The use of adult stem cells in research and therapy is not as  controversial  as the use of  embryonic stem cells , because the production of adult stem cells does not require the destruction of an  embryo . Additionally, in instances where adult stem cells are obtained from the intended recipient (an  autograft ), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research. [ 61 ]


With the increasing demand of human adult stem cells for both research and clinical purposes (typically 1–5 million cells per kg of body weight are required per treatment) it becomes of utmost importance to bridge the gap between the need to expand the cells in vitro and the capability of harnessing the factors underlying replicative senescence. Adult stem cells are known to have a limited lifespan in vitro and to enter replicative senescence almost undetectably upon starting in vitro culturing. [ 62 ]


Hematopoietic stem cells  (HSCs) are vulnerable to  DNA damage  and  mutations  that increase with age. [ 63 ]  This vulnerability may explain the increased risk of slow growing blood cancers (myeloid malignancies) in the elderly. [ 63 ]   Several factors appear to influence HSC aging including responses to the production of  reactive oxygen species  that may cause DNA damage and genetic mutations as well as altered  epigenetic  profiling. [ 64 ]


Also called perinatal stem cells, these multipotent stem cells are found in  amniotic fluid  and umbilical cord blood. These stem cells are very active, expand extensively without feeders and are not tumorigenic.  Amniotic stem cells  are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines. [ 65 ]
Amniotic stem cells are a topic of active research.


Use of stem cells from  amniotic fluid  overcomes the ethical objections to using human embryos as a source of cells.  Roman Catholic  teaching forbids the use of embryonic stem cells in experimentation; accordingly, the  Vatican  newspaper " Osservatore Romano " called amniotic stem cells "the future of medicine". [ 66 ]


It is possible to collect amniotic stem cells for donors or for autologous use: the first US amniotic stem cells bank [ 67 ] [ 68 ]  was opened in 2009 in Medford, MA, by  Biocell Center  Corporation [ 69 ] [ 70 ] [ 71 ]  and collaborates with various hospitals and universities all over the world. [ 72 ]


Adult stem cells have limitations with their potency; unlike  embryonic stem cells  (ESCs), they are not able to differentiate into cells from all three  germ layers . As such, they are deemed  multipotent .


However,  reprogramming  allows for the creation of pluripotent cells,  induced pluripotent stem cells  (iPSCs), from adult cells. These are not adult stem cells, but somatic cells (e.g. epithelial cells) reprogrammed to give rise to cells with pluripotent capabilities. Using genetic reprogramming with protein  transcription factors , pluripotent stem cells with ESC-like capabilities have been derived. [ 73 ] [ 74 ] [ 75 ]  The first demonstration of induced pluripotent stem cells was conducted by  Shinya Yamanaka  and his colleagues at  Kyoto University . [ 76 ]  They used the transcription factors  Oct3/4 ,  Sox2 ,  c-Myc , and  Klf4  to reprogram mouse fibroblast cells into pluripotent cells. [ 73 ] [ 77 ]  Subsequent work used these factors to induce pluripotency in human fibroblast cells. [ 78 ]   Junying Yu ,  James Thomson , and their colleagues at the  University of Wisconsin–Madison  used a different set of factors, Oct4, Sox2, Nanog and Lin28, and carried out their experiments using cells from human  foreskin . [ 73 ] [ 79 ]  However, they were able to replicate  Yamanaka 's finding that inducing pluripotency in human cells was possible.


Induced pluripotent stem cells differ from embryonic stem cells. They share many similar properties, such as  pluripotency  and differentiation potential, the expression of  pluripotency  genes,  epigenetic  patterns,  embryoid body  and  teratoma  formation, and viable  chimera  formation, [ 76 ] [ 77 ]  but there are many differences within these properties. The chromatin of iPSCs appears to be more "closed" or methylated than that of ESCs. [ 76 ] [ 77 ]  Similarly, the gene expression pattern between ESCs and iPSCs, or even iPSCs sourced from different origins. [ 76 ]  There are thus questions about the "completeness" of  reprogramming  and the somatic memory of induced pluripotent stem cells. Despite this, inducing somatic cells to be pluripotent appears to be viable.


As a result of the success of these experiments,  Ian Wilmut , who helped create the first cloned animal  Dolly the Sheep , has announced that he will abandon  somatic cell nuclear transfer  as an avenue of research. [ 80 ]


The ability to induce pluripotency benefits developments in  tissue engineering . By providing a suitable scaffold and microenvironment, iPSC can be differentiated into cells of therapeutic application, and for  in vitro  models to study toxins and pathogenesis. [ 81 ]


Induced pluripotent stem cells provide several therapeutic advantages. Like ESCs, they are  pluripotent . They thus have great differentiation potential; theoretically, they could produce any cell within the human body (if  reprogramming  to pluripotency was "complete"). [ 76 ]  Moreover, unlike ESCs, they potentially could allow doctors to create a pluripotent stem cell line for each individual patient. [ 82 ]  Frozen blood samples can be used as a valuable source of induced pluripotent stem cells. [ 83 ]   Patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection. [ 82 ]  Despite their current limited use therapeutically, iPSCs hold great potential for future use in medical treatment and research.


The key factors controlling the cell cycle also regulate  pluripotency . Thus, manipulation of relevant genes can maintain pluripotency and reprogram somatic cells to an induced pluripotent state. [ 39 ]  However, reprogramming of somatic cells is often low in efficiency and considered  stochastic . [ 84 ]


With the idea that a more rapid cell cycle is a key component of pluripotency, reprogramming efficiency can be improved. Methods for improving pluripotency through manipulation of cell cycle regulators include: overexpression of Cyclin D/Cdk4, phosphorylation of  Sox2  at S39 and S253, overexpression of Cyclin A and Cyclin E, knockdown of Rb, and knockdown of members of the  Cip/Kip  family or the Ink family. [ 39 ]  Furthermore, reprogramming efficiency is correlated with the number of cell divisions happened during the stochastic phase, which is suggested by the growing inefficiency of reprogramming of older or slow diving cells. [ 85 ]


Lineage is an important procedure to analyze developing embryos. Since cell lineages shows the relationship between cells at each division. This helps in analyzing stem cell lineages along the way which helps recognize stem cell effectiveness, lifespan, and other factors. With the technique of cell lineage mutant genes can be analyzed in stem cell clones that can help in genetic pathways. These pathways can regulate how the stem cell perform. [ 86 ]


To ensure self-renewal, stem cells undergo two types of cell division (see  Stem cell division and differentiation  diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a  progenitor cell  with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally  differentiating  into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as  receptors ) between the daughter cells. [ 87 ]


An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular  niche . Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in  Drosophila  germarium have identified the signals  decapentaplegic  and adherens junctions that prevent germarium stem cells from differentiating. [ 88 ] [ 89 ]


In the United States, Executive Order 13505 established that federal money can be used for research in which approved human embryonic stem-cell (hESC) lines are used, but it cannot be used to derive new lines. [ 90 ]  The National Institutes of Health (NIH) Guidelines on Human Stem Cell Research, effective July 7, 2009, implemented the Executive Order 13505 by establishing criteria which hESC lines must meet to be approved for funding. [ 91 ]  The NIH Human Embryonic Stem Cell Registry can be accessed online and has updated information on cell lines eligible for NIH funding. [ 92 ]   There are 486 approved lines as of January 2022. [ 93 ]


Stem cell therapy is the use of stem cells to treat or prevent a disease or condition.  Bone marrow transplant  is a form of stem cell therapy that has been used for many years because it has proven to be effective in clinical trials. [ 94 ] [ 95 ]  Stem cell implantation may help in strengthening the left-ventricle of the heart, as well as retaining the heart tissue to patients who have suffered from heart attacks in the past. [ 96 ]


For over 90 years,  hematopoietic stem cell transplantation  (HSCT) has been used to treat people with conditions such as  leukaemia  and  lymphoma ; this is the only widely practiced form of stem-cell therapy. [ 94 ] [ 97 ] [ 98 ]  As of 2016 [update] , the only established therapy using stem cells is  hematopoietic stem cell transplantation . [ 99 ]  This usually takes the form of a  bone-marrow  transplantation, but the cells can also be derived from  umbilical cord blood . Research is underway to develop various sources for stem cells as well as to apply stem-cell treatments for  neurodegenerative diseases [ 100 ] [ 101 ] [ 102 ]  and conditions such as  diabetes  and  heart disease .


Stem cell treatments may lower symptoms of the disease or condition that is being treated. The lowering of symptoms may allow patients to reduce the drug intake of the disease or condition. Stem cell treatment may also provide knowledge for society to further stem cell understanding and future treatments. [ 103 ]  The physicians' creed would be to do no injury, and stem cells make that simpler than ever before. Surgical processes by their character are harmful. Tissue has to be dropped as a way to reach a successful outcome. One may prevent the dangers of surgical interventions using stem cells. Additionally, there's a possibility of disease, and whether the procedure fails, further surgery may be required. Risks associated with anesthesia can also be eliminated with stem cells. [ 104 ]  On top of that, stem cells have been harvested from the patient's body and redeployed in which they're wanted. Since they come from the patient's own body, this is referred to as an autologous treatment. Autologous remedies are thought to be the safest because there's likely zero probability of donor substance rejection.


Stem cell treatments may require  immunosuppression  because of a requirement for radiation before the transplant to remove the person's previous cells, or because the patient's immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated.


Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types. [ 105 ]


Some stem cells form tumors after transplantation; [ 106 ]  pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency. [ 107 ]


Ethical concerns are also raised about the practice of using or researching embryonic stem cells. Harvesting cells from the blastocyst results in the death of the blastocyst. The concern is whether or not the blastocyst should be considered as a human life. [ 108 ]  The debate on this issue is mainly a philosophical one, not a scientific one.


