Comprehensive coverage

Cracking the genome - the fascinating story of unraveling the contours of our genome

Kevin Davis. Translated from English: Atalia Zilber. Ofakim series, published by Am Oved, 275 pages, NIS 84

Yaron Groner

DNA structure, human fingerprint and genealogy

In one of the pages of the "Books" supplement, the editor explains to the embarrassed reader how to distinguish, even before reading, whether the book in front of him is fiction (literature) or non-fiction (non-fiction). "Very simply (suggests the editor) you have to start from the end.
If there is a key, an index, most likely it is "non-fiction".

According to this definition, Kevin Davis' book, "Cracking the Genome", is real non-fiction. Those who start from the end will find not only a key, but also a special section called "Notes", and it includes a detailed collection of references to the articles mentioned in the book and mentions of events intertwined in the plot. But despite the technical definition, according to which the book is not fiction, it is written in a narrative language and has a plot that mixes loves and hates (not only for science) and the pursuit of honor and money, and there is even a "happy ending". Therefore, for those of you who are too impatient to read the review to the end, I will recommend at this point to run and buy.

Now that the book in its Hebrew translation is in your hands, first look at the cover; Its design in the Hebrew edition deserves attention. The core of the cover image is not the plastic film woven in the form of a double helix, which symbolizes the structure of DNA, but the images in the background, which tell a story. In the center of the picture is a fingerprint of a person, below it and on both sides, in the form of a relief, a drawing of a family genealogy appears. At the bottom of the cover image is a colorful zig-zag and in the background a photo of striped columns: these two models demonstrate the two methods for determining the sequence of bases in DNA (the floor, in the translator's language). The striped columns show the manual method by which DNA fragments were sequenced many years before the genome project. The colorful zig-zag shows the automated method by which the massive project of mapping the human genome was completed.

And what is the story that the cover photo tells? The day will not be far, and by means of DNA sequencing, which will be taken from a drop of blood of each of us, it will be possible to produce the personal fingerprint of our genome. With the help of this information it will be possible not only to place us in the family tree, but also to identify which defects and diseases - or alternatively abilities and talents - we inherited from our parents and what from this we passed on to our descendants.

The back cover, as back covers do, abounds in superlatives, although not in a blatant way, except for one exaggerated statement that recurs in one form or another throughout the book and compares the tremendous achievement of cracking the genome sequence to the invention of the wheel. I suggested to the readers to free themselves from the very beginning of the impression that this statement may evoke, and not to search among the pages of the book for signs that characterize inventions such as the theory of relativity and discoveries such as the periodic table or Mendel's laws of inheritance. Instead, it is better to concentrate on monitoring - which requires attention - the course of events and trying to understand the individuals who are acting. Also those who played key roles in the years leading up to the start of the project, but mainly those who engaged in the craft and brought about the tremendous achievement of deciphering the human genome; An achievement (not an invention), whose immediate and future consequences for the lives of each of us are far-reaching. This is also the reason why "Cracking the Genome" is a must-read for anyone of sound mind who wants to understand the scientific happenings in our world and how they affect, and will continue to affect, our lives. The author was right to choose to quote in the opening pages one of the heroes of the drama, Craig Venter, who said that "the sequence is only the beginning".

The story actually begins in 1953, the year when James Watson and Francis Crick discovered the structure of DNA (the double helix) and created a turning point in molecular biology. Another 50 years passed before the information encoded in the DNA was decoded. The process, or the race, as it is called in the book, continued over the last decade of the last century and the book in front of us is a continuous and flowing description of the events from the pen of Kevin Davis, the founding editor of the scientific journal "Nature Genetics". Davis describes the race to crack the genome on its scientific, political and economic aspects, while emphasizing the participants, the humans, their weaknesses and struggles
The power and prestige they managed while the project progressed.

But what exactly is the genome project? In 1990, after extensive discussions that were accompanied by public debates, the US federal government allocated three billion dollars over 15 years for a program designed to determine the sequence of bases in human DNA. That is, to decipher and read the three billion letters that make up the encyclopedia of life.

