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Tuesday, August 22, 2023

Leo Szilard

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Leo_Szilard

Leo Szilard
Szilard, c. 1960
Born
Leó Spitz

February 11, 1898
DiedMay 30, 1964 (aged 66)
Citizenship
  • Hungary
  • Germany
  • United States
Alma mater
Known for
Awards
Scientific career
FieldsPhysics, biology
Institutions
ThesisÜber die thermodynamischen Schwankungserscheinungen (1923)
Doctoral advisorMax von Laue
Other academic advisorsAlbert Einstein
Signature

Leo Szilard (/ˈsɪlɑːrd/; Hungarian: Szilárd Leó, pronounced [ˈsilaːrd ˈlɛoː]; born Leó Spitz; February 11, 1898 – May 30, 1964) was a Hungarian-German-American physicist and inventor. He conceived the nuclear chain reaction in 1933, patented the idea in 1936, and in late 1939 wrote the letter for Albert Einstein's signature that resulted in the Manhattan Project that built the atomic bomb.

Together with Enrico Fermi, he applied for a nuclear reactor patent in 1944. In addition to the nuclear reactor, Szilard coined and submitted the earliest known patent applications and the first publications for the concepts of electron microscope (1928), the linear accelerator (1928), and the cyclotron (1929) in Germany, proving him as the originator of the idea of these devices. Between 1926 and 1930, he worked with Einstein on the development of the Einstein refrigerator. His inventions, discoveries, and contributions related to biological science are also equally important, they include the discovery of feedback inhibition and the invention of the chemostat. According to Theodore Puck and Philip I. Marcus, Szilárd gave essential advice which made the earliest cloning of the human cell a reality.

According to György Marx, he was one of the Hungarian scientists known as The Martians.

Szilard initially attended Palatine Joseph Technical University in Budapest, but his engineering studies were interrupted by service in the Austro-Hungarian Army during World War I. He left Hungary for Germany in 1919, enrolling at Technische Hochschule (Institute of Technology) in Berlin-Charlottenburg, but became bored with engineering and transferred to Friedrich Wilhelm University, where he studied physics. He wrote his doctoral thesis on Maxwell's demon, a long-standing puzzle in the philosophy of thermal and statistical physics. Szilard was the first scientist of note to recognize the connection between thermodynamics and information theory.

After Adolf Hitler became chancellor of Germany in 1933, Szilard urged his family and friends to flee Europe while they still could. He moved to England, where he helped found the Academic Assistance Council, an organization dedicated to helping refugee scholars find new jobs. While in England he discovered a means of isotope separation known as the Szilard–Chalmers effect.

Foreseeing another war in Europe, Szilard moved to the United States in 1938, where he worked with Enrico Fermi and Walter Zinn on means of creating a nuclear chain reaction. He was present when this was achieved within the Chicago Pile-1 on December 2, 1942. He worked for the Manhattan Project's Metallurgical Laboratory at the University of Chicago on aspects of nuclear reactor design. He drafted the Szilard petition advocating a demonstration of the atomic bomb, but the Interim Committee chose to use them against cities without warning.

He publicly sounded the alarm against the possible development of salted thermonuclear bombs, a new kind of nuclear weapon that might annihilate mankind. Diagnosed with bladder cancer in 1960, he underwent a cobalt-60 treatment that he had designed. He helped found the Salk Institute for Biological Studies, where he became a resident fellow. Szilard founded Council for a Livable World in 1962 to deliver "the sweet voice of reason" about nuclear weapons to Congress, the White House, and the American public. He died in his sleep of a heart attack in 1964.

Early life

He was born as Leó Spitz in Budapest, Kingdom of Hungary, on February 11, 1898. His middle-class Jewish parents, Lajos (Louis) Spitz, a civil engineer, and Tekla Vidor, raised Leó on the Városligeti Fasor in Pest. He had two younger siblings, a brother, Béla, born in 1900, and a sister, Rózsi, born in 1901. On October 4, 1900, the family changed its surname from the German "Spitz" to the Hungarian "Szilárd", a name that means "solid" in Hungarian. Despite having a religious background, Szilard became an agnostic. From 1908 to 1916 he attended the Lutheran gymnasium school in his home town along with others such as Edward Teller. Showing an early interest in physics and a proficiency in mathematics, in 1916 he won the Eötvös Prize, a national prize for mathematics.

Leo Szilard in 1915

With World War I raging in Europe, Szilard received notice on January 22, 1916, that he had been drafted into the 5th Fortress Regiment, but he was able to continue his studies. He enrolled as an engineering student at the Palatine Joseph Technical University, which he entered in September 1916. The following year he joined the Austro-Hungarian Army's 4th Mountain Artillery Regiment, but immediately was sent to Budapest as an officer candidate. He rejoined his regiment in May 1918 but in September, before being sent to the front, he fell ill with Spanish Influenza and was returned home for hospitalization. Later he was informed that his regiment had been nearly annihilated in battle, so the illness probably saved his life. He was discharged honorably in November 1918, after the Armistice.

