Cryobiology

From Wikipedia, the free encyclopedia

Cryobiology is the branch of biology that studies the effects of low temperatures on living things within Earth's cryosphere or in science. The word cryobiology is derived from the Greek words κρῧος [kryos], "cold", βίος [bios], "life", and λόγος [logos], "word" (hence science). In practice, cryobiology is the study of biological material or systems at temperatures below normal. Materials or systems studied may include proteins, cells, tissues, organs, or whole organisms. Temperatures may range from moderately hypothermic conditions to cryogenic temperatures.

Areas of study

At least six major areas of cryobiology can be identified: 1) study of cold-adaptation of microorganisms, plants (cold hardiness), and animals, both invertebrates and vertebrates (including hibernation), 2) cryopreservation of cells, tissues, gametes, and embryos of animal and human origin for (medical) purposes of long-term storage by cooling to temperatures below the freezing point of water. This usually requires the addition of substances which protect the cells during freezing and thawing (cryoprotectants), 3) preservation of organs under hypothermic conditions for transplantation, 4) lyophilization (freeze-drying) of pharmaceuticals, 5) cryosurgery, a (minimally) invasive approach for the destruction of unhealthy tissue using cryogenic gases/fluids, and 6) physics of supercooling, ice nucleation/growth and mechanical engineering aspects of heat transfer during cooling and warming, as applied to biological systems. Cryobiology would include cryonics, the low temperature preservation of humans and mammals with the intention of future revival, although this is not part of mainstream cryobiology, depending heavily on speculative technology yet to be invented. Several of these areas of study rely on cryogenics, the branch of physics and engineering that studies the production and use of very low temperatures.

Cryopreservation in nature

Many living organisms are able to tolerate prolonged periods of time at temperatures below the freezing point of water. Most living organisms accumulate cryoprotectants such as antinucleating proteins, polyols, and glucose to protect themselves against frost damage by sharp ice crystals. Most plants, in particular, can safely reach temperatures of −4 °C to −12 °C.

Bacteria

Three species of bacteria, Carnobacterium pleistocenium, Chryseobacterium greenlandensis, and Herminiimonas glaciei, have reportedly been revived after surviving for thousands of years frozen in ice. Certain bacteria, notably Pseudomonas syringae, produce specialized proteins that serve as potent ice nucleators, which they use to force ice formation on the surface of various fruits and plants at about −2 °C. The freezing causes injuries in the epithelia and makes the nutrients in the underlying plant tissues available to the bacteria. Listeria grows slowly in temperatures as low as -1.5 °C and persists for some time in frozen foods.

Plants

Many plants undergo a process called hardening which allows them to survive temperatures below 0 °C for weeks to months.

Animals

Invertebrates

Nematodes that survive below 0 °C include Trichostrongylus colubriformis and Panagrolaimus davidi. Cockroach nymphs (Periplaneta japonica) survive short periods of freezing at -6 to -8 °C. The red flat bark beetle (Cucujus clavipes) can survive after being frozen to -150 °C. The fungus gnat Exechia nugatoria can survive after being frozen to -50 °C, by a unique mechanism whereby ice crystals form in the body but not the head. Another freeze-tolerant beetle is Upis ceramboides. See insect winter ecology and antifreeze protein. Another invertebrate that is briefly tolerant to temperatures down to -273 °C is the tardigrade.

The larvae of Haemonchus contortus, a nematode, can survive 44 weeks frozen at -196 °C.

Vertebrates

For the wood frog (Rana sylvatica), in the winter, as much as 45% of its body may freeze and turn to ice. "Ice crystals form beneath the skin and become interspersed among the body's skeletal muscles. During the freeze, the frog's breathing, blood flow, and heartbeat cease. Freezing is made possible by specialized proteins and glucose, which prevent intracellular freezing and dehydration." The wood frog can survive up to 11 days frozen at -4 °C.

Other vertebrates that survive at body temperatures below 0 °C include painted turtles (Chrysemys picta), gray tree frogs (Hyla versicolor), box turtles (Terrapene carolina - 48 hours at -2 °C), spring peeper (Pseudacris crucifer), garter snakes (Thamnophis sirtalis- 24 hours at -1.5 °C), the chorus frog (Pseudacris triseriata), Siberian salamander (Salamandrella keyserlingii - 24 hours at -15.3 °C), European common lizard (Lacerta vivipara) and Antarctic fish such as Pagothenia borchgrevinki. Antifreeze proteins cloned from such fish have been used to confer frost-resistance on transgenic plants.

Hibernating Arctic ground squirrels may have abdominal temperatures as low as −2.9 °C (26.8 °F), maintaining subzero abdominal temperatures for more than three weeks at a time, although the temperatures at the head and neck remain at 0 °C or above.

Applied cryobiology

Historical background

Boyle

Cryobiology history can be traced back to antiquity. As early as in 2500 BC, low temperatures were used in Egypt in medicine. The use of cold was recommended by Hippocrates to stop bleeding and swelling. With the emergence of modern science, Robert Boyle studied the effects of low temperatures on animals.

In 1949, bull semen was cryopreserved for the first time by a team of scientists led by Christopher Polge. This led to a much wider use of cryopreservation today, with many organs, tissues and cells routinely stored at low temperatures. Large organs such as hearts are usually stored and transported, for short times only, at cool but not freezing temperatures for transplantation. Cell suspensions (like blood and semen) and thin tissue sections can sometimes be stored almost indefinitely in liquid nitrogen temperature (cryopreservation). Human sperm, eggs, and embryos are routinely stored in fertility research and treatments. Controlled-rate and slow freezing are well established techniques pioneered in the early 1970s which enabled the first human embryo frozen birth (Zoe Leyland) in 1984. Since then, machines that freeze biological samples using programmable steps, or controlled rates, have been used all over the world for human, animal, and cell biology – 'freezing down' a sample to better preserve it for eventual thawing, before it is deep frozen, or cryopreserved, in liquid nitrogen. Such machines are used for freezing oocytes, skin, blood products, embryo, sperm, stem cells, and general tissue preservation in hospitals, veterinary practices, and research labs. The number of live births from 'slow frozen' embryos is some 300,000 to 400,000 or 20% of the estimated 3 million in vitro fertilized births. Dr Christopher Chen, Australia, reported the world’s first pregnancy using slow-frozen oocytes from a British controlled-rate freezer in 1986.

Cryosurgery (intended and controlled tissue destruction by ice formation) was carried out by James Arnott in 1845 in an operation on a patient with cancer. Cryosurgery is not common.

Preservation techniques

Cryobiology as an applied science is primarily concerned with low-temperature preservation. Hypothermic storage is typically above 0 °C but below normothermic (32 °C to 37 °C) mammalian temperatures. Storage by cryopreservation, on the other hand, will be in the −80 to −196 °C temperature range. Organs, and tissues are more frequently the objects of hypothermic storage, whereas single cells have been the most common objects cryopreserved.

A rule of thumb in hypothermic storage is that every 10 °C reduction in temperature is accompanied by a 50% decrease in oxygen consumption. Although hibernating animals have adapted mechanisms to avoid metabolic imbalances associated with hypothermia, hypothermic organs, and tissues being maintained for transplantation require special preservation solutions to counter acidosis, depressed sodium pump activity. and increased intracellular calcium. Special organ preservation solutions such as Viaspan (University of Wisconsin solution), HTK, and Celsior have been designed for this purpose. These solutions also contain ingredients to minimize damage by free radicals, prevent edema, compensate for ATP loss, etc.

Cryopreservation of cells is guided by the "two-factor hypothesis" of American cryobiologist Peter Mazur, which states that excessively rapid cooling kills cells by intracellular ice formation and excessively slow cooling kills cells by either electrolyte toxicity or mechanical crushing. During slow cooling, ice forms extracellularly, causing water to osmotically leave cells, thereby dehydrating them. Intracellular ice can be much more damaging than extracellular ice.

For red blood cells, the optimum cooling rate is very rapid (nearly 100 °C per second), whereas for stem cells the optimum cooling rate is very slow (1 °C per minute). Cryoprotectants, such as dimethyl sulfoxide and glycerol, are used to protect cells from freezing. A variety of cell types are protected by 10% dimethyl sulfoxide. Cryobiologists attempt to optimize cryoprotectant concentration (minimizing both ice formation and toxicity) and cooling rate. Cells may be cooled at an optimum rate to a temperature between −30 and −40 °C before being plunged into liquid nitrogen.

