There are no signs of sex-linked dwarfism in the first weeks of age. Some individuals can be identified as dwarfs at 8–10 weeks of age, but classification is more precise when the chickens are five months old or more. At this point differences between normal and dwarf sibs is evident in all males and in 98% of the females. [ 1 ]  These dwarfs reach sexual maturity and reproduce normally.


Normal females are always of genotype  Dw/- , while dwarf females are always of genotype  dw/- , because female is the  heterogametic sex  having only one  Z  chromosome. That is, females carrying a sex-linked gene of dwarfism are always pure and exhibit the trait. On the other hand, normal males may be either homozygous  Dw/Dw  or heterozygous  Dw/dw , but dwarf males are always homozygous  dw/dw .


Double dose of dwarf gene causes the dwarfism to be much more evident in males than in females. The above picture illustrates the comparative size of two full-sib roosters born the same day: Left: Normal sibling of genotype  Dw/dw . Right: Dwarf sibling of genotype  dw/dw .


Among the main factors involved in growth regulation,  thyroid hormones  tiroxine (T4)  triiodothyronine  (T3), growth hormone (GH), and its related growth factor, Insulin-like growth factor-I (IGF-I), were the most studied in dwarfs. [ 15 ]


Sex-linked dwarf chickens are characterized by low circulating levels of T3 and IGF-I in spite of normal or even increased levels of T4 and GH. The T3 deficiency is explained by a lower peripheral activity of T4 monodeiodination which could be related to an abnormal T4 uptake by the cell, particularly the hepatocyte. The low production of IGF-I could be related to a deficient GH receptor, as suggested by the decreased GH binding observed in the liver of dwarf birds. Both T3 and IGF-I synthesis may share common pathways since thyroidectomy also decreases IGF-I level while a GH injection stimulates the T4 to T3 monodeiodination in the normal embryo but not in the dwarf. Further studies are needed on the GH receptor and the T4 uptake in the hepatic cell to identify the common point where the dwarf gene could act. Ovulation rate and lipomobilisation are decreased in adult dwarfs but these findings are not yet easily related to the endocrinological changes observed during growth [ 16 ]


Administration of triiodothyronine (T3) in the diet, from day of hatch until 8 weeks of age, to sex-linked dwarf chickens stimulates growth but can not fully restore a normal growth rate. [ 17 ] [ 18 ]


Sex-linked dwarfism in chickens is a form of growth hormone resistance that resembles the  Laron syndrome  in humans, characterized by reductions in stature and plasma insulin-like growth factor-I (IGF-I) levels. [ 19 ]


Variants in chicken growth hormone receptor (GHR) gene lead to sex-linked dwarf chickens, but effects of different variants are distinct. [ 20 ]


Bantam dwarfism is a variety of dwarfism existing in many breeds of  bantam  chickens. Bantam chickens are also called miniatures. These birds are popular as pets, but Bantam hens are also renowned for hatching and  brooding  because they are very protective mothers  and will attack anything that gets near their young.


The reciprocal crosses made between normal sized chickens with Bantams revealed that Bantams carry one or several sex-linked dominant genes that reduce body size. [ 21 ] [ 22 ]  This mutation is present in  Sebright Bantams  and probably other bantams. This mutation is thought to be an allele at the  Dw  locus and to be different from the allele  dw . [ 23 ]


In genetics, the common convention is that most dominant alleles are written as capital letters and recessive alleles as lower-case letters (see:  Dominance (genetics) ). In spite of this, literature refers to the gene of Bantam dwarfism with the lower-case symbol  dw B .


A second type of sex-linked recessive dwarfism was found in a sex-linked dwarf chicken population. This mutation is thought to be an allele or the  Dw  locus and to be different from the  dw  allele. This conclusion is based on the fact that males heterozygous for  dw M / dw  produce female offspring which fall into two populations with respect to shank length. [ 24 ]  The evidence is inconclusive as to whether this allele is different or the same as the  dw B  allele.


Up to the present level of knowledge the  dominance  order of the alleles of locus  Dw  is:  dw B  >  Dw  >  dw .


In other words, allele  dw B  for Bantam dwarfism is   dominant  over the normal allele  Dw , and the last is dominant over the sex-linked recessive allele  dw . The existence of a second recessive allele has not yet been confirmed.


Sex-linked recessive dwarfism found application in poultry industry in the last decades of the 20th century. The application in broiler production is based on the known fact that dwarf female parents give 100% normal progeny when they are mated with normal male parents. The resulting progeny males are 100% heterozygotes  Dw / dw  and the females are hemizygotes  Dw /-.


In commercial broiler chicken production the use of dwarf female parents acquired a great importance. [ 25 ]  Nowadays, the majority of broiler breeders in Europe are the standard, fast growing genotype, but 18-20% of the broiler breeders are dwarf parental females that produce standard and alternative (medium or slow growing) broilers. [ 26 ]  The use of dwarfism also found application in commercial egg production. Dwarf Leghorn layers need less housing space, so the main advantage is to allow a more efficient use of housing space producing more eggs per unit of surface, but the smallest size of their eggs imposes a serious drawback to this purpose.


Under current practice, normal parent poultry breeding stock potentially face welfare problems. Intensive selection for production traits, especially growth rate, is associated with increased nutritious requirement and thus feed consumption, but also reproductive dysfunctions and decreased sexual activity in broiler breeders. A first resulting serious welfare problem is the subsequent severe feed restriction which is applied during rearing, in order to prevent health problems and to reach better egg production. This severe feed restriction has negative effects on bird welfare as it causes chronic stress resulting from hunger. [ 27 ]  The use of normal fast growing broiler breeder hens require dedicated programmes of feed restriction, both to maximise egg and chick production and secondly to avoid metabolic disorders and mortality in broiler breeders. The negative correlation between muscle growth and reproduction effectiveness is known as the "broiler breeder paradox". [ 28 ] [ 29 ]  Using dwarf broiler breeder hens is a good alternative, because dwarf hens combine relatively good reproductive fitness with  ad libitum  feeding. [ 28 ]


With respect to bird welfare the use of slow growing birds is a viable alternative to reduce the negative effects of feed restriction. Dwarf broiler breeders do not need to be (severely) feed restricted. [ 27 ] [ 30 ]
The resulting male progeny grow as fast as progeny from normal female parents. [ 31 ] [ 32 ]  The use of female broiler female parent breeders improves feed efficiency [ 33 ]  and allows a reduction of feed costs up to 33%. [ 34 ]  They take up 20-30% less housing space and have more tolerance to heat. [ 35 ]  Comparative performance tests proved that these are important advantages in tropical environments. [ 36 ]


Embark  is a canine genomics and biotechnology company based in  Boston , Massachusetts. The company offers dog  DNA  testing services to consumers, breeders, and veterinarians.


Embark was founded in  Austin, Texas , in 2015 by brothers Adam Boyko and Ryan Boyko,  Matt Salzberg , and  Spencer Wells . [ 1 ] [ 2 ]  Prior to the formation of the company, the Boyko brothers spent nearly a decade collecting thousands of DNA samples from dogs for research into the origin of dogs and what DNA can reveal about their health. This led to the formation of Embark, which sells dog DNA tests to dog owners, veterinarians, and breeders. [ 1 ] [ 3 ] [ 4 ] [ 5 ]  Embark's stated goals are to help pet owners better understand their dog's health and risk for  heritable diseases , and to advance canine DNA research in general. [ 1 ]


Adam Boyko is an associate professor at  Cornell University College of Veterinary Medicine . [ 5 ]  Ryan Boyko, the company’s CEO, was an independent researcher at Cornell [ 1 ]  and studied computer science and biology at  Harvard University . [ 6 ]  Wells directed the  Genographic Project  at the  National Geographic Society , and Salzberg is a founder of meal delivery company  Blue Apron . [ 1 ]


In March 2016, Embark launched publicly with a presentation by the Boyko brothers at  South by Southwest . [ 1 ] [ 7 ] [ 8 ]  That year, the startup began offering its DNA tests for dogs. [ 9 ]  In 2016, Embark raised a $1.6 million seed round investment, from lead investors Slow Ventures and Aspiration Growth Fund. [ 1 ]  The company raised an additional $4.5 million in seed funding in the summer of 2017, led by Founder Collective, and including  23andMe  founder  Anne Wojcicki . [ 2 ] [ 10 ]


In 2017, Embark relocated its headquarters from Austin to Boston, with its main science team remaining in  Ithaca, New York . [ 9 ] [ 3 ]  That year, the company was inducted into the McGovern Center, Cornell's incubator for life science companies. [ 11 ]  Embark is a research partner of Cornell University College of Veterinary Medicine. [ 5 ] [ 8 ]


The company uses submitted genetic data for research unless the customer opts out, raising privacy concerns. [ 12 ]  Some veterinarians have expressed skepticism about the lack of standards in DNA testing for dogs and the difficulty in properly analyzing and understanding the data, while acknowledging the potential of genetics to treat diseases. [ 13 ] [ 14 ] [ 15 ]  In 2018,  NPR  reported on shortcomings for DNA tests for dogs, including an incorrect analysis of the genetic data that can lead to unnecessary medical treatment and questionable clinical decisions. [ 16 ]   In 2018, science journal  Nature  ran an article by a veterinarian and two scientists stating that "pet genetics must be reined in" to avoid misinterpreting data. [ 17 ]


In July 2017, Embark worked with Cornell University to test more than 6,000 dogs of various breeds in order to identify the genetic mutation that causes blue eyes, which was the first research of its kind to be conducted on non-humans. Dog owners conducted DNA tests from Embark, completed online surveys, and Embark and Cornell analyzed the data. [ 12 ] [ 18 ]  Researchers discovered a genetic tweak in  Siberian Huskies  that can cause blue-eyed dogs. [ 18 ]


Adam Boyko was part of a team of scientists who in 2015 discovered that the origin of domestic dogs was near Central Asia 15,000 years ago. [ 19 ]  In 2016, he was the senior author of a study by Cornell College of Veterinary Medicine researchers that was the largest genetic study of dogs to ever be completed, with a collection of samples that included the DNA of more than 10,000 dogs from around the world. The researchers compared dogs of different purebred breeds in a large-scale genome-wide association study. It was published in the journal  Nature Communication . [ 20 ]


Eugenics  ( / j uː ˈ dʒ ɛ n ɪ k s /   yoo- JEN -iks ; from  Ancient Greek     εύ̃  (eû)  'good, well' and    -γενής  (genḗs)  'born, come into being, growing/grown') [ 1 ]  is a set of beliefs and practices that aim to improve the  genetic  quality of a  human population . [ 2 ] [ 3 ] [ 4 ]  Historically, eugenicists have attempted to alter the frequency of various human  phenotypes  by inhibiting the fertility of people and groups they considered inferior, or promoting that of those considered superior. [ 5 ]


The contemporary  history of eugenics  began in the late 19th century, when a popular eugenics movement emerged in the United Kingdom, [ 6 ]  and then spread to many countries, including the United States, Canada, Australia, [ 7 ]  and most European countries (e.g.  Sweden  and  Germany ). In this period, people from across the political spectrum espoused eugenic ideas. Consequently, many countries adopted eugenic policies, intended to improve the quality of their populations' genetic stock.