Stem cell tourism is the part of the  medical tourism  industry in which patients  travel to  obtain stem cell procedures. [ 109 ]


The United States  has had an explosion of "stem cell clinics". [ 110 ]   Stem cell procedures are highly profitable for clinics.  The advertising sounds authoritative but the efficacy and safety of the procedures is unproven.  Patients sometimes experience complications, such as spinal tumors [ 111 ]  and death. The high expense can also lead to financial problems. [ 111 ]  According to researchers, there is a need to educate the public, patients, and doctors about this issue. [ 112 ]


According to the  International Society for Stem Cell Research , the largest academic organization that advocates for stem cell research, stem cell therapies are under development and cannot yet be said to be proven. [ 113 ] [ 114 ]  Doctors should inform patients that clinical trials continue to investigate whether these therapies are safe and effective but that unethical clinics present them as proven. [ 115 ]


Some of the fundamental  patents  covering human embryonic stem cells are owned by the  Wisconsin Alumni Research Foundation  (WARF) – they are patents 5,843,780, 6,200,806, and 7,029,913 invented by  James A. Thomson . WARF does not enforce these patents against academic scientists, but does enforce them against companies. [ 116 ]


In 2006, a request for the  US Patent and Trademark Office  (USPTO) to re-examine the three patents was filed by the Public Patent Foundation [ 117 ]  on behalf of its client, the non-profit patent-watchdog group  Consumer Watchdog  (formerly the Foundation for Taxpayer and Consumer Rights). [ 116 ]    In the re-examination process, which involves several rounds of discussion between the USPTO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents, [ 118 ]  however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not. [ 119 ] [ 120 ]  Consumer Watchdog appealed the granting of the '913 patent to the USPTO's Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the '913 patent were not patentable. [ 121 ]  However, WARF was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in January 2013 the amended claims were allowed. [ 122 ]


In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the US  Court of Appeals for the Federal Circuit  (CAFC), the federal appeals court that hears patent cases. [ 123 ]  At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had  legal standing  to appeal; the case could not proceed until that issue was resolved. [ 124 ]


Diseases and conditions where stem cell treatment is being investigated include:


Research is underway to develop various sources for stem cells. [ 147 ]


Research is attempting to generating  organoids  using stem cells, which would allow for further understanding of human development,  organogenesis , and modeling of human diseases. [ 148 ]  Engineered ‘synthetic organizer’ (SO) cells can instruct stem cells to grow into specific tissues and organs. The program used native and synthetic  cell adhesion protein molecules  (CAMs) that help make cells sticky. The organizer cells self-assembled around mouse ESCs. These cells were engineered to produce  morphogens  (signaling molecules) that direct cellular development based on their concentration. Delivered morphogens disperse, leaving higher concentrations closer to the source and lower concentrations further away. These gradients signal cells' ultimate roles, such as nerve, skin cell, or connective tissue. The engineered organizer cells were also fitted with a chemical switch that enabled the researchers to turn the delivery of cellular instructions on and off, as well as a ‘suicide switch’ for eliminating the cells when needed. SOs carry spatial and biochemical information,  allowing considerable discretion in organoid formation. [ 149 ]


Hepatotoxicity  and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the  drug development  process. [ 150 ]


In August 2021, researchers in the  Princess Margaret Cancer Centre  at the  University Health Network  published their discovery of a dormancy mechanism in key stem cells which could help develop cancer treatments in the future. [ 151 ]


This is a  list of countries by  stem cell  research trials  for the purpose of commercializing treatments as of June 2020, using data from  ClinicalTrials.gov . [ 1 ]


George Streisinger  (December 27, 1927 – August 11, 1984) was an American molecular biologist and co-founder of the Institute of Molecular Biology at the  University of Oregon . [ 1 ]  He was the first person to clone a vertebrate, cloning  zebrafish  in his University of Oregon laboratory. [ 2 ]  He also pioneered work in the genetics of the T-even bacterial viruses. In 1972, along with William Franklin Dove he was awarded a  Guggenheim Fellowship  award, and in 1975 he was selected as a member of the  National Academy of Sciences , making him the second Oregonian to receive the distinction. [ 3 ]  The University of Oregon's Institute of Molecular Biology named their main building "Streisinger Hall" in his honor. [ 4 ]


George Streisinger was born in  Budapest ,  Hungary , on December 27, 1927. Because they were Jewish, in 1937, his family left Budapest for New York to escape Nazi persecution. Streisinger attended New York public schools and graduated from the  Bronx High School of Science  in 1944. He obtained a B.S. degree from  Cornell University  in 1950, and a Ph.D. from the University of Illinois in 1953. He completed postdoctoral studies at the California Institute of Technology from 1953 to 1956. He married Lotte Sielman in 1949. Streisinger accepted a post at the University of Oregon Institute of Molecular Biology in Eugene in 1960. Streisinger was well known as an innovative professor in and out of the classroom, conscripting a dance class to illustrate protein synthesis, and often requested beginning and non-major biology students. He was very politically active, organizing grass-roots resistance to the Vietnam war and legislative opposition to  John Kennedy's civil defense program . He testified to successfully ban mutagenic herbicides in  Douglas fir  reforestation, and led and won a battle to exclude secret war department research from the University of Oregon campus.


His wife, Lotte, was a noted artist and community activist, and the founder of the  Eugene Saturday Market , the inspiration for the Portland Oregon Saturday Market. [ 5 ] [ 6 ]


Following his graduation from Cornell, George under- took graduate studies in the genetics of T-even coliphage with  Salvador Luria  in the Bacteriology Department of the University of Illinois.  His studies revealed phenotypic mixing, in which a phage with a host-range genotype of one phage type was found in a particle who was phenotypically dissimilar. When published in 1956, these studies had profound impact on the study of viral biology.
During his postdoc at Caltech, with  Jean Weigle , he undertook further studies on T2 × T4 hybrids, which led to the discovery of DNA modification (by glucosylation).
At the University of Oregon, Streisinger pioneered the study of zebrafish in his lab. Zebrafish can be genetically modified easily, and researchers can modify them to mimic the traits of certain diseases. In analyzing these created diseases, scientists seek solutions to diseases which affect humans. Over 9,000 researchers [ 7 ]  in 1,551 labs [ 8 ]  throughout 31 countries study  zebrafish , and many of them received their initial training at the University of Oregon. [ 9 ]


In  molecular biology ,  subcloning  is a technique used to move a particular DNA sequence from a  parent  vector  to a  destination vector .


Subcloning is not to be confused with  molecular cloning , a related technique.


Restriction enzymes  are used to excise the gene of interest (the  insert ) from the parent.  The insert is purified in order to isolate it from other DNA molecules.  A common purification method is  gel isolation .  The number of copies of the gene is then amplified using  polymerase chain reaction  (PCR).


Simultaneously, the same  restriction enzymes  are used to digest (cut) the destination.  The idea behind using the same restriction enzymes is to create  complementary   sticky ends , which will facilitate  ligation  later on.  A  phosphatase , commonly  calf-intestinal alkaline phosphatase  (CIAP), is also added to prevent self-ligation of the destination vector.  The digested destination vector is isolated/purified.


The insert and the destination vector are then mixed together with DNA ligase.  A typical molar ratio of insert genes to destination vectors is 3:1; [ 1 ]  by increasing the insert concentration, self-ligation is further decreased.  After letting the reaction mixture sit for a set amount of time at a specific temperature (dependent upon the size of the strands being ligated; for more information see  DNA ligase ), the insert should become successfully incorporated into the destination  plasmid .


The plasmid is often  transformed  into a  bacterium  like  E. coli . Ideally when the bacterium  divides  the plasmid should also be replicated.  In the best case scenario, each bacterial cell should have several copies of the plasmid.  After a good number of bacterial colonies have grown, they can be  miniprepped  to harvest the plasmid DNA.


In order to ensure growth of only transformed bacteria (which carry the desired plasmids to be harvested), a  marker gene  is used in the destination vector for  selection .  Typical marker genes are for  antibiotic resistance  or nutrient  biosynthesis . So, for example, the "marker gene" could be for resistance to the antibiotic ampicillin. If the bacteria that were supposed to pick up the desired plasmid had picked up the desired gene then they would also contain the "marker gene". Now the bacteria that picked up the plasmid would be able to grow in ampicillin whereas the bacteria that did not pick up the desired plasmid would still be vulnerable to destruction by the ampicillin. Therefore, successfully transformed bacteria would be "selected."


In this example, a gene from mammalian gene library will be subcloned into a bacterial plasmid (destination platform).  The bacterial plasmid is a piece of circular DNA which contains regulatory elements allowing for the bacteria to produce a gene product ( gene expression ) if it is placed in the correct place in the plasmid.  The production site is flanked by two restriction enzyme cutting sites "A" and "B" with incompatible sticky ends.


The mammalian DNA does not come with these restriction sites, so they are built in by  overlap extension PCR .  The primers are designed to put the restriction sites carefully, so that the coding of the protein is in-frame, and a minimum of extra amino acids is implanted on either side of the protein.


Both the PCR product containing the mammalian gene with the new restriction sites and the destination plasmid are subjected to restriction digestion, and the digest products are purified by  gel electrophoresis .


The digest products, now containing compatible sticky ends with each other (but incompatible sticky ends with themselves) are subjected to ligation, creating a new plasmid which contains the background elements of the original plasmid with a different insert.


The plasmid is  transformed  into bacteria and the identity of the insert is confirmed by  DNA sequencing .


The  T7 expression system  is used in the field of  microbiology  to clone  recombinant DNA  using strains of  E. coli . [ 1 ]  It is the most popular system for expressing recombinant proteins in E. coli. [ 2 ]


By 2021, this system had been described in over 220,000 research publications. [ 3 ]


The sequencing and annotating of the genome of the T7 bacteriophage took place in the 1980s at the  U.S. Department of Energy 's  Brookhaven National Laboratory , under the senior biophysicist  F. William Studier . Soon, the lab was able to clone the  T7 RNA polymerase  and use it, along with the powerful T7 promoter, to transcribe copious amounts of almost any gene. [ 4 ]  The development of the T7 expression system has been considered the most successful biotechnology developed at the Brookhaven National Laboratory, being licensed by over 900 companies which has generated over $55 million for the lab. [ 5 ]


An expression vector, most commonly the pET expression vector, is engineered to integrate two essential components: a T7 promoter and a gene of interest downstream of the  promoter  and under its control. The expression vector is  transformed  into one of several relevant strains of E. coli, most frequently BL21(DE3). The E. coli cell also has its own chromosome, which possesses a gene that is expressed to produce  T7 RNA polymerase . (This polymerase originates from the  T7 phage , a  bacteriophage   virus  which infects E. coli bacterial cells and is capable of integrating its DNA into the host DNA, as well as overriding its cellular machinery to produce more copies of itself.) T7 RNA polymerase is responsible for beginning transcription at the T7 promoter of the transformed vector. The T7 gene is itself under the control of a lac promoter. Normally, both the lac promoter and the T7 promoter are repressed in the E. coli cell by the  Lac repressor . In order to initiate transcription, an  inducer  must bind to the lac repressor and prevent it from inhibiting the gene expression of the T7 gene. Once this happens, the gene can be normally transcribed to produce T7 RNA polymerase. T7 RNA polymerase, in turn, can bind to the T7 promoter on the expression vector and begin transcribing its downstream gene of interest. To stimulate this process, the inducer  IPTG  can be added to the system. IPTG is a reagent which mimics the structure of  allolactose , and can therefore bind to the lac repressor and prevent it from inhibiting gene expression. Once enough IPTG is added, the T7 gene is normally transcribed and so transcription of the gene of interest downstream of the T7 promoter also begins. [ 6 ]  Expression of a recombinant protein under the control of the T7 promoter is 8x faster than protein expression under the control of E. coli RNA polymerase. [ 7 ]  Basal levels of expression of T7 RNA polymerase in the cell are also inhibited by the bacteriophage T7 lysozyme, which results in a delay of the accumulation of T7 RNA polymerase until after lysozymic activity is saturated. [ 8 ]


