Epilepsy is thought to affect between 1 and 3 per cent of the world’s
population, making it one of the commonest neurological diseases. Despite
this, scientists know remarkably little about the biochemical changes underlying
the disorder.

People have epileptic seizures when their nerves fire electric signals
in an uncoordinated way, causing fits and unconsciousness. Although epilepsy
can be brought on by trauma, infectious diseases and oxygen deprivation,
the cause is sometimes genetic.

Among the many known forms of epilepsy is a group called progressive
myoclonus epilepsies which are usually inherited and can lead to serious
illness. Unverricht-Lunborg disease is one of this group.

Seizures begin during childhood, and features such as tremor, stammering
and emotional impairment develop gradually through adulthood. Unlike some
types of epilepsy, people who suffer from it experience relatively little
intellectual decline.

Unverricht-Lunborg disease is most common in the Baltic region of Europe,
where it affects around 1 in 20,000 people. Not surprisingly, it was a group
in Finland which set out to look for the defective gene.

The team at the University of Helsinki, led by a human geneticist, Albert
de la Chapelle, studied the inheritance of dozens of DNA markers from generation
to generation in 12 affected families. The markers detect small variations
in DNA sequences between individuals. Should one marker always be inherited
with the presence of epilepsy, the chances would be high that the marker
signalled the chromosome containing the epilepsy gene.

Using markers from chromosome 21, the group successfully mapped the
epilepsy gene close to one end of this chromosome (Proceedings of the National
Academy of Sciences, vol 88, p 3696).

The next step will be to use the markers as a starting point for isolating
large stretches of the DNA. Then the researchers will sort and examine the
sequences in order to identify the epilepsy gene.

They might be lucky. The position of the epilepsy gene on the chromosome
map happens to coincide with that for a known gene called S100. S100 codes
for a protein that binds calcium ions in the glial cells that are common
in the central nervous system. De la Chapelle’s group thinks S100 might
just be the epilepsy gene it is looking for.

Two years ago, researchers from the Howard Hughes Medical Centre in
Salt Lake City, Utah, mapped the first epilepsy gene – for a very rare form
of seizure by the name of benign familial neonatal convulsions (BFNC). The
group mapped the gene to chromosome 20, but they also have yet to identify
the gene itself.

Understanding such minor forms of seizure may shed light on more serious
forms.

Parkinson’s disease is a neurological condition characterised by muscular
tremors and shaking, loss of balance, and dementia. The brains of sufferers
are deficient in certain neurochemicals, such as L-dopa and dopamine, which
transmit electrical signals in the brain.

Fred Gage and his colleagues at the University of California in San
Diego injected modified cells from rat skin into the brains of rats that
were suffering from a type of neurological damage that resembles Parkinson’s
disease (Proceedings of the National Academy of Sciences, 15 November, vol
86).

The researchers first modified the cells by introducing a genetically
engineered virus that contained the gene for the enzyme tyrosine hydroxylase.
The enzyme catalyses the conversion of tyrosine into L-dopa, and is produced
in small amounts by the cells. Next, Gage and his colleagues injected the
modified cells into the brains of the rats. They found that brain function
improved by 40 per cent.

In the brain, the injected cells produce L-dopa which is converted to
dopamine and other neurotransmitters. This allows some normal brain functions
to be restored. Gage and his colleagues stress, however, that the transplant
method is not yet ready to be applied to humans.

An advantage of the method is that it holds out the possibility of injecting
skin cells from the same animal or individual as the recipient. This would
greatly reduce the chance that the transplanted material would be rejected.

Unfortunately, the technique is not as effective as transplanting fetal
tissue to the brain. However, research with fetal tissue is now hampered
in the US by a ban on federal funding for research that involves transplants
of human fetal tissue from abortions.

Researchers have been quick to point out, however, that the moratorium
on funding is harming the study of many important human disorders, including
diabetes, cancer, AIDS and Parkinson’s disease. At present, money for such
work can only come from charities and private sources.

