Chickens (Gallus gallus domesticus) and their eggs have been used extensively as research models throughout the history of biology. Today they continue to serve as an important model for normal human biology as well as pathological disease processes.
Human fascination with the chicken and its egg are so deeply rooted in history that it is hard to say exactly when avian exploration began. As early as 1400 BCE, ancient Egyptians artificially incubated chicken eggs to propagate their food supply. The developing chicken in the egg first appears in written history after catching the attention of the famous Greek philosopher, Aristotle, around 350 BCE. As Aristotle opened chicken eggs at various time points of incubation, he noted how the organism changed over time. Through his writing of Historia Animalium , he introduced some of the earliest studies of embryology based on his observations of the chicken in the egg.
Aristotle recognized significant similarities between human and chicken development. From his studies of the developing chick, he was able to correctly decipher the role of the placenta and umbilical cord in the human.
Chick research of the 16th century significantly modernized ideas about human physiology. European scientists, including Ulisse Aldrovandi, Volcher Cotier and William Harvey, used the chick to demonstrate tissue differentiation, disproving the widely held belief of the time that organisms are "preformed" in their adult version and only grow larger during development. Distinct tissue areas were recognized that grew and gave rise to specific structures, including the blastoderm, or chick origin. Harvey also closely watched the development of the heart and blood and was the first to note the directional flow of blood between veins and arteries. The relatively large size of the chick as a model organism allowed scientists during this time to make these significant observations without the help of a microscope.
Expanding use of the microscope coupled with a new technique in the late 18th century unveiled the developing chick for close-up examination. By cutting a hole in the eggshell and covering it with another piece of shell, scientists were able to look directly into the egg while it continued to develop without dehydration. Soon studies of the developing chick identified the three embryonic germ layers: ectoderm, mesoderm and endoderm, giving rise to the field of embryology.
Host versus graft response was first described in the chicken embryo. James Murphy (biologist) (1914) found that rat tissues that could not grow in adult chickens survived in the developing chick. In an immunocompetent animal, like the mature chicken, the host immune cells attack the foreign tissue. Since the immune system of the chick is not functional until about day 14 of incubation, foreign tissue can grow. Eventually, Murphy showed that the acceptance of tissue grafts was host-specific in immunologically competent animals. [1] [2]
Culturing virus was once technically difficult. In 1931, Ernest Goodpasture and Alice Miles Woodruff developed a new technique that used chicken eggs to propagate a pox virus. [3] Building on their success, the chick was used to isolate the mumps virus for vaccine development and it is still used to culture some viruses and parasites today.
The ability of chicken embryonic nerves to infiltrate a mouse tumor suggested to Rita Levi-Montalcini that the tumor must produce a diffusible growth factor (1952). She identified Nerve Growth Factor (NGF) leading to the discovery of a large family of growth factors which are key regulators during normal development and disease processes including cancer. [4]
The adult chicken has also made significant contributions to the advancement of science. By inoculating chickens with cholera bacteria (Pasteurella multocida) from an overgrown, and thereby attenuated, culture Louis Pasteur produced the first lab-derived attenuated vaccine (1860s). Great advances in immunology and oncology continued to characterize the 20th century, for which we indebted to the chicken model.
Peyton Rous (1879-1970) won the Nobel prize for discovering that viral infection of chicken could induce sarcoma (Rous, 1911). Steve Martin followed up on this work and identified a component of a chicken retrovirus, Src, which became the first known oncogene. J. Michael Bishop and Harold Varmus with their colleagues (1976) extended these findings to humans, showing that cancer causing oncogenes in mammals are induced by mutations to proto-oncogenes. [5] [6]
Discoveries in the chicken ultimately divided the adaptive immune response into antibody (B-cell) and cell-mediated (T-cell) responses. Chickens missing their bursa, an organ with an unknown function at the time, could not be induced to make antibodies. Through these experiments, Bruce Glick, correctly deduced that bursa was responsible for making the cells that produced antibodies. [7] Bursa cells were termed B-cells for Bursa to differentiate them from thymus derived T-cells.
The chicken embryo is a unique model that overcomes many limitations to studying the biology of cancer in vivo. The chorioallantoic membrane (CAM), a well-vascularized extra-embryonic tissue located underneath the eggshell, has a successful history as a biological platform for the molecular analysis of cancer including viral oncogenesis, [8] carcinogenesis, [9] tumor xenografting, [1] [10] [11] [12] [13] tumor angiogenesis, [14] and cancer metastasis. [15] [16] [17] [18] Since the chicken embryo is naturally immunodeficient, the CAM readily supports the engraftment of both normal and tumor tissues. [18] The avian CAM successfully supports most cancer cell characteristics including growth, invasion, angiogenesis, and remodeling of the microenvironment.
