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Monday, May 31, 2021

Wisdom

From Wikipedia, the free encyclopedia

Wisdom Defending Youth Against Love by Meynier, c. 1810

Wisdom, sapience, or sagacity is the ability to think and act using knowledge, experience, understanding, common sense and insight. Wisdom is associated with attributes such as unbiased judgment, compassion, experiential self-knowledge, self-transcendence and non-attachment, and virtues such as ethics and benevolence.

Wisdom has been defined in many different ways, including several distinct approaches to assess the characteristics attributed to wisdom.

Definitions

Early mention of wisdom in Beowulf

The Oxford English Dictionary defines wisdom as "Capacity of judging rightly in matters relating to life and conduct; soundness of judgement in the choice of means and ends; sometimes, less strictly, sound sense, esp. in practical affairs: opp. to folly;" also "Knowledge (esp. of a high or abstruse kind); enlightenment, learning, erudition." Charles Haddon Spurgeon defined wisdom as "the right use of knowledge". Robert I. Sutton and Andrew Hargadon defined the "attitude of wisdom" as "acting with knowledge while doubting what one knows". Psycanics defines wisdom as "the ability to foresee the consequences of action" (allowing one to avoid negative consequences and produce the desired positive ones.) In social and psychological sciences, several distinct approaches to wisdom exist, with major advances made in the last two decades with respect to operationalization and measurement of wisdom as a psychological construct. Wisdom is the capacity to have foreknowledge of something, to know the consequences (both positive and negative) of all the available course of actions, and to yield or take the options with the most advantage either for present or future implication.

Mythological and philosophical perspectives

The ancient Greeks considered wisdom to be an important virtue, personified as the goddesses Metis and Athena. Metis was the first wife of Zeus, who, according to Hesiod's Theogony, had devoured her pregnant; Zeus earned the title of Mêtieta ("The Wise Counselor") after that, as Metis was the embodiment of wisdom, and he gave birth to Athena, who is said to have sprung from his head. Athena was portrayed as strong, fair, merciful, and chaste. Apollo was also considered a god of wisdom, designated as the conductor of the Muses (Musagetes), who were personifications of the sciences and of the inspired and poetic arts; According to Plato in his Cratylus, the name of Apollo could also mean "Ballon" (archer) and "Omopoulon" (unifier of poles [divine and earthly]), since this god was responsible for divine and true inspirations, thus considered an archer who was always right in healing and oracles: "he is an ever-darting archer". Apollo was considered the god who prophesied through the priestesses (Pythia) in the Temple of Apollo (Delphi), where the aphorism "know thyself" (gnōthi seauton)[a] was inscribed (part of the wisdom of the Delphic maxims). He was contrasted with Hermes, who was related to the sciences and technical wisdom, and, in the first centuries after Christ, was associated with Thoth in an Egyptian syncretism, under the name Hermes Trimegistus. Greek tradition recorded the earliest introducers of wisdom in the Seven Sages of Greece.

To Socrates and Plato, philosophy was literally the love of wisdom (philo-sophia). This permeates Plato's dialogues; in The Republic the leaders of his proposed utopia are philosopher kings who understand the Form of the Good and possess the courage to act accordingly. Aristotle, in Metaphysics, defined wisdom as understanding why things are a certain way (causality), which is deeper than merely knowing things are a certain way. He was the first to make the distinction between phronesis and sophia.

According to Plato and Xenophon, the Pythia of the Delphic Oracle answered the question "who is the wisest man in Greece?" by stating Socrates was the wisest. According to Plato's Apology, Socrates decided to investigate the people who might be considered wiser than him, concluding they lacked true knowledge:

[…] οὗτος μὲν οἴεταί τι εἰδέναι οὐκ εἰδώς, ἐγὼ δέ, ὥσπερ οὖν οὐκ οἶδα, οὐδὲ οἴομαι [I am wiser than this man; for neither of us really knows anything fine and good, but this man thinks he knows something when he does not, whereas I, as I do not know anything, do not think I do either.]

— Apology to Socrates 21d

Thus it became popularly immortalized in the phrase "I know that I know nothing" that it is wise to recognize one's own ignorance and to value epistemic humility.

The ancient Romans also valued wisdom which was personified in Minerva, or Pallas. She also represents skillful knowledge and the virtues, especially chastity. Her symbol was the owl which is still a popular representation of wisdom, because it can see in darkness. She was said to be born from Jupiter's forehead.

Wisdom is also important within Christianity. Jesus emphasized it. Paul the Apostle, in his first epistle to the Corinthians, argued that there is both secular and divine wisdom, urging Christians to pursue the latter. Prudence, which is intimately related to wisdom, became one of the four cardinal virtues of Catholicism. The Christian philosopher Thomas Aquinas considered wisdom to be the "father" (i.e. the cause, measure, and form) of all virtues.

In Buddhist traditions, developing wisdom plays a central role where comprehensive guidance on how to develop wisdom is provided. In the Inuit tradition, developing wisdom was one of the aims of teaching. An Inuit Elder said that a person became wise when they could see what needed to be done and did it successfully without being told what to do.

In many cultures, the name for third molars, which are the last teeth to grow, is etymologically linked with wisdom, e.g., as in the English wisdom tooth. It has its nickname originated from the classical tradition, which in the Hippocratic writings has already been called sóphronistér (in Greek, related to the meaning of moderation or teaching a lesson), and in Latin dens sapientiae (wisdom tooth), since they appear at the age of maturity in late adolescence and early adulthood.

Educational perspectives

Truth and Wisdom assist History in writing by Jacob de Wit, 1754

Public schools in the US have an approach to character education. Eighteenth century thinkers such as Benjamin Franklin, referred to this as training wisdom and virtue. Traditionally, schools share the responsibility to build character and wisdom along with parents and the community.

Nicholas Maxwell, a contemporary philosopher in the United Kingdom, advocates that academia ought to alter its focus from the acquisition of knowledge to seeking and promoting wisdom. This he defines as the capacity to realize what is of value in life, for oneself and others. He teaches that new knowledge and technological know-how increase our power to act. Without wisdom though, Maxwell claims this new knowledge may cause human harm as well as human good.

Psychological perspectives

Psychologists have begun to gather data on commonly held beliefs or folk theories about wisdom. Initial analyses indicate that although "there is an overlap of the implicit theory of wisdom with intelligence, perceptiveness, spirituality and shrewdness, it is evident that wisdom is an expertise in dealing with difficult questions of life and adaptation to the complex requirements."

Such implicit theories stand in contrast to the explicit theories and empirical research on resulting psychological processes underlying wisdom. Opinions on the exact psychological definitions of wisdom vary, but there is some consensus that critical to wisdom are certain meta-cognitive processes affording life reflection and judgment about critical life matters. These processes include recognizing the limits of one's own knowledge, acknowledging uncertainty and change, attention to context and the bigger picture, and integrating different perspectives of a situation. Cognitive scientists suggest that wisdom requires coordinating such reasoning processes, as they may provide insightful solutions for managing one's life. Notably, such reasoning is both theoretically and empirically distinct from general intelligence. Robert Sternberg has suggested that wisdom is not to be confused with general (fluid or crystallized) intelligence. In line with this idea, researchers have shown empirically that wise reasoning is distinct from IQ. Several more nuanced characterizations of wisdom are listed below.

Baltes and colleagues in Wisdom: its structure and function in regulating lifespan successful development defined wisdom as "the ability to deal with the contradictions of a specific situation and to assess the consequences of an action for themselves and for others. It is achieved when in a concrete situation, a balance between intrapersonal, inter- personal and institutional interests can be prepared". Balance itself appears to be a critical criterion of wisdom. Empirical research started to provide support to this idea, showing that wisdom-related reasoning is associated with achieving balance between intrapersonal and interpersonal interests when facing personal life challenges, and when setting goals for managing interpersonal conflicts.

Researchers in the field of positive psychology have defined wisdom as the coordination of "knowledge and experience" and "its deliberate use to improve well being." Under this definition, wisdom is further defined with the following facets:

  • Problem Solving with self-knowledge and sustainable actions.
  • Contextual sincerity to the circumstances with knowledge of its negative (or constraints) and positive aspects.
  • Value based consistent actions with knowledge of diversity in ethical opinions.
  • Tolerance towards uncertainty in life with unconditional acceptance.
  • Empathy with oneself to understand one's own emotions (or to be emotionally oriented), morals...etc. and others feelings including the ability to see oneself as part of a larger whole.