Gage says that transplants of fetal cells are a more effective method
of alleviating the symptoms of Parkinson’s disease because they produce
quite naturally the neurotransmitters that are deficient. Nevertheless,
Gage is optimistic about the technique of transplanting skin cells, despite
its limitations. ‘We think this approach has potential and should be pursued,’
he says.

Together with conflicting results in relation to another mental illness,
schizophrenia, the latest research underlines the many difficulties remaining
in mapping the genes that cause complex hereditary disorders.

Molecular geneticists have scored tremendous success recently in mapping,
and eventually isolating, the genes responsible for common genetic disorders
such as cystic fibrosis and Duchenne muscular dystrophy. Many researchers
are applying similar methods towards understanding more complex traits,
including psychiatric illnesses, where there is controversy about the relative
contributions of genetics and the environment to the development of the
disease. Knowledge of the genetic basis for mental disorders is vital to
an understanding of the biochemical basis of the illness and for accurate
diagnosis of the condition.

In the last two years, geneticists have claimed major breakthroughs
in identifying possible genes that predispose people to schizophrenia and
manic depression. In 1988, a group from the University of London led by
Hugh Gurling found evidence for a gene on chromosome 5 that predisposed
people to schizophrenia. Their study focused on seven families from Iceland
and England. However, at least two other groups, examining families from
Sweden and Scotland, have failed to reproduce the findings. The results
appear to confirm what many researchers have long believed – that schizophrenia
is a heterogeneous disorder that is probably caused by defects in many genes
and not just one.

Now, uncertainties have appeared in the study of a supposed gene for
manic depression. Two years ago, a collaborative study by groups from the
University of Miami, Massachusetts Institute of Technology and Yale University,
found evidence for a predisposing gene for manic depression at the tip of
chromosome 11. In that study of a large family from the Amish community
in Pennsylvania (often favoured in genetic studies because of their extensive
genealogical records), the joint effort found a correlation between two
genetic markers on chromosome 11 and the inheritance of the disease.

The gene for an enzyme called tyrosine hydroxylase was in the same area
of the chromosome as the defective gene, and was therefore a likely candidate
as the cause of the abnormality. But research by John Kelsoe and Edward
Ginns of the National Institute of Health and the National Cancer Institute
subsequently showed that this gene was too distant from the defective gene
to be one and the same.

Their finding promoted a re-examination of the previous study and this
time, as reported in Nature, the correlation between the inheritance of
manic depression and the markers was greatly diminished. Two family members
who appeared normal at the time of the original study had later developed
the illness, invalidating much of the previous analysis. Although the new
study does not rule out the possibility of a predisposing gene on chromosome
11, it strongly suggests that conclusions drawn from the earlier results
were premature.

Despite the setback, the results of an Israeli study, which found that
the gene responsible for another form of manic depression called bipolar
affective illness was on the X chromosome, are not affected.

Researchers are beginning to appreciate the difficulties in examining
the genetics of mental illness and other complex hereditary disorders. Many
of these are probably caused by more than one gene, complicating the genetic
studies. To aid the analysis of these disorders, there must be better agreement
in defining and diagnosing psychiatric conditions, so that results from
various groups can be compared. Geneticists such as Kenneth Kidd are proposing
that the statistical scores conventionally used to map genes for complex
mental disorders must be made more stringent.

The conflicting findings of geneticists around the world underline the
poorly understood interaction between genes and the environment in causing
psychiatric illnesses.

Each year, it seems, there is a certain amount of debate regarding the
recipients of the Nobel prizes, and in particular who was left off the list.
By this measure, 1989 was a vintage year. There is no doubt that Bishop
and Varmus, both of the University of California in San Francisco, are worthy
winners of the Nobel prize for their work on cancer. About 10 years ago,
they made a major breakthrough in our understanding of how a cell can turn
cancerous. They showed that, in animal cells, viral genes capable of causing
cancer in fact originated in the cell. Large families of such genes (oncogenes)
have since been discovered in many species, including humans. Bishop and
Varmus had previously shared the prestigious Lasker Award, often a forerunner
to the Nobel nomination, with three other cancer specialists, one of whom
was Weinberg.