During the  COVID-19 pandemic ,  mRNA vaccines  have been developed by  Moderna  and  Pfizer  to combat the spread of the virus. Both Moderna and Pfizer have relied on the T7 expression system to generate the large quantities of mRNA needed to manufacture the vaccines. [ 9 ] [ 4 ]


TA cloning  (also known as  rapid cloning  or  T cloning ) is a  subcloning  technique that avoids the use of  restriction enzymes [ 1 ]  and is easier and quicker than traditional subcloning. The technique relies on the ability of  adenine  (A) and  thymine  (T) (complementary basepairs) on different DNA fragments to hybridize and, in the presence of  ligase , become ligated together.  PCR  products are usually amplified using  Taq DNA polymerase  which preferentially adds an adenine to the 3' end of the product. Such PCR amplified inserts are cloned into linearized  vectors  that have complementary 3'  thymine  overhangs. [ 2 ]


The insert is created by PCR using  Taq polymerase . This polymerase lacks 3' to 5' proofreading activity and, with a high probability, adds a single, 3'- adenine  overhang to each end of the PCR product. It is best if the PCR primers have  guanines  at the 5' end as this maximizes probability of Taq DNA polymerase adding the terminal adenosine overhang. [ 3 ]  Thermostable polymerases containing extensive 3´ to 5´ exonuclease activity should not be used as they do not leave the 3´ adenine-overhangs. [ 4 ]


The target vector is linearized and cut with a blunt-end restriction enzyme. This vector is then tailed with dideoxythymidine triphosphate (ddTTP) using  terminal transferase . It is important to use ddTTP to ensure the addition of only one T residue. This tailing leaves the vector with a single 3'-overhanging thymine residue on each blunt end. [ 5 ]  Manufacturers commonly sell TA Cloning "kits" with a wide range of prepared vectors that have already been linearized and tagged with an overhanging thymine.


Given that there is no need for restriction enzymes other than for generating the linearized vector, the procedure is much simpler and faster than traditional  subcloning . There is also no need to add restriction sites when designing primers and thus shorter primers can be used saving time and money. In addition, in instances where there are no viable restriction sites that can be used for traditional cloning, TA cloning is often used as an alternative. The major downside of TA cloning is that directional cloning is not possible, so the gene has a 50% chance of getting cloned in the reverse direction. [ 1 ]


The  teletransportation paradox  or  teletransport paradox  (also known in alternative forms as the  duplicates paradox ) is a  thought experiment  on the  philosophy of identity  that challenges common intuitions on the nature of  self  and  consciousness , formulated by  Derek Parfit  in his 1984 book  Reasons and Persons . [ 1 ]


The Polish science-fiction writer  Stanisław Lem  described the same problem in the mid-twentieth century. He put it in writing in his philosophical text  Dialogs  in 1957. Similarly, in Lem's  Star Diaries   ("Fourteenth Voyage") of 1957, the hero visits a planet and finds himself recreated from a backup record, after his death from a meteorite strike, which on this planet is a very commonplace procedure. In chapter 6 of his later discursive book " Summa Technologiae ", first published in 1964, he discussed in detail the identity paradoxes associated with teleportation and hibernation of human beings.


Similar questions of identity have been raised as early as 1775.


I would be glad to know your Lordship's opinion whether when my brain has lost its original structure, and when some hundred years after the same materials are fabricated so curiously as to become an intelligent being, whether, I say that being will be me; or, if, two or three such beings should be formed out of my brain; whether they will all be me, and consequently one and the same intelligent being.


Derek Parfit and others consider a hypothetical "teletransporter", a machine that puts you to sleep, records your molecular composition, breaking you down into atoms, and relaying its recording to Mars at the speed of light.  On Mars, another machine re-creates you (from local stores of carbon, hydrogen, and so on), each atom in exactly the same relative position.  Parfit poses the question of whether or not the teletransporter is actually a method of travel, or if it simply kills and makes an exact replica of the user. [ 3 ]


Then the teleporter is upgraded. The teletransporter on Earth is modified to not destroy the person who enters it, but instead it can simply make infinite replicas, all of whom would claim to remember entering the teletransporter on Earth in the first place.


Using thought experiments such as these, Parfit argues that any criteria we attempt to use to determine sameness of person will be lacking, because there is no further fact.  What matters, to Parfit, is simply "Relation R", psychological connectedness, including memory, personality, and so on. [ 4 ]


Parfit continues this logic to establish a new context for morality and social control. He cites that it is morally wrong for one person to harm or interfere with another person and it is incumbent on society to protect individuals from such transgressions. That accepted, it is a short extrapolation to conclude that it is also incumbent on society to protect an individual's "Future Self" from such transgressions; tobacco use could be classified as an abuse of a Future Self's right to a healthy existence. Parfit resolves the logic to reach this conclusion, which appears to justify incursion into personal freedoms, but he does not explicitly endorse such invasive control. [ citation needed ]


Parfit's conclusion is similar to  David Hume's view  and also to the view of the self in some forms of  Buddhism , though it does not restrict itself to a mere reformulation of them. For besides being  reductive , Parfit's view is also  deflationary : in the end, "what matters" is not personal identity, but rather mental continuity and connectedness. [ citation needed ]


The  Tianjin animal cloning center  was planned in 2015 and "to be put into use in the first half of 2016" [ 1 ]  in the  Tianjin Economic-Technological Development Area  of  Tianjin , China,  [ 2 ]  but as of 2022, no opening has been reported.


The factory was announced to be developed by Sinica, a subsidiary of the Chinese company Boyalife, along with the Institute of Molecular Medicine at   Peking University , the Tianjin International Joint Academy of Biomedicine, and the  Sooam Bioengineering Research Institute  in South Korea. [ 1 ]


The 14,000-square-metre facility would have hosted a laboratory, a cloning center, a gene bank, and educational exhibits for the public. [ 2 ]  The consortium planned to spend 200 million RMB (US$31 million) to produce 100,000 cloned cattle per year for China's rapidly growing beef market, and then expand to one million cattle per year [ 3 ] [ 1 ]  (China planned to buy one million head of cattle from Australia in 2016 at a cost of US$2 billion [ 4 ] ). In addition to cows, the factory had planned to clone many different types of animals, including dogs, horses, and endangered and  extinct  animals. [ 5 ] [ 6 ]


Tong Dizhou  ( Chinese :  童第周 ; May 28, 1902 – March 30, 1979) was a Chinese  embryologist  known for his contributions to the field of  cloning . He was a  vice president  of  Chinese Academy of Science .


Born in  Yinxian ,  Zhejiang  province, Tong graduated from  Fudan University  in 1924 with a degree in biology, and received a PhD in zoology in 1930 from  Free University Brussels .


In 1963, Tong inserted  DNA  of a male carp into the egg of a female carp and became the first to successfully  clone  a fish. [ 1 ]  He is regarded as "the father of China's clone".


Tong was also an academician at the  Chinese Academy of Sciences  and the first director of its Institute of Oceanology from its founding in 1950 until 1978.


Tong died on 30 March 1979 at Beijing Hospital in Beijing.


This article about a  biologist  is a  stub . You can help Wikipedia by  expanding it .


This biographical article about a Chinese scientist is a  stub . You can help Wikipedia by  expanding it .


Topoisomerase-based cloning (TOPO cloning)  is a  molecular biology  technique in which  DNA  fragments are  cloned  into specific  vectors  without the requirement for  DNA ligases . Taq polymerase has a nontemplate-dependent terminal transferase activity that adds a single deoxyadenosine (A) to the 3'-end of the PCR products. This characteristic is exploited in "sticky end" TOPO TA cloning. [ 1 ]  For "blunt end" TOPO cloning, the recipient vector does not have overhangs and blunt-ended DNA fragments can be cloned.


The technique utilizes the inherent biological activity of  DNA topoisomerase  I. The biological role of topoisomerase is to cleave and rejoin  supercoiled  DNA ends to facilitate replication.  Vaccinia virus  topoisomerase I specifically recognize DNA sequence 5´-(C/T)CCTT-3'. During  replication , the enzyme digests DNA specifically at this sequence, unwinds the DNA and, re-ligates it again at the 3' phosphate group of the  thymidine  base. [ 1 ]


The vectors in commercially available TOPO kits have been added to the topoisomerase site embedded in a beta-galactosidase cassette allowing blue-white scanning. The vector ends thus self-assemble, resulting in the production of blue colonies that do not need to be selected and sequenced for potential positive clones.


