Myasthenia gravis

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Myasthenia_gravis 

 

Myasthenia gravis
Eye deviation and a drooping eyelid in a person with myasthenia gravis trying to open her eyes
Specialty	Neurology
Symptoms	Varying degrees muscle weakness, double vision, drooping eyelids, trouble talking, trouble walking
Usual onset	Women under 40, men over 60
Duration	Long term
Causes	Autoimmune disease
Diagnostic method	Blood tests for specific antibodies, edrophonium test, nerve conduction studies
Differential diagnosis	Guillain–Barré syndrome, botulism, organophosphate poisoning, brainstem stroke
Treatment	Medications, surgical removal of the thymus, plasmapheresis
Medication	Acetylcholinesterase inhibitors (neostigmine, pyridostigmine), immunosuppressants
Frequency	50 to 200 per million

Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, drooping eyelids, trouble talking, and trouble walking. Onset can be sudden. Those affected often have a large thymus or develop a thymoma.

Myasthenia gravis is an autoimmune disease of the neuro-muscular junction which results from antibodies that block or destroy nicotinic acetylcholine receptors (AChR) at the junction between the nerve and muscle. This prevents nerve impulses from triggering muscle contractions. Most cases are due to immunoglobulin G1 (IgG1) and IgG3 antibodies that attack AChR in the postsynaptic membrane, causing complement-mediated damage and muscle weakness. Rarely, an inherited genetic defect in the neuromuscular junction results in a similar condition known as congenital myasthenia. Babies of mothers with myasthenia may have symptoms during their first few months of life, known as neonatal myasthenia. Diagnosis can be supported by blood tests for specific antibodies, the edrophonium test, or a nerve conduction study.

MG is generally treated with medications known as acetylcholinesterase inhibitors, such as neostigmine and pyridostigmine. Immunosuppressants, such as prednisone or azathioprine, may also be used. The surgical removal of the thymus may improve symptoms in certain cases. Plasmapheresis and high-dose intravenous immunoglobulin may be used during sudden flares of the condition. If the breathing muscles become significantly weak, mechanical ventilation may be required. Once intubated acetylcholinesterase inhibitors may be temporarily held to reduce airway secretions.

MG affects 50 to 200 per million people. It is newly diagnosed in three to 30 per million people each year. Diagnosis has become more common due to increased awareness. MG most commonly occurs in women under the age of 40 and in men over the age of 60. It is uncommon in children. With treatment, most of those affected lead relatively normal lives and have a normal life expectancy. The word is from the Greek mys, "muscle" and astheneia "weakness", and the Latin gravis, "serious".

Signs and symptoms

The initial, main symptom in MG is painless weakness of specific muscles, not fatigue. The muscle weakness becomes progressively worse during periods of physical activity and improves after periods of rest. Typically, the weakness and fatigue are worse toward the end of the day. MG generally starts with ocular (eye) weakness; it might then progress to a more severe generalized form, characterized by weakness in the extremities or in muscles that govern basic life functions.

Eyes

In about two-thirds of individuals, the initial symptom of MG is related to the muscles around the eye. Eyelid drooping (ptosis may occur due to weakness of m. levator palpebrae superioris) and double vision (diplopia, due to weakness of the extraocular muscles). Eye symptoms tend to get worse when watching television, reading, or driving, particularly in bright conditions. Consequently, some affected individuals choose to wear sunglasses. The term "ocular myasthenia gravis" describes a subtype of MG where muscle weakness is confined to the eyes, i.e. extraocular muscles, m. levator palpebrae superioris, and m. orbicularis oculi. Typically, this subtype evolves into generalized MG, usually after a few years.

Eating

The weakness of the muscles involved in swallowing may lead to swallowing difficulty (dysphagia). Typically, this means that some food may be left in the mouth after an attempt to swallow, or food and liquids may regurgitate into the nose rather than go down the throat (velopharyngeal insufficiency). Weakness of the muscles that move the jaw (muscles of mastication) may cause difficulty chewing. In individuals with MG, chewing tends to become more tiring when chewing tough, fibrous foods. Difficulty in swallowing, chewing, and speaking is the first symptom in about one-sixth of individuals.

Speaking

Weakness of the muscles involved in speaking may lead to dysarthria and hypophonia. Speech may be slow and slurred, or have a nasal quality. In some cases, a singing hobby or profession must be abandoned.

Head and neck

Due to weakness of the muscles of facial expression and muscles of mastication, facial weakness may manifest as the inability to hold the mouth closed (the "hanging jaw sign") and as a snarling expression when attempting to smile. With drooping eyelids, facial weakness may make the individual appear sleepy or sad. Difficulty in holding the head upright may occur.

Other

The muscles that control breathing and limb movements can also be affected; rarely do these present as the first symptoms of MG, but develop over months to years.^[19] In a myasthenic crisis, a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life.^[20] Crises may be triggered by various biological stressors such as infection, fever, an adverse reaction to medication, or emotional stress.^[20]

Pathophysiology

MG is an autoimmune synaptopathy. The disorder occurs when the immune system malfunctions and generates antibodies that attack the body's tissues. The antibodies in MG attack a normal human protein, the nicotinic acetylcholine receptor, or a related protein called MuSK, a muscle-specific kinase. Other, less frequent antibodies are found against LRP4, agrin, and titin proteins.

Human leukocyte antigen haplotypes are associated with increased susceptibility to myasthenia gravis and other autoimmune disorders. Relatives of people with myasthenia gravis have a higher percentage of other immune disorders.

The thymus gland cells form part of the body's immune system. In those with myasthenia gravis, the thymus gland is large and abnormal. It sometimes contains clusters of immune cells that indicate lymphoid hyperplasia, and the thymus gland may give wrong instructions to immune cells.

• 

  Neuromuscular junction: 1. Axon 2. Muscle cell membrane 3. Synaptic vesicle 4. Nicotinic acetylcholine receptor 5. Mitochondrion

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  A juvenile thymus shrinks with age.

