The next time you consider summary execution for a worm when digging in the garden, think again. Its relations are involved in research that could help cure human diseases.
The power of the emerging genetic technologies has brought something of a revolution to biochemical research. Scientists are now able to use insects and nematodes in the development of disease "models" for human ailments.
The model doesn't have to exactly mimic the progress of human disease, explained Dr John Connolly, a Trinity College graduate who is now involved in neurological disease research at the Fondation Jean-Dausset CEPH in Paris.
Dr Connolly and his former classmate and now a researcher at the University of California, San Francisco, Dr Kevin Mitchell, and Dr Michael Gill of Trinity, organised last week's Life and Death of the Brain neuroscience symposium. The event brought some of the world's leading neurobiological researchers to Dublin.
CEPH, a non-profit private research institute, is developing tools for human genetics studies. These technologies are being focused on a range of disease processes, and Dr Connolly's area of specialisation is the neurological diseases. "We work on a variety of human degenerative disorders," he said.
Central to his current research activity is a microscopic worm just a single millimetre long, Caenorhabditis elegans. Although the worm appears to have no common ground with humans, nor is its central nervous system anyway similar, it can none the less be used to study our diseases.
The key that enables this is the hidden commonality that links all living organisms, DNA, the blueprint of life. If traced back far enough, there is a common ancestry for living organisms on this planet. As the trial and error iterations of evolution advanced, useful biochemical processes were retained and processes that ceased to be relevant were lost.
Some species went off on evolutionary tangents but they took with them those useful biochemical tricks that helped them to survive. This has produced a startling situation whereby there are duplicate genes that cross the species boundary. Identical genes produce identical proteins whether they are operating in a fruit fly or a human.
"There is a remarkable degree of gene conservation between worms and humans," Dr Connolly said. Even if a matching gene does not exist, researchers are able to insert duplicate genes in the worm, enabling its similar cell chemistry to produce the human protein.
C. elegans is therefore doing service in the fight against Huntington's disease, an inherited brain disorder that can produce severe involuntary movements. Dr Connolly and his group at CEPH have succeeded in producing a transgenic worm that carries a human gene known to cause Huntington's disease.
The Huntington's gene was discovered by an international team which included another Trinity man, Prof Michael Conneally, now distinguished professor of medical and molecular genetics and neurology at Indiana University, who was a speaker at last week's conference.
This gene was inserted in C. elegans and began to produce its protein. It causes catastrophic changes in humans, but in the worm, it disturbs the way it responds to a touch stimulus, basically causing it to remain motionless.
Dr Connolly has confirmed that the model carries the human gene and he is now ready to begin a series of worm DNA mutations. The worms will be treated with a known DNA disrupter, a chemical mutagen that scrambles segments of DNA into new combinations. The treatment can be given to successive generations of C. elegans, with unique new combinations forming each time.
The object is to see whether a new mutated gene might form that produces a protein that in turn blocks the effects of the Huntington's gene. Any worm that develops such a gene would be easily identifiable, being the only worm in the family that again responds to a touch stimulus by moving about.
"Now we can screen using genetic technology for mutations that suppress the neurodegenerative disorder," Dr Connolly said.
Huntington's is an inherited disease but not all the members of a family will develop it. There are obviously genes in these individuals which prevent the Huntington's gene from causing disease.
The hope is that a disease-blocking gene will be identified in the worms. The DNA sequence of this gene can then be identified and researchers can search to see if there is a human equivalent.
This process allows the scientists to work back into human DNA from DNA sequences found in the worms. Obviously it would be impossible to experiment on humans in this way, but the findings which arise from the worm studies should be applicable in a human context if a matching gene is found.
"We are trying to short-circuit the long process in studying the biochemistry in human disease," Dr Connolly explained. Even if a match isn't found, the protein produced by the disease-resistant worms might have potential as a novel pharmaceutical product.
It will probably be years before such research, even if immediately successful, delivers treatments or cures for these diseases. Long before that, however, useful new biochemical information about how these diseases operate will become available and should help in efforts to develop useful new drugs.