human
Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
with a subset of cells with a distinct
genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
than other cells, that is, having genetic chimerism. In contrast, an individual where each cell contains genetic material from a human and an animal is called a ''
human–animal hybrid
A human–animal hybrid and animal–human hybrid is an organism that incorporates elements from both humans and non-human animals. Technically, in a ''human–animal Hybrid (biology), hybrid'', each cell has both human and non-human genetic mate ...
'', while an organism that contains a mixture of human and non-human cells would be a ''human-animal chimera''.
Mechanisms
Some consider
mosaicism
Mosaicism or genetic mosaicism is a condition in which a multicellular organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg. Mosaicism is o ...
to be a form of chimerism, while others consider them to be distinct.
Mosaicism involves a
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
of the genetic material in a cell, giving rise to a subset of cells that are different from the rest.
Natural chimerism is the fusion of more than one fertilized
zygote
A zygote (; , ) is a eukaryote, eukaryotic cell (biology), cell formed by a fertilization event between two gametes.
The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individ ...
in the early stages of
prenatal development
Prenatal development () involves the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal de ...
. It is much rarer than mosaicism.
In artificial chimerism, an individual has one
cell lineage
Cell lineage denotes the developmental history of a tissue or organ from the fertilized egg. This is based on the tracking of an organism's cellular ancestry due to the cell divisions and relocation as time progresses. This starts with the origina ...
that was inherited genetically at the time of the formation of the human embryo and the other that was introduced through a procedure, including
organ transplantation
Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be trans ...
or
blood transfusion
Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
. Specific types of transplants that could induce this condition include bone marrow transplants and organ transplants, as the recipient's body essentially works to permanently incorporate the new blood stem cells into it.
Examples
Natural chimerism
Natural chimerism has been documented in humans in several instances.
* The Dutch sprinter
Foekje Dillema
Foekje Dillema (; 18 September 19265 December 2007) was a Dutch track and field athlete. She competed in Sprint (running), sprinting where she was a rival of Fanny Blankers-Koen. When she refused a Sex verification in sports, sex verification te ...
was expelled from the 1950 national team after she refused a mandatory sex test in July 1950; later investigations revealed a Y-chromosome in her body cells, and the analysis showed that she was probably a 46,XX/46,XY mosaic female.
* In 1953, a human chimera was reported in the ''
British Medical Journal
''The BMJ'' is a fortnightly peer-reviewed medical journal, published by BMJ Publishing Group Ltd, which in turn is wholly-owned by the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world ...
''. A woman was found to have blood containing two different blood types. Apparently this resulted from her twin brother's cells living in her body. A 1996 study found that such blood group chimerism is not rare.
* In 2002, an article in the ''New England Journal of Medicine'' described a woman, later identified as Karen Keegan, in whom tetragametic chimerism was unexpectedly identified after she underwent preparations for kidney transplant. Those preparations for the transplant required the patient and her immediate family to undergo histocompatibility testing, the result of which had suggested that she was not the biological mother of two of her three children.
* In 2002, Lydia Fairchild was denied public assistance in
Washington state
Washington, officially the State of Washington, is a state in the Pacific Northwest region of the United States. It is often referred to as Washington State to distinguish it from the national capital, both named after George Washington ...
when DNA evidence appeared to show that she was not the mother of her children. A lawyer for the prosecution heard of the case of Karen Keegan in New England, and suggested the possibility to the defense, who were able to show that Fairchild, too, was a chimera with two sets of DNA, and that one of those sets could have produced the children.
* In 2009, singer Taylor Muhl's large torso birthmark was diagnosed as resulting from chimerism.
Non-intentional chimerism related to treatments
* Several cases of chimera phenomena have been reported in bone marrow recipients.
** In 2019, the blood and seminal fluid of a man in Reno, Nevada (who had undergone a
vasectomy
Vasectomy is an elective surgical procedure that results in male sterilization, often as a means of permanent contraception. During the procedure, the male vasa deferentia are cut and tied or sealed so as to prevent sperm from entering into ...
), exhibited only the genetic content of his bone marrow donor. Swabs from his lips, cheek and tongue showed mixed DNA content.
** The DNA content of semen from an assault case in 2004 matched that of a man who had been in prison at the time of the assault, but who had been a bone marrow donor for his brother, who was later determined to have committed the crime.
** In 2008, a man was killed in a traffic accident that occurred in Seoul, South Korea. A DNA analysis to identify him revealed that his blood, along with some of his organs, appeared to show that he was female. It was later determined that he had received a bone marrow transplant from his daughter.