Historically, the idea of  eugenics  has been used to argue for a broad array of practices ranging from  prenatal care  for mothers deemed genetically desirable to the forced sterilization and murder of those deemed unfit. [ 5 ]  To  population geneticists , the term has included the avoidance of  inbreeding  without altering  allele frequencies ; for example, British-Indian scientist  J. B. S. Haldane  wrote in 1940 that "the motor bus, by breaking up inbred village communities, was a powerful eugenic agent." [ 8 ]  Debate as to what exactly counts as eugenics continues today. [ 9 ]  Early eugenicists were mostly concerned with factors of measured  intelligence  that often correlated strongly with social class.


Although it originated as a  progressive social movement  in the 19th century, [ 10 ] [ 11 ] [ 12 ] [ 13 ]  in contemporary usage in the 21st century, the term is closely associated with  scientific racism . New,  liberal eugenics  seeks to dissociate itself from old, authoritarian eugenics by rejecting coercive state programs and relying on parental choice. [ 14 ]


Eugenic programs included both  positive  measures, such as encouraging individuals deemed particularly "fit" to reproduce, and  negative  measures, such as marriage prohibitions and  forced sterilization  of people deemed unfit for reproduction. [ 5 ] [ 16 ] [ 17 ] : 104–155


In other words, positive eugenics is aimed at encouraging reproduction among the genetically advantaged, for example, the eminently intelligent, the healthy, and the successful. Possible approaches include financial and political stimuli, targeted demographic analyses,  in vitro  fertilization, egg transplants, and cloning. [ 18 ]  Negative eugenics aimed to eliminate, through sterilization or segregation, those deemed physically, mentally, or morally "undesirable". This includes abortions, sterilization, and other methods of family planning. [ 18 ]  Both positive and negative eugenics can be coercive; in Nazi Germany, for example, abortion was illegal for women deemed by the state to be fit. [ 19 ]


Euthenics  ( / j uː ˈ θ ɛ n ɪ k s / ) is the study of improvement of human functioning and  well-being  by improvement of  living conditions . [ 20 ]  "Improvement" is conducted by altering external factors such as  education  and the controllable  environments , including  environmentalism , education regarding  employment ,  home economics ,  sanitation , and  housing , as well as the prevention and removal of  contagious disease  and  parasites .


In a  New York Times  article of May 23, 1926, Rose Field notes of the description, "the simplest [is] efficient living". [ 21 ]  It is also described as "a right to environment", [ 22 ]  commonly as dual to a "right of birth" that correspondingly falls under the purview of eugenics. [ 23 ]


The influential historian of education  Abraham Flexner  questions its scientific value in stating:


[T]he “science” is artificially pieced together of bits of mental hygiene, child guidance, nutrition, speech development and correction, family problems, wealth consumption, food preparation, household technology, and horticulture. A nursery school and a school for little children are also included. The institute is actually justified in an official publication by the profound question of a girl student who is reported as asking, “What is the connection of Shakespeare with having a baby?” The Vassar Institute of Euthenics bridges this gap! [ 25 ]


Eugenicist  Charles Benedict Davenport  noted in his article "Euthenics and Eugenics," reprinted in  Popular Science Monthly :


Thus the two schools of euthenics and eugenics stand opposed, each viewing the other unkindly. Against eugenics it is urged that it is a fatalistic doctrine and deprives life of the stimulus toward effort.  Against euthenics the other side urges that it demands an endless amount of money to patch up conditions in the vain effort to get greater efficiency.  Which of the two doctrines is true?


The thoughtful mind must concede that, as is so often the case where doctrines are opposed, each view is partial, incomplete and really false. The truth does not exactly lie between the doctrines; it comprehends them both.


[...] [I]n the generations to come, the teachings and practice of euthenics [...] [may] yield greater result because of the previous practice of the principles of eugenics. [ 26 ]


The more rational the race becomes, the better roads, ships, tools, machines, foods, medicines and the like it will produce to aid itself, though it will need them less. The more sagacious and just and humane the original nature that is bred into man, the better schools, laws, churches, traditions and customs it will fortify itself by. There is no so certain and economical a way to improve man's environment as to improve his nature. [ 27 ]


According to  Plutarch , in  Sparta  every proper citizen's child was inspected by the council of elders, the  Gerousia , which determined whether or not the child was fit to live. [ 28 ]  If the child was deemed incapable of living a Spartan life, the child was usually killed in a chasm near the  Taygetus  mountain known as the  Apothetae . [ 29 ] [ 30 ]  Further trials intended to discern a child's fitness included bathing them in  wine  and exposing them to the elements to fend for themselves, with the intention of ensuring that only those considered strongest survived and procreated. [ 31 ]


The lack of sources by contemporary Greeks mentioning Spartan eugenics and the lack of archeological evidence has brought ideas about Spartan eugenics into question. While  infanticide  was practiced by Greeks, no contemporary sources support Plutarch's claims of mass infanticide motivated by eugenics. [ 32 ]  In 2007 the suggestion that infants were dumped near Mount Taygete was called into question due to a lack of physical evidence. Anthropologist Theodoros Pitsios' research found only bodies from adolescence up to the age of approximately 35. [ 33 ] [ 34 ]


Plato's political philosophy  included the belief that human reproduction should be cautiously monitored and controlled by the state. [ 35 ]  He advocated that  selective breeding  should be applied to both humans and animals. Plato recognized that this form of government control would not be readily accepted, and proposed the truth be concealed from the public via a fixed lottery. Mates, in Plato's  Republic , would be chosen by a "marriage number" in which the quality of the individual would be quantitatively analyzed, and persons of high numbers would be allowed to procreate with other persons of high numbers. This would then lead to predictable results and the improvement of the human race. Plato acknowledged the failure of the "marriage number" since "gold soul" persons could still produce "bronze soul" children. [ 36 ]  Plato's ideas may have been one of the earliest attempts to mathematically analyze  genetic inheritance , prefiguring some of what would much later become known as  Mendelian genetics . [ 37 ]


The geographer  Strabo  ( c.  64 BCE –  c.  24 CE) stated that the  Samnites  would take ten  virgin  women and ten young men who were considered to be the best representation of their  sex  and  mate  them. Any selected male committing a dishonorable act would be separated from his partner. [ 38 ]


The term  eugenics  and its modern field of study were first formulated by  Francis Galton  in 1883, [ 40 ] [ 41 ] [ 42 ] [ a ]  directly drawing on the recent work delineating  natural selection  by his half-cousin  Charles Darwin . [ 44 ] [ 45 ] [ 46 ] [ b ]  He published his observations and conclusions chiefly in his influential book  Inquiries into Human Faculty and Its Development . Galton himself defined it as "the study of all agencies under human control which can improve or impair the racial quality of future generations". [ 48 ]  The first to systematically apply Darwinism theory to human relations, Galton believed that various desirable human qualities were also  hereditary  ones, although Darwin strongly disagreed with this elaboration of his theory. [ 49 ]


Eugenics became an academic discipline at many colleges and universities and received funding from various sources. [ 50 ]  Organizations were formed to win public support for and to sway opinion towards responsible eugenic values in parenthood, including the British  Eugenics Education Society  of 1907 and the  American Eugenics Society  of 1921. Both sought support from leading clergymen and modified their message to meet religious ideals. [ 51 ]  In 1909, the Anglican clergymen  William Inge  and  James Peile  both wrote for the Eugenics Education Society. Inge was an invited speaker at the 1921  International Eugenics Conference , which was also endorsed by the Roman Catholic Archbishop of New York  Patrick Joseph Hayes . [ 51 ]


Three  International Eugenics Conferences  presented a global venue for eugenicists, with meetings in 1912 in London, and in 1921 and 1932 in New York City.  Eugenic policies in the United States  were first implemented by state-level legislators in the early 1900s. [ 52 ]  Eugenic policies also took root in France, Germany, and Great Britain. [ 53 ]  Later, in the 1920s and 1930s, the eugenic policy of  sterilizing  certain mental patients was implemented in other countries including Belgium, [ 54 ]  Brazil, [ 55 ]   Canada , [ 56 ]   Japan  and  Sweden .


Frederick Osborn 's 1937 journal article "Development of a Eugenic Philosophy" framed eugenics as a  social philosophy —a philosophy with implications for  social order . [ 57 ]  That definition is not universally accepted. Osborn advocated for higher rates of  sexual reproduction  among people with desired traits ("positive eugenics") or reduced rates of sexual reproduction or  sterilization  of people with less-desired or undesired traits ("negative eugenics").


In addition to being practiced in a number of countries, eugenics was internationally organized through the  International Federation of Eugenics Organizations . [ 58 ]  Its scientific aspects were carried on through research bodies such as the  Kaiser Wilhelm Institute of Anthropology, Human Heredity, and Eugenics , [ 59 ]  the Cold Spring Harbor Carnegie Institution for  Experimental Evolution , [ 60 ]  and the  Eugenics Record Office . [ 61 ]  Politically, the movement advocated measures such as sterilization laws. [ 62 ]  In its moral dimension, eugenics rejected the doctrine that all human beings are born equal and redefined moral worth purely in terms of genetic fitness. [ 63 ]  Its racist elements included pursuit of a pure " Nordic race " or " Aryan " genetic pool and the eventual elimination of "unfit" races. [ 64 ] [ 65 ]


Many leading British politicians subscribed to the theories of eugenics.  Winston Churchill  supported the British Eugenics Society and was an honorary vice president for the organization. Churchill believed that eugenics could solve "race deterioration" and reduce crime and poverty. [ 47 ] [ 66 ] [ 67 ]


As a social movement, eugenics reached its greatest popularity in the early decades of the 20th century, when it was practiced around the world and promoted by governments, institutions, and influential individuals. Many countries enacted [ 68 ]  various eugenics policies, including:  genetic screenings ,  birth control , promoting differential birth rates,  marriage restrictions , segregation (both  racial segregation  and sequestering the mentally ill),  compulsory sterilization ,  forced abortions  or  forced pregnancies , ultimately culminating in  genocide . By 2014, gene selection (rather than "people selection") was made possible through advances in  genome editing , [ 69 ]  leading to what is sometimes called  new eugenics , also known as "neo-eugenics", "consumer eugenics", or "liberal eugenics"; which focuses on individual freedom and allegedly pulls away from racism, sexism or a focus on intelligence. [ 70 ]


Early critics of the philosophy of eugenics included the American sociologist  Lester Frank Ward , [ 71 ]  the English writer  G. K. Chesterton , and Scottish tuberculosis pioneer and author  Halliday Sutherland . [ c ]  Ward's 1913 article "Eugenics, Euthenics, and Eudemics", Chesterton's 1917 book  Eugenics and Other Evils , [ 73 ]  and  Franz Boas ' 1916 article " Eugenics " (published in  The Scientific Monthly ) [ 74 ]  were all harshly critical of the rapidly growing movement.


