Animals in Scientific Research
Science of the Future - Nobel Prizes
Considering that medicine is essentially applied chemistry, and is based on the laws of physics, it is not surprising that many technological advances are the result of basic science research in chemistry and physics. Many Nobel Prizes awarded for Chemistry, and many that were awarded for Physics, have made contributions to the study of medicine as well.
Although an exhaustive review of the Nobel laureates in Chemistry and Physics is beyond the scope of this section, it is worth mentioning briefly the chemists and physicists whose contributions have had monumental implications for the practice of medicine. Even the brief overview of Nobel Prize laureates below demonstrates the critical importance of the basic sciences in medical discovery and treatment.
Physics
1901 W. C. Röntgen
On November 8, 1895, Röntgen proved the existence of x-rays. He never divulged exactly how he did the experiment, but did admit that it was a serendipitous rather than intentional discovery. X-rays had probably been seen by a number of physicists prior to Röntgen; however, he was the first to provide explanation. The medical implications of his explanation (diagnostics x-rays, therapeutic radiation, CAT scanners, etc.) are well known. Less well known is the fact that his discovery also led to the discovery of the electron and the developmental model of the atom. The discovery of x-rays revolutionized the world.
1903 Marie Curie, Pierre Curie and Antoine Becquerel
These three won the prize for their discovery of the elements polonium and radium, and Marie Curie’s postulation that the nucleus was the source of the radiation. Like the discovery of x-rays, the discovery of radiation was serendipitous. Becquerel placed some photographic plates in a drawer with what turned out to be a radiation source. When he returned to the drawer several days later, he noticed that the plates had changed. Within three weeks of his discovery he had proven that uranium emitted radiation. He also contributed a detailed experiment, on himself, of the effects of radiation on the skin. The fact that radiation could change the skin was well known but had not been documented in detail. Becquerel placed a small amount of radioactive material in his waistcoat pocket. He documented the skin changes and continued his experiment on seeds.
The importance of the discovery of radium cannot be overstated because it laid the foundation for the development of diagnostic and therapeutic x-rays, which were later to be used in medicine. This Prize also illustrates another principle we have mentioned before. There are times when animals, humans, or tissue obtained from either will give accurate results. Marie Curie died from leukemia secondary to radiation exposure. Radiation was not thought to be a hazard until women working in a watch factory contracted leukemia at rates far higher than the general population. The women painted radium onto the dials of the watches and in order to maintain a fine point on the brush, they touched the brush to their tongue. Consequently, they developed cancer of the tongue, mouth and jaw. This linked radiation to cancer. It is unfortunate society had to learn of radiation’s dangers in this fashion. Exposing tissue to radiation would have revealed its harmful affects. Many cite this as an example of when mice, dogs, cats and other animals would have given the same results as humans. And they are right. But around the same time, animals were also being exposed to asbestos—a very dangerous substance to humans—and “proving” it safe for humans.
1905 P. E. A. von Lenard
Lenard discovered and developed the cathode ray, which has been extensively used in physiology experiments.
1909 Marchese G. Marconi and Karl Braun
Marconi developed technology concerning the thermionic valve, which aided in the performance of physiology experiments.
1915 William Henry Bragg and William L. Bragg
The Braggs introduced x-ray crystallography, which was later used by Watson, Crick, Franklin, and Wilkins to unravel the DNA double helix.
1952 Edward M. Purcell and Felix Bloch
These scientists’ research on nuclear magnetic resonance led to the development of the MRI scanner. They discovered the physical phenomenon that “certain atomic nuclei that have been knocked out of alignment in a strong magnetic field by a burst of radiation will realign and emit characteristic resonance frequency signals that provide a kind of chemical signature.” This is central to MRI operation. All molecules in your body contain hydrogen. When one enters an MRI machine, all the hydrogen ions point in random directions. The magnet in the machine makes them all align in the same direction. Radio waves are then sent through the body, which results in some of the hydrogen ions spinning. When the radio waves are turned off, the ions take their aligned position again. The computer measures how long this takes, as every tissue has a different rate for realigning. Then the picture is generated.
