Dissecting a breakthrough: the unexpected importance of basic scientific research in improving public health.

ON THE FIRST DAY of the nineteenth century, an Italian astronomer by the name of Piazzi discovered the asteroid Ceres, one of the thousands of minor planets revolving around the sun in the asteroid belt between the orbits of Mars and Jupiter. Unbeknownst to the astronomer, the discovery would ultimately prove to be of great importance to human health.

Although Piazzi's discovery caused a great deal of excitement in astronomical circles, within five or six weeks he lost the little planet, in all likelihood because it went around the sun or behind the sun, and was no longer visible from Earth. The time that it could be observed was of such a short interval that a precise orbit wasn't determined for this little planet. So, when Ceres returned to a position visible from Earth, no one knew where to look for it.

In the meantime, German mathematician Karl Friedrich Gauss, probably the greatest mathematician of all time, discovered a very important and far reaching principle which came to be known as the principle of least squares. Gauss made the first application of his discovery in calculating a precise orbit for the asteroid that had disappeared, and when astronomers looked for this asteroid in the position he predicted it would be, which was in October of the same year, indeed they found it there. And this was regarded in astronomical circles as little short of a miracle, such that Gauss became famous overnight and his principle of least squares came to be one of the most important tools in further scientific discoveries.

How could the discovery of this little planet, and the rediscovery of it by Gauss, be of such importance to our health today? The answer lies in the development of x-ray crystallography more than a century later in 1912. However, to reach that conclusion we must step back to look at how several other discoveries made during the nineteenth century contributed. One was the development of modern algebraic theories which, on the face of it, has no possible connection to human health. A second, circa 1820, was the discovery of group theory by the young French mathematician Galois. It turned out that group theory was the basis of the essential method used for studying all kinds of symmetry, in particular symmetries of crystals. Crystals, as is commonly known, are very symmetrical objects, and the proper study of these crystals depended upon Galois' theory of groups.

Another essential development in the science of x-ray crystallography was the invention by the French mathematician Fourier of what has come to be known as modern harmonic analysis, or Fourier theory. Finally there was the research by German physicist P.P. Ewald, who was writing his doctoral dissertation in the year 1912, the title of which was, "On the Propagation of Electro-Magnetic Radiation in a Medium Consisting of a Regular Arrangement of Resonators."

Again, one may wonder how any of this could have anything to do with the improvement of human health. And, again, the explanation is that the work was instrumental in the creation of the science of x-ray crystallography. Because when Ewald described his findings to the German physicist Max von Laue, von Lane had only one question: were they valid for wavelengths of arbitrary size? Ewald's answer was yes, whereupon Max von Laue suggested an experiment that would direct a beam of x-rays at a crystal. He predicted that the crystal would scatter the x-rays in different directions with different intensities, and that the nature of this so-called diffraction pattern would be uniquely determined by the structure of the crystal, meaning the arrangement of the atoms in the crystal. The experiment was conducted and von Laue's prediction was dramatically confirmed.

"The year 1912 therefore marked the beginning of the science of x-ray crystallography. The development of this science in the twentieth century must be considered one of the most remarkable developments in the whole history of science because, again, it provided a connection between the diffraction pattern and the structure of the crystals, or the arrangement of the atoms in the crystal. Methods based on this experiment were developed and strengthened to the point that it has become easy to determine crystal and molecular structures routinely, even for very complex molecules consisting of thousands of atoms, which means that protein molecules can be clarified by means of this experiment.

Now the relationship to human health becomes clear. Once it became possible to determine molecular structures of biologically important molecules routinely and easily, it became possible to relate molecular structures to life processes. In other words, one could understand how living things work at the molecular level, meaning that one could finally design drugs routinely and with specified properties. And so it became possible to improve the therapies for treating and preventing disease. We are now in a position of being able to design drugs that will do precisely what we want them to do with a minimum of adverse side effects. Thus the improvement to human health became more routine, from reducing cholesterol levels and high blood pressure to treating diabetes and other diseases.

All of this became possible only because of the preceding discoveries, from the discovery of the planet Ceres, to Gauss' discovery of least squares, to the discovery of x-ray diffraction and x-ray crystallography, all of which had been done with no thought of the possible usefulness in improving public health. In short, none of these things would have become possible without the development of basic scientific research. And by that I don't necessarily mean basic biomedical science, but science in general. One can hardly ask for a greater benefit than the improvement of public health for the betterment of society as a whole.

RELATED ARTICLE: Nobel Laureate Herbert A. Hauptman, Ph.D.

After more than twenty years with the Naval Research Laboratory in Washington DC, Herbert A. Hauptman, Ph.D. joined the staff of the Hauptman-Woodward Medical Research Institute in 1970. He was looking for a fresh venue in which to quietly practice his craft. Then, in 1985 the Royal Swedish Academy of Sciences awarded him the Nobel Prize in Chemistry, changing his life forever. A mathematician by training, Hauptman would seem an unlikely candidate for the Nobel Prize in Chemistry. However, despite the fact that he had taken only one chemistry course in his life, he was able to use classical mathematics to resolve an issue that had stymied chemists for decades.

Around 1950 Hauptman turned his attention to an interesting puzzle regarding the structure of crystals. Since 1912 chemists had known that a beam of x-rays directed towards a crystal is scattered when it strikes atoms, and the scattered radiation forms a pattern that can be recorded on film. Although the positions of the atoms in the crystal determine the nature of this so-called diffraction pattern, the puzzle for chemists was that they couldn't readily work backwards from the diffraction data to the atomic arrangement. After perplexing chemists for more than forty years, this problem was finally solved by Hauptman's mathematical approach. Unfortunately, the procedures he developed, known as "direct methods," weren't immediately understood and appreciated by the chemists who study crystals, and it was many years before his approach was recognized. Today there are more than 12,000 crystallographers worldwide, and most or all of them use these techniques.

The structures of thousands of molecules have now been solved by crystallographers using Hauptman's direct methods, and many new molecular structures are added to the list each year. Many new drugs have been designed as a result of the information obtained in these studies.

Reprinted with permission of the Hauptman-Woodward Medical Research Institute

Herbert Hauptman, Ph.D., is the president of the Hauptman-Woodward Medical Research Institute, chairman of the Board of Directors of the New York State Institute on Superconductivity, research professor of biophysical sciences at the State University of New York at Buffalo, and the 1985 recipient of the Nobel Prize in Chemistry. This article is adapted from his speech in acceptance of the 2006 Isaac Asimov Humanist Contributions to Science award at the 65th Annual Conference of the American Humanist Association, held May 11-14, 2006.