Several biologists were also antagonistic to the eugenics movement, including  Lancelot Hogben . [ 75 ]  Other biologists who were themselves eugenicists, such as  J. B. S. Haldane  and  R. A. Fisher , however, also expressed skepticism in the belief that sterilization of "defectives" (i.e. a purely negative eugenics) would lead to the disappearance of undesirable genetic traits. [ 76 ]


Among institutions, the  Catholic Church  was an opponent of state-enforced sterilizations, but accepted isolating people with hereditary diseases so as not to let them reproduce. [ 77 ]  Attempts by the Eugenics Education Society to persuade the British government to legalize voluntary sterilization were opposed by Catholics and by the  Labour Party . [ 78 ]  The  American Eugenics Society  initially gained some Catholic supporters, but Catholic support declined following the 1930 papal encyclical  Casti connubii . [ 51 ]  In this,  Pope Pius XI  explicitly condemned sterilization laws: "Public magistrates have no direct power over the bodies of their subjects; therefore, where no crime has taken place and there is no cause present for grave punishment, they can never directly harm, or tamper with the integrity of the body, either for the reasons of eugenics or for any other reason." [ 79 ]


In fact, more generally, "[m]uch of the opposition to eugenics during that era, at least in Europe, came from the right." [ 17 ] : 36   The eugenicists' political successes in  Germany  and  Scandinavia  were not at all matched in such countries as  Poland  and  Czechoslovakia , even though measures had been proposed there, largely because of the Catholic church's moderating influence. [ 80 ]


Dysgenics   refers to any decrease in the prevalence of traits deemed to be either socially desirable or generally adaptive to their environment due to  selective pressure  disfavouring their reproduction. [ 81 ]


In 1915 the term was used by  David Starr Jordan  to describe the supposed deleterious effects of modern warfare on group-level genetic fitness because of its tendency to kill physically healthy men while preserving the disabled at home. [ 82 ] [ 83 ]  Similar concerns had been raised by early eugenicists and  social Darwinists  during the 19th century, and continued to play a role in scientific and public policy debates throughout the 20th century. [ 84 ]


More recent concerns about supposed dysgenic effects in human populations were advanced by the controversial psychologist and self-described " scientific racist " [ 85 ]   Richard Lynn , notably in his 1996 book  Dysgenics: Genetic Deterioration in Modern Populations , which argued that changes in  selection pressures  and decreased  infant mortality  since the  Industrial Revolution  have resulted in an increased propagation of deleterious traits and  genetic disorders . [ 86 ] [ 87 ]


Compulsory sterilization , also known as forced or coerced sterilization, refers to any government-mandated program to  involuntarily   sterilize  a specific group of people. Sterilization removes a person's capacity to reproduce, and is usually done by surgical or  chemical  means.


Purported justifications for compulsory sterilization have included  population control , eugenics, limiting the spread of  HIV , and  ethnic genocide .


Eugenic feminism was a current of the  women's suffrage movement  which overlapped with eugenics. [ 93 ]  Originally coined by the Lebanese-British physician and vocal eugenicist  Caleb Saleeby , [ 94 ] [ 95 ] [ 96 ]  the term has since been applied to summarize views held by prominent feminists of Great Britain and the United States. Some early suffragettes in Canada, especially a group known as  The Famous Five , also pushed for various eugenic policies.


Following the  Mexican Revolution , the eugenics movement gained prominence in Mexico. Seeking to change the genetic make-up of the country's population, proponents of  eugenics in Mexico  focused primarily on rebuilding the population, creating healthy citizens, and ameliorating the effects of perceived social ills such as alcoholism, prostitution, and venereal diseases. Mexican eugenics, at its height in the 1930s, influenced the state's health, education, and welfare policies. [ 101 ]


The scientific reputation of eugenics started to decline in the 1930s, a time when  Ernst Rüdin  used eugenics as a justification for the  racial policies of Nazi Germany .  Adolf Hitler  had praised and incorporated eugenic ideas in  Mein Kampf  in 1925 and emulated eugenic legislation for the sterilization of "defectives" that had been pioneered in the United States once he took power. [ 105 ]  Some common early 20th century eugenics methods involved identifying and classifying individuals and their families, including the poor, mentally ill, blind, deaf, developmentally disabled,  promiscuous women , homosexuals, and  racial groups  (such as the  Roma  and  Jews in Nazi Germany ) as "degenerate" or "unfit", and therefore led to segregation, institutionalization, sterilization, and even  mass murder . [ 106 ]  The Nazi policy of identifying German citizens deemed mentally or physically unfit and then systematically killing them with poison gas, referred to as the  Aktion T4  campaign, is understood by historians to have paved the way for the  Holocaust . [ 107 ] [ 108 ] [ 109 ]


"All practices aimed at eugenics, any use of the human body or any of its parts for financial gain, and  human cloning  shall be prohibited."


By the end of  World War II , many eugenics laws were abandoned, having become associated with  Nazi Germany . [ 111 ]   H. G. Wells , who had called for "the sterilization of failures" in 1904, [ 112 ]  stated in his 1940 book  The Rights of Man: Or What Are We Fighting For?  that among the human rights, which he believed should be available to all people, was "a prohibition on  mutilation , sterilization,  torture , and any bodily punishment". [ 113 ]  After World War II, the practice of "imposing measures intended to prevent births within [a national, ethnical, racial or religious] group" fell within the definition of the new international crime of genocide, set out in the  Convention on the Prevention and Punishment of the Crime of Genocide . [ 114 ]  The  Charter of Fundamental Rights of the European Union  also proclaims "the prohibition of eugenic practices, in particular those aiming at selection of persons". [ 115 ]


Lee Kuan Yew , the  founding father  of  Singapore , actively promoted eugenics as late as 1983. [ 116 ]  In 1984, Singapore began providing financial incentives to highly educated women to encourage them to have more children. For this purpose was introduced the "Graduate Mother Scheme" that incentivized graduate women to get married as much as the rest of their populace. [ 117 ]  The incentives were extremely unpopular and regarded as eugenic, and were seen as discriminatory towards Singapore's non-Chinese ethnic population. In 1985, the incentives were partly abandoned as ineffective, while the government matchmaking agency, the  Social Development Network , remains active. [ 118 ] [ 119 ] [ 120 ]


Developments in  genetic ,  genomic , and  reproductive technologies  at the beginning of the 21st century have raised numerous questions regarding the ethical status of eugenics, sparking  renewed interest  in the topic.


Liberal eugenics, also called new eugenics, aims to make genetic interventions morally acceptable by rejecting coercive state programs and relying on parental choice. [ 121 ] [ 14 ]  Bioethicist  Nicholas Agar , who coined the term, argues for example that the state should only intervene to forbid interventions that excessively limit a child’s ability to shape their own future. [ 122 ]  Unlike "authoritarian" or "old" eugenics, liberal eugenics draws on modern scientific knowledge of  genomics  to enable informed choices aimed at improving well-being. [ 14 ]   Julien Savulescu  further argues that some eugenic practices like  prenatal screening  for  Down syndrome  are already widely practiced, without being labeled "eugenics", as they are seen as enhancing freedom rather than restricting it. [ 123 ]


Some critics, such as  UC Berkeley  sociologist  Troy Duster , have argued that modern genetics is a "back door to eugenics". [ 124 ]  This view was shared by then-White House Assistant Director for Forensic Sciences,  Tania Simoncelli , who stated in a 2003 publication by the Population and Development Program at  Hampshire College  that advances in  pre-implantation genetic diagnosis  (PGD) are moving society to a "new era of eugenics", and that, unlike the Nazi eugenics, modern eugenics is consumer driven and market based, "where children are increasingly regarded as made-to-order consumer products". [ 125 ]  The United Nations'  International Bioethics Committee  also noted that while  human genetic engineering  should not be confused with the  20th century eugenics movements , it nonetheless challenges the idea of human equality and opens up new forms of discrimination and stigmatization for those who do not want or cannot afford the technology. [ 126 ]


In 2025, geneticist  Peter Visscher  published a paper in  Nature ,  arguing genome editing of human embryos and germ cells may become feasible in the 21st century, and raising ethical considerations in the context of previous eugenics movements. [ 127 ] [ 128 ]  A response argued that human embryo genetic editing is "unsafe and unproven". [ 129 ]   Nature  also published an editorial, stating: "The fear that polygenic gene editing could be used for eugenics looms large among them, and is, in part, why no country currently allows genome editing in a human embryo, even for single variants". [ 128 ]


One general concern that many bring to the table, is that the reduced  genetic diversity  some argue to be a likely feature of long-term, species-wide eugenics plans, [ 130 ]  could eventually result in  inbreeding depression , [ 130 ]  increased spread of  infectious disease , [ 131 ] [ 132 ] [ better source needed ]  and decreased resilience to changes in the environment. [ 133 ] [ better source needed ]


In his original lecture "Darwinism, Medical Progress and Eugenics",  Karl Pearson  claimed that everything concerning eugenics fell into the field of medicine. [ 134 ]  Anthropologist  Aleš Hrdlička  said in 1918 that "[t]he growing science of eugenics will essentially become applied anthropology." [ 135 ]  The economist  John Maynard Keynes  was a lifelong proponent of eugenics and described it as a branch of sociology. [ 136 ] [ 137 ]


In a 2006 newspaper article, Richard Dawkins said that discussion regarding eugenics was inhibited by the shadow of Nazi misuse, to the extent that some scientists would not admit that breeding humans for certain abilities is at all possible. He believes that it is not physically different from breeding domestic animals for traits such as speed or herding skill. Dawkins felt that enough time had elapsed to at least ask just what the ethical differences were between breeding for ability versus training athletes or forcing children to take music lessons, though he could think of persuasive reasons to draw the distinction. [ 138 ]


Amanda Caleb, Professor of Medical Humanities at  Geisinger Commonwealth School of Medicine , says "Eugenic laws and policies are now understood as part of a specious devotion to a pseudoscience that actively dehumanizes to support political agendas and not true science or medicine." [ 139 ]


