Are Genes Destined To Become The Genies Of The Future?

Not too long ago it was unimaginable that we might be able to see within the body without surgery, or view tiny structures such as miniscule cell organelles or molecular components like atoms. Today we are reaching into the vastness of outer space and the minuteness of inner space. Confocal microscopes permit us to see the intricate structures of the cell as a three-dimensional image. Anyone who watches TV or reads newspapers is aware that our genes are under intense investigation by scientists all over the world. Enterprising companies seem to spring up daily with an eye to making a profit from this burgeoning new industry. Several articles on some intriguing progress in genomics appeared in the January 8, 2003 issue of JAMA. I will attempt to review the meat of two related articles in this discussion.

Brian Vastag wrote about a new invention, made about 5 years ago, called gene chips or DNA microarrays in his presentation "Gene Chips Inch Toward the Clinic." These "chips" measure the level of a relative of DNA called RNA. By measuring levels of messenger RNA in a cell, the researcher is able to analyze which genes are active or quiescent. The result provides a way to determine the normal, or abnormal activity of a cell. This can lead to such advances as an ability to predict the likelihood of an early cancer to metastasize later, or even whether chemotherapy will work. A team from the Whitehead Institute-Massachusetts Institute of Technology Center for Genome Research reported just this sort of capability. They managed to identify a gene expression signature in several cancers that become metastatic leading to early death. There are 16000 genes on the chips. Of these, a set of 128 best signaled whether a tumor was primary or metastatic. However, careful study of the data enabled the researchers to locate 17 of the genes that could predict just about as well as the 128. If all goes well, Ramaswamy, an oncologist at Dana Farber Cancer Institute involved in the study, says, "… you can imagine having some kind of generic tool to look for whether a cancer is going to metastasize or not." However, he cautions that it will be years before this technique might be available for everyday clinical use.

Similar work has resulted in a "lymphochip" for predicting response to chemotherapy when treating patients with diffuse large B-cell lymphoma. Researchers at several centers, including the National Cancer Institute, are involved in this work. All this is excellent, but there is a growing problem of too little cooperation between the various centers studying microarray analysis with regard to organizing the data so that it is understandable to all. Each center tends to utilize its own individual technique and data language because there are too many factors that can disturb tissue samples, leading to unique solutions, and specific coding language by each center. Efforts are now underway to standardize these procedures.

Vastag followed his first article with a brief exposé about the subject of genetic microarrays by John Quackenbush, PhD, obtained when reporters visited him at The Institute for Genomic Research. He described the gene chips as postage-sized glass slides on which two robots print tens of thousands of gene fragments. The object is to cram as much information onto each chip so that you can "mine the hell out of the data." Cancer predictability is not the only capability envisioned. For example, it may be possible to determine when heart muscle is starved for oxygen. Over the long run, the hope is that we can eventually piece all the information together into one large web of pathways, which will permit us to sort out and utilize the information for clinical use.

Yes, the gene is definitely out of the bottle. Whether this intriguing new science will eventually bestow magical benefits similar to the granted wishes of mythological genies, awaits the future. Let us hope that it won't take too long.

Cram 'em, squeeze 'em, push 'em in, No matter if they're thick or thin. The more we've got, the more we learn, The harder we work, the more we earn. So cram 'em, squeeze 'em, push 'em in, There's plenty of room on the head of a pin. Then some day soon the world will know, And when we win our fame will grow.