In January 1919, Szilard resumed his engineering studies, but Hungary was in a chaotic political situation with the rise of the Hungarian Soviet Republic under Béla Kun. Szilard and his brother Béla founded their own political group, the Hungarian Association of Socialist Students, with a platform based on a scheme of Szilard's for taxation reform. He was convinced that socialism was the answer to Hungary's post-war problems, but not that of Kun's Hungarian Socialist Party, which had close ties to the Soviet Union. When Kun's government tottered, the brothers officially changed their religion from "Israelite" to "Calvinist", but when they attempted to re-enroll in what was now the Budapest University of Technology, they were prevented from doing so by nationalist students because they were Jews.

Convinced that there was no future for him in Hungary, Szilard left for Berlin via Austria on December 25, 1919, and enrolled at the Technische Hochschule (Institute of Technology) in Berlin-Charlottenburg. He was soon joined by his brother Béla. Szilard became bored with engineering, and his attention turned to physics. This was not taught at the Technische Hochschule, so he transferred to Friedrich Wilhelm University, where he attended lectures given by Albert Einstein, Max Planck, Walter Nernst, James Franck and Max von Laue. He also met fellow Hungarian students Eugene Wigner, John von Neumann and Dennis Gabor.

Szilard's doctoral dissertation on thermodynamics Über die thermodynamischen Schwankungserscheinungen (On The Manifestation of Thermodynamic Fluctuations), praised by Einstein, won top honors in 1922. It involved a long-standing puzzle in the philosophy of thermal and statistical physics known as Maxwell's demon, a thought experiment originated by the physicist James Clerk Maxwell. The problem was thought to be insoluble, but in tackling it Szilard recognized the connection between thermodynamics and information theory. Szilard was appointed as assistant to von Laue at the Institute for Theoretical Physics in 1924. In 1927 he finished his habilitation and became a Privatdozent (private lecturer) in physics. For his habilitation lecture, he produced a second paper on Maxwell's Demon, Über die Entropieverminderung in einem thermodynamischen System bei Eingriffen intelligenter Wesen (On the reduction of entropy in a thermodynamic system by the intervention of intelligent beings), that had actually been written soon after the first. This introduced the thought experiment now called the Szilard engine and became important in the history of attempts to understand Maxwell's demon. The paper is also the first equation of negative entropy and information. As such, it established Szilard as one of the founders of information theory, but he did not publish it until 1929, and did not pursue it further. Cybernetics, via the work of Norbert Wiener and Claude E. Shannon, would later develop the concept into a general theory in the 1940s and 1950s—though, during the time of the Cybernetics Meetings, John Von Neumann pointed out that Szilard first equated information with entropy in his review of Wiener's Cybernetics book.

Throughout his time in Berlin, Szilard worked on numerous technical inventions. In 1928 he submitted a patent application for the linear accelerator, not knowing of Gustav Ising's prior 1924 journal article and Rolf Widerøe's operational device, and in 1929 applied for one for the cyclotron. He was also the first person to conceive the idea of the electron microscope, and submitted the earliest patent for one in 1928. Between 1926 and 1930, he worked with Einstein to develop the Einstein refrigerator, notable because it had no moving parts. He did not build all of these devices, or publish these ideas in scientific journals, and so credit for them often went to others. As a result, Szilard never received the Nobel Prize, but Ernest Lawrence was awarded it for the cyclotron in 1939, and Ernst Ruska for the electron microscope in 1986.

An image from the Fermi–Szilard "neutronic reactor" patent

Szilard received German citizenship in 1930, but was already uneasy about the political situation in Europe. When Adolf Hitler became chancellor of Germany on January 30, 1933, Szilard urged his family and friends to flee Europe while they still could. He moved to England, and transferred his savings of £1,595 (£120,500 today) from his bank in Zurich to one in London. He lived in hotels where lodging and meals cost about £5.5 a week. For those less fortunate, he helped found the Academic Assistance Council, an organization dedicated to helping refugee scholars find new jobs, and persuaded the Royal Society to provide accommodation for it at Burlington House. He enlisted the help of academics such as Harald Bohr, G. H. Hardy, Archibald Hill and Frederick G. Donnan. By the outbreak of World War II in 1939, it had helped to find places for over 2,500 refugee scholars.

On the morning of September 12, 1933, Szilard read an article in The Times summarizing a speech given by Lord Rutherford in which Rutherford rejected the feasibility of using atomic energy for practical purposes. The speech remarked specifically on the recent 1932 work of his students, John Cockcroft and Ernest Walton, in "splitting" lithium into alpha particles, by bombardment with protons from a particle accelerator they had constructed. Rutherford went on to say:

We might in these processes obtain very much more energy than the proton supplied, but on the average we could not expect to obtain energy in this way. It was a very poor and inefficient way of producing energy, and anyone who looked for a source of power in the transformation of the atoms was talking moonshine. But the subject was scientifically interesting because it gave insight into the atoms.