The first major challenge to conventional eugenics based on genetic inheritance was made in 1915 by  Thomas Hunt Morgan . He demonstrated the event of  genetic mutation  occurring outside of inheritance involving the discovery of the hatching of a  fruit fly ( Drosophila melanogaster )  with white eyes from a family with red eyes, [ 47 ] : 336–337   demonstrating that major genetic changes occurred outside of inheritance. [ 47 ] : 336–337  [ clarification needed ]  Additionally, Morgan criticized the view that certain traits, such as  intelligence  and criminality, were hereditary because these traits were  subjective . [ 140 ] [ d ]


Pleiotropy  occurs when one  gene  influences multiple, seemingly unrelated  phenotypic traits , an example being  phenylketonuria , which is a human disease that affects multiple systems but is caused by one gene defect. [ 143 ]  Andrzej Pękalski, from the  University of Wroclaw , argues that eugenics can cause harmful loss of genetic diversity if a eugenics program selects a pleiotropic gene that could possibly be associated with a positive trait. Pękalski uses the example of a coercive government eugenics program that prohibits people with  myopia  from breeding but has the unintended consequence of also selecting against high intelligence since the two go together. [ 144 ]


While the science of genetics has increasingly provided means by which certain characteristics and conditions can be identified and understood, given the complexity of human genetics, culture, and psychology, at this point there is no agreed objective means of determining which traits might be ultimately desirable or undesirable. Some conditions such as  sickle-cell disease  and  cystic fibrosis  respectively confer immunity to malaria and resistance to  cholera  when a single copy of the recessive allele is contained within the genotype of the individual, so eliminating these genes is undesirable in places where such diseases are common. [ 133 ]  Such cases in which, furthermore, even individual organisms' massive suffering or even death due to the odd 25 percent of  homozygotes  ineliminable by natural section under a  Mendelian pattern of inheritance  may be justified for the greater ecological good that is  conspecifics  incur a greater so-called  heterozygote advantage  in turn. [ 145 ]


Edwin Black , journalist, historian, and author of  War Against the Weak , argues that eugenics is often deemed a  pseudoscience  because what is defined as a genetic improvement of a desired trait is a cultural choice rather than a matter that can be determined through objective scientific inquiry. [ 2 ]  This aspect of eugenics is often considered to be tainted with  scientific racism  and pseudoscience. [ 2 ] [ 146 ]


In a book directly addressed at socialist eugenicist  J.B.S. Haldane  and his once-influential  Daedalus ,  Betrand Russell , had one serious objection of his own: eugenic policies might simply end up being used to reproduce existing power relations "rather than to make men happy." [ 148 ]


Environmental ethicist   Bill McKibben  argued against  germinal choice technology  and other advanced biotechnological strategies for human enhancement. He writes that it would be morally wrong for humans to tamper with fundamental aspects of themselves (or their children) in an attempt to overcome universal human limitations, such as vulnerability to  aging ,  maximum life span  and biological constraints on physical and cognitive ability. Attempts to "improve" themselves through such manipulation would remove limitations that provide a necessary context for the experience of meaningful human choice. He claims that human lives would no longer seem  meaningful  in a world where such limitations could be overcome with technology. Even the goal of using germinal choice technology for clearly therapeutic purposes should be relinquished, he argues, since it would inevitably produce temptations to tamper with such things as cognitive capacities. He argues that it is possible for societies to benefit from renouncing particular technologies, using  Ming China ,  Tokugawa Japan  and the contemporary  Amish  as examples. [ 149 ]


Bioethicist  Stephen Wilkinsonhas said that some aspects of modern genetics can be classified as eugenics, but that this classification does not inherently make modern genetics immoral. [ 150 ]


Historian  Nathaniel C. Comfort  has claimed that the change from state-led reproductive-genetic decision-making to individual choice has moderated the worst abuses of eugenics by transferring the decision-making process from the state to patients and their families. [ 151 ] [ 152 ]


In their book published in 2000,  From Chance to Choice: Genetics and Justice , bioethicists  Allen Buchanan ,  Dan Brock ,  Norman Daniels  and  Daniel Wikler  argued that liberal societies have an obligation to encourage as wide an adoption of eugenic enhancement technologies as possible (so long as such policies do not infringe on individuals'  reproductive rights  or exert undue pressures on prospective parents to use these technologies) in order to maximize  public health  and minimize the inequalities that may result from both natural genetic endowments and unequal access to genetic enhancements. [ 17 ]


Savulescu coined the term  procreative beneficence.  He describes it as the  moral obligation  (rather than mere permission) of  parents  who can select among potential children to choose those expected to have the best life prospects. For instance through  preimplantation genetic diagnosis  (PGD) and subsequent  embryo selection  or  selective termination . [ 153 ] [ 154 ] [ 155 ]  A similar position was defended by  John Harris . [ 156 ]  One argument is that some traits such as memory are "all-purpose means", in the sense of being instrumental in realizing whatever life plans the child may come to have. [ 157 ] [ 158 ]


The novel  Brave New World  by the English author  Aldous Huxley  (1931), is a  dystopian   social science fiction  novel which is set in a futuristic  World State , whose citizens are environmentally engineered into an intelligence-based  social hierarchy .


Various works by the author  Robert A. Heinlein  mention the  Howard Foundation , a group which attempts to improve human longevity through  selective breeding .


Among  Frank Herbert 's other works, the  Dune  series, starting with  the eponymous 1965 novel , describes selective breeding by a powerful sisterhood, the  Bene Gesserit , to produce a supernormal male being, the  Kwisatz Haderach . [ 160 ]


The  Star Trek  franchise features a race of genetically engineered humans which is known as "Augments", the most notable of them is  Khan Noonien Singh . These "supermen" were the cause of the  Eugenics Wars , a dark period in Earth's fictional history, before they were deposed and exiled. They appear in many of the franchise's story arcs, most frequently, they appear as villains. [ 161 ] [ e ]


The film  Gattaca  (1997) provides a fictional example of a  dystopian  society that uses eugenics to decide what people are capable of and their place in the world. The title alludes to the letters  G ,  A ,  T  and  C , the four  nucleobases  of  DNA , and depicts the possible consequences of  genetic discrimination  in the present societal framework. Relegated to the role of a cleaner owing to his genetically projected death at age 32 due to a heart condition (being told: "The only way you'll see the inside of a spaceship is if you were cleaning it"), the protagonist observes enhanced astronauts as they are demonstrating their superhuman athleticism. Although it was not a box office success, it was critically acclaimed and influenced the debate over  human genetic engineering  in the public consciousness. [ 164 ] [ 165 ] [ f ]  As to its accuracy, its production company,  Sony Pictures , consulted with a  gene therapy  researcher and prominent critic of eugenics known to have stated that "[w]e should not step over the line that delineates treatment from enhancement", [ 168 ]   W. French Anderson , to ensure that the portrayal of science was realistic. Disputing their success in this mission, Philim Yam of  Scientific American  called the film "science bashing" and  Nature 's  Kevin Davies called it a "surprisingly pedestrian affair", while  molecular biologist   Lee Silver  described its extreme  determinism  as "a  straw man ". [ 169 ] [ 170 ]


In his 2018 book  Blueprint , the  behavioral geneticist   Robert Plomin  writes that while  Gattaca  warned of the dangers of genetic information being used by a totalitarian state, genetic testing could also favor better  meritocracy  in democratic societies which already administer a variety of  standardized tests  to select people for education and employment. He suggests that  polygenic scores  might supplement testing in a manner that is essentially free of biases. [ 171 ]


Law professors  George Annas  and  Lori Andrews  have similarly argued that the use of these technologies could lead to such human- posthuman   caste  warfare. [ 162 ] [ 163 ]


Accordingly,  Lee M. Silver  stated that " Gattaca  is a film that all geneticists should see if for no other reason than to understand the perception of our trade held by so many of the public-at-large". [ 167 ]


Expected progeny differences  (EPD) are an evaluation of an  animal ’s genetic worth as a parent. They are based on  animal models  which combine all information known about an individual and its relatives to create a  genetic profile  of the animal’s merits. These profiles are then compared to other individuals of the same breed.


An example of a set of EPDs looks like the following  chart . Each set of letters stands for a specific measurement with an accuracy reading and percent rank below it. Each EPD is compared to the  breed   average  of a given year. The number given by the EPD is the amount above or below this given average.


Growth EPDs measure the amount of weight a given offspring will gain due to the parent's  genetics .


Calving  ease predicts the level of difficulty first time  heifers  will have during birth. These are determined by the percentage of  unassisted births  for that particular animal. [ 1 ]


Birth weight  measures how much above or below the breed's average an  offspring  will gain due to the parent. It does not necessarily predict the exact weight of all offspring, but instead gives a general prediction of how much extra or less weight an offspring will weigh compared to if it had been sired by another bull. High birth weight is the biggest cause of difficulty in calving, so having a  bull  with a low birth weight EPD is high beneficial. [ 1 ]


Weaning  and  yearling  weight measure the amount of weight an offspring has gained by the time it is weaned and at the one year mark. Typically the weaning weight is measured at the 205-day mark and the yearling weight is taken at the 365-day mark. Typically a larger number is favored for both of these traits. [ 2 ]


Milk EPDs give an estimate for the maternal portion of the weaning weight that determined by  milk production  of the  dam . It is measured in pounds of weaning weight of a bull's grandprogeny due to the milk production of the bull's daughters. [ 2 ]


Scrotal  circumference is an indicator of a bull's  fertility . A larger circumference is preferred and is an indicator for his sons to have a larger scrotal circumference and his daughters to reach  puberty  sooner and therefore have  calves  sooner. [ 2 ]


Gestation  length is an indicator of the probability of  dystocia . The longer a calf is  in utero  the larger it will be at birth and the greater the chance of it having dystocia. It also gives the cow a larger postpartum interval between  pregnancies . A shorter gestation length is usually preferred because of this. [ 2 ]


Stayability is an indicator EPD of  longevity  of a bull's daughter in a  cow  herd. The higher the EPD value the greater chance a cow will stay in a herd over six years and continue producing quality offspring. [ 2 ]


Carcass weight  predicts what an animal's total  retail  product will be compared to other animals of that breed. It does not however predict percent retail value, or the actual amount of sellable  meat  that can be produced from the carcass. [ 3 ]


Fat  thickness determined the expected external and seam fat the animal will contain. These two factors contribute to the greatest waste in an animal and best way to reduce  economic loss . Fat thickness EPDs can help producers reduce this loss, by using animals with mid range EPDs, so as not to have too little or too much fat. [ 3 ]


Marbling  EPDs are also important in the  beef  industry for predicting palatability in a beef carcass. They show the estimated  USDA  Quality grading System and marbling score an animal would receive if it were  slaughtered . This EDP is different in that it is measured in units of marbling score, and not in weight gained by an animal. Higher values indicate the presence of genes that will produce more  intramuscular fat . [ 3 ]


EPDs are used in both  scientific research  and in typical  farm  usage. Through mathematical equations and computing power EPDs can be generated for use in both situations. Through EPDs certain  phenotypes  can be chosen for over others. Use of EPSs and  DNA markers  can help when choosing certain traits over others. By using certain EPDs of an animal one can rapidly improve genetics of a herd, especially for highly heritable traits such as marbling. In addition, by using a combination of EPDs and DNA markers, EPDs can be made more accurate.  When new DNA markers are used, they can help adjust the EPD according to the  genotype  and therefore produce a more accurate measurement. [ 4 ]


To determine how accurate EPDs are for an individual, samples of all of a bull's offspring are looked at and compared to what their expected outcome should have been. The EPDs can then be changed based on the values that are gathered. The higher the accuracy rate, the closer most of the  progeny  will be to the EPD values listed. Accuracy is not an indicator of beneficial EPDs, but rather shows how close the EPD is to the true genetic potential of the animal. [ 2 ]  The closer an accuracy value is to 1, the more accurate the EPDs can be thought to be. Other factors can affect the progeny as well, such as non genetic effects including feed, weather, environment, as well as  random Mendelian sampling .