Two years earlier, in 1988, when the first ideas about the project were just being thrown into space, I was invited to give a lecture at the prestigious convention that takes place once a year near New York, at the place with the picturesque name of Cold Spring Harbor. The theme of the convention, which was organized that year by James Watson, the discoverer of the structure of DNA, was "the molecular biology of the human race". The organizer asked me to present the work of my research group, which a few years earlier had begun to investigate the molecular biology of Down syndrome. We had the right to be first, since already at the beginning of the research we were able to isolate and sequence for the first time a gene from chromosome no. 21, which is known to be the chromosome involved in causing Down's syndrome. About 15 years later, the circle was closed, when together with our colleagues at the Weizmann Institute's Genome Center, we participated in the global corporation that sequenced the entire 21st chromosome, as part of the Genome Project.

As part of the convention in Cold Spring Harbor, a special meeting was convened dedicated to the debate on whether to continue the genome project or stop it. Senior researchers in molecular biology participated and expressed their opinion. I was surprised by the variety of opinions and the intensity of emotions that the proposed project evoked even then, even before it began. Particularly interesting were the opinions of renowned scientists and Nobel laureates such as David Baltimore and Dan Nathans (deceased), who expressed concern that the tremendous technical effort and resources that would be invested in the proposed project would come at the expense of pure basic science, which is largely dependent on federal government funds. Even then, non-scientific political aspects were added to the discussion, one of the original ones voiced by Dan Koshland, a biochemist of the same name and editor of the prestigious journal "Science". Prof. Cushland stood up and with American nonchalance said: "The time has come for us, the biologists, to have a national project that costs billions of dollars." And so, two years later, the race to decipher the DNA sequence began.

But the debates among the scientific community continued and even intensified. James Watson, who was appointed the first director of the project, resigned after a few years due to differences of opinion with the director of the NIH (- NIH, the US National Institutes of Health - is the federal authority through which the huge budgets are channeled to finance the project). It is interesting and symbolic that the subject of the dispute was the moral justification behind the requirement to register patents on genes that are discovered while carrying out the genome project. This demand was put forward by an NHI researcher, Craig Winter, who shortly afterwards appeared at center stage, and was supported by Brendin Haley, director of the National Institutes of Health. James Watson, who strongly opposed this possibility, submitted his resignation. He was replaced by Francis Collins, a molecular geneticist of stature and organizational ability.

Here is perhaps the place to explain: the genome project quickly became an American national project
for a global project, which was conducted in national centers established close to the institutions
scientists around the world. An international steering committee assigned to each center, accordingly
For its size, the DNA segments - the chromosomes - which he will sequence out of 46
The chromosomes present in man.

Close to the appointment of Francis Collins as director of the genome project, the affair at its center broke out
Craig Venter stood and that her scientific and non-scientific influence on the progress of the project
And its ending is described in the book with great precision and in bright colors. It is evident that the author is not only found
in details, but lives and breathes the happenings. Venter, a picturesque figure, a talented scientist
And a technocrat with a sense of business, burst into the arena when, contrary to convention, he proved that
The use of the "shotgun" technology (a technology that is fundamentally different from the one they adopted
The Genome Project participants) is a cheaper and faster alternative to deciphering DNA sequences.
Venter proposed to abandon the method used by the national centers and adopt the
The "shotgun" method.

A few words about the difference between the two methods. While the public project took a method of
An orderly progression follows the thumb side as each center concatenates the chromosomes
assigned to him, Venter proposed to adopt a method based on cutting the entire genome into pieces
smallness and the floor of all the pieces, without considering the chromosome they belong to.
When the flooring process is finished, Venter suggested, it will be possible to use the computer
A powerful one who will arrange the pieces and connect the information in them into one sequence that will give the sequence
the genome. Venter's proposal was received with skepticism by the directors of the national centers,
and Collins at their head, and they rejected her.

When Venter realized that on the basis of a theoretical argument he would not be able to convince of the rightness of his way,
In 1998 he founded a large private company, in partnership with Perkin Elmer, to build instruments
the floor Immediately upon the establishment of the company, Venter issued a statement that the company he founded, "Clera
Genomics" named it, will complete the genome floor within three years (ie in 2001
instead of 2005, the estimated completion date of the public project) and costing 300
A million dollars only. Venter attacked head-on in dramatic press conferences the
The public project and its managers with allegations of inefficiency and waste of public money.
He made cynical use of the fact that for the first eight years of the project
(1998-1990) only 3% of the genome was sequenced in the national centers (the slowness was due, between
the rest, from the need to develop appropriate technologies). Venter's declaration that society
By owning it you will complete the task faster and cheaper than leading to a world war
Between him, with his partners (the Perkin Elmer company), and the managers of the public project.