TOPO vectors are designed in such a way that they carry this specific sequence 5´-(C/T)CCTT-3' at the two linear ends. The linear vector DNA already has the topoisomerase enzyme covalently attached to both of its strands' free 3' ends. This is then mixed with PCR products. When the free 5' ends of the PCR product strands attach to the topoisomerase 3' end of each vector strand, the strands are covalently linked by the already bound topoisomerase. This reaction proceeds efficiently when this solution is incubated at room temperature with the required salt. Different types of vectors are used for cloning fragments amplified by either Taq or Pfu polymerase as Taq polymerase (unlike Pfu) leaves an extra "A" nucleotide at the 3'end during amplification. [ 1 ]


The TA TOPO cloning technique relies on the ability of adenine (A) and thymine (T) (complementary base pairs) on different DNA fragments to hybridize and, in the presence of ligase or topoisomerase, become ligated together.
The insert is created by PCR using Taq DNA polymerase, a polymerase that lacks 3' to 5' proofreading activity and with a high probability adds a single, 3'-adenine overhang to each end of the PCR product. It is best if the PCR primers have guanines at the 5' end as this maximizes probability of Taq DNA polymerase adding the terminal adenosine overhang. Thermostable polymerases containing extensive 3´ to 5´ exonuclease activity should not be used as they do not leave the 3´ adenine-overhangs.
The target vector is linearized and cut with a blunt-end restriction enzyme. This vector is then tailed with dideoxythymidine triphosphate (ddTTP) using terminal transferase. It is important to use ddTTP to ensure the addition of only one T residue. This tailing leaves the vector with a single 3'-overhanging thymine residue on each blunt end. [ 1 ]


Polymerases (such as Phusion) or restriction enzymes that produce blunt ends can also be used for TOPO cloning. Rather than relying on sticky ends, the blunt end TOPO vector has blunt ends where the topoisomerase molecules are bound. Commercial kits, such as the Zero Blunt® Cloning Kit from Invitrogen, are available. [ 2 ]


In  genetic engineering ,  transposon tagging  is a process where  transposons  (transposable elements) are amplified inside a biological cell by a tagging technique. Transposon tagging has been used with several  species  to isolate  genes . [ 1 ] [ self-published source? ]  Even without knowing the nature of the specific genes, the process can still be used. [ 1 ]


By molecular separation of  transposons , from a cell nucleus, the  cloning  is enabled for genes which contain the transposons. [ 2 ] [ self-published source? ]


By using transposon tagging, researchers have been able to add genetic elements from  maize  (corn) [ 3 ]  and  Antirrhinum  into some other species (such as  tobacco , [ 4 ]  aspen [ 5 ]  and others). [ 2 ]  A gene responsible for a particular  phenotype  can be cloned within a given species, when movement is accompanied by the presence of a mutant phenotype. [ 2 ]


This article about  biological engineering  is a  stub . You can help Wikipedia by  expanding it .


In  placental   mammals , the  umbilical cord  (also called the  navel string , [ 1 ]   birth cord  or  funiculus umbilicalis ) is a conduit between the developing  embryo  or  fetus  and the  placenta . During  prenatal development , the umbilical cord is physiologically and genetically part of the fetus and (in humans) normally contains two  arteries  (the  umbilical arteries ) and one  vein  (the  umbilical vein ), buried within  Wharton's jelly . The umbilical vein supplies the fetus with  oxygenated ,  nutrient -rich  blood  from the  placenta .  Conversely, the fetal heart pumps low-oxygen, nutrient-depleted blood through the umbilical arteries back to the placenta.


The umbilical cord develops from and contains remnants of the  yolk sac  and  allantois . It forms by the fifth week of  development , replacing the yolk sac as the source of nutrients for the embryo. [ 2 ]  The cord is not directly connected to the mother's circulatory system, but instead joins the  placenta , which transfers materials to and from the maternal blood without allowing direct mixing.  The length of the umbilical cord is approximately equal to the  crown-rump length  of the fetus throughout  pregnancy . The umbilical cord in a full term  neonate  is usually about 50  centimeters  (20  in ) long and about 2 centimeters (0.75 in) in diameter. This diameter decreases rapidly within the placenta. The fully patent umbilical artery has two main layers: an outer layer consisting of circularly arranged smooth muscle cells and an inner layer which shows rather irregularly and loosely arranged cells embedded in abundant  ground substance  staining  metachromatic . [ 3 ]  The smooth muscle cells of the layer are rather poorly differentiated, contain only a few tiny  myofilaments  and are thereby unlikely to contribute actively to the process of post-natal closure. [ 3 ]


Umbilical cord can be detected on ultrasound by six weeks of gestation and well-visualised by eight to nine weeks of gestation. [ 4 ]


The umbilical  cord lining  is a good source of mesenchymal and epithelial stem cells. Umbilical cord  mesenchymal stem cells  (UC-MSC) have been used clinically to treat osteoarthritis, autoimmune diseases, and multiple other conditions. Their advantages include a better harvesting, and multiplication, and immunosuppressive properties that define their potential for use in transplantations. Their use would also overcome the ethical objections raised by the use of  embryonic stem cells . [ 5 ]


The umbilical cord contains  Wharton's jelly , a gelatinous substance made largely from  mucopolysaccharides  that protects the blood vessels inside. It contains one vein, which carries oxygenated, nutrient-rich blood to the fetus,  and two arteries that carry deoxygenated, nutrient-depleted blood away. [ 6 ]  Occasionally, only two vessels (one vein and one artery) are present in the umbilical cord. This is sometimes related to fetal abnormalities, but it may also occur without accompanying problems.


It is unusual for a vein to carry oxygenated blood and for arteries to carry deoxygenated blood (the only other examples being the  pulmonary veins  and  arteries , connecting the lungs to the heart). However, this naming convention reflects the fact that the umbilical vein carries blood towards the fetus' heart, while the umbilical arteries carry blood away.


The blood flow through the umbilical cord is approximately 35 ml / min at 20 weeks, and 240 ml / min at 40  weeks of gestation . [ 7 ]  Adapted to the weight of the fetus, this corresponds to 115 ml / min / kg at 20 weeks and 64 ml / min / kg at 40 weeks. [ 7 ]


For  terms of location , the  proximal  part of an umbilical cord refers to the segment closest to the embryo or fetus in embryology and fetal medicine, and closest to the placenta in placental pathology, and opposite for the  distal  part, respectively. [ 8 ]


The umbilical cord enters the fetus via the  abdomen , at the point which (after separation) will become the  umbilicus  (belly button or navel). Within the fetus, the umbilical vein continues towards the  transverse fissure  of the  liver , where it splits into two.  One of these branches joins with the  hepatic portal vein  (connecting to its left branch), which carries blood into the liver.  The second branch (known as the  ductus venosus ) bypasses the liver and flows into the  inferior vena cava , which carries blood towards the heart.  The two umbilical arteries branch from the  internal iliac arteries  and pass on either side of the  urinary bladder  into the umbilical cord, completing the circuit back to the placenta. [ 9 ]


After birth, the umbilical cord stump will dry up and drop away by the time the baby is three weeks old. [ 10 ]  If the stump still has not separated after three weeks, it might be a sign of an underlying problem, such as an infection or immune system disorder. [ 10 ]


In absence of external interventions, the umbilical cord  occludes  physiologically shortly after birth, explained both by a swelling and collapse of  Wharton's jelly  in response to a reduction in temperature and by  vasoconstriction  of the blood vessels by smooth muscle contraction. In effect, a natural clamp is created, halting the flow of blood. In air at 18 °C, this physiological clamping will take three minutes or less. [ 11 ]  In  water birth , where the water temperature is close to body temperature, normal pulsation can be five minutes and longer.


Closure of the umbilical artery by vasoconstriction consists of multiple constrictions which increase in number and degree with time. There are segments of dilations with trapped uncoagulated blood between the constrictions before complete occlusion. [ 12 ]  Both the partial constrictions and the ultimate closure are mainly produced by muscle cells of the outer circular layer. [ 3 ]  In contrast, the inner layer seems to serve mainly as a plastic tissue which can easily be shifted in an  axial  direction and then folded into the narrowing lumen to complete the closure. [ 3 ]  The vasoconstrictive occlusion appears to be mainly mediated by  serotonin [ 13 ] [ 14 ]  and  thromboxane A 2 . [ 13 ]  The artery in cords of preterm infants contracts more to  angiotensin II  and  arachidonic acid  and is more sensitive to  oxytocin  than in term ones. [ 14 ]  In contrast to the contribution of Wharton's jelly, cooling causes only temporary vasoconstriction. [ 14 ]


Within the child, the umbilical vein and ductus venosus close up, and degenerate into fibrous remnants known as the  round ligament of the liver  and the  ligamentum venosum  respectively. Part of each umbilical artery closes up (degenerating into what are known as the  medial umbilical ligaments ), while the remaining sections are retained as part of the circulatory system.


A number of abnormalities can affect the umbilical cord, which can cause problems that affect both mother and child: [ 15 ]


The cord can be clamped at different times; however, delaying the clamping of the umbilical cord until at least one minute after birth improves outcomes as long as there is the ability to treat the small risk of  jaundice  if it occurs. [ 18 ]  Clamping is followed by cutting of the cord, which is painless due to the absence of  nerves .  The cord is extremely tough, like thick  sinew , and so cutting it requires a suitably sharp instrument.  While umbilical severance may be delayed until after the cord has stopped pulsing (one to three minutes after birth), there is ordinarily no significant loss of either venous or arterial blood while cutting the cord. Current evidence neither supports, nor refutes, delayed cutting of the cord, according to the  American Congress of Obstetricians and Gynecologists  (ACOG) guidelines.


There are umbilical cord clamps which incorporate a knife. These clamps are safer and faster, allowing one to first apply the cord clamp and then cut the umbilical cord.  After the cord is clamped and cut, the newborn wears a plastic clip on the navel area until the compressed region of the cord has dried and sealed sufficiently.


The length of umbilical left attached to the newborn varies by practice; in most hospital settings the length of cord left attached after clamping and cutting is minimal. In the United States, however, where the birth occurred outside of the hospital and an  emergency medical technician  (EMT) clamps and cuts the cord, a longer segment up to 18 cm (7 in) in length [ 19 ] [ 20 ]  is left attached to the newborn.


The remaining umbilical stub remains for up to ten days as it dries and then falls off.