In addition to the EPD and accuracy shown in a chart, often the percent rank is also given. This shows what percentile the animal ranks for the given EPD. The higher the  percentile , the better the EPD is for that characteristic. The better the EPDs for a given bull, the higher chance its progeny will have a given characteristic. [ 5 ]


In  medicine , a  family history  ( FH  or  FHx ) consists of information about disorders of direct blood relatives of the patient. [ 1 ]   Genealogy  typically includes very little of the  medical history  of the  family , but the medical history could be considered a specific  subset  of the total history of a family. [ citation needed ]  Accurate knowledge of a patient's family history may identify a predisposition to developing certain illnesses, which can inform clinical decisions and allow effective management or even prevention of conditions. [ 2 ] [ 3 ]


Early mentions of family medical histories in medical literature date from the 1840s. Henry Ancell mentioned inquiring about the family history of a patient in a medical case study in 1842, noting that the patient's presenting concern appears to be present in relatives and remarking on the prolific reproduction of her female relatives. [ 4 ]  In 1849, W.H. Walshe argued in a lecture at  University College London Hospital  that in addition to a history of the presenting disease itself, a physician should also collect family history. [ 5 ]   Walshe's lecture does not define or justify the family history, which may suggest that taking one was already in common practice. However, later 19th-century physicians did provide a specific apologia for family histories and in some cases explicitly noted that they were not yet being taken routinely.


James Begbie  argued that understanding the health of the entire family, including cousins, can help predict otherwise unpredictable illnesses that run in the family. [ 6 ]   Begbie's use of the family history for both predictive and normative evaluation of the family anticipated  Francis Galton , who championed the routine family history as a  eugenic  strategy in his 1883 text,  Inquiries into Human Faculty and Its Development . Galton writes:


"The investigation of human eugenics—that is, of the conditions under which men of a high type are produced—is at present extremely hampered by the want of full family histories, both medical and general, extending over three or four generations. There is no such difficulty in investigating animal eugenics, because the generations of horses, cattle, dogs, etc., are brief, and the breeder of any such stock lives long enough to acquire a large amount of experience from his own personal observation. A man, however, can rarely be familiar with more than two or three generations of his contemporaries before age has begun to check his powers; his working experience must therefore be chiefly based upon records. Believing, as I do, that human eugenics will become recognised before long as a study of the highest practical importance, it seems to me that no time ought to be lost in encouraging and directing a habit of compiling personal and family histories." [ 7 ]


Galton argued in the early 1900s for the development of eugenic certification based on consulting these histories. [ 8 ]  Starting in the 1920s, family medical histories were used by government eugenics bodies to evaluate candidates for  compulsory sterilization . [ 9 ] [ 10 ]  Eugenics Boards such as the  Eugenics Board of North Carolina  also considered family medical histories for the issuance of eugenic certificates marking a candidate as fit for marriage and reproduction. [ 11 ]  The  Disability History Museum  includes a mock eugenic certificate from circa 1924 which was intended to be sent as a love note. [ 12 ]


Although sometimes neglected, [ 13 ]  many healthcare professionals glean information on family morbidity of particular diseases (e.g.  cardiovascular diseases ,  autoimmune disorders ,  mental disorders ,  diabetes ,  cancer ) to assess whether a person is at risk of developing similar problems.


Family histories may be imprecise because of various possible reasons:


Some medical conditions are carried only by the female line such as  X-linked conditions  and some  Mitochondrial diseases .  Tracing female ancestors can be difficult in societies that change the woman's family name when she marries. Death records often give the maiden name of the deceased, and possibly also the deceased's mother's maiden name. Some of the most useful records for tracing women are wills and probate records.


Other medical conditions are carried only by the male line, though these  Y-linked conditions  are rare owing to the small size of the Y Chromosome. Tracing male ancestors may be impossible if the conception is due to rape or sexual activity outside of marriage.


Attaining the age when family members are diagnosed with a certain disease can also be helpful for screening purposes, like colon and breast cancer.


Not all positive family histories imply a genetic cause. If various members of the same family have been exposed to the same  toxin , then they may develop similar symptoms without a genetic cause.


If a patient has a strong family history of a particular disorder (or group of disorders), this will generally lead to a lower threshold for investigating symptoms or initiating treatment. This is seen particularly in cardiac disease, where strong family history is considered a significant  cardiovascular  risk factor. [ 14 ]


In diseases with a known hereditary component, many otherwise healthy people with a positive family history are tested early, with the aim of an early diagnosis and intervention to prevent the symptoms from developing. This has become accepted in  hemochromatosis  and various other disorders.


FamilyTreeDNA  is a division of  Gene by Gene , a commercial  genetic testing  company based in  Houston ,  Texas .  FamilyTreeDNA offers analysis of  autosomal DNA ,  Y-DNA , and  mitochondrial DNA  to individuals for genealogical purpose. With a database of more than two million records, it is the most popular company worldwide for Y-DNA and mitochondrial DNA, and the fourth most popular for autosomal DNA. In Europe, it is the most common also for autosomal DNA. [ 2 ] [ 3 ]  FamilyTreeDNA as a division of Gene by Gene were acquired by MYDNA, Inc., an Australian company, in January 2021. [ 4 ]


FamilyTreeDNA was founded based on an idea conceived by  Bennett Greenspan , a lifelong entrepreneur and genealogy enthusiast. In 1999, Greenspan had entered semi-retirement and was working on his family history.  He began work on his mother's Nitz lineage. [ 5 ] [ 6 ] [ 7 ]  When faced with a roadblock in his work, he remembered two cases of genetics being used to prove ancestry that had recently been covered by the media.  These were a study by University of Arizona researchers showing that many Cohen men from both Ashkenazic and Sephardic groups share the same Y-chromosome [ 8 ]  and a study that showed that male descendants of a paternal uncle of US President  Thomas Jefferson  (who presumably shared his Y-chromosome) and male-line descendants of his freed slave Sally Hemings shared the same Y-chromosome and a recent common ancestry. [ 9 ]


Greenspan had both Nitz cousins in California and had discovered someone in Argentina with the same ancestral surname and the same ancestral location in Eastern Europe. Wishing to use the same method of DNA comparison for his own genealogy, he contacted Dr. Michael Hammer at the University of Arizona. Greenspan discovered that academic labs did not offer testing directly to the public and that in general direct to consumer testing for genealogy was not commercially available either. Their conversation inspired him to start a company dedicated to using genetics to help solve genealogy mysteries. [ 7 ] [ 10 ] [ 11 ]


It was early 2000 when Greenspan with his business partners Max Blankfeld and Jim Warren officially launched FamilyTreeDNA. [ 1 ]  Initially, the Arizona Research Labs at the University of Arizona performed all testing for FamilyTreeDNA. FamilyTreeDNA includes among its scientific staff, Dr. Michael Hammer (PhD), one of a team of scientists that first published on the  Cohen Modal Haplotype  in 1997 in the journal Nature. [ 8 ]


FamilyTreeDNA began with a proof in concept group of twenty-four tests that returned results in January. The company began by offering 12 STR marker Y-chromosome tests much like those used in many scientific publications of the time in March 2000. FamilyTreeDNA became widely known for its Y-chromosome STR testing for the Cohen Modal Haplotype. [ 12 ]


They added an interface by which genealogists could run surname research studies. The first person to create such a project through the FamilyTreeDNA site was Doug Mumma, who founded the Mumma project. [ 12 ]   Such projects can also focus on specific regions and niche populations.


The first tests offered by FamilyTreeDNA were Y-chromosome STR and mitochondrial DNA ( mtDNA ) tests like those used by published academic studies at the time. [ 13 ]


FamilyTreeDNA's initial Y-chromosome tests were described as 11 marker tests. They eventually began to call this a 12 STR marker test as one of the STRS (DYS385) almost always had two copies. This they billed as a method to affirm or disprove a genealogical connection on the direct paternal line. [ citation needed ]


FamilyTreeDNA's first mtDNA tests were for  HVR1  (hypervariable region 1) of the mtDNA. [ citation needed ]  Eventually, they added a Plus test that tested for both HVR1 and HVR2. [ citation needed ]


In the early days, they did not confirm haplogroups for either mtDNA or Y-DNA. [ citation needed ]


In 2006, FamilyTreeDNA bought out the assets of DNA-Fingerprint, which was a German paternity testing company that offered à la carte testing to the genetic genealogy testing community. With this buyout, Thomas and Astrid Krahn, who had owned DNA-Fingerprint, moved to Houston, Texas, and helped open the Genomics Research Center. [ citation needed ]


The Genomics Research Center initially did testing for many of the same products that had been sold by DNA-Fingerprint. They began to offer individual and panels of Y-chromosome SNP tests using Sanger testing methods. They also offered the mtDNA full genome test and upgrades to it using the Sanger testing method. [ citation needed ]


Soon came the launch of the  Walk Through the Y  (WTY) test. The WTY test offered the most adventurous of citizen scientists the chance to seek the discovery of new Y-chromosome SNPs. [ 14 ]


Meanwhile, most testing continued to be done at the University of Arizona lab. The demand for additional test types led Greenspan and Blankfeld to move all testing to their own testing lab in Houston, Texas under the Genealogy by Genetics, Ltd. parent company. [ 1 ]


Between 2007 and 2010, FamilyTreeDNA forged several new partnerships that allowed them to access additional international markets.


iGENEA


The first of FamilyTreeDNA's new partnerships was with the Switzerland-based iGENEA company. It was formed alongside the closing of DNA-Fingerprint and Thomas Krahn's helping open the Genomic Research Center in Houston. Their website is available in English, French, German, Italian, and Spanish. [ 15 ] [ 16 ]


African DNA


In late 2007,  Henry Louis Gates  created African DNA in partnership with FamilyTreeDNA to help promote genetic testing for personal ancestry among African Americans. [ 17 ]


DNA Ancestry & Family Origin


DNA Ancestry & Family Origin DNA Ancestry & Family Origin is a genetic genealogy testing partnership between FamilyTreeDNA and Eastern Biotech & Life Sciences. Their website is available in both English and Arabic. [ 18 ]


MyHeritage


In November 2008, a dynamic partnership with  MyHeritage  was launched, allowing users to incorporate DNA testing and advanced family tree technologies into their family history research. MyHeritage is a website offering online, mobile and software platforms for discovering, preserving and sharing family history worldwide. [ 19 ]


In January 2021 it was announced that MYDNA, Inc. a Melbourne, Australia, genomics company, had acquired Family Tree DNA and its parent company Gene by Gene. [ 4 ]  MYDNA, Inc has historically specialized in  pharmacogenomics  and  nutrigenomics . [ 20 ]  Dr Lior Rauchberger commenced his role as CEO of MYDNA, Inc immediately. While  Gene by Gene  co-founders Bennett Greenspan and Max Blankfeld joined the MYDNA, Inc Board of Directors.


