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Friday, February 22, 2019

Bacillus thuringiensis

From Wikipedia, the free encyclopedia

Bacillus thuringiensis (Bt)
Bt-toxin-crystals.jpg
Spores and bipyramidal crystals of Bacillus thuringiensis morrisoni strain T08025
Scientific classification
Domain: Bacteria
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Bacillaceae
Genus: Bacillus
Species:
B. thuringiensis
Binomial name
Bacillus thuringiensis
Berliner 1915

Gram stain of Bacillus thuringiensis under 1000 × magnification
 
Bacillus thuringiensis (or Bt) is a Gram-positive, soil-dwelling bacterium, commonly used as a biological pesticide. B. thuringiensis also occurs naturally in the gut of caterpillars of various types of moths and butterflies, as well on leaf surfaces, aquatic environments, animal feces, insect-rich environments, and flour mills and grain-storage facilities. It has also been observed to parasitize other moths such as Cadra calidella—in laboratory experiments working with C. calidella, many of the moths were diseased due to this parasite.

During sporulation, many Bt strains produce crystal proteins (proteinaceous inclusions), called δ-endotoxins, that have insecticidal action. This has led to their use as insecticides, and more recently to genetically modified crops using Bt genes, such as Bt corn. Many crystal-producing Bt strains, though, do not have insecticidal properties. The subspecies israelensis is commonly used for control of mosquitoes and of fungus gnats.

Taxonomy and discovery

B. thuringiensis was first discovered in 1901 by Japanese biologist Ishiwatari Shigetane (石渡 繁胤) in silkworms. He named it Bacillus sotto, using the Japanese word sottō (卒倒, ‘collapse’), here referring to bacillary paralysis. In 1911, German microbiologist Ernst Berliner independently rediscovered it when he isolated it as the cause of a disease called Schlaffsucht in flour moth caterpillars in Thuringia (hence the specific name thuringiensis, "Thuringian"). B. sotto would later be reassigned as B. thuringiensis var. sotto.

In 1976, Robert A. Zakharyan reported the presence of a plasmid in a strain of B. thuringiensis and suggested the plasmid's involvement in endospore and crystal formation. B. thuringiensis is closely related to B. cereus, a soil bacterium, and B. anthracis, the cause of anthrax; the three organisms differ mainly in their plasmids. Like other members of the genus, all three are aerobes capable of producing endospores.

Tubulin was long thought to be specific to eukaryotes. More recently, however, several prokaryotic proteins have been shown to be related to tubulin.

Subspecies

There are several dozen recognized subspecies of Bacillus thuringiensis. Subspecies commonly used as insecticides include Bacillus thuringiensis subspecies kurstaki (Btk), subspecies israelensis (Bti) and subspecies aizawa.

Mechanism of insecticidal action

Upon sporulation, B. thuringiensis forms crystals of proteinaceous insecticidal δ-endotoxins (called crystal proteins or Cry proteins), which are encoded by cry genes. In most strains of B. thuringiensis, the cry genes are located on a plasmid (cry is not a chromosomal gene in most strains).

Cry toxins have specific activities against insect species of the orders Lepidoptera (moths and butterflies), Diptera (flies and mosquitoes), Coleoptera (beetles), Hymenoptera (wasps, bees, ants and sawflies) and against nematodes. Thus, B. thuringiensis serves as an important reservoir of Cry toxins for production of biological insecticides and insect-resistant genetically modified crops. When insects ingest toxin crystals, their alkaline digestive tracts denature the insoluble crystals, making them soluble and thus amenable to being cut with proteases found in the insect gut, which liberate the toxin from the crystal. The Cry toxin is then inserted into the insect gut cell membrane, paralyzing the digestive tract and forming a pore. The insect stops eating and starves to death; live Bt bacteria may also colonize the insect which can contribute to death. The midgut bacteria of susceptible larvae may be required for B. thuringiensis insecticidal activity.

It has been shown that a small RNA called BtsR1 can silence the Cry toxin when outside the host by binding to the RBS site of the Cry5Ba toxin transcript and inhibiting its expression. The silencing results in increased ingestion by C. elegans and is relieved inside the host, resulting in host death.

In 1996 another class of insecticidal proteins in Bt was discovered; the vegetative insecticidal proteins (Vip). Vip proteins do not share sequence homology with Cry proteins, in general do not compete for the same receptors, and some kill different insects than do Cry proteins.

In 2000, a novel functional group of Cry protein, designated parasporin, was discovered from noninsecticidal B. thuringiensis isolates. The proteins of parasporin group are defined as B. thuringiensis and related bacterial parasporal proteins that are not hemolytic, but capable of preferentially killing cancer cells. As of January 2013, parasporins comprise six subfamilies: PS1 to PS6.

Use of spores and proteins in pest control

Spores and crystalline insecticidal proteins produced by B. thuringiensis have been used to control insect pests since the 1920s and are often applied as liquid sprays. They are now used as specific insecticides under trade names such as DiPel and Thuricide. Because of their specificity, these pesticides are regarded as environmentally friendly, with little or no effect on humans, wildlife, pollinators, and most other beneficial insects, and are used in organic farming; however, the manuals for these products do contain many environmental and human health warnings, and a 2012 European regulatory peer review of five approved strains found, while data exist to support some claims of low toxicity to humans and the environment, the data are insufficient to justify many of these claims.

New strains of Bt are developed and introduced over time as insects develop resistance to Bt, or the desire occurs to force mutations to modify organism characteristics or to use homologous recombinant genetic engineering to improve crystal size and increase pesticidal activity or broaden the host range of Bt and obtain more effective formulations. Each new strain is given a unique number and registered with the U.S. EPA and allowances may be given for genetic modification depending on "its parental strains, the proposed pesticide use pattern, and the manner and extent to which the organism has been genetically modified". Formulations of Bt that are approved for organic farming in the US are listed at the website of the Organic Materials Review Institute (OMRI) and several university extension websites offer advice on how to use Bt spore or protein preparations in organic farming.