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  The nicotinic acetylcholine receptor

In pregnancy

For women who are pregnant and already have MG, in a third of cases, they have been known to experience an exacerbation of their symptoms, and in those cases, it usually occurs in the first trimester of pregnancy. Signs and symptoms in pregnant mothers tend to improve during the second and third trimesters. Complete remission can occur in some mothers. Immunosuppressive therapy should be maintained throughout pregnancy, as this reduces the chance of neonatal muscle weakness, and controls the mother's myasthenia.

About 10–20% of infants with mothers affected by the condition are born with transient neonatal myasthenia (TNM), which generally produces feeding and respiratory difficulties that develop about 12 hours to several days after birth. A child with TNM typically responds very well to acetylcholinesterase inhibitors, and the condition generally resolves over a period of three weeks, as the antibodies diminish, and generally does not result in any complications. Very rarely, an infant can be born with arthrogryposis multiplex congenita, secondary to profound intrauterine weakness. This is due to maternal antibodies that target an infant's acetylcholine receptors. In some cases, the mother remains asymptomatic.

Diagnosis

MG can be difficult to diagnose, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders.

Three types of myasthenic symptoms in children can be distinguished:

1. Transient neonatal myasthenia occurs in 10 to 15% of babies born to mothers afflicted with the disorder, and disappears after a few weeks.
2. Congenital myasthenia, the rarest form, occurs when genes are present from both parents.
3. Juvenile myasthenia gravis is most common in females.

Congenital myasthenias cause muscle weakness and fatigability similar to those of MG. The signs of congenital myasthenia usually are present in the first years of childhood, although they may not be recognized until adulthood.

Classification

Myasthenia Gravis Foundation of America Clinical Classification

Class	Description
I	Any eye muscle weakness, possible ptosis, no other evidence of muscle weakness elsewhere
II	Eye muscle weakness of any severity, mild weakness of other muscles
IIa	Predominantly limb or axial muscles
IIb	Predominantly bulbar and/or respiratory muscles
III	Eye muscle weakness of any severity, moderate weakness of other muscles
IIIa	Predominantly limb or axial muscles
IIIb	Predominantly bulbar and/or respiratory muscles
IV	Eye muscle weakness of any severity, severe weakness of other muscles
IVa	Predominantly limb or axial muscles
IVb	Predominantly bulbar and/or respiratory muscles
V	Intubation needed to maintain airway

When diagnosed with MG, a person is assessed for his or her neurological status and the level of illness is established. This is usually done using the accepted Myasthenia Gravis Foundation of America Clinical Classification scale.

Physical examination

During a physical examination to check for MG, a doctor might ask the person to perform repetitive movements. For instance, the doctor may ask one to look at a fixed point for 30 seconds and to relax the muscles of the forehead, because a person with MG and ptosis of the eyes might be involuntarily using the forehead muscles to compensate for the weakness in the eyelids. The clinical examiner might also try to elicit the "curtain sign" in a person by holding one of the person's eyes open, which in the case of MG will lead the other eye to close.

Blood tests

If the diagnosis is suspected, serology can be performed:

• One test is for antibodies against the acetylcholine receptor; the test has a reasonable sensitivity of 80–96%, but in ocular myasthenia, the sensitivity falls to 50%.
• A proportion of the people without antibodies against the acetylcholine receptor have antibodies against the MuSK protein.
• In specific situations, testing is performed for Lambert-Eaton syndrome.

Electrodiagnostics

A chest CT-scan showing a thymoma (red circle)

 

Photograph of a person showing right partial ptosis (left picture), the left lid shows compensatory pseudo lid retraction because of equal innervation of the m. levator palpabrae superioris (Hering's law of equal innervation): Right picture: after an edrophonium test, note the improvement in ptosis.

Muscle fibers of people with MG are easily fatigued, which the repetitive nerve stimulation test can help diagnose. In single-fiber electromyography, which is considered to be the most sensitive (although not the most specific) test for MG, a thin needle electrode is inserted into different areas of a particular muscle to record the action potentials from several samplings of different individual muscle fibers. Two muscle fibers belonging to the same motor unit are identified, and the temporal variability in their firing patterns is measured. Frequency and proportion of particular abnormal action potential patterns, called "jitter" and "blocking", are diagnostic. Jitter refers to the abnormal variation in the time interval between action potentials of adjacent muscle fibers in the same motor unit. Blocking refers to the failure of nerve impulses to elicit action potentials in adjacent muscle fibers of the same motor unit.

Ice test

Applying ice for 2–5 minutes to the muscles reportedly has a sensitivity and specificity of 76.9% and 98.3%, respectively, for the identification of MG. Acetylcholinesterase is thought to be inhibited at the lower temperature, which is the basis for this diagnostic test. This generally is performed on the eyelids when ptosis is present and is deemed positive if a ≥2-mm rise in the eyelid occurs after the ice is removed.

Edrophonium test

This test requires the intravenous administration of edrophonium chloride or neostigmine, drugs that block the breakdown of acetylcholine by cholinesterase (acetylcholinesterase inhibitors). This test is no longer typically performed, as its use can lead to life-threatening bradycardia (slow heart rate) which requires immediate emergency attention. Production of edrophonium was discontinued in 2008.

Imaging

A chest X-ray may identify widening of the mediastinum suggestive of thymoma, but computed tomography or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas and are generally done for this reason. MRI of the cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles.

Pulmonary function test

The forced vital capacity may be monitored at intervals to detect increasing muscular weakness. Acutely, negative inspiratory force may be used to determine adequacy of ventilation; it is performed on those individuals with MG.

Management

Treatment is by medication and/or surgery. Medication consists mainly of acetylcholinesterase inhibitors to directly improve muscle function and immunosuppressant drugs to reduce the autoimmune process. Thymectomy is a surgical method to treat MG.

Medication

Neostigmine, chemical structure

 

Azathioprine, chemical structure

Worsening may occur with medication such as fluoroquinolones, aminoglycosides, and magnesium. About 10% of people with generalized MG are considered treatment-refractory. Autologous hematopoietic stem cell transplantation (HSCT) is sometimes used in severe, treatment-refractory MG. Available data provide preliminary evidence that HSCT can be an effective therapeutic option in carefully selected cases.

Efgartigimod alfa was approved for medical use in the United States in December 2021.