The Gallus gallus genome was sequenced by Sanger shotgun sequencing [19] and mapped with extensive BAC contig-based physical mapping. [20] There are significant, fundamental similarities between the human and chicken genomes. However, differences between human and chicken genomes help to identify functional elements: the genes and their regulatory elements, which are most likely to be conserved through time. Publication of the chicken genome enables expansion of transgenic techniques for advancing research within the chick model system.[ citation needed ]
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.
Harold Eliot Varmus is an American Nobel Prize-winning scientist. He is currently the Lewis Thomas University Professor of Medicine at Weill Cornell Medicine and a senior associate at the New York Genome Center.
Polyomaviridae is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while others, such as Simian Virus 40, have been identified in humans to a lesser extent. Most of these viruses are very common and typically asymptomatic in most human populations studied. BK virus is associated with nephropathy in renal transplant and non-renal solid organ transplant patients, JC virus with progressive multifocal leukoencephalopathy, and Merkel cell virus with Merkel cell cancer.
An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the letters "RNA" removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.
Marek's disease is a highly contagious viral neoplastic disease in chickens. It is named after József Marek, a Hungarian veterinarian who described it in 1907. Marek's disease is caused by an alphaherpesvirus known as "Marek's disease virus" (MDV) or Gallid alphaherpesvirus 2 (GaHV-2). The disease is characterized by the presence of T cell lymphoma as well as infiltration of nerves and organs by lymphocytes. Viruses related to MDV appear to be benign and can be used as vaccine strains to prevent Marek's disease. For example, the related herpesvirus found in turkeys (HVT), causes no apparent disease in the birds, and continues to be used as a vaccine strain for prevention of Marek's disease.
Gammaretrovirus is a genus in the Retroviridae family. Example species are the murine leukemia virus and the feline leukemia virus. They cause various sarcomas, leukemias and immune deficiencies in mammals, reptiles and birds.
Rous sarcoma virus (RSV) is a retrovirus and is the first oncovirus to have been described. It causes sarcoma in chickens.
Francis Peyton Rous was an American pathologist at the Rockefeller University known for his works in oncoviruses, blood transfusion and physiology of digestion. A medical graduate from the Johns Hopkins University, he was discouraged to become a practicing physician due to severe tuberculosis. After three years of working as an instructor of pathology at the University of Michigan, he became dedicated researcher at the Rockefeller Institute for Medical Research for the rest of his career.
Murine respirovirus, formerly Sendai virus (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an enveloped, 150-200 nm–diameter, negative sense, single-stranded RNA virus of the family Paramyxoviridae. It typically infects rodents and it is not pathogenic for humans or domestic animals.
v-Src is a gene found in Rous sarcoma virus (RSV) that encodes a tyrosine kinase that causes a type of cancer in chickens.
Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src, is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. It belongs to a family of Src family kinases and is similar to the v-Src gene of Rous sarcoma virus. It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. Two transcript variants encoding the same protein have been found for this gene.
Gyrovirus is a genus of viruses, in the family Anelloviridae. Until 2011, chicken anemia virus was the only Gyrovirus identified, but since then gyroviruses have also been identified in humans. Diseases associated with this genus include: chicken infectious anemia, which is associated with depletion of cortical thymocytes and erythroblastoid cells.
Avian sarcoma leukosis virus (ASLV) is an endogenous retrovirus that infects and can lead to cancer in chickens; experimentally it can infect other species of birds and mammals. ASLV replicates in chicken embryo fibroblasts, the cells that contribute to the formation of connective tissues. Different forms of the disease exist, including lymphoblastic, erythroblastic, and osteopetrotic.
The chorioallantoic membrane (CAM), also known as the chorioallantois, is a highly vascularized membrane found in the eggs of certain amniotes like birds and reptiles. It is formed by the fusion of the mesodermal layers of two extra-embryonic membranes – the chorion and the allantois. It is the avian homologue of the mammalian placenta. It is the outermost extra-embryonic membrane which lines the non-vascular egg shell membrane.
Avian orthoreovirus, also known as avian reovirus, is an orthoreovirus from the Reoviridae family. Infection causes arthritis and tenosynovitis in poultry. It can also cause respiratory disease.
Peter K. Vogt is an American molecular biologist, virologist and geneticist. His research focuses on retroviruses and viral and cellular oncogenes.
In ovo is Latin for in the egg. In medical usage it refers to the growth of live virus in chicken egg embryos for vaccine development for human use, as well as an effective method for vaccination of poultry against various Avian influenza and coronaviruses. During the incubation period, the virus replicates in the cells that make up the chorioallantoic membrane.
The avian immune system is the system of biological structures and cellular processes that protects birds from disease.
Breast cancer metastatic mouse models are experimental approaches in which mice are genetically manipulated to develop a mammary tumor leading to distant focal lesions of mammary epithelium created by metastasis. Mammary cancers in mice can be caused by genetic mutations that have been identified in human cancer. This means models can be generated based upon molecular lesions consistent with the human disease.