Szilard was so annoyed at Rutherford's dismissal that, on the same day, he conceived of the idea of nuclear chain reaction (analogous to a chemical chain reaction), using recently discovered neutrons. The idea did not use the mechanism of nuclear fission, which was not yet discovered, but Szilard realized that if neutrons could initiate any sort of energy-producing nuclear reaction, such as the one that had occurred in lithium, and could be produced themselves by the same reaction, energy might be obtained with little input, since the reaction would be self-sustaining. Szilard filed for a patent on the concept of the neutron-induced nuclear chain reaction in June 1934, which was granted in March 1936. Under section 30 of the Patents and Designs Act (1907, UK), Szilard was able to assign the patent to the British Admiralty to ensure its secrecy, which he did. Consequently, his patent was not published until 1949 when the relevant parts of the Patents and Designs Act (1907, UK) were repealed by the Patents Act (1949, UK). Richard Rhodes described Szilard's moment of inspiration:

In London, where Southampton Row passes Russell Square, across from the British Museum in Bloomsbury, Leo Szilard waited irritably one gray Depression morning for the stoplight to change. A trace of rain had fallen during the night; Tuesday, September 12, 1933, dawned cool, humid and dull. Drizzling rain would begin again in early afternoon. When Szilard told the story later he never mentioned his destination that morning. He may have had none; he often walked to think. In any case another destination intervened. The stoplight changed to green. Szilard stepped off the curb. As he crossed the street time cracked open before him and he saw a way to the future, death into the world and all our woe, the shape of things to come.

Prior to conceiving the nuclear chain reaction, in 1932 Szilard had read H. G. Wells' The World Set Free, a book describing continuing explosives which Wells termed "atomic bombs"; Szilard wrote in his memoirs the book had made "a very great impression on me." When Szilard assigned his patent to the Admiralty to keep the news from reaching the notice of the wider scientific community, he wrote, "Knowing what this [a chain reaction] would mean—and I knew it because I had read H. G. Wells—I did not want this patent to become public."

In early 1934, Szilard began working at St Bartholomew's Hospital in London. Working with a young physicist on the hospital staff, Thomas A. Chalmers, he began studying radioactive isotopes for medical purposes. It was known that bombarding elements with neutrons could produce either heavier isotopes of an element, or a heavier element, a phenomenon known as the Fermi Effect after its discoverer, the Italian physicist Enrico Fermi. When they bombarded ethyl iodide with neutrons produced by a radonberyllium source, they found that the heavier radioactive isotopes of iodine separated from the compound. Thus, they had discovered a means of isotope separation. This method became known as the Szilard–Chalmers effect, and was widely used in the preparation of medical isotopes. He also attempted unsuccessfully to create a nuclear chain reaction using beryllium by bombarding it with X-rays.

Manhattan Project

Columbia University

Szilard visited Béla and Rose and her husband Roland (Lorand) Detre, in Switzerland in September 1937. After a rainstorm, he and his siblings spent an afternoon in an unsuccessful attempt to build a prototype collapsible umbrella. One reason for the visit was that he had decided to emigrate to the United States, as he believed that another war in Europe was inevitable and imminent. He reached New York on the liner RMS Franconia on January 2, 1938. Over the next few months he moved from place to place, conducting research with Maurice Goldhaber at the University of Illinois at Urbana–Champaign, and then the University of Chicago, University of Michigan and the University of Rochester, where he undertook experiments with indium but again failed to initiate a chain reaction.

Army Intelligence report on Enrico Fermi and Leo Szilard

In November 1938, Szilard moved to New York City, taking a room at the King's Crown Hotel near Columbia University. He encountered John R. Dunning, who invited him to speak about his research at an afternoon seminar in January 1939. That month, Niels Bohr brought news to New York of the discovery of nuclear fission in Germany by Otto Hahn and Fritz Strassmann, and its theoretical explanation by Lise Meitner, and Otto Frisch. When Szilard found out about it on a visit to Wigner at Princeton University, he immediately realized that uranium might be the element capable of sustaining a chain reaction.

Unable to convince Fermi that this was the case, Szilard set out on his own. He obtained permission from the head of the physics department at Columbia, George B. Pegram, to use a laboratory for three months. To fund his experiment, he borrowed $2,000 from a fellow inventor, Benjamin Liebowitz. He wired Frederick Lindemann at Oxford and asked him to send a beryllium cylinder. He persuaded Walter Zinn to become his collaborator, and hired Semyon Krewer to investigate processes for manufacturing pure uranium and graphite.

Szilard and Zinn conducted a simple experiment on the seventh floor of Pupin Hall at Columbia, using a radium–beryllium source to bombard uranium with neutrons. Initially nothing registered on the oscilloscope, but then Zinn realized that it was not plugged in. On doing so, they discovered significant neutron multiplication in natural uranium, proving that a chain reaction might be possible. Szilard later described the event: "We turned the switch and saw the flashes. We watched them for a little while and then we switched everything off and went home." He understood the implications and consequences of this discovery, though. "That night, there was very little doubt in my mind that the world was headed for grief".

