training and utilize his scientific expertise and entrepreneurial experience to promote cancer treatment and research in Nepal. He recently visited Nepal to introduce the CRISPR SARS-CoV-2 testing strategy. He worked as an expert consultant in testing strategies to the Ministry of Health and Population. Medicos Next… had a chance to talk to him during his visit.

Could you please tell us about yourself?

I am a research scientist in the lab of Nobel Laureate Dr. Phillip A. Sharp at the Koch Institute of Integrative Cancer Research at MIT. Founder of Biogen and several other biotech companies, Dr. Sharp is considered the pioneer of biotechnology industry. Dr. Sharp’s mentor was also a Nobel Laureate and one of his graduate students has won a Nobel prize, as well. I am privileged to be trained in the lab of Dr. Sharp, which has an illustrious history of Nobel Laureates in three scientific generations.

I received Ph.D. from Cornell University in 2017. As a graduate student, I co-developed a genomic assay to measure precise and instantaneous gene expression profiles from cells. This technology helped to understand how cancers hijack cell programs to grow out of control and eventually become lethal. Because of our and others’ discoveries, we can now block cell circuits that cancer cells rely on to proliferate.

During my postdoctoral training with Dr. Sharp, I have developed and patented a novel methodology for single-cell nascent RNA sequencing. Our technology can be used in blood biopsy, which helps to identify cancers before they metastasize to other organs, allowing early intervention to cure cancer. Our technology is also being used to understand why some cancers are resistant to immunotherapy, which is the most promising cancer treatment therapy as of now.

How did the pandemic affect your scientific research?

Like it or not, most of the globe was caught unprepared by the pandemic. In today’s world, we are faced with many challenges that require our unwavering attention. The needs we face in daily lives are more urgent than a global crisis that we have not faced for a few decades, at least of this scale. So, it would be disingenuous to say that any of us were prepared for the pandemic.

Our work is primarily conducted in labs. So, when the number of hours at the bench was rationed, it severely limited our productivity. The movement within the building and the use of core facilities were limited. Scientific interactions within and across the institutions were severed.

However, certain experiences and trainings during the postdoctoral studies might have softened the blow of pandemic for research scientists like us. Being served with multiple bouts of crisis, small and big, in laboratories on a daily basis, we are undeterred by crisis. So, the psychological toll might have been smaller compared to other professions, but the consequence of the pandemic in the progress of scientific research was bluntly felt.

What was it like at the start of the pandemic? How has your role evolved over the last several months?

The beginning of the pandemic was confusing, uncertain, and worrisome. None of us knew how long it would last, so we were focused on preserving the ongoing experiments. We were given notice of a few days to wrap up experiments. Some experiments are conducted over several months, especially with the mouse studies. The thought of losing extended time, and therefore, progress made over some months was a scary feeling.

However, institutions like MIT knew the stake at hand and became very proactive to preserve our work. They identified critical projects and let 5% of the workforce to return to labs. We rationed the time allocated to each lab. This ensured incremental progress on our work.

As the pandemic progressed, we also explored into COVID-19 work. I helped in developing a new RT-PCR test of SARS-CoV-2, which is currently licensed by a U.S. and a Japanese company.

In Nepal, in the 12 month period between Jan 30, 2020, and Jan 10, 2021, there have been 265,000 cases of COVID-19 infection (of which 258,000 have recovered) and 1912 deaths (0.7%). Keeping these figures in mind, how do you think Nepal has handled the pandemic?

I think Nepal handled the pandemic relatively well. There were weaknesses in terms of test numbers and contact tracing; nevertheless, despite being a nation with low-resource and severe lack of preparedness in all fronts, I believe the concerned officials genuinely tried their best to help. Whether their effort was adequate or not is a different question.

We also made a few mistakes along the way. We rolled out antibody tests way too earlier and deployed as diagnostic tool, which it is not. We were also unnecessarily entangled on the debate of accuracy of antigen tests. We failed to comprehend the usability of rapid antigen tests. I am a strong proponent of antigen-tests for symptomatic patients, but some of our colleagues complicated the usability of antigen tests which were widely used by other nations.

I believe our effort should not be judged on how we handled this pandemic—most nations in the world were caught off guard—but how we will prepare for future pandemics.

What is CRISPR technology, and how would CRISPR SARS-CoV-2 kit help Nepal?

CRISPR is a molecular scissor with wide application. CRISPR SARS-CoV-2 kit leverages the unique property of Cas13a enzyme, which is the collateral cleavage of RNA once the Cas13a/guide-RNA complex finds its target.

This technology is uniquely suited in Nepal for several reasons. It is cheaper and faster than RT-PCR despite both methods detecting viral RNA with similar sensitivity and specificity. More importantly, it can be used in mass surveillance at airports or ground crossings, as one plate reader takes 10 minutes to read 190 patient samples, or in remote areas and point-of-care without the need of large equipment.

Please tell us about your association with Sherlock Biosciences’ 221b Foundation.

I am not associated with Sherlock Biosciences’ 221b Foundation. We wrote a grant to Open Philanthropy Project, which was awarded to Sherlock Biosciences’ 221b Foundation for administration.

What is the purpose of your visit this time?

We wanted to introduce the CRISPR SARS-CoV-2 testing strategy in Nepal. There are new variants circulating in the world, which are much more transmissible. We have also become complacent in testing and don’t know the extent of COVID-19 spread at the community-wide scale. Increasing the testing capacity using CRISPR SARSCoV- 2 kits would help us understand and plan a national strategy to combat the pandemic.

Any clue about when Nepal may start vaccinating and which vaccine is the most suitable for us?

I don’t have expertise in vaccines and national policy in vaccination. However, I do think that AstraZeneca’s vaccine manufactured in India might be a suitable candidate for Nepal in terms of price and logistics. The Johnson & Johnson vaccine, once it is approved, might be the best option for us as it only requires one dose compared to two doses common with currently available vaccines.

Nevertheless, it is important to understand the power of RNA vaccines for future. Although it is expensive currently, and its price may come down in future, it can be manufactured rapidly as shown by Pfizer-BionTech and Moderna vaccines. More importantly, I believe that mRNA vaccines will enable a single vaccination for multiple diseases. A long mRNA that codes for several proteins from pathogens, such as measles, malaria, rubella, TB, etc., can be the future of vaccination, which makes the vaccination drive less tedious and more efficient.

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