Use of Bt genes in genetic engineering of plants for pest control

The Belgian company Plant Genetic Systems (now part of Bayer CropScience) was the first company (in 1985) to develop genetically modified crops (tobacco) with insect tolerance by expressing cry genes from B. thuringiensis; the resulting crops contain delta endotoxin. The Bt tobacco was never commercialized; tobacco plants are used to test genetic modifications since they are easy to manipulate genetically and are not part of the food supply.

Bt toxins present in peanut leaves (bottom dish) protect it from extensive damage caused to unprotected peanut leaves by lesser cornstalk borer larvae (top dish).[52]

Usage

In 1995, potato plants producing CRY 3A Bt toxin were approved safe by the Environmental Protection Agency, making it the first human-modified pesticide-producing crop to be approved in the USA, though many plants produce pesticides naturally, including tobacco, coffee plants, cocoa, and black walnut. This was the 'New Leaf' potato, and it was removed from the market in 2001 due to lack of interest.

In 1996, genetically modified maize producing Bt Cry protein was approved, which killed the European corn borer and related species; subsequent Bt genes were introduced that killed corn rootworm larvae.

The Bt genes engineered into crops and approved for release include, singly and stacked: Cry1A.105, CryIAb, CryIF, Cry2Ab, Cry3Bb1, Cry34Ab1, Cry35Ab1, mCry3A, and VIP, and the engineered crops include corn and cotton.

Corn genetically modified to produce VIP was first approved in the US in 2010.

In India, by 2014, more than seven million cotton farmers, occupying twenty-six million acres, had adopted Bt cotton.

Monsanto developed a soybean expressing Cry1Ac and the glyphosate resistance gene for the Brazilian market, which completed the Brazilian regulatory process in 2010.

Kenyans examining insect-resistant transgenic Bt corn

Safety studies

The use of Bt toxins as plant-incorporated protectants prompted the need for extensive evaluation of their safety for use in foods and potential unintended impacts on the environment.

Dietary risk assessment

Concerns over the safety of consumption of genetically-modified plant materials that contain Cry proteins have been addressed in extensive dietary risk assessment studies. While the target pests are exposed to the toxins primarily through leaf and stalk material, Cry proteins are also expressed in other parts of the plant, including trace amounts in maize kernels which are ultimately consumed by both humans and animals.
Toxicology studies
Animal models have been used to assess human health risk from consumption of products containing Cry proteins. The United States Environmental Protection Agency recognizes mouse acute oral feeding studies where doses as high as 5,000 mg/kg body weight resulted in no observed adverse effects. Research on other known toxic proteins suggests that toxicity occurs at much lower doses, further suggesting that Bt toxins are not toxic to mammals. The results of toxicology studies are further strengthened by the lack of observed toxicity from decades of use of B. thuringiensis and its crystalline proteins as an insecticidal spray.
Allergenicity studies
Introduction of a new protein raised concerns regarding the potential for allergic responses in sensitive individuals. Bioinformatic analysis of known allergens has indicated there is no concern of allergic reactions as a result of consumption of Bt toxins. Additionally, skin prick testing using purified Bt protein resulted in no detectable production of toxin-specific IgE antibodies, even in atopic patients.
Digestibility studies
Studies have been conducted to evaluate the fate of Bt toxins that are ingested in foods. Bt toxin proteins have been shown to digest within minutes of exposure to simulated gastric fluids. The instability of the proteins in digestive fluids is an additional indication that Cry proteins are unlikely to be allergenic, since most known food allergens resist degradation and are ultimately absorbed in the small intestine.

Ecological risk assessment

Ecological risk assessment aims to ensure there is no unintended impact on non-target organisms and no contamination of natural resources as a result of the use of a new substance, such as the use of Bt in genetically-modified crops. The impact of Bt toxins on the environments where transgenic plants are grown has been evaluated to ensure no adverse effects outside of targeted crop pests.
Persistence in environment
Concerns over possible environmental impact from accumulation of Bt toxins from plant tissues, pollen dispersal, and direct secretion from roots have been investigated. Bt toxins may persist in soil for over 200 days, with half-lives between 1.6 and 22 days. Much of the toxin is initially degraded rapidly by microorganisms in the environment, while some is adsorbed by organic matter and persists longer. Some studies, in contrast, claim that the toxins do not persist in the soil. Bt toxins are less likely to accumulate in bodies of water, but pollen shed or soil runoff may deposit them in an aquatic ecosystem. Fish species are not susceptible to Bt toxins if exposed.
Impact on non-target organisms
The toxic nature of Bt proteins has an adverse impact on many major crop pests, but ecological risk assessments have been conducted to ensure safety of beneficial non-target organisms that may come into contact with the toxins. Widespread concerns over toxicity in non-target lepidopterans, such as the monarch butterfly, have been disproved through proper exposure characterization, where it was determined that non-target organisms are not exposed to high enough amounts of the Bt toxins to have an adverse effect on the population. Soil-dwelling organisms, potentially exposed to Bt toxins through root exudates, are not impacted by the growth of Bt crops.

Insect resistance

Multiple insects have developed a resistance to B. thuringiensis. In November 2009, Monsanto scientists found the pink bollworm had become resistant to the first-generation Bt cotton in parts of Gujarat, India - that generation expresses one Bt gene, Cry1Ac. This was the first instance of Bt resistance confirmed by Monsanto anywhere in the world. Monsanto responded by introducing a second-generation cotton with multiple Bt proteins, which was rapidly adopted. Bollworm resistance to first-generation Bt cotton was also identified in Australia, China, Spain, and the United States. Additionally, the Indian mealmoth, a common grain pest, is also developing a resistance since B. thuringiensis has been extensively used as a biological control agent against the moth. Studies in the cabbage looper have suggested that a mutation in the membrane transporter ABCC2 can confer resistance to B. thuringiensis.