While they had demonstrated that the fission of uranium produced more neutrons than it consumed, this was still not a chain reaction. Szilard persuaded Fermi and Herbert L. Anderson to try a larger experiment using 500 pounds (230 kg) of uranium. To maximize the chance of fission, they needed a neutron moderator to slow the neutrons down. Hydrogen was a known moderator, so they used water. The results were disappointing. It became apparent that hydrogen slowed neutrons down, but also absorbed them, leaving fewer for the chain reaction. Szilard then suggested Fermi use carbon, in the form of graphite. He felt he would need about 50 tonnes (49 long tons; 55 short tons) (50.8 metric ton) of graphite and 5 tonnes (4.9 long tons; 5.5 short tons) of uranium. As a back-up plan, Szilard also considered where he might find a few tons of heavy water; deuterium would not absorb neutrons like ordinary hydrogen, but would have the similar value as a moderator. Such quantities of material would require a lot of money.

Szilard drafted a confidential letter to the President, Franklin D. Roosevelt, explaining the possibility of nuclear weapons, warning of the German nuclear weapon project, and encouraging the development of a program that could result in their creation. With the help of Wigner and Edward Teller, he approached his old friend and collaborator Einstein in August 1939, and persuaded him to sign the letter, lending his fame to the proposal. The Einstein–Szilárd letter resulted in the establishment of research into nuclear fission by the U.S. government, and ultimately to the creation of the Manhattan Project. Roosevelt gave the letter to his aide, Brigadier General Edwin M. "Pa" Watson with the instruction: "Pa, this requires action!"

An Advisory Committee on Uranium was formed under Lyman J. Briggs, a scientist and the director of the National Bureau of Standards. Its first meeting on October 21, 1939, was attended by Szilard, Teller, and Wigner, who persuaded the Army and Navy to provide $6,000 for Szilard to purchase supplies for experiments—in particular, more graphite. A 1940 Army intelligence report on Fermi and Szilard, prepared when the United States had not yet entered World War II, expressed reservations about both. While it contained some errors of fact about Szilard, it correctly noted his dire prediction that Germany would win the war.

Fermi and Szilard met with Herbert G. MacPherson and V. C. Hamister of the National Carbon Company, who manufactured graphite, and Szilard made another important discovery. He asked about impurities in graphite, and learned from MacPherson that it usually contained boron, a neutron absorber. He then had special boron-free graphite produced. Had he not done so, they might have concluded, as the German nuclear researchers did, that graphite was unsuitable for use as a neutron moderator. Like the German researchers, Fermi and Szilard still believed that enormous quantities of uranium would be required for an atomic bomb, and therefore concentrated on producing a controlled chain reaction. Fermi determined that a fissioning uranium atom produced 1.73 neutrons on average. It was enough, but a careful design was called for to minimize losses. Szilard worked up various designs for a nuclear reactor. "If the uranium project could have been run on ideas alone," Wigner later remarked, "no one but Leo Szilard would have been needed."

Metallurgical Laboratory

14 men and one woman, all wearing formal suit jackets, with Szilard also wearing a lab coat
The Metallurgical Laboratory scientists, with Szilard second from right, in the lab coat.

At its December 6, 1941, meeting, the National Defense Research Committee resolved to proceed with an all-out effort to produce atomic bombs. This decision was given urgency by the Japanese attack on Pearl Harbor the following day that brought the United States into World War II. It was formally approved by Roosevelt in January 1942. Arthur H. Compton from the University of Chicago was appointed head of research and development. Against Szilard's wishes, Compton concentrated all the groups working on reactors and plutonium at the Metallurgical Laboratory of the University of Chicago. Compton laid out an ambitious plan to achieve a chain reaction by January 1943, start manufacturing plutonium in nuclear reactors by January 1944, and produce an atomic bomb by January 1945.

In January 1942, Szilard joined the Metallurgical Laboratory in Chicago as a research associate, and later the chief physicist. Alvin Weinberg noted that Szilard served as the project "gadfly", asking all the embarrassing questions. Szilard provided important insights. While uranium-238 did not fission readily with slow, moderated neutrons, it might still fission with the fast neutrons produced by fission. This effect was small but crucial. Szilard made suggestions that improved the uranium canning process, and worked with David Gurinsky and Ed Creutz on a method for recovering uranium from its salts.

A vexing question at the time was how a production reactor should be cooled. Taking a conservative view that every possible neutron must be preserved, the majority opinion initially favored cooling with helium, which would absorb very few neutrons. Szilard argued that if this was a concern, then liquid bismuth would be a better choice. He supervised experiments with it, but the practical difficulties turned out to be too great. In the end, Wigner's plan to use ordinary water as a coolant won out. When the coolant issue became too heated, Compton and the director of the Manhattan Project, Brigadier General Leslie R. Groves, Jr., moved to dismiss Szilard, who was still a German citizen, but the Secretary of War, Henry L. Stimson, refused to do so. Szilard was therefore present on December 2, 1942, when the first man-made self-sustaining nuclear chain reaction was achieved in the first nuclear reactor under viewing stands of Stagg Field, and shook Fermi's hand.