A  Cochrane review  in 2013 came to the conclusion that delayed cord clamping (between one and three minutes after birth) is "likely to be beneficial as long as access to treatment for jaundice requiring phototherapy is available". [ 21 ]  In this review delayed clamping, as contrasted to early, resulted in no difference in risk of severe maternal  postpartum hemorrhage  or neonatal mortality, and a low  Apgar score . On the other hand, delayed clamping resulted in an increased birth weight of on average about 100 g, and an increased  hemoglobin  concentration of on average 1.5 g/dL with half the risk of being iron deficient at three and six months, but an increased risk of jaundice requiring  phototherapy . [ 21 ]


In 2012, the American College of Obstetricians and Gynecologists officially endorsed delaying clamping of the umbilical cord for 30–60 seconds with the newborn held below the level of the placenta in all cases of preterm delivery based largely on evidence that it reduces the risk of intraventricular hemorrhage in these children by 50%. [ 22 ] [ obsolete source ]  In the same committee statement, ACOG also recognize several other likely benefits for preterm infants, including "improved transitional circulation, better establishment of red blood cell volume, and decreased need for blood transfusion". In January 2017, a revised Committee Opinion extended the recommendation to term infants, citing data that term infants benefit from increased hemoglobin levels in the newborn period and improved iron stores in the first months of life, which may result in improved developmental outcomes. ACOG recognized a small increase in the incidence of jaundice in term infants with delayed cord clamping, and recommended policies be in place to monitor for  and treat neonatal jaundice. ACOG also noted that delayed cord clamping is not associated with increased risk of postpartum hemorrhage. [ 23 ]


Several studies have shown benefits of delayed cord clamping: A meta-analysis [ 24 ]  showed that delaying clamping of the umbilical cord in full-term neonates for a minimum of two minutes following birth is beneficial to the newborn in giving improved  hematocrit , iron status as measured by  ferritin  concentration and stored iron, as well as a reduction in the risk of anemia ( relative risk , 0.53; 95% CI, 0.40–0.70). [ 24 ]  A decrease was also found in a study from 2008. [ 25 ]  Although there is higher hemoglobin level at 2 months, this effect did not persist beyond 6 months of age. [ 26 ]  Not clamping the cord for three minutes following the birth of a baby improved outcomes at four years of age. [ 27 ]  A delay of three minutes or more in umbilical cord clamping after birth reduce the prevalence of anemia in infants. [ 28 ]


Negative effects of delayed cord clamping include an increased risk of  polycythemia . Still, this condition appeared to be benign in studies. [ 24 ]  Infants whose cord clamping occurred later than 60 seconds after birth had a higher rate of  neonatal jaundice  requiring  phototherapy . [ 26 ]


Delayed clamping is not recommended as a response to cases where the newborn is not breathing well and needs resuscitation. Rather, the recommendation is instead to immediately clamp and cut the cord and perform  cardiopulmonary resuscitation . [ 29 ]  The umbilical cord pulsating is not a guarantee that the baby is receiving enough oxygen. [ 30 ]


Some parents choose to omit cord severance entirely, a practice called " lotus birth " or umbilical nonseverance.  The entire intact umbilical cord is allowed to dry and separates on its own (typically on the 3rd day after birth), falling off and leaving a healed umbilicus. [ 31 ]  The  Royal College of Obstetricians and Gynaecologists  has warned about the risks of infection as the decomposing placenta tissue becomes a nest for infectious bacteria such as  Staphylococcus . [ 32 ]  In one such case, a 20-hour old baby whose parents chose UCNS was brought to the hospital in an agonal state, was diagnosed with  sepsis  and required an antibiotic treatment for six weeks. [ 33 ] [ 34 ]


As the umbilical vein is directly connected to the central circulation, it can be used as a route for placement of a venous catheter for infusion and medication. The umbilical vein catheter is a reliable alternative to percutaneous peripheral or central venous catheters or intraosseous canulas and may be employed in resuscitation or intensive care of the newborn.


From 24 to 34 weeks of gestation, when the fetus is typically viable, blood can be taken from the cord in order to test for abnormalities (particularly for  hereditary  conditions). This diagnostic  genetic test  procedure is known as  percutaneous umbilical cord blood sampling . [ 35 ]


The blood within the umbilical cord, known as  cord blood , is a rich and readily available source of primitive,  undifferentiated   stem cells  (of type  CD34 -positive and  CD38 -negative). These cord blood cells can be used for  bone marrow transplant .


Some parents choose to have this blood diverted from the baby's umbilical blood transfer through early cord clamping and cutting, to freeze for long-term storage at a  cord blood bank  should the child ever require the cord blood stem cells (for example, to replace  bone marrow  destroyed when treating  leukemia ). This practice is controversial, with critics asserting that early cord blood withdrawal at the time of birth actually increases the likelihood of childhood disease, due to the high volume of blood taken (an average of 108ml) in relation to the baby's total supply (typically 300ml). [ 25 ]   The  Royal College of Obstetricians and Gynaecologists  stated in 2006 that "there is still insufficient evidence to recommend directed commercial cord blood collection and stem-cell storage in low-risk families". [ 36 ]


The  American Academy of Pediatrics  has stated that cord blood banking for self-use should be discouraged (as most conditions requiring the use of stem cells will already exist in the cord blood), while banking for general use should be encouraged. [ 37 ]   In the future, cord blood-derived embryonic-like stem cells (CBEs) may be banked and matched with other patients, much like blood and transplanted tissues. The use of CBEs could potentially eliminate the ethical difficulties associated with  embryonic stem cells  (ESCs). [ 38 ]


While the American Academy of Pediatrics discourages private banking except in the case of existing medical need, it also says that information about the potential benefits and limitations of cord blood banking and transplantation should be provided so that parents can make an informed decision.


In the United States, cord blood education has been supported by legislators at the federal and state levels. In 2005, the National Academy of Sciences published an  Institute of Medicine (IoM) report  which recommended that expectant parents be given a balanced perspective on their options for cord blood banking. In response to their constituents, state legislators across the country are introducing legislation intended to help inform physicians and expectant parents on the options for donating, discarding or banking lifesaving newborn stem cells. Currently 17 states, representing two-thirds of U.S. births, have enacted legislation recommended by the IoM guidelines.


The use of cord blood stem cells in treating conditions such as brain injury [ 39 ]   and Type 1 Diabetes [ 40 ]   is already being studied in humans, and earlier stage research is being conducted for treatments of stroke, [ 41 ] [ 42 ]  and hearing loss. [ 43 ]


Cord blood stored with private banks is typically reserved for use of the donor child only. In contrast, cord blood stored in public banks is accessible to anyone with a closely matching tissue type and demonstrated need. [ 44 ]  The use of cord blood from public banks is increasing. Currently it is used in place of a bone marrow transplant in the treatment of blood disorders such as leukemia, with donations released for transplant through one registry, Netcord.org, [ 45 ]  passing 1,000,000 as of January 2013. Cord blood is used when the patient cannot find a matching bone marrow donor; this "extension" of the donor pool has driven the expansion of public banks.


The umbilical cord in some mammals, including cattle and sheep, contains two distinct umbilical veins. There is only one umbilical vein in the human umbilical cord. [ 46 ]


In some animals, the mother will gnaw through the cord, thus separating the placenta from the offspring.  The cord along with the placenta is often eaten by the mother, to provide nourishment and to dispose of tissues that would otherwise attract scavengers or predators. [ citation needed ]  In  chimpanzees , the mother leaves the cord in place and nurses her young with the cord and placenta attached until the cord dries out and separates naturally, within a day of birth, at which time the cord is discarded.  (This was first documented by zoologists in the wild in 1974. [ 47 ] )


Some species of  shark — hammerheads ,  requiems  and  smooth-hounds —are  viviparous  and have an umbilical cord attached to their placenta. [ 48 ]


The term "umbilical cord" or just "umbilical" has also come to be used for other cords with similar functions, such as the hose connecting  surface-supplied divers  to their surface supply of air and/or heating, or  space-suited   astronauts  to their spacecraft. Engineers sometimes use the term to describe a complex or critical cable connecting a component, especially when composed of bundles of conductors of different colors, thickness and types, terminating in a single multi-contact disconnect.


In multiple American and international studies,  cancer-causing  chemicals have been found in the blood of umbilical cords. These originate from certain plastics, computer circuit boards, fumes and synthetic fragrances among others. Over 300  chemical   toxicants  have been found, including  bisphenol A  (BPA),  tetrabromobisphenol A  (TBBPA),  Teflon -related  perfluorooctanoic acid ,  galaxolide  and  synthetic musks  among others. [ 49 ]  The studies in America showed higher levels in  African Americans ,  Hispanic Americans  and  Asian Americans  due, it is thought, to living in areas of higher pollution. [ 50 ]


The  United Nations Declaration on Human Cloning  was a nonbinding statement against all forms of  human cloning  approved by a divided  UN General Assembly .


The vote came in March 2005, [ 1 ]  after four years of debate and an end to attempts for an international ban.


In the 191-nation assembly, there were 84 votes in favor of a nonbinding statement, 34 against and 37 abstentions.


Proposed by  Honduras , the statement was largely supported by  Roman Catholic  countries and opposed by countries with active  embryonic stem cell  research programs. Many  Islamic  nations abstained.


The UN Declaration on Human Cloning, as it is named, calls for all member states to adopt a ban on human cloning, which it says is "incompatible with human  dignity  and the protection of human life."


The  US , which has long pushed for a complete ban, voted in favor of the statement while traditional ally  Britain , where  therapeutic cloning  is legal and regulated, voted against it.


The statement should have no impact on countries that allow therapeutic cloning, such as Britain and  South Korea , as it is not legally binding.


"The foes of therapeutic cloning are trying to portray this as a victory for their ideology,"  Bernard Siegel , a  Florida  attorney who lobbies to defend therapeutic cloning, said in a  Reuters  report. "But this confusing declaration is an effort to mask their failure last November to impose a treaty on the world banning therapeutic cloning."


Vegetative reproduction  (also known as  vegetative propagation ,  vegetative multiplication  or  cloning ) is a form of  asexual reproduction  occurring in plants in which a new plant grows from a fragment or  cutting  of the parent plant or  specialized reproductive structures, which are sometimes called  vegetative propagules . [ 1 ] [ 2 ] [ 3 ]


Many plants naturally reproduce this way, but it can also be induced  artificially .  Horticulturists  have developed asexual propagation techniques that use vegetative propagules to replicate plants. Success rates and difficulty of propagation vary greatly.   Monocotyledons  typically lack a  vascular cambium , making them more challenging to propagate.


Plant propagation  is the process of plant reproduction of a species or cultivar, and it can be sexual or asexual. It can happen through the use of vegetative parts of the plants, such as   leaves ,  stems , and  roots  to produce new plants or through growth from specialized vegetative plant parts. [ 4 ]


While many plants reproduce by vegetative reproduction, they rarely exclusively use that method to reproduce. Vegetative reproduction is not evolutionary advantageous; it does not allow for genetic diversity and could lead plants to accumulate deleterious mutations. [ 5 ]  Vegetative reproduction is favored when it allows plants to produce more  offspring  per unit of resource than reproduction through seed production. [ 6 ]  In general, juveniles of a plant are easier to propagate vegetatively. [ 7 ]


Although most plants normally reproduce sexually, many can reproduce vegetatively, or can be induced to do so via hormonal treatments. This is because  meristematic cells  capable of  cellular differentiation  are present in many plant tissues.


Vegetative propagation is usually considered a  cloning  method. [ 8 ]  However, root cuttings of thornless blackberries ( Rubus fruticosus ) will revert to thorny type because the  adventitious shoot  develops from a cell that is genetically thorny. Thornless blackberry is a chimera, with the epidermal layers genetically thornless but the tissue beneath it genetically thorny. [ 9 ]


Grafting is often not a complete cloning method because seedlings are used as rootstocks. In that case, only the top of the plant is clonal. In some crops, particularly apples, the rootstocks are vegetatively propagated so the entire graft can be clonal if the scion and rootstock are both clones.  Apomixis  (including apospory and diplospory) is a type of reproduction that does not involve fertilization. In flowering plants, unfertilized seeds are produced, or  plantlets  that grow instead of flowers. Hawkweed ( Hieracium ), dandelion ( Taraxacum ), some citrus ( Citrus ) and many grasses such as Kentucky bluegrass ( Poa pratensis ) all use this form of asexual reproduction.  Bulbils  are sometimes formed instead of the flowers of garlic.