Acetylcholinesterase inhibitors

Acetylcholinesterase inhibitors can provide symptomatic benefit and may not fully remove a person's weakness from MG. While they might not fully remove all symptoms of MG, they still may allow a person the ability to perform normal daily activities. Usually, acetylcholinesterase inhibitors are started at a low dose and increased until the desired result is achieved. If taken 30 minutes before a meal, symptoms will be mild during eating, which is helpful for those who have difficulty swallowing due to their illness. Another medication used for MG, atropine, can reduce the muscarinic side effects of acetylcholinesterase inhibitors. Pyridostigmine is a relatively long-acting drug (when compared to other cholinergic agonists), with a half-life around four hours with relatively few side effects. Generally, it is discontinued in those who are being mechanically ventilated, as it is known to increase the amount of salivary secretions. A few high-quality studies have directly compared cholinesterase inhibitors with other treatments (or placebo); their practical benefit may be so significant that conducting studies in which they would be withheld from some people would be difficult.

Immune suppressants

The steroid prednisone might also be used to achieve a better result, but it can lead to the worsening of symptoms and takes weeks to achieve its maximal effectiveness. Due to the myriad symptoms that steroid treatments can cause, it is not the preferred method of treatment. Other immune suppressing medications may also be used including rituximab or azathioprine.

Plasmapheresis and IVIG

If the myasthenia is serious (myasthenic crisis), plasmapheresis can be used to remove the putative antibodies from the circulation. Also, intravenous immunoglobulins (IVIGs) can be used to bind the circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in weeks, and often are associated with high costs, which make them prohibitive; they are generally reserved for when MG requires hospitalization.

Surgery

As thymomas are seen in 10% of all people with the MG, they are often given a chest X-ray and CT scan to evaluate their need for surgical removal of their thymus glands and any cancerous tissue that may be present. Even if surgery is performed to remove a thymoma, it generally does not lead to the remission of MG. Surgery in the case of MG involves the removal of the thymus, although in 2013, no clear benefit was indicated except in the presence of a thymoma. A 2016 randomized, controlled trial, however, found some benefits.

Physical measures

People with MG should be educated regarding the fluctuating nature of their symptoms, including weakness and exercise-induced fatigue. Exercise participation should be encouraged with frequent rest. In people with generalized MG, some evidence indicates a partial home program including training in diaphragmatic breathing, pursed-lip breathing, and interval-based muscle therapy may improve respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance.

Medical imaging

In people with myasthenia gravis, older forms of iodinated contrast used for medical imaging have caused an increased risk of exacerbation of the disease, but modern forms have no immediate increased risk.

Prognosis

The prognosis of people with MG is generally good, as is quality of life, when given very good treatment. Monitoring of a person with MG is very important, as at least 20% of people diagnosed with it will experience a myasthenic crisis within two years of their diagnosis, requiring rapid medical intervention. Generally, the most disabling period of MG might be years after the initial diagnosis. In the early 1900s, 70% of detected cases died from lung problems; now, that number is estimated to be around 3–5%, an improvement attributed to increased awareness and medications to manage symptoms.

Epidemiology

MG occurs in all ethnic groups and both sexes. It most commonly affects women under 40 and people from 50 to 70 years old of either sex, but it has been known to occur at any age. Younger people rarely have thymoma. Prevalence in the United States is estimated at between 0.5 and 20.4 cases per 100,000, with an estimated 60,000 Americans affected. In the United Kingdom, an estimated 15 cases of MG occur per 100,000 people.

History

The first to write about MG were Thomas Willis, Samuel Wilks, Erb, and Goldflam. The term "myasthenia gravis pseudo-paralytica" was proposed in 1895 by Jolly, a German physician. Mary Walker treated a person with MG with physostigmine in 1934. Simpson and Nastuck detailed the autoimmune nature of the condition. In 1973, Patrick and Lindstrom used rabbits to show that immunization with purified muscle-like acetylcholine receptors caused the development of MG-like symptoms.

Research

Immunomodulating substances, such as drugs that prevent acetylcholine receptor modulation by the immune system, are currently being researched. Some research recently has been on anti-c5 inhibitors for treatment research as they are safe and used in the treatment of other diseases. Ephedrine seems to benefit some people more than other medications, but it has not been properly studied as of 2014. In the laboratory, MG is mostly studied in model organisms, such as rodents. In addition, in 2015, scientists developed an in vitro functional, all-human, neuromuscular junction assay from human embryonic stem cells and somatic-muscle stem cells. After the addition of pathogenic antibodies against the acetylcholine receptor and activation of the complement system, the neuromuscular co-culture shows symptoms such as weaker muscle contractions.

Soviet atomic bomb project

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Soviet_atomic_bomb_project 

 

Soviet atomic bomb project
The mushroom cloud from the first air-dropped bomb test in 1951. This picture is confused with RDS-27 and RDS-37 tests.
Operational scope	Operational R&D
Location	Atomgrad, Semipalatinsk, Chagan
Planned by	NKVD, NKGB GRU, MGB, PGU
Date	1942–1949
Executed by	Soviet Union
Outcome	The successful development of nuclear weapons Further escalation of the Cold War

The Soviet atomic bomb project was the classified research and development program that was authorized by Joseph Stalin in the Soviet Union to develop nuclear weapons during and after World War II.

Although the Soviet scientific community discussed the possibility of an atomic bomb throughout the 1930s, going as far as making a concrete proposal to develop such a weapon in 1940, the full-scale program was not initiated and prioritized until Operation Barbarossa.

Because of the conspicuous silence of the scientific publications on the subject of nuclear fission by German, American, and British scientists, Russian physicist Georgy Flyorov suspected that the Allied powers had secretly been developing a "superweapon" since 1939. Flyorov wrote a letter to Stalin urging him to start this program in 1942. Initial efforts were slowed due to the German invasion of the Soviet Union and remained largely composed of the intelligence gathering from the Soviet spy rings working in the U.S. Manhattan Project.

After Stalin learned of the atomic bombings of Hiroshima and Nagasaki, the program was pursued aggressively and accelerated through effective intelligence gathering about the German nuclear weapon project and the American Manhattan Project. The Soviet efforts also rounded up captured German scientists to join their program, and relied on knowledge passed by spies to Soviet intelligence agencies.