Slow cooling methods rely on the fact that cells contain few nucleating agents, but contain naturally occurring vitrifying substances that can prevent ice formation in cells that have been moderately dehydrated. Some cryobiologists are seeking mixtures of cryoprotectants for full vitrification (zero ice formation) in preservation of cells, tissues, and organs. Vitrification methods pose a challenge in the requirement to search for cryoprotectant mixtures that can minimize toxicity.

In humans

Human gametes and two-, four- and eight-cell embryos can survive cryopreservation at -196 °C for 10 years under well-controlled laboratory conditions.

Cryopreservation in humans with regards to infertility involves preservation of embryos, sperm, or oocytes via freezing. Conception, in vitro, is attempted when the sperm is thawed and introduced to the 'fresh' eggs, the frozen eggs are thawed and sperm is placed with the eggs and together they are placed back into the uterus or a frozen embryo is introduced to the uterus. Vitrification has flaws and is not as reliable or proven as freezing fertilized sperm, eggs, or embryos as traditional slow freezing methods because eggs alone are extremely sensitive to temperature. Many researchers are also freezing ovarian tissue in conjunction with the eggs in hopes that the ovarian tissue can be transplanted back into the uterus, stimulating normal ovulation cycles. In 2004, Donnez of Louvain in Belgium reported the first successful ovarian birth from frozen ovarian tissue. In 1997, samples of ovarian cortex were taken from a woman with Hodgkin's lymphoma and cryopreserved in a (Planer, UK) controlled-rate freezer and then stored in liquid nitrogen. Chemotherapy was initiated after the patient had premature ovarian failure. In 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy and after five months, reimplantation signs indicated recovery of regular ovulatory cycles. Eleven months after reimplantation, a viable intrauterine pregnancy was confirmed, which resulted in the first such live birth – a girl named Tamara.

Therapeutic hypothermia, e.g. during heart surgery on a "cold" heart (generated by cold perfusion without any ice formation) allows for much longer operations and improves recovery rates for patients.

Scientific societies

The Society for Cryobiology was founded in 1964 to bring together those from the biological, medical, and physical sciences who have a common interest in the effects of low temperatures on biological systems. As of 2007, the Society for Cryobiology had about 280 members from around the world, and one-half of them are US-based. The purpose of the Society is to promote scientific research in low temperature biology, to improve scientific understanding in this field, and to disseminate and apply this knowledge to the benefit of mankind. The Society requires of all its members the highest ethical and scientific standards in the performance of their professional activities. According to the Society's bylaws, membership may be refused to applicants whose conduct is deemed detrimental to the Society; in 1982, the bylaws were amended explicitly to exclude "any practice or application of freezing deceased persons in the anticipation of their reanimation", over the objections of some members who were cryonicists, such as Jerry Leaf. The Society organizes an annual scientific meeting dedicated to all aspects of low-temperature biology. This international meeting offers opportunities for presentation and discussion of the most up-to-date research in cryobiology, as well as reviewing specific aspects through symposia and workshops. Members are also kept informed of news and forthcoming meetings through the Society newsletter, News Notes. The 2011–2012 president of the Society for Cryobiology was John H. Crowe.

The Society for Low Temperature Biology was founded in 1964 and became a registered charity in 2003 with the purpose of promoting research into the effects of low temperatures on all types of organisms and their constituent cells, tissues, and organs. As of 2006, the society had around 130 (mostly British and European) members and holds at least one annual general meeting. The program usually includes both a symposium on a topical subject and a session of free communications on any aspect of low-temperature biology. Recent symposia have included long-term stability, preservation of aquatic organisms, cryopreservation of embryos and gametes, preservation of plants, low-temperature microscopy, vitrification (glass formation of aqueous systems during cooling), freeze drying and tissue banking. Members are informed through the Society Newsletter, which is presently published three times a year.

Journals

Cryobiology (publisher: Elsevier) is the foremost scientific publication in this area, with about 60 refereed contributions published each year. Articles concern any aspect of low-temperature biology and medicine (e.g. freezing, freeze-drying, hibernation, cold tolerance and adaptation, cryoprotective compounds, medical applications of reduced temperature, cryosurgery, hypothermia, and perfusion of organs).

Cryo Letters is an independent UK-based rapid communication journal which publishes papers on the effects produced by low temperatures on a wide variety of biophysical and biological processes, or studies involving low-temperature techniques in the investigation of biological and ecological topics.

Biopreservation and Biobanking (formerly Cell Preservation Technology) is a peer-reviewed quarterly scientific journal published by Mary Ann Liebert, Inc. dedicated to the diverse spectrum of preservation technologies including cryopreservation, dry-state (anhydrobiosis), and glassy-state and hypothermic maintenance. Cell Preservation Technology has been renamed Biopreservation and Biobanking and is the official journal of International Society for Biological and Environmental Repositories.

Cryobiology is the branch of biology that studies the effects of low temperatures on living things within Earth's cryosphere or in science. The word cryobiology is derived from the Greek words κρῧος [kryos], "cold", βίος [bios], "life", and λόγος [logos], "word" (hence science). In practice, cryobiology is the study of biological material or systems at temperatures below normal. Materials or systems studied may include proteins, cells, tissues, organs, or whole organisms. Temperatures may range from moderately hypothermic conditions to cryogenic temperatures.

Areas of study

At least six major areas of cryobiology can be identified: 1) study of cold-adaptation of microorganisms, plants (cold hardiness), and animals, both invertebrates and vertebrates (including hibernation), 2) cryopreservation of cells, tissues, gametes, and embryos of animal and human origin for (medical) purposes of long-term storage by cooling to temperatures below the freezing point of water. This usually requires the addition of substances which protect the cells during freezing and thawing (cryoprotectants), 3) preservation of organs under hypothermic conditions for transplantation, 4) lyophilization (freeze-drying) of pharmaceuticals, 5) cryosurgery, a (minimally) invasive approach for the destruction of unhealthy tissue using cryogenic gases/fluids, and 6) physics of supercooling, ice nucleation/growth and mechanical engineering aspects of heat transfer during cooling and warming, as applied to biological systems. Cryobiology would include cryonics, the low temperature preservation of humans and mammals with the intention of future revival, although this is not part of mainstream cryobiology, depending heavily on speculative technology yet to be invented. Several of these areas of study rely on cryogenics, the branch of physics and engineering that studies the production and use of very low temperatures.

Cryopreservation in nature

Many living organisms are able to tolerate prolonged periods of time at temperatures below the freezing point of water. Most living organisms accumulate cryoprotectants such as antinucleating proteins, polyols, and glucose to protect themselves against frost damage by sharp ice crystals. Most plants, in particular, can safely reach temperatures of −4 °C to −12 °C.

Bacteria

Three species of bacteria, Carnobacterium pleistocenium, Chryseobacterium greenlandensis, and Herminiimonas glaciei, have reportedly been revived after surviving for thousands of years frozen in ice. Certain bacteria, notably Pseudomonas syringae, produce specialized proteins that serve as potent ice nucleators, which they use to force ice formation on the surface of various fruits and plants at about −2 °C. The freezing causes injuries in the epithelia and makes the nutrients in the underlying plant tissues available to the bacteria. Listeria grows slowly in temperatures as low as -1.5 °C and persists for some time in frozen foods.

Plants

Many plants undergo a process called hardening which allows them to survive temperatures below 0 °C for weeks to months.

Animals

Invertebrates

Nematodes that survive below 0 °C include Trichostrongylus colubriformis and Panagrolaimus davidi. Cockroach nymphs (Periplaneta japonica) survive short periods of freezing at -6 to -8 °C. The red flat bark beetle (Cucujus clavipes) can survive after being frozen to -150 °C. The fungus gnat Exechia nugatoria can survive after being frozen to -50 °C, by a unique mechanism whereby ice crystals form in the body but not the head. Another freeze-tolerant beetle is Upis ceramboides. See insect winter ecology and antifreeze protein. Another invertebrate that is briefly tolerant to temperatures down to -273 °C is the tardigrade.

The larvae of Haemonchus contortus, a nematode, can survive 44 weeks frozen at -196 °C.

Vertebrates

For the wood frog (Rana sylvatica), in the winter, as much as 45% of its body may freeze and turn to ice. "Ice crystals form beneath the skin and become interspersed among the body's skeletal muscles. During the freeze, the frog's breathing, blood flow, and heartbeat cease. Freezing is made possible by specialized proteins and glucose, which prevent intracellular freezing and dehydration." The wood frog can survive up to 11 days frozen at -4 °C.