A nice example of how physics is tied to medicine is the fact that in 2003, American Paul C. Lauterbur of the University of Illinois and Briton Sir Peter Mansfield won the 2003 Nobel Prize for Medicine for discoveries also related to magnetic resonance imaging. Lauterbur, discovered the possibility of creating a two-dimensional picture by producing variations in a magnetic field, the key to the MRI technique while Mansfield showed how the signals the body emits in response to the magnetic field could be mathematically analyzed, which made it possible to develop a useful imaging technique. Mansfield also showed how extremely fast imaging could be achievable. This became technically possible within medicine a decade later.
As an illustration of what is wrong with the traditional system and mindset of biomedical research, Lauterbur attempted to publish his seminal paper about the MRI scanner in the prestigious journal Nature in 1973, but was denied. After being awarded the Prize, he stated: “You could write the history of science in the last 50 years in terms of papers rejected by Science or Nature.” (Lauterbur’s article was eventually published in Nature only after he had appealed against the rejection. Nature also rejected: Krebs paper announcing the Krebs cycle in 1937; Cerenkov’s paper on radiation; Hideki Yukawa’s paper on the meson; work on photosynthesis by Johann Deisenhofer, Robert Huber and Hartmut Michel; and initially rejected (but eventual accepted) Stephen Hawking’s black-hole radiation paper. For more see http://www2.uah.es/jmc.)
Chemistry
1911 Marie Curie
Marie Curie won a second Nobel for her work with radiation in medicine. She and her daughter Irene toured the country teaching physicians how to use the first x-ray machines. Today cancers of the breast, uterus, cervix, mouth, and others are treated with radiation and radiation implants.
1926 Theodor Svedberg
Svedberg won the Prize for developing the ultracentrifuge, which separated particles hitherto inseparable and which is still in use today. That he was honored in the same year he published his article was very unusual and denoted the significance of the discovery.
1929 Hans von Euler-Chelpin and Sir Arthur Harden
These scientists won the prize for contributions to our knowledge of enzymes and nucleic acids. Their research was essential for the development of modern medicine.
1935 Irène Curie and Fédérick Joliot
The husband-wife team won for their discovery that bombarding non-radioactive elements with nuclear particles induced radiation.
1937 Walter Haworth
Haworth won the prize for his research involving vitamins and carbohydrates.
1938 Richard Kuhn and Paul Karrer
These scientists were honored for advancing the knowledge of vitamins and carotenoids.
1939 Adolf Butenandt and Leopold Ruzicka
Butenandt and Ruzicka did extensive research on sex hormones that led to cortisone and birth control pill production.
1946 William Stanley and James Northrop
These two Americans won half of the Prize for new methods of preparing pure viruses and enzymes. The knowledge this revealed about viruses and enzymes created a revolution in medicine and substantiated the field of virology.
1947 Sir Robert Robinson
Robinson conducted research on chemicals such as atropine, quinine, cocaine, and morphine in addition to monumental work on steroids.
1948 Arne Tiselius
Tiselius was responsible for the in vitro technique known as protein electrophoresis. This, in addition to Svedberg’s development of the ultracentrifuge, a project on which Tiselius was an assistant, revolutionized chemistry and medicine. Today, electrophoresis is used in every biochemical, molecular biology and clinical laboratory in the world; it is performed hundreds of thousands of times per day on patients, and nearly everyone has had this process done on their blood at some time in their lives. The Mayo Clinic did approximately 50,000 electrophoresis procedures in 1993.
1952 A. J. P. Martin and R. L. M. Synge
These two Englishmen invented the chemical process of partition chromatography, which was also used by Watson and Crick when elucidating the structure of DNA.
