Dr. Francis Crick
July 4, 2000
Greetings from Southern California!
I am very honored to receive, with Jim Watson, the award of the prestigious Liberty Medal. We are being recognized because in 1953 we put forward the double-helical model of DNA, using the x-ray data of Rosalind Franklin, Maurice Wilkins and their collaborators.
Many people now know that DNA is a double helix but the key feature of the structure is the pairing of the bases. The base A, on one strand, pairs with the base T on the other. In a similar way, G pairs with C. The number plate on my car reads “AT GC” and I find that, even now, many people don’t know what it signifies. If they ask me, I tell them: “That’s the secret of life!”
Thus genes are written in a four-letter language (A, T, G and C) and the genetic information is conveyed by the exact sequence of these bases on any bit of DNA, just as the meaning of an English sentence depends on the exact sequences of its letters.
Since that time there have been major advances. Molecular biologists have learned how to copy any piece of DNA, to cut it in special places and to join pieces of DNA together. They do not usually use ordinary chemical reactions, but instead the tools Nature uses to do these jobs. These proteins—these enzymes—act more quickly, more accurately and more selectivity than smaller chemicals.
With the polymerase chain reaction we can copy again and again any particular piece of DNA, so that from a few molecules of it in a test tube we can synthesize many millions of identical ones.
In addition, scientists have devised rapid methods of sequencing any particular stretch of DNA. More recently, robots have been invented to do this automatically.
The powerful methods now available have made it possible to sequence, almost completely, the entire genetic material—the entire genome—of a number of organisms. Not merely those of various viruses and bacteria (which are relatively small) but already those of a yeast, a nematode and a fruit fly, which are considerably bigger. Before long we expect to have most of the sequence of the human genome (which is bigger still) and after that the sequence of the mouse genome and, eventually, that of many other animals. Nor have plants been neglected. A preliminary sequence of rice has already been announced and that of other plants will soon follow.
The extent and speed of these advances are truly remarkable. Few people, a generation ago, would have guessed that so much would have been achieved by now.
The enormous flood of precise information is going to transform biology and medicine completely, but it is important to realize that it is only a beginning. Most genes code for some particular protein—proteins are the machine tools of the cell. We can translate the base sequence of any such gene into the corresponding one-dimension sequence of amino acids which make up the polypeptide chain of a particular protein. But this polypeptide chain needs to fold itself up to form the correct three-dimensional structure of the protein. For some proteins the 3-D structure has been found by x-ray analysis, but as yet, it is difficult for us to predict the correct three-dimensional shape from the one-dimensional sequence and it is the 3-D shape that matters. We can sometimes make a good guess as to how a particular gene product might act—whether it breaks down a particular small molecule, for example, or whether it acts as a channel in a cell membrane, and so on—but the true function of each gene product will have to be established for each particular gene. As we may have as many as 50,000 different genes—this number is, at the moment, only a very rough estimate—it is going to take some time to find out what each gene does.
After that the next job will be to discover how fast each gene acts and exactly what controls these rates. This rate, of course, is different in different parts of your body. Muscles need the activity of genes making muscle proteins; nerves need genes making nerve proteins, and so on. The rate at which genes act involves feedback processes. Such systems are called “non-linear dynamic systems.” Not much is yet known about these theoretically and they are not easy to study experimentally.
The details of all this are not important. What is important is to grasp that we see before us vast new regions of biology to explore; that we are only just beginning this exploration; and that it will take many scientists, worldwide, many, many years of hard work before we can begin to understand exactly how our bodies and our brains work, how they developed in the womb, and how they evolved since life began on earth several billion years ago.
What impact will all these discoveries make on ordinary people? Even branches of biology such as ecology and environment studies will be altered, but the main impact is likely to be on medicine and agriculture. And they will affect not only the developed countries but also the developing ones.
Already these new techniques have given us some insight into the causes of cancer, and also of diseases such as Huntington’s and early-onset Alzheimer’s. They are helping us to understand and combat AIDS and other infections. New pest-resistant crops have been produced which could help agriculture, especially Third World agriculture. Several domestic animals have already been cloned.
DNA can be used to establish paternity, both for people and for chimpanzees in the wild. It has also shown that a disconcerting number of condemned criminals are in fact innocent. So far, efforts to alter people’s genes for medical reasons have been disappointing, but there have been one or two successes.
Jim Watson has agreed that he will discuss some of the possible future developments in greater detail, and also touch on the many ethical and legal problems that they are likely to produce. It is impossible to predict the future in detail but it is sometimes possible to see general trends. One can only hope that, on balance, all this work will produce more good than evil. In particular, that it will increase freedom from deprivation, one of the freedoms delineated in the concept of freedom associated with The Liberty Medal.
Thank you again for this honor.