Meristem tissue makes the process of asexual reproduction possible. It is normally found in stems, leaves, and tips of stems and roots and consists of  undifferentiated cells  that are constantly dividing allowing for plant growth and give rise to plant tissue systems. The meristem tissue's ability to continuously divide allows for vegetative propagation to occur. [ 10 ]


Another important ability  that  allows for vegetative propagation is the ability to develop  adventitious roots  which arise from other vegetative parts of the plants such as the stem or leaves. These roots allow for the development of new plants from body parts from other plants. [ 11 ]


There are several advantages of vegetative reproduction, mainly that the produced offspring are  clones  of their parent plants. If a plant has favorable traits, it can continue to pass down its advantageous  genetic information  to its offspring. It can be economically beneficial for commercial growers to clone a certain plant to ensure consistency throughout their crops. [ 12 ]  Vegetative propagation also allows plants to avoid the costly and complex process of producing  sexual reproduction organs  such as  flowers  and the subsequent  seeds  and  fruits . [ 13 ]  Developing an ace  cultivar  is extremely difficult, so, once farmers develop the desired traits in, for example, a lily, they use  grafting  and  budding  to ensure the consistency of the new cultivar and its successful production on a commercial level. However, as can be seen in many  variegated  plants, this does not always apply, because many plants actually are  chimeras  and cuttings might reflect the attributes of only one or some of the parent cell lines. Vegetative propagation also allows plants to circumvent the immature  seedling phase  and reach the  mature  phase faster. [ 14 ]  In nature, that increases the chances for a plant to successfully reach maturity, and, commercially, it saves farmers a lot of time and money as it allows for faster crop overturn. [ 15 ]


Vegetative reproduction offers research advantages in several areas of biology and has practical usage when it comes to  afforestation . The most common use made of vegetative propagation by forest geneticists and tree breeders has been to move  genes  from selected trees to some convenient location, usually designated a  gene bank ,  clone bank , clone-holding orchard, or seed orchard where their genes can be  recombined  in  pedigreed  offspring. [ 15 ]


Some analyses suggest that vegetative reproduction is a characteristic which makes a plant species more likely to become invasive. Since vegetative reproduction is often faster than sexual reproduction, it "quickly increases populations and may contribute to recovery following disturbance" (such as fires and floods). [ 16 ]


A major disadvantage of vegetative propagation is that it prevents species  genetic diversity  which can lead to reductions in  crop yields . [ 17 ] [ 18 ]  The plants are genetically identical and are all, therefore, susceptible to pathogenic  plant viruses ,  bacteria  and  fungi  that can wipe out entire crops. [ 19 ]


Natural vegetative propagation is mostly a  process  found in  herbaceous  and  woody   perennial  plants, and typically involves structural modifications of the  stem , although any horizontal, underground part of a plant (whether stem, leaf, or  root ) can contribute to vegetative reproduction of a plant. Most plant species that survive and significantly expand by vegetative reproduction would be  perennial  almost by definition, since specialized organs of vegetative reproduction, like seeds of annuals, serve to survive  seasonally  harsh conditions. A plant that persists in a location through vegetative reproduction of individuals over a long period of time constitutes a  clonal colony .


In a sense, this process is not one of reproduction but one of survival and expansion of biomass of the individual. When an individual  organism  increases in size via cell multiplication and remains intact, the process is called "vegetative growth". However, in vegetative reproduction, the new plants that result are new individuals in almost every respect except genetic. Of considerable interest is how this process appears to reset the  aging clock . [ 20 ]


As previously mentioned, plants vegetatively propagate both artificially and naturally. Most common methods of natural vegetative reproduction involve the development of a new plant from specialized structures of a mature plant. In addition to  adventitious roots , roots that arise from plant structures other than the root, such as stems or leaves,  modified stems , leaves and roots play an important role in plants' ability to naturally propagate. The most common modified stems, leaves and roots that allow for vegetative propagation are: [ 21 ]


Also known as  stolons , runners are modified stems that, unlike rhizomes, grow from existing stems just below the soil surface. As they are propagated, the  buds  on the modified stems produce roots and stems. Those buds are more separated than the ones found on the rhizome. [ 22 ]


Examples of plants that use runners are  strawberries  and  currants .


Bulbs  are inflated parts of the stem within which lie the central shoots of new plants. They are typically underground and are surrounded by plump and layered leaves that provide  nutrients  to the new plant. [ 23 ]


Examples of plants that use bulbs are  shallots ,  lilies  and  tulips .


Tubers  develop from either the stem or the root. Stem tubers grow from rhizomes or runners that swell from storing nutrients while root tubers propagate from roots that are modified to store nutrients and get too large and produce a new plant. [ 22 ]


Examples of stem tubers are  potatoes  and  yams  and examples of root tubers are  sweet potatoes  and  dahlias .


Corms  are solid enlarged underground stems that store nutrients in their fleshy and solid stem tissue and are surrounded by papery leaves. Corms differ from bulbs in that their centers consists of solid tissue while bulbs consist of layered leaves. [ 24 ]


Examples of plants that use corms are  gladiolus  and  taro .


Also known as  root sprouts , suckers are plant stems that arise from buds on the base of the parent plant's stems or roots. [ 25 ]


Examples of plants that use suckers are  apple ,  elm , and  banana trees .


Plantlets  are miniature structures that arise from meristem in leaf margins that eventually develops roots and drop from the leaves they grew on. [ 26 ]


An example of a plant that uses plantlets is the  Bryophyllum daigremontianum  (syn.  Kalanchoe daigremontianum ), which is also known as  mother of thousands  for its many plantlets.


Keikis  are additional offshoots which develop on vegetative stems or  flower stalks  of several orchids  genera . [ 14 ]


Examples of plants that use keikis are the  Phalaenopsis ,  Epidendrum , and  Dendrobium  genera of  orchids .


Apomixis  is the process of asexual reproduction through seed, in the absence of meiosis and fertilization, generating clonal progeny of maternal origin. [ 27 ]


Vegetative propagation of particular  cultivars  that have desirable characteristics is very common practice. It is used by farmers and  horticulturalists  to produce better crops with desirable qualities. The most common methods of  artificial vegetative propagation  are: [ 21 ]


A  cutting  is a part of the plant, usually a stem or a leaf, is cut off and planted. Adventitious roots grow from cuttings and a new plant eventually develops. Usually those cuttings are treated with  hormones  before being planted to induce growth. [ 28 ]


Grafting  involves attaching a  scion , or a desired cutting, to the stem of another plant called stock that remains rooted in the ground. Eventually both tissue systems become grafted or integrated and a plant with the characteristics of the grafted plant develops, [ 29 ]  e.g. mango, guava, etc.


Layering  is a process which includes the bending of plant branches or stems so that they touch the ground and are covered with soil. Adventitious roots develop from the underground part of the plant, which is known as the layer. This method of vegetative reproduction also occurs naturally. Another similar method,  air layering , involved the scraping and replanting of tree branches which develop into trees. Examples are Jasmine and Bougainvillea. [ 30 ]


Suckers  grow and form a dense compact mat that is attached to the parent plant. Too many suckers can lead to smaller crop size, so excess suckers are  pruned , and mature suckers are transplanted to a new area where they develop into new plants. [ 31 ]


In  tissue culture , plant cells are taken from various parts of the plant and are  cultured  and nurtured in a sterilized medium. The mass of developed tissue, known as the  callus , is then cultured in a hormone-ladened medium and eventually develops into plantlets which are then planted and eventually develop into grown plants. [ 12 ] [ 32 ]


An offset is the lower part of a single culm with the rhizome axis basal to it and its roots. Planting of these is the most convenient way of propagating bamboo.


ViaGen Pets , based in Cedar Park, Texas, is a division of TransOva Genetics, that offers animal  cloning  services to pet owners. ViaGen Pets division was launched in 2016. [ 1 ]


ViaGen Pets offers cloning as well as DNA preservation services, sometimes called tissue or cell banking. [ 2 ]


ViaGen's subsidiary, Start Licensing, owns a cloning patent which is licensed to their only competitor as of 2018, who also offers animal cloning services. [ 3 ]


The cloning process used by both ViaGen and their competitor is  somatic cell nuclear transfer, the same as which was used for cloning  Dolly the Sheep . [ 3 ]


ViaGen Pets began by offering cloning to the livestock and equine industry in 2003, [ 1 ]  and later included cloning of cats and dogs in 2016. [ 4 ]


This United States corporation or company article is a  stub . You can help Wikipedia by  expanding it .


In plants,  vivipary  occurs when seeds or embryos begin to develop before they detach from the parent. Plants such as some  Iridaceae  and  Agavoideae  grow cormlets in the axils of their inflorescences. These fall and in favourable circumstances they have effectively a whole season's start over fallen seeds. Similarly, some  Crassulaceae , such as  Bryophyllum , develop and drop plantlets from notches in their leaves, ready to grow. Such production of embryos from somatic tissues is asexual  vegetative reproduction  that amounts to  cloning .