On 29 August 1949, the Soviet Union secretly conducted its first successful weapon test (First Lightning, based on the American "Fat Man" design) at the Semipalatinsk-21 in Kazakhstan. Stalin alongside Soviet political officials and scientists were elated at the successful test. A nuclear armed Soviet Union sent its rival Western neighbors, and particularly the United States into a state of unprecedented trepidation. From 1949 onwards the Soviet Union manufactured and tested nuclear weapons on a large scale. The nuclear capabilities these tests helped develop were crucial to projecting and maintaining its global status. In total, the Soviet Union conducted 715 nuclear weapon tests throughout the course of the Cold War. A nuclear-armed Soviet Union escalated the Cold War with the United States to the possibility of nuclear war and ushered in the doctrine of mutually assured destruction.

Early efforts

Background origins and roots

Main articles: Timeline of Russian inventions and technology records and History of the periodic table

As early as 1910 in Russia, independent research was being conducted on radioactive elements by several Russian scientists. Despite the hardship faced by the Russian academy of sciences during the national revolution in 1917, followed by the violent civil war in 1922, Russian scientists had made remarkable efforts toward the advancement of physics research in the Soviet Union by the 1930s. Before the first revolution in 1905, the mineralogist Vladimir Vernadsky had made a number of public calls for a survey of Russia's uranium deposits but none were heeded. Such early efforts were independently and privately funded by various organizations until 1922 when the Radium Institute in Petrograd (now Saint Petersburg) opened and industrialized the research.

From the 1920s until the late 1930s, Russian physicists had been conducting joint research with their European counterparts on the advancement of atomic physics at the Cavendish Laboratory run by a New Zealand physicist, Ernest Rutherford, where Georgi Gamov and Pyotr Kapitsa had studied and researched.

Influential research towards the advancement of nuclear physics was guided by Abram Ioffe, who was the director at the Leningrad Physical-Technical Institute (LPTI), having sponsored various research programs at various technical schools in the Soviet Union. The discovery of the neutron by the British physicist James Chadwick further provided promising expansion of the LPTI's program, with the operation of the first cyclotron to energies of over 1 MeV, and the first "splitting" of the atomic nucleus by John Cockcroft and Ernest Walton. Russian physicists began pushing the government, lobbying in the interest of the development of science in the Soviet Union, which had received little interest due to the upheavals created during the Russian revolution and the February Revolution. Earlier research was directed towards the medical and scientific exploration of radium; a supply of it was available as it could be retrieved from borehole water from the Ukhta oilfields.

In 1939, German chemist Otto Hahn reported his discovery of fission, achieved by the splitting of uranium with neutrons that produced the much lighter element barium. This eventually led to the realization among Russian scientists, and their American counterparts, that such reaction could have military significance. The discovery excited the Russian physicists, and they began conducting their independent investigations on nuclear fission, mainly aiming towards power generation, as many were skeptical of possibility of creating an atomic bomb anytime soon. Early efforts were led by Yakov Frenkel (a physicist specialised on condensed matter), who did the first theoretical calculations on continuum mechanics directly relating the kinematics of binding energy in fission process in 1940. Georgy Flyorov's and Lev Rusinov's collaborative work on thermal reactions concluded that 3-1 neutrons were emitted per fission only days after similar conclusions had been reached by the team of Frédéric Joliot-Curie.

World War II and accelerated feasibility

Main article: Eastern Front (World War II)

 

The 1942 Russian report on the feasibility of uranium titled: Disposition No. 2352: "On the organization of work on uranium.

After a strong lobbying of Russian scientists, the Soviet government initially set up a commission that was to address the "uranium problem" and investigate the possibility of chain reaction and isotope separation. The Uranium Problem Commission was ineffective because the German invasion of Soviet Union eventually limited the focus on research, as Russia became engaged in a bloody conflict along the Eastern Front for the next four years. The Soviet atomic weapons program had no significance, and most work was unclassified as the papers were continuously published as public domain in academic journals.

Joseph Stalin, the Soviet leader, had mostly disregarded the atomic knowledge possessed by the Russian scientists as had most of the scientists working in the metallurgy and mining industry or serving in the Soviet Armed Forces technical branches during the World War II's eastern front in 1940–42.

In 1940–42, Georgy Flyorov, a Russian physicist serving as an officer in the Soviet Air Force, noted that despite progress in other areas of physics, the German, British, and American scientists had ceased publishing papers on nuclear science. Clearly, they each had active secret research programs. The dispersal of Soviet scientists had sent Abram Ioffe’s Radium Institute from Leningrad to Kazan; and the wartime research program put the "uranium bomb" programme third, after radar and anti-mine protection for ships. Kurchatov had moved from Kazan to Murmansk to work on mines for the Soviet Navy.

In April 1942, Flyorov directed two classified letters to Stalin, warning him of the consequences of the development of atomic weapons: "the results will be so overriding [that] it won't be necessary to determine who is to blame for the fact that this work has been neglected in our country." The second letter, by Flyorov and Konstantin Petrzhak, highly emphasized the importance of a "uranium bomb": "it is essential to manufacture a uranium bomb without a delay."

Upon reading the Flyorov letters, Stalin immediately pulled Russian physicists from their respective military services and authorized an atomic bomb project, under engineering physicist Anatoly Alexandrov and nuclear physicist Igor V. Kurchatov. For this purpose, the Laboratory No. 2 near Moscow was established under Kurchatov. Kurchatov was chosen in late 1942 as the technical director of the Soviet bomb program; he was awed by the magnitude of the task but was by no means convinced of its utility against the demands of the front. Abram Ioffe had refused the post as he was too old, and recommended the young Kurchatov.

At the same time, Flyorov was moved to Dubna, where he established the Laboratory of Nuclear Reactions, focusing on synthetic elements and thermal reactions. In late 1942, the State Defense Committee officially delegated the program to the Soviet Army, with major wartime logistical efforts later being supervised by Lavrentiy Beria, the head of NKVD.