Other vertebrates that survive at body temperatures below 0 °C include painted turtles (Chrysemys picta), gray tree frogs (Hyla versicolor), box turtles (Terrapene carolina - 48 hours at -2 °C), spring peeper (Pseudacris crucifer), garter snakes (Thamnophis sirtalis- 24 hours at -1.5 °C), the chorus frog (Pseudacris triseriata), Siberian salamander (Salamandrella keyserlingii - 24 hours at -15.3 °C), European common lizard (Lacerta vivipara) and Antarctic fish such as Pagothenia borchgrevinki. Antifreeze proteins cloned from such fish have been used to confer frost-resistance on transgenic plants.

Hibernating Arctic ground squirrels may have abdominal temperatures as low as −2.9 °C (26.8 °F), maintaining subzero abdominal temperatures for more than three weeks at a time, although the temperatures at the head and neck remain at 0 °C or above.

Applied cryobiology

Historical background

Boyle

Cryobiology history can be traced back to antiquity. As early as in 2500 BC, low temperatures were used in Egypt in medicine. The use of cold was recommended by Hippocrates to stop bleeding and swelling. With the emergence of modern science, Robert Boyle studied the effects of low temperatures on animals.

In 1949, bull semen was cryopreserved for the first time by a team of scientists led by Christopher Polge. This led to a much wider use of cryopreservation today, with many organs, tissues and cells routinely stored at low temperatures. Large organs such as hearts are usually stored and transported, for short times only, at cool but not freezing temperatures for transplantation. Cell suspensions (like blood and semen) and thin tissue sections can sometimes be stored almost indefinitely in liquid nitrogen temperature (cryopreservation). Human sperm, eggs, and embryos are routinely stored in fertility research and treatments. Controlled-rate and slow freezing are well established techniques pioneered in the early 1970s which enabled the first human embryo frozen birth (Zoe Leyland) in 1984. Since then, machines that freeze biological samples using programmable steps, or controlled rates, have been used all over the world for human, animal, and cell biology – 'freezing down' a sample to better preserve it for eventual thawing, before it is deep frozen, or cryopreserved, in liquid nitrogen. Such machines are used for freezing oocytes, skin, blood products, embryo, sperm, stem cells, and general tissue preservation in hospitals, veterinary practices, and research labs. The number of live births from 'slow frozen' embryos is some 300,000 to 400,000 or 20% of the estimated 3 million in vitro fertilized births. Dr Christopher Chen, Australia, reported the world’s first pregnancy using slow-frozen oocytes from a British controlled-rate freezer in 1986.

Cryosurgery (intended and controlled tissue destruction by ice formation) was carried out by James Arnott in 1845 in an operation on a patient with cancer. Cryosurgery is not common.

Preservation techniques

Cryobiology as an applied science is primarily concerned with low-temperature preservation. Hypothermic storage is typically above 0 °C but below normothermic (32 °C to 37 °C) mammalian temperatures. Storage by cryopreservation, on the other hand, will be in the −80 to −196 °C temperature range. Organs, and tissues are more frequently the objects of hypothermic storage, whereas single cells have been the most common objects cryopreserved.

A rule of thumb in hypothermic storage is that every 10 °C reduction in temperature is accompanied by a 50% decrease in oxygen consumption. Although hibernating animals have adapted mechanisms to avoid metabolic imbalances associated with hypothermia, hypothermic organs, and tissues being maintained for transplantation require special preservation solutions to counter acidosis, depressed sodium pump activity. and increased intracellular calcium. Special organ preservation solutions such as Viaspan (University of Wisconsin solution), HTK, and Celsior have been designed for this purpose. These solutions also contain ingredients to minimize damage by free radicals, prevent edema, compensate for ATP loss, etc.

Cryopreservation of cells is guided by the "two-factor hypothesis" of American cryobiologist Peter Mazur, which states that excessively rapid cooling kills cells by intracellular ice formation and excessively slow cooling kills cells by either electrolyte toxicity or mechanical crushing. During slow cooling, ice forms extracellularly, causing water to osmotically leave cells, thereby dehydrating them. Intracellular ice can be much more damaging than extracellular ice.

For red blood cells, the optimum cooling rate is very rapid (nearly 100 °C per second), whereas for stem cells the optimum cooling rate is very slow (1 °C per minute). Cryoprotectants, such as dimethyl sulfoxide and glycerol, are used to protect cells from freezing. A variety of cell types are protected by 10% dimethyl sulfoxide. Cryobiologists attempt to optimize cryoprotectant concentration (minimizing both ice formation and toxicity) and cooling rate. Cells may be cooled at an optimum rate to a temperature between −30 and −40 °C before being plunged into liquid nitrogen.

Slow cooling methods rely on the fact that cells contain few nucleating agents, but contain naturally occurring vitrifying substances that can prevent ice formation in cells that have been moderately dehydrated. Some cryobiologists are seeking mixtures of cryoprotectants for full vitrification (zero ice formation) in preservation of cells, tissues, and organs. Vitrification methods pose a challenge in the requirement to search for cryoprotectant mixtures that can minimize toxicity.

In humans

Human gametes and two-, four- and eight-cell embryos can survive cryopreservation at -196 °C for 10 years under well-controlled laboratory conditions.

Cryopreservation in humans with regards to infertility involves preservation of embryos, sperm, or oocytes via freezing. Conception, in vitro, is attempted when the sperm is thawed and introduced to the 'fresh' eggs, the frozen eggs are thawed and sperm is placed with the eggs and together they are placed back into the uterus or a frozen embryo is introduced to the uterus. Vitrification has flaws and is not as reliable or proven as freezing fertilized sperm, eggs, or embryos as traditional slow freezing methods because eggs alone are extremely sensitive to temperature. Many researchers are also freezing ovarian tissue in conjunction with the eggs in hopes that the ovarian tissue can be transplanted back into the uterus, stimulating normal ovulation cycles. In 2004, Donnez of Louvain in Belgium reported the first successful ovarian birth from frozen ovarian tissue. In 1997, samples of ovarian cortex were taken from a woman with Hodgkin's lymphoma and cryopreserved in a (Planer, UK) controlled-rate freezer and then stored in liquid nitrogen. Chemotherapy was initiated after the patient had premature ovarian failure. In 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy and after five months, reimplantation signs indicated recovery of regular ovulatory cycles. Eleven months after reimplantation, a viable intrauterine pregnancy was confirmed, which resulted in the first such live birth – a girl named Tamara.

Therapeutic hypothermia, e.g. during heart surgery on a "cold" heart (generated by cold perfusion without any ice formation) allows for much longer operations and improves recovery rates for patients.

Scientific societies

The Society for Cryobiology was founded in 1964 to bring together those from the biological, medical, and physical sciences who have a common interest in the effects of low temperatures on biological systems. As of 2007, the Society for Cryobiology had about 280 members from around the world, and one-half of them are US-based. The purpose of the Society is to promote scientific research in low temperature biology, to improve scientific understanding in this field, and to disseminate and apply this knowledge to the benefit of mankind. The Society requires of all its members the highest ethical and scientific standards in the performance of their professional activities. According to the Society's bylaws, membership may be refused to applicants whose conduct is deemed detrimental to the Society; in 1982, the bylaws were amended explicitly to exclude "any practice or application of freezing deceased persons in the anticipation of their reanimation", over the objections of some members who were cryonicists, such as Jerry Leaf. The Society organizes an annual scientific meeting dedicated to all aspects of low-temperature biology. This international meeting offers opportunities for presentation and discussion of the most up-to-date research in cryobiology, as well as reviewing specific aspects through symposia and workshops. Members are also kept informed of news and forthcoming meetings through the Society newsletter, News Notes. The 2011–2012 president of the Society for Cryobiology was John H. Crowe.

The Society for Low Temperature Biology was founded in 1964 and became a registered charity in 2003 with the purpose of promoting research into the effects of low temperatures on all types of organisms and their constituent cells, tissues, and organs. As of 2006, the society had around 130 (mostly British and European) members and holds at least one annual general meeting. The program usually includes both a symposium on a topical subject and a session of free communications on any aspect of low-temperature biology. Recent symposia have included long-term stability, preservation of aquatic organisms, cryopreservation of embryos and gametes, preservation of plants, low-temperature microscopy, vitrification (glass formation of aqueous systems during cooling), freeze drying and tissue banking. Members are informed through the Society Newsletter, which is presently published three times a year.

Journals

Cryobiology (publisher: Elsevier) is the foremost scientific publication in this area, with about 60 refereed contributions published each year. Articles concern any aspect of low-temperature biology and medicine (e.g. freezing, freeze-drying, hibernation, cold tolerance and adaptation, cryoprotective compounds, medical applications of reduced temperature, cryosurgery, hypothermia, and perfusion of organs).

Cryo Letters is an independent UK-based rapid communication journal which publishes papers on the effects produced by low temperatures on a wide variety of biophysical and biological processes, or studies involving low-temperature techniques in the investigation of biological and ecological topics.