Secondary pests

Several studies have documented surges in "sucking pests" (which are not affected by Bt toxins) within a few years of adoption of Bt cotton. In China, the main problem has been with mirids, which have in some cases "completely eroded all benefits from Bt cotton cultivation". The increase in sucking pests depended on local temperature and rainfall conditions and increased in half the villages studied. The increase in insecticide use for the control of these secondary insects was far smaller than the reduction in total insecticide use due to Bt cotton adoption. Another study in five provinces in China found the reduction in pesticide use in Bt cotton cultivars is significantly lower than that reported in research elsewhere, consistent with the hypothesis suggested by recent studies that more pesticide sprayings are needed over time to control emerging secondary pests, such as aphids, spider mites, and lygus bugs.

Similar problems have been reported in India, with both mealy bugs and aphids although a survey of small Indian farms between 2002 and 2008 concluded Bt cotton adoption has led to higher yields and lower pesticide use, decreasing over time.

Controversies

There are controversies around GMOs on several levels, including whether making them is ethical, whether food produced with them is safe, whether such food should be labeled and if so how, whether agricultural biotech is needed to address world hunger now or in the future, and more specifically to GM crops—intellectual property and market dynamics; environmental effects of GM crops; and GM crops' role in industrial agricultural more generally. There are also issues specific to Bt transgenic crops.

Lepidopteran toxicity

The most publicized problem associated with Bt crops is the claim that pollen from Bt maize could kill the monarch butterfly. The paper produced a public uproar and demonstrations against Bt maize; however by 2001 several follow-up studies coordinated by the USDA had asserted that "the most common types of Bt maize pollen are not toxic to monarch larvae in concentrations the insects would encounter in the fields." Similarly, Bacillus thuringiensis has been widely used for controlling Spodoptera littoralis larvae growth due to their detrimental pest activities in Africa and Southern Europe. However, S. littoralis showed resistance to many strains of B. thuriginesis and were only effectively controlled by few strains.

Wild maize genetic mixing

A study published in Nature in 2001 reported Bt-containing maize genes were found in maize in its center of origin, Oaxaca, Mexico. In 2002, paper concluded, "the evidence available is not sufficient to justify the publication of the original paper." A significant controversy happened over the paper and Nature's unprecedented notice.

A subsequent large-scale study, in 2005, failed to find any evidence of genetic mixing in Oaxaca. A 2007 study found the "transgenic proteins expressed in maize were found in two (0.96%) of 208 samples from farmers' fields, located in two (8%) of 25 sampled communities." Mexico imports a substantial amount of maize from the US, and due to formal and informal seed networks among rural farmers, many potential routes are available for transgenic maize to enter into food and feed webs. One study found small-scale (about 1%) introduction of transgenic sequences in sampled fields in Mexico; it did not find evidence for or against this introduced genetic material being inherited by the next generation of plants. That study was immediately criticized, with the reviewer writing, "Genetically, any given plant should be either non-transgenic or transgenic, therefore for leaf tissue of a single transgenic plant, a GMO level close to 100% is expected. In their study, the authors chose to classify leaf samples as transgenic despite GMO levels of about 0.1%. We contend that results such as these are incorrectly interpreted as positive and are more likely to be indicative of contamination in the laboratory."

Colony collapse disorder

As of 2007, a new phenomenon called colony collapse disorder (CCD) began affecting bee hives all over North America. Initial speculation on possible causes included new parasites, pesticide use, and the use of Bt transgenic crops. The Mid-Atlantic Apiculture Research and Extension Consortium found no evidence that pollen from Bt crops is adversely affecting bees. According to the USDA, "Genetically modified (GM) crops, most commonly Bt corn, have been offered up as the cause of CCD. But there is no correlation between where GM crops are planted and the pattern of CCD incidents. Also, GM crops have been widely planted since the late 1990s, but CCD did not appear until 2006. In addition, CCD has been reported in countries that do not allow GM crops to be planted, such as Switzerland. German researchers have noted in one study a possible correlation between exposure to Bt pollen and compromised immunity to Nosema." The actual cause of CCD was unknown in 2007, and scientists believe it may have multiple exacerbating causes.

Beta-exotoxins

Some isolates of B. thuringiensis produce a class of insecticidal small molecules called beta-exotoxin, the common name for which is thuringiensin. A consensus document produced by the OECD says: "Beta-exotoxins are known to be toxic to humans and almost all other forms of life and its presence is prohibited in B. thuringiensis microbial products"

History of surgery

From Wikipedia, the free encyclopedia


Surgery is the branch of medicine that deals with the physical manipulation of a bodily structure to diagnose, prevent, or cure an ailment. Ambroise Paré, a 16th-century French surgeon, stated that to perform surgery is, "To eliminate that which is superfluous, restore that which has been dislocated, separate that which has been united, join that which has been divided and repair the defects of nature." 

Since humans first learned to make and handle tools, they have employed their talents to develop surgical techniques, each time more sophisticated than the last; however, until the industrial revolution, surgeons were incapable of overcoming the three principal obstacles which had plagued the medical profession from its infancy — bleeding, pain and infection. Advances in these fields have transformed surgery from a risky "art" into a scientific discipline capable of treating many diseases and conditions.

Origins

The first surgical techniques were developed to treat injuries and traumas. A combination of archaeological and anthropological studies offer insight into man's early techniques for suturing lacerations, amputating unsalvageable limbs, and draining and cauterizing open wounds. Many examples exist: some Asian tribes used a mix of saltpeter and sulfur that was placed onto wounds and lit on fire to cauterize wounds; the Dakota people used the quill of a feather attached to an animal bladder to suck out purulent material; the discovery of needles from the stone age seem to suggest they were used in the suturing of cuts (the Maasai used needles of acacia for the same purpose); and tribes in India and South America developed an ingenious method of sealing minor injuries by applying termites or scarabs who bit the edges of the wound and then twisted the insects' neck, leaving their heads rigidly attached like staples.

