New technology lets scientists 'scan' human genes much faster Technique developed at Hopkins gives better picture of interaction

October 20, 1995|By JONATHAN BOR | JONATHAN BOR,SUN STAFF

Comparing their invention to a bar-code scanner at a grocery store, scientists at the Johns Hopkins Oncology Center have developed a new method to rapidly detect genes and measure their activity in cells.

The technology -- which melds new computer software, new techniques and equipment already found in advanced laboratories -- can scan about 1,000 genes in a few hours, gathering information that might otherwise take years to collect.

Dr. Kenneth W. Kinzler, an oncologist who co-directed the project, said the technology is a research tool that should give scientists a sophisticated view of how genes interact in cells to cause and fight disease -- or create specialized organs and tissues.

It should reveal, for instance, the precise differences between liver cells and pancreatic cells -- or healthy cells and cancerous ones.

There are about 150,000 genes in each cell, but only about a third of them are active in a given cell.

The combinations that are active account for the differences between cells and, for that matter, between tissues in various parts of the body.

Scientists across the world have identified and mapped about half the genes that define a person.

Technology, however, has limited them to studying one gene at a time -- rather than the actions of many working together.

"This gives you the chance to compare lots of genes at once instead of just one gene," Dr. Kinzler said of his new technology. "It's a more dynamic picture, a bigger picture."

"The way a lot of science is done today is to look at one gene at a time for its change and expression," said Dr. Jeffrey Trent, scientific director of the National Center for Human Genome Research.

"That's not really the way we should be looking at it. We should be looking at it as a whole.

"This [technology] will allow us to look at collections of genes that are turned on -- what's on together, what's off together."

A description of the technology, called SAGE, appears in this week's edition of the journal Science.

The acronym stands for serial analysis of gene expression.

The lead authors are Dr. Kinzler and Dr. Bert Vogelstein, a leading cancer researcher known for major insights into the genetics of colon cancer.

The Hopkins Oncology Center has applied for a patent and licensed the techniques to a biotechnology company, PharmaGenics Inc. of Allendale, N.J.

The scientists expect that pharmaceutical companies may be interested, since many are trying to gain insights into the genetics of disease.

Genes are made of thousands of "base pairs" -- couplings of molecules that are strung along the double helix of DNA.

The new technology works on the premise that each gene can be identified by recognizing just nine or 10 pairs that make a gene unique.

They amount to a kind of cellular bar-code, a unique identifier that is similar to stripes used by retailers to distinguish one product from another.

Extending the analogy, Dr. Kinzler noted that stores use bar codes not only to link a product with its price, but also to count the number of times a product has been purchased on a given day.

Similarly, SAGE counts the number of times a gene copies itself -- an indication of whether a gene is active inside a cell, and how much so.

SAGE is not a single device but a combination of new techniques and computer software developed by the Hopkins team.

It also makes use of a machine called an automated sequencer, hardware already used by many scientists to analyze genes.

One of its immediate uses will be to gain a deeper understanding of cancer.

"We're interested in identifying genes that have different activity in cancer tissue vs. normal tissue," Dr. Kinzler said.

"Once we identify those genes, our next step is to identify what their function is in the cancer cell vs. the normal cell."

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