Szilard started to acquire high-quality graphite and uranium, which were the necessary materials for building a large-scale chain reaction experiment. The success of this demonstration and technological breakthrough at the University of Chicago were partially due to Szilard’s new atomic theories, his uranium lattice design, and the identification and mitigation of a key graphite impurity (boron) through a joint collaboration with graphite suppliers.

Szilard became a naturalized citizen of the United States in March 1943. The Army offered Szilard $25,000 for his inventions before November 1940, when he officially joined the project. He refused. He was the co-holder, with Fermi, of the patent on the nuclear reactor. In the end he sold his patent to the government for reimbursement of his expenses, some $15,416, plus the standard $1 fee. He continued to work with Fermi and Wigner on nuclear reactor design, and is credited with coining the term "breeder reactor".

With an enduring passion for the preservation of human life and political freedom, Szilard hoped that the U.S. government would not use nuclear weapons, but that the mere threat of such weapons would force Germany and Japan to surrender. He also worried about the long-term implications of nuclear weapons, predicting that their use by the United States would start a nuclear arms race with the USSR. He drafted the Szilárd petition advocating that the atomic bomb be demonstrated to the enemy, and used only if the enemy did not then surrender. The Interim Committee instead chose to use atomic bombs against cities over the protests of Szilard and other scientists. Afterwards, he lobbied for amendments to the Atomic Energy Act of 1946 that placed nuclear energy under civilian control.

After the war

Szilard and Norman Hilberry at the site of CP-1, at the University of Chicago, some years after the war. It was demolished in 1957.

In 1946, Szilard secured a research professorship at the University of Chicago that allowed him to research in biology and the social sciences. He teamed up with Aaron Novick, a chemist who had worked at the Metallurgical Laboratory during the war. The two men saw biology as a field that had not been explored as much as physics, and was ready for scientific breakthroughs. It was a field that Szilard had been working on in 1933 before he had become subsumed in the quest for a nuclear chain reaction. The duo made considerable advances. They invented the chemostat, a device for regulating the growth rate of the microorganisms in a bioreactor and developed methods for measuring the growth rate of bacteria. They discovered feedback inhibition, an important factor in processes such as growth and metabolism. Szilard gave essential advice to Theodore Puck and Philip I. Marcus for their first cloning of a human cell in 1955.

Personal life

Before his relationship with his later wife Gertrud "Trude" Weiss, Leo Szilard's life partner in the period 1927–1934 was the kindergarten teacher and opera singer Gerda Philipsborn, who also worked as a volunteer in a Berlin asylum organization for refugee children and in 1932 moved to India to continue this work. Szilard married Trude Weiss, a physician, in a civil ceremony in New York on October 13, 1951. They had known each other since 1929 and had frequently corresponded and visited each other ever since. Weiss took up a teaching position at the University of Colorado in April 1950, and Szilard began staying with her in Denver for weeks at a time when they had never been together for more than a few days before. Single people living together was frowned upon in the conservative United States at the time and, after they were discovered by one of her students, Szilard began to worry that she might lose her job. Their relationship remained a long-distance one, and they kept news of their marriage quiet. Many of his friends were shocked, having considered Szilard a born bachelor.

Salk Institute for Biological Studies, La Jolla, San Diego

Writings

In 1949 Szilard wrote a short story titled "My Trial as a War Criminal" in which he imagined himself on trial for crimes against humanity after the United States lost a war with the Soviet Union. He publicly sounded the alarm against the possible development of salted thermonuclear bombs, explaining in a University of Chicago Round Table radio program on February 26, 1950, that sufficiently big thermonuclear bomb rigged with specific but common materials, might annihilate mankind. His comments, as well as those of Hans Bethe, Harrison Brown, and Frederick Seitz (the three other scientists who participated in the program), were attacked by the Atomic Energy Commission's former Chairman David Lilienthal, and the criticisms plus a response from Szilard were published. Time compared Szilard to Chicken Little while the AEC dismissed his ideas, but scientists debated whether it was feasible or not. The Bulletin of the Atomic Scientists commissioned a study by James R. Arnold, who concluded that it was. Physicist W. H. Clark suggested that a 50 megaton cobalt bomb did have the potential to produce sufficient long-lasting radiation to be a doomsday weapon, in theory, but was of the view that, even then, "enough people might find refuge to wait out the radioactivity and emerge to begin again."

Szilard published a book of short stories, The Voice of the Dolphins (1961), in which he dealt with the moral and ethical issues raised by the Cold War and his own role in the development of atomic weapons. The title story described an international biology research laboratory in Central Europe. This became reality after a meeting in 1962 with Victor F. Weisskopf, James Watson and John Kendrew. When the European Molecular Biology Laboratory was established, the library was named The Szilard Library and the library stamp features dolphins. Other honors that he received included the Atoms for Peace Award in 1959, and the Humanist of the Year in 1960. A lunar crater on the far side of the Moon was named after him in 1970. The Leo Szilard Lectureship Award, established in 1974, is given in his honor by the American Physical Society.

