The Unselfish Gene
- From: "whitesickle@xxxxxxx" <whitesickle@xxxxxxx>
- Date: Sun, 12 Mar 2006 12:49:28 -0500 (EST)
The unselfish gene
The new biology is reasserting the primacy of the whole organism - the
individual - over the behaviour of isolated genes
Johnjoe McFadden
Friday May 6, 2005
The Guardian
What is a gene? Scientists eager to uncover genes for heart disease,
autism, schizophrenia, homosexuality, criminality or even genius are
finding that their quarry is far more nebulous than they imagined.
Uncovering the true nature of genes has turned biology on its head and
is in danger of undermining the whole gene-hunting enterprise.
The first clues turned up in study of the cell's metabolic pathways.
These pathways are like Britain's road networks that bring in raw
materials (food) and transport them to factories (enzymes) where the
useful components (molecules) are assembled into shiny new products
(more cells). A key concept was the "rate-limiting step", a metabolic
road under strict traffic control that was thought to orchestrate the
dynamics of the entire network.
Biotechnologists try to engineer cells to make products but their
efforts are often hindered, apparently by the tendency of the key genes
controlling the rate-limiting steps to reassert their own agenda.
Scientists fought back by genetically engineering these genes to
prevent them taking control. When they inserted the engineered genes
back into the cells they expected to see an increase in yields of their
products. But they were disappointed. The metabolic pathways slipped
back into making more cells, rather than more products.
Geneticists were similarly puzzled by an abundance of genes with no
apparent function. Take the "prion gene". This is the normal gene that
in mad cow disease is transformed into the pathogenic brain-destroying
protein. But what does it normally do? The standard way to investigate
what a gene does is to inactivate it and see what happens. But
geneticists who inactivated the mouse's prion gene found that the
mutant mice were perfectly normal. The prion gene, like many other
genes, seems to lack a function.
But a gene without function isn't really a gene at all. By definition,
a "gene" has to make a difference; otherwise it is invisible to natural
selection. Genes are those units of heredity that wrinkled Mendel's
peas and are responsible for making your eyes blue, green or brown. A
century of reductionist biology has tracked them down, through Watson
and Crick's double helix, to the billions of A, T, G and C gene letters
that were spewed out of the DNA sequencers. But now it seems that the
genes, at the level of DNA, are not the same as genes at the level of
function.
The answer to these riddles is being unravelled in an entirely new way
of doing biology: systems biology. Let's return to that road network.
We may identify a particular road, say the A45, that takes goods from
Birmingham to Coventry, and call it the BtoC road, or BtoC gene.
Blocking the A45 might be expected to prevent goods from Birmingham
reaching Coventry. But of course it doesn't. because there are lots of
other ways for the goods to get through. In truth the "road" (or gene)
from BtoC isn't just the A45 but includes all those other routes.
Rather than having a single major function, most genes, like roads,
probably play a small part in lots of tasks within the cell. By
dissecting biology into its genetic atoms, reductionism failed to
account for these multitasking genes. So the starting point for systems
biologists isn't the gene but rather a mathematical model of the entire
cell. Instead of focusing on key control points, systems biologists
look at the system properties of the entire network. In this new vision
of biology, genes aren't discrete nuggets of genetic information but
more diffuse entities whose functional reality may be spread across
hundreds of interacting DNA segments.
This radical new gene concept has major implications for the gene
hunters. Despite decades of research few genes have been found that
play anything more than a minor role in complex traits like heart
disease, autism, schizophrenia or intelligence. The reason may be that
such genes simply don't exist. Rather than being "caused" by single
genes these traits may represent a network perturbation generated by
small, almost imperceptible, changes in lots of genes.
And what about "selfish genes", the concept introduced by the Oxford
biologist Richard Dawkins to describe how some genes promote their own
proliferation, even at the expense of the host organism? The concept
has been hugely influential but has tended to promote a reductionist
gene-centric view of biology. This viewpoint has been fiercely
criticised by many biologists, such as the late Stephen Jay Gould, who
argued that the unit of biology is the individual not her genes.
Systems biology is reasserting the primacy of the whole organism - the
system - rather than the selfish behaviour of any of its components.
Systems biology courses are infiltrating curricula in campuses across
the globe and systems biology centres are popping up in cities from
London to Seattle. The British biological research funding body, the
BBSRC, has just announced the creation of three systems biology centres
in the UK. These centres are very different from traditional biology
departments as they tend to be staffed by physicists, mathematicians
and engi neers, alongside biologists. Rather like the systems they
study, systems biology centres are designed to promote interactivity
and networking.
And of course, outside of biology, there will be many who will be
saying, "I told you so". Holistic approaches have always dominated the
humanities and social sciences. The first eight chapters of Salman
Rushdie's Midnight's Children describes the lives of the narrator's
grandparents, parents, aunts, uncles and friends against the backdrop
of the tumultuous politics of 20th-century India and Pakistan. The
reason, according to the narrator, is that "to understand just one
life, you have to swallow the world". Perhaps biologists ought to have
read more.
· Johnjoe McFadden is professor of molecular genetics at the
University of Surrey and author of Quantum Evolution
.
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