NOBEL LAUREATES WITH THEIR CONTRIBUTION IN BIOMEDICAL ENGINEERING Nobel Prizes and Biomedical Engineering In the year 1901 Wilhelm Conrad Röntgen received Nobel Prize in recognition of the extraordinary services he has rendered by the discovery of the remarkable rays subsequently named after him. Röntgen is considered the father of diagnostic radiology, the medical specialty which uses imaging to diagnose disease. He was the first scientist to observe and record X-rays, first finding them on November 8, 1895. Radiography was the first medical imaging technology. He had been fiddling with a set of cathode ray instruments and was surprised to find a flickering image cast by his instruments separated from them by some W. C. Röntgenn distance. He knew that the image he saw was not being cast by the cathode rays (now known as beams of electrons) as they could not penetrate air for any significant distance. After some considerable investigation, he named the new rays "X" to indicate they were unknown. In the year 1903 Niels Ryberg Finsen received Nobel Prize in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science. In beautiful but simple experiments Finsen demonstrated that the most refractive rays (he suggested as the “chemical rays”) from the sun or from an electric arc may have a stimulating effect on the tissues. If the irradiation is too strong, however, it may give rise to tissue damage, but this may to some extent be prevented by pigmentation of the skin as in the negro or in those much exposed to Niels Ryberg Finsen the sun. In small-pox Finsen thought that the multiple scars might be avoided if the patient was protected from the chemical rays. The experiments with such patients were successful. On the other hand chemical rays free from heat rays might be used to obtain a useful effect either by concentration on particular area - and this led to the treatment of lupus vulgaris or other skin diseases - or employed as general sun-baths, which on Finsen's suggestion was tried in cases of tuberculosis and the results were promising. In the year 1911 Allvar Gullstrand received Nobel Prize for his work on the dioptrics of the eye. He researched the way the eye refracts light, and invented the slit lamp for eye exams: a device still used by ophthalmologists. His reflex-free ophthalmoscope (1911) is also a valuable instrument to the ophthalmological diagnostician. He detailed the structure of the cornea and improved corrective lenses for people who had undergone cataract surgery. He is noted for his research on astigmatism and for improving the ophthalmoscope and corrective lenses for use after removal of a Allvar Gullstrand cataract from the eye. In the year 1912, Alexis Carrel received Nobel Prize in recognition of his work on vascular suture and the transplantation of blood-vessels and organs. Carrel's researches were mainly concerned with experimental surgery and the transplantation of tissues and whole organs. As early as 1902 he published, in the Alexis Carrel Lyons Medical, a technique for the end-to-end anastomosis of blood vessels and in 1910 he demonstrated that blood-vessels could be kept for long periods in cold storage before they were used as transplants in surgery. Earlier, in 1908, he had devised methods for the transplantation of whole organs and later, in 1935, in collaboration with Charles Lindbergh, the airman who was the first to flow across the Atlantic, he devised a machine for supplying a sterile respiratory system to organs removed from the body, Lindbergh having solved the mechanical problems involved. He discussed this aspect of his work and its implications in his book The Culture of Organs. Carrel also published the well-known book entitled Man, the Unknown and, in collaboration with Georges Debelly, a book on Treatment of Infected Wounds. In collaboration with the French surgeon Theodore Tuffier, who was a pioneer of thoracic surgery, Carrel performed on the heart a successful series of valvotomies, and in collaboration with Burrows he grew sarcoma cells in tissue cultures by the technique of Harrison. In the year 1922 the Nobel Prize prize was divided equally between Sir Archibald Vivian Hill for his discovery relating to the production of heat in the muscle and Otto Fritz Meyerhof for his discovery of the fixed relationship between the consumption of oxygen and the metabolism of lactid acid in the muscle. Sir Archibald Vivian Hill worked on muscle function, especially the observation and measurement of thermal changes associated with muscle function, which was later extended to similar studies on the mechanism of the passage of nerve impulses. A very sensitive technique was developed and he was eventually able to measure temperature changes of the order of A. V. Hill Otto Fritz Meyerhof ' 0.003°C over periods of only hundredths of a second. He was the