Cancer diagnosis and treatment

In 1960, Szilard was diagnosed with bladder cancer. He underwent cobalt therapy at New York's Memorial Sloan-Kettering Hospital using a cobalt 60 treatment regimen that his doctors gave him a high degree of control over. A second round of treatment with an increased dose followed in 1962. The higher dose did its job and his cancer never returned.

Last years

Szilard spent his last years as a fellow of the Salk Institute for Biological Studies in the La Jolla community of San Diego, California, which he had helped to create. Szilard founded Council for a Livable World in 1962 to deliver "the sweet voice of reason" about nuclear weapons to Congress, the White House, and the American public. He was appointed a non-resident fellow there in July 1963, and became a resident fellow on April 1, 1964, after moving to San Diego in February. With Trude, he lived in a bungalow on the property of the Hotel del Charro. On May 30, 1964, he died there in his sleep of a heart attack; when Trude awoke, she was unable to revive him. His remains were cremated.

His papers are in the library at the University of California, San Diego. In February 2014, the library announced that they received funding from the National Historical Publications and Records Commission to digitize its collection of his papers, extending from 1938 to 1998.

Patents

Recognition and remembrance

Hyperlipidemia

From Wikipedia, the free encyclopedia
 
A 4-ml sample of hyperlipidemic blood in a vacutainer with EDTA. Left to settle for four hours without centrifugation, the lipids separated into the top fraction.

SpecialtyCardiology
Differential diagnosisHypertriglyceridemia

Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.

Lipids (water-insoluble molecules) are transported in a protein capsule. The size of that capsule, or lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it contains determines the fate of the particle and its influence on metabolism.

Hyperlipidemias are divided into primary and secondary subtypes. Primary hyperlipidemia is usually due to genetic causes (such as a mutation in a receptor protein), while secondary hyperlipidemia arises due to other underlying causes such as diabetes. Lipid and lipoprotein abnormalities are common in the general population and are regarded as modifiable risk factors for cardiovascular disease due to their influence on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.

Classification

Hyperlipidemias may basically be classified as either familial (also called primary) when caused by specific genetic abnormalities or acquired (also called secondary) when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism. Also, hyperlipidemia may be idiopathic, that is, without a known cause.

Hyperlipidemias are also classified according to which types of lipids are elevated, that is hypercholesterolemia, hypertriglyceridemia or both in combined hyperlipidemia. Elevated levels of Lipoprotein(a) may also be classified as a form of hyperlipidemia.

Familial (primary)

Familial hyperlipidemias are classified according to the Fredrickson classification, which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation. It was later adopted by the World Health Organization (WHO). It does not directly account for HDL, and it does not distinguish among the different genes that may be partially responsible for some of these conditions.

Fredrickson classification of hyperlipidemias
Hyperlipo-
proteinemia
OMIM Synonyms Defect Increased lipoprotein Main symptoms Treatment Serum appearance Estimated prevalence
Type I a 238600 Buerger-Gruetz syndrome or familial hyperchylomicronemia Decreased lipoprotein lipase (LPL) Chylomicrons Acute pancreatitis, lipemia retinalis, eruptive skin xanthomas, hepatosplenomegaly Diet control Creamy top layer One in 1,000,000
b 207750 Familial apoprotein CII deficiency Altered ApoC2
c 118830
LPL inhibitor in blood
Type II a 143890 Familial hypercholesterolemia LDL receptor deficiency LDL Xanthelasma, arcus senilis, tendon xanthomas Bile acid sequestrants, statins, niacin Clear One in 500 for heterozygotes
b 144250 Familial combined hyperlipidemia Decreased LDL receptor and increased ApoB LDL and VLDL
Statins, niacin, fibrate Turbid One in 100
Type III 107741 Familial dysbetalipoproteinemia Defect in Apo E 2 synthesis IDL Tuberoeruptive xanthomas and palmar xanthomas Fibrate, statins Turbid One in 10,000
Type IV 144600 Familial hypertriglyceridemia Increased VLDL production and decreased elimination VLDL Can cause pancreatitis at high triglyceride levels Fibrate, niacin, statins Turbid One in 100
Type V 144650
Increased VLDL production and decreased LPL VLDL and chylomicrons
Niacin, fibrate Creamy top layer and turbid bottom
Relative prevalence of familial forms of hyperlipoproteinemia

Type I hyperlipoproteinemia exists in several forms:

Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis, steatosis, and organomegaly, and lipemia retinalis.

Type II

Hyperlipoproteinemia type II is further classified into types IIa and IIb, depending mainly on whether elevation in the triglyceride level occurs in addition to LDL cholesterol.

Type IIa

This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma, and premature cardiovascular disease. The incidence of this disease is about one in 500 for heterozygotes, and one in 1,000,000 for homozygotes.

