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. "Achieving the instruction book is a dizzying moment. It will be possible to divide all of biology and medicine into what we knew before it and what we will know after it," 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 are 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 list of parts of a person. It is like thousands of parts of a Boeing airplane. Just because you have them, does not necessarily mean that we know how to put them together The next challenge will be to find out if we can figure out how to fly this plane."
He says that in a short time 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 the DNA sequences with the click of a mouse that scientists from the Public Consortium of the Genome Project deposit into 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 man 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 High School Mathematics Olympiad and lost to the Soviets. He studied mathematics at Princeton and later continued his studies 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 pioneered the use of rapid methods for deciphering DNA. But DNA sequencing alone does not provide much knowledge until a good way to organize the new information is found. 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 an enormous 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 deluge 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 talks about will bring about a fundamental change in medicine, which he likens 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. It makes slight improvements. Since the first cell, everyone uses the same mechanism. You should not think of the thousands of human genes as thousands of completely different genes, but as different variations on 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 involves ethical problems. We do not yet know how to replace genes properly, and treating humans as in a manufacturing plant would not be correct. The genetic diagnosis, which could give patients the opportunity to receive medical treatment adapted to their unique genetic structure, could also provide the fuel for discrimination Genetically. Understanding human genetic circuits, which will provide cures for countless diseases, may lead some people to conclude that humans are nothing more than designed machines. Play the DNA cassette provided at birth. It seems to me that the greatest impact of the genome project may be precisely 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 a 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 being redefined. Interesting For me to know, for example, if we could 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
