Human genome at ten: Life is complicated.

Abstract

ered by many to be a simple science, a pursuit of expedition, observation and experimentation. At the dawn of the twentieth century, while Albert Einstein and Max Planck were writing mathematical equations that distilled the fundamental physics of the Universe, a biologist was winning the Nobel prize for describing how to make dogs drool on command. The molecular revolution that dawned with the discovery of the structure of DNA in 1953 changed all that, making biology more quantitative and respectable, and promising to unravel the mysteries behind everything from evolution to disease origins. The human genome sequence, drafted ten years ago, promised to go even further, helping scientists trace ancestry, decipher the marks of evolution and find the molecular underpinnings of disease, guiding the way to more accurate diagnosis and targeted, personalized treatments. The genome promised to lay bare the blueprint of human biology. That hasn’t happened, of course, at least not yet. In some respects, sequencing has provided clarification. Before the Human Genome Project began, biologists guessed that the genome could contain as many as 100,000 genes that code for proteins. The true number, it turns out, is closer to 21,000, and biologists now know what many of those genes are. But at the same time, the genome sequence did what biological discoveries have done for decades. It opened the door to a vast labyrinth of new questions. Few predicted, for example, that sequencing the genome would undermine the primacy of genes by unveiling whole new classes of elements — sequences that make RNA or have a regulatory role without coding for proteins. Non-coding DNA is crucial to biology, yet knowing that it is there hasn’t made it any easier to understand what it does. “We fooled ourselves into thinking the genome was going to be a transparent blueprint, but it’s not,” says Mel Greaves, a cell biologist at the Institute of Cancer Research in Sutton, UK. Instead, as sequencing and other new technologies spew forth data, the complexity of biology has seemed to grow by orders of magnitude. Delving into it has been like zooming into a Mandelbrot set — a space that is determined by a simple equation, but that reveals ever more intricate patterns as one peers closer at its boundary. With the ability to access or assay almost any bit of information, biologists are now struggling with a very big question: can one ever truly know an organism — or even a cell, an organelle or a molecular pathway — down to the finest level of detail? Imagine a perfect knowledge of inputs, outputs and the myriad interacting variables, enabling a predictive model. How tantalizing this notion is depends somewhat on the scientist; some say it is enough to understand the basic principles that govern life, whereas others are compelled to reach for an answer to the next question, unfazed by the ever increasing intricacies. “It seems like we’re climbing a mountain that keeps getting higher and higher,” says Jennifer Doudna, a biochemist at the University of California, Berkeley. “The more we know, the more we realize there is to know.”

DOI: 10.1038/464664a
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@article{Hayden2010HumanGA, title={Human genome at ten: Life is complicated.}, author={Erika Check Hayden}, journal={Nature}, year={2010}, volume={464 7289}, pages={664-7} }