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The Mad Hatters

The discoveries of Watson and Crick challenged analysts to attempt to forecast future conquests

Carlos Haag

They were previously described as “two mad hatters talking over tea” and in reality these two guys, as celebrated as the model of the helix that they revealed, have led biology into the world of wonderland. “Did we realize at that time the significance of our discovery? Well, Jim Watson recalls that he announced in The Eagle, his local pub, that they had discovered the secret of life.” Francis Crick says in a text exclusively ceded to the magazinePesquisa FAPESP . “On the morning of Saturday the 28th of February of 1953, Jim had painstakingly built up the metal models that we had been making of DNA and noted that an A to T pair had a format similar to that of a C to G pair. At that moment we saw that the pairs of bases obeyed these rules”, he says.

“The models had the correct symmetry, linked by a perpendicular double axis to the axis of the helix”, he recalls. Curiously enough, Watson didn?t like the idea. “He attempted, without success, to build a dorsal spine as if the two chains were in parallel. But this demanded a rotation of 18 degrees between one nucleotide and another, too narrow, the situation was that the anti-parallel chains demanded 36 degrees and the rotation was much easier”, he adds. The Rosetta Stone of genetic configuration had been revealed.

“The double helix initiated a chain reaction of discoveries as to life functions and new revelations came much more rapidly”, reveals Victor McElheny, former director do Cold Spring Harbor Laboratory, visiting professor for the program of Science and Technology at MIT and author of the recently published bookWatson and DNA: Making a Scientific Revolution . With unusual modesty, Crick has some reservations about the importance of his work. “No doubt it was fundamental. But we did not foresee the sequencing of the human genome. At the maximum we saw as far as genetic coding, through we had thought erroneously that ribosome RNA was the RNA messenger”, Crick says.

“We thought that to sequence DNA would be something extremely difficult and that it would have taken a very long time. And neither did we forecast recombinant DNA”, he says. “But this is part of science. Rarely can one correctly forecast something more than ten to fifteen years ahead. Unexpected discoveries can frequently completely alter the picture”, the researcher evaluates. McElheny recognizes that the current future owes a lot to the efforts of Watson. “He forced everything forward. Jim knew that it was necessary to make people understand what the discovery meant and that it is a revolution based on large problems. And, after the discovery of the double helix, he also encouraged many young talents to enter the field to work. Watson taught generations of scientists how to think about biology”, the researcher observed.

“He wanted all of the sequencing of the As, Ts, Gs and Cs of human DNA, more than three billion, to see the light of day during the fiftieth anniversary of the discovery of the model, when he himself will be seventy five”, the author of the biography of the scientist reveals. “It?s a pity that a large part of the celebrations of this year are concentrated around the discovery itself, on the present state of science of DNA and in the hopes, which we hold in awe, of the use of biological knowledge”, he warns. “Little attention has been given to the cascade of discoveries and many surprises over these fifty years and which have led us to present understanding of genetics.

But I have no doubt that the wish of Jim Watson will accomplished and he will get a wonderful anniversary present.” “The future? Note that , at least in prokaryotic terms, the determination of the sequencing from the DNA to the RNA and to the protein (what Jim incorrectly calls the Central Dogma) and, in information terms, a process that is simply self-feeding”, Crick notes. “Actually, for the future, we are being confronted not with a single process, but with dynamic non-linear systems, whose theory is fragmented, complex and confusing. This and the interactions of groups of proteins in large molecules are the problems that await us in the future”, the scientist evaluates. “It seems that there are no limits to the questions that await us, but I won?t live to see their solutions. However, many of you will make it to witness the birth of new radical techniques and the arrival at new discoveries. Good luck!” Crick says.

Playful thoughts

The journalist Kevin Davies, editor of the magazineBio-IT World and the author ofCracking the Genome , echoes Francis Crick?s declarations. “If we think of genetics as a football field, for sure we are playing in the first half. The genetics of the twentieth century began with the rediscovery of Mendel?s Laws and finished with the sequencing of the genome. However, we have another one hundred years to really understand how this information can be codified into health and illnesses”, he analyzes. If there are lots of promises for the future, what can we truly expect on the new frontiers of research? “The emphasis is already on the genes, especially those that can self-modify, as for example in cancers. However, many studies have already returned to the study of proteomics.

Nevertheless, scientists warn that the genes are merely a child?s play when compared to proteins”, Kevin Davies believes.”Today the vast science of DNA confronts many new questions. Now that the sequencing of human DNA is almost complete, there is the necessity of making a complete dictionary about all of the proteins that are “particular” to DNA and we also need to create a grammar language for the way in which these proteins interact one with another. Biologists are struggling to give some attention to the recent discovery of a swarm of small molecules of RNA that have many functions in the control of the processes involving life”, McElheny warns.

The poetic words of Watson are not without reason: “We grew up thinking that our destiny had been in the stars. Now we know that, to a large degree, our destiny lies in the genes.” “Play close attention to the words “to a large degree”: even Watson agrees that the genes in themselves do not completely determine our behavior and personality. However, on determining the key variations in our unique DNA sequencing, we could say to you, in the very initial stages, if you are destined to suffer from Alzheimer, cancer or something else”, Davies underlines.