Most seed-bearing fruits produce a hormone that suppresses germination until after the fruit or parent plant dies, or the seeds pass through an animal's digestive tract. At this stage, the hormone's effect will dissipate and germination will occur once conditions are suitable. Some species lack this suppressant hormone as a central part of their reproductive strategy. For example, fruits that develop in climates without large seasonal variations. [ 1 ]  This phenomenon occurs most frequently on ears of corn, tomatoes, strawberries, peppers, pears, citrus fruits, and plants that grow in mangrove environments. [ 2 ]


In some species of  mangroves , for instance, the seed germinates and grows from its own resources while still attached to its parent. Seedlings of some species are dispersed by currents if they drop into the water, but others develop a heavy, straight taproot that commonly penetrates mud when the seedling drops, thereby effectively planting the seedling. This contrasts with the examples of vegetative reproduction mentioned above, in that the mangrove plantlets are true seedlings produced by  sexual reproduction . [ citation needed ]


In some trees, like  jackfruit , some citrus, and avocado, the seeds can be found already germinated while the fruit goes overripe; strictly speaking this condition cannot be described as vivipary [ citation needed ] , but the moist and humid conditions provided by the fruit mimic a wet soil that encourages germination. However, the seeds also can germinate under moist soil. [ 3 ]


In some species of cacti, such as  Escobaria vivipara ,  seeds germinate while still inside of the fruit. [ 4 ]  When the fruit is broken open, it bears many cacti propagules. This is thought to be an adaptation to rapid photoperiod, or daylight changes, since  Escobaria vivipara  is one of the few cacti that naturally occurs above the frost line in Canada. [ 5 ]


Vivipary includes reproduction via embryos, such as shoots or  bulbils , as opposed to germinating externally from a dropped, dormant  seed , as is usual in plants; [ 6 ] [ 7 ]


A few plants are  pseudoviviparous  – instead of reproducing with seeds, there are  Monocots  that can reproduce asexually by creating new  plantlets  in their  spikelets . [ 8 ]  Examples are  seagrass  species belonging to the genus  Posidonia [ 9 ]  and the alpine meadow-grass,  Poa alpina . [ 10 ]


Sir Ian Wilmut  (7 July 1944 – 10 September 2023) was a British  embryologist  and the chair of the  Scottish Centre for Regenerative Medicine [ 4 ]  at the  University of Edinburgh . [ 5 ]  He is best known as the leader of the research group that in 1996 first  cloned  a mammal from an adult  somatic cell , a  Finnish Dorset  lamb named  Dolly . [ 6 ] [ 7 ]


Wilmut was appointed  OBE  in 1999 for services to embryo development [ 8 ]  and  knighted  in the  2008 New Year Honours . [ 9 ]  He,  Keith Campbell  and  Shinya Yamanaka  jointly received the 2008  Shaw Prize  for Medicine and Life Sciences for their work on  cell differentiation  in mammals. [ 3 ]


Wilmut was born in  Hampton Lucy ,  Warwickshire , England, on 7 July 1944. [ 10 ]  Wilmut's father, Leonard Wilmut, was a mathematics teacher who suffered from  diabetes  for fifty years, which eventually caused him to become blind. [ 11 ]  The younger Wilmut attended the  Boys' High School  in  Scarborough , where his father taught. [ 12 ]  His early desire was to embark on a naval career, but he was unable to do so due to his  colour blindness . [ 13 ]  As a schoolboy, Wilmut worked as a farm hand on weekends, which inspired him to study  Agriculture  at the  University of Nottingham . [ 12 ] [ 14 ]


In 1966, Wilmut spent eight weeks working in the laboratory of  Christopher Polge , who is credited with developing the technique of  cryopreservation  in 1949. [ 15 ]  The following year Wilmut joined Polge's laboratory to undertake a  Doctor of Philosophy  degree at the  University of Cambridge , from where he graduated in 1971 with a thesis on  semen cryopreservation . [ 16 ]  During this time he was a postgraduate student at  Darwin College . [ 17 ]


After completing his PhD, he was involved in research focusing on gametes and embryogenesis, including working at the  Roslin Institute . [ 12 ]


Wilmut was the leader of the research group that in 1996 first cloned a mammal, a lamb named  Dolly . [ 18 ] [ 19 ]  She died of a respiratory disease in 2003. In 2008 Wilmut announced that he would abandon the technique of  somatic cell nuclear transfer [ 20 ]  by which Dolly was created in favour of an alternative technique developed by  Shinya Yamanaka . This method has been used in mice to derive  pluripotent  stem cells from differentiated adult skin cells, thus circumventing the need to generate embryonic stem cells. Wilmut believed that this method holds greater potential for the treatment of degenerative conditions such as  Parkinson's disease  and to treat stroke and heart attack patients. [ 21 ]


Dolly was a bonus, sometimes when scientists work hard, they also get lucky, and that's what happened. [ 22 ]


Wilmut led the team that created Dolly, but in 2006 admitted his colleague  Keith Campbell [ 23 ]  deserved "66 per cent" of the invention that made Dolly's birth possible, and that the statement "I did not create Dolly" was accurate. [ 24 ]  His supervisory role is consistent with the post of  principal investigator  held by Wilmut at the time of Dolly's creation.


Wilmut was an Emeritus Professor at the  Scottish Centre for Regenerative Medicine [ 25 ]  at the  University of Edinburgh  and in 2008 was  knighted  in the  New Year Honours  for services to science. [ 13 ]


Wilmut and Campbell, in conjunction with  Colin Tudge , published  The Second Creation  in 2000. [ 26 ] [ 10 ]
In 2006 Wilmut's book  After Dolly: The Uses and Misuses of Human Cloning  was published, [ 27 ]  co-authored with  Roger Highfield .


Wilmut died from complications of  Parkinson's disease  on 10 September 2023, aged 79. [ 28 ] [ 10 ]


In 1998 he received the  Lord Lloyd of Kilgerran Award [ 29 ]  and the Golden Plate Award of the  American Academy of Achievement . [ 30 ]


Wilmut was appointed  Officer of the Order of the British Empire (OBE)  in the  1999 Birthday Honours  "for services to Embryo Development" [ 17 ] [ 31 ]  and a  Fellow of the Royal Society (FRS) in 2002 . [ 32 ]  He was also an elected  Fellow of the Academy of Medical Sciences  in 1999 [ 33 ]  and  Fellow of the Royal Society of Edinburgh  in 2000. [ 34 ]  He was elected an  EMBO Member  in 2003. [ 35 ]


In 1997 Wilmut was  Time  magazine man of the year runner up. [ 22 ]  He was  knighted  in the  2008 New Year Honours  for services to science. [ 17 ] [ 36 ]


Samuel H. Wood  is a scientist and fertility specialist. In 2008, he became the first man to clone himself, donating his own  DNA  via  somatic cell nuclear transfer  (SCNT) to produce mature human embryos that were his clones.


Wood completed undergraduate studies in psychology at  Loma Linda University  in 1979. His graduate training includes a  M.A.  in psychology from the  University of Richmond  (1980), an  M.D.  (1985) and a  Ph.D.  (1986) from  Medical College of Virginia , and an  MBA  from  San Diego State University  (1997). [ 1 ]


Wood's early scholarship laid the foundation for his future scientific endeavors, beginning with an initial focus on  DNA . While attending the  Medical College of Virginia , Wood researched isolating a DNA  nuclear matrix  of  HeLa cells  using a poly(dT) template. He and his colleagues discovered that HeLa cell primase in these cells is in a bound form and they determined the presence of multiple forms of polymerase α. [ 2 ]  Wood further studied DNA, in the form of nucleoids, while in his clinical residency in  Obstetrics and Gynecology  at the  University of North Carolina at Chapel Hill .  The properties of two types of "subnuclear systems" (preparations of non-DNased-digested  nuclei  vs. DNased-digested nuclei) were differentiated along with their respective ability to retain elongation in response to increasing concentrations of salt. [ 3 ]


Wood then turned his attention to treating premenstrual syndrome (PMS) as well as improving pregnancy rates when using donated eggs.  During a fellowship in  reproductive endocrinology  and  infertility , Wood studied the usefulness of  fluoxetine  (tradename Prozac or Sarafem) for patients experiencing severe PMS.  He and his research team found this medication significantly reduced behavioral and physical symptoms during the  luteal phase  without suffering significant side effects or treatment complications. [ 4 ]  The collaborators subsequently investigated the efficacy of  RU 486  (commonly referred to as "the  abortion  pill") in treating PMS but found symptoms experienced with administration of low-dose RU 486 to be virtually indistinguishable from subjects receiving a  placebo . [ 5 ]


Upon opening a private practice, Wood continued to expand the knowledge base in the field of infertility.  He and his team analyzed data over a 5-year period for both fresh and frozen  egg donation  cases with and without use of a  gestational surrogate . They found a previously undiscovered "uterine factor" to consider when egg donation resulted in repeated pregnancy failure. Furthermore, they found successful implantation rates were significantly higher for surrogates in both fresh and frozen embryo transfers. [ 6 ]   Additionally, surrogates showed a significantly higher pregnancy rate following frozen embryo transfers than their non-surrogate counterparts.


Wood entered the arena of  stem cell  research shortly after the first published study of  nuclear transfer stem cells  (NTSC), also known as human therapeutic cloning, was withdrawn when the principal author's claims were called into question due to falsified data and ethical deviation from scientific research standards. [ 7 ]  Australian scientist  Andrew French , best known for his work with somatic cell nuclear transfer (SCNT) in the mammalian reproduction process, co-investigated with Wood and French's Australian colleague, Alan Trounson. Based on meticulous mammalian study review, the researchers concluded that the rigorous procedures developed for mammalian reproduction held promise for practical application in  human embryonic stem cell  (hESC) line production. Furthermore, they specifically proposed hESC research should steer away from attempting to produce viable offspring, focusing efforts on the use of cloned embryos as a viable source for deriving stem cell lines instead. [ 8 ]


In 2008, Wood created  embryo  copies of himself by placing his skin cells in a woman's egg, marking the first time anyone had done so with adult skin cells. [ 9 ] [ 10 ] [ 11 ]  The five cloned embryos were later destroyed, [ 10 ] [ 11 ] [ 12 ]  In January 2008, Wood and Andrew French,  Stemagen's  chief scientific officer in  California , announced that they had successfully created the first five mature human embryos using  DNA  from adult skin cells, aiming to provide a less-controversial source of viable embryonic  stem cells . [ 9 ]  Dr. Wood and a colleague donated skin cells and the DNA from those cells was transferred into human eggs. It is not clear if the embryos produced would have been capable of further development, but Dr. Wood stated that if that were possible, using the technology for reproductive cloning would be both unethical and illegal. The five cloned embryos, created in Stemagen Corporation lab in  La Jolla , were later destroyed. [ 12 ]


Wood and five other researchers published their findings in the online research journal  Stem Cells  in an article entitled  Development of Human cloned Blastocyst Following Somatic Cell Nuclear Transfer (SCNT) with Adult Fibroblasts. [ 9 ] [ 13 ]


Gordon Woods  (July 14, 1952 – August 20, 2009) was an American  veterinary scientist  who co-created  Idaho Gem , the world's first  cloned   mule . Idaho Gem was the first clone born in the horse family. [ 1 ]


Woods was raised in northern Idaho. He obtained his  bachelor's degree  from the  University of Idaho . Woods received a  doctorate  of  veterinary medicine  from  Colorado State University . He later obtained a second doctorate in  reproductive biology  from the  University of Wisconsin–Madison . [ 1 ]


Woods first taught  veterinary medicine  at  Cornell University . [ 1 ]


Woods founded the Northwest Equine Reproduction Laboratory in Idaho in 1986. He moved to Moscow, Idaho, and he taught at Washington State University in Pullman, WA until he joined the  faculty  of the  University of Idaho  in 1988 as an Animal and Veterinary Science Department professor. [ 1 ]


Woods, along with colleagues Dr.  Dirk Vanderwall  of University of Idaho and Dr. Ken White of  Utah State University , led a team of scientists in 2003 that cloned  Idaho Gem , the world's first cloned  mule . The cloning of Idaho Gem was a part of a larger  scientific study  intended to understand human diseases.  Horses ,  mules , and other  equines  have lower rates of  cancer  than humans. Woods, Vanderwall, White and their team hoped that the cloning of mules and other equines would provide an important scientific insight into the different cancer rates between humans and equines. Woods was particularly interested in the role that  calcium  played in the development of cancer. Horses and mules have less calcium in their  cell walls  than humans. [ 1 ]


Woods' colleague, Dirk Vanderwall, later explained Woods' goals during the Idaho Gem cloning, "That certainly was another primary focus of Gordon's...to use the horse as a model to try to understand age-onset diseases in people. Gordon's hypothesis was that excessive  intracellular  calcium in human cells could be an underlying factor in age-onset diseases." [ 1 ]


Woods departed the University of Idaho in 2007 and joined the faculty of  Colorado State University . [ 1 ]  He became a professor in the school's College of Veterinary Medicine and Biomedical Sciences.