Services provided by FamilyTreeDNA are made in own laboratory meeting  CLIA  and  CAP  standards and they are based on various biotechnology products, including for example sequencing platform NovaSeq by  Illumina, Inc. [ 21 ]


In May 2010, FamilyTreeDNA launched an autosomal  microarray  chip based DNA test. They called the new product Family Finder. The initial product used an  Affymetrix  microarray chip, but FamilyTreeDNA changed to the Illumina OmniExpress chip and retested all customers who had results from the Affymetrix chip for forward compatibility. [ 22 ]


Family Finder allows customers to match relatives as distant as about fifth cousins. Family Finder also includes a component called myOrigins.  The results of this test provide percentages of a DNA associated with general regions or specific ethnic groups (e.g. Western Europe, Asia, Jewish, Native American, etc.). Notably, unlike other testing companies, they chose to strip out markers for mendelian medical issues, [ 23 ] [ 24 ] [ 25 ]  mtDNA results, and Y-DNA SNP results.


The company markets a range of  Y-DNA  tests. The Y-chromosome is inherited from father to son, so testers can discover relatives with the same patrilineage. In many cultures these relatives will often share the same surname, since surnames are also inherited father to son. These tests cover 37-111 STR markers depending on the test, and vary in price according to the number of markers covered. [ 22 ]  FTDNA introduced their "Big Y" test in 2013. Big Y tests approximately 15 million locations on the Y chromosome, looking for novel and shared SNPs. [ 26 ]  By the end of 2021, FTDNA had identified over 50,000 branches in the tree of all Y-DNA results. [ 27 ]


FamilyTreeDNA also sells  mtDNA  testing, offering the choice of either a limited  hypervariable region  test, or a full sequence test of the entire mitochondrial DNA chromosome. [ 22 ]


FamilyTreeDNA staff were instrumental in developing the Geno 2.0 Next Generation product for the second phase of the  Genographic Project . [ 28 ]  Geno 2.0 samples for both public and scientific study were run at the Genomics Research Center in Houston, Texas (operated by FamilyTreeDNA's parent company, Gene by Gene, Ltd.) until 2016, when Geno 2.0 began utilizing  Helix  for DNA sequencing. [ 29 ] [ 30 ]


In September 2012, Greenspan and Blankfeld restructured FamilyTreeDNA's parent company, Genealogy by Genetics, Ltd. This included their renaming Genealogy by Genetics, Ltd. as  Gene by Gene , Ltd. [ 31 ] [ 32 ] [ 33 ] [ 34 ]  After restructuring, the business consisted of four divisions, one of these being FamilyTreeDNA for genealogical DNA tests. It is  Gene by Gene , Ltd. that operates the Genomics Research Center (GRC) lab in Houston, Texas. [ 31 ] [ 34 ] [ 35 ]  In January 2021, Gene by Gene was acquired by MYDNA Inc. Gene by Gene now works together with MYDNA improving genomics testing for a broad range of clinical and non-clinical services.


In December 2018, FamilyTreeDNA changed its terms of service to  allow law enforcement to use their service to identify suspects of "a violent crime"  (defined as child abduction, sexual assault or homicide) [ 36 ]  or identify the remains of victims. The company confirmed it was working with the FBI on at least a handful of cases. [ 37 ] [ 38 ] [ 39 ]  As of March 2019, the company instituted a policy allowing its customers to opt out of law enforcement access to their genetic data. All customers were automatically opted in to such exposure except those living in the European Union who were opted out by default. [ 40 ]  Law enforcement officers will be required to go through a more rigorous process in order to access the database, while customers who opt out of allowing the FBI to access their data will still be able to search for possible relatives as before. “Users now have the ability to opt out of matching with DNA relatives whose accounts are flagged as being created to identify the remains of a deceased individual or a perpetrator of homicide or sexual assault, also referred to as Law Enforcement Matching (LEM),” the company wrote in an email to customers. [ 41 ]  In May 2019 FamilyTreeDNA prevented access to its Y-DNA database ysearch.org and its mtDNA data base mitosearch making it more difficult for law enforcement agencies to identify crime suspects. [ 42 ]  In August 2019, FamilyTreeDNA reported that about 50 law enforcement agencies had submitted DNA samples for matching and that almost 150 cases had been submitted. [ 36 ]  By spring 2020, only around 3% of about 2 million users have opted out. [ 43 ]  By August 2020, the company helped solve at least 27 cases. [ 44 ]


Female sperm  can refer to either:


Since the late 1980s, scientists have explored how to produce sperm where all of the chromosomes come from a female donor. [ 3 ]


Creating female sperm was first raised as a possibility in a patent filed in 1991 [ 4 ]  by injecting
a female's cells into a male's testicles, though the patent focused mostly on injecting altered male cells into a male's testes to correct genetic diseases. In 1997, Japanese scientists partially confirmed such techniques by creating chicken female sperm in a similar manner. "However, the ratio of produced  W chromosome -bearing (W-bearing)  spermatozoa  fell substantially below expectations. It is therefore concluded that most of the W-bearing  PGC  could not differentiate into spermatozoa because of restricted  spermatogenesis ." [ 5 ]  These simple transplantation methods follow from earlier observations by developmental biologists that germ  stem cells  are autonomous in the sense that they can begin the processes to become both sperm and eggs.


One potential roadblock to injecting a female's cells into a male's testicles is that the male's immune system might attack and destroy the female's cells. In usual circumstances, when foreign cells (such as cells or organs from other people, or infectious bacteria) are put into a human body, the immune system will reject such cells or organs. However, a special property of testicles is that they are  immune-privileged , that is, a male's immune system will not attack foreign cells (such as a female's cells) injected into the sperm-producing part of the testicles. Thus, a female's cells will remain in the male's testicles long enough to be converted into sperm.


However, there are more serious challenges. Biologists have well established that male sperm production relies on certain genes on the  Y chromosome , which, when missing or defective, lead to such males producing little to no sperm in their testicles. An analogy, then, is that XX cells have complete Y chromosome deficiency. While many genes on the Y chromosome have backups (homologues) on other chromosomes, a few genes such as RBMY on the Y chromosome do not have such backups, and their effects must be compensated to convert a female's cells from into sperm. In 2007, a patent application was filed [ 6 ]  on methods for creating human female sperm using artificial or natural Y chromosomes and testicular transplantation. [ 2 ]  Key to successful creation of female sperm (and  male eggs ) will be inducing male  epigenetic  markings for female cells that initially have female markings, with techniques for doing so disclosed in the patent application. [ 7 ]


In 2018, Chinese research scientists produced 29 viable mice offspring from two female mice by creating sperm-like structures from haploid  embryonic stem cells  using  gene editing  to alter imprinted regions of DNA. Experts noted that there was little chance of these techniques being applied to humans in the near future. [ 8 ] [ 9 ]


Fertility fraud  is the failure on the part of a  fertility doctor  to obtain consent from a patient before inseminating her with his own sperm. This normally occurs in the context of people using  assisted reproductive technology  (ART) to address fertility issues.


The term is also used in cases where donor eggs are used without consent [ 1 ]  and more broadly, in instances where doctors and other medical professionals exploit opportunities that arise when people use assisted reproductive technology to address fertility issues. This may give rise to a number of different  types of fraud  involving insurance, unnecessary procedures, theft of eggs, and other issues related to fertility treatment. [ 2 ]


The main sense of fertility fraud is non-consensual insemination of a patient by her doctor, but there are other types as well. [ 3 ] [ 4 ]


The first " test tube baby " was facilitated by  Robert Edwards  in 1978, and he allegedly used eggs without the consent of the women involved. [ 1 ]


One of the earliest cases involving egg theft occurred in 1987 in Garden Grove, California, in a clinic run by doctor  Ricardo Asch , [ 5 ]  and his partners doctors Sergio Stone and Jose Balmaceda. [ 6 ]  Asch took eggs from women undergoing diagnostic procedures and used them in fertility procedures in other women. [ 5 ]
Asch and his two partners were accused of taking eggs and embryos from patients without their consent, using them to cause pregnancies in other women, and defrauding insurance companies. [ 7 ]  The eggs of at least 20 women were used, [ 8 ]  and at least fifteen live births resulted. [ 9 ]  Thirty-five patients filed legal actions against Asch. [ 7 ]  An estimated 67 women were victims of egg or embryo theft. [ 5 ]  Asch and Balmaceda left the country and avoided trial. Stone faced trial in the case and was sentenced to three years probation for mail fraud. He was fined $50,000 by the judge in the case, required to repay more than $14,000 in restitution to insurance companies, and had to wear an electronic monitoring device. [ 6 ]


In the "Egg Affair" in Israel in 2000, police investigated two doctors who were accused of intentionally creating extra eggs in patients needing fertility procedures, and then without their patients' knowledge harvesting and selling the eggs to other fertility patients. [ 10 ]


In Italy in 2016, famed Italian gynecologist  Severino Antinori , known as the "grandmothers' obstetrician" because of his reputation for helping women over 60 to bear children, was arrested on suspicion of stealing eggs by removing them from a patient's ovaries without her consent under the guise of performing a procedure on her to remove an ovarian cyst. Antinori had recently hired a Spanish nurse at his clinic, and then diagnosed her with an ovarian cyst for the sole purpose of harvesting her eggs without her knowledge. Antinori was arrested at a Rome airport, charged with aggravated robbery and causing personal injury, and placed under house arrest. [ 11 ] [ 12 ]


There have been numerous cases of a healthcare provider fraudulently substituting their own sperm for donor sperm, resulting in pregnancy and birth. [ 4 ]


There are many other types of fertility fraud, and they may take place at various stages of the process: [ 3 ] [ 4 ]


Hundreds of children have been fathered by non-consensual insemination worldwide by their physicians, including in the United States, Canada, and the Netherlands, but without specific laws outlawing it, the legal consequences are unclear. Sometimes other laws related to fertility fraud are used against the physician, such as mail, travel, or wire fraud, while others face civil suits. Some physicians have faced ethics charges by the governing bodies of their profession and lost their license to practice medicine. [ 4 ]


In the United States, medical students in the 1960s and 1970s donated sperm, and later while trying to develop their practice as a physician, may have gone on to use their own sperm in order to establish a track record of success. There were no laws on the books at the time prohibiting such activity. [ 30 ]


Activists have pushed for legislation that would make fertility fraud a crime, and as of February 2022, seven U.S. states have passed laws, and seven others were considering it. [ 30 ]


In the United States, over fifty fertility doctors have been accused of fraud in connection with donating sperm according to a February 2022 news report. [ 30 ]


In 2020, Somethin' Else and  Sony Music Entertainment  released a podcast telling the story of Jan Karbaat and his children called "The Immaculate Deception".