Biopreservation and Biobanking (formerly Cell Preservation Technology) is a peer-reviewed quarterly scientific journal published by Mary Ann Liebert, Inc. dedicated to the diverse spectrum of preservation technologies including cryopreservation, dry-state (anhydrobiosis), and glassy-state and hypothermic maintenance. Cell Preservation Technology has been renamed Biopreservation and Biobanking and is the official journal of International Society for Biological and Environmental Repositories.

 

Cryptobiosis

From Wikipedia, the free encyclopedia

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

Cryptobiosis or anabiosis is a metabolic state of life entered by an organism in response to adverse environmental conditions such as desiccation, freezing, and oxygen deficiency. In the cryptobiotic state, all measurable metabolic processes stop, preventing reproduction, development, and repair. When environmental conditions return to being hospitable, the organism will return to its metabolic state of life as it was prior to the cryptobiosis.

Forms

Anhydrobiosis

Anhydrobiosis in the tardigrade Richtersius coronifer

Anhydrobiosis is the most studied form of cryptobiosis and occurs in situations of extreme desiccation. The term anhydrobiosis derives from the Greek for "life without water" and is most commonly used for the desiccation tolerance observed in certain invertebrate animals such as bdelloid rotifers, tardigrades, brine shrimp, nematodes, and at least one insect, a species of chironomid (Polypedilum vanderplanki). However, other life forms exhibit desiccation tolerance. These include the resurrection plant Craterostigma plantagineum, the majority of plant seeds, and many microorganisms such as bakers' yeast. Studies have shown that some anhydrobiotic organisms can survive for decades, even centuries, in the dry state.

Invertebrates undergoing anhydrobiosis often contract into a smaller shape and some proceed to form a sugar called trehalose. Desiccation tolerance in plants is associated with the production of another sugar, sucrose. These sugars are thought to protect the organism from desiccation damage. In some creatures, such as bdelloid rotifers, no trehalose has been found, which has led scientists to propose other mechanisms of anhydrobiosis, possibly involving intrinsically disordered proteins.

In 2011, Caenorhabditis elegans, a nematode that is also one of the best-studied model organisms, was shown to undergo anhydrobiosis in the dauer larva stage. Further research taking advantage of genetic and biochemical tools available for this organism revealed that in addition to trehalose biosynthesis, a set of other functional pathways is involved in anhydrobiosis at the molecular level. These are mainly defense mechanisms against reactive oxygen species and xenobiotics, expression of heat shock proteins and intrinsically disordered proteins as well as biosynthesis of polyunsaturated fatty acids and polyamines. Some of them are conserved among anhydrobiotic plants and animals, suggesting that anhydrobiotic ability may depend on a set of common mechanisms. Understanding these mechanisms in detail might enable modification of non-anhydrobiotic cells, tissues, organs or even organisms so that they can be preserved in a dried state of suspended animation over long time periods.

As of 2004, such an application of anhydrobiosis is being applied to vaccines. In vaccines, the process can produce a dry vaccine that reactivates once it is injected into the body. In theory, dry-vaccine technology could be used on any vaccine, including live vaccines such as the one for measles. It could also potentially be adapted to allow a vaccine's slow release, eliminating the need for boosters. This proposes to eliminate the need for refrigerating vaccines, thus making dry vaccines more widely available throughout the developing world where refrigeration, electricity, and proper storage are less accessible.

Based on similar principles, lyopreservation has been developed as a technique for preservation of biological samples at ambient temperatures. Lyopreservation is a biomimetic strategy based on anhydrobiosis to preserve cells at ambient temperatures. It has been explored as an alternative technique for cryopreservation. The technique has the advantages of being able to preserve biological samples at ambient temperatures, without the need for refrigeration or use of cryogenic temperatures.

Anoxybiosis

In situations lacking oxygen (a.k.a., anoxia), many cryptobionts (such as M. tardigradum) take in water and become turgid and immobile, but can survive for prolonged periods of time. Some ectothermic vertebrates and some invertebrates, such as brine shrimps, copepods, nematodes, and sponge gemmules, are capable of surviving in a seemingly inactive state during anoxic conditions for months to decades.

Studies of the metabolic activity of these idling organisms during anoxia have been mostly inconclusive. This is because it is difficult to measure very small degrees of metabolic activity reliably enough to prove a cryptobiotic state rather than ordinary metabolic rate depression (MRD). Many experts are skeptical of the biological feasibility of anoxybiosis, as the organism is managing to prevent damage to its cellular structures from the environmental negative free energy, despite being both surrounded by plenty of water and thermal energy and without using any free energy of its own. However, there is evidence that the stress-induced protein p26 may act as a protein chaperone that requires no energy in cystic Artemia franciscana (sea monkey) embryos, and most likely an extremely specialized and slow guanine polynucleotide pathway continues to provide metabolic free energy to the A. franciscana embryos during anoxic conditions. It seems that A. franciscana approaches but does not reach true anoxybiosis.

Chemobiosis

Chemobiosis is the cryptobiotic response to high levels of environmental toxins. It has been observed in tardigrades.

Cryobiosis

Cryobiosis is a form of cryptobiosis that takes place in reaction to decreased temperature. Cryobiosis initiates when the water surrounding the organism's cells has been frozen, stopping molecule mobility allows the organism to endure the freezing temperatures until more hospitable conditions return. Organisms capable of enduring these conditions typically feature molecules that facilitate freezing of water in preferential locations while also prohibiting the growth of large ice crystals that could otherwise damage cells. One such organism is the lobster.

Osmobiosis

Osmobiosis is the least studied of all types of cryptobiosis. Osmobiosis occurs in response to increased solute concentration in the solution the organism lives in. Little is known for certain, other than that osmobiosis appears to involve a cessation of metabolism.

Examples

The brine shrimp Artemia salina, which can be found in the Makgadikgadi Pans in Botswana, survives over the dry season when the water of the pans evaporates, leaving a virtually desiccated lake bed.

The tardigrade, or water bear, can undergo all five types of cryptobiosis. While in a cryptobiotic state, its metabolism reduces to less than 0.01% of what is normal, and its water content can drop to 1% of normal. It can withstand extreme temperature, radiation, and pressure while in a cryptobiotic state.

Some nematodes and rotifers can also undergo cryptobiosis.

 

Cryonics

From Wikipedia, the free encyclopedia

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

Technicians prepare a body for cryopreservation in 1985.

Cryonics (from Greek: κρύος kryos meaning 'cold') is the low-temperature freezing (usually at −196 °C or −320.8 °F or 77.1 K) and storage of a human corpse or severed head, with the speculative hope that resurrection may be possible in the future. Cryonics is regarded with skepticism within the mainstream scientific community. It is generally viewed as a pseudoscience, and its practice has been characterized as quackery.

Cryonics procedures can begin only after the "patients" are clinically and legally dead. Cryonics procedures may begin within minutes of death, and use cryoprotectants to prevent ice formation during cryopreservation. It is, however, not possible for a corpse to be reanimated after undergoing vitrification, as this causes damage to the brain including its neural networks. The first corpse to be frozen was that of Dr. James Bedford in 1967. As of 2014, about 250 dead bodies had been cryopreserved in the United States, and 1,500 people had made arrangements for cryopreservation of their corpses.

Economic reality means it is highly improbable that any cryonics corporation could continue in business long enough to take advantage of the claimed long-term benefits offered. Early attempts of cryonic preservations were performed in the 1960s and early 1970s which ended in failure with companies going out of business, and their stored corpses thawed and disposed of.

Conceptual basis

Cryonicists argue that as long as brain structure remains intact, there is no fundamental barrier, given our current understanding of physical law, to recovering its information content. Cryonics proponents go further than the mainstream consensus in saying that the brain does not have to be continuously active to survive or retain memory. Cryonics controversially states that a human survives even within an inactive brain that has been badly damaged, provided that original encoding of memory and personality can, in theory, be adequately inferred and reconstituted from what structure remains.

Cryonics uses temperatures below −130 °C, called cryopreservation, in an attempt to preserve enough brain information to permit the future revival of the cryopreserved person. Cryopreservation may be accomplished by freezing, freezing with cryoprotectant to reduce ice damage, or by vitrification to avoid ice damage. Even using the best methods, cryopreservation of whole bodies or brains is very damaging and irreversible with current technology.

Cryonics advocates hold that in the future the use of some kind of presently-nonexistent nanotechnology may be able to help bring the dead back to life and treat the diseases which killed them. Mind uploading has also been proposed.

Cryonics in practice

Cryonics can be expensive. As of 2018, the cost of preparing and storing corpses using cryonics ranged from US$28,000 to $200,000.

