All Together Now
BY MAUREEN McCANN, ASPB President, National Renewable Energy Laboratory
It’s a rare experience to sit for an hour on the second level of a parking garage with a growing sense of elation. This morning, I drove my husband Nick for his first shot of vaccine against SARS-CoV2. We sat in the queue of cars and thought of all the families that, in that single hour, shared the overwhelming relief of a family member protected, the feeling of community with strangers.
No surprise that Science’s Breakthrough of the Year 2020 is the development of multiple safe and effective vaccines against COVID (Cohen, 2020). Thirty years ago, protein expression was demonstrated from direct injection of RNA constructs in mouse muscles (Wolff et al., 1990). A new field of investigation into RNA-based vaccines emerged, and in one example, a paper was published demonstrating that mRNA technology for antigens of pathogens causing lethal Ebola, H1N1 influenza, and Toxoplasma gondii could be used to elicit an effective immune response with a single dose (Chahal et al., 2016). Both Pfizer and Moderna vaccines are based on structural analyses of coronavirus surface proteins that identified two critical amino acids in the spike protein that, if mutated, would stabilize the structure in the pre-fusion conformation that is recognized by human antibodies. Innovations in delivery mechanisms were critical to protect the mRNA inside fat droplets for its passage from needle tip into human cells. Other vaccine developers have adopted more traditional pathways using attenuated strains or recombinant spike protein presented on the surface of other viruses.
However, the mRNA-based vaccines are a new wave of technology with the potential for very rapid adjustment to new strains of SARS-CoV2 as they arise, and now with demonstrated efficacy in human populations. Although the Pfizer vaccine requires ultra-low-temperature freezers to preserve it, the Moderna vaccine is stable if refrigerated, suggesting that further innovation could overcome the requirement for specialized infrastructure. Beyond the current pandemic, there is huge potential for the application of mRNA-based vaccines to tackle a whole range of infectious diseases in both developed and developing countries. The speed of transition from genome sequence to shots in arms inside a year seems breathtaking, but it was powered by long-term research investment in fundamental biology.
The sense of community felt in a parking garage with our fellow citizens can be amplified a hundredfold within the global community of science. Some of you used your own expertise as biologists to work on improved diagnostic tests or the design of face masks; others contributed supplies and lab equipment to friends and colleagues working in the area of infectious disease. High-performance computing and synchrotron sources were used to solve crystal structures of SARS-CoV2 genome-encoded proteins and to identify drug targets for therapeutics. For biologists, this is a moment to be proud.
It is also a moment to reflect on our past and future impact as plant biologists in the area of human health. I remember being inspired in the 1980s by the work of the Arntzen lab in developing edible plant vaccines for childhood diseases using bananas as the delivery system (Arntzen, 2015). Synthetic production of the antimalarial artemisinin depended on isolation of the active compound from Artemisia annua by Nobel prize winner Youyou Tu and elucidation of its biosynthetic pathway (Chang et al., 2007). A decade ago, the anti-Ebola vaccine ZMapp used recombinant antibodies produced in tobacco plants (Qiu et al., 2014). And more recently, in partnership with GlaxoSmithKline, the biopharmaceutical company Medicago announced the start of Phase 3 clinical testing of their COVID-19 vaccine candidate, made by expressing spike protein in virus-like particles that can be harvested from tobacco plants (Medicago, 2021). These are just a few examples of how plant metabolic complexity and plasticity have enriched the arsenal of drugs and enabled new production platforms.
A decade has passed since an era of precision medicine was jointly declared by the U.S. National Academy of Science, National Academy of Engineering, National Institutes of Health, and National Science Foundation as it became possible to probe the interactions among genes, the environment, and lifestyle. The pandemic has highlighted the deep divide in health outcomes by race, income level, and geography. Only policy changes can address the underlying inequalities that give rise to these divides. However, we can consider how our research might enable access to nutritious and affordable food as a tool in disease prevention, and to new medicines in disease treatment. With sharper tools in our tool kit, we can begin to dissect the gene–gene and gene–environment interactions among humans, the plants we consume, and human microbiomes. We can amplify products from natural pathways in plants, and we can develop synthetic and semisynthetic pathways in plants or using plant genes in microbial chassis. Let’s engage in a conversation at the intersection of plant biology, precision medicine, and ways to develop plant-based technologies with accessibility and equity at front of mind.
This year we were forced to confront the nature of our connections with one another, as scientists and as global citizens. As the silos isolating disciplines of the life sciences continue to dissolve, I hope that we continue to use our training as plant biologists to contribute to research focused on human health and disease as biologists specialized in plants. I hope that we can tackle the planetary challenge of climate change with the same urgency and teamwork that was brought to bear on a tiny virus. I never want to forget that feeling of elation, sitting in a parking garage, separated in our cars and yet all together.
Arntzen, C. (2015). Plant-made pharmaceuticals: From ‘edible vaccines’ to Ebola therapeutics. Plant Biotechnology Journal 13: 1013–1016. https://doi.org/10.1111/pbi.12460
Chahal, J. S., Khan, O. F., Cooper, C. L., et al. (2016). Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. PNAS 113: E4133–E4142. https://doi.org/10.1073/pnas.1600299113
Chang, M. C. Y., Eachus, R. A., Trieu, W., et al. (2007). Engineering Escherichia coli for production of functionalized terpenoids using plant P450s. Nature Chemical Biology 3: 274–277. https://doi.org/10.1038/nchembio875
Cohen, J. (2020). Shots of hope. Science 370: 1392–1394. https://doi.org/10.1126/science.370.6523.1392
Medicago. (2021). Medicago and GSK start Phase 3 trial of adjuvanted Covid-19 vaccine candidate (Press release). https://www.medicago.com/en/media-room/medicago-and-gsk-start-phase-3-trial-of-adjuvanted-covid-19-vaccine-candidate/
Qiu, X., Wong, G., Audet, J., et al. (2014). Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514: 47–53. https://doi.org/10.1038/nature13777
Wolff, J. A., Malone, R. W., Williams, P., et al. (1990). Direct gene transfer into mouse muscle in vivo. Science 23: 1465–1468. https://doi.org/10.1126/science.1690918