Trepanation

The oldest operation for which evidence exists is trepanation (also known as trepanning, trephination, trephining or burr hole from Greek τρύπανον and τρυπανισμός), in which a hole is drilled or scraped into the skull for exposing the dura mater to treat health problems related to intracranial pressure and other diseases. In the case of head wounds, surgical intervention was implemented for investigating and diagnosing the nature of the wound and the extent of the impact while bone splinters were removed preferably by scraping followed by post operation procedures and treatments for avoiding infection and aiding in the healing process. Evidence has been found in prehistoric human remains from Proto-Neolithic and Neolithic times, in cave paintings, and the procedure continued in use well into recorded history (being described by ancient Greek writers such as Hippocrates). Out of 120 prehistoric skulls found at one burial site in France dated to 6500 BCE, 40 had trepanation holes. Folke Henschen, a Swedish doctor and historian, asserts that Soviet excavations of the banks of the Dnieper River in the 1970s show the existence of trepanation in Mesolithic times dated to approximately 12000 BCE. The remains suggest a belief that trepanning could cure epileptic seizures, migraines, and certain mental disorders.

There is significant evidence of healing of the bones of the skull in prehistoric skeletons, suggesting that many of those that proceeded with the surgery survived their operation. In some studies, the rate of survival surpassed 50%.

Setting bones

Examples of healed fractures in prehistoric human bones, suggesting setting and splinting have been found in the archeological record. Among some treatments used by the Aztecs, according to Spanish texts during the conquest of Mexico, was the reduction of fractured bones: "...the broken bone had to be splinted, extended and adjusted, and if this was not sufficient an incision was made at the end of the bone, and a branch of fir was inserted into the cavity of the medulla..." Modern medicine developed a technique similar to this in the 20th century known as medullary fixation.

Bloodletting

Hirudo medicinalis. Leeches for bloodletting
 
Bloodletting is one of the oldest medical practices, having been practiced among diverse ancient peoples, including the Mesopotamians, the Egyptians, the Greeks, the Mayans, and the Aztecs. In Greece, bloodletting was in use around the time of Hippocrates, who mentions bloodletting but in general relied on dietary techniques. Erasistratus, however, theorized that many diseases were caused by plethoras, or over abundances, in the blood, and advised that these plethoras be treated, initially, by exercise, sweating, reduced food intake, and vomiting. Herophilus advocated bloodletting. Archagathus, one of the first Greek physicians to practice in Rome, practiced bloodletting extensively. The art of bloodletting became very popular in the West, and during the Renaissance one could find bloodletting calendars that recommended appropriate times to bloodlet during the year and books that claimed bloodletting would cure inflammation, infections, strokes, manic psychosis and more.

Antiquity

Mesopotamia

The Sumerians saw sickness as a divine punishment imposed by different demons when an individual broke a rule. For this reason, to be a physician, one had to learn to identify approximately 6,000 possible demons that might cause health problems. To do this, the Sumerians employed divining techniques based on the flight of birds, position of the stars and the livers of certain animals. In this way, medicine was intimately linked to priests, relegating surgery to a second-class medical specialty.

Nevertheless, the Sumerians developed several important medical techniques: in Ninevah archaeologists have discovered bronze instruments with sharpened obsidian resembling modern day scalpels, knives, trephines, etc. The Code of Hammurabi, one of the earliest Babylonian code of laws, itself contains specific legislation regulating surgeons and medical compensation as well as malpractice and victim's compensation:
215. If a physician make a large incision with an operating knife and cure it, or if he open a tumor (over the eye) with an operating knife, and saves the eye, he shall receive ten shekels in money.
217. If he be the slave of some one, his owner shall give the physician two shekels.
218. If a physician make a large incision with the operating knife, and kill him, or open a tumor with the operating knife, and cut out the eye, his hands shall be cut off.
220. If he had opened a tumor with the operating knife, and put out his eye, he shall pay half his value.

Egypt

Pictures of surgery tools at Kom Ombo, Egypt
 
Around 3100 BCE Egyptian civilization began to flourish when Narmer, the first Pharaoh of Egypt, established the capital of Memphis. Just as cuneiform tablets preserved the knowledge of the ancient Sumerians, hieroglyphics preserved the Egyptian's.

In the first monarchic age (2700 BCE) the first treaty on surgery was written by Imhotep, the vizier of Pharaoh Djoser, priest, astronomer, physician and first notable architect. So much was he famed for his medical skill that he became the Egyptian god of medicine. Other famous physicians from the Ancient Empire (from 2500 to 2100 BCE) were Sachmet, the physician of Pharaoh Sahure and Nesmenau, whose office resembled that of a medical director.

On one of the doorjambs of the entrance to the Temple of Memphis there is the oldest recorded engraving of a medical procedure: circumcision and engravings in Kom Ombo, Egypt depict surgical tools. Still of all the discoveries made in ancient Egypt, the most important discovery relating to ancient Egyptian knowledge of medicine is the Ebers Papyrus, named after its discoverer Georg Ebers. The Ebers Papyrus, conserved at the University of Leipzig, is considered one of the oldest treaties on medicine and the most important medical papyri. The text is dated to about 1550 BCE and measures 20 meters in length. The text includes recipes, a pharmacopoeia and descriptions of numerous diseases as well as cosmetic treatments. It mentions how to surgically treat crocodile bites and serious burns, recommending the drainage of pus-filled inflammation but warns against certain diseased skin.

Edwin Smith Papyrus

Plates vi and vii of the Edwin Smith Papyrus (around the 17th century BC), among the earliest medical texts
 
The Edwin Smith Papyrus is a lesser known papyrus dating from the 1600 BCE and only 5 meters in length. It is a manual for performing traumatic surgery and gives 48 case histories. The Smith Papyrus describes a treatment for repairing a broken nose, and the use of sutures to close wounds. Infections were treated with honey. For example, it gives instructions for dealing with a dislocated vertebra:
Thou shouldst bind it with fresh meat the first day. Thou shouldst loose his bandages and apply grease to his head as far as his neck, (and) thou shouldst bind it with ymrw . Thou shouldst treat it afterwards with honey every day, (and) his relief is sitting until he recovers.

