New Frontiers of Biology
By Karen Hopkin

On a factory floor in Cambridge, Massachusetts, a few laboratory robots pick bacterial clones off supersize petri plates. Each clone contains a fragment of foreign DNA—genetic material from a human or a mouse. The robots feed these clones into an assembly line, where the DNA is purified, processed, and loaded onto automated sequencing machines. Operating around the clock, these machines can churn out roughly 50 million letters of raw DNA sequence per day. A technician wanders by when the sequencers run low on reagents or the robots need fresh plates.

Biology has entered its industrial age. In just 15 months, the Whitehead/MIT Center for Genome Research—which is located in a warehouse that once stored popcorn and beer—produced more than one billion letters of the 3.2-billion-letter human genome sequence.

This industrial revolution has turned biology into an information science. To manage and mine the mountains of data now being generated by DNA sequencing and analysis projects, biologists have had to collaborate with computer scientists to create databases to store this information and programs to search through it for the patterns that will reveal something meaningful about the way cells and organisms work.

More important, this information explosion is changing the way biological research is being done. Individual researchers can now accomplish years’ worth of work in a single morning. In Eric Lander’s laboratory, for example, postdoctoral fellow David Altshuler was searching for genes involved in diabetes. He found that a particular genetic variation—a small change in the nucleotide sequence—in a gene called PPAR-gamma appeared to show up more frequently in people with the disease. But does this variation cause diabetes? Perhaps some other variation in another part of the gene is more important.

In the past, Altshuler would have had to clone the gene, sequence it, collect variants from a large population, and compare those sequences. Instead, he simply logged on to the Web and found that several different labs had already sequenced that region of the human genome. One lab had even sequenced the corresponding segment of the mouse genome. By comparing these sequences, Altshuler was able to identify the regulatory regions of the gene, those that had been conserved throughout evolution. This database check allowed Altshuler to identify the DNA sequences he needed to focus on in his continued search for variations important in diabetes. With the information at hand, Altshuler accomplished approximately 15 years’ worth of work before lunch.

The accumulation of data and the development of information-age technologies not only are accelerating the pace of discovery but also are allowing biologists to take a broader perspective of how genes, and the proteins they encode, work together inside cells and organisms—and how their malfunction leads to disease. For example, using DNA microarrays, built from bits of sequenced genomes, researchers can now monitor the activity of hundreds or thousands of genes at once. Comparing these detailed genetic profiles, geneticists can classify different cancers and perhaps even predict what type of therapy would work best against a particular tumor.

Using similar large-scale approaches, scientists can also investigate the activities of hundreds or thousands of proteins at once. In Stuart Schreiber’s laboratory, researchers are generating millions of compounds that they can use to perturb the activity of proteins involved in many dynamic cellular processes, from the movement of chromosomes during cell division to the molecular events that drive the development of complex organs and even whole organisms. The small molecules used to dissect these biological systems may eventually provide new types of drugs for the treatment of human diseases, which arise when proteins function improperly—or not at all.

The ultimate goal of all these projects is to understand how genes and proteins work together to lay the foundation for life. Thanks in large part to the powerful new technologies developed over the past few years, we are closer than ever to persuading cells to reveal the molecular mechanisms that make life possible.

For biology, the revolution has just begun. Like astronomers with a new telescope, biologists are using their new instruments to make broad observations, to assemble a bigger picture of the universe that is the cell. But much detailed work remains to be done. Altshuler, for example, still had to examine PPAR-gamma sequences from several thousand individuals before he could confirm the genetic variation that was associated with an increased risk of diabetes. And if Schreiber and his colleagues were to isolate a compound that somehow blocks the uncontrolled proliferation of cancer cells, that molecule would have to be tested extensively in cultured cells, animals, and eventually humans before it could be considered an effective anticancer therapy.

In the closing moments of the 20th century, biologists made stunning progress in sequencing our genome and the genomes of dozens of other organisms. But the best is still to come. As we learn to decipher the information locked in these genomes, we will come closer to understanding life’s molecular secrets. And we stand poised to see how we fit in—each of us unique yet fundamentally related to every living thing on Earth.

© 2012 Howard Hughes Medical Institute. A philanthropy serving society through biomedical research and science education.
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