When used at high concentrations, cryoprotectants can stop ice formation completely. Cooling and solidification without crystal formation is called vitrification. The first cryoprotectant solutions able to vitrify at very slow cooling rates while still being compatible with whole organ survival were developed in the late 1990s by cryobiologists Gregory Fahy and Brian Wowk for the purpose of banking transplantable organs. This has allowed animal brains to be vitrified, warmed back up, and examined for ice damage using light and electron microscopy. No ice crystal damage was found; cellular damage was due to dehydration and toxicity of the cryoprotectant solutions.

Costs can include payment for medical personnel to be on call for death, vitrification, transportation in dry ice to a preservation facility, and payment into a trust fund intended to cover indefinite storage in liquid nitrogen and future revival costs. As of 2011, U.S. cryopreservation costs can range from $28,000 to $200,000, and are often financed via life insurance. KrioRus, which stores bodies communally in large dewars, charges $12,000 to $36,000 for the procedure. Some customers opt to have only their brain cryopreserved ("neuropreservation"), rather than their whole body.

As of 2014, about 250 corpses have been cryogenically preserved in the U.S., and around 1,500 people have signed up to have their remains preserved. As of 2016, four facilities exist in the world to retain cryopreserved bodies: three in the U.S. and one in Russia.

Considering the lifecycle of corporations, it is extremely unlikely that any cryonics company could continue to exist for sufficient time to take advantage even of the supposed benefits offered: historically, even the most robust corporations have only a one-in-a-thousand chance of surviving even one hundred years. Many cryonics companies have failed; as of 2018, all but one of the pre-1973 batch had gone out of business, and their stored corpses have been defrosted and disposed of.

Obstacles to success

Preservation damage

Cryopreservation has long been used by medical laboratories to maintain animal cells, human embryos, and even some organized tissues, for periods as long as three decades. Recovering large animals and organs from a frozen state is however not considered possible at the current level of scientific knowledge. Large vitrified organs tend to develop fractures during cooling, a problem worsened by the large tissue masses and very low temperatures of cryonics. Without cryoprotectants, cell shrinkage and high salt concentrations during freezing usually prevent frozen cells from functioning again after thawing. Ice crystals can also disrupt connections between cells that are necessary for organs to function.

In 2016, Robert L. McIntyre and Gregory Fahy at the cryobiology research company 21st Century Medicine, Inc. won the Small Animal Brain Preservation Prize of the Brain Preservation Foundation by demonstrating to the satisfaction of neuroscientist judges that a particular implementation of fixation and vitrification called aldehyde-stabilized cryopreservation could preserve a rabbit brain in "near perfect" condition at −135 °C, with the cell membranes, synapses, and intracellular structures intact in electron micrographs. Brain Preservation Foundation President, Ken Hayworth, said, "This result directly answers a main skeptical and scientific criticism against cryonics—that it does not provably preserve the delicate synaptic circuitry of the brain." However the price paid for perfect preservation as seen by microscopy was tying up all protein molecules with chemical crosslinks, completely eliminating biological viability.

Actual cryonics organizations use vitrification without a chemical fixation step, sacrificing some structural preservation quality for less damage at the molecular level. Some scientists, like Joao Pedro Magalhaes, have questioned whether using a deadly chemical for fixation eliminates the possibility of biological revival, making chemical fixation unsuitable for cryonics.

Outside the cryonics community, many scientists have strong skepticism toward cryonics methods. Cryobiologist Dayong Gao states that "we simply don't know if (subjects have) been damaged to the point where they've 'died' during vitrification because the subjects are now inside liquid nitrogen canisters." Biochemist Ken Storey argues (based on experience with organ transplants), that "even if you only wanted to preserve the brain, it has dozens of different areas, which would need to be cryopreserved using different protocols."

Revival

Revival would require repairing damage from lack of oxygen, cryoprotectant toxicity, thermal stress (fracturing), freezing in tissues that do not successfully vitrify, finally followed by reversing the cause of death. In many cases, extensive tissue regeneration would be necessary.

Legal issues

Historically, a person had little control regarding how their body was treated after death as religion held jurisdiction over the ultimate fate of their body. However, secular courts began to exercise jurisdiction over the body and use discretion in carrying out of the wishes of the deceased person. Most countries legally treat preserved individuals as deceased persons because of laws that forbid vitrifying someone who is medically alive. In France, cryonics is not considered a legal mode of body disposal; only burial, cremation, and formal donation to science are allowed. However, bodies may legally be shipped to other countries for cryonic freezing. As of 2015, the Canadian province of British Columbia prohibits the sale of arrangements for body preservation based on cryonics. In Russia, cryonics falls outside both the medical industry and the funeral services industry, making it easier in Russia than in the U.S. to get hospitals and morgues to release cryonics candidates.

In London in 2016, the English High Court ruled in favor of a mother's right to seek cryopreservation of her terminally ill 14-year-old daughter, as the girl wanted, contrary to the father's wishes. The decision was made on the basis that the case represented a conventional dispute over the disposal of the girl's body, although the judge urged ministers to seek "proper regulation" for the future of cryonic preservation following concerns raised by the hospital about the competence and professionalism of the team that conducted the preservation procedures. In Alcor Life Extension Foundation v. Richardson, the Iowa Court of Appeals ordered for the disinterment of Richardson, who was buried against his wishes for cryopreservation.

A detailed legal examination by Jochen Taupitz concludes that cryonic storage is legal in Germany for an indefinite period of time.

Ethics

In 2009, writing in Bioethics, David Shaw examines the ethical status of cryonics. The arguments against it include changing the concept of death, the expense of preservation and revival, lack of scientific advancement to permit revival, temptation to use premature euthanasia, and failure due to catastrophe. Arguments in favor of cryonics include the potential benefit to society, the prospect of immortality, and the benefits associated with avoiding death. Shaw explores the expense and the potential payoff, and applies an adapted version of Pascal's Wager to the question.

In 2016, Charles Tandy wrote in favor of cryonics, arguing that honoring someone's last wishes is seen as a benevolent duty in American and many other cultures.

History

See also: Cryopreservation § History

Cryopreservation was applied to human cells beginning in 1954 with frozen sperm, which was thawed and used to inseminate three women. The freezing of humans was first scientifically proposed by Michigan professor Robert Ettinger when he wrote The Prospect of Immortality (1962). In April 1966, the first human body was frozen—though it had been embalmed for two months—by being placed in liquid nitrogen and stored at just above freezing. The middle-aged woman from Los Angeles, whose name is unknown, was soon thawed out and buried by relatives.

The first body to be cryopreserved and then frozen with the hope of future revival was that of James Bedford, claimed by Alcor's Mike Darwin to have occurred within around two hours of his death from cardiorespiratory arrest (secondary to metastasized kidney cancer) on January 12, 1967. Bedford's corpse is the only one frozen before 1974 still preserved today. In 1976, Ettinger founded the Cryonics Institute; his corpse was cryopreserved in 2011. Robert Nelson, "a former TV repairman with no scientific background" who led the Cryonics Society of California, was sued in 1981 for allowing nine bodies to thaw and decompose in the 1970s; in his defense, he claimed that the Cryonics Society had run out of money. This led to the lowered reputation of cryonics in the U.S.

In 2018, a Y-Combinator startup called Nectome was recognized for developing a method of preserving brains with chemicals rather than by freezing. The method is fatal, performed as euthanasia under general anethesia, but the hope is that future technology would allow the brain to be physically scanned into a computer simulation, neuron by neuron.

Demographics

According to The New York Times, cryonicists are predominantly non-religious white males, outnumbering women by about three to one. According to The Guardian, as of 2008, while most cryonicists used to be young, male, and "geeky", recent demographics have shifted slightly towards whole families.

In 2015, Du Hong, a 61-year-old female writer of children's literature, became the first known Chinese national to have their head cryopreserved.

Reception

Cryonics is generally regarded as a fringe pseudoscience. The Society for Cryobiology have rejected as members those who practiced cryonics, and have issued a public statement saying that cryonics is "not science", and that it is a "personal choice" how people want to have their dead bodies disposed of.

Russian company KrioRus is the only non-US vendor of cryonics services. Yevgeny Alexandrov, chair of the Russian Academy of Sciences commission against pseudoscience, said there was "no scientific basis" for cryonics, and that the company's offering was based on "unfounded speculation".

Although scientists have expressed skepticism about cryonics in media sources, the Norwegian philosopher Ole Martin Moen has written that it only receives a "minuscule" amount of attention from academia.

