The characterization of the genetic material of the ancient goat contributed to the understanding of the demography of the ancient world * Can the extraction of genetic material from the remains of thousands of years old animals help in finding a vaccine for tuberculosis?
By Uri Nitzan
Photo: Harissa Fanousi
Right: Prof. Patricia Smith, Prof. Chuck
Greenblatt, Prof. Ariela Oppenheim and Dr. Marina Fairman.
In the late 80s, a new technology came into use for the massive replication of DNA strands. The method, known as PCR, makes it possible to produce billions of copies from a single DNA amplifier within hours, and the research possibilities it opened up for scientists earned the father of the idea, Prof. Cary Mullis, a Nobel Prize.
The study of "ancient DNA" is an example of a field of research that could only be founded after the PCR method was developed and perfected. Immediately after the death of the organism, an accelerated process of breaking DNA begins in the cells, therefore the amount of ancient DNA that can be extracted from them is small and the length of the available strands is limited. Usually this is a strand containing only a few hundred nucleic acids - a tiny percentage of the billions that made up the total hereditary material in the original cell.
The PCR allows the researchers to duplicate the tiny DNA strands, thus producing a large amount of DNA that will allow the continuation of the research work until the sequence of the strands is deciphered. In 1992, Prof. Mark Spiegelman from the University of London, relying on the PCR method, succeeded in isolating the DNA of an ancient tuberculosis bacterium. Spiegelman hypothesized that the crooked spinal cord of a 500-year-old skeleton was the result of tuberculosis, and from the DNA samples taken from the affected vertebrae, the DNA of the bacterium was indeed isolated.
The founder of the field in Israel is Prof. Chuck Greenblatt, from the Department of Parasitology at the Hebrew University, who immigrated to Israel from the USA in 1967 and was one of the first researchers of the "Leishmania" parasite that causes the "Jericho Rose". The first steps in the study of ancient DNA in Israel In 1995, Marina Fairman and Prof. Pat Smith tried to extract and characterize DNA from a baby's skeleton. that was uncovered in Masada," says Greenblatt, "but we were unable to complete the research, mainly due to a lack of technological means."
Later, Prof. Greenblatt channeled the advanced analysis methods of the DNA for the study of the buried scrolls of the Dead Sea. Most of the scrolls were written on goat or sheep skin. Thanks to the storage conditions, they were well preserved, and even after two thousand years it is possible to extract DNA from them and characterize the population of animals from which the skin was taken.
At the end of last week, 37 volumes were published, including about 900 scrolls, but there are still thousands of pieces of parchment that researchers have not been able to decipher. Familiarity with DNA will make it easier for researchers to sort them, connect the pieces that have a genetic match between them and reassemble the textual puzzle. The use of DNA analysis in the study of the scrolls is currently being done at a relatively slow pace: Prof. Greenblatt estimates that several dozen pieces of parchment have been studied to date, and he hopes that in the coming years the improvement of analysis technology will speed up the research.
During the work, the genetic "profile" of the ancient goat and the goat was compiled, and the differences between them were defined. The characterization of the hereditary material of the ancient goat and the definition of its subspecies (according to the region where they were discovered) contributed to the understanding of the demography of the ancient world. "The description of the geographic distribution of the goat," says Greenblatt, "allows us to follow the migration of peoples and evaluate the relationships between different populations."
At the same time, the researchers tried to isolate from the pieces of parchment remnants of pathogens (disease agents), such as the Brucella and tuberculosis bacteria, which are transmitted from animals to humans. Prof. Greenblatt's laboratory focuses on researching the tuberculosis bacterium which still kills millions of people a year in the third world and is a threat to patients in the West as well. In order to investigate ancient strains of the tuberculosis bacterium, DNA samples were taken from skeletons that were uncovered on three continents and dated to different historical periods.
In the state of Wyoming in the USA, a deep cave was discovered, which for 20 thousand years served as a natural trap for animals. More than 40 thousand bones were piled up on the bottom of the cave, and so far the remains of more than 20 species of animals have been identified. Samples from the bones were sent to Prof. Greenblatt, and only from the bison were they able to isolate a DNA segment of the tuberculosis bacterium by examining the bones of three other animals, Belonging to tuberculosis-resistant species, no DNA remains of the bacterium were found. The migration of the bison to North America probably took place 17 thousand years ago, and it is no coincidence that the earliest tuberculosis epidemic in the region, the 'white plague', dates back to that period."
Other important findings were discovered in a church in the town of Vák in Hungary. A wall in the church suddenly collapsed, and behind it were discovered 240 mummified bodies and an archive documenting the lives of the dead, their family relationships and the cause of their death. The mummies date from 1830-1780 and in many of the samples sent to Israel, remains of the tuberculosis bacteria were discovered. "In addition to samples from the USA and Hungary, we tested samples from the Middle Ages, taken from skeletons in Latvia," says Greenblatt, "and based on the data, we started running the genome project of the ancient tuberculosis bacterium."
Tracking the evolution of the bacterial strains allows scientists to define the geographic areas to which the different strains have spread and to assess their degree of lethality. "We see which strains survived, and where," says Greenblatt, "and we are able to assess the severity of the disease they caused in the people from whose bones the samples were taken. In terms of dealing with the disease, the genetic knowledge we accumulate is relevant both to the antibiotic industry and to the many researchers who are trying to develop a vaccine for the tuberculosis bacterium."