Dominique Stehelin, currently working at the Pasteur Institute in Paris,
was formerly a postdoctoral researcher with Bishop and Varmus. As such,
he performed some of the crucial experiments, and coauthored two papers
detailing the results, for which Bishop and Varmus have now been rewarded.
The key question is not whether he did the experiments or not (Varmus readily
acknowledges that he did some of the most difficult work) but who provided
the ideas and direction for the research. In this regard, Varmus leaves
absolutely no doubt, pointedly stating that Stehelin worked ‘under supervision’.

The argument has taken on rather nationalistic overtones. Stehelin has
appeared on French television offering his laboratory notebooks for verification
of his claims. His colleagues have pointed out that because he was the first
author on some of the important research papers, he deserves an equal share
of credit. What they fail to mention, however, is that it is a convention
to list the postdoctoral researcher first, and the supervisors last, in
the list of authors.

In the US, co-workers of Bishop and Varmus at the time of the disputed
research were quick to play down Stehelin’s contributions. Many were more
surprised that a different name was not also chosen by the Nobel committee.

Robert Weinberg, a professor of biology at the Whitehead Institute in
Cambridge, Massachusetts, and the Massachusetts Institute of Technology
(MIT), was extremely diplomatic after the news of the award became public.
He offered the winners his congratulations, and described how his own work
had flowed from the studies of Bishop and Varmus. However, David Baltimore,
head of the Whitehead Institute and a previous Nobel laureate, and even
Varmus himself, expressed surprise and disappointment at Weinberg’s omission.

Although Weinberg did not work directly with Bishop and Varmus, his
group has been responsible for three of the most important findings in oncogene
research this decade. Some years ago, it described the first DNA mutation
in a human oncogene giving rise to cancer, having first shown that DNA from
a tumour could itself cause cancer when transferred into other cells. More
recently, Weinberg has been leading the study of a new type of gene family,
called ‘anti-oncogenes’, which appear to keep cancer in check in cells.
So significant have Weinberg’s contributions been that his name was widely
tipped as a future Nobel prize winner.

The 1989 award for medicine is the first given directly for cancer research,
and of course the committee could give additional prizes in this large field
in the next few years. But in the rapidly developing world of medicine,
and molecular medicine in particular, there are many researchers worthy
of the world’s most prestigious prize. To name just a few, there could be
awards for the study of AIDS, gene structure and the control of gene expression,
or human genetic disorders such as Duchenne muscular dystrophy and cystic
fibrosis. It will be too bad if Weinberg has been overlooked for good.

Another award this year, that for chemistry, also caused some surprise
among American researchers. The prize was shared by Thomas Cech of the University
of Colorado, and Sidney Altman, a Canadian working at Yale. They were deservedly
rewarded for independently discovering that RNA, known as the genetic messenger
within cells, also possesses catalytic and replicative properties that could
explain the origin of life on the planet.

The two men differed in their reaction to the news. At a press conference,
Altman unfurled a Yale banner and gave credit to co-workers past and present.
Cech, on the other hand, was more relaxed. When asked what he would be doing
with his share of the $450,000 prize, he joked ‘My two daughters have a
talent for spending money!’

Cech wins the award at the young age of 41. His research was highy original
and innovative, and the only surprise perhaps is that he wins the award
so soon. However, American researchers also expected another MIT biologist,
Phillip Sharp, to win an award for pioneering work on RNA. Like Weinberg,
Sharp will have to wonder if he has missed his chance.

All in all, it has not been the best of years for MIT: two near misses
in the Nobel stakes, coupled with speculation that Baltimore, one of its
most famous faculty members, would be moving to New York to become president
of the Rockefeller University. To add insult to injury, a Harvard professor
shared the physics prize.

The Nobel committee probably does not welcome allegations and disputes
in the media. But for the rest of us, the publicity this year has highlighted
the human side of research, and demonstrated that, yes, science can be fun!

Kevin Davies is a research fellow at the Children’s Hospital in Boston,
Massachusetts.