This theoretical model has not been tested empirically, with an exception of a broad link between wisdom-related reasoning and well-being.

Grossmann and colleagues have synthesized prior psychological literature, indicating that in the face of ill-defined life situations wisdom involves certain cognitive processes affording unbiased, sound judgment: (i) intellectual humility or recognition of limits of own knowledge; (ii) appreciation of perspectives broader than the issue at hand; (iii) sensitivity to the possibility of change in social relations; and (iv) compromise or integration of different perspectives. Grossmann found that habitual speaking and thinking of oneself in the third person increases these characteristics, which means that such a habit makes a person wiser. Importantly, Grossmann highlights the fundamental role of contextual factors, including the role of culture, experiences, and social situations for understanding, development, and propensity of showing wisdom, with implications for training and educational practice. This situated account of wisdom ushered a novel phase of wisdom scholarship, using rigorous evidence-based methods to understand contextual factors affording sound judgment. For instance, Grossmann and Kross have identified a phenomenon they called "the Solomon's paradox" - wiser reflections on other people's problems as compared to one's own. It is named after King Solomon, the third leader of the Jewish Kingdom, who has shown a great deal of wisdom when making judgments about other people's dilemmas but lacked insight when it came to important decisions in his own life.

Empirical scientists have also begun to focus on the role of emotions in wisdom. Most researchers would agree that emotions and emotion regulation would be key to effectively managing the kinds of complex and arousing situations that would most call for wisdom. However, much empirical research has focused on the cognitive or meta-cognitive aspects of wisdom, assuming that an ability to reason through difficult situations would be paramount. Thus, although emotions would likely play a role in determining how wisdom plays out in real events and on reflecting on past events, only recently has empirical evidence started to provide robust evidence on how and when different emotions improve or harm a person's ability to deal wisely with complex events. One notable finding concerns the positive relationship between diversity of emotional experience and wise reasoning, irrespective of emotional intensity.

Measuring wisdom

Measurement of wisdom often depends on researcher's theoretical position about the nature of wisdom. A major distinction here concerning either viewing wisdom as a stable personality trait or rather as a context-bound process The former approach often capitalizes on single-shot questionnaires. However, recent studies indicated that such single-shot questionnaires produce biased responses, which is antithetical to the wisdom construct and neglects the notion that wisdom is best understood in the contexts when it is most relevant, namely in complex life challenges. In contrast, the latter approach advocates for measuring wisdom-related features of cognition, motivation, and emotion on the level of a specific situation. Use of such state-level measures provides less biased responses as well as greater power in explaining meaningful psychological processes. Furthermore, a focus on the level of the situation has allowed wisdom researchers to develop a fuller understanding of the role of context itself for producing wisdom. Specifically, studies showed evidence of cross-cultural and within-cultural variability and systematic variability in reasoning wisely across contexts and in daily life.

Many, but not all, studies find that adults' self-ratings of perspective and wisdom do not depend on age. This belief stands in contrast to the popular notion that wisdom increases with age. The answer to the question of age-wisdom association depends on how one defines wisdom, and the methodological framework used to evaluate theoretical claims. Most recent work suggests that the answer to this question also depends on the degree of experience in a specific domain, with some contexts favoring older adults, others favoring younger adults, and some not differentiating age groups. Notably, rigorous longitudinal work is necessary to fully unpack the question of age-wisdom relationship and such work is still outstanding, with most studies relying on cross-sectional observations.

Sapience

Sapience is closely related to the term "sophia" often defined as "transcendent wisdom", "ultimate reality", or the ultimate truth of things. Sapiential perspective of wisdom is said to lie in the heart of every religion, where it is often acquired through intuitive knowing. This type of wisdom is described as going beyond mere practical wisdom and includes self-knowledge, interconnectedness, conditioned origination of mind-states and other deeper understandings of subjective experience. This type of wisdom can also lead to the ability of an individual to act with appropriate judgement, a broad understanding of situations and greater appreciation/compassion towards other living beings.

The word sapience is derived from the Latin sapientia, meaning "wisdom". The corresponding verb sapere has the original meaning of "to taste", hence "to perceive, to discern" and "to know"; its present participle sapiens was chosen by Carl Linnaeus for the Latin binomial for the human species, Homo sapiens.

Religious perspectives

Ancient Near East

In Mesopotamian religion and mythology, Enki, also known as Ea, was the God of wisdom and intelligence. Divine Wisdom allowed the provident designation of functions and the ordering of the cosmos, and it was achieved by humans in following me-s (in Sumerian, order, rite, righteousness), restoring the balance. In addition to hymns to Enki or Ea dating from the third millennium BC., there is amongst the clay tablets of Abu Salabikh from 2600 BC, considered as being the oldest dated texts, an "Hymn to Shamash", in which it is recorded written:

Wide is the courtyard of Shamash night chamber, (just as wide is the womb of) a wise pregnant woman! Sin, his warrior, wise one, heard of the offerings and came down to his fiesta. He is the father of the nation and the father of intelligence

The concept of Logos or manifest word of the divine thought, a concept also present in the philosophy and hymns of Egypt and Ancient Greece (being central to the thinker Heraclitus), and substantial in the Abrahamic traditions, seems to have been derived from Mesopotamian culture.

Sia represents the personification of perception and thoughtfulness in the traditional mythology adhered to in Ancient Egypt. Thoth, married to Maat (in ancient Egyptian, meaning order, righteousness, truth), was also important and regarded as a national introducer of wisdom.

Zoroastrianism

In the Avesta hymns traditionally attributed to Zoroaster, the Gathas, Ahura Mazda means "Lord" (Ahura) and "Wisdom" (Mazda), and it is the central deity who embodies goodness, being also called "Good Thought" (Vohu Manah). In Zoroastrianism in general, the order of the universe and morals is called Asha (in Avestan, truth, righteousness), which is determined by the designations of this omniscient Thought and also considered a deity emanating from Ahura (Amesha Spenta); it is related to another ahura deity, Spenta Mainyu (active Mentality). It says in Yazna 31:

To him shall the best befall, who, as one that knows, speaks to me Right's truthful word of Welfare and of Immortality; even the Dominion of Mazda which Good Thought shall increase for him. About which he in the beginning thus thought, "let the blessed realms be filled with Light", he it is that by his wisdom created Right.

Hebrew Bible and Judaism

The word wisdom (חכם) is mentioned 222 times in the Hebrew Bible. It was regarded as one of the highest virtues among the Israelites along with kindness (חסד) and justice (צדק). Both the books of Proverbs and Psalms urge readers to obtain and to increase in wisdom.

In the Hebrew Bible, wisdom is represented by Solomon, who asks God for wisdom in 2 Chronicles 1:10. Much of the Book of Proverbs, which is filled with wise sayings, is attributed to Solomon. In Proverbs 9:10, the fear of the Lord is called the beginning of wisdom. In Proverbs 1:20, there is also reference to wisdom personified in female form, "Wisdom calls aloud in the streets, she raises her voice in the marketplaces." In Proverbs 8:22–31, this personified wisdom is described as being present with God before creation began and even taking part in creation itself.

The Talmud teaches that a wise person is a person who can foresee the future. Nolad is a Hebrew word for "future," but also the Hebrew word for birth, so one rabbinic interpretation of the teaching is that a wise person is one who can foresee the consequences of his/her choices (i.e. can "see the future" that he/she "gives birth" to).

Hellenistic religion and Gnosticism

Christian theology

In Christian theology, "wisdom" (From Hebrew: חכמה transliteration: chokmâh pronounced: khok-maw', Greek: Sophia, Latin: Sapientia) describes an aspect of God, or the theological concept regarding the wisdom of God.

David and Abigail, Abigail was a "wise woman" who helped David, 1860 woodcut by Julius Schnorr von Karolsfeld

There is an oppositional element in Christian thought between secular wisdom and Godly wisdom. Paul the Apostle states that worldly wisdom thinks the claims of Christ to be foolishness. However, to those who are "on the path to salvation" Christ represents the wisdom of God (1 Corinthians 1:17–31). Wisdom is considered one of the seven gifts of the Holy Spirit according to Anglican, Catholic, and Lutheran belief. 1 Corinthians 12:8–10 gives an alternate list of nine virtues, among which wisdom is one.

The book of Proverbs in the Old Testament of the Bible primarily focuses on wisdom, and was primarily written by one of the wisest kings according to Jewish history, King Solomon. Proverbs is found in the Old Testament section of the Bible and gives direction on how to handle various aspects of life; one's relationship with God, marriage, dealing with finances, work, friendships and persevering in difficult situations faced in life.