discoverer of the phenomenon that heat was produced as a result of the passage of nerve impulses. His researches gave rise to an enthusiastic following in the field of biophysics, a subject whose growth owes much to him. Otto Fritz Meyerhof's own account of his earlier work states that he was occupied chiefly with oxidation mechanisms in cells and with extending methods of gas analysis through the calorimetric measurement of heat production. In this manner he studied the metabolism of sea-urchin eggs, blood corpuscles, and various bacteria and especially the respiratory processes of nitrifying bacteria. He also studied the effects of narcotics and methylene blue on oxidation processes, and the respiration of killed cells. The physico-chemical analogy between oxygen respiration and alcoholic fermentation caused him to study both these processes in the same subject, namely, yeast extract. By this work he discovered a co-enzyme of respiration, which could be found in all the cells and tissues up till then investigated. At the same time he also found a co-enzyme of alcoholic fermentation. He also discovered the capacity of the SH-group to transfer oxygen; after Hopkins had isolated from cells the SH bodies concerned, Meyerhof showed that the unsaturated fatty acids in the cell are oxidized with the help of the sulphydryl group. After studying closer the respiration of muscle, Meyerhof investigated the energy changes in muscle. Of Meyerhof's many achievements, perhaps the most important is his proof that, in isolated but otherwise intact frog muscle, the lactic acid formed is reconverted to carbohydrate in the presence of oxygen, and his preparation of a KC1 extract of muscle which could carry out all the steps of glycolysis with added glycogen and hexose-diphosphate in the presence of hexokinase derived from yeast. In this system glucose was also glycolysed and this was the foundation of the Embden-Meyerhof theory of glycolysis. For his discovery of the fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle, Meyerhof was awarded, together with the English physiologist A.V. Hill, the Nobel Prize for Physiology or Medicine for 1922. The discovery of Otto Meyerhof and his students that some phosphorylated compounds are rich in energy led to a revolution, not only of our concepts of muscular contraction, but of the entire significance of cellular metabolism. A continuously increasing number of enzymatic reactions are becoming known in which the energy of adenosine triphosphate, the compound isolated by his associate Lohmann, provides the energy for endergonic synthesis reactions. The importance of this discovery for the understanding of cellular mechanisms is generally recognized and can hardly be overestimated. In 1925 Meyerhof succeeded in extracting the glycolytic enzyme system from muscle, retracing a pathway which Buchner and Harden and Young had explored in yeast. This proved to be a decisive step for the analysis of glycolysis. Meyerhof and his associates were able to reconstruct in vitro the main steps of the complicated chain of reactions leading from glycogen to lactic acid. They verified some, and extended other, parts of the scheme proposed by Gustav Embden in 1932, shortly before his death. In the year 1924 Willem Einthoven received Nobel Prize for his discovery of the mechanism of the electrocardiogram. Willem Einthoven decided to carry out a thorough analysis of A.D. Waller's electrocardiogram - a study which has remained classic in its field. This investigation led Einthoven to intensify his research. To avoid complex mathematical corrections, he finally devised the string galvanometer which did not involve these calculations. Although the principle in itself was obvious, and practical applications of it were made in other fields of study, the instrument had Willem Einthoven to be precisioned and refined to make it usable for physiologists, and this took three years of laborious work. As a result of this, a galvanometer was produced which could be used in medical science as well as in technology; an instrument which was incomparable in its adaptability and speed of adjustment. His machine, first called an Einthoven galvanometer, had a thin metallic wire held between two electromagnets, with the wire connected to electrodes on the patient's chest, and the patient's hands and one foot bathed in salt-water tubs. An electromagnetic field made the wire quiver ever-so-slightly as the heart contracted and relaxed, and using photographic film and shining light on the wire, Einthoven's machine could accurately measure and record the strength and rate of a patient's heartbeat. The machine weighed about 600 pounds, and operating it required a team of five technicians. Present day electrocardiographs are much smaller and more accurate, but the underlying principles remain fundamentally the same.