April 12, 2002 

By NICHOLAS WADE
 
 
 

Philosophers and theologians may speculate about the
essence of human nature, but biologists have a
kick-the-tires test that should, in principle, deliver an
exact definition. By comparing humans and their close
cousin, the chimpanzee, at the finest level possible, they
believe, they can find the special ingredient that must be
mixed into animal clay to make it human. 

Pursuing this goal with a sophisticated tool called a gene
expression chip, researchers have now compared the genetic
activity of the chimp and human brain, the organ that
presumably holds the vital difference. Despite reports from
anatomists that the two species' brains seemed to differ
only in size - the human brain has more than three times
the volume - the gene chip has brought to light numerous
differences in how the brain cells of the species operate
at the genetic level. 

The finding is reported today in the journal Science by Dr.
Svante Paabo of the Max Planck Institute for Evolutionary
Anthropology in Leipzig, Germany, and colleagues in
Germany, the Netherlands and the University of California
at San Diego. 

Previous efforts to find fundamental human-chimp
differences have proved surprisingly difficult. Language, a
defining human characteristic, is mediated by an area of
the brain that is larger in the left hemisphere of the
human brain than in the right. But a few years ago Dr.
Patrick Gannon of the Mount Sinai School of Medicine in New
York found the same asymmetry in chimpanzee brains. 

On the genetic level, although the chimpanzee genome has
not yet been decoded, scientists have long known from
sampling bits of it that chimp DNA is 98.7 percent
identical with human DNA. If just the genes are compared,
the similarity increases to 99.2 percent. Scientists have
been hard put to explain how the two species differ so much
in body and behavior when they seem to have an almost
equivalent set of genes. 

Dr. Paabo's results seem to offer a rescue from this
embarrassment. Even though human and chimp genes are very
similar, those used to operate brain cells show very
different patterns of activity, the study found. 

Using autopsy material from the cerebral cortex of people
and chimps who had died natural deaths, Dr. Paabo's team
showed that a given gene might produce a lot of protein in
human brain cells but very little in a chimp, and that this
pattern was widespread. 

With another kind of test they compared gene activity
levels in blood, liver and brain and found that in the
first two tissues humans and chimps were quite similar. But
the gene activity levels in the human brain were strikingly
different from those in the chimp, suggesting that the rate
of evolution of human brain genes has been five times
faster than that of the chimp brain genes. 

This finding fits well with other evidence suggesting that
an explosive evolutionary development took place, at least
in the human lineage, after the comparatively recent split
between the common ancestors of chimps and people some five
million years ago, Dr. Gannon said. 

The differences in gene activity level found by the Paabo
team do not explain how chimp and human brains are
different, but they set the stage for doing so, since
scientists can now explore the differently behaving genes
one by one. 

"By highlighting which genes are differentially expressed,
this study provides the key entry point into the pathways
that may be involved in cognitive differences between
chimps and humans," said Dr. James Sikela, an expert on the
genetics of brain development and evolution at the
University of Colorado. 

When a gene is activated, the cell copies the gene's
information onto another molecule and then uses this
chemical transcript to synthesize a specific protein. 

The activity of genes can be measured by gene chips, which
contain versions of up to 18,000 human genes anchored on a
glass slide to different sites in a grid-shaped array.
Fluid extracted from living cells is washed over the array,
and the square containing each gene lights up if a copy of
that gene is present in the fluid. 

Chimp gene chips are not yet available. But a gene chip
studded with human genes can detect the activity of genes
in a chimpanzee neuron reasonably well. 

Because language seems so central to human distinctiveness,
there has been considerable excitement over the discovery
last year of the first gene apparently related to language.
Identified by Dr. Anthony P. Monaco of the University of
Oxford, the gene is known as FOXP2. 

It would be of some interest to know if FOXP2 shows a
different pattern of activity in chimps. But the gene,
being novel, was not included in the gene chips. Dr. Paabo
said he was studying the gene's behavior in chimps in a
separate experiment, which he could not yet talk about. 

Although the study reported today shows differences in the
operation of the adult chimp and human brains, the basic
architecture of the brain is constructed during an animal's
development. The genes that direct the unfolding of this
plan can be studied only in tissue from human fetuses,
which is hard to obtain. 

As for the chimp side, Dr. Paabo said he was not prepared
to do anything to chimpanzees that could not be ethically
done to humans. Dr. Ajit Varki, his colleague at the
University of San Diego who supplied the chimp autopsy
material, agreed. "The ethical position of most people is
that you should not euthanize a chimp for experimental
purposes," he said.