Solomon and Lady Wisdom by Julius Schnorr von Karolsfeld, 1860

According to King Solomon, wisdom is gained from God, "For the Lord gives wisdom; from His mouth come knowledge and understanding" Proverbs 2:6. And through God's wise aide, one can have a better life: "He holds success in store for the upright, he is a shield to those whose walk is blameless, for he guards the course of the just and protects the way of his faithful ones" Proverbs 2:7-8. "Trust in the LORD with all your heart and lean not on your own understanding; in all your ways submit to him, and he will make your paths straight" Proverbs 3:5-6. Solomon basically states that with the wisdom one receives from God, one will be able to find success and happiness in life.

There are various verses in Proverbs that contain parallels of what God loves, which is wise, and what God does not love, which is foolish. For example, in the area of good and bad behaviour Proverbs states, "The way of the wicked is an abomination to the Lord, But He loves him who pursues righteousness (Proverbs 15:9). In relation to fairness and business it is stated that, "A false balance is an abomination to the Lord, But a just weight is His delight" (Proverbs 11:1; cf. 20:10,23). On the truth it is said, "Lying lips are an abomination to the Lord, But those who deal faithfully are His delight" (12:22; cf. 6:17,19). These are a few examples of what, according to Solomon, are good and wise in the eyes of God, or bad and foolish, and in doing these good and wise things, one becomes closer to God by living in an honorable and kind manner.

Solomon's Wisdom, 1860 woodcut by Julius Schnorr von Karolsfeld

King Solomon continues his teachings of wisdom in the book of Ecclesiastes, which is considered one of the most depressing books of the Bible. Solomon discusses his exploration of the meaning of life and fulfillment, as he speaks of life's pleasures, work, and materialism, yet concludes that it is all meaningless. "'Meaningless! Meaningless!" says the Teacher [Solomon]. 'Utterly meaningless! Everything is meaningless'...For with much wisdom comes much sorrow, the more knowledge, the more grief" (Ecclesiastes 1:2,18) Solomon concludes that all life's pleasures and riches, and even wisdom, mean nothing if there is no relationship with God.

The book of James, written by the apostle James, is said to be the New Testament version of the book of Proverbs, in that it is another book that discusses wisdom. It reiterates Proverbs message of wisdom coming from God by stating, "If any of you lacks wisdom, you should ask God, who gives generously to all without finding fault, and it will be given to you." James 1:5. James also explains how wisdom helps one acquire other forms of virtue, "But the wisdom that comes from heaven is first of all pure; then peace-loving, considerate, submissive, full of mercy and good fruit, impartial and sincere." James 3:17. In addition, through wisdom for living James focuses on using this God-given wisdom to perform acts of service to the less fortunate.

Apart from Proverbs, Ecclesiastes, and James, other main books of wisdom in the Bible are Job, Psalms, and 1 and 2 Corinthians, which give lessons on gaining and using wisdom through difficult situations.

Indian religions

In the Indian traditions, wisdom can be called prajña or vijñana.

Developing wisdom is of central importance in Buddhist traditions, where the ultimate aim is often presented as "seeing things as they are" or as gaining a "penetrative understanding of all phenomena", which in turn is described as ultimately leading to the "complete freedom from suffering". In Buddhism, developing wisdom is accomplished through an understanding of what are known as the Four Noble Truths and by following the Noble Eightfold Path. This path lists mindfulness as one of eight required components for cultivating wisdom.

Buddhist scriptures teach that a wise person is usually endowed with good and maybe bodily conduct, and sometimes good verbal conduct, and good mental conduct.(AN 3:2) A wise person does actions that are unpleasant to do but give good results, and doesn't do actions that are pleasant to do but give bad results (AN 4:115). Wisdom is the antidote to the self-chosen poison of ignorance. The Buddha has much to say on the subject of wisdom including:

  • He who arbitrates a case by force does not thereby become just (established in Dhamma). But the wise man is he who carefully discriminates between right and wrong.
  • He who leads others by nonviolence, righteously and equitably, is indeed a guardian of justice, wise and righteous.
  • One is not wise merely because he talks much. But he who is calm, free from hatred and fear, is verily called a wise man.
  • By quietude alone one does not become a sage (muni) if he is foolish and ignorant. But he who, as if holding a pair of scales, takes the good and shuns the evil, is a wise man; he is indeed a muni by that very reason. He who understands both good and evil as they really are, is called a true sage.

To recover the original supreme wisdom of self-nature (Buddha-nature or Tathagata) covered by the self-imposed three dusty poisons (the kleshas: greed, anger, ignorance) Buddha taught to his students the threefold training by turning greed into generosity and discipline, anger into kindness and meditation, ignorance into wisdom. As the Sixth Patriarch of Chán Buddhism, Huineng, said in his Platform Sutra,"Mind without dispute is self-nature discipline, mind without disturbance is self-nature meditation, mind without ignorance is self-nature wisdom." In Mahayana and esoteric buddhist lineages, Mañjuśrī is considered as an embodiment of Buddha wisdom.

In Hinduism, wisdom is considered a state of mind and soul where a person achieves liberation.

The god of wisdom is Ganesha and the goddess of knowledge is Saraswati.

The Sanskrit verse to attain knowledge is:

असतो मा सद्गमय । Asatō mā sadgamaya
तमसो मा ज्योतिर्गमय । tamasō mā jyōtirgamaya
मृत्योर्मा अमृतं गमय । mr̥tyōrmā amr̥taṁ gamaya
ॐ शान्तिः शान्तिः शान्तिः ॥ Om śāntiḥ śāntiḥ śāntiḥ
- Br̥hadāraṇyakopaniṣat 1.3.28

"Lead me from the unreal to the real.
Lead me from darkness to light.
Lead me from death to immortality.
May there be peace, peace, and peace".
Brihadaranyaka Upanishad 1.3.28.

Wisdom in Hinduism is knowing oneself as the truth, basis for the entire Creation, i.e., of Shristi. In other words, wisdom simply means a person with Self-awareness as the one who witnesses the entire creation in all its facets and forms. Further it means realization that an individual through right conduct and right living over an unspecified period comes to realize their true relationship with the creation and the Paramatma.

Islam

The Arabic term corresponding to Hebrew Chokmah is حكمة ḥikma. The term occurs a number of times in the Quran, notably in Sura 2:269: "He gives wisdom to whom He wills, and whoever has been given wisdom has certainly been given much good. And none will remember except those of understanding." (Quran 2:269). and Sura 22:46: "Have they not travelled in the land, and have they hearts wherewith to feel and ears wherewith to hear? For indeed it is not the eyes that grow blind, but it is the hearts, which are within the bosoms, that grow blind."Quran 22:46 Sura 6: 151: "Say: "Come, I will rehearse what Allah (God) hath (really) prohibited you from": Join not anything as equal with Him; be good to your parents; kill not your children on a plea of want;― We provide sustenance for you and for them;― come not nigh to shameful deeds, whether open or secret; take not life, which Allah hath made sacred, except by way of justice and law: thus doth He command you, that ye may learn wisdom" (Quran 6:151).

The Sufi philosopher Ibn Arabi considers al-Hakim ("The Wise") as one of the names of the Creator. Wisdom and truth, considered divine attributes, were concepts related and valued in the Islamic sciences and philosophy since their beginnings, and the first Arab philosopher, Al-Kindi says at the beginning of his book:

We must not be ashamed to admire the truth or to acquire it, from wherever it comes. Even if it should come from far-flung nations and foreign peoples, there is for the student of truth nothing more important than the truth, nor is the truth demeaned or diminished by the one who states or conveys it; no one is demeaned by the truth, rather all are ennobled by it.

— Al-Kindi, On First Philosophy

Chinese religion

The Buddhist term Prajñā was translated into Chinese as 智慧 (pinyin zhìhuì, characters "knowledge" and "bright, intelligent").

According to the Doctrine of the Mean, Confucius said:

"Love of learning is akin to wisdom. To practice with vigor is akin to humanity. To know to be shameful is akin to courage (zhi, ren, yong.. three of Mengzi's sprouts of virtue)."

Compare this with the Confucian classic Great Learning, which begins with: "The Way of learning to be great consists in manifesting the clear character, loving the people, and abiding in the highest good." One can clearly see the correlation with the Roman virtue prudence, especially if one interprets "clear character" as "clear conscience". (From Chan's Sources of Chinese Philosophy).