India

Archaeologists made the discovery that the people of Indus Valley Civilization, even from the early Harappan periods (c. 3300 BCE), had knowledge of medicine and dentistry. The physical anthropologist that carried out the examinations, Professor Andrea Cucina from the University of Missouri-Columbia, made the discovery when he was cleaning the teeth from one of the men. Later research in the same area found evidence of teeth having been drilled, dating back 9,000 years to 7000 BCE.

Sushruta (c. 600 BCE) is considered as the "founding father of surgery". His period is usually placed between the period of 1200 BC - 600 BC. One of the earliest known mention of the name is from the Bower Manuscript where Sushruta is listed as one of the ten sages residing in the Himalayas. Texts also suggest that he learned surgery at Kasi from Lord Dhanvantari, the god of medicine in Hindu mythology. He was an early innovator of plastic surgery who taught and practiced surgery on the banks of the Ganges in the area that corresponds to the present day city of Varanasi in Northern India. Much of what is known about Sushruta is in Sanskrit contained in a series of volumes he authored, which are collectively known as the Sushruta Samhita. It is one of the oldest known surgical texts and it describes in detail the examination, diagnosis, treatment, and prognosis of numerous ailments, as well as procedures on performing various forms of cosmetic surgery, plastic surgery and rhinoplasty.

Greece and the Hellenized world

Engraving of Hippocrates by Peter Paul Rubens, 1638.
 
Surgeons are now considered to be specialized physicians, whereas in the early ancient Greek world a trained general physician had to use his hands (χείρ in Greek) to carry out all medical and medicinal processes including for example the treating of wounds sustained on the battlefield, or the treatment of broken bones (a process called in Greek: χειρουργείν).

In The Iliad Homer names two doctors, “the two sons of Asklepios, the admirable physicians Podaleirius and Machaon and one acting doctor, Patroclus. Because Machaon is wounded and Podaleirius is in combat Eurypylus asks Patroclus “to cut out this arrow from my thigh, wash off the blood with warm water and spread soothing ointment on the wound."

Hippocrates

The Hippocratic Oath, written in the 5th century BC provides the earliest protocol for professional conduct and ethical behavior a young physician needed to abide by in life and in treating and managing the health and privacy of his patients. The multiple volumes of the Hippocratic corpus and the Hippocratic Oath elevated and separated the standards of proper Hippocratic medical conduct and its fundamental medical and surgical principles from other practitioners of folk medicine often laden with superstitious constructs, and/or of specialists of sorts some of whom would endeavor to carry out invasive body procedures with dubious consequences, such as lithotomy. Works from the Hippocratic corpus include; On the Articulations or On Joints, On Fractures, On the Instruments of Reduction, The Physician's Establishment or Surgery, On Injuries of the Head, On Ulcers, On Fistulae, and On Hemorrhoids.

Celsus and Alexandria

Herophilus of Chalcedon and Erasistratus of Ceos were two great Alexandrians who laid the foundations for the scientific study of anatomy and physiology. Alexandrian surgeons were responsible for developments in ligature (hemostasis), lithotomy, hernia operations, ophthalmic surgery, plastic surgery, methods of reduction of dislocations and fractures, tracheotomy, and mandrake as anesthesia. Most of what we know of them comes from Celsus and Galen of Pergamum (Greek: Γαληνός)

Galen

Galen's On the Natural Faculties, Books I, II, and III, is an excellent paradigm of a very accomplished Greek surgeon and physician of the 2nd century Roman era, who carried out very complex surgical operations and added significantly to the corpus of animal and human physiology and the art of surgery. He was one of the first to use ligatures in his experiments on animals. Galen is also known as "The king of the catgut suture"

China

In China, instruments resembling surgical tools have also been found in the archaeological sites of Bronze Age dating from the Shang Dynasty, along with seeds likely used for herbalism.

Hua Tuo

Woodblock printing by Utagawa Kuniyoshi of Hua Tuo
 
Hua Tuo (140–208) was a famous Chinese physician during the Eastern Han and Three Kingdoms era. He was the first person to perform surgery with the aid of anesthesia, some 1600 years before the practice was adopted by Europeans. Bian Que (Pien Ch'iao) was a "miracle doctor" described by the Chinese historian Sima Qian in his Shiji who was credited with many skills. Another book, Liezi (Lieh Tzu) describes that Bian Que conducted a two way exchange of hearts between people. This account also credited Bian Que with using general anesthesia which would place it far before Hua Tuo, but the source in Liezi is questioned and the author may have been compiling stories from other works. Nonetheless, it establishes the concept of heart transplantation back to around 300 CE.

Middle Ages

Paul of Aegina's (c. 625 – c. 690 CE) Pragmateia or Compendiem was highly influential. Abulcasis repeats the material, largely verbatim.

Hunayn ibn Ishaq (809–873) was an Arab Nestorian Christian physician who translated many Greek medical and scientific texts, including those of Galen, writing the first systematic treatment of ophthalmology

Persian physician Muhammad ibn Zakariya al-Razi (854–925), "the Islamic Hippocrates" advanced experimental medicine, pioneering ophthalmology and founding pediatrics

In the 9th century the Medical School of Salerno in southwest Italy was founded, making use of Arabic texts and flourishing through the 13th century. 

Egypt-born Jewish physician Isaac Israeli ben Solomon (832–892) left many medical works written in Arabic that were translated and adopted by European universities in the early 13th century. 

Persian physician Ali ibn Abbas al-Majusi (d. 994) worked at the Al-Adudi Hospital in Baghdad, leaving The Complete Book of the Medical Art, which stressed the need for medical ethics and discussed the anatomy and physiology of the human brain. 