In 2020, HBO released the documentary  Baby God  chronicling the life of Quincy Fortier.  [ 13 ]


In 2021, The Dutch three-part miniseries  Seeds of Deceit  tells the story of Dutch fertility doctor Jan Karbaat, who inseminated his patients with his own sperm. [ 25 ]


In 2022, Netflix released the documentary  Our Father  by  Jason Blum  in the  true crime  genre about the Donald Cline case in the 1970s and 1980s, to mixed reviews. [ 31 ] [ 32 ]


Gene by Gene  is a commercial  genetic testing  company based in  Houston, Texas . [ 1 ]  The company was owned by  Bennett Greenspan  and Max Blankfeld, and was the parent company of  Family Tree DNA . In January 2021, Gene by Gene was acquired by US based parent company myDNA Inc. [ 2 ]  Gene by Gene and Australia company myDNA Life Private Ltd. are both subsidiaries of parent company, myDNA Inc. The current Chief Executive Officer of myDNA Inc. is, Dr Lior Rauchberger.


Genealogy by Genetics, Ltd. was formed in 2000 with the creation of FamilyTreeDNA. In September 2012, Greenspan and Blankfeld restructured the company and renamed it Gene by Gene, Ltd. [ 3 ] [ 4 ]  After restructuring, the business comprises four divisions; DNA DTC, DNA Findings, DNA Traits, and Family Tree DNA. [ 4 ] [ 5 ]


Family Tree DNA was the first commercial company to develop DNA testing for  genealogical purposes . [ 6 ]  It has been operational since April 2000.


Family Tree DNA originally partnered with the  University of Arizona  for testing. [ 7 ] [ 8 ]  However, Greenspan and Blankfeld started their own testing laboratory, the Houston-based Genomics Research Center (GRC), under the Genealogy by Genetics, Ltd. parent company in 2007. [ 3 ] [ 9 ] [ 10 ]  As of November 2012 [update] , the GRC processed more than five million discrete DNA tests for over 700,000 individuals and organizations. [ 11 ] [ 12 ] [ 13 ]  All public participation kits from the  Genographic Project  are currently processed at the GRC laboratory. [ 14 ] [ 15 ]  In April 2013, Gene by Gene announced it had signed an agreement with the  MD Anderson Cancer Center  to provide instruction, training and supervision to the center's undergraduate molecular genetic technology students. [ 16 ] [ 17 ]


With the opening of the GRC, Greenspan and Blankfeld formed additional business units between 2008 and 2012 under the Genealogy by Genetics company to sell non-genealogical genetic tests. [ 18 ] [ 19 ]  They launched DNA Traits in 2008. In an interview in 2008, Greenspan said "Mendelian disorders are genealogy—we either have had a disaster in our families and therefore we know that someone carries the mutation, or they are hidden and depending upon whom we marry they might create a personal disaster for the family who is a carrier". [ 18 ] [ 19 ]  DNA Traits offers  Clinical Laboratory Improvement Amendments  (CLIA)-regulated health diagnostic tests to identify genetic disorders and susceptibility to inherited diseases and other characteristics, and serves certified medical professionals and researchers. [ 20 ]   DNA Findings  offers certified relationship tests, including paternity and siblingship tests. DNA DTC was created to serve the  Direct-To-Consumer  (DTC) market and institutional clients such as life science companies, contract research organizations, academic institutions and public-sector research facilities. [ 4 ] [ 13 ] [ 21 ]


In January 2021 it was announced that myDNA Inc, a genomics company headquartered in Houston, Texas, had acquired Gene by Gene. [ 2 ]   myDNA, Inc. also has an Australian subsidiary myDNA Life, Private Ltd., that has historically specialized in  pharmacogenomics  and  nutrigenomics . [ 22 ]
Dr Lior Rauchberger commenced his role as CEO of the newly incorporated myDNA, Inc immediately. While Gene by Gene co-founders Bennett Greenspan and Max Blankfeld joined the myDNA, Inc. Board of Directors.


Gene delivery  is the process of introducing foreign genetic material, such as  DNA  or  RNA , into host  cells . [ 1 ]  Gene delivery must reach the  genome  of the host cell to induce  gene expression . [ 2 ]  Successful gene delivery requires the foreign gene delivery to remain stable within the host cell and can either integrate into the  genome  or replicate independently of it. [ 3 ]  This requires foreign DNA to be synthesized as part of a  vector , which is designed to enter the desired host cell and deliver the  transgene  to that cell's genome. [ 4 ]  Vectors utilized as the method for gene delivery can be divided into two categories, recombinant viruses and synthetic vectors (viral and non-viral). [ 2 ] [ 5 ]


In complex multicellular  eukaryotes  (more specifically  Weissmanists ), if the  transgene  is incorporated into the host's  germline  cells, the resulting host cell can pass the transgene to its  progeny . If the transgene is incorporated into  somatic  cells, the transgene will stay with the somatic cell line, and thus its host organism. [ 6 ]


Gene delivery is a necessary step in  gene therapy  for the introduction or silencing of a gene to promote a therapeutic outcome in patients and also has applications in the genetic modification of crops. There are many different methods of gene delivery for various types of cells and tissues. [ 6 ]


Viral based vectors emerged in the 1980s as a tool for transgene expression. In 1983, Albert Siegel described the use of viral vectors in plant transgene expression although viral manipulation via cDNA cloning was not yet available. [ 7 ]  The first virus to be used as a vaccine vector was the  vaccinia  virus in 1984 as a way to protect chimpanzees against  hepatitis B . [ 8 ]   Non-viral gene delivery was first reported on in 1943 by Avery et al. who showed cellular phenotype change via  exogenous DNA  exposure. [ 9 ]


There are a variety of methods available to deliver genes to host cells. When genes are delivered to bacteria or plants the process is called  transformation  and when it is used to deliver genes to animals it is called  transfection . This is because transformation has a  different meaning  in relation to animals, indicating progression to a cancerous state. [ 10 ]  For some bacteria no external methods are need to introduce genes as they are naturally able to  take up foreign DNA . [ 11 ]  Most cells require some sort of intervention to make the cell membrane permeable to DNA and allow the DNA to be stably inserted into the hosts  genome .


Chemical based methods of gene delivery can use natural or synthetic compounds to form particles that facilitate the transfer of genes into cells. [ 2 ]  These synthetic vectors have the ability to electrostatically bind DNA or RNA and compact the genetic information to accommodate larger genetic transfers. [ 5 ]  Chemical vectors usually enter cells by  endocytosis  and can protect genetic material from degradation. [ 6 ]


One of the simplest method involves altering the environment of the cell and then stressing it by giving it a  heat shock . Typically the cells are incubated in a solution containing  divalent   cations  (often  calcium chloride ) under cold conditions, before being exposed to a heat pulse. Calcium chloride partially disrupts the cell membrane, which allows the recombinant DNA to enter the host cell. It is suggested that exposing the cells to divalent cations in cold condition may change or weaken the cell surface structure, making it more permeable to DNA. The heat-pulse is thought to create a thermal imbalance across the cell membrane, which forces the DNA to enter the cells through either cell pores or the damaged cell wall.


Another simple methods involves using  calcium phosphate   to bind the DNA and then exposing it to cultured cells. The solution, along with the DNA, is  encapsulated  by the cells and a small amount of DNA can be integrated into the genome. [ 12 ]


Liposomes  and  polymers  can be used as vectors to deliver DNA into cells. Positively charged liposomes bind with the negatively charged DNA, while polymers can be designed that interact with DNA. [ 2 ]  They form lipoplexes and polyplexes respectively, which are then up-taken by the cells. [ 13 ]   The two systems can also be combined. [ 6 ]  Polymer-based non-viral vectors uses polymers to interact with DNA and form polyplexes. [ 6 ]


The use of engineered inorganic and organic  nanoparticles  is another non-viral approach for gene delivery. [ 14 ] [ 15 ]


Artificial gene delivery can be mediated by physical methods which uses force to introduce genetic material through the cell membrane. [ 2 ]


Electroporation  is a method of promoting  competence .  Cells are briefly shocked with an  electric field  of 10-20  kV /cm, which is thought to create holes in the cell membrane through which the plasmid DNA may enter.  After the electric shock, the holes are rapidly closed by the cell's membrane-repair mechanisms.


Another method used to transform plant cells is  biolistics , where particles of gold or tungsten are coated with DNA and then shot into young plant cells or plant embryos. [ 16 ]  Some genetic material enters the cells and transforms them. This method can be used on plants that are not susceptible to  Agrobacterium  infection and also allows transformation of plant  plastids . Plants cells can also be transformed using electroporation, which uses an electric shock to make the cell membrane permeable to plasmid DNA. Due to the damage caused to the cells and DNA the transformation efficiency of biolistics and electroporation is lower than agrobacterial transformation. [ 17 ]


Microinjection  is where DNA is injected through the cell's  nuclear envelope  directly into the  nucleus . [ 11 ]


Sonoporation  is the transient permeation of  cell membranes  assisted by  ultrasound , typically in the presence of gas  microbubbles . [ 18 ]  Sonoporation allows for the entry of genetic material into cells. [ 19 ] [ 20 ]


Photoporation  is when laser pulses are used to create pores in a cell membrane to allow entry of genetic material.


Magnetofection  uses magnetic particles complexed with DNA and an external magnetic field concentrate nucleic acid particles into target cells.


A hydrodynamic capillary effect can be used to manipulate cell permeability.