HLPIIa is a rare genetic disorder characterized by increased levels of LDL cholesterol in the blood due to the lack of uptake (no Apo B receptors) of LDL particles. This pathology, however, is the second-most common disorder of the various hyperlipoproteinemias, with individuals with a heterozygotic predisposition of one in every 500 and individuals with homozygotic predisposition of one in every million. These individuals may present with a unique set of physical characteristics such as xanthelasmas (yellow deposits of fat underneath the skin often presenting in the nasal portion of the eye), tendon and tuberous xanthomas, arcus juvenilis (the graying of the eye often characterized in older individuals), arterial bruits, claudication, and of course atherosclerosis. Laboratory findings for these individuals are significant for total serum cholesterol levels two to three times greater than normal, as well as increased LDL cholesterol, but their triglycerides and VLDL values fall in the normal ranges.

To manage persons with HLPIIa, drastic measures may need to be taken, especially if their HDL cholesterol levels are less than 30 mg/dL and their LDL levels are greater than 160 mg/dL. A proper diet for these individuals requires a decrease in total fat to less than 30% of total calories with a ratio of monounsaturated:polyunsaturated:saturated fat of 1:1:1. Cholesterol should be reduced to less than 300 mg/day, thus the avoidance of animal products and to increase fiber intake to more than 20 g/day with 6g of soluble fiber/day. Exercise should be promoted, as it can increase HDL. The overall prognosis for these individuals is in the worst-case scenario if uncontrolled and untreated individuals may die before the age of 20, but if one seeks a prudent diet with correct medical intervention, the individual may see an increased incidence of xanthomas with each decade, and Achilles tendinitis and accelerated atherosclerosis will occur.

Type IIb

The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl-CoA, and an increase in B-100 synthesis. They may also be caused by the decreased clearance of LDL. Prevalence in the population is 10%.

Type III

This form is due to high chylomicrons and IDL (intermediate density lipoprotein). Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Its prevalence has been estimated to be approximately 1 in 10,000.

It is associated with hypercholesterolemia (typically 8–12 mmol/L), hypertriglyceridemia (typically 5–20 mmol/L), a normal ApoB concentration, and two types of skin signs (palmar xanthomata or orange discoloration of skin creases, and tuberoeruptive xanthomata on the elbows and knees). It is characterized by the early onset of cardiovascular disease and peripheral vascular disease. Remnant hyperlipidemia occurs as a result of abnormal function of the ApoE receptor, which is normally required for clearance of chylomicron remnants and IDL from the circulation. The receptor defect causes levels of chylomicron remnants and IDL to be higher than normal in the blood stream. The receptor defect is an autosomal recessive mutation or polymorphism.

Type IV

Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.

This form is due to high triglyceride level. Other lipoprotein levels are normal or increased a little.

Treatment include diet control, fibrates and niacins. Statins are not better than fibrates when lowering triglyceride levels.

Type V

Hyperlipoproteinemia type V, also known as mixed hyperlipoproteinemia familial or mixed hyperlipidemia, is very similar to type I, but with high VLDL in addition to chylomicrons.

It is also associated with glucose intolerance and hyperuricemia.

In medicine, combined hyperlipidemia (or -aemia) (also known as "multiple-type hyperlipoproteinemia") is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterized by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia type IIB. It is the most common inherited lipid disorder, occurring in about one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 has this disorder. The elevated triglyceride levels (>5 mmol/L) are generally due to an increase in very low density lipoprotein (VLDL), a class of lipoprotein prone to cause atherosclerosis.

Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin) can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.

Unclassified familial forms

These unclassified forms are extremely rare:

Acquired (secondary)

Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis and other complications of the chylomicronemia syndrome. The most common causes of acquired hyperlipidemia are:

Other conditions leading to acquired hyperlipidemia include:

Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia.

Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food.

Presentation

Relation to cardiovascular disease

Hyperlipidemia predisposes a person to atherosclerosis. Atherosclerosis is the accumulation of lipids, cholesterol, calcium, fibrous plaques within the walls of arteries. This accumulation narrows the blood vessel and reduces blood flow and oxygen to muscles of the heart. Over time fatty deposits can build up, hardening and narrowing the arteries until organs and tissues don't receive enough blood to properly function. If arteries that supply the heart with blood are affected, a person might have angina (chest pain). Complete blockage of the artery causes infarction of the myocardial cells, also known as heart attack. Fatty buildup in the arteries can also lead to stroke, if a blood clot blocks blood flow to the brain.

Screening

Adults 20 years and older should have the cholesterol checked every four to six years. Serum level of Low Density Lipoproteins (LDL) cholesterol, High Density Lipoproteins (HDL) Cholesterol, and triglycerides are commonly tested in primary care setting using a lipid panel. Quantitative levels of lipoproteins and triglycerides contribute toward cardiovascular disease risk stratification via models/calculators such as Framingham Risk Score, ACC/AHA Atherosclerotic Cardiovascular Disease Risk Estimator, and/or Reynolds Risk Scores. These models/calculators may also take into account of family history (heart disease and/or high blood cholesterol), age, gender, Body-Mass-Index, medical history (diabetes, high cholesterol, heart disease), high sensitivity CRP levels, coronary artery calcium score, and ankle-brachial index. The cardiovascular stratification further determines what medical intervention may be necessary to decrease the risk of future cardiovascular disease.

