There’s a great article in July 2009’s Smithsonian Magazine about the exciting discovery of a new class of genes, and the hope that this discovery brings to the research of cancer and other diseases.
In 1953, the structure of DNA was discovered. It was revealed to be a double helix, resembling a long twisted ladder composed of polymer, with each rung of the ladder, called a base, consisting of a chain of chemical compounds. The exact sequence of these chemical compounds is what holds the genetic code, or the instructions that the gene carries.
Throughout the subsequent years of genetic research, two basic assumptions about genes were held. The first was that an individual gene is quite complex and large, usually composed of 10,000 or more chemical bases. The second assumption was that the main function of any gene is to cause cells to make proteins, which then have their own unique functions to perform.
Recently, a new way of looking at genetics has been forming, and this altered view is resulting in new advances in disease research.
Scientists studying genetic mutations in worms in 1993 found themselves searching in vain for the specific genes responsible for the mutations, finding that the section of DNA where the gene must be was too small to hold a gene. When they began to work together, they realized that they were looking at a small segment of DNA that was exactly the same as a standard-sized segment of DNA.
This newly-recognized class of gene was very small, being 70 rather than 10,000 bases long, and it did not cause any protein to be made. Instead it made a different genetic material which was named microRNA. Standard RNA is also made by more-familiar genes, but in their case it acts as a simple messenger in the process of making proteins. MicroRNA is the actual end-result of these new small DNA segments, and it uses a unique method to function. The microRNA attaches itself to the standard RNA that it matches in ordinary genes, thus blocking it from producing its protein.
In 2000, a second microRNA gene in worms was discovered. Scientists then began to look for these microRNA genes in other species. In 2001, the scientific community finished work on mapping the human genome, and were also mapping the genomes of other animals. It was then found that the same microRNA gene found in the worms studied earlier was also present in humans, and many other species as well. At this same time, many additional microRNA genes were also being identified.
At this point, scientists Carlo Croce and George Calin revisited an earlier mystery by comparing a segment of DNA involved in leukemia that could not be located to the known microRNA genes, and discovered that two of them were located in the exact missing segment. They went on to find that 68% of leukemia patients in fact had little to none of these two microRNAs produced, while people without this leukemia possessed many of them. They then concluded that these two microRNAs must suppress this leukemia. In 2002 they published their findings, becoming the first to assert that the lack of microRNAs causes cancer.
Following their discovery, it has been found that for every cancer which is examined, an alteration in microRNA can be found. Then Croce began to study what this new connection meant. In 2003, he and Chang-Gong Lui, a microchip developer, designed a tool called a microarray, which tests for the presence of microRNA. Using this tool, they found that certain microRNAs seem to be unique to certain types of cancer. This realization is invaluable for those patients whose cancer has metastasized, as different treatments need to be prescribed based on where the cancer originated.
Croce and his fellow scientists also discovered that the levels of two specific microRNAs could be used to accurately predict lung cancer survival rates. Additionally, they also found the microRNAs that predicted the eventual severity in cases of leukemia. This is significant as this information could be used to determine a patient’s best course of treatment. Also, as with more-familiar genes, microRNA genes can either encourage cancer if they produce too many microRNAs, or suppress cancer, as cancer will occur if they are missing or damaged. MicroRNAs are also found to interact with conventional cancer genes, but this interaction is yet to be understood.
To date, about 40 microRNA genes associated with cancer have been identified, and microRNAs seem to also be involved in other diseases such as heart disease, Alzheimer’s, schizophrenia and more. And when scientists step back and look at disease research in general, armed with this new perspective, they note that there are many diseases that seem to have a genetic cause, but the specific gene responsible has not been able to be found. How many of these diseases are truly caused by previously unimagined microRNA abnormalities?
Researchers now estimate that humans have at least 1000 microRNA genes, which seem to affect at least 25% of our 25,000 conventional genes. Only an assumption has kept scientists from finding these microRNA genes until now. The technology necessary to study them has been available for decades.
It is hoped that microRNAs might eventually be used as therapies. In recent experiments, Croce reports that he has been able to halt cancer growth in mice with injections of the appropriate microRNA.
Archaeologists working at the Hohle Fels Cave dig in the Ach Valley, 140 km west of Munich Germany, have discovered clear evidence that music was a part of Paleolithic life, when modern humans colonized Europe over 35,000 years ago.
