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Why did the completion of the DNA sequencing of the tuberculosis bacterium strike a chord, and what is the uproar in the genome world about?

Note, 27/2/2021: One of the scientific successes of the fight against the corona epidemic was the deciphering of the genomic sequence of the virus and even comparing it with that of similar viruses in animals. Forgetting that this ability is new. In the XNUMXs, it took many months to decipher the genome of even a simple creature like a virus, let alone the more complex bacteria. It took ten years to decipher the human genome - of one person (Craig Venter). Today, for a hundred dollars, you can get a genomic profile that describes the genetic diseases that person carries, as well as their origin.

Science defeated the corona with the help of technologies developed at the time. The ones who failed by the way are the politicians.

Comparison between the lungs of a tuberculosis patient versus a healthy person. Image:
Comparison between the lungs of a tuberculosis patient versus a healthy person. Image:

The article was published on June 19, 1997, with the permission of the author:

This week it was learned that scientists at the Sanger Center in England and the Pasteur Institute in France completed the biochemical reading of the complete DNA sequence of the tuberculosis bacterium. By itself, "sequencing" the genome of a bacterium is no longer exciting news in the world of science. Because, in the last three years, about a dozen genetic encyclopedias of various bacteria have already been deciphered. The headlines the event received were due to three reasons. First, the sequenced genome belongs to a famous bacterium. This is the tuberculosis bacterium, known by its Latin name MICOBACTERIUM TUBERCULOSIS and is considered the leading cause of death, especially in the third world. Second, the genome of this bacterium is relatively large, 4.4 million DNA bases - the second longest of all the bacterial genomes sequenced so far. And thirdly, the publication happened at the end of a fascinating race: another research group, that of the pioneer of bacterial sequencing, Craig Venter from the United States, was defeated very close to the finish line.

Venter is known as the troublemaker of the genomic world. He independently founded a private research institution in Washington, TIGR, at the gate of which stands a statue of a tiger symbolizing fighting spirit. A few years ago, Venter initiated, against the advice of all the genome experts in the world, a project for rapid and targeted sequencing of those few percentages of the human genome that encode the proteins themselves. It is argued against him that he covets the icing on the cake and that this violates the spirit of the genome project, since it should also encompass the intermediate sections, the terra incognita of biology.

About a month ago Venter dropped a new bombshell: he announced the establishment of a company that will sequence the entire human genome in three years instead of seven, and at a tenth of the price. The genome world was like a concoction: was it possible for one person to defeat about twenty genome centers in the world? The storm has not yet subsided, but it seems that finally a compromise will be reached between Venter's methods and the accepted methods, and that this will be to the benefit of all. In 1995 Venter was also the first who dared, contrary to the opinion of many, to attack "in one blow" an entire genome of a bacterium. The main challenge was computerization and TIGR met it successfully. It turned out that so far Venter was right in his actions and today many are following in his footsteps, including huge expansion efforts in biotechnological companies whose genome research is at the top of their commercial agenda. It can be safely asserted that Venter's courage three years ago led directly to the current success in the tuberculosis matter as well.

Bacteria are the simplest organisms endowed with the ability to live independently. This is in contrast to viruses, which do not have a life of their own and all their activity depends on the host cell in which they reside. The bacterium functions as a living being for everything: assembles and breaks down thousands of substances, builds itself, communicates with its environment and produces offspring by division. The smallness of bacteria will be illustrated if it is said that at the point at the end of this sentence a "demonstration" of about a hundred thousand of them can be gathered. The bacterium's genome, the genetic program that enables its construction and functions, contains several million chemical letters. This amount of information is equivalent to the full text of the "Haaretz" newspaper for an entire week! If we had such a wonderful miniaturization method at our disposal today, we could produce an information CD that would contain about one hundred million gigabytes, compared to a few gigabytes with existing technologies.

Why does a bacterium, a tiny single cell, need so much information? What is north in the genome of a bacterium? Questions like these are the driving force behind hundreds of scientists working day and night, perfecting robotics and supercomputing and wondering about the meaning of the resulting DNA sequences. They study the overall combination of thousands of genes in a logical-chemical network, each northern component of which is an elaborate protein "machine". The co-ordination of all these within the bacterium is much more complicated than that of the mechanisms of an advanced fighter plane. If we fully understand this, even if only in a tiny way, we will perhaps know the secret of life. We should not expect this to happen immediately upon completion of the decoding of the sequence: many decades of intensive experimental and theoretical work are expected. But reading the DNA text is a fundamental condition for starting the fascinating journey of discovery. And what about curing tuberculosis and other bacterial diseases? The genome of the particular bacterium contains essential information about the special properties of the invading organism. The tuberculosis bacterium is able to defend itself for many years against the sophisticated immune attack mechanism developed by superior beings in their war against foreign invaders. The bacterium "cheats" our immune system, using methods somewhat similar to those used by the AIDS virus. In the new study, evidence was discovered that hundreds of the northern proteins in the bacterium's genome are involved in the defense it has developed, and their understanding will enable the perfecting of our counter-attack with unconventional biochemical methods, including new vaccine components. Furthermore: even the antibiotic drugs of the types known to us are aimed at specific protein targets in the bacterium, and the knowledge obtained will enable new recipes, against which the bacterium has no resistance.

The human genome contains about three billion bases, that is, it is about a thousand times larger than that of a bacterium. At the beginning of the next millennium, with the completion of the first phase of the human genome project, the human DNA text will be placed before us - equivalent to about twenty years of daily newspaper issues. This goal will be achieved through international cooperation and also through fruitful competition between the parties involved, including those who are now struggling to decipher the tuberculosis bacterium. If the full understanding of a bacterium takes decades, cracking the secrets of a human being may take many hundreds of years. The same technologies, and the same genetic, biochemical and computer science skills, which will help in understanding the bacteria, will serve us faithfully also in the long futuristic journey to understand ourselves.

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