You say to-MAY-to, I say to-MAH-to! You say genetics, I say genomics!
Genomics is the hot new word in DNA circles, and it shows how much the field of genetics has changed in a decade.
It used to be simple: Genetics was about how traits--and diseases--are passed down from one generation to the next. Every family has its own lore about how you got your brown eyes from Mom--and your temper from Grandfather Harry. As the saying goes, it's in the genes!
But today, the story in the genes is much more complicated. Even the word "genetics" has a whiff of Old Think, an image of an old man in a garden of peas. Indeed, traditional genetics took a narrow, somewhat rigid view, looking at one gene at a time. In medicine, genetics usually meant focusing on rare diseases caused by a single defective gene.
Genomics is New Think. The term was coined about 10 years ago at Bar Harbor's Jackson Laboratory where scientists study mouse genetics as a window on human genetics. The word, made up from GENe and chromosOME, refers to the whole genetic blueprint that makes up a person--or a mouse or a worm or a fruit fly.
In genomics, researchers look at all the genes at once. A gene is a close-up--the genome is big picture. If genes were words, the genome would be a book.
"Genetics is the science of heredity. Genomics is the science of the heredity apparatus itself," says Kenneth Paigen, director of Jackson Laboratory. "The challenge is how to understand the enormous interaction [of genes] with respect to health and to disease."
Scientists not only have to identify genes (about 100,000 genes in a person) and locate their chromosomal addresses, but they must also determine what genes do at the molecular level and why they are significant. As physician Andrew Feinberg of Johns Hopkins University School of Medicine explains: "Most geneticists today do genomics."
At a conference here last week on the future of gene studies, researchers expanded the lexicon with "physio-genomics," functional genomics, even "prote-omics," meaning the study of proteins, the products of genes.
Most important for the public, genomics widens the field of medical genetics to include such common diseases as diabetes, heart disease and cancer. These complex chronic illnesses result from interactions of a number of genes as well as environmental factors.
In one study of high blood pressure, for example, Gary Churchill of Jackson Laboratory and his colleagues at Boston University have found about half a dozen candidate genes that play a role in making people sensitive to salt, which puts them at risk for hypertension. Researchers know that hundreds of genes are involved in hypertension, but they speculate that only a few may be key to the development of disease.
"What we're doing that's new is looking at more than one gene at a time," explains Churchill. The hope is that once scientists unravel the interaction of key genes and identify the steps in the cell that lead to disease, they can design drugs that interfere with the process.
"The medical goals are therapeutic," continues Churchill. "These pathways of interactive genes give us targets for drug companies to intervene on the cell surface."
Genomics-based drug development has become the buzzword in drug company laboratories. Much research has already gone into cancer to understand the steps that turn a normal cell into malignant disease. Says physician Thomas Caskey of Merck Research Laboratories: "We're getting our feet wet in cancer and we'll move on probably to atherosclerosis [hardening of the arteries] next."
Meanwhile, the whole concept of gene therapy has changed.
In its early crude form, gene therapy involved replacing a defective gene with a whole new normal gene in hopes of curing a person with a disorder caused by a single gene. Initial efforts proved disappointing. Not only was it difficult to get a whole gene into a person, but the body's immune system rose up and destroyed the "foreign" invader.
Now gene therapy is more subtle. Instead of replacing the whole gene, some new therapies insert only the most critical part of a gene, using carriers or "vectors" that are less likely to be attacked as foreign.
Federal health officials predict that in 10 years, gene therapy will be successful for a few inherited diseases such as hemophilia. In 20 years, they say, cancer therapy will target precisely the molecular Achilles' heel of a tumor, and gene-based designer drugs for diabetes and hypertension will be on the market.
Excitement runs high here at this meeting of luminaries in the field of genomics. But there's also a dose of Down East caution. Medicine moves much more slowly than laboratory science and as they say in Maine--sometimes you can't get "theah" from "heah."