In plants the DNA is often inserted using  Agrobacterium -mediated recombination , [ 21 ]  taking advantage of the  Agrobacterium s  T-DNA  sequence that allows natural insertion of genetic material into plant cells. [ 22 ]  Plant tissue are cut into small pieces and soaked in a fluid containing suspended  Agrobacterium . The bacteria will attach to many of the plant cells exposed by the cuts. The bacteria uses  conjugation  to transfer a DNA segment called  T-DNA  from its plasmid into the plant. The transferred DNA is piloted to the plant cell nucleus and integrated into the host plants genomic DNA.The plasmid T-DNA is integrated semi-randomly into the  genome  of the host cell. [ 23 ]


By modifying the plasmid to express the gene of interest, researchers can insert their chosen gene stably into the plants genome. The only essential parts of the T-DNA are its two small (25 base pair) border repeats, at least one of which is needed for plant transformation. [ 24 ] [ 25 ]  The genes to be introduced into the plant are cloned into a  plant transformation vector  that contains the T-DNA region of the  plasmid . An alternative method is  agroinfiltration . [ 26 ] [ 27 ]


Virus  mediated gene delivery utilizes the ability of a virus to inject its DNA inside a host cell and takes advantage of the virus' own ability to replicate and implement their own genetic material. Viral methods of gene delivery are more likely to induce an immune response, but they have high efficiency. [ 6 ]   Transduction  is the process that describes virus-mediated insertion of DNA into the host cell. Viruses are a particularly effective form of gene delivery because the structure of the virus prevents degradation via  lysosomes  of the DNA it is delivering to the nucleus of the host cell. [ 28 ]  In gene therapy a gene that is intended for delivery is packaged into a replication-deficient viral particle to form a  viral vector . [ 29 ]  Viruses used for gene therapy to date include retrovirus, adenovirus, adeno-associated virus and herpes simplex virus. However, there are drawbacks to using viruses to deliver genes into cells. Viruses can only deliver very small pieces of DNA into the cells, it is labor-intensive and there are risks of random insertion sites,  cytopathic effects  and mutagenesis. [ 30 ]


Viral vector based gene delivery uses a  viral vector  to deliver genetic material to the host cell. This is done by using a virus that contains the desired gene and removing the part of the viruses genome that is infectious. [ 2 ]  Viruses are efficient at delivering genetic material to the host cell's nucleus, which is vital for replication. [ 2 ]


RNA-based viruses were developed because of the ability to transcribe directly from infectious RNA transcripts.  RNA vectors are quickly expressed and expressed in the targeted form since no processing is required [source needed]. Retroviral vectors include oncoretroviral,  lentiviral  and  human foamy virus  are RNA-based viral vectors that reverse transcript and integrated into the host genome, permits long-term transgene expression . [ 2 ]


DNA-based viral vectors include  Adenoviridae ,  adeno-associated virus  and  herpes simplex virus . [ 2 ]


Several of the methods used to facilitate gene delivery have applications for therapeutic purposes.  Gene therapy  utilizes gene delivery to deliver genetic material with the goal of treating a disease or condition in the cell. Gene delivery in therapeutic settings utilizes non- immunogenic  vectors capable of cell specificity that can deliver an adequate amount of transgene expression to cause the desired effect. [ 3 ]


Advances in  genomics  have enabled a variety of new methods and gene targets to be identified for possible applications.  DNA microarrays  used in a variety of  next-gen sequencing  can identify thousands of genes simultaneously, with analytical software looking at gene expression patterns, and  orthologous  genes in  model species  to identify function. [ 31 ]  This has allowed a variety of possible vectors to be identified for use in gene therapy. As a method for creating a new class of vaccine, gene delivery has been utilized to generate a  hybrid  biosynthetic vector to deliver a possible vaccine. This vector overcomes traditional barriers to gene delivery by combining  E. coli  with a  synthetic polymer  to create a vector that maintains plasmid DNA while having an increased ability to avoid degradation by target cell lysosomes. [ 32 ]


Gene doping  is the hypothetical non-therapeutic use of  gene therapy  by athletes in order to improve their performance in those  sporting events  which prohibit such applications of genetic modification technology, [ 1 ] [ 2 ]  and for reasons other than the treatment of disease. As of April 2015 [update] , there is no evidence that gene doping has been used for athletic performance-enhancement in any sporting events. [ 1 ]  Gene doping would involve the use of  gene transfer  to increase or decrease  gene expression  and  protein biosynthesis  of a specific human protein; this could be done by directly injecting the gene carrier into the person, or by taking cells from the person, transfecting the cells, and administering the cells back to the person. [ 1 ]


The historical development of interest in gene doping by athletes and concern about the risks of gene doping and how to detect it moved in parallel with the development of the field of gene therapy, especially with the publication in 1998 of work on a  transgenic mouse  overexpressing  insulin-like growth factor 1  that was much stronger than normal mice, even in old age, preclinical studies published in 2002 of a way to deliver  erythropoietin  (EPO) via gene therapy, and publication in 2004 of the creation of a "marathon mouse" with much greater endurance than normal mice, created by delivering the gene expressing  PPAR gamma  to the mice. The scientists generating these publications were all contacted directly by athletes and coaches seeking access to the technology.  The public became aware of that activity in 2006 when such efforts were part of the evidence presented in the trial of a German coach.


Scientists themselves, as well as bodies including the  World Anti-Doping Agency  (WADA), the  International Olympic Committee , and the  American Association for the Advancement of Science , started discussing the risk of gene doping in 2001, and by 2003 WADA had added gene doping to the list of banned doping practices, and shortly thereafter began funding research on methods to detect gene doping.


Genetic enhancement includes manipulation of genes or  gene transfer  by healthy athletes for the purpose of physically improving their performance. Genetic enhancement includes gene doping and has potential for abuse among athletes, all while opening the door to political and ethical controversy. [ 3 ]


The history of concern about the potential for gene doping follows the  history of gene therapy , the medical use of genes to treat diseases, which was first clinically tested in the 1990s. [ 4 ]   Interest by the athletic community was especially spurred by the creation in a university lab of a "mighty mouse", created by administering a virus carrying the gene expressing  insulin-like growth factor 1  to mice; the mice were stronger and remained strong even as they aged, without exercise. [ 4 ]  The lab had been seeking treatments for  muscle wasting  diseases, but when their work was made public, the lab was inundated with calls from athletes seeking the treatment, with one coach offering his whole team. [ 5 ]  The scientist told  The New York Times  in 2007:  "I was quite surprised, I must admit.  People would try to entice me, saying things like, 'It'll help advance your research.' Some offered to pay me."  He also told the  Times  that every time similar research is published he gets calls and that he explains that, even should the treatment became ready for use in people, which would take years, there would be serious risks, including death; he also said that even after he explains this, the athletes still want it. [ 5 ]


In 1999, the field of gene therapy was set back when  Jesse Gelsinger  died in a gene therapy clinical trial, suffering a massive inflammatory reaction to the drug. [ 4 ] [ 6 ]  This led regulatory authorities in the US and Europe to increase safety requirements in clinical trials even beyond the initial restrictions that had been put in place at the beginning of the biotechnology era to deal with the risks of  recombinant DNA . [ 7 ]


In June 2001, Theodore Friedmann, one of the pioneers of gene therapy, and  Johann Olav Koss , an Olympic gold medallist in speed skating, published a paper that was the first public warning about gene doping. [ 7 ] [ 8 ]  Also in June 2001, a Gene Therapy Working Group, convened by the Medical Commission of the International Olympic Committee noted that "we are aware that there is the potential for abuse of gene therapy medicines and we shall begin to establish procedures and state-of-the-art testing methods for identifying athletes who might misuse such technology". [ 7 ]


Research was published in 2002 about a preclinical gene therapy called  Repoxygen , which delivered the gene encoding   erythropoietin  (EPO) as a potential treatment for  anemia . [ 4 ]   The scientists from that company also received calls from athletes and coaches. [ 4 ]   In that same year the  World Anti-Doping Agency  held its first meeting to discuss the risk of gene doping, [ 7 ] [ 9 ]  and the US  President's Council on Bioethics  discussed gene doping in the context of  human enhancement  at several sessions. [ 10 ] [ 11 ] [ 12 ]


In 2003, the field of gene therapy took a step forward and a step back; first gene therapy drug was approved,  Gendicine , which was approved in China for the treatment of certain cancers, [ 13 ]  but children in France who had seemingly been effectively treated with gene therapy for  severe combined immunodeficiency (non-human)  began developing leukemia. [ 6 ]   In 2003 the  BALCO scandal  became public, in which chemists, trainers and athletes conspired to evade doping controls with new and undetectable doping substances. [ 7 ]   In 2003 the World Doping Agency proactively added gene doping to the list of banned doping practices. [ 4 ]  Also in 2003, a symposium convened by the  American Association for the Advancement of Science  focused on the issue. [ 14 ]


Research published in 2004 showed that mice given gene therapy coding for a protein called  PPAR gamma  had about double the endurance of untreated mice and were dubbed "marathon mice"; those scientists received calls from athletes and coaches. [ 4 ]   Also in 2004 the World Anti-Doping Agency began to fund research to detect gene doping, and formed a permanent expert panel to advise it on risks and to guide the funding. [ 4 ] [ 9 ]


In 2006 interest from athletes in gene doping received widespread media coverage due its mention during the trial of a German coach who was accused and found guilty of giving his athletes  performance enhancing drugs  without their knowledge; an email in which the coach attempted to obtain Repoxygen was read in open court by a prosecutor. [ 4 ] [ 5 ]  This was the first public disclosure that athletes were interested in gene doping. [ 4 ]


In 2011 the second gene therapy drug was approved;  Neovasculgen , which delivers the gene encoding  VEGF , was approved in Russia to treat  peripheral artery disease . [ 15 ] [ 16 ]


In 2012  Glybera , a treatment for a rare  inherited disorder , became the first treatment to be approved for clinical use in either Europe or the United States. [ 17 ] [ 18 ]


As the field of gene therapy has developed, the risk of gene doping becoming a reality has increased with it. [ 6 ]


There are numerous genes of interest as agents for gene doping. [ 1 ] [ 19 ] [ 7 ]  They include  erythropoietin ,  insulin-like growth factor 1 ,  human growth hormone ,  myostatin ,  vascular endothelial growth factor ,  fibroblast growth factor ,  endorphin ,  enkephalin  and  alpha-actinin-3 . [ 1 ] [ 19 ]


The risks of gene doping would be similar to those of gene therapy: immune reaction to the native protein leading to the equivalent of a  genetic disease , massive inflammatory response, cancer, and death, and in all cases, these risks would be undertaken for short-term gain as opposed to treating a serious disease. [ 6 ] [ 7 ]


Alpha-actinin-3  is found only in  skeletal muscle  in humans, and has been identified in several genetic studies as having a different  polymorphism  in world-class athletes compared with normal people.  One form that causes the gene to make more protein is found in sprinters and is related to increased power; another form that causes the gene to make less protein is found in endurance athletes. [ 19 ] [ 20 ]   Gene doping agents could be designed with either polymorphism, or for endurance athletes, some DNA construct that interfered with expression like a  small interfering RNA . [ 19 ]