Another bone of contention was the availability of information. While the public project participants drove
Publish in the public domain (on the Internet) every day all sequence data
Created on the same day, the agreement between Celera and Perkin Elmer was that the data
that Celera produces will not be published but will be kept secret and will be used to identify important genes.
This arrangement will allow Celera to register patents on those genes that may be used for purposes
drug development. As Celera's activities progressed, the war of words heated up
Between the speakers of the public project and Celera, at the same time with a steep increase in price
Celera's stock. The managers of the public project accused Celera of being exploitative
the openness of the public project and its transparency, and uses the data that is published
in the public for her private needs, all this to glorify the financial assets of
The shareholders, led by Craig Venter. The Salara people, for their part, blamed the project
the public in clumsiness, inefficiency and wasting funds that could have been used for the purposes
other sciences. The exchange of mutual accusations escalated and attempts were made to compromise
between the parties and reach cooperation between them failed.

Until in the spring of 2000, President Bill Clinton entered the picture (yes, he is also in this conflict
Intervene and with great success). Under pressure from the president, the parties entered into negotiations which
led in June 2000 to the joint announcement of President Clinton and the British Prime Minister
Tony Blair for completing the first draft of the human genome sequence. version
The final one after editing and proofreading has not yet been finalized.

The book in front of us not only reliably and clearly describes the drama and upheaval
the events; It also combines - and this is its strength and uniqueness - reliable descriptions
and accurate of the important discoveries in molecular biology that were made in the past, and which
Their consequences find expression now with the availability of the information that is produced
from the genome project. The book also describes the important discoveries made along the way
The race to sequence the genome.

The combination of describing past and present discoveries teaches us an instructive chapter on form
Scientific thinking and the progress of biological research. The key to success or failure of
A popular science book is the author's ability to tell a story, and Davis stands
Good luck with this task. Davis's advantage is that he is also an understanding scientist
all the intricacies of the scientific happenings and also a newspaper editor, who trusts writing
bright Therefore, he also managed to describe not only the drama that accompanied the process, but also
the magnitude of the achievement and the elation that surrounded the scientific community when it was completed
the task. A good way to describe it is David Baltimore, Nobel laureate and great
The researchers in molecular biology, quoted from his words: "I saw a lot of biology
Exciting in the 40 years that have passed, and yet my body shuddered when I first read the
The article describing the contours of our genome" (this quote from Baltimore
It does not appear in the copy of the English original provided to me by the editor, but there is no doubt that it does
said the things I asked him).

The professional, current and faithful translation of Atalia Zilber brings us a document
Fascinating and properly written that is both enjoyable to read and brings readers closer to Hebrew
to scientific and ethical issues that are on the public agenda in the world. The editing
The scientific, on the other hand, is not free from disruptions and embarrassing mistakes. For example, concepts
that have an accepted Hebrew translation such as the disease "muscular degeneration" appear in their name
The obscure foreign "muscular dystrophy" or the translation of the concept the human race
to the "human race", while the common expression is "the human race".

I also regret that the Hebrew edition does not include the term Genome in the name
The book, and thereby contributed to the displacement of the common disruption in Hebrew of using the whistle
In the pronunciation of the term (genome). This strange disruption has penetrated our language to such an extent that
A knowledgeable and meticulous writer like David Grossman took pains in his latest book "In the body I understand"
Punctuate the concept with a whistle (p. 113), for the sake of removing doubt.

Whoever follows my recommendation and reads the book will enjoy and learn. And those of us who
Followed the drama in the last ten years, will embrace the past and enjoy the spectacle
The detailed place. For them, the achievement of cracking the genome is surely gone
.fiction

Kevin Davies Cracking the Genome

Prof. Yoram Gruner is a researcher in the Department of Molecular Genetics at the Weizmann Institute of Science

Leave a Reply

Email will not be published. Required fields are marked *

This site uses Akismat to prevent spam messages. Click here to learn how your response data is processed.