In 1945, the Arzamas 16 site, near Moscow, was established under Yakov Zel'dovich and Yuli Khariton who performed calculations on nuclear combustion theory, alongside Isaak Pomeranchuk. Despite early and accelerated efforts, it was reported by historians that efforts on building a bomb using weapon-grade uranium seemed hopeless to Russian scientists. Igor Kurchatov had harboured doubts working towards the uranium bomb, but made progress on a bomb using weapon-grade plutonium after British data was provided by the NKVD.

The situation dramatically changed when the Soviet Union learned of the atomic bombings of Hiroshima and Nagasaki in 1945.

Immediately after the atomic bombing, the Soviet Politburo took control of the atomic bomb project by establishing a special committee to oversee the development of nuclear weapons as soon as possible. On 9 April 1946, the Council of Ministers created KB–11 ('Design Bureau-11') that worked towards mapping the first nuclear weapon design, primarily based on the American approach and detonated with weapon-grade plutonium. From then on work on the program was carried out quickly, resulting in the first nuclear reactor near Moscow on 25 October 1946.

Organization and administration

The German assistance

Main article: Russian Alsos

From 1941 to 1946, the Soviet Union's Ministry of Foreign Affairs handled the logistics of the atomic bomb project, with Foreign Minister Vyacheslav Molotov controlling the direction of the program. However, Molotov proved to be a weak administrator, and the program stagnated. In contrast to American military administration in their atomic bomb project, the Russians' program was directed by political dignitaries such as Molotov, Lavrentiy Beria, Georgii Malenkov, and Mikhail Pervukhin—there were no military members.

After the atomic bombings of Hiroshima and Nagasaki, the program's leadership changed, when Stalin appointed Lavrentiy Beria on 22 August 1945. Beria is noted for leadership that helped the program to its final implementation.

Beria understood the necessary scope and dynamics of research. This man, who was the personification of evil to modern Russian history, also possessed the great energy and capacity to work. The scientists who met him could not fail to recognize his intelligence, his will power, and his purposefullness. They found him first-class administrator who could carry a job through to completion...

— Yulii Khariton, The First War of Physics: The Secret History of the Atom Bomb, 1939-1949^[31]

The new Committee, under Beria, retained Georgii Malenkov and added Nikolai Voznesensky and Boris Vannikov, People's Commissar for Armament. Under the administration of Beria, the NKVD co-opted atomic spies of the Soviet Atomic Spy Ring into the American program, and infiltrated the German nuclear program whose nuclear scientists were later instrumental in attaining the feasibility of Soviet nuclear weapons.

Espionage

Soviet atomic ring

Main articles: Nuclear espionage and Atomic spies

 

The 1945 sketch of circular shaped implosion-type passed by the American spies for the Soviet Union. This schematic was part of the development of RDS-1, test fired in Kazakhstan in 1949.

The nuclear and industrial espionages in the United States by American sympathisers of communism who were controlled by their rezident Russian officials in North America greatly aided the speed of the Soviet nuclear program from 1942–54. The willingness in sharing classified information to the Soviet Union by recruited American communist sympathizers increased when the Soviet Union faced possible defeat during the German invasion in World War II. The Russian intelligence network in the United Kingdom also played a vital role in setting up the spy rings in the United States when the Russian State Defense Committee approved resolution 2352 in September 1942.

For this purpose, the spy Harry Gold, controlled by Semyon Semyonov, was used for a wide range of espionage that included industrial espionage in the American chemical industry and obtaining sensitive atomic information that was handed over to him by the British physicist Klaus Fuchs. Knowledge and further technical information that were passed by the American Theodore Hall, a theoretical physicist, and Klaus Fuchs had a significant impact on the direction of Russian development of nuclear weapons.

Leonid Kvasnikov, a Russian engineer turned KGB officer, was assigned for this special purpose and moved to New York City to coordinate such activities. Anatoli Yatzkov, another NKVD official in New York, was also involved in obtaining sensitive information gathered by Sergei Kournakov from Saville Sax.

The existence of Russian spies was exposed by the U.S. Army's secretive Venona project in 1943.

For example, Soviet work on methods of uranium isotope separation was altered when it was reported, to Kurchatov's surprise, that the Americans had opted for the Gaseous diffusion method. While research on other separation methods continued throughout the war years, the emphasis was placed on replicating U.S. success with gaseous diffusion. Another important breakthrough, attributed to intelligence, was the possibility of using plutonium instead of uranium in a fission weapon. Extraction of plutonium in the so-called "uranium pile" allowed bypassing of the difficult process of uranium separation altogether, something that Kurchatov had learned from intelligence from the Manhattan project.

Soviet intelligence management in the Manhattan Project

Main articles: History of Soviet and Russian espionage in the United States and History of Soviet espionage

In 1945, the Soviet intelligence obtained rough blueprints of the first U.S. atomic device. Alexei Kojevnikov has estimated, based on newly released Soviet documents, that the primary way in which the espionage may have sped up the Soviet project was that it allowed Khariton to avoid dangerous tests to determine the size of the critical mass: "tickling the dragon's tail", as it was called in the U.S., consumed a good deal of time and claimed at least two lives; see Harry Daghlian and Louis Slotin.

The published Smyth Report of 1945 on the Manhattan Project was translated into Russian, and the translators noted that a sentence on the effect of "poisoning" of Plutonium-239 in the first (lithograph) edition had been deleted from the next (Princeton) edition by Groves. This change was noted by the Russian translators, and alerted the Soviet Union to the problem (which had meant that reactor-bred plutonium could not be used in a simple gun-type bomb like the proposed Thin Man).

One of the key pieces of information, which Soviet intelligence obtained from Fuchs, was a cross-section for D-T fusion. This data was available to top Soviet officials roughly three years before it was openly published in the Physical Review in 1949. However, this data was not forwarded to Vitaly Ginzburg or Andrei Sakharov until very late, practically months before publication. Initially both Ginzburg and Sakharov estimated such a cross-section to be similar to the D-D reaction. Once the actual cross-section become known to Ginzburg and Sakharov, the Sloika design become a priority, which resulted in a successful test in 1953.

