Exploring organisms cell by cell

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Science  21 Dec 2018:
Vol. 362, Issue 6421, pp. 1333
DOI: 10.1126/science.aaw3633

In an imaginary universe, you have discovered a set of planets, each with its own complex civilization with many culturally distinct nations. You face the daunting task of exploring each planet, mapping national boundaries, and characterizing different cultural features. In discussing this challenge with your colleagues, you come up with an alternative plan. You can divide each planet into small sectors, tag each sector for identification, send out many small probes to land in random locations and send back data, and then use the tagging information to computationally assemble the information into detailed atlases and travel guides. Science's Breakthrough of the Year recognizes the application of this tag-analyze-assemble approach to one of the most fundamental and fascinating processes in biology—the seemingly miraculous transformation of single cells into complex organisms—providing rich information about cell-type inventories and laying the foundation for many future studies.

A zebrafish embryo, 30 hours postfertilization, reveals descendants (fluorescently labeled) of cells that were transplanted 22 hours earlier.


This achievement builds on the 2002 Nobel Prize–winning work of John Sulston and colleagues who had mapped the development of the roundworm Caenorhabditis elegans by painstakingly watching larvae mature cell by cell through microscopes. This revealed the sequence of cell divisions that resulted in elaborate structures, which led to the characterization of important processes. With today's technologies, especially massively parallel DNA sequencing and advanced fluorescence microscopy, the cells that comprise C. elegans have been mapped again using tag-analyze-assemble methods based on gene expression patterns within each cell. The same approaches have been used to map the cellular anatomy of organisms of increasing complexity and size. An additional benefit is that the gene expression signals that define each cell type also provide fundamental information about the biochemistry and biology of each cell. The large and rich datasets that have been generated, and the techniques that will produce more, constitute exciting breakthroughs in developmental biology.

Nucleic acid–based technologies also underlie some of this year's runners-up, including advanced methods in forensics that combine sequence and other databases, elucidation of the breeding habits of earlier hominids, and long-awaited advances in RNA-based therapies. A range of technologies has also led to important conceptual advances in the organizational principles within cells. Technologies that elucidated large biological molecular structures have been applied to smaller molecules, resulting in a remarkable advance in analytical chemistry. Exploration has revealed insights into the ancient history of our planet. Strange lifeforms, known from fossils hundreds of millions of years old, now appear to be ancestors of modern animals rather than lines that went extinct. A crater discovered under the ice in Greenland likely resulted from a large meteorite impact. One source of other cosmic visitors, high-energy neutrinos, has been found to be types of galaxies with a massive black hole at their centers.

Other events have highlighted cultural issues. The #MeTooSTEM movement has brought much needed attention to sexual harassment within the scientific community. Further progress is essential to allow individuals of all genders to pursue their training and careers without dealing with the realities of substantially unchecked harassment. The announcement of the birth of babies with genomes that had been intentionally modified in a manner that appears to violate many long-standing ethical principles reminds us that scientific results, no matter how exciting and full of potential, must be applied with appropriate care and respect for ethical international norms. Finally, we are challenged by the changing climate of our own planet. Powerful storms associated with large amounts of rainfall and other events are occurring with increasing frequency, illustrating the considerable urgency for appropriate actions. We must work together across global borders and cultures to drive effective steps to arrest harmful climate change.

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