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For the next chapter in the "Sefer of Life"/the book is deciphered - now it remains to read it - a commentary following P

Eight months after the publication of the draft, the complete genome map is presented today - a great achievement but the story is not over. The genomics chapter is almost closed, but the proteomics chapter - the understanding of the composition of proteins and their effect - is beginning to be written. The medical benefits are enormous, but the scientists warn against "genetic intoxication"

Eight months ago, Bill Clinton and Tony Blair called each other via satellite to announce one of the greatest scientific achievements of all time: the decoding of the human genome or "Book of Life". But this PR stunt is not supported by research data or scientific conclusions. This week scientists get their first chance to glimpse the evidence, with the official publication of the human genome in the journals 'Nature' and 'Science'.
The two bodies that competed in deciphering the genome - the Human Genome Project and Celera, an American biotechnology company - have already published dozens of scientific articles. Their most interesting conclusion concerns the very limited number of genes that the genome contains - about 30 thousand. That's about the same number as a mouse and only double that of a fly or worm. Most scientists expected to find 100 thousand genes, and some estimated that the number of genes would even amount to 140 thousand.

The low number of genes will certainly disappoint those who think that a larger number indicates improved quality. Eric Lander, from the Whitehead Institute for Genomic Research in the US says: "It is seen as a kind of violation of human dignity."

But you can look at it another way: if the number of genes needed to determine a person's "specification" is similar to that of other animals, then human biology reaches incredible levels of richness and complexity.

Biologists will have to stop thinking about individual genes, which give instructions for creating individual proteins (proteins are molecules such as hormones and enzymes that control biological processes). Instead, all of our DNA - the genome - should be seen as a very complex system.

As Craig Venter, Celera's president, puts it, "There are no 'bad' or 'good' genes, there are only networks that exist at different levels in different connection methods, and in different states of sensitivity to external influences. The idea that one gene equals one disease, or that one gene produces an important protein, is thrown out the window."

No one knows how many proteins there are. The answer will be revealed in the coming years through the developing field of proteomics - the successor of the field of genomics. But Venter estimates that there are about 250 proteins in our body - about 10 for each gene - to carry out the necessary work for the proper functioning of the body.

John Solston, from the Sanger Center near Cambridge, where a third of the human genome has been deciphered, says that the results prove that we achieve human complexity, not by adding additional protein production instructions, but "by increasing the variety and selection of genes that control other genes." Many human genes can be called in different ways, and many proteins can be modified by other proteins without the intervention of genes.

"A complex picture of gene and protein control is created, when genes are turned on and off with extraordinary subtlety - during the development of a human being from a fertilized egg to an adult, and to maintain our bodies on a daily basis," says Richard Gallagher, the publisher of Nature.

Some experts said earlier this week that the surprisingly low number of genes would be good for medicine, because there would be fewer genes to understand. But the opposite logic may be true: the complex interactions between genes may make it difficult to cure diseases by treating one or two genes, for example, with gene therapy. This fact may explain why gene therapy has been so disappointing in clinical trials over the past decade. The emerging field of stem cell technologies - replacing failed cells with new cells with more "life force" - may yield better results, because the patient receives the entire genetic system at once.

The genomes that will be published this week are sequences, consisting of the genetic load of five volunteers in the case of Celera, and the load of a dozen volunteers in the case of the public project. All major racial groups are represented. The results show that the DNA of two unrelated individuals is 99.9% identical - on average, about three million of the three billion "letters" that make up the genetic code are different from person to person.

But the biological differences are even smaller than that number suggests, according to Venter. Most of the differences between the genetic codes of different individuals have no effect "and only about 10,000 genetic differences (between individuals with no family relationship) will have biological significance", he predicts.

Discovering the biological differences that do have an effect is one of the important remaining tasks for the human genome project. It will be a basis, for example, for pharmacogenomics - to understand why certain people with a certain disease respond better than others to a certain drug treatment.