In Taoism, wisdom is construed as adherence to the Three Treasures (Taoism): charity, simplicity, and humility. "He who knows other men is discerning [智]; he who knows himself is intelligent [明]." (知人者智,自知者明。Tao Te Ching 33)

Others

In Norse mythology, the god Odin is especially known for his wisdom, often acquired through various hardships and ordeals involving pain and self-sacrifice. In one instance he plucked out an eye and offered it to Mímir, guardian of the well of knowledge and wisdom, in return for a drink from the well. In another famous account, Odin hanged himself for nine nights from Yggdrasil, the World Tree that unites all the realms of existence, suffering from hunger and thirst and finally wounding himself with a spear until he gained the knowledge of runes for use in casting powerful magic. He was also able to acquire the mead of poetry from the giants, a drink of which could grant the power of a scholar or poet, for the benefit of gods and mortals alike.

In Baháʼí Faith scripture, "The essence of wisdom is the fear of God, the dread of His scourge and punishment, and the apprehension of His justice and decree." Wisdom is seen as a light, that casts away darkness, and "its dictates must be observed under all circumstances". One may obtain knowledge and wisdom through God, his Word, and his Divine Manifestation and the source of all learning is the knowledge of God.

In the Star Wars universe, wisdom is valued in the narrative of the films, in which George Lucas figured issues of spirituality and morals, recurrent in mythological and philosophical themes; one of his inspirations was Joseph Campbell's The Hero of a Thousand Faces. Master Yoda is generally considered a popular figure of wisdom, evoking the image of an "Oriental Monk", and he is frequently quoted, analogously to Chinese thinkers or Eastern sages in general. Psychologist D. W. Kreger's book "The Tao of Yoda" adapts the wisdom of the Tao Te Ching in relation to Yoda's thinking. Knowledge is canonically considered one of the pillars of the Jedi, which is also cited in the non-canon book The Jedi Path, and wisdom can serve as a tenet for Jediism. The Jedi Code also states: "Ignorance, yet knowledge." In a psychology populational study published by Grossmann and team in 2019, master Yoda is considered wiser than Spock, another fictional character (from the Star Trek series), due to his emodiversity trait, which was positively associated to wise reasoning in people: "Yoda embraces his emotions and aims to achieve a balance between them. Yoda is known to be emotionally expressive, to share a good joke with others, but also to recognize sorrow and his past mistakes".

Wisdom is learning how to understand, who to be and how to live.

Sunday, May 30, 2021

Computer-aided design

From Wikipedia, the free encyclopedia

Example: 2D CAD drawing
 
Example: 3D CAD model

Computer-aided design (CAD) is the use of computers (or workstations) to aid in the creation, modification, analysis, or optimization of a design. CAD software is used to increase the productivity of the designer, improve the quality of design, improve communications through documentation, and to create a database for manufacturing. Designs made through CAD software are helpful in protecting products and inventions when used in patent applications. CAD output is often in the form of electronic files for print, machining, or other manufacturing operations. The term CADD (for computer aided design and drafting) is also used.

Its use in designing electronic systems is known as electronic design automation (EDA). In mechanical design it is known as mechanical design automation (MDA) or computer-aided drafting (CAD), which includes the process of creating a technical drawing with the use of computer software.

CAD software for mechanical design uses either vector-based graphics to depict the objects of traditional drafting, or may also produce raster graphics showing the overall appearance of designed objects. However, it involves more than just shapes. As in the manual drafting of technical and engineering drawings, the output of CAD must convey information, such as materials, processes, dimensions, and tolerances, according to application-specific conventions.

CAD may be used to design curves and figures in two-dimensional (2D) space; or curves, surfaces, and solids in three-dimensional (3D) space.

CAD is an important industrial art extensively used in many applications, including automotive, shipbuilding, and aerospace industries, industrial and architectural design, prosthetics, and many more. CAD is also widely used to produce computer animation for special effects in movies, advertising and technical manuals, often called DCC digital content creation. The modern ubiquity and power of computers means that even perfume bottles and shampoo dispensers are designed using techniques unheard of by engineers of the 1960s. Because of its enormous economic importance, CAD has been a major driving force for research in computational geometry, computer graphics (both hardware and software), and discrete differential geometry.

The design of geometric models for object shapes, in particular, is occasionally called computer-aided geometric design (CAGD).

Overview of CAD software

Starting around the mid-1960s, with the IBM Drafting System, computer-aided design systems began to provide more capability than just an ability to reproduce manual drafting with electronic drafting, the cost-benefit for companies to switch to CAD became apparent. The benefits of CAD systems over manual drafting are the capabilities one often takes for granted from computer systems today; automated generation of bills of materials, auto layout in integrated circuits, interference checking, and many others. Eventually, CAD provided the designer with the ability to perform engineering calculations. During this transition, calculations were still performed either by hand or by those individuals who could run computer programs. CAD was a revolutionary change in the engineering industry, where draftsmen, designers, and engineering roles begin to merge. It did not eliminate departments as much as it merged departments and empowered draftsmen, designers, and engineers. CAD is an example of the pervasive effect computers were beginning to have on the industry. Current computer-aided design software packages range from 2D vector-based drafting systems to 3D solid and surface modelers. Modern CAD packages can also frequently allow rotations in three dimensions, allowing viewing of a designed object from any desired angle, even from the inside looking out. Some CAD software is capable of dynamic mathematical modeling.

CAD technology is used in the design of tools and machinery and in the drafting and design of all types of buildings, from small residential types (houses) to the largest commercial and industrial structures (hospitals and factories).

CAD is mainly used for detailed engineering of 3D models or 2D drawings of physical components, but it is also used throughout the engineering process from conceptual design and layout of products, through strength and dynamic analysis of assemblies to definition of manufacturing methods of components. It can also be used to design objects such as jewelry, furniture, appliances, etc. Furthermore, many CAD applications now offer advanced rendering and animation capabilities so engineers can better visualize their product designs. 4D BIM is a type of virtual construction engineering simulation incorporating time or schedule-related information for project management.

CAD has become an especially important technology within the scope of computer-aided technologies, with benefits such as lower product development costs and a greatly shortened design cycle. CAD enables designers to layout and develop work on screen, print it out and save it for future editing, saving time on their drawings.

Uses

Computer-aided design is one of the many tools used by engineers and designers and is used in many ways depending on the profession of the user and the type of software in question.

CAD is one part of the whole digital product development (DPD) activity within the product lifecycle management (PLM) processes, and as such is used together with other tools, which are either integrated modules or stand-alone products, such as:

CAD is also used for the accurate creation of photo simulations that are often required in the preparation of environmental impact reports, in which computer-aided designs of intended buildings are superimposed into photographs of existing environments to represent what that locale will be like, where the proposed facilities are allowed to be built. Potential blockage of view corridors and shadow studies are also frequently analyzed through the use of CAD.

CAD has been proven to be useful to engineers as well. Using four properties which are history, features, parameterization, and high-level constraints. The construction history can be used to look back into the model's personal features and work on the single area rather than the whole model. Parameters and constraints can be used to determine the size, shape, and other properties of the different modeling elements. The features in the CAD system can be used for the variety of tools for measurement such as tensile strength, yield strength, electrical, or electromagnetic properties. Also its stress, strain, timing, or how the element gets affected in certain temperatures, etc.

Types

A simple procedure of recreating a solid model out of 2D sketches.

There are several different types of CAD, each requiring the operator to think differently about how to use them and design their virtual components in a different manner for each.

There are many producers of the lower-end 2D systems, including a number of free and open-source programs. These provide an approach to the drawing process without all the fuss over scale and placement on the drawing sheet that accompanied hand drafting since these can be adjusted as required during the creation of the final draft.

3D wireframe is basically an extension of 2D drafting (not often used today). Each line has to be manually inserted into the drawing. The final product has no mass properties associated with it and cannot have features directly added to it, such as holes. The operator approaches these in a similar fashion to the 2D systems, although many 3D systems allow using the wireframe model to make the final engineering drawing views.

3D "dumb" solids are created in a way analogous to manipulations of real-world objects (not often used today). Basic three-dimensional geometric forms (prisms, cylinders, spheres, and so on) have solid volumes added or subtracted from them as if assembling or cutting real-world objects. Two-dimensional projected views can easily be generated from the models. Basic 3D solids don't usually include tools to easily allow motion of components, set limits to their motion, or identify interference between components.