Gordon Woods died unexpectedly at the Medical Center of the Rockies in  Loveland, Colorado , at the age of 57. He was survived by his wife, Shauna, to whom he had been married for 37 years, four children, six grandchildren and his mother. [ 1 ]


Human genetic variation  is the genetic differences in and among  populations . There may be multiple variants of any given gene in the human population ( alleles ), a situation called  polymorphism .


No two humans are genetically identical. Even  monozygotic twins  (who develop from one zygote) have infrequent genetic differences due to mutations occurring during development and gene  copy-number variation . [ 1 ]  Differences between individuals, even closely related individuals, are the key to techniques such as  genetic fingerprinting .


The human genome has a total length of approximately 3.2 billion  base pairs  (bp) in 46 chromosomes of DNA as well as slightly under 17,000 bp DNA in cellular  mitochondria . In 2015, the typical difference between an individual's genome and the reference genome was estimated at 20 million base pairs (or 0.6% of the total). [ 2 ]  As of 2017, there were a total of 324 million known variants from sequenced  human genomes . [ 3 ]


Comparatively speaking, humans are a genetically homogeneous species. Although a small number of genetic variants are found more frequently in certain geographic regions or in people with ancestry from those regions, this variation accounts for a small portion (~15%) of human genome variability. The majority of variation exists within the members of each human population. For comparison,  rhesus macaques  exhibit 2.5-fold greater DNA sequence diversity compared to humans. [ 4 ]  These rates differ depending on what macromolecules are being analyzed. Chimpanzees have more genetic variance than humans when examining nuclear DNA, but humans have more genetic variance when examining at the level of proteins. [ 5 ]


The lack of discontinuities in genetic distances between human populations, absence of discrete branches in the human species, and striking homogeneity of human beings globally, imply that there is no scientific basis for inferring races or subspecies in humans, and for most  traits , there is much more variation  within  populations than between them. [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ]
Despite this, modern genetic studies have found substantial average genetic differences across human populations in traits such as skin colour, bodily dimensions, lactose and starch digestion, high altitude adaptions, drug response, taste receptors, and predisposition to developing particular diseases. [ 14 ] [ 12 ]  The greatest diversity is found within and among populations in  Africa , [ 15 ]  and gradually declines with increasing distance from the African continent, consistent with the  Out of Africa  theory of human origins. [ 15 ]


The study of human genetic variation has evolutionary significance and medical applications. It can help scientists reconstruct and understand patterns of past human migration. In medicine, study of human genetic variation may be important because some disease-causing alleles occur more often in certain population groups. For instance, the mutation for  sickle-cell anemia  is more often found in people with ancestry from certain sub-Saharan African, south European, Arabian, and Indian populations, due to the evolutionary pressure from mosquitos carrying malaria in these regions.


New findings show that each human has on average 60 new mutations compared to their parents. [ 16 ] [ 17 ]


Causes of differences between individuals include  independent assortment , the  exchange of genes (crossing over and recombination)  during reproduction (through  meiosis ) and various  mutational  events.


There are at least three reasons why genetic variation exists between populations.  Natural selection  may confer an adaptive advantage to individuals in a specific environment if an allele provides a competitive advantage. Alleles under selection are likely to occur only in those geographic regions where they confer an advantage. A second important process is  genetic drift , which is the effect of random changes in the gene pool, under conditions where  most mutations are neutral  (that is, they do not appear to have any positive or negative selective effect on the organism). Finally, small migrant populations have statistical differences – called the  founder effect  – from the overall populations where they originated; when these migrants settle new areas, their descendant population typically differs from their population of origin: different genes predominate and it is less genetically diverse.


In humans, the main cause is  genetic drift . [ 18 ]  Serial  founder effects  and past small population size (increasing the likelihood of genetic drift) may have had an important influence in neutral differences between populations.  [ citation needed ]   The second main cause of genetic variation is due to the high degree of  neutrality of most mutations . A small, but significant number of genes appear to have undergone recent natural selection, and these selective pressures are sometimes specific to one region. [ 19 ] [ 20 ]


Genetic variation among humans occurs on many scales, from gross alterations in the human  karyotype  to single  nucleotide  changes. [ 21 ]   Chromosome abnormalities  are detected in 1 of 160 live human births. Apart from  sex chromosome disorders , most cases of aneuploidy result in death of the developing fetus ( miscarriage ); the most common extra  autosomal  chromosomes among live births are  21 ,  18  and  13 . [ 22 ]


Nucleotide diversity  is the average proportion of nucleotides that differ between two individuals. As of 2004, the human nucleotide diversity was estimated to be 0.1% [ 23 ]  to 0.4% of  base pairs . [ 24 ]  In 2015, the  1000 Genomes Project , which sequenced one thousand individuals from 26 human populations, found that "a typical [individual] genome differs from the reference human genome at 4.1 million to 5.0 million sites … affecting 20 million bases of sequence"; the latter figure corresponds to 0.6% of total number of base pairs. [ 2 ]  Nearly all (>99.9%) of these sites are small differences, either single nucleotide polymorphisms or brief insertions or deletions ( indels ) in the genetic sequence, but structural variations account for a greater number of base-pairs than the SNPs and indels. [ 2 ] [ 25 ]


As of 2017 [update] , the Single Nucleotide Polymorphism Database ( dbSNP ), which lists SNP and other variants, listed 324 million variants found in sequenced human genomes. [ 3 ]


A  single nucleotide polymorphism  (SNP) is a difference in a single nucleotide between members of one species that occurs in at least 1% of the population. The 2,504 individuals characterized by the  1000 Genomes Project  had 84.7 million SNPs among them. [ 2 ]  SNPs are the most common type of sequence variation, estimated in 1998 to account for 90% of all sequence variants. [ 26 ]  Other sequence variations are single base exchanges, deletions and insertions. [ 27 ]  SNPs occur on average about every 100 to 300 bases [ 28 ]  and so are the major source of heterogeneity.


A functional, or non-synonymous, SNP is one that affects some factor such as  gene splicing  or  messenger RNA , and so causes a  phenotypic  difference between members of the species. About 3% to 5% of human SNPs are functional (see  International HapMap Project ). Neutral, or synonymous SNPs are still useful as genetic markers in  genome-wide association studies , because of their sheer number and the stable inheritance over generations. [ 26 ]


A coding SNP is one that occurs inside a gene. There are 105 Human Reference SNPs that result in premature  stop codons  in 103 genes. This corresponds to 0.5% of coding SNPs. They occur due to segmental duplication in the genome. These SNPs result in loss of protein, yet all these SNP alleles are common and are not purified in  negative selection . [ 29 ]


Structural variation  is the variation in structure of an organism's  chromosome . Structural variations, such as copy-number variation and  deletions ,  inversions ,  insertions  and  duplications , account for much more human genetic variation than single nucleotide diversity. This was concluded in 2007 from analysis of the  diploid   full sequences  of the genomes of two humans:  Craig Venter  and  James D. Watson . This added to the two  haploid  sequences which were amalgamations of sequences from many individuals, published by the  Human Genome Project  and  Celera Genomics  respectively. [ 30 ]


According to the 1000 Genomes Project, a typical human has 2,100 to 2,500 structural variations, which include approximately 1,000 large deletions, 160 copy-number variants, 915  Alu  insertions, 128  L1  insertions, 51 SVA insertions, 4  NUMTs , and 10 inversions. [ 2 ]


A copy-number variation (CNV) is a difference in the genome due to deleting or duplicating large regions of DNA on some chromosome. It is estimated that 0.4% of the genomes of unrelated humans differ with respect to copy number. When copy number variation is included, human-to-human genetic variation is estimated to be at least 0.5% (99.5% similarity). [ 31 ] [ 32 ] [ 33 ] [ 34 ]  Copy number variations are inherited but can also arise during development. [ 35 ] [ 36 ] [ 37 ] [ 38 ]


A visual map with the regions with high genomic variation of the modern-human reference assembly relatively to a
Neanderthal of 50k [ 39 ]  has been built by Pratas et al. [ 40 ]


Epigenetic  variation is variation in the chemical tags that attach to  DNA  and affect how genes get read. The tags, "called epigenetic markings, act as switches that control how genes can be read." [ 41 ]  At some alleles, the epigenetic state of the DNA, and associated phenotype, can be  inherited across generations of individuals . [ 42 ]


Genetic variability is a measure of the tendency of individual  genotypes  in a population to vary (become different) from one another. Variability is different from  genetic diversity , which is the amount of variation seen in a particular population.  The variability of a trait is how much that trait tends to vary in response to environmental and  genetic  influences.


In  biology , a cline is a continuum of  species , populations, varieties, or forms of organisms that exhibit gradual phenotypic and/or genetic differences over a geographical area, typically as a result of environmental heterogeneity. [ 43 ] [ 44 ] [ 45 ]  In the scientific study of human genetic variation, a gene cline can be rigorously defined and subjected to quantitative metrics.


In the study of  molecular evolution , a haplogroup is a group of similar  haplotypes  that share a  common ancestor  with a  single nucleotide polymorphism  (SNP) mutation. The study of haplogroups provides information about ancestral origins dating back thousands of years. [ 46 ]