Total cholesterol

The combined quantity of LDL and HDL. A total cholesterol of higher than 240 mg/dL is abnormal, but medical intervention is determined by the breakdown of LDL and HDL levels.

LDL cholesterol

LDL, commonly known as "bad cholesterol", is associated with increased risk of cardiovascular disease. LDL cholesterol transports cholesterol particles throughout the body, and can build up in the walls of the arteries, making them hard and narrow. LDL cholesterol is produced naturally by the body, but eating a diet high in saturated fat, trans fats, and cholesterol can increase LDL levels. Elevated LDL levels are associated with diabetes, hypertension, hypertriglyceridemia, and atherosclerosis. In a fasting lipid panel, a LDL greater than 160 mg/dL is abnormal.

HDL cholesterol

HDL, also known as "good cholesterol", is associated with decreased risk of cardiovascular disease. HDL cholesterol carries cholesterol from other parts of the body back to the liver and then removes the cholesterol from the body. It can be affected by acquired or genetic factors, including tobacco use, obesity, inactivity, hypertriglyceridemia, diabetes, high carbohydrate diet, medication side effects (beta-blockers, androgenic steroids, corticosteroids, progestogens, thiazide diuretics, retinoic acid derivatives, oral estrogens, etc.) and genetic abnormalities (mutations ApoA-I, LCAT, ABC1). Low level is defined as less than 40 mg/dL.

Triglycerides

Triglyceride level is an independent risk factor for cardiovascular disease and/or metabolic syndrome. Food intake prior to testing may cause elevated levels, up to 20%. Normal level is defined as less than 150 mg/dL. Borderline high is defined as 150 to 199 mg/dL. High level is between 200 and 499 mg/dL. Greater than 500 mg/dL is defined as very high, and is associated with pancreatitis and requires medical treatment.

Screening age

Health organizations does not have a consensus on the age to begin screening for hyperlipidemia. The CDC recommends cholesterol screenings once between ages 9 and 11, once again between 17 and 21, and every 4 to 6 years in adulthood. Doctors may recommend more frequent screenings for people with a family history of early heart attacks, heart disease, or if a child has obesity or diabetes. USPSTF recommends men older than 35 and women older than 45 to be screened. NCE-ATP III recommends all adults older than 20 to be screened as it may lead potential lifestyle modification that can reduce risks of other diseases. However, screening should be done for those with known CHD or risk-equivalent conditions (e.g. Acute Coronary Syndrome, history of heart attacks, Stable or Unstable angina, Transient ischemic attacks, Peripheral arterial disease of atherosclerotic origins, coronary or other arterial revascularization).

Screening frequency

Adults 20 years and older should have the cholesterol checked every four to six years, and most screening guidelines recommends testing every 5 years. USPSTF recommends increased frequency for people with elevated risk of CHD, which may be determined using cardiovascular disease risk scores.

Management

Management of hyperlipidemia includes maintenance of a normal body weight, increased physical activity, and decreased consumption of refined carbohydrates and simple sugars. Prescription drugs may be used to treat some people having significant risk factors, such as cardiovascular disease, LDL cholesterol greater than 190 mg/dL or diabetes. Common medication therapy is a statin.

HMG-CoA reductase inhibitors

Competitive inhibitors of HMG-CoA reductase, such as lovastatin, atorvastatin, fluvastatin, pravastatin, simvastatin, rosuvastatin, and pitavastatin, inhibit the synthesis of mevalonate, a precursor molecule to cholesterol. This medication class is especially effective at decreasing elevated LDL cholesterol. Major side effects include elevated transaminases and myopathy.

Fibric acid derivatives

Fibric acid derivatives, such as gemfibrozil and fenofibrate, function by increasing the lipolysis in adipose tissue via activation of peroxisome proliferator-activated receptor-α. They decrease VLDL – very low density lipoprotein – and LDL in some people. Major side effects include rashes, GI upset, myopathy, or increased transaminases.

Niacin

Niacin, or vitamin B3 has a mechanism of action that is poorly understood, however it has been shown to decrease LDL cholesterol and triglycerides, and increase HDL cholesterol. The most common side effect is flushing secondary to skin vasodilation. This effect is mediated by prostaglandins and can be decreased by taking concurrent aspirin.

Bile acid binding resins

Bile acid binding resins, such as colestipol, cholestyramine, and colesevelam, function by binding bile acids, increasing their excretion. They are useful for decreasing LDL cholesterol. The most common side effects include bloating and diarrhea.

Sterol absorption inhibitors

Inhibitors of intestinal sterol absorption, such as ezetimibe, function by decreasing the absorption of cholesterol in the GI tract by targeting NPC1L1, a transport protein in the gastrointestinal wall. This results in decreased LDL cholesterol.

Prevention

Quitting smoking, lowering intake of saturated fat and alcohol, losing excess body weight, and eating a low-salt diet that emphasizes fruits, vegetables, and whole grains can help reduce blood cholesterol.

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