Abulcasis (936–1013) (Abu al-Qasim Khalaf ibn al-Abbas Al-Zahrawi) was an Andalusian-Arab physician and scientist who practised in the Zahra suburb of Cordoba. He is considered a great medieval surgeon, though he added little to Greek surgical practices. His works on surgery were influential.

Persian physician Avicenna (980–1037) wrote The Canon of Medicine, a synthesis of Greek and Arab medicine that dominated European medicine until the mid-17th century.

African-born Italian Benedictine monk (Muslim convert) Constantine the African (died 1099) of Monte Cassino translated many Arabic medical works into Latin.

Spanish Muslim physician Avenzoar (1094–1162) performed the first tracheotomy on a goat, writing Book of Simplification on Therapeutics and Diet, which became popular in Europe.

Spanish Muslim physician Averroes (1126–1198) was the first to explain the function of the retina and to recognize acquired immunity with smallpox.

In Europe, universities such as Montpellier, Padua and Bologna were particularly renowned.

In the late 12th century Rogerius Salernitanus composed his Chirurgia, laying the foundation for modern Western surgical manuals. Roland of Parma and Surgery of the Four Masters were responsible for spreading Roger's work to Italy, France, and England. Roger seems to have been influenced more by the 6th-century Aëtius and Alexander of Tralles, and the 7th-century Paul of Aegina, than by the Arabs. Hugh of Lucca (1150−1257) founded the Bologna School and rejected the theory of "laudable pus".

In the 13th century in Europe skilled town craftsmen called barber-surgeons performed amputations and set broken bones while suffering lower status than university educated doctors. By 1308 the Worshipful Company of Barbers in London was flourishing. With little or no formal training, they generally had a bad reputation that was not to improve until the development of academic surgery as a specialty of medicine rather than an accessory field in the 18th-century Age of Enlightenment.

Guy de Chauliac (1298–1368) was one of the most eminent surgeons of the Middle Ages. His Chirurgia Magna or Great Surgery (1363) was a standard text for surgeons until well into the seventeenth century."

Early modern Europe

Andreas Vesalius (1514–1564)
 
Ambroise Paré (c. 1510–1590), father of modern military surgery.
 
Wilhelm Fabry (1540–1634), father of German surgery
 
There were some important advances to the art of surgery during this period. Andreas Vesalius (1514–1564), professor of anatomy at the University of Padua was a pivotal figure in the Renaissance transition from classical medicine and anatomy based on the works of Galen, to an empirical approach of 'hands-on' dissection. His anatomic treatise De humani corporis fabrica exposed many anatomical errors in Galen and advocated that all surgeons should train by engaging in practical dissections themselves.

The second figure of importance in this era was Ambroise Paré (sometimes spelled "Ambrose" (c. 1510 – 1590)), a French army surgeon from the 1530s until his death in 1590. The practice for cauterizing gunshot wounds on the battlefield had been to use boiling oil, an extremely dangerous and painful procedure. Paré began to employ a less irritating emollient, made of egg yolk, rose oil and turpentine. He also described more efficient techniques for the effective ligation of the blood vessels during an amputation.

Another important early figure was German surgeon Wilhelm Fabry (1540–1634), "the Father of German Surgery", who was the first to recommend amputation above the gangrenous area, and to describe a windlass (twisting stick) tourniquet. His Swiss wife and assistant Marie Colinet (1560–1640 improved the techniques for Caesarean Section, introducing the use of heat for dilating and stimulating the uterus during labor. In 1624 she became the first to use a magnet to remove metal from a patient's eye, although he received the credit.

Modern surgery

Scientific surgery

John Hunter (1728–1793), father of modern scientific surgery
 
Benjamin Bell (1749–1806) by Sir Henry Raeburn. c1780
 
The discipline of surgery was put on a sound, scientific footing during the Age of Enlightenment in Europe (1715–89). An important figure in this regard was the Scottish surgical scientist (in London) John Hunter (1728–1793), generally regarded as the father of modern scientific surgery. He brought an empirical and experimental approach to the science and was renowned around Europe for the quality of his research and his written works. Hunter reconstructed surgical knowledge from scratch; refusing to rely on the testimonies of others he conducted his own surgical experiments to determine the truth of the matter. To aid comparative analysis, he built up a collection of over 13,000 specimens of separate organ systems, from the simplest plants and animals to humans. 

Hunter greatly advanced knowledge of venereal disease and introduced many new techniques of surgery, including new methods for repairing damage to the Achilles tendon and a more effective method for applying ligature of the arteries in case of an aneurysm. He was also one of the first to understand the importance of pathology, the danger of the spread of infection and how the problem of inflammation of the wound, bone lesions and even tuberculosis often undid any benefit that was gained from the intervention. He consequently adopted the position that all surgical procedures should be used only as a last resort.

Hunter's student Benjamin Bell (1749–1806) became the first scientific surgeon in Scotland, advocating the routine use of opium in post-operative recovery, and counseling surgeons to "save skin" to speed healing; his great-grandson Joseph Bell (1837–1911) became the inspiration for Arthur Conan Doyle's literary hero Sherlock Holmes. 

Percivall Pott (1714–1788), engraved from an original picture by Nathaniel Dance-Holland, National Library of Medicine, Images from the History of Medicine.
 
Other important 18th- and early 19th-century surgeons included Percival Pott (1714–1788), who first described tuberculosis on the spine and first demonstrated that a cancer may be caused by an environmental carcinogen after he noticed a connection between chimney sweep's exposure to soot and their high incidence of scrotal cancer. Astley Paston Cooper (1768–1841) first performed a successful ligation of the abdominal aorta. James Syme (1799–1870) pioneered the Symes Amputation for the ankle joint and successfully carried out the first hip disarticulation. Dutch surgeon Antonius Mathijsen invented the Plaster of Paris cast in 1851.