In the 1990s, with the declassification of Soviet intelligence materials, which showed the extent and the type of the information obtained by the Soviets from US sources, a heated debate ensued in Russia and abroad as to the relative importance of espionage, as opposed to the Soviet scientists' own efforts, in the making of the Soviet bomb. The vast majority of scholars agree that whereas the Soviet atomic project was first and foremost a product of local expertise and scientific talent, it is clear that espionage efforts contributed to the project in various ways and most certainly shortened the time needed to develop the atomic bomb.

Comparing the timelines of H-bomb development, some researchers came to the conclusion that the Soviets had a gap in access to classified information regarding the H-bomb at least between late 1950 and some time in 1953. Earlier, e.g., in 1948, Fuchs gave the Soviets a detailed update of the classical super progress, including an idea to use lithium, but did not explain it was specifically lithium-6. By 1951 Teller accepted the fact that the "classical super" scheme wasn't feasible, following results obtained by various researchers (including Stanislaw Ulam) and calculations performed by John von Neumann in late 1950.

Yet the research for the Soviet analogue of "classical super" continued until December 1953, when the researchers were reallocated to a new project working on what later became a true H-bomb design, based on radiation implosion. This remains an open topic for research, whether the Soviet intelligence was able to obtain any specific data on Teller-Ulam design in 1953 or early 1954. Yet, Soviet officials directed the scientists to work on a new scheme, and the entire process took less than two years, commencing around January 1954 and producing a successful test in November 1955. It also took just several months before the idea of radiation implosion was conceived, and there is no documented evidence claiming priority. It is also possible that Soviets were able to obtain a document lost by John Wheeler on a train in 1953, which reportedly contained key information about thermonuclear weapon design.

Initial thermonuclear designs

Main articles: Thermonuclear weapon and Thermobaric weapon

 

Early Russian design on thermonuclear device dated back to 1955.

Early ideas of the fusion bomb came from espionage and internal Soviet studies. Though the espionage did help Soviet studies, the early American H-bomb concepts had substantial flaws, so it may have confused, rather than assisted, the Soviet effort to achieve nuclear capability. The designers of early thermonuclear bombs envisioned using an atomic bomb as a trigger to provide the needed heat and compression to initiate the thermonuclear reaction in a layer of liquid deuterium between the fissile material and the surrounding chemical high explosive. The group would realize that a lack of sufficient heat and compression of the deuterium would result in an insignificant fusion of the deuterium fuel.

Andrei Sakharov's study group at FIAN in 1948 came up with a second concept in which adding a shell of natural, unenriched uranium around the deuterium would increase the deuterium concentration at the uranium-deuterium boundary and the overall yield of the device, because the natural uranium would capture neutrons and itself fission as part of the thermonuclear reaction. This idea of a layered fission-fusion-fission bomb led Sakharov to call it the sloika, or layered cake. It was also known as the RDS-6S, or Second Idea Bomb. This second bomb idea was not a fully evolved thermonuclear bomb in the contemporary sense, but a crucial step between pure fission bombs and the thermonuclear "supers". Due to the three-year lag in making the key breakthrough of radiation compression from the United States the Soviet Union's development efforts followed a different course of action. In the United States they decided to skip the single-stage fusion bomb and make a two-stage fusion bomb as their main effort. Unlike the Soviet Union, the analog RDS-7 advanced fission bomb was not further developed, and instead, the single-stage 400-kiloton RDS-6S was the Soviet's bomb of choice.

The RDS-6S Layer Cake design was detonated on 12 August 1953, in a test given the code name by the Allies of "Joe 4". The test produced a yield of 400 kilotons, about ten times more powerful than any previous Soviet test. Around this time the United States detonated its first super using radiation compression on 1 November 1952, code-named Mike. Though the Mike was about twenty times greater than the RDS-6S, it was not a design that was practical to use, unlike the RDS-6S.

Following the successful launching of the RDS-6S, Sakharov proposed an upgraded version called RDS-6SD. This bomb was proved to be faulty, and it was neither built nor tested. The Soviet team had been working on the RDS-6T concept, but it also proved to be a dead end.

In 1954, Sakharov worked on a third concept, a two-stage thermonuclear bomb. The third idea used the radiation wave of a fission bomb, not simply heat and compression, to ignite the fusion reaction, and paralleled the discovery made by Ulam and Teller. Unlike the RDS-6S boosted bomb, which placed the fusion fuel inside the primary A-bomb trigger, the thermonuclear super placed the fusion fuel in a secondary structure a small distance from the A-bomb trigger, where it was compressed and ignited by the A-bomb's x-ray radiation. The KB-11 Scientific-Technical Council approved plans to proceed with the design on 24 December 1954. Technical specifications for the new bomb were completed on 3 February 1955, and it was designated the RDS-37.

The RDS-37 was successfully tested on 22 November 1955 with a yield of 1.6 megaton. The yield was almost a hundred times greater than the first Soviet atomic bomb six years before, showing that the Soviet Union could compete with the United States. and would even exceed them in time.

Logistical problems

The single largest problem during the early Soviet program was the procurement of raw uranium ore, as the Soviet Union had limited domestic sources at the beginning of their nuclear program. The era of domestic uranium mining can be dated exactly, to November 27, 1942, the date of a directive issued by the all-powerful wartime State Defense Committee. The first Soviet uranium mine was established in Taboshar, present-day Tajikistan, and was producing at an annual rate of a few tons of uranium concentrate by May 1943. Taboshar was the first of many officially secret Soviet closed cities related to uranium mining and production.

Demand from the experimental bomb project was far higher. The Americans, with the help of Belgian businessman Edgar Sengier in 1940, had already blocked access to known sources in Congo, South Africa, and Canada. In December 1944 Stalin took the uranium project away from Vyacheslav Molotov and gave to it to Lavrentiy Beria. The first Soviet uranium processing plant was established as the Leninabad Mining and Chemical Combine in Chkalovsk (present-day Buston, Ghafurov District), Tajikistan, and new production sites identified in relative proximity. This posed a need for labor, a need that Beria would fill with forced labor: tens of thousands of Gulag prisoners were brought to work in the mines, the processing plants, and related construction.

