Thursday, September 13, 2001

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"The term was introduced by Conrad H. Waddington in 1942.1 To paraphrase an erudite epistolary exchange in Science, he is said to contrast genetics with epigenetics , the study of the processes by which genotype gives rise to phenotype. In 1942 we had barely any clue as to what those processes are, so "epigenetic" had no connotation of the underlying chemical mechanism, whatever it was that modulated cell differentiation.

In 1994, as cited in the same issue of Science, Robin Holliday voiced a commonly apprehended drift in meaning, and redefined epigenetic as "Nuclear inheritance which is not based on differences in DNA sequence." These two memes are freely circulating and can cause muddle or mischief mainly when they recombine, namely when epigenetic-H is automatically applied to epigenetic-W."

"This neology of nucleic, epinucleic, extranucleic, has attracted few followers, I think largely because so few people had really thought through the distinctions. There is much merit in Ben Johnson's caution about unbridled proliferation of terms: "A man coins not a new word without some peril, and less fruit; for if it happen to be received, the praise is but moderate; if refus'd, the scorn is assur'd." But is a polysemy to be preferred, with thought-muddling as a further peril?"

redux [08.16.01]
Science Behind the Scenes of Gene Expression
[ summary can be viewed for free once registered]

"Some of the weirdest genetic phenomena have very little to do with the genes themselves. True, as the units of DNA that define the proteins needed for life, genes have played biology's center stage for decades. But whereas the genes always seem to get star billing, work over the past few years suggests that they are little more than puppets. An assortment of proteins and, sometimes, RNAs, pull the strings, telling the genes when and where to turn on or off."

""The unit of inheritance, i.e., a gene, [now] extends beyond the sequence to epigenetic modifications of that sequence," explains Emma Whitelaw, a biochemist at the University of Sydney, Australia."

""[Epigenetic effects] give you a mechanism by which the environment can very stably change things," says Rudolph Jaenisch, a developmental biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. Researchers are hoping to harness these effects to design drugs that correct cancer and other diseases brought on by gene misregulation."

redux [11.09.00]
New England Journal of Medicine Pharmacogenomics -- Teaching Old Drugs New Tricks

"Traditionally, cancer treatments have been selected on the basis of tumor type, pathological features, clinical stage, the patient's age and performance status, and other nonmolecular considerations. We have generally accepted with a certain fatalism that some patients pigeonholed into a given category will have a response to a particular therapy, whereas others will not. The difference is often viewed as a matter of luck, like the result of a coin toss, but in fact, treatment response can be predicted in some cases, whereas it is close to impossible to predict the results of a coin toss. The field of pharmacogenomics, through the study of large numbers of genes that influence drug activity, toxicity, and metabolism, provides the opportunity to tailor drug treatments and to eliminate many of the uncertainties of current therapy for cancer. "

"In this issue of the Journal, Esteller and colleagues (2) provide clinical evidence of an intriguingly different sort of mechanism -- an epigenetic one that does not involve any change in DNA sequence -- to explain the resistance of some gliomas to nitrosourea alkylating agents."

"Such comprehensive approaches to biology can be characterized as "omic" research (6) -- that is, research in which one generates large resources of information on biologic molecules in aggregate without necessarily knowing in advance which pieces of information and which correlations will prove most important. (7) "Omic" research is hypothesis-driven, but the hypothesis relates to information and its usefulness, rather than to particular molecules or processes. "Omics" began with genomics and the Human Genome Project. Then, as coined by various researchers, there came proteomics, kinomics (for the kinases in aggregate), CHOmics (for the carbohydrates), metabolomics, immunomics, toxicomics, and clinomics -- as well as compound forms, such as functional genomics, structural genomics, and pharmacogenomics. In view of the study by Esteller et al., (2) and as we search for other clinically relevant instances in which promoter methylation affects therapy, can "pharmacomethylomics" be far behind?"

redux [07.11.00]
Wired News Following Cancer's Red Flags

"Genes are tricksters. They can be turned on or off -- and whether they're on or off decides whether the gene-owner will develop disease.

Gene researchers have embarked on a new field of research, called epigenomics, to determine whether genes are in the on or off position. This type of marker could prove an important diagnostic or therapeutic tool for all types of cancer.

"At Johns Hopkins, researchers are performing clinical trials on about 15 patients with leukemia and other cancers to find out if epigenomics might give pharmaceutical companies a lead for developing cancer drugs.

The research, like all epigenomics research, is studying a chemical found in everyone's DNA called cytosine. Cytosine is the only chemical of the four that make up human DNA (the others are adenine, thymine, and guanine) that is prone to a phenomenon called methylation. When cytosine is methylated, it tuns off its gene. "

Biospace.Com Big Picture Biology

"For most of us, formal biology education begins with complex systems--the traditional dissection of a frog in high school biology class is virtually a rite of passage in the U.S.

But the way many people learn about and invest in biotechnology is at the smallest end of the spectrum--the genome, now often described as the "periodic table" of biology. Genomics and all its related buzzwords have been responsible for much of the media attention, government grants, and investment capital heaped on the biotech industry over the past decade.

But just as there is a whole lot of chemistry that happens in between the periodic table and a birthday cake, there is a lot of biology in between the genome and a living organism. With the completion of biology's periodic table within sight, academics and industry players alike are pondering the best way to apply our hard won knowledge.

The only problem is, the path from genome to system seems to get harder the more we learn."