While some neuroscientists contend that all the subtleties of a human mind are contained in its anatomical structure, few neuroscientists will comment directly upon the topic of cryonics due to its speculative nature. Individuals who intend to be frozen are often "looked at as a bunch of kooks". Cryobiologist Kenneth B. Storey said in 2004 that cryonics is impossible and will never be possible, as cryonics proponents are proposing to "over-turn the laws of physics, chemistry, and molecular science". Neurobiologist Michael Hendricks has said that "Reanimation or simulation is an abjectly false hope that is beyond the promise of technology and is certainly impossible with the frozen, dead tissue offered by the 'cryonics' industry".

William T. Jarvis has written that "Cryonics might be a suitable subject for scientific research, but marketing an unproven method to the public is quackery".

According to cryonicist Aschwin de Wolf and others, cryonics can often produce intense hostility from spouses who are not cryonicists. James Hughes, the executive director of the pro-life-extension Institute for Ethics and Emerging Technologies, chooses not to personally sign up for cryonics, calling it a worthy experiment but stating laconically that "I value my relationship with my wife."

Cryobiologist Dayong Gao states that "People can always have hope that things will change in the future, but there is no scientific foundation supporting cryonics at this time." While it is universally agreed that "personal identity" is uninterrupted when brain activity temporarily ceases during incidents of accidental drowning (where people have been restored to normal functioning after being completely submerged in cold water for up to 66 minutes), one argument against cryonics is that a centuries-long absence from life might interrupt the conception of personal identity, such that the revived person would "not be themself".

Maastricht University bioethicist David Shaw raises the argument that there would be no point in being revived in the far future if one's friends and families are dead, leaving them all alone; he notes, however, that family and friends can also be frozen, that there is "nothing to prevent the thawed-out freezee from making new friends", and that a lonely existence may be preferable to no existence at all for the revived. The technology required to revive any corpse preserved in such a manner does not currently exist, so any such conjecture remains speculative.

In fiction

Main article: Suspended animation in fiction

Suspended animation is a popular subject in science fiction and fantasy settings. It is often the means by which a character is transported into the future.

A survey in Germany found that about half of the respondents were familiar with cryonics, and about half of those familiar with cryonics had learned of the subject from films or television.

In popular culture

The town of Nederland, Colorado, hosts an annual Frozen Dead Guy Days festival to commemorate a substandard attempt at cryopreservation.

Notable people

See also: List of people who arranged for cryonics

Corpses subjected to the cryonics process include those of baseball players Ted Williams and son John Henry Williams (in 2002 and 2004, respectively), engineer and doctor L. Stephen Coles (in 2014), economist and entrepreneur Phil Salin, and software engineer Hal Finney (in 2014).

People known to have arranged for cryonics upon death include PayPal founders Luke Nosek and Peter Thiel, and Oxford transhumanists Nick Bostrom and Anders Sandberg. Larry King previously arranged for cryonics, but according to Inside Edition, later changed his mind.

Disgraced financier Jeffrey Epstein wanted to have his head and penis frozen after death so that he could "seed the human race with his DNA."

The corpses of some are mistakenly believed to have undergone cryonics – for instance, the urban legend suggesting Walt Disney's corpse was cryopreserved is false; it was cremated and interred at Forest Lawn Memorial Park Cemetery. Robert A. Heinlein, who wrote enthusiastically of the concept in The Door into Summer (serialized in 1956), was cremated and had his ashes distributed over the Pacific Ocean. Timothy Leary was a long-time cryonics advocate and signed up with a major cryonics provider, but he changed his mind shortly before his death and was not cryopreserved.

Embryo space colonization

From Wikipedia, the free encyclopedia

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

 

8-cell embryo for transfer in in-vitro fertilization

Embryo space colonization is a theoretical interstellar space colonization concept that involves sending a robotic mission to a habitable terrestrial planet, dwarf planet, minor planet or natural satellite transporting frozen early-stage human embryos or the technological or biological means to create human embryos. The proposal circumvents the most severe technological problems of other mainstream interstellar colonization concepts. In contrast to the sleeper ship proposal, it does not require the more technically challenging 'freezing' of fully developed humans (see cryonics).

Various concepts

Embryo space colonization concepts involve various concepts of delivering the embryos from Earth to an extrasolar planet around another star system.

• The most straightforward concept is to make use of embryo cryopreservation. Modern medicine has made it possible to store frozen embryos in various low-development stages (up to several weeks into the development of the embryo).
• The technologically more challenging but more flexible scenario calls for just carrying the biological means to create embryos, that is various samples of donated sperm and egg cells.
• Self replicating machines could spread out to interstellar space, bring uploaded human minds with them and/or receive them via radio or laser transmission and build artificial electronic brains/bodies as needed. The uploaded humans can raise the children.

Mission at target planet

Regardless of the cargo used in any embryo space colonization scenario, the basic concept is that upon arrival of the embryo-carrying spacecraft (EIS) at the target planet, fully autonomous robots would build the first settlement on the planet and start growing food. More ambitiously, the planet may be terraformed first. Thereafter the first embryos could be unfrozen (or created using biosequenced or natural sperm and egg cells as outlined above).

In any event, one of the technologies needed for the proposal are artificial uteri. The embryos would need to develop in such artificial uteri until a large enough population existed to procreate by natural biological means.

Comparison to other interstellar colonization concepts

• Proposals of sleeper ships and generation ships require very large spacecraft to transport humans, life support systems and other equipment or food as well as an even larger propulsion system for a long period in time. Even optimistic proposals would require such a major effort for such ships that the resources required on Earth would involve a large part of mankind devoted to the mission or would even exceed available resources. In contrast, an EIS would have feasible small dimensions in the range of today's spacecraft, as the most important "cargo" would not need much space or weigh very much.
• Sleeper ship proposals call for freezing adult humans. While there is research into hibernation, the complexity of a living fully developed human body may make the sleeper ship proposals much more difficult.
• While sleeper ships and generation ships would deliver to a prospective colony world a population that has undergone some degree of education, training, and socialization in areas reconcilable with those of the sponsor culture (e.g. historical, scientific, and technical education, language acquisition, an understanding of the original mission and broader cultural norms), individuals who are born into colony worlds through embryo space colonization would initially lack this education.

Difficulties in implementing the concept

Artist's impression from 2005 of the planet HD 69830 d. Embryo space colonization depends on the existence of a habitable terrestrial exoplanet.

Like every proposal for interstellar colonization, embryo space colonization depends on solutions to still-unsolved technological problems. Some of these are:

• Robotics: Whether it will be possible to develop fully autonomous robots that can build the first settlement on the target planet and raise the first humans, is unclear. Because the initial probe must be maximally compact, the industrial robots that build the habitat would themselves have to be built autonomously from local materials. Though such technology does not yet exist, there are strong economic incentives to develop it, which are unrelated to space colonization.
• Artificial Intelligence: It would be challenging to create an artificial intelligence that could serve as an adequate artificial parent and successfully raise human children who have no contact with other human beings. Its design would have to include strategies for the transmission of terrestrial culture and language, as well as the prerequisites for healthy psychological functioning, to persons who cannot interact with Earth.
• Artificial Uterus: Artificial wombs exist today but they are not available for full-term development of fetuses. Human embryos have been successfully grown in artificial uteri for 13 days. There is a 14-day rule, codified into law in twelve countries, preventing human embryos from being kept in artificial uteri past 14 days.
• Long-duration computers: Computer hardware would need to function reliably over long periods of time, in the range of several thousands of years.
• Propulsion: Furthermore, a propulsion system would be required that could accelerate the EIS to a high speed and slow it down again upon nearing the destination. Even assuming a speed one hundred times faster than any of today's space probes and a target planet within a couple of hundred light years would lead to a journey lasting several thousand years.
• Exoplanet found: Finally this depends on the existence of an exoplanet qualifying for colonization within a reachable distance. Current or future science missions like the Hubble, James Webb, or TESS space telescopes may very well yield results for this requirement in the near future.

Further unknowns that affect the feasibility of embryo space colonization are:

• Biological: Will genetic material survive intact on a space mission that could potentially last centuries? Exposure to cosmic rays is known to irreparably damage DNA. What other symbiotic lifeforms does a human need to live a healthy life? For example, gut flora and many other species of microorganisms may be necessary for proper biological and immunological functioning. Babies normally acquire these from their mothers and the wider environment, but this would not be the case for embryos in colonization ships.
• Ethical: In addition to the question of whether it is technically feasible to raise children without human contact, there is the further question of whether this is morally permissible. It is found to be unethical to deliberately create children that will grow up without parents, yet embryo space colonization requires this. Controversial value judgments would also need to be made about whose DNA should be the basis of the space colony. Should they be selected by some metric of merit, or randomly from the general population? Either choice presents ethical problems. Should the parenting AI firmly steer the children to maximize the chances of the colony's success, or should it accept the risk of allowing them significant autonomy? Which languages and cultural values should be transmitted to the colonists? Should they be raised according to some value system that exists on Earth, or create one that is somehow optimized? Are there truths that should be kept from them? The possibility of a new civilization that starts without a cultural legacy might appeal to cults that want their values to become a norm for an entire society. Is it permissible to allow them have their own embryo colonies, where the AI indoctrinates the colonists only in the cult's value system? The difficulty of answering these and other ethical questions may become a non-technological obstacle to embryo space colonization.

