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The book is already here, you just have to learn to read - an interview with one of the heads of the human genome project

The biggest impact of the human genome project may be precisely the way we choose to look at ourselves and others, who we are and what we want to be. This is the opinion of Dr. Eric Lander, who with his colleagues recently finished deciphering about a third of the human genome

by Tamara Traubman

In a few weeks, maybe even days, the scientists of the Human Genome Project will publish the first draft of the genome, the complex and complicated instruction book for creating a person, in which all the secrets of life are contained. "Getting the instruction book is a dizzying moment. It will be possible to divide all of biology and medicine into what we knew before and what we will know after," said Dr. Eric Lander, Director of the Genome Center at the Whitehead Institute at MIT. Lander and his colleagues at the institute this month finished deciphering a billion DNA bases, which is about a third of the human genome. The other two thirds are divided between all the other universities in the world, which have been working since 1990 on decoding the genome.

A few weeks ago, when he came to Tel Aviv for two busy days, including receiving an honorary doctorate from Tel Aviv University, he spoke about science in the era after the decoding of the human genome. Decoding itself provides little understanding, Lander said. “It's still just an instruction book. We don't know how to read it."

In Lander's laboratory, which looks more like a manufacturing plant full of machines and computers, 35 scientists and technicians work. In the last ten years, they have focused on deciphering the genome, which means identifying the exact sequence of the DNA bases in the human genome. The chemical bases of DNA are divided into four types, each type is marked with a different letter: A, T, G and C. In the different combinations of these four letters is written all the information necessary to create life: what will be the appearance of a person, what will be the daily tasks of the cells: the metabolism that turns food into energy, when to stop reproducing and how to communicate with other cells. Disruption of one letter (for example, when the letter G appears where the letter A should be) may cause illness.

The end result of decoding the genome is a long chain of letters. But from the raw sequence it is still impossible to know where the scattered genes are, and more importantly: what their role is and what they are responsible for. "Now that we have 87% of the genome, we have to learn to read it, try to understand its meaning," Lander said. "We are very proud that we were able to obtain such wonderful literature, but learning to read is the important thing. We now get the complete human parts list. It's like thousands of parts of a Boeing airplane. The fact that you have them, does not necessarily mean that we know how to connect them. The next challenge will be to find out if we understand how to fly this plane."

He says that before long the entire genome will be put on a CD-ROM, and in ten years they will not understand how it is possible to practice biology without knowing the DNA sequence. Already today, anyone can connect to the database on the Internet and download with the click of the mouse the DNA sequences that scientists from the public consortium of the Genome Project deposit in it every day.

Dr. Lander, who is considered by scientists to be one of the most important leaders in the genome project, is actually a mathematician without any academic degree in biology. This lively person first opened a biology textbook when he was only 30 years old. Lander was born in Brooklyn to a lower-middle-class family, and at school was considered a mathematical genius. He attended Stuyvesant High School for Mathematics and Science in Manhattan, achieving the highest grades in his class. In '74 he participated in the World Mathematics Olympiad for high schools. His team came in second place and lost to the Soviets. As an adult, he studied mathematics at Princeton and was chosen to deliver the farewell speech at graduation. He later went on to study mathematics at Oxford.

Today he deals with issues that only a person with a real background in mathematics can deal with. The "Boston Globe" newspaper compared him to Henry Ford, the American car manufacturer who pioneered the moving film method. Lander was a pioneer in the use of rapid methods for deciphering DNA. But the DNA sequence itself does not provide much knowledge until a good way is found to organize the new information. If all the DNA letters in the human genome were printed in a book, it would take 11 years to read it all at a rate of ten letters per second. The traditional discipline of biology does not have the tools to deal with such a huge amount of information.

Today, Lander devotes much of his time to a new field that combines biology and computers, bioinformatics, which aims to bring order to the chaos of biology. With his colleagues he developed algorithms to organize the new flood of data, and with their help it will be possible to identify genes that will eventually yield what he calls "the complete catalog of human genes".

The "gene catalog" that Lander is talking about will bring about a fundamental change in medicine, which he compares today to a mechanic who does not know all the parts of the car he is servicing. "In fact, the more you know, the more surprised you are that people manage to do what they do in medicine today."

Twentieth century genetics was characterized by laboratory work that focused on investigating a single gene at a time. Lander developed statistical models that allowed scientists to track tens or even hundreds of genes at a time. He predicts that this global approach will dominate in the current century. It will enable new biological insights, which will be especially essential to understand complex processes such as aging, cancer development and heart disease, which are not the result of one gene but of many genes.

Lander compares the genome project to the periodic table. Just as Mendeleev arranged the chemical elements in a logical order, which until then seemed unrelated, Lander believes that it will be possible to classify the thousands of human genes into several superfamilies. "Evolution does not go back to the drawing board every time. She makes minor improvements. Since the first cell everyone uses the same mechanism. One should not think of the thousands of human genes as thousands of completely different genes, but as different variations of a common theme."

Lander realized a long time ago that it was easier to identify disease-related genes by working with small, isolated populations that originated from a few founding ancestors and did not accumulate much genetic variation. Thus, for example, he found a gene associated with diabetes among the inhabitants of the Bothnia region in western Finland. Lander, himself a Jew, says that Israel is an interesting place to locate genetic diversity, because the Jews have preserved their genetic uniqueness even in the Diaspora, and today many Jewish ethnic groups are concentrated in Israel. "It was interesting to see that the Y chromosome is similar in Jews and Palestinians."

"We need to approach this new world with a clear mind, mixed with tension," Lander said. "Changing the genome and improving it involve ethical problems. We still don't know how to replace genes properly, and treating humans like in a manufacturing plant would not be right. The genetic diagnosis, which could give patients the opportunity to receive medical treatment adapted to their unique genetic makeup, could also provide the fuel for genetic discrimination. Understanding the human genetic circuits, which will provide a cure for countless diseases, may lead some people to conclude that humans are nothing more than machines designed to play the DNA tape provided at birth. It seems to me that the greatest impact of the genome project may actually be the way we choose to look at ourselves and others. Dealing with these challenges, some of them quite insidious, requires constant vigilance, lest we lose touch and stop seeing why we are actually here, who we are and what we want to be."

At the end of breakfast by the sea, before leaving for a meeting with the employees of the Israeli bioinformatics company Compugene, he said: "The question is what will we do with all this in the 21st century. Can we really understand the secrets of biology? The limits of our knowledge and possibilities are redefined. I'm interested in knowing, for example, if we can ever sketch a bacterium or a peacock knowing only its DNA sequence."
{Appeared in Haaretz newspaper, 16/6/2000}

* The Hidan site was part of the IOL portal from the Haaretz group until 2002

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