There are two types of 3D solid modeling

  • Parametric modeling allows the operator to use what is referred to as "design intent". The objects and features created are modifiable. Any future modifications can be made by changing how the original part was created. If a feature was intended to be located from the center of the part, the operator should locate it from the center of the model. The feature could be located using any geometric object already available in the part, but this random placement would defeat the design intent. If the operator designs the part as it functions the parametric modeler is able to make changes to the part while maintaining geometric and functional relationships.
  • Direct or explicit modeling provide the ability to edit geometry without a history tree. With direct modeling, once a sketch is used to create geometry the sketch is incorporated into the new geometry and the designer just modifies the geometry without needing the original sketch. As with parametric modeling, direct modeling has the ability to include relationships between selected geometry (e.g., tangency, concentricity).

Top-end systems offer the capabilities to incorporate more organic, aesthetic, and ergonomic features into designs. Freeform surface modeling is often combined with solids to allow the designer to create products that fit the human form and visual requirements as well as they interface with the machine.

Technology

A CAD model of a computer mouse

Originally software for CAD systems was developed with computer languages such as Fortran, ALGOL but with the advancement of object-oriented programming methods this has radically changed. Typical modern parametric feature-based modeler and freeform surface systems are built around a number of key C modules with their own APIs. A CAD system can be seen as built up from the interaction of a graphical user interface (GUI) with NURBS geometry or boundary representation (B-rep) data via a geometric modeling kernel. A geometry constraint engine may also be employed to manage the associative relationships between geometry, such as wireframe geometry in a sketch or components in an assembly.

Unexpected capabilities of these associative relationships have led to a new form of prototyping called digital prototyping. In contrast to physical prototypes, which entail manufacturing time in the design. That said, CAD models can be generated by a computer after the physical prototype has been scanned using an industrial CT scanning machine. Depending on the nature of the business, digital or physical prototypes can be initially chosen according to specific needs.

Today, CAD systems exist for all the major platforms (Windows, Linux, UNIX and Mac OS X); some packages support multiple platforms.

Currently, no special hardware is required for most CAD software. However, some CAD systems can do graphically and computationally intensive tasks, so a modern graphics card, high speed (and possibly multiple) CPUs and large amounts of RAM may be recommended.

The human-machine interface is generally via a computer mouse but can also be via a pen and digitizing graphics tablet. Manipulation of the view of the model on the screen is also sometimes done with the use of a Spacemouse/SpaceBall. Some systems also support stereoscopic glasses for viewing the 3D model. Technologies which in the past were limited to larger installations or specialist applications have become available to a wide group of users. These include the CAVE or HMDs and interactive devices like motion-sensing technology

Software

CAD software enables engineers and architects to design, inspect and manage engineering projects within an integrated graphical user interface (GUI) on a personal computer system. Most applications support solid modeling with boundary representation (B-Rep) and NURBS geometry, and enable the same to be published in a variety of formats. A geometric modeling kernel is a software component that provides solid modeling and surface modeling features to CAD applications.

Based on market statistics, commercial software from Autodesk, Dassault Systems, Siemens PLM Software, and PTC dominate the CAD industry. The following is a list of major CAD applications, grouped by usage statistics.

Synthetic biology

Synthetic Biology Research at NASA Ames Research Center.

Synthetic biology (SynBio) is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.

It is a branch of science that encompasses a broad range of methodologies from various disciplines, such as biotechnology, genetic engineering, molecular biology, molecular engineering, systems biology, membrane science, biophysics, chemical and biological engineering, electrical and computer engineering, control engineering and evolutionary biology.

Due to more powerful genetic engineering capabilities and decreased DNA synthesis and sequencing costs, the field of synthetic biology is rapidly growing. In 2016, more than 350 companies across 40 countries were actively engaged in synthetic biology applications; all these companies had an estimated net worth of $3.9 billion in the global market.

Definition

Synthetic biology currently has no generally accepted definition. Here are a few examples:

  • "the use of a mixture of physical engineering and genetic engineering to create new (and, therefore, synthetic) life forms"
  • "an emerging field of research that aims to combine the knowledge and methods of biology, engineering and related disciplines in the design of chemically synthesized DNA to create organisms with novel or enhanced characteristics and traits"
  • "designing and constructing biological modules, biological systems, and biological machines or, re-design of existing biological systems for useful purposes"
  • “applying the engineering paradigm of systems design to biological systems in order to produce predictable and robust systems with novel functionalities that do not exist in nature” (The European Commission, 2005) This can include the possibility of a molecular assembler, based upon biomolecular systems such as the ribosome

Synthetic biology has traditionally been divided into two different approaches: top down and bottom up.

  1. The top down approach involves using metabolic and genetic engineering techniques to impart new functions to living cells.
  2. The bottom up approach involves creating new biological systems in vitro by bringing together 'non-living' biomolecular components, often with the aim of constructing an artificial cell.

Biological systems are thus assembled module-by-module. Cell-free protein expression systems are often employed, as are membrane-based molecular machinery. There are increasing efforts to bridge the divide between these approaches by forming hybrid living/synthetic cells, and engineering communication between living and synthetic cell populations.

History

1910: First identifiable use of the term "synthetic biology" in Stéphane Leduc's publication Théorie physico-chimique de la vie et générations spontanées. He also noted this term in another publication, La Biologie Synthétique in 1912.

1961: Jacob and Monod postulate cellular regulation by molecular networks from their study of the lac operon in E. coli and envisioned the ability to assemble new systems from molecular components.

1973: First molecular cloning and amplification of DNA in a plasmid is published in P.N.A.S. by Cohen, Boyer et al. constituting the dawn of synthetic biology.

1978: Arber, Nathans and Smith win the Nobel Prize in Physiology or Medicine for the discovery of restriction enzymes, leading Szybalski to offer an editorial comment in the journal Gene:

The work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes, but also has led us into the new era of synthetic biology where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated.

1988: First DNA amplification by the polymerase chain reaction (PCR) using a thermostable DNA polymerase is published in Science by Mullis et al. This obviated adding new DNA polymerase after each PCR cycle, thus greatly simplifying DNA mutagenesis and assembly.

2000: Two papers in Nature report synthetic biological circuits, a genetic toggle switch and a biological clock, by combining genes within E. coli cells.

2003: The most widely used standardized DNA parts, BioBrick plasmids, are invented by Tom Knight. These parts will become central to the international Genetically Engineered Machine competition (iGEM) founded at MIT in the following year.

Synthetic Biology Open Language (SBOL) standard visual symbols for use with BioBricks Standard

2003: Researchers engineer an artemisinin precursor pathway in E. coli.

2004: First international conference for synthetic biology, Synthetic Biology 1.0 (SB1.0) is held at the Massachusetts Institute of Technology, USA.

2005: Researchers develop a light-sensing circuit in E. coli. Another group designs circuits capable of multicellular pattern formation.

2006: Researchers engineer a synthetic circuit that promotes bacterial invasion of tumour cells.

2010: Researchers publish in Science the first synthetic bacterial genome, called M. mycoides JCVI-syn1.0. The genome is made from chemically-synthesized DNA using yeast recombination.

2011: Functional synthetic chromosome arms are engineered in yeast.

2012: Charpentier and Doudna labs publish in Science the programming of CRISPR-Cas9 bacterial immunity for targeting DNA cleavage. This technology greatly simplified and expanded eukaryotic gene editing.

2019: Scientists at ETH Zurich report the creation of the first bacterial genome, named Caulobacter ethensis-2.0, made entirely by a computer, although a related viable form of C. ethensis-2.0 does not yet exist.

2019: Researchers report the production of a new synthetic (possibly artificial) form of viable life, a variant of the bacteria Escherichia coli, by reducing the natural number of 64 codons in the bacterial genome to 59 codons instead, in order to encode 20 amino acids.

Perspectives

Engineers view biology as a technology (in other words, a given system includes biotechnology or its biological engineering) Synthetic biology includes the broad redefinition and expansion of biotechnology, with the ultimate goals of being able to design and build engineered live biological systems that process information, manipulate chemicals, fabricate materials and structures, produce energy, provide food, and maintain and enhance human health, as well as advance fundamental knowledge of biological systems and our environment.

Studies in synthetic biology can be subdivided into broad classifications according to the approach they take to the problem at hand: standardization of biological parts, biomolecular engineering, genome engineering, metabolic engineering.

Biomolecular engineering includes approaches that aim to create a toolkit of functional units that can be introduced to present new technological functions in living cells. Genetic engineering includes approaches to construct synthetic chromosomes or minimal organisms like Mycoplasma laboratorium.

