A leading MIT scientist describes a remarkable control system that oversees our DNA, which was discovered only a few years ago, writes Dick Ahlstrom
It was designated the scientific "breakthrough of the year" in 2002. It represents nothing short of a revolution in biological science. It is the "most exciting discovery of the last decade". What is it? RNA interference.
It relates to the ability of small segments of RNA (ribonucleic acid), no more than 21 to 23 base pairs long, to control how our genes function. They interfere directly with the production of proteins inside the cell, in effect controlling the genetic machinery that helps keep us alive or goes wrong to cause disease. RNA interference, RNAi, has the potential to change our lives, deliver new medical treatments, better explain the course of evolution and a lot more besides, according to most commentators. Yet this revolution is just a few short years old.
Nobel laureate Prof Phillip Sharp is a leading proponent and researcher in the RNAi field and last week he came to Dublin to explain its import. He was also here to receive the inaugural UCD Ulysses Medal, instituted by University College Dublin to celebrate the 150th anniversary of its foundation.
The medal will now be presented annually to international leaders in science and recipients are asked to deliver a talk. Naturally Sharp chose RNAi, describing the latest findings in this remarkable research area.
Currently the Salvador E Luria professor of biology and director of the McGovern institute for brain research at the Massachusetts Institute of Technology, Sharp is also the recipient with Richard Roberts of the 1993 Nobel Prize in Physiology or Medicine for the discovery in 1977 of RNA splicing.
Their work provided one of the first indications of the startling phenomenon of "discontinuous genes" in mammalian cells. The discovery that genes contain nonsense segments that are edited out by cells when using genetic information is important in understanding the genetic causes of cancer and other diseases. The finding opened an entirely new area in molecular biology.
The discoveries relating to RNAi are now coming thick and fast, according to Sharp, who was quoted earlier this month in Environmental Health Perspectives saying, "There's not an area of biological science this will not touch."
Also known as short interfering RNAs (siRNAs), this vital method for controlling gene function was unknown until recently. "We had no concept that siRNAs were important for controlling biological systems until 2000," says Sharp.
They oversee gene expression and also key biological steps including development. "At least 500 human genes encode these siRNAs yet they were unknown until 2000. It means there are still discoveries to be made at a fundamental level," he suggests.
Before RNAi was discovered, protein production inside the cell seemed so simple. The genetic blueprint DNA provides a template for producing messenger RNA, which in turn provides the "recipe" for the manufacture of proteins inside the cell in structures known as ribosomes.
RNAi has shown that the actual process is far more complicated. It exerts unimagined control over cellular processes by interfering with DNA and messenger RNA to dictate protein production.
"siRNA gives us a way to silence human genes in cells and silence their function," says Sharp. "It led to a revolution in cell biology. We are in the midst of at least a mini-revolution. We are now beginning to appreciate the existence of a whole other regulatory system for our genes."
The field is so new that even as new discoveries about how RNAi works are being announced, research groups around the world are looking at the possibility of using the technique to control cellular activity. "It has opened a new window on the possibility of the creation of new therapies."
A human trial using RNAi for the control of the most common form of age related blindness, macular degeneration, is already under way, he said. And only two months ago a researcher announced in Nature Medicine that siRNAs sprayed into the nasal passages of a mouse protected it from infection with the RSV virus, a common cause of pneumonia in infants.
"I think these are reasons to expect this is a new therapeutic approach," says Sharp. "It is so new we don't really understand the ramifications of the discovery. All of this is possibly the tip of the iceberg," he adds.
"What we need to know now is how much of the important physiology of the brain is related to siRNAs, or cancer or the liver. We are just at the start of answering that question."