Anesthesia

Crawford Long (1815–1878)
 
James Young Simpson (1811–1870)
 
John Snow (1813–1858)

Modern pain control through anesthesia was discovered in the mid-19th century. Before the advent of anesthesia, surgery was a traumatically painful procedure and surgeons were encouraged to be as swift as possible to minimize patient suffering. This also meant that operations were largely restricted to amputations and external growth removals. 

Beginning in the 1840s, surgery began to change dramatically in character with the discovery of effective and practical anesthetic chemicals such as ether, first used by the American surgeon Crawford Long (1815–1878), and chloroform, discovered by James Young Simpson (1811–1870) and later pioneered in England by John Snow (1813–1858), physician to Queen Victoria, who in 1853 administered chloroform to her during childbirth, and in 1854 disproved the miasma theory of contagion by tracing a cholera outbreak in London to an infected water pump. In addition to relieving patient suffering, anesthesia allowed more intricate operations in the internal regions of the human body. In addition, the discovery of muscle relaxants such as curare allowed for safer applications. American surgeon J. Marion Sims (1813–83) received credit for helping found Gynecology, but later was criticized for failing to use anesthesia on African test subjects.

Antiseptic surgery

The introduction of anesthetics encouraged more surgery, which inadvertently caused more dangerous patient post-operative infections. The concept of infection was unknown until relatively modern times. The first progress in combating infection was made in 1847 by the Hungarian doctor Ignaz Semmelweis who noticed that medical students fresh from the dissecting room were causing excess maternal death compared to midwives. Semmelweis, despite ridicule and opposition, introduced compulsory hand washing for everyone entering the maternal wards and was rewarded with a plunge in maternal and fetal deaths, however the Royal Society dismissed his advice. 

Until the pioneering work of British surgeon Joseph Lister in the 1860s, most medical men believed that chemical damage from exposures to bad air was responsible for infections in wounds, and facilities for washing hands or a patient's wounds were not available. Lister became aware of the work of French chemist Louis Pasteur, who showed that rotting and fermentation could occur under anaerobic conditions if micro-organisms were present. Pasteur suggested three methods to eliminate the micro-organisms responsible for gangrene: filtration, exposure to heat, or exposure to chemical solutions. Lister confirmed Pasteur's conclusions with his own experiments and decided to use his findings to develop antiseptic techniques for wounds. As the first two methods suggested by Pasteur were inappropriate for the treatment of human tissue, Lister experimented with the third, spraying carbolic acid on his instruments. He found that this remarkably reduced the incidence of gangrene and he published his results in The Lancet. Later, on 9 August 1867, he read a paper before the British Medical Association in Dublin, on the Antiseptic Principle of the Practice of Surgery, which was reprinted in The British Medical Journal. His work was groundbreaking and laid the foundations for a rapid advance in infection control that saw modern antiseptic operating theaters widely used within 50 years. 

Lister continued to develop improved methods of antisepsis and asepsis when he realized that infection could be better avoided by preventing bacteria from getting into wounds in the first place. This led to the rise of sterile surgery. Lister instructed surgeons under his responsibility to wear clean gloves and wash their hands in 5% carbolic solution before and after operations, and had surgical instruments washed in the same solution. He also introduced the steam sterilizer to sterilize equipment. His discoveries paved the way for a dramatic expansion to the capabilities of the surgeon; for his contributions he is often regarded as the father of modern surgery. These three crucial advances - the adoption of a scientific methodology toward surgical operations, the use of anaesthetic and the introduction of sterilized equipment - laid the groundwork for the modern invasive surgical techniques of today. 

In the late 19th century William Stewart Halstead (1852–1922) laid out basic surgical principles for asepsis known as Halsteads principles. Halsted also introduced the latex medical glove. After one of his nurses suffered skin damage due to having to sterilize her hands with carbolic acid, Halsted had a rubber glove that could be dipped in carbolic acid designed.

X-rays

Wilhelm Roentgen (1845–1925)
 
The use of X-rays as an important medical diagnostic tool began with their discovery in 1895 by German physicist Wilhelm Röntgen. He noticed that these rays could penetrate the skin, allowing the skeletal structure to be captured on a specially treated photographic plate.

Modern technologies

In the past century, a number of technologies have had a significant impact on surgical practice. These include Electrosurgery in the early 20th century, practical Endoscopy beginning in the 1960s, and Laser surgery, Computer-assisted surgery and Robotic surgery, developed in the 1980s.

The Rise Of The Silicon Brain



Depositphotos enhanced by CogWorld

Introduction

The rise of the silicon brain that can give rise to thought, emotion and behavior in a machine seems to be on the way. This is mainly due to rapid advances in software and hardware that are paving the way for next generation computational systems with cognitive abilities modeled after the human brain. This will prove to be a significant evolutionary development and especially important to enhancing machine intelligence for the complex problems that need to be solved for the future of humanity. So, as we envision a rapidly evolving silicon brain taking in the data from its surroundings in cyberspace, geospace, space (CGS) and run the data through some known/unknown computing processes and then tell the computer/machine to act, feel or behave in a certain way seems to bring humanity a lot more questions than answers. This is mainly because it is not known how the information on the silicon brain will be processed, stored or recalled; how the computer commands will emerge and become effective, and even how the silicon brain will experience the sensory world around it in CGS, and how it will think, feel or empathize.

As we evaluate all these emerging questions surrounding the rise of the silicon brain, there is an intense effort already going on to create neuromorphic chips that can mimic the human brain. There is also an initiative emerging to create a neuromorphic chip based on an octopus brain. While the emerging neuromorphic chips are still nowhere near as capable as a human brain or octopus brain, much is expected to change for machine intelligence very rapidly in the coming years, as these chips begin learning to process available sensory data from CGS to evolve their abilities in real time for the goals defined for them.