* Another instance of treatment-related human chimerism was published in 1998, where a male human had some partially developed female organs due to chimerism. He had been conceived by
in-vitro fertilization
In vitro fertilisation (IVF) is a process of fertilisation in which an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating the ovulatory process, then removing an ovum or ova (egg or eggs) from t ...
.
Human-animal chimeras
Human-animal chimeras include humans having undergone non-human to human
xenotransplantation
Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another.transplantation of living
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
* Cellphone, a phone connected to a cellular network
* Clandestine cell, a penetration-resistant form of a secret or outlawed organization
* Electrochemical cell, a de ...
organ
Organ and organs may refer to:
Biology
* Organ (biology), a group of tissues organized to serve a common function
* Organ system, a collection of organs that function together to carry out specific functions within the body.
Musical instruments
...
s from one
species
A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...
to another.Xenotransplantation Definition by the World Health Organization
Patient derived xenograft
Patient derived xenografts (PDX) are models of cancer where the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. It is a form of xenotransplantation. PDX models are used to create an environment that ...
s are created by xenotransplantation of human
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
cells into
immunocompromised
Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...
mice, and is a research technique frequently used in pre-clinical
oncology
Oncology is a branch of medicine that deals with the study, treatment, diagnosis, and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's Etymology, etymological origin is the Greek word ὄγ ...
research.
*The first stable human-animal chimeras to actually exist were first created by
Shanghai Second Medical University
The Shanghai Jiao Tong University School of Medicine (), formerly Shanghai Second Medical University, is a public medical school in Shanghai, China.
Clinical medicine of SJTUSM is consistently ranked first among medical schools nationally an ...
scientists in 2003, the result of having fused human cells with rabbit eggs.
* In 2017, a human-pig chimera was reported to have been created; the chimera was also reported to have 0.001% human cells, with the balance being pig. The embryo consisted mostly pig cells and some human cells. Scientists stated that they hope to use this technology to address the shortage of donor organs.
* In 2021, a human-monkey chimera was created as a joint project between the
Salk Institute
The Salk Institute for Biological Studies is a scientific research institute in the La Jolla community of San Diego, California. The independent, non-profit institute was founded in 1960 by Jonas Salk, the developer of the polio vaccine; among th ...
in the US and Kunming University in China and published in the journal ''Cell''. This involved injecting human stem cells into monkey embryos. The embryos were only allowed to grow for a few days, but the study demonstrated that some of these embryos still had human stem cells surviving at the end of the experiments. Because humans are more closely related to monkeys than other animals, it means there is more chance of the chimeric embryos surviving for longer periods so that organs can develop. The project has opened up possibilities into organ transplantation as well as ethical concerns particularly concerning human brain development in primates.
Chimera identification
Non-artificial chimerism has traditionally been considered to be rare due the low amount of reported cases in medical literature. However, this may be due to the fact that humans might not often be aware of this condition to begin with. There are usually no signs or symptoms for chimerism other than a few physical symptoms such as hyper-pigmentation, hypo-pigmentation, Blaschko's lines, body asymmetry or
heterochromia iridum
Heterochromia is a variation in coloration most often used to describe color differences of the iris, but can also be applied to color variation of hair or skin. Heterochromia is determined by the production, delivery, and concentration of mela ...
(possessing two different colored eyes). However, these signs do not necessarily mean an individual is a chimera and should only be seen as possible symptoms. Again, forensic investigation or curiosity over an unexpected maternity/paternity DNA test result usually leads to the accidental discovery of this condition. By simply undergoing a DNA test, which usually consists of either a swift cheek swab or a blood test, the discovery of the once unknown second genome is made, therefore identifying that individual as a chimera.
Chimerism and intersex
The concept of a "human hermaphrodite" resulting from chimerism is largely a misconception. Most
intersex
Intersex people are those born with any of several sex characteristics, including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical binar ...
individuals are not chimeras, and most human chimeras are not observed to have intersex traits. Theoretically, if a gynandromorphic human chimera were to have fully functioning male and female gonad tissue, such an individual could self-fertilize; this hypothesis is backed by the fact that
hermaphroditic
A hermaphrodite () is a sexually reproducing organism that produces both male and female gametes. Animal species in which individuals are either male or female are gonochoric, which is the opposite of hermaphroditic.