Biomolecular design refers to the general idea of de novo design and additive combination of biomolecular components. Each of these approaches share a similar task: to develop a more synthetic entity at a higher level of complexity by inventively manipulating a simpler part at the preceding level.

On the other hand, "re-writers" are synthetic biologists interested in testing the irreducibility of biological systems. Due to the complexity of natural biological systems, it would be simpler to rebuild the natural systems of interest from the ground up; In order to provide engineered surrogates that are easier to comprehend, control and manipulate. Re-writers draw inspiration from refactoring, a process sometimes used to improve computer software.

Enabling technologies

Several novel enabling technologies were critical to the success of synthetic biology. Concepts include standardization of biological parts and hierarchical abstraction to permit using those parts in synthetic systems. Basic technologies include reading and writing DNA (sequencing and fabrication). Measurements under multiple conditions are needed for accurate modeling and computer-aided design (CAD).

DNA and gene synthesis

Driven by dramatic decreases in costs of oligonucleotide ("oligos") synthesis and the advent of PCR, the sizes of DNA constructions from oligos have increased to the genomic level. In 2000, researchers reported synthesis of the 9.6 kbp (kilo bp) Hepatitis C virus genome from chemically synthesized 60 to 80-mers. In 2002 researchers at Stony Brook University succeeded in synthesizing the 7741 bp poliovirus genome from its published sequence, producing the second synthetic genome, spanning two years. In 2003 the 5386 bp genome of the bacteriophage Phi X 174 was assembled in about two weeks. In 2006, the same team, at the J. Craig Venter Institute, constructed and patented a synthetic genome of a novel minimal bacterium, Mycoplasma laboratorium and were working on getting it functioning in a living cell.

In 2007 it was reported that several companies were offering synthesis of genetic sequences up to 2000 base pairs (bp) long, for a price of about $1 per bp and a turnaround time of less than two weeks. Oligonucleotides harvested from a photolithographic- or inkjet-manufactured DNA chip combined with PCR and DNA mismatch error-correction allows inexpensive large-scale changes of codons in genetic systems to improve gene expression or incorporate novel amino-acids (see George M. Church's and Anthony Forster's synthetic cell projects.) This favors a synthesis-from-scratch approach.

Additionally, the CRISPR/Cas system has emerged as a promising technique for gene editing. It was described as "the most important innovation in the synthetic biology space in nearly 30 years". While other methods take months or years to edit gene sequences, CRISPR speeds that time up to weeks. Due to its ease of use and accessibility, however, it has raised ethical concerns, especially surrounding its use in biohacking.

Sequencing

DNA sequencing determines the order of nucleotide bases in a DNA molecule. Synthetic biologists use DNA sequencing in their work in several ways. First, large-scale genome sequencing efforts continue to provide information on naturally occurring organisms. This information provides a rich substrate from which synthetic biologists can construct parts and devices. Second, sequencing can verify that the fabricated system is as intended. Third, fast, cheap, and reliable sequencing can facilitate rapid detection and identification of synthetic systems and organisms.

Microfluidics

Microfluidics, in particular droplet microfluidics, is an emerging tool used to construct new components, and to analyse and characterize them. It is widely employed in screening assays.

Modularity

The most used standardized DNA parts are BioBrick plasmids, invented by Tom Knight in 2003. Biobricks are stored at the Registry of Standard Biological Parts in Cambridge, Massachusetts. The BioBrick standard has been used by thousands of students worldwide in the international Genetically Engineered Machine (iGEM) competition.

While DNA is most important for information storage, a large fraction of the cell's activities are carried out by proteins. Tools can send proteins to specific regions of the cell and to link different proteins together. The interaction strength between protein partners should be tunable between a lifetime of seconds (desirable for dynamic signaling events) up to an irreversible interaction (desirable for device stability or resilient to harsh conditions). Interactions such as coiled coils, SH3 domain-peptide binding or SpyTag/SpyCatcher offer such control. In addition it is necessary to regulate protein-protein interactions in cells, such as with light (using light-oxygen-voltage-sensing domains) or cell-permeable small molecules by chemically induced dimerization.

In a living cell, molecular motifs are embedded in a bigger network with upstream and downstream components. These components may alter the signaling capability of the modeling module. In the case of ultrasensitive modules, the sensitivity contribution of a module can differ from the sensitivity that the module sustains in isolation.

Modeling

Models inform the design of engineered biological systems by better predicting system behavior prior to fabrication. Synthetic biology benefits from better models of how biological molecules bind substrates and catalyze reactions, how DNA encodes the information needed to specify the cell and how multi-component integrated systems behave. Multiscale models of gene regulatory networks focus on synthetic biology applications. Simulations can model all biomolecular interactions in transcription, translation, regulation and induction of gene regulatory networks.

Synthetic transcription factors

Studies have considered the components of the DNA transcription mechanism. One desire of scientists creating synthetic biological circuits is to be able to control the transcription of synthetic DNA in unicellular organisms (prokaryotes) and in multicellular organisms (eukaryotes). One study tested the adjustability of synthetic transcription factors (sTFs) in areas of transcription output and cooperative ability among multiple transcription factor complexes. Researchers were able to mutate functional regions called zinc fingers, the DNA specific component of sTFs, to decrease their affinity for specific operator DNA sequence sites, and thus decrease the associated site-specific activity of the sTF (usually transcriptional regulation). They further used the zinc fingers as components of complex-forming sTFs, which are the eukaryotic translation mechanisms.

Applications

Biological computers

A biological computer refers to an engineered biological system that can perform computer-like operations, which is a dominant paradigm in synthetic biology. Researchers built and characterized a variety of logic gates in a number of organisms, and demonstrated both analog and digital computation in living cells. They demonstrated that bacteria can be engineered to perform both analog and/or digital computation. In human cells research demonstrated a universal logic evaluator that operates in mammalian cells in 2007. Subsequently, researchers utilized this paradigm to demonstrate a proof-of-concept therapy that uses biological digital computation to detect and kill human cancer cells in 2011. Another group of researchers demonstrated in 2016 that principles of computer engineering, can be used to automate digital circuit design in bacterial cells. In 2017, researchers demonstrated the 'Boolean logic and arithmetic through DNA excision' (BLADE) system to engineer digital computation in human cells.

Biosensors

A biosensor refers to an engineered organism, usually a bacterium, that is capable of reporting some ambient phenomenon such as the presence of heavy metals or toxins. One such system is the Lux operon of Aliivibrio fischeri, which codes for the enzyme that is the source of bacterial bioluminescence, and can be placed after a respondent promoter to express the luminescence genes in response to a specific environmental stimulus. One such sensor created, consisted of a bioluminescent bacterial coating on a photosensitive computer chip to detect certain petroleum pollutants. When the bacteria sense the pollutant, they luminesce. Another example of a similar mechanism is the detection of landmines by an engineered E.coli reporter strain capable of detecting TNT and its main degradation product DNT, and consequently producing a green fluorescent protein (GFP).

Modified organisms can sense environmental signals and send output signals that can be detected and serve diagnostic purposes. Microbe cohorts have been used.

Cell transformation

Cells use interacting genes and proteins, which are called gene circuits, to implement diverse function, such as responding to environmental signals, decision making and communication. Three key components are involved: DNA, RNA and Synthetic biologist designed gene circuits that can control gene expression from several levels including transcriptional, post-transcriptional and translational levels.

Traditional metabolic engineering has been bolstered by the introduction of combinations of foreign genes and optimization by directed evolution. This includes engineering E. coli and yeast for commercial production of a precursor of the antimalarial drug, Artemisinin.

Entire organisms have yet to be created from scratch, although living cells can be transformed with new DNA. Several ways allow constructing synthetic DNA components and even entire synthetic genomes, but once the desired genetic code is obtained, it is integrated into a living cell that is expected to manifest the desired new capabilities or phenotypes while growing and thriving. Cell transformation is used to create biological circuits, which can be manipulated to yield desired outputs.

By integrating synthetic biology with materials science, it would be possible to use cells as microscopic molecular foundries to produce materials with properties whose properties were genetically encoded. Re-engineering has produced Curli fibers, the amyloid component of extracellular material of biofilms, as a platform for programmable nanomaterial. These nanofibers were genetically constructed for specific functions, including adhesion to substrates, nanoparticle templating and protein immobilization.

