Life after the Central Dogma
The biotech industry was launched on the scientific myth that organisms are hardwired in their genes, a myth thoroughly exploded by scientific findings accumulating since the mid 1970s and especially so since genome sequences have been accumulating (see Living with the Fluid Genome, by Mae-Wan Ho ).
We bring you the latest surprises that tell you why our health and environmental policies based on genetic engineering and genomics are completely misguided; and more importantly, why the new genetics demands a thoroughly ecological approach.
It is amazing how much scientific and religious fundamentalism have in common. The late Francis Crick won the Nobel Prize jointly with James Watson and Maurice Wilkins for working out the structure of DNA; and rather like the new 'Potentate' of biology, issued the "Central Dogma" to the faithful, which decreed that genetic information flows linearly from DNA to RNA to protein, and never in reverse. That was just another way of saying that organisms are hardwired in their genetic makeup, and that the environment has little if any influence on the structure and function of the genes.
The Central Dogma goes hand in glove with the other dogma of biology, the neo-Darwinian theory of evolution by natural selection, which says that the genetic material mutate at random, and individuals which happen to have good genes leave more offspring, just as individuals with bad genes are weeded out. The neo-Darwinian theory is beloved of the status quo, because it endows the rich and powerful with a certain mystique, as those who have won the race in the struggle for survival of the fittest, of being in possession of good genes (= good breeding); while the poor and dispossessed have only their bad genes to blame.
Since the mid-1970s, if not before, molecular geneticists studying the genetic material have been turning up evidence that increasingly contradicts the Central Dogma. There is an immense amount of necessary cross talk between genes and the environment in the life of the organism, which not only changes the function of the genes but also the structure of the genes and genomes. By the early 1980s, the new genetics of the "fluid genome" has emerged.
But apart from a few heretics like Barry Commoner and myself, no one dared to say a word against the Central Dogma or the neo-Darwinian theory of evolution.
Things may have changed within the past two years, thanks to the good sense and good management of the public gene sequencing consortium to insist on depositing gene sequences in a single public database, freely available to all researchers.
This database is not much use for business and drug discovery; that much is clear, as one after another 'bioinformatics' company that tried to horde the data has gone out of business. But, collected in one freely accessible central database, it is very good for research that exposes the poverty of the genetic determinism ideology that has led to the creation of the database in the first place.
The evidence against the Central Dogma has piled up to such an extent that rumblings of "challenging the dogma" and "a new theory is needed to replace the central dogma" can even be heard in the mainstream scientific journals. Though Dr. Ewan Birney, who gave the Royal Society's inaugural Francis Crick Lecture in December 2003, still paid elaborate homage to the Central Dogma, with arrows pointing strictly one-way from DNA to RNA to protein, leaving out all the many more arrows that point in reverse.
What are the latest surprises that the fluid and flexible genome has in store? One area is the importance and pervasiveness of epigenetics, specifically, chemical markings on the DNA and proteins binding to the DNA in the chromosomes that determine patterns of gene expression, or which bits of the genetic text is actually read. That is overwhelmingly determined by experience. In an earlier issue (SiS 20), we showed the mother's diet and stress can affect patterns of gene expression in the embryo and foetus, which determines the individuals' health prospects much later in life.
Now, researchers are finding genes that are marked for life in rat pups, strictly by how their mothers care for them during their first week of life after birth (see "Caring mothers reduce response to stress for life", this series). It leaves one in no doubt that the environment is giving the instruction of which genes to turn on.
Only a few years ago, people were referring to the 98% or more of the genome that doesn't code for proteins as "junk DNA". Not any more. The genome has a definite 'architecture' that holds up beneath the fluidity. There is a high degree of non-randomness in the parts of the genome that undergo change. While some parts are hypermutable, certain families of sequences are 'homogenized' to be nearly identical (see "Keeping in concert", this series), while still others are 'ultraconservative' in that they have remained absolutely unchanged in hundreds of millions of years of evolution ("Are ultraconserved elements indispensable?" this series). And when cells get into a tight corner metabolically speaking, there may even be genes that mutate to get them out of it ("To mutate or not to mutate", this series).
Most of all, there is a big treasure trove within the apparent junkyard of the genome. Many sequences that don't code for proteins are involved in regulating development and gene expression. Many of the surprises are associated with findings that indicate most of the action is not in proteins, but in the numerous species of RNA 'interfering' at all levels of the 'readout' of genetic information: with the DNA, with other RNA species, and with proteins (see "RNA subverting the genetic text", this series).
All of this goes against the very grain of the Central Dogma that posits linear, mechanistic control. Instead, layers upon layers of chaotic complexity are coordinated, it seems, by mutual agreement, in an incredibly elaborate, exquisite dance of life that dances itself freely and spontaneously into being.
It is not so much that we need a new theory to replace the central dogma; it is more important than that. We need a new way of knowing and being organisms that will prevent us from mistaking organisms for instruments and machines. That's the real challenge.
Article first published 03/09/04
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