Through the social and economic disruption that COVID-19 caused in 2020, the biomedical research community rose to the challenge and accomplished unprecedented feats of scientific acumen. With a new year ahead of us, even as the pandemic grinds on, we at The Scientist thought it was an opportune time to ask what might be on the life science innovation radar for 2021 and beyond. We tapped three members of the independent judging panel that helped name our Top 10 Innovations of 2020 to share their thoughts (via email) on the year ahead.

Paul Blainey: Value is shifting from the impact of individual technologies (mass spectrometry, cloning, sequencing, PCR, induced pluripotent stem cells, next generation sequencing, genome editing, etc.) to impact across technologies. In 2021, I think researchers will increasingly leverage multiple technologies together in order to generate new insights, as well as become more technology-agnostic as multiple technologies present plausible paths toward research goals.

Kim Kamdar: Partially in reaction to the COVID-19 pandemic, one 2021 headline will be the continued innovation focused on consumerization of healthcare, which is redefining how consumers engage with providers across each stage of care. Consumers are even selective about their healthcare choices now, and the retail powerhouses like CVS and Walmart have and will continue to develop solutions to meet the needs of their customers. While this was already underway prior to the pandemic, the crisis has spurred on this activity with the goal of making healthcare more accessible and affordable and ultimately delivering on better health outcomes for all Americans.

Robert Meagher: I think this is easymRNA delivery. This is something that has been in development for years for numerous applications, but the successful development and FDA emergency use authorization of two COVID-19 vaccines based on this technology shines a very bright spotlight on this technology. The vaccine trials and now widespread use of the vaccines will give developers a lot of data about the technology, and sets a baseline for understanding safety and side effects when considering future therapeutic applications outside of infectious disease.

PB:Single-cell technology is here to stay, although its use will continue to change. One analogy to be drawn is the shift we saw from the popularity ofde novo genome sequencing (during the human genome project and the early part of the NGS [next-generation sequencing] era to the rich array of re-sequencing applications practiced today. I expect new ways to use single-cell technology will continue to be discovered for some time to come.

KK: Innovation in single-cell technology has the potential to transform biological research driving to a level of resolution that provides a more nuanced picture of complex biology. Cost has been a key barrier for broader adoption of single-cell analysis. As better technology is developed, cost will be reduced and there will be an explosion in single-cell research. This dynamic will also allow for broader adoption of single-cell technology from translational research to clinical applications particularly in oncology and immunology.

RM: Yesthere is continuing innovation in this space, and room for continued innovation. One area that we have seen development recently, and I see it continuing, is to study single cells not just in isolation, but coupled with spatial information: understanding single cells and their interactions with their neighbors. I also wonder if the COVID-19 pandemic will spur increased interest in applying single-cell techniques to problems in infectious disease, immunology, and microbiology. A lot of the existing methods for single-cell RNA analysis (for example) work well for human or mammalian cells, but dont work for bacteria or viruses.

PB: The promises of CRISPR and gene editing are extraordinary. I cant wait to see how that field continues to develop.

KK: Much of the CRISPR technology focus since it was unveiled in 2012 has been on its utility to modify genes in human cells with the goal of treating genetic disease. More recently, scientists have shown the potential of using the CRISPR gene-editing technology for treatment of viral disease (essentially a programmable anti-viral that could be used to treat diseases like HIV, HBV, SARS, etc. . . .). These findings, published in Nature Communications, showed that CRISPR can be used to eliminate simian immunodeficiency virus (SIV) in rhesus macaque monkeys. If replicated in humans, in studies that will be initiated this year, CRISPR could be utilized to address HIV/AIDS and potentially make a major impact by moving a chronic disease to one with a functional cure.

PB: New therapeutic modalities that expand the addressable set of diseases are particularly exciting. Cell-based therapies offer versatile platforms for biological engineering that leverage the power of human biology. It is also encouraging to see somatic cell genome editing technology advance toward the clinic for the treatment of serious diseases.

The level of innovation that occurred in 2020 to combat COVID-19 will provide a more rapid, focused, and actionable reaction to future pandemics.

Kim Kamdar, Domain Associates

RM: Besides the great success with mRNA-based vaccines that sets the stage for other clinical technologies based on mRNA delivery, the other area that is really in the spotlight this year is diagnostics. There are a lot of labs and companies, both small and large, that have some really innovative products and ideas for portable and point-of-care diagnostics. For a long time, this was often thought of in terms of a problem for the developing world, or resource-limited locations: think, for example, of diagnostics for neglected tropical diseases. But the COVID-19 pandemic and the associated need for diagnostic testing on a massive scale has caused us to rethink what resource-limited means, and to understand the challenge posed by bottlenecks in supply chains, skilled personnel, and high-complexity laboratory facility. There has been a lot of foundational research over the past couple of decades in rapid, portable, easy-to-use diagnostics, but translating these to clinically useful products often seemed to stall, I suspect for lack of a lucrative market for such tests. But we are now starting to see FDA [emergency use authorization for] home-based tests and other novel diagnostic technologies to address needs with the COVID-19 pandemic, and I suspect that this paves the way for these technologies to start being applied to other diagnostic testing needs.