The individuals of many ...
animal species commonly reproduce in this way, and it has been observed in a rabbit. However, no such case of functional self-fertilization has ever been documented in humans; and it is non-existent or extremely rare in mammals, especially in humans. While humans are known to have sex characteristics that diverge from typical males or typical females, these individuals fall under the social umbrella of intersex conditions and traits, and some consider the term "hermaphrodite" to be a slur when applied to them.
Legislation
The Human Chimera Prohibition Act
On 11 July 2005, a bill known as The Human Chimera Prohibition Act was introduced into the
United States Congress
The United States Congress is the legislature, legislative branch of the federal government of the United States. It is a Bicameralism, bicameral legislature, including a Lower house, lower body, the United States House of Representatives, ...
by Senator
Samuel Brownback
Samuel Dale Brownback (born September 12, 1956) is an American attorney, politician, and diplomat who served as a United States senator from Kansas from 1996 to 2011 and as the 46th governor of Kansas from 2011 to 2018. A member of the Republic ...
; however, it died in Congress sometime in the next year. The bill was introduced based on findings that science had progressed to the point where human and nonhuman species could be merged to create new forms of life. Because of this, ethical issues might arise as the line blurred between humans and other animals, and according to the bill with this blurring of lines would come a show of disrespect for human dignity. The final claim brought up in The Human Chimera Prohibition Act was that there was an increasing amount of zoonotic diseases, and that the creation of human-animal chimeras might allow these diseases to reach humans.
On 22 August 2016, another bill, The Human-Animal Chimera Prohibition Act of 2016, was introduced to the
United States House of Representatives
The United States House of Representatives is a chamber of the Bicameralism, bicameral United States Congress; it is the lower house, with the U.S. Senate being the upper house. Together, the House and Senate have the authority under Artic ...
by Christopher H. Smith. It identified a human-animal chimera as:
* a human embryo into which a nonhuman cell or cells (or the component parts thereof) had been introduced to render the embryo's membership in the species ''Homo sapiens'' uncertain;
* a chimera human/animal embryo produced by fertilizing a human egg with nonhuman sperm;
* a chimera human/animal embryo produced by fertilizing a nonhuman egg with human sperm;
* an embryo produced by introducing a nonhuman nucleus into a human egg;
* an embryo produced by introducing a human nucleus into a nonhuman egg;
* an embryo containing at least haploid sets of chromosomes from both a human and a nonhuman life form;
* a nonhuman life form engineered such that human gametes developed within the body of a nonhuman life form; or
* a nonhuman life form engineered such that it contained a human brain or a brain derived wholly or predominantly from human neural tissues.
The bill would have prohibited the attempts to create a human-animal chimera, the transfer or attempt to transfer a human embryo into a nonhuman womb, the transfer or attempt to transfer a nonhuman embryo into a human womb, and the transport or receipt of an animal chimera for any purpose. Proposed penalties for violations of this bill included fines and/or imprisonment of up to 10 years. The bill was referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations on October 11, 2016, but died there.
Patenting
In the U.S., efforts into creating a chimeric entity appeared to be legal when the topic first came up. Developmental biologist
Stuart Newman
Stuart Alan Newman (born April 4, 1945 in New York City) is a professor of cell biology and anatomy at New York Medical College in Valhalla, NY, United States. His research centers around three program areas: cellular and molecular mechanisms o ...
, a professor at
New York Medical College
New York Medical College (NYMC or New York Med) is a Private university, private medical school in Valhalla, New York. Founded in 1860, it is a member of the Touro University System.
NYMC offers advanced degrees through its three schools: the ...
in Valhalla, N.Y., applied for a patent on a human-animal chimera in 1997 as a challenge to the U.S. Patent and Trademark Office and the
U.S. Congress
The United States Congress is the legislative branch of the federal government of the United States. It is a bicameral legislature, including a lower body, the U.S. House of Representatives, and an upper body, the U.S. Senate. They both ...
, motivated by his moral and scientific opposition to the notion that living things can be patented at all. Prior legal precedent had established that genetically engineered entities, in general, could be patented, even if they were based on beings occurring in nature. After a seven-year process, Newman's patent finally received a flat rejection. The legal process had created a paper trail of arguments, giving Newman what he claimed was a victory. ''
The Washington Post
''The Washington Post'', locally known as ''The'' ''Post'' and, informally, ''WaPo'' or ''WP'', is an American daily newspaper published in Washington, D.C., the national capital. It is the most widely circulated newspaper in the Washington m ...
'' ran an article on the controversy that stated that it had raised "profound questions about the differences—and similarities—between humans and other animals, and the limits of treating animals as property."