Domestic production was still insufficient when the Soviet F-1 reactor, which began operation in December 1946, was fueled using uranium confiscated from the remains of the German atomic bomb project. This uranium had been mined in the Belgian Congo, and the ore in Belgium fell into the hands of the Germans after their invasion and occupation of Belgium in 1940. In 1945, the Uranium enrichment through electromagnetic method under Lev Artsimovich also failed due to USSR's inability to build the parallel American Oak Ridge site and the limited power grid system could not produce the electricity for their program.

Further sources of uranium in the early years of the program were mines in East Germany (via the deceptively-named SAG Wismut), Czechoslovakia, Bulgaria, Romania (the Băița mine near Ștei) and Poland. Boris Pregel sold 0.23 tonnes of uranium oxide to the Soviet Union during the war, with the authorisation of the U.S. Government.

Eventually, large domestic sources were discovered in the Soviet Union (including those now in Kazakhstan).

The uranium for the Soviet nuclear weapons program came from mine production in the following countries,

Year	USSR	Germany	Czechoslovakia	Bulgaria	Poland
1945	14.6 t
1946	50.0 t	15 t	18 t	26.6 t
1947	129.3 t	150 t	49.1 t	7.6 t	2.3 t
1948	182.5 t	321.2 t	103.2 t	18.2 t	9.3 t
1949	278.6 t	767.8 t	147.3 t	30.3 t	43.3 t
1950	416.9 t	1,224 t	281.4 t	70.9 t	63.6 t

Important nuclear tests

See also: List of nuclear weapons tests of the Soviet Union

 

The Soviet program of nuclear weapons produces the stockpile (shown in black and white) reaching at its height in 1986 exceeding the United States stockpiles.

RDS-1

RDS-1, the first Soviet atomic test was internally code-named First Lightning (Первая молния, or Pervaya Molniya) August 29, 1949, and was code-named by the Americans as Joe 1. The design was very similar to the first US "Fat Man" plutonium bomb, using a TNT/hexogen implosion lens design.

RDS-2

On September 24, 1951, the 38.3 kiloton device RDS-2 was tested based on a tritium "boosted" uranium implosion device with a levitated core. This test was code named Joe 2 by the CIA.

RDS-3

RDS-3 was the third Soviet atomic bomb. On October 18, 1951, the 41.2 kiloton device was detonated - a boosted weapon using a composite construction of levitated plutonium core and a uranium-235 shell. Code named Joe 3 in the USA, this was the first Soviet air-dropped bomb test. Released at an altitude of 10 km, it detonated 400 meters above the ground.

RDS-4

RDS-4 represented a branch of research on small tactical weapons. It was a boosted fission device using plutonium in a "levitated" core design. The first test was an air drop on August 23, 1953, yielding 28 kilotons. In 1954, the bomb was also used during Snowball exercise in Totskoye, dropped by Tu-4 bomber on the simulated battlefield, in the presence of 40,000 infantry, tanks, and jet fighters. The RDS-4 comprised the warhead of the R-5M, the first medium-range ballistic missile in the world, which was tested with a live warhead for the first and only time on February 5, 1956

RDS-5

RDS-5 was a small plutonium based device, probably using a hollow core. Two different versions were made and tested.

RDS-6

RDS-6, the first Soviet test of a hydrogen bomb, took place on August 12, 1953, and was nicknamed Joe 4 by the Americans. It used a layer-cake design of fission and fusion fuels (uranium 235 and lithium-6 deuteride) and produced a yield of 400 kilotons. This yield was about ten times more powerful than any previous Soviet test. When developing higher level bombs, the Soviets proceeded with the RDS-6 as their main effort instead of the analog RDS-7 advanced fission bomb. This led to the third idea bomb which is the RDS-37.

RDS-9

A much lower-power version of the RDS-4 with a 3-10 kiloton yield, the RDS-9 was developed for the T-5 nuclear torpedo. A 3.5 kiloton underwater test was performed with the torpedo on September 21, 1955.

RDS-37

The first Soviet test of a "true" hydrogen bomb in the megaton range was conducted on November 22, 1955. It was dubbed RDS-37 by the Soviets. It was of the multi-staged, radiation implosion thermonuclear design called Sakharov's "Third Idea" in the USSR and the Teller–Ulam design in the USA.

Joe 1, Joe 4, and RDS-37 were all tested at the Semipalatinsk Test Site in Kazakhstan.

Tsar Bomba (RDS-220)

The Tsar Bomba (Царь-бомба) was the largest, most powerful thermonuclear weapon ever detonated. It was a three-stage hydrogen bomb with a yield of about 50 megatons. This is equivalent to ten times the amount of all the explosives used in World War II combined. It was detonated on October 30, 1961, in the Novaya Zemlya archipelago, and was capable of approximately 100 megatons, but was purposely reduced shortly before the launch. Although weaponized, it was not entered into service; it was simply a demonstrative testing of the capabilities of the Soviet Union's military technology at that time. The heat of the explosion was estimated to potentially inflict third degree burns at 100 km distance of clear air.

Chagan

Chagan was a shot in the Nuclear Explosions for the National Economy (also known as Project 7), the Soviet equivalent of the US Operation Plowshare to investigate peaceful uses of nuclear weapons. It was a subsurface detonation. It was fired on January 15, 1965. The site was a dry bed of the river Chagan at the edge of the Semipalatinsk Test Site, and was chosen such that the lip of the crater would dam the river during its high spring flow. The resultant crater had a diameter of 408 meters and was 100 meters deep. A major lake (10,000 m³) soon formed behind the 20–35 m high upraised lip, known as Chagan Lake or Balapan Lake.

The photo is sometimes confused with RDS-1 in literature.

Secret cities

Main article: Atomgrads

 

The Radioaktivnost' warning sign left at the now-ruined and abandoned Laboratory B in Sungulʹ, ca. 2009.

During the Cold War, the Soviet Union created at least nine closed cities, known as Atomgrads, in which nuclear weapons-related research and development took place. After the dissolution of the Soviet Union, all of the cities changed their names (most of the original code-names were simply the oblast and a number). All are still legally "closed", though some have parts of them accessible to foreign visitors with special permits (Sarov, Snezhinsk, and Zheleznogorsk).