Need for Increased Computing Power

As we rapidly move towards neuromorphic computing, it is important to understand why there is a need to move away from traditional chips and towards neuromorphic chips. One of the main reasons is we are simply running out of computing capacity as existing and emerging technologies are accelerating global computing power consumption. Now, as technologies like artificial intelligence, machine learning blockchain and the internet of things begin to require significant computing power, there is a need to not only process computation more efficiently, but also evolve both hardware and software. Neuromorphic computing may solve this ongoing problem of computing power by doing all the functioning in the chip rather than sending messages back and forth with the larger server/cloud and by being event driven and only operating when it needs to, thereby imitating the brain. As a result, the rise of neuromorphic chips and computing seems to bring much-needed energy efficiency for low energy requirements, high performance speeds, greater resilience, the capability to learn from its CGS environment, and the much-needed increase in computing power. That brings us to an important question: what will be the impact of the increased computing power on the nation’s economy?

Neuromorphic Computing Chips: Future of Artificial Intelligence and Blockchain

Neuromorphic computing chips may be the future of not only artificial intelligence but also of blockchain, as they give us an ability to develop low energy consuming cryptocurrency as well as distributed systems. In addition, it further allows the integration of individuals and entities across nations: its government, industries, organizations and academia (NGIOA) by potentially creating new modes of connectivity, efficiency, collaboration, learning and problem solving in real time. That brings us to an important question: how will neuromorphic chips change the way new ideas, innovations and initiatives are developed across nations?

As seen over the years, there have been formidable advances in computing and software. However, the developments have so far only been dedicated to software and not on hardware. Neuromorphic computing and chips bring the much-needed evolution in computer hardware, allowing us to enhance machine intelligence for the complex problems that need to be solved for the future of humanity. With the evolving computing power, nations need to individually and collectively begin to evaluate where to apply the power of computing chips first. Perhaps it is time to apply the power of neuromorphic chips and make the national digital infrastructure resilient to the destructive power of electromagnetic spectrum/electronic warfare.

Emerging Systems on a Chip

Much like humans, the emerging neuromorphic chips enabling intelligent machines that will be able to understand and interact with the human ecosystem in cyberspace, geospace and space (CGS) seems to be a fundamentally disruptive innovation. We have seen many advances already, from the emerging SpiNNaker system and many other systems. We also have many interesting applied research initiatives emerging from across nations, such as information processing in the human/octopus silicon brain to green cryptocurrency initiatives and more. Each of these initiatives is using their own neuromorphic computing architecture and approach.

It is a known fact that the human brain is incredibly complex, with a network of 100 billion neurons that function individually in an environment that is not fully understood by humans yet. The same can be said for the octopus brain.

To regulate human bodily functions and respond to external stimuli, the human brain neurons work with electrical and biochemical networks and environments. Moreover, while what is consciousness is still debated and not agreed upon and not fully understood yet, it seems the neurons play an important role in human/machine consciousness. Now, it is believed that much of what the human brain does is built into the wiring, which are the neurons. So, the question is what do we know about what controls the neurons?

While over the years, much about the human brain genome has been decoded; understanding of the human brain remains complex with many unknowns. This is especially important from the perspective that nearly 90 percent of the human brain is composed of glial cells, and not neurons, and the glial cells are just coming to be understood. So, the question is, are glial cells controlling neurons? If so, how will we create silicon glial cells that will be perhaps necessary not only to clean up molecular trash created by neurons, but also to play a role in learning and memory, to help repair damaged silicon brain areas and to perhaps control neurons and neural pathways by providing the necessary biochemical environment. Now it is also believed that glial cells can communicate with neurons and with each other through what is commonly known as gap junctions across large areas of the human brain. How important are gap junctions and would they play a role in a silicon brain? And, when almost every disease of the human brain is partly or solely the result of glial malfunction, should we also not focus on mimicking glial cells replication on neuromorphic chips to prevent future machine malfunctions? If not, how are we creating a silicon brain without some sort of silicon glial cells? What will be the impact if we do and if we don't?

Acknowledging this emerging reality, Risk Group initiated the much-needed discussion on The Future of Systems on a Chip with Prof. Stephen Furber on Risk Roundup.

What's Next

The lines are seemingly blurring between a human/octopus brain and a silicon brain. So, as we dream and work towards building/creating a silicon brain that thinks like a human brain or octopus brain, is intelligent and has the potential to build entire systems on a chip, it is important to evaluate the promise and perils of our pursuit for human/octopus like intelligence in computers or machines.

While the silicon brain is aiming to improve intelligent machines to be able to handle complex systems tasks efficiently, the ultimate goal is to understand how the physical processes in neuromorphic chips turn into behaviors and perception of the human world!


 
About the Author

Jayshree Pandya (née Bhatt), Founder and CEO of Risk Group LLC, is a scientist, a visionary, an expert in disruptive technologies and a globally recognized thought leader and influencer. She is actively engaged in driving the global discussions on existing and emerging technologies, technology transformation and nation preparedness.

Her work focuses on the impact of existing and emerging technological innovations on nations, nation preparedness and the survival, security and sustainability of humanity. Her research in this context evaluates the evolution of intelligence in all forms, researches strategic security risks emerging from disruptive innovations, reviews the diminishing capacities of the risk management infrastructure, points out the changing role of decision makers, defines dynamic decision-making approaches with machine intelligence, integrates all components of a nation: governments, industries, organizations and academia (NGIOA) and defines strategic security risks so that nations can improve the state of risk-resilience across cyberspace, geospace and space (CGS). As nations make a move from centralization towards decentralization, the re-defining and re-designing of systems at all levels evaluated in Dr. Pandya’s comprehensive research scholarship includes artificial intelligence, machine learning, deep learning, internet of things, blockchain, cryptocurrency, quantum computing, virtual reality, synthetic biology, big data analytics, drones, nanosatellites, biotechnology, nanotechnology, gene editing and much more. Her research is much needed for the survival and security of humanity today and in the coming tomorrow.

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Equality (mathematics)

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