“The science of DNA, certainly in the field of medicine, is going to help to extend human life and make it less sorrowful. This science has been crucial in the identification of the virus that causes Aids and for formulating some of the drugs that help to combat this illness. The work on DNA covers the genetic aspects of human illnesses: the genes that interact with our environment to cause cancer or other illnesses”, McElheny goes on. The environment is another key word in the future vision of DNA. “We already face a moral dilemma because of the mapping of genes.

When we crack this map and we establish the linkage between genes and behavior, we could come face to face with undesirable truths”, the sociologist Francis Fukuyama believes, worried about what he calls “the disregard by some scientists with ethical questions about the future of genetic manipulation”. Last year he published the studyOur Posthuman Future: Consequences of the Biotechnology Revolution (that in a translated form by Rocco should reach Brazil later this year). “We have been easy prey to scientists since the time of Francis Bacon believing that, as they believe, that all scientific progress is for our good. Up until now what keeps in place the fundamental pillar of equality between races, sexes and peoples is our belief that there are no differences between them.

From the moment in which genetic maps dissect these diversities, we will be faced with a moral dilemma that could “prove right ” biases that have already been overcome”, the researcher evaluates. James Watson is known by his detractors as an inflexible scientist who would denounce any attempt to close down a question in biological research because of the risks and ethical dilemmas. “In the same way as the biologists at the times of Mendel and Darwin, he totally rejects the idea that life is and always will be, in some manner, something to be left unknown. Furthermore, he hates the hypothesis that to dismember problems into small pieces that can be solved and resolved as a whole, violates some holistic principle”, McElheny defends.

“To attempt to regulate future procedures is an absurd risk. People believe that there is a choice when the question is genetic manipulation and this is no longer in place. Genetic research is inevitable.” Gregory Stock, the director of the Program on Medicine Technology at the University of California (UCLA), agrees. “I am absolutely convinced that, in less than a decade, we will have carried out broad population studies associating certain genetic patterns with traits related to health and longevity”, the American researcher says. James Watson himself couldn?t have said it better. Or he would have said: “To understand human nature is, I believe, one of the major goals for this century: to what degree we are really controlled by genes. This is the big issue.” Watson evaluates.

“All you have to do is to have a word with Francis Crick?s mother to know that he is not a product of her creation. She was fantastic, but they had nothing in common. The singularity of Francis comes from qualities that I found to be very agreeable. How much of this comes from genes? I do not know, but my bet is that it could not be very much”, he jokes. Everything becomes complicated when we are informed, how we are, that there are notable genetic similarities between us and our closest primitive ancestors, without speaking about our genetic proximity with other species. “What makes us unique? This is a major question and explains the reason why our scientists have been going crazy to sequence the chimpanzee genome, because we share 98.5% of our DNA.

However, the 1.5% difference could unveil clues to the key for the genetic differences that separate us from our primate cousins”, Kevin Davies evaluates. “To look for places on the DNA in which there are small and specific differences from one person to another helps in the objectives of medicine that is more ? individualistic? than that of today”, McElheny stated. “We are only slightly different. And so? It is enough just to look to perceive how in truth we are different”, Watson believes. Nevertheless, ethical dilemmas also include the exploration of the manipulation of DNA for materialistic ends.

“Ethical problems coming from the new ability to alter seedlings or to diagnose genetic illnesses are not very different from ancient ethical dilemmas in medicine.Everything depends on how one defines ?the good life? and if we can manage to have all people with access to abundant food and modern medical attention. Is it ethical to impede farmers to use genetically modified seedlings that are more resistant to pests? Is it ethical to allow a fetus to be born that brings with it genes capable of generating a catastrophic physical defect?” McElheny questions.

“It has always been possible to make use of science for evil. The issue is: have we improved our lifestyle over the last one hundred years? One doesn?t have to think much to reply with a yes and I certainly believe that over the next one hundred years we are going to manage to make it even better. I fervently believe that a crucial disaster is to imagine the return to our environment of some infectious disease. Imagine if something like that was to kill off half of the world population: we would be in a recession for decades.

I believe that knowledge is something fine and that people, or at least a good percentage of them and for a good part of their time, try to make use of knowledge in a constructive manner. But even at that, most certainly, our future will reserve for us more Hitlers, Stalins and Idi Amins”, Watson explains. Therefore, should we await a glorious genetic future, as seen in good fiction books, or should we fear the “post human society” of Francis Fukuyama? “Biology is always overshadowed by fictional fantasies about human beings created to be slaves. We already have large-scale slavery without any manipulation of our genes. The real human problems are greater than the fantastic ones and have been with us since the beginning”, McElheny says.

“DNA is a celebrated icon, but it is important for us to keep in mind that it does not control all human behavior or to dread any manipulation of its structure. Environment is crucial and, in spite of all of the promises of genetics, there is no doubt that a fraction of all of the money spent on the genome project could save many lives if it were spent on diseases such as malaria that affect Third World countries”, Kevin Davies says. Therefore the double, helix or scientists, should not give us cause for fear. After all, how can one resist the candor with which Watson defined the discovery of the secret of life, as he announced in the pub The Eagle some fifty years ago: “Francis and I are famous only because DNA is so beautiful!” Most certainly nobody doubts this.

Read more

50 Years of DNA by Julie Clayton and Carina Davis. Nature Palgrave, R$ 116.14DNA: The Secret of Life by James Watson. Knopf, R$ 167.55The two books came out during this semester in the USA and England. Advance orders can be placed with the Livraria Cultura, phone (11) 3170-4033