Designed proteins

The Top7 protein was one of the first proteins designed for a fold that had never been seen before in nature

Natural proteins can be engineered, for example, by directed evolution, novel protein structures that match or improve on the functionality of existing proteins can be produced. One group generated a helix bundle that was capable of binding oxygen with similar properties as hemoglobin, yet did not bind carbon monoxide. A similar protein structure was generated to support a variety of oxidoreductase activities  while another formed a structurally and sequentially novel ATPase. Another group generated a family of G-protein coupled receptors that could be activated by the inert small molecule clozapine N-oxide but insensitive to the native ligand, acetylcholine; these receptors are known as DREADDs. Novel functionalities or protein specificity can also be engineered using computational approaches. One study was able to use two different computational methods – a bioinformatics and molecular modeling method to mine sequence databases, and a computational enzyme design method to reprogram enzyme specificity. Both methods resulted in designed enzymes with greater than 100 fold specificity for production of longer chain alcohols from sugar.

Another common investigation is expansion of the natural set of 20 amino acids. Excluding stop codons, 61 codons have been identified, but only 20 amino acids are coded generally in all organisms. Certain codons are engineered to code for alternative amino acids including: nonstandard amino acids such as O-methyl tyrosine; or exogenous amino acids such as 4-fluorophenylalanine. Typically, these projects make use of re-coded nonsense suppressor tRNA-Aminoacyl tRNA synthetase pairs from other organisms, though in most cases substantial engineering is required.

Other researchers investigated protein structure and function by reducing the normal set of 20 amino acids. Limited protein sequence libraries are made by generating proteins where groups of amino acids may be replaced by a single amino acid. For instance, several non-polar amino acids within a protein can all be replaced with a single non-polar amino acid. One project demonstrated that an engineered version of Chorismate mutase still had catalytic activity when only 9 amino acids were used.

Researchers and companies practice synthetic biology to synthesize industrial enzymes with high activity, optimal yields and effectiveness. These synthesized enzymes aim to improve products such as detergents and lactose-free dairy products, as well as make them more cost effective. The improvements of metabolic engineering by synthetic biology is an example of a biotechnological technique utilized in industry to discover pharmaceuticals and fermentive chemicals. Synthetic biology may investigate modular pathway systems in biochemical production and increase yields of metabolic production. Artificial enzymatic activity and subsequent effects on metabolic reaction rates and yields may develop "efficient new strategies for improving cellular properties ... for industrially important biochemical production".

Designed nucleic acid systems

Scientists can encode digital information onto a single strand of synthetic DNA. In 2012, George M. Church encoded one of his books about synthetic biology in DNA. The 5.3 Mb of data was more than 1000 times greater than the previous largest amount of information to be stored in synthesized DNA. A similar project encoded the complete sonnets of William Shakespeare in DNA. More generally, algorithms such as NUPACK, ViennaRNA, Ribosome Binding Site Calculator, Cello, and Non-Repetitive Parts Calculator enables the design of new genetic systems.

Many technologies have been developed for incorporating unnatural nucleotides and amino acids into nucleic acids and proteins, both in vitro and in vivo. For example, in May 2014, researchers announced that they had successfully introduced two new artificial nucleotides into bacterial DNA. By including individual artificial nucleotides in the culture media, they were able to exchange the bacteria 24 times; they did not generate mRNA or proteins able to use the artificial nucleotides.

Space exploration

Synthetic biology raised NASA's interest as it could help to produce resources for astronauts from a restricted portfolio of compounds sent from Earth. On Mars, in particular, synthetic biology could lead to production processes based on local resources, making it a powerful tool in the development of manned outposts with less dependence on Earth. Work has gone into developing plant strains that are able to cope with the harsh Martian environment, using similar techniques to those employed to increase resilience to certain environmental factors in agricultural crops.

Synthetic life

Gene functions in the minimal genome of the synthetic organism, Syn 3.

One important topic in synthetic biology is synthetic life, that is concerned with hypothetical organisms created in vitro from biomolecules and/or chemical analogues thereof. Synthetic life experiments attempt to either probe the origins of life, study some of the properties of life, or more ambitiously to recreate life from non-living (abiotic) components. Synthetic life biology attempts to create living organisms capable of carrying out important functions, from manufacturing pharmaceuticals to detoxifying polluted land and water. In medicine, it offers prospects of using designer biological parts as a starting point for new classes of therapies and diagnostic tools.

A living "artificial cell" has been defined as a completely synthetic cell that can capture energy, maintain ion gradients, contain macromolecules as well as store information and have the ability to mutate. Nobody has been able to create such a cell.

A completely synthetic bacterial chromosome was produced in 2010 by Craig Venter, and his team introduced it to genomically emptied bacterial host cells. The host cells were able to grow and replicate. The Mycoplasma laboratorium is the only living organism with completely engineered genome.

The first living organism with 'artificial' expanded DNA code was presented in 2014; the team used E. coli that had its genome extracted and replaced with a chromosome with an expanded genetic code. The nucleosides added are d5SICS and dNaM.

In May 2019, researchers, in a milestone effort, reported the creation of a new synthetic (possibly artificial) form of viable life, a variant of the bacteria Escherichia coli, by reducing the natural number of 64 codons in the bacterial genome to 59 codons instead, in order to encode 20 amino acids.

In 2017 the international Build-a-Cell large-scale research collaboration for the construction of synthetic living cell was started, followed by national synthetic cell organizations in several countries, including FabriCell, MaxSynBio and BaSyC. The European synthetic cell efforts were unified in 2019 as SynCellEU initiative.

Drug delivery platforms

Engineered bacteria-based platform

Bacteria have long been used in cancer treatment. Bifidobacterium and Clostridium selectively colonize tumors and reduce their size. Recently synthetic biologists reprogrammed bacteria to sense and respond to a particular cancer state. Most often bacteria are used to deliver a therapeutic molecule directly to the tumor to minimize off-target effects. To target the tumor cells, peptides that can specifically recognize a tumor were expressed on the surfaces of bacteria. Peptides used include an affibody molecule that specifically targets human epidermal growth factor receptor 2 and a synthetic adhesin. The other way is to allow bacteria to sense the tumor microenvironment, for example hypoxia, by building an AND logic gate into bacteria. The bacteria then only release target therapeutic molecules to the tumor through either lysis or the bacterial secretion system. Lysis has the advantage that it can stimulate the immune system and control growth. Multiple types of secretion systems can be used and other strategies as well. The system is inducible by external signals. Inducers include chemicals, electromagnetic or light waves.

Multiple species and strains are applied in these therapeutics. Most commonly used bacteria are Salmonella typhimurium, Escherichia Coli, Bifidobacteria, Streptococcus, Lactobacillus, Listeria and Bacillus subtilis. Each of these species have their own property and are unique to cancer therapy in terms of tissue colonization, interaction with immune system and ease of application.

Cell-based platform

The immune system plays an important role in cancer and can be harnessed to attack cancer cells. Cell-based therapies focus on immunotherapies, mostly by engineering T cells.

T cell receptors were engineered and ‘trained’ to detect cancer epitopes. Chimeric antigen receptors (CARs) are composed of a fragment of an antibody fused to intracellular T cell signaling domains that can activate and trigger proliferation of the cell. A second generation CAR-based therapy was approved by FDA.

Gene switches were designed to enhance safety of the treatment. Kill switches were developed to terminate the therapy should the patient show severe side effects. Mechanisms can more finely control the system and stop and reactivate it. Since the number of T-cells are important for therapy persistence and severity, growth of T-cells is also controlled to dial the effectiveness and safety of therapeutics.

Although several mechanisms can improve safety and control, limitations include the difficulty of inducing large DNA circuits into the cells and risks associated with introducing foreign components, especially proteins, into cells.

Ethics

The creation of new life and the tampering of existing life has raised ethical concerns in the field of synthetic biology and are actively being discussed.

Common ethical questions include:

  • Is it morally right to tamper with nature?
  • Is one playing God when creating new life?
  • What happens if a synthetic organism accidentally escapes?
  • What if an individual misuses synthetic biology and creates a harmful entity (e.g., a biological weapon)?
  • Who will have control of and access to the products of synthetic biology?
  • Who will gain from these innovations? Investors? Medical patients? Industrial farmers?
  • Does the patent system allow patents on living organisms? What about parts of organisms, like HIV resistance genes in humans?
  • What if a new creation is deserving of moral or legal status?

The ethical aspects of synthetic biology has 3 main features: biosafety, biosecurity, and the creation of new life forms. Other ethical issues mentioned include the regulation of new creations, patent management of new creations, benefit distribution, and research integrity.