PB: Seeing the suffering and destruction wrought by COVID-19, it is obvious that we need to be prepared with more extensive, equitable, and better-coordinated response plans going forward. While rapid vaccine development and testing were two bright spots last year, there are so many important areas that demand progress. As we learn about how important details become in a crisisno matter how small or mundanediagnostic technologies and the calibration of public health measures are two areas that merit major focus.

KK: The life science community response to the COVID-19 pandemic has already proven to be light-years ahead of previous responses particularly in areas such as vaccine development and diagnostics. It took more than a year to sequence the genome of the SARS virus in 2002. The COVID-19 genome was sequenced in under a month from the first case being identified. Scientists and clinicians were able to turn that initial information to multiple approved vaccines at a blazing speed. Utilizing messenger RNA (mRNA) as a new therapeutic modality for vaccine development has now been validated. Vaccine science has been forever changed. The pandemic has also focused a much-needed level of attention to diagnostics, forcing a rethink of how to increase access, affordability, and actionability of diagnostic testing. The level of innovation that occurred in 2020 to combat COVID-19 will provide a more rapid, fo
cused, and actionable reaction to future pandemics. In addition, the elevation of a science advisor (Dr. Eric Lander) to a cabinet level position in the Biden administration bodes well for our future ability to ground in data and as President Biden himself framed, refresh and reinvigorate our national science and technology strategy to set us on a strong course for the next 75 years, so that our children and grandchildren may inhabit a healthier, safer, more just, peaceful, and prosperous world.

RM: One thing that really kick-started research to address COVID-19 was the early availability of the complete genome sequence of the SARS-CoV-2 virus, and the ongoing timely deposition of new sequences in nearreal-time as isolates were sequenced. This is in contrast to cases where deposition of large number of sequences may lag an outbreak by months or even years. I foresee the nearreal-time sharing of sequence information to become the new standard. Making the virus itself widely and inexpensively available, in inactivated form, as well as well-characterized synthetic viral RNA standards and proteins also helped spur research.

A trend Im less fond of is the rapid publication of nonpeer reviewed results as preprints online. Theres a great benefit to getting new information out to the community ASAP, but unfortunately I think the rush to get preprints up in some cases results in spreading misleading information. This problem is compounded with uncritical, breathless press releases accompanying the posting of preprints, as opposed to waiting for peer-review acceptance of a manuscript to issue a press release. I think the solution may lie in journals considering innovative approaches to speeding up peer review, or a way to at least perform a basic check for rigor prior to posting a preliminary version of the manuscript. Right now the extremes are: post an unreviewed preprint, or wait months or even years with multiple rounds of peer review including extensive additional experiments to satisfy the curiosity of multiple reviewers for high impact publications. Is there a way to prevent manuscripts from being published as preprints with obvious methodological errors or errors in statistical analysis, while also enabling interesting, well-done yet not fully polished manuscripts to be available to the community?

Paul Blaineyis an associate professor of biological engineering at MIT and a core member of the Broad Institute of MIT and Harvard University. The Blainey lab integrates new microfluidic, optical, molecular, and computational tools for application in biology and medicine. The group emphasizes quantitative single-cell and single-molecule approaches, aiming to enable studies that generate data with the power to reveal the workings of natural and engineered biological systems across a range of scales. Blainey has a financial interest in several companies that develop and/or apply life science technologies: 10X Genomics, GALT, Celsius Therapeutics, Next Generation Diagnostics, Cache DNA, and Concerto Biosciences.

Kim Kamdaris managing partner at Domain Associates, a healthcare-focused venture fund creating and investing in biopharma, device, and diagnostic companies. She began her career as a scientist and pursued drug-discovery research at Novartis/Syngenta for nine years.

Robert Meagheris a principal member of Technical Staff at Sandia National Laboratories. His main research interest is the development of novel techniques and devices for nucleic acid analysis, particularly applied to problems in infectious disease, biodefense, and microbial communities. Most recently this has led to approaches for simplified molecular diagnostics for emerging viral pathogens that are suitable for use at the point of need or in the developing world. Meaghers comments represent his professional opinion but do not necessarily represent the views of the US Department of Energy or the United States government.

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Experts Predict the Hottest Life Science Tech in 2021 and Beyond - The Scientist