1954 Linus Pauling
Pauling, of vitamin C fame, won the prize for discoveries concerning the nature of the human hemoglobin molecule. (Hemoglobin is the molecule in the red blood cell that transports oxygen.) He examined the differences between hemoglobin molecules in patients with sickle cell anemia and patients without the disease. His discoveries in human cells allowed future scientists to elucidate the mechanism of sickle cell anemia. This was indeed a landmark discovery. Pauling’s contributions to science and medicine are legendary.
1957 Alexander Todd
Todd’s research on cell components revealed new facts concerning nucleotides and nucleotide co-enzymes. This work was very important for a greater working knowledge of the nucleus of the cell and hence important for genetics and molecular biology. It helped explain how DNA could influence genetics.
1958 and 1980 Frederick Sanger
Sanger’s studies of lysine metabolism led to award-winning revelations regarding insulin in 1958. His work showed that small differences in the insulin molecule between species accounted for the adverse reactions some diabetic patients had to non-human insulin. Once again, it is the small differences that are so important when using animal data to treat humans. He also contributed to knowledge of nucleic acids, for which he won the 1980 prize. His research was instrumental in allowing the synthesis of human insulin.
1962 Max Perutz and John Kendrew
The Nobel Foundation honored Perutz and Kendrew’s lifelong work elucidating the structure and nature of the hemoglobin and myoglobin molecules. The scientists used and perfected x-ray diffraction—a technique that has become a mainstay of such research.
1964 Dorothy Mary Crowfoot-Hodgkin
Crowfoot-Hodgkin used x-ray crystalline methods to determine the structure of vitamin B12.
1976 William N. Lipscomb Jr.
Lipscomb received the prize for contributions to the field of radiation oncology. His work with boron has been used to treat certain types of cancer via radiation.
1982 Aaron Klug
Klug developed crystallographic electron microscopy. He used the technique to study nucleic acid-protein complexes, chromatin, histones, and DNA.
1991 Richard R. Ernst
Ernst earned recognition for his work on nuclear magnetic resonance, the groundwork for the MRI scanner. Ernst expanded on the work of Purcell and Bloch, perfecting the technology to the point that it could be used daily by scientists and physicians. He worked on the “pulse-Fourier transform MR signal detection techniques…added dimensionality to the NMR spectroscopy…improved the efficiency and accuracy of the acquisition of the MRI data needed to reconstruct the second dimension.” We owe the MRI scanner to his contribution.
2002 John B. Fenn, Koichi Tanaka, and Kurt Wüthrich
These three scientists won the Nobel Prize in chemistry for developing methods of identifying and analyzing large biological molecules, such as proteins. Fenn and Tanaka were honored for finding two ways to extend the technique of mass spectrometry so that researchers could identify and analyze large molecules by separating and spreading them out as a cloud in a gas without losing their original structure. Wuethrich was honored for improving nuclear magnetic resonance, so that scientists could develop three-dimensional images of molecules in a solution.
2003 Peter Agre and Rod MacKinnon
Human beings consist of about 70% salt water so it was fitting that the 2003 Nobel Prize in Chemistry was awarded to two scientists, Peter Agre, of Johns Hopkins University Medical School in Baltimore, and Rod MacKinnon, of The Rockefeller University in New York, whose discoveries clarified how salts (ions) and water are transported out of and into the cells of the body. The discoveries have afforded us a fundamental molecular understanding of how, for example, the kidneys recover water from primary urine and how the electrical signals in our nerve cells are generated and propagated. This is of great importance for our understanding of many diseases of e.g., the kidneys, heart, muscles and nervous system.
Defects in the genes encoding aquaporin-family proteins are now recognized to be the basis of number of human diseases. For example, mutations in the water channel of the human eye are associated with congenital cataract formation. MacKinnon was awarded the Prize for his structural and mechanistic studies of ion channels. Inherited and acquired mutations in ion channels are associated with many human diseases, including cystic fibrosis and heart arrhythmias.
The 2003 Prize illustrated how contemporary biochemistry reaches down to the atomic level in its quest to understand the fundamental processes of life.
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