 

Systematics

From Wikipedia, the free encyclopedia

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

A comparison of phylogenetic and phenetic (character-based) concepts

Biological systematics is the study of the diversification of living forms, both past and present, and the relationships among living things through time. Relationships are visualized as evolutionary trees (synonyms: cladograms, phylogenetic trees, phylogenies). Phylogenies have two components: branching order (showing group relationships) and branch length (showing amount of evolution). Phylogenetic trees of species and higher taxa are used to study the evolution of traits (e.g., anatomical or molecular characteristics) and the distribution of organisms (biogeography). Systematics, in other words, is used to understand the evolutionary history of life on Earth.

The word systematics is derived from Latin word `systema', which means systematic arrangement of organisms. Carl Linnaeus used 'Systema Naturae' as the title of his book.

Branches and applications

In the study of biological systematics, researchers use the different branches to further understand the relationships between differing organisms. These branches are used to determine the applications and uses for modern day systematics.

Biological systematics classifies species by using three specific branches. Numerical systematics, or biometry, uses biological statistics to identify and classify animals. Biochemical systematics classifies and identifies animals based on the analysis of the material that makes up the living part of a cell—such as the nucleus, organelles, and cytoplasm. Experimental systematics identifies and classifies animals based on the evolutionary units that comprise a species, as well as their importance in evolution itself. Factors such as mutations, genetic divergence, and hybridization all are considered evolutionary units.

With the specific branches, researchers are able to determine the applications and uses for modern-day systematics. These applications include:

• Studying the diversity of organisms and the differentiation between extinct and living creatures. Biologists study the well-understood relationships by making many different diagrams and "trees" (cladograms, phylogenetic trees, phylogenies, etc.).
• Including the scientific names of organisms, species descriptions and overviews, taxonomic orders, and classifications of evolutionary and organism histories.
• Explaining the biodiversity of the planet and its organisms. The systematic study is that of conservation.
• Manipulating and controlling the natural world. This includes the practice of 'biological control', the intentional introduction of natural predators and disease.

Definition and relation with taxonomy

John Lindley provided an early definition of systematics in 1830, although he wrote of "systematic botany" rather than using the term "systematics".

In 1970 Michener et al. defined "systematic biology" and "taxonomy" (terms that are often confused and used interchangeably) in relationship to one another as follows:

Systematic biology (hereafter called simply systematics) is the field that (a) provides scientific names for organisms, (b) describes them, (c) preserves collections of them, (d) provides classifications for the organisms, keys for their identification, and data on their distributions, (e) investigates their evolutionary histories, and (f) considers their environmental adaptations. This is a field with a long history that in recent years has experienced a notable renaissance, principally with respect to theoretical content. Part of the theoretical material has to do with evolutionary areas (topics e and f above), the rest relates especially to the problem of classification. Taxonomy is that part of Systematics concerned with topics (a) to (d) above.

The term "taxonomy" was coined by Augustin Pyramus de Candolle while the term "systematic" was coined by Carl Linnaeus the father of taxonomy.

Taxonomy, systematic biology, systematics, biosystematics, scientific classification, biological classification, phylogenetics: At various times in history, all these words have had overlapping, related meanings. However, in modern usage, they can all be considered synonyms of each other.

For example, Webster's 9th New Collegiate Dictionary of 1987 treats "classification", "taxonomy", and "systematics" as synonyms. According to this work, the terms originated in 1790, c. 1828, and in 1888 respectively. Some claim systematics alone deals specifically with relationships through time, and that it can be synonymous with phylogenetics, broadly dealing with the inferred hierarchy of organisms. This means it would be a subset of taxonomy as it is sometimes regarded, but the inverse is claimed by others.

Europeans tend to use the terms "systematics" and "biosystematics" for the study of biodiversity as a whole, whereas North Americans tend to use "taxonomy" more frequently. However, taxonomy, and in particular alpha taxonomy, is more specifically the identification, description, and naming (i.e. nomenclature) of organisms, while "classification" focuses on placing organisms within hierarchical groups that show their relationships to other organisms. All of these biological disciplines can deal with both extinct and extant organisms.

Systematics uses taxonomy as a primary tool in understanding, as nothing about an organism's relationships with other living things can be understood without it first being properly studied and described in sufficient detail to identify and classify it correctly. Scientific classifications are aids in recording and reporting information to other scientists and to laymen. The systematist, a scientist who specializes in systematics, must, therefore, be able to use existing classification systems, or at least know them well enough to skilfully justify not using them.

Phenetics was an attempt to determine the relationships of organisms through a measure of overall similarity, making no distinction between plesiomorphies (shared ancestral traits) and apomorphies (derived traits). From the late-20th century onwards, it was superseded by cladistics, which rejects plesiomorphies in attempting to resolve the phylogeny of Earth's various organisms through time. Today's systematists generally make extensive use of molecular biology and of computer programs to study organisms.

Taxonomic characters

Taxonomic characters are the taxonomic attributes that can be used to provide the evidence from which relationships (the phylogeny) between taxa are inferred. Kinds of taxonomic characters include:

Morphological characters General external morphology Special structures (e.g. genitalia) Internal morphology (anatomy) Embryology Karyology and other cytological factors Physiological characters Metabolic factors Body secretions Genic sterility factors Molecular characters Immunological distance Electrophoretic differences Amino acid sequences of proteins DNA hybridization DNA and RNA sequences Restriction endonuclease analyses Other molecular differences

Behavioral characters Courtship and other ethological isolating mechanisms Other behavior patterns Ecological characters Habit and habitats Food Seasonal variations Parasites and hosts Geographic characters General biogeographic distribution patterns Sympatric-allopatric relationship of populations

Artificial womb

From Wikipedia, the free encyclopedia

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

 

Artificial womb

Figure from a 2017 Nature Communications paper describing an extra-uterine life support system, or "biobag", used to grow lamb fetuses.

An artificial uterus or artificial womb is a device that would allow for extracorporeal pregnancy by growing a fetus outside the body of an organism that would normally carry the fetus to term.

An artificial uterus, as a replacement organ, would have many applications. It could be used to assist male or female couples in the development of a fetus. This can potentially be performed as a switch from a natural uterus to an artificial uterus, thereby moving the threshold of fetal viability to a much earlier stage of pregnancy. In this sense, it can be regarded as a neonatal incubator with very extended functions. It could also be used for the initiation of fetal development. An artificial uterus could also help make fetal surgery procedures at an early stage an option instead of having to postpone them until term of pregnancy.

In 2016, scientists published two studies regarding human embryos developing for thirteen days within an ecto-uterine environment. Currently, a 14-day rule prevents human embryos from being kept in artificial wombs longer than 14 days. This rule has been codified into law in twelve countries.

In 2017, fetal researchers at the Children's Hospital of Philadelphia published a study showing they had grown premature lamb fetuses for four weeks in an extra-uterine life support system.

Components

An artificial uterus, sometimes referred to as an 'exowomb', would have to provide nutrients and oxygen to nurture a fetus, as well as dispose of waste material. The scope of an artificial uterus (or "artificial uterus system" to emphasize a broader scope) may also include the interface serving the function otherwise provided by the placenta, an amniotic tank functioning as the amniotic sac, as well as an umbilical cord.

Nutrition, oxygen supply and waste disposal

A woman may still supply nutrients and dispose of waste products if the artificial uterus is connected to her. She may also provide immune protection against diseases by passing of IgG antibodies to the embryo or fetus.