"If you were able to identify the patients whose treatment would lead to a toxic reaction, compared to those for whom the drug would be beneficial, then there would be a potential treasure trove of drugs that were discovered or partially developed and could not be used until now," says Mike Dexter, director of the Wellcome Trust, a British charity. which contributed 210 million pounds to the public project. "The information we are gathering now will give us the ability to conduct diagnostic tests, which will allow us to use existing drugs in a better way, and will give us the ability to develop new drugs."

Another important avenue of research will be to compare the human genome in detail with that of other animals. The differences will help reveal the functions of genes, most of which are still unknown. The DNA genome is currently being deciphered by Celera and a public-private consortium, and Venter believes "that we already know that there are only 300 human genes that do not have a counterpart in the mouse genome."

Meanwhile, computer scientists are developing methods to reduce the cost of decoding DNA so that the genomes of individual individuals can be decoded regularly. If miniaturization and automation technologies continue to cut decoding costs by a factor of 10 every decade, Gallagher believes that by 2020 it will be possible to decode individual genomes for several thousand pounds each.

George Church, director of the Lipper Center for Computational Genetics at Harvard University, points out that the information contained in one genome can be put on a standard DVD. He is confident that fairly inexpensive technologies will soon be developed to read this information.

Researchers caution that such information will need to be used judiciously, as health, behavior and other characteristics are influenced by many factors. As Celera scientists conclude in the journal 'Science': "There are two false claims that should be avoided: determinism - the idea that every characteristic of a person is directly linked to the genome; And reductionism - according to which, now that the human genetic code is fully known, it is only a matter of time before our understanding of gene functions and interactions between them will provide us with a comprehensive causal description of human variation."

by Tamara Traubman

Geneva. Humanity received today the "book of life" of man. This book - which consists of a sequence of DNA units that together make up the human genome - was until a few years ago considered an unknown country.
Today, 3.2 billion DNA units - with the exception of some areas that contain mainly DNA sequences that current machines cannot decipher - are found on the Internet, in a database called the "Gene Bank".

"In the last 40 years," said biologist Prof. David Baltimore, "I have witnessed many exciting discoveries in biology. But I still got chills when I first read the reports describing our genome."
The human genome sequence was cracked by two bodies: a public consortium of academic institutions, and the American company Celera.
The provocative statements of the president of Celera, Dr. Craig Venter, created intense competition between the two entities, which sometimes exceeded the limits of healthy competition. Dr. Venter returned and announced that on
By using the method he developed, he will succeed in deciphering the genome before the public consortium, and that the sequence he will produce will be better.

Who really had a better streak? From an examination of the two sequences it becomes clear that both contain an almost identical number of DNA units (the sequence of the public project is slightly larger). When examining in detail the differences between the two sequences, it seems that the sequence of the public project is more "processed". The project scientists analyzed a larger amount of data and, based on this analysis, deduced in which regions genes are located and what their presumed function is.
Celera's success in obtaining a draft of the genome within a year shows what can be achieved today with the help of the new decoding machines, supercomputers and strong faith of wealthy investors.

Dr. Venter used to say that the decoding of the genome will only serve as an infrastructure for the company's main mission. This designation is the new scientific field called bioinformatics. Bioinformatics people use powerful computers to interpret the information written in DNA. Interpreting the vast information written in DNA and finding medical applications for it are currently the hottest fields in genomics. Even after decoding the DNA, you still have to find out where along the chain the gene starts and where it ends.

In this respect, the genome is like a message from another world that must be learned how to read. Our genome, like any message from another world, will change our world, when we understand its full meaning. Although the study of the genome has already begun, it will be decades before every detail of it is known.

Along with the human genome sequence, a map including 1.42 million small genetic variations was also published. The scientific name of these variations is branches, and they are changes in one DNA unit. Each such small change may change less than ten percent, but like winning the lottery, the right combination of branches can prevent a certain person from developing heart disease, despite eating chocolate and high-fat foods all his life, while another person will suffer a heart attack as early as age 35. The Chapter Next in the "Book of Life" will be the identification of the influence of the branches on man, and the investigation of the proteins - the substances that the body produces according to the instructions written in the genes.
{Appeared in Haaretz newspaper, 12/2/2001}

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