Cold War name	Current name	Established	Primary function(s)
Arzamas-16	Sarov	1946	Weapons design and research, warhead assembly
Sverdlovsk-44	Novouralsk	1946	Uranium enrichment
Chelyabinsk-40 and later 65	Ozyorsk	1947	Plutonium production, component manufacturing
Sverdlovsk-45	Lesnoy	1947	Uranium enrichment, warhead assembly
Tomsk-7	Seversk	1949	Uranium enrichment, component manufacturing
Krasnoyarsk-26	Zheleznogorsk	1950	Plutonium production
Zlatoust-36	Tryokhgorny	1952	Warhead assembly
Penza-19	Zarechny	1955	Warhead assembly
Krasnoyarsk-45	Zelenogorsk	1956	Uranium enrichment
Chelyabinsk-70	Snezhinsk	1957	Weapons design and research

Environmental and public health effects

Main articles: Totskoye nuclear exercise, Kyshtym disaster, Chernobyl disaster, Andreev Bay nuclear accident, Public health problems in the Aral Sea region, Nyonoksa radiation accident, and 2022 Russian invasion of Ukraine

 

The former Soviet nuclear devices left behind large amounts of radioactive isotopes, which have contaminated air, water, and soil in the areas immediately surrounding them, enough to double the normal rate of ¹⁴C from the atmosphere, and due to the increase in biomass and necromass.

The Soviets started experimenting with nuclear technology in 1943 with very little regard of nuclear safety as there were no reports of accidents that were ever made public to learn from, and the public was kept in hidden about the radiation dangers. Many of the nuclear devices left behind radioactive isotopes which have contaminated air, water and soil in the areas immediately surrounding, downwind and downstream of the blast site. According to the records that the Russian government released in 1991, the Soviet Union tested 969 nuclear devices between 1949 and 1990— the more nuclear testing than any nation in the planet. Soviet scientists conducted the tests with little regard for environmental and public health consequences. The detrimental effects that the toxic waste generated by weapons testing and processing of radioactive materials are still felt to this day. Even decades later, the risk of developing various types of cancer, especially that of the thyroid and the lungs, continues to be elevated far above national averages for people in affected areas. Iodine-131, a radioactive isotope that is a major byproduct of fission-based weapons, is retained in the thyroid gland, and so poisoning of this kind is commonplace in impacted populations.

The Soviets set off 214 nuclear devices in the open atmosphere between 1949 and 1962, the year the United Nations banned atmospheric tests worldwide. The billions of radioactive particles released into the air exposed countless people to extremely mutagenic and carcinogenic materials, resulting in a myriad of deleterious genetic maladies and deformities. The majority of these tests took place at the Semipalatinsk Test Site, or the Polygon, located in northeast of Kazakhstan. The testing at Semipalatinsk alone exposed hundreds of thousands of Kazakh citizens to the harmful effects, and the site continues to be one of the most highly irradiated places on the planet. When the earliest tests were being conducted, even the scientists had only a poor understanding of the medium-and long-term effects of radiation exposure— many did not notify each other of their work if they had serious accidents or expose of radiation. In fact, the Semipalatinsk was chosen as the primary site for open-air testing precisely because the Soviets were curious about the potential for lasting harm that their weapons held.

The ecosystem collapse of the receding Aral sea in Central Asia has left huge plains covered with salt and toxic chemicals from nuclear weapons testing, industrial projects, and pesticides and fertilizer runoff.

 

The 1996 level of Cesium-137 contamination over Ukraine after an unsafe operation led to a serious accident in 1986.

Contamination of air and soil due to atmospheric testing is only part of a wider issue. Water contamination due to improper disposal of spent uranium and decay of sunken nuclear-powered submarines is a major problem in the Kola Peninsula in northwest Russia. Although the Russian government states that the radioactive power cores are stable, various scientists have come forth with serious concerns about the 32,000 spent nuclear fuel elements that remain in the sunken vessels. There have been no major incidents other than the explosion and sinking of a nuclear-powered submarine in August 2000, but many international scientists are still uneasy at the prospect of the hulls eroding, releasing uranium into the sea and causing considerable contamination. Although the submarines pose an environmental risk, they have yet to cause serious harm to public health. However, water contamination in the area of the Mayak test site, especially at Lake Karachay, is extreme, and has gotten to the point where radioactive byproducts have found their way into drinking water supplies. It has been an area of concern since the early 1950s, when the Soviets began disposing of tens of millions of cubic meters of radioactive waste by pumping it into the small lake. Half a century later, in the 1990s, there are still hundreds of millions of curies of waste in the Lake, and at points contamination has been so severe that a mere half-hour of exposure to certain regions would deliver a dose of radiation sufficient to kill 50% of humans. Although the area immediately surrounding the lake is devoid of population, the lake has the potential to dry up in times of drought. Most significantly, in 1967, it dried up and winds carried radioactive dust over thousands of square kilometers, exposing at least 500,000 citizens to a range of health risks. To control dust, Soviet scientists piled concrete on top of the lake. Although this was effective in helping mediate the amount of dust, the weight of the concrete pushed radioactive materials into closer contact with standing underground groundwater.^[61]: A166 It is difficult to gauge the overall health and environmental effects of the water contamination at Lake Karachay because figures on civilian exposure are unavailable, making it hard to show causation between elevated cancer rates and radioactive pollution specifically from the lake.

Contemporary efforts to manage radioactive contamination in the former Soviet Union are few and far between. Public awareness of the past and present dangers, as well as the Russian government's investment in current cleanup efforts, are likely dampened by the lack of media attention STS and other sites have gotten in comparison to isolated nuclear incidents such as Hiroshima, Nagasaki, Chernobyl and Three-Mile Island. The domestic government's investment in cleanup measures seems to be driven by economic concerns rather than care for public health. The most significant political legislation in this area is a bill agreeing to turn the already contaminated former weapons complex Mayak into an international radioactive waste dump, accepting cash from other countries in exchange for taking their radioactive byproducts of nuclear industry. Although the bill stipulates that the revenue go towards decontaminating other test sites such as Semipalatinsk and the Kola Peninsula, experts doubt whether this will actually happen given the current political and economic climate in Russia.