Ethical issues have surfaced for recombinant DNA and genetically modified organism (GMO) technologies and extensive regulations of genetic engineering and pathogen research were in place in many jurisdictions. Amy Gutmann, former head of the Presidential Bioethics Commission, argued that we should avoid the temptation to over-regulate synthetic biology in general, and genetic engineering in particular. According to Gutmann, "Regulatory parsimony is especially important in emerging technologies...where the temptation to stifle innovation on the basis of uncertainty and fear of the unknown is particularly great. The blunt instruments of statutory and regulatory restraint may not only inhibit the distribution of new benefits, but can be counterproductive to security and safety by preventing researchers from developing effective safeguards.".

The "creation" of life

One ethical question is whether or not it is acceptable to create new life forms, sometimes known as "playing God". Currently, the creation of new life forms not present in nature is at small-scale, the potential benefits and dangers remain unknown, and careful consideration and oversight are ensured for most studies. Many advocates express the great potential value—to agriculture, medicine, and academic knowledge, among other fields—of creating artificial life forms. Creation of new entities could expand scientific knowledge well beyond what is currently known from studying natural phenomena. Yet there is concern that artificial life forms may reduce nature's "purity" (i.e., nature could be somehow corrupted by human intervention and manipulation) and potentially influence the adoption of more engineering-like principles instead of biodiversity- and nature-focused ideals. Some are also concerned that if an artificial life form were to be released into nature, it could hamper biodiversity by beating out natural species for resources (similar to how algal blooms kill marine species). Another concern involves the ethical treatment of newly created entities if they happen to sense pain, sentience, and self-perception. Should such life be given moral or legal rights? If so, how?

Biosafety and biocontainment

What is most ethically appropriate when considering biosafety measures? How can accidental introduction of synthetic life in the natural environment be avoided? Much ethical consideration and critical thought has been given to these questions. Biosafety not only refers to biological containment; it also refers to strides taken to protect the public from potentially hazardous biological agents. Even though such concerns are important and remain unanswered, not all products of synthetic biology present concern for biological safety or negative consequences for the environment. It is argued that most synthetic technologies are benign and are incapable of flourishing in the outside world due to their "unnatural" characteristics as there is yet to be an example of a transgenic microbe conferred with a fitness advantage in the wild.

In general, existing hazard controls, risk assessment methodologies, and regulations developed for traditional genetically modified organisms (GMOs) are considered to be sufficient for synthetic organisms. "Extrinsic" biocontainment methods in a laboratory context include physical containment through biosafety cabinets and gloveboxes, as well as personal protective equipment. In an agricultural context they include isolation distances and pollen barriers, similar to methods for biocontainment of GMOs. Synthetic organisms may offer increased hazard control because they can be engineered with "intrinsic" biocontainment methods that limit their growth in an uncontained environment, or prevent horizontal gene transfer to natural organisms. Examples of intrinsic biocontainment include auxotrophy, biological kill switches, inability of the organism to replicate or to pass modified or synthetic genes to offspring, and the use of xenobiological organisms using alternative biochemistry, for example using artificial xeno nucleic acids (XNA) instead of DNA. Regarding auxotrophy, bacteria and yeast can be engineered to be unable to produce histidine, an important amino acid for all life. Such organisms can thus only be grown on histidine-rich media in laboratory conditions, nullifying fears that they could spread into undesirable areas.

Biosecurity

Some ethical issues relate to biosecurity, where biosynthetic technologies could be deliberately used to cause harm to society and/or the environment. Since synthetic biology raises ethical issues and biosecurity issues, humanity must consider and plan on how to deal with potentially harmful creations, and what kinds of ethical measures could possibly be employed to deter nefarious biosynthetic technologies. With the exception of regulating synthetic biology and biotechnology companies, however, the issues are not seen as new because they were raised during the earlier recombinant DNA and genetically modified organism (GMO) debates and extensive regulations of genetic engineering and pathogen research are already in place in many jurisdictions.

European Union

The European Union-funded project SYNBIOSAFE has issued reports on how to manage synthetic biology. A 2007 paper identified key issues in safety, security, ethics and the science-society interface, which the project defined as public education and ongoing dialogue among scientists, businesses, government and ethicists. The key security issues that SYNBIOSAFE identified involved engaging companies that sell synthetic DNA and the biohacking community of amateur biologists. Key ethical issues concerned the creation of new life forms.

A subsequent report focused on biosecurity, especially the so-called dual-use challenge. For example, while synthetic biology may lead to more efficient production of medical treatments, it may also lead to synthesis or modification of harmful pathogens (e.g., smallpox). The biohacking community remains a source of special concern, as the distributed and diffuse nature of open-source biotechnology makes it difficult to track, regulate or mitigate potential concerns over biosafety and biosecurity.

COSY, another European initiative, focuses on public perception and communication. To better communicate synthetic biology and its societal ramifications to a broader public, COSY and SYNBIOSAFE published SYNBIOSAFE, a 38-minute documentary film, in October 2009.

The International Association Synthetic Biology has proposed self-regulation. This proposes specific measures that the synthetic biology industry, especially DNA synthesis companies, should implement. In 2007, a group led by scientists from leading DNA-synthesis companies published a "practical plan for developing an effective oversight framework for the DNA-synthesis industry".

United States

In January 2009, the Alfred P. Sloan Foundation funded the Woodrow Wilson Center, the Hastings Center, and the J. Craig Venter Institute to examine the public perception, ethics and policy implications of synthetic biology.

On July 9–10, 2009, the National Academies' Committee of Science, Technology & Law convened a symposium on "Opportunities and Challenges in the Emerging Field of Synthetic Biology".

After the publication of the first synthetic genome and the accompanying media coverage about "life" being created, President Barack Obama established the Presidential Commission for the Study of Bioethical Issues to study synthetic biology. The commission convened a series of meetings, and issued a report in December 2010 titled "New Directions: The Ethics of Synthetic Biology and Emerging Technologies." The commission stated that "while Venter's achievement marked a significant technical advance in demonstrating that a relatively large genome could be accurately synthesized and substituted for another, it did not amount to the “creation of life”. It noted that synthetic biology is an emerging field, which creates potential risks and rewards. The commission did not recommend policy or oversight changes and called for continued funding of the research and new funding for monitoring, study of emerging ethical issues and public education.

Synthetic biology, as a major tool for biological advances, results in the "potential for developing biological weapons, possible unforeseen negative impacts on human health ... and any potential environmental impact". These security issues may be avoided by regulating industry uses of biotechnology through policy legislation. Federal guidelines on genetic manipulation are being proposed by "the President's Bioethics Commission ... in response to the announced creation of a self-replicating cell from a chemically synthesized genome, put forward 18 recommendations not only for regulating the science ... for educating the public".

Opposition

On March 13, 2012, over 100 environmental and civil society groups, including Friends of the Earth, the International Center for Technology Assessment and the ETC Group issued the manifesto The Principles for the Oversight of Synthetic Biology. This manifesto calls for a worldwide moratorium on the release and commercial use of synthetic organisms until more robust regulations and rigorous biosafety measures are established. The groups specifically call for an outright ban on the use of synthetic biology on the human genome or human microbiome. Richard Lewontin wrote that some of the safety tenets for oversight discussed in The Principles for the Oversight of Synthetic Biology are reasonable, but that the main problem with the recommendations in the manifesto is that "the public at large lacks the ability to enforce any meaningful realization of those recommendations".

Health and safety

The hazards of synthetic biology include biosafety hazards to workers and the public, biosecurity hazards stemming from deliberate engineering of organisms to cause harm, and environmental hazards. The biosafety hazards are similar to those for existing fields of biotechnology, mainly exposure to pathogens and toxic chemicals, although novel synthetic organisms may have novel risks. For biosecurity, there is concern that synthetic or redesigned organisms could theoretically be used for bioterrorism. Potential risks include recreating known pathogens from scratch, engineering existing pathogens to be more dangerous, and engineering microbes to produce harmful biochemicals. Lastly, environmental hazards include adverse effects on biodiversity and ecosystem services, including potential changes to land use resulting from agricultural use of synthetic organisms.

Existing risk analysis systems for GMOs are generally considered sufficient for synthetic organisms, although there may be difficulties for an organism built "bottom-up" from individual genetic sequences. Synthetic biology generally falls under existing regulations for GMOs and biotechnology in general, and any regulations that exist for downstream commercial products, although there are generally no regulations in any jurisdiction that are specific to synthetic biology.

Thermodynamic diagrams

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Thermodynamic_diagrams Thermodynamic diagrams are diagrams used to repr...