Artificial supply and disposal have the potential advantage of allowing the fetus to develop in an environment that is not influenced by the presence of disease, environmental pollutants, alcohol, or drugs which a human may have in the circulatory system. There is no risk of an immune reaction towards the embryo or fetus that could otherwise arise from insufficient gestational immune tolerance. Some individual functions of an artificial supplier and disposer include:

• Waste disposal may be performed through dialysis.
• For oxygenation of the embryo or fetus, and removal of carbon dioxide, extracorporeal membrane oxygenation (ECMO) is a functioning technique, having successfully kept goat fetuses alive for up to 237 hours in amniotic tanks. ECMO is currently a technique used in selected neonatal intensive care units to treat term infants with selected medical problems that result in the infant's inability to survive through gas exchange using the lungs. However, the cerebral vasculature and germinal matrix are poorly developed in fetuses, and subsequently, there is an unacceptably high risk for intraventricular hemorrhage (IVH) if administering ECMO at a gestational age less than 32 weeks. Liquid ventilation has been suggested as an alternative method of oxygenation, or at least providing an intermediate stage between the womb and breathing in open air.
• For artificial nutrition, current techniques are problematic. Total parenteral nutrition, as studied on infants with severe short bowel syndrome, has a 5-year survival of approximately 20%.
• Issues related to hormonal stability also remain to be addressed.

Theoretically, animal suppliers and disposers may be used, but when involving an animal's uterus the technique may rather be in the scope of interspecific pregnancy.

Uterine wall

In a normal uterus, the myometrium of the uterine wall functions to expel the fetus at the end of a pregnancy, and the endometrium plays a role in forming the placenta. An artificial uterus may include components of equivalent function. Methods have been considered to connect an artificial placenta and other "inner" components directly to an external circulation.

Interface (artificial placenta)

An interface between the supplier and the embryo or fetus may be entirely artificial, e.g. by using one or more semipermeable membranes such as is used in extracorporeal membrane oxygenation (ECMO).

There is also potential to grow a placenta using human endometrial cells. In 2002, it was announced that tissue samples from cultured endometrial cells removed from a human donor had successfully grown. The tissue sample was then engineered to form the shape of a natural uterus, and human embryos were then implanted into the tissue. The embryos correctly implanted into the artificial uterus' lining and started to grow. However, the experiments were halted after six days to stay within the permitted legal limits of in vitro fertilisation (IVF) legislation in the United States.

A human placenta may theoretically be transplanted inside an artificial uterus, but the passage of nutrients across this artificial uterus remains an unsolved issue.

Amniotic tank (artificial amniotic sac)

The main function of an amniotic tank would be to fill the function of the amniotic sac in physically protecting the embryo or fetus, optimally allowing it to move freely. It should also be able to maintain an optimal temperature. Lactated Ringer's solution can be used as a substitute for amniotic fluid.

Umbilical cord

Theoretically, in case of premature removal of the fetus from the natural uterus, the natural umbilical cord could be used, kept open either by medical inhibition of physiological occlusion, by anti-coagulation as well as by stenting or creating a bypass for sustaining blood flow between the mother and fetus.

Research and development

Emanuel M. Greenberg

Emanuel M. Greenberg wrote various papers on the topic of the artificial womb and its potential use in the future.

On 22 July 1954 Emanuel M. Greenberg filed a patent on the design for an artificial womb. The patent included two images of the design for an artificial womb. The design itself included a tank to place the fetus filled with amniotic fluid, a machine connecting to the umbilical cord, blood pumps, an artificial kidney, and a water heater. He was granted the patent on 15 November 1955.

On 11 May 1960, Greenberg wrote to the editors of the American Journal of Obstetrics and Gynecology. Greenberg claimed that the journal had published the article "Attempts to Make an 'Artificial Uterus'", which failed to include any citations on the topic of the artificial uterus. According to Greenberg, this suggested that the idea of the artificial uterus was a new one although he himself had published several papers on the topic.

Juntendo University in Tokyo

In 1996, Juntendo University in Tokyo developed the extra-uterine fetal incubation (EUFI). The project was led by Yoshinori Kuwabara, who was interested in the development of immature newborns. The system was developed using fourteen goat fetuses that were then placed into artificial amniotic fluid under the same conditions of a mother goat. Kuwabara and his team succeeded in keeping the goat fetuses in the system for three weeks. The system, however, ran into several problems and was not ready for human testing. Kuwabara remained hopeful that the system would be improved and would later be used on human fetuses.

Children's Hospital of Philadelphia

In 2017, researchers at the Children's Hospital of Philadelphia were able to further develop the extra-uterine system. The study uses fetal lambs which are then placed in a plastic bag filled with artificial amniotic fluid. The system consist in 3 main components: a pumpless arteriovenous circuit, a closed sterile fluid environment and an umbilical vascular access. Regarding the pumpless arteriovenous circuit, the blood flow is driven exclusively by the fetal heart, combined with a very low resistance oxygenator to most closely mimic the normal fetal/placental circulation. The closed sterile fluid environment is important to ensure sterility. Scientists developed a technique for umbilical cord vessel cannulation that maintains a length of native umbilical cord (5–10 cm) between the cannula tips and the abdominal wall, to minimize decannulation events and the risk of mechanical obstruction. The umbilical cord of the lambs are attached to a machine outside of the bag designed to act like a placenta and provide oxygen and nutrients and also remove any waste. The researchers kept the machine "in a dark, warm room where researchers can play the sounds of the mother's heart for the lamb fetus." The system succeeded in helping the premature lamb fetuses develop normally for a month. Indeed, scientists have run 8 lambs with maintenance of stable levels of circuit flow equivalent to the normal flow to the placenta. Specifically, they have run 5 fetuses from 105 to 108 days of gestation for 25–28 days, and 3 fetuses from 115 to 120 days of gestation for 20–28 days. The longest runs were terminated at 28 days due to animal protocol limitations rather than any instability, suggesting that support of these early gestational animals could be maintained beyond 4 weeks. Alan Flake, a fetal surgeon at the Children's Hospital of Philadelphia hopes to move testing to premature human fetuses, but this could take anywhere from three to five years to become a reality. Flake, who led the study, calls the possibility of their technology recreating a full pregnancy a "pipe dream at this point" and does not personally intend to create the technology to do so.

Eindhoven University of Technology (NL)

Since 2016, researchers of TU/e and partners aim to develop an artificial womb, which is an adequate substitute for the protective environment of the maternal womb in case of premature birth, preventing health complications. The artificial womb and placenta will provide a natural environment for the baby with the goal to ease the transition to newborn life. The perinatal life support (PLS) system will be developed using breakthrough technology: a manikin will mimic the infant during testing and training, advanced monitoring and computational modeling will provide clinical guidance.

The consortium of 3 European universities working on the project consists out of Aachen, Milaan and Eindhoven. In 2019 this consortium was granted a subsidy of 3 million euro, and a second grant of 10 M is in progress. Together, the PLS partners provide joint medical, engineering, and mathematical expertise to develop and validate the Perinatal Life Support system using breakthrough simulation technologies. The interdisciplinary consortium will push the development of these technologies forward and combine them to establish the first ex vivo fetal maturation system for clinical use. This project, coordinated by the Eindhoven University of Technology brings together world-leading experts in obstetrics, neonatology, industrial design, mathematical modelling, ex vivo organ support, and non-invasive fetal monitoring. This consortium is led by professor Frans van de Vosse and Professor and doctor Guid Oei. in 2020 the spin off Juno Perinatal Healthcare has been set up by engineers Jasmijn Kok and Lyla Kok, assuring valorisation of the research done.

Philosophical considerations

Bioethics

The development of artificial uteri and ectogenesis raises bioethical and legal considerations, and also has important implications for reproductive rights and the abortion debate.

Artificial uteri may expand the range of fetal viability, raising questions about the role that fetal viability plays within abortion law. Within severance theory, for example, abortion rights only include the right to remove the fetus, and do not always extend to the termination of the fetus. If transferring the fetus from a woman's womb to an artificial uterus is possible, the choice to terminate a pregnancy in this way could provide an alternative to aborting the fetus.

There are also theoretical concerns that children who develop in an artificial uterus may lack "some essential bond with their mothers that other children have".

Gender equality and LGBT

In the 1970 book The Dialectic of Sex, feminist Shulamith Firestone wrote that differences in biological reproductive roles are a source of gender inequality. Firestone singled out pregnancy and childbirth, making the argument that an artificial womb would free "women from the tyranny of their reproductive biology."

Arathi Prasad argues in her column on The Guardian in her article "How artificial wombs will change our ideas of gender, family and equality" that "It will [...] give men an essential tool to have a child entirely without a woman, should they choose. It will ask us to question concepts of gender and parenthood." She furthermore argues for the benefits for same-sex couples: "It might also mean that the divide between mother and father can be dispensed with: a womb outside a woman’s body would serve women, trans women and male same-sex couples equally without prejudice."

See also

• Amniotic fluid
• Apheresis
• Ectogenesis
• Embryo space colonization
• Extracorporeal membrane oxygenation
• Hemodialysis
• In vitro fertilisation
• Male pregnancy
• Postgenderism
• Tissue engineering