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Myriam Kirkman-Oh
A computational method enables rapid analysis of the blocklike pattern of genetic variation in the mouse genome, which can be used in analyzing mouse models of human disease. The cover stories in the journal Science explore new approaches to understanding how genes are expressed and how they function.
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Science
updated 10/21/2004 8:05:57 PM ET 2004-10-22T00:05:57

Ten or 20 years from now, a droplet of blood may be all your doctor needs to catch a cancer in its earliest stages. That droplet could also reveal which genetic diseases you might develop later in life and which medicines, tailored to your genetic makeup, are right for you.

This vision of medicine comes from genomics pioneer Leroy Hood, courtesy of a sizzling new field called “systems biology.” Hood, who recently founded the Institute for Systems Biology in Seattle, also helped invent the automated gene sequencer and several other technologies that made sequencing the human genome possible.

Writing in Friday’s issue of the journal Science — published by AAAS, the nonprofit science society — Hood describes the medical transformations that he thinks are imminent.

Predictive, preventive, personalized
Hood believes that in 10 to 20 years medicine’s focus will have shifted away from treating existing diseases, typically late in their progression, to preventing disease before it sets in.

Our individual genome sequences, or at least sections of them, may be part of our medical files, and routine blood tests will involve thousands of measurements to test for various diseases and genetic predispositions to other conditions.

Find out how scientists decode our DNA“I’ll guarantee you we’ll see this predictive medicine in 10 years or so,” Hood said.

The next transition he envisions will affect drug research and will involve extensive maps of the molecular interactions in the body that lead to disease. These maps are now emerging from the systems biology laboratories that have sprung up in recent years.

Before long, drug companies may be able to target specific spots on these maps with new therapies. This approach should make drug research less expensive, Hood said, allowing companies to design drugs for less common diseases.

Further into the future, medicine will become personalized, with therapies that match patients’ genetic makeups, according to Hood.

“If you bring in predictive medicine, each of us will have to be treated differently, since we’re all different in our DNA. That’s going to be an enormous revolution in medicine,” Hood said.

This development won’t happen quickly, however, and issues of cost and confidentiality will need to be resolved in the process. Nonetheless, Hood believes the potential benefits of personalized medicine will make the transformation worthwhile.

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This trend will have implications for “how physicians are trained and how you explain this new kind of medicine to the public, and it will certainly change in many fundamental ways the health care industry, including insurance,” Hood said.

Parts of a whole
What will make this medical revolution possible, according to Hood, is systems biology. This discipline, which is actually a blend of biology, computing and micro/nanotechnology, tries to understand the behavior of a “whole,” such as the human body, in terms of the interactions among its parts — its genes, proteins and other molecules.

Browse our dictionary of genetic termsThe appeal of this approach is that each part of the system is ultimately “knowable,” as Hood puts it. Though disease as a whole can bewilder and exasperate, looking at the problem in terms of its parts makes the potential causes more concrete. The number of genes or proteins in our cells may be large, but it’s finite.

“At the heart of systems biology is this idea that you want to identify the elements of a system and measure their interactions and relationships as you perturb the system,” Hood said.

This perturbation often takes the form of genetic engineering to “knock out” the expression of certain genes. Then scientists study how their tinkering has affected the health of the whole system.

In a classic experiment, Hood and his colleagues used this approach on yeast to map out all of the genes and proteins involved in one aspect of the organism’s metabolism. Another major study identified a 55-gene network in the sea urchin that controls development.

These efforts produce a mind-boggling amount of data, since each cell in our bodies contains many thousands of genes and proteins. Processing this information requires sophisticated computing and ultraefficient lab equipment that can quickly sort, test and analyze multitudes of single cells or molecules. The yeast metabolism study, for example, required approximately 100,000 measurements.

In the blood
So what does all this have to do with human health? Disease is a “perturbation” of the system by either genetic or environmental changes, or both, according to Hood.

Look into the future of geneticsOnce researchers have mapped out the full network of genes or proteins that interact in a certain type of tissue, they can tweak pieces of the network in different samples and compare the results. Ultimately, these sorts of experiments may turn up molecular changes involved in cancer, inflammation or any number of other conditions.

In many cases, these changes may include proteins that cells secrete into the bloodstream, which is where Hood’s idea of a blood test for cancer comes in.

For example, he and his colleagues recently compared several types of prostate tissues, some healthy, some with early-stage cancer and some with late-stage cancer, and cataloged the differences in gene expression among the three types.

The cancerous tissues had different genetic “signatures” that involved, in part, proteins that circulate in the blood. The researchers then developed a test to measure one of these proteins. Such a test could be a useful complement to the existing prostate-specific antigen or “PSA” tests currently used to test for prostate cancer, according to Hood.

Dealing with a data deluge
Developing more tests like this one depends on continued progress on several different fronts. While biologists have been feverishly trying to identify the genes and other elements in the human genome, other researchers must develop the technology and methods for collecting and analyzing ever-larger amounts of information.

Storing this data deluge in a way that scientists can share is another pressing challenge. The Signal Transduction Knowledge Environment maintained by Science is one example of an expanding database for this purpose.

“There will be enormous scientific and engineering challenges to achieve this vision — far greater than those associated with the Human Genome Project. Predictive, preventive and personalized medicine will transform science, industry, education and society in ways that we are only beginning to imagine,” Hood and his colleagues write in their Science article.

© 2013 American Association for the Advancement of Science

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