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CRISPR, the Future of Life Science Research But Still Much to Learn

Building a scientific framework that distills the rules of life is a challenge scientists are now tackling. This is leading to an exciting array of projects that will lead to breakthroughs in such things as treating diseases and in understanding aging.

Science seeks to explain the world around us, and the most satisfactory explanations are those that allow us to predict as yet unknown phenomena. Mendeleev not only explained patterns in the properties of atomic elements, he also correctly predicted the existence of eight more elements. In addition to being intellectually satisfying, prediction moves science into the realm of technology, which enables reliable, robust applications.

Predictive models in biology are often built on observations, from Mendel inferring the laws of inheritance from his experiments breeding peas and Darwin postulating the theory of evolution from his detailed surveys of flora and fauna to Franklin, Watson and Crick which ultimately revealed the structure of DNA and its double helical structure. Despite these and many other significant advances, however, it remains challenging to distill the rules of life into a complete framework of operating principles.

Today, thanks to a combination of novel technologies and growing scientific insights, scientists are now tackling precisely this challenge. Many large-scale projects aimed at observing life at high-resolution and comprehensive sweep are underway, including:

Feng Zhang is the 2017 winner of the $500,000 Lemelson-MIT Prize, which honors mid-career inventors dedicated to improving the world through outstanding technological invention. He is a core member of the Broad Institute of MIT and Harvard, an investigator at the McGovern Institute for Brain Research, James and Patricia Poitras Professor in Neuroscience at MIT, and associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT. Zhang is a pioneer of the revolutionary CRISPR gene editing technology who has received numerous awards for his work. He plans to use a portion of the Lemelson-MIT Prize money to support STEM education and innovation programs that develop and excite interest in science and engineering among middle and high school students.

• 1,000 Genomes Project, which aims to create a comprehensive database of human genetic variation – the small changes to our DNA that make each of us unique;
• Human Cell Atlas, a global project to map every cell type in the body, an endeavor which will be enormously helpful for connecting the genomic DNA blueprint to the actual structures built by these plans;
• Brain Connectome, which seeks to describe the complete wiring diagram of the human brain, allowing researchers to chart the ways our brains process and connect information.

Data and findings from these and many other projects help researchers to elucidate mechanisms of complex biological processes such as diseases and aging.

These projects highlight the depth of observation biologists are now capable of, accelerating the pace with which we are able to study the breadth of the natural biological diversity. Curiosity-driven research has unexpectedly led to many transformative technologies and applications. Indeed, some of the most powerful tools for biological research have resulted from basic curiosity-led discoveries and have been harnessed from nature. Restriction enzymes, which were gathered from bacteria, launched the era of molecular biology and made possible the production of human insulin using bacteria. A more recent example of which is the development of microbial adaptive immune systems, CRISPR, for gene editing. These naturally occurring systems help microbes defend themselves from invading viruses using an elegant mechanism that has been studied by microbiologists for more than twenty years. In recent years, components of CRISPR systems, such as Cas9, have been harnessed for use in human cells and are now accelerating development in the fields of human therapeutics, agriculture, and scientific research around the world. Although we have only explored the tip of the biological diversity iceberg, it is clear that some organisms have developed novel solutions to biological problems, and there is much to be gained by studying these unusual mechanisms.

The rapid development of new molecular tools is also reciprocally broadening our ability to study the breadth of natural diversity. For nearly a century, much of life science research has been performed using a handful of organisms, chosen for their suitability for laboratory work. The rapidly expanding molecular toolbox can now be applied much more widely, opening access to myriad new species, from salamanders with unique regenerative capabilities to natural strains of crops that are resistant to drought. Moreover, scientists can now choose to study their specific questions using the most suitable model systems rather than being limited to a handful of laboratory strains that are limited in their ability to model human diseases.

Together, these two modes of observation are fueling a boom in biotechnology. Data from in-depth observations of the human genome are being used to inform the design and development of therapeutics while broad surveys of microbial communities are identifying new enzymes with biotechnological applications.

Given all of these exciting developments in life science research and biotechnology, it is even more important than ever to provide training and mentoring opportunities for students interested in science and engineering, especially students from diverse backgrounds. I am deeply indebted to the numerous mentors and educational experiences in science and engineering that I have been so fortunate to learn from in my own education. I will use some of the Lemelson-MIT Prize money to support STEM education and innovation, including supporting organizations, such as the Center for Excellence in Education and the Society for Science and the Public, which have sponsored programs that have played important roles in helping middle and high school students develop and celebrate their interests in science and engineering. It is an exciting time in biology and there is so much more we can do to nurture the next generation of scientists and engineers who will create new transformative technologies that will solve the numerous important challenges that face the world today.

Feng Zhang is the 2017 winner of the $500,000 Lemelson-MIT Prize, which honors mid-career inventors dedicated to improving the world through outstanding technological invention. He is a core member of the Broad Institute of MIT and Harvard

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