Fifty years after unveiling the structure of DNA, the scientific community at Boston University and beyond still owes a huge debt to James Watson and Francis Crick.
Many programs and departments would not exist without the discovery of the double helix. The biology and bioengineering departments at Boston University, as well as a substantial portion of the medical program, rely on DNA research and its technological applications.
In light of the 50th anniversary of Watson and Crick’s discovery in early 1953, scientists at BU have expressed their appreciation for the discovery, the endeavors it fueled and the constant struggles fought and won in during the first fifty years of DNA research. It is an appreciation they believe should never be lost.
‘Watson and Crick made a revolutionary discovery,’ said Professor Maxim Frank-Kamenetskii. ‘It is so important to have historical perspective in science. If you teach only from the present, you lose so much.’
As a professor of biomedical engineering and as a structural biologist who has worked with DNA for over 40 years, Frank-Kamenetskii dually understands the continuing impact and relevance of Watson and Crick’s find. Early each semester, he photocopies Watson and Crick’s famous proposal for his biology students. It is always among the first readings for his class: an excellent introduction and a straightforward outline of things to come.
The paper, ‘Molecular Structure of Nucleic Acids,’ which first appeared in the British journal ‘Nature’ on April 2, 1953, describes in under a thousand words the structure of a DNA molecule. At a single page in length, the paper is not the most taxing assignment; however, much like the structure of DNA itself, the beauty of the paper springs from its simplicity.
Long before Watson and Crick published their paper, researchers had struggled with the problem of finding a molecular basis of heredity. In 1869 Friedrich Miescher isolated a substance he called ‘nuclein’ in cells, but did not explore its possibilities as genetic material. In fact, for years chromosomal protein (an incredibly complex molecule), not DNA, was thought to be the building block of heredity. DNA was seen as too uniform a molecule to account for the diverse range of hereditary traits expressed by all organisms.
Even after it became apparent that DNA was in fact genetic material, the trend in science was against simplicity. The scramble for the structure of DNA yielded complex models triple helixes, inside-out structures that appear ridiculous in retrospect.
‘The discovery of the structure of DNA was the triumph of a reductionalist ideology,’ Frank-Kamenetskii said. ‘I remember as a student there were many experts in the field that considered it ridiculous to think it was that simple. They could not believe genes were made of anything less complicated than protein.’
Watson and Crick’s work revealed that the structure of DNA was a double chain of sugar (deoxyribose) and phosphate groups with nucleotide bases adenine, thymine, guanine, cytosine (A, T, G and C, respectively) extended between them like rungs on a ladder. Based on experimental x-ray diffraction data unwittingly provided by their colleague Rosalind Franklin, Watson and Crick deduced that the structure of DNA must be helical.
Despite her contribution of valuable data to their work, Franklin did not live to receive the Nobel Prize granted to Watson, Crick, and her colleague Maurice Wilkins in 1962. As a rule, the Nobel Committee does not grant awards posthumously. Franklin died of cancer in 1958, at the age of 38.
In order to fit the double helix, they concluded that the bases must be bonded in complimentarily pairs. A binds only to T, and G binds only to C. The structure proposed by Watson and Crick explained the consistent ratio of nucleotide bases found in previous studies, and suggested a model for flawless replication of genetic material. It is this facet of DNA that has been most important to scientists over the past fifty years.
‘Once the structure was known, you could hang other information off of it. Watson and Crick’s work opened the door,’ said Cassandra Smith, deputy director of the Boston University Center for Advanced Biotechnology.
But nothing comes easily, especially in science.
Scientists pursuing the new field of DNA research were faced with several daunting difficulties. With the exception of bacterial samples, DNA was expensive and hard to come by. Additionally, very little could be done for lack of sufficient technology. There was not yet a method for reading the coded information, nor a way of determining the sequence of the nucleotide bases. With few tools at their disposal, scientists edged cautiously into the unknown.
‘We were in total darkness,’ Frank-Kamenetskii said.
In the beginning, only a small community of researchers knew about DNA. However, with the breakthroughs of the 1970s and 1980s and the applications that developed from them, the molecule that was once shunned in favor of protein became, in Frank-Kamenetskii’s words, ‘a household name.’
In 1971 nearly two decades after the discovery of the double helix methods were developed for reading and cutting DNA. Another major technical breakthrough came in the 1980s, with the discovery of PCR or, polymerase chain reaction. This process amplifies a chosen sequence of DNA in a test tube, creating a multitude of copies of the same sequence. Recombinant technology and PCR paved the way for many of the DNA-related innovations we know today.
Professor Smith’s recent work includes isolating the genetic causes of schizophrenia and developing a DNA-antibody that targets cancer cells. For her work with schizophrenia, Smith used normal DNA as a template to spot mutations in the DNA of people with the disease. Functional analysis, the use of DNA as a source of information, is a traditional application. It comprises the majority of work done with DNA.
In her other project, Smith has implemented a more recent innovation in DNA technology. Smith uses DNA as material ‘LEGO blocks for building other molecules’ instead of as a catalogue of information. Because of its unique structure, DNA is an excellent building block for antibodies.
‘Using DNA, I can develop many different types of antibodies very quickly, and make a lot of them,’ Smith said. ‘It’s a very agile molecule.’
Smith’s projects seem a far cry from the days of cardboard models and x-ray diffraction, but it shares in the same tradition of hard work and sacrifice common to all scientists. In this regard, the 50th anniversary also marks the first fifty years of a struggle towards better knowledge and understanding of the human race and its origins. Although half a century old, the struggle has only just begun.
‘At this point we don’t even know why 80 percent of the human genome is there. It’s a whole new language we must learn,’ Smith said. ‘Science is very tough, one of the toughest things you can do. It can be rewarding doing things no one has ever done before but you’ve really got to love doing it.’