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102-638: The concept of the Hayflick limit was advanced by American anatomist Leonard Hayflick in 1961, at the Wistar Institute in Philadelphia , Pennsylvania. Hayflick demonstrated that a normal human fetal cell population will divide between 40 and 60 times in cell culture before entering a senescence phase. This finding refuted the contention by Alexis Carrel that normal cells are immortal . Hayflick interpreted his discovery to be aging at

204-425: A virion , consists of nucleic acid surrounded by a protective coat of protein called a capsid . These are formed from protein subunits called capsomeres . Viruses can have a lipid "envelope" derived from the host cell membrane . The capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological distinction. Virally-coded protein subunits will self-assemble to form

306-622: A basic optical microscope. In 2013, the Pandoravirus genus was discovered in Chile and Australia, and has genomes about twice as large as Megavirus and Mimivirus. All giant viruses have dsDNA genomes and they are classified into several families: Mimiviridae , Pithoviridae, Pandoraviridae , Phycodnaviridae , and the Mollivirus genus. Some viruses that infect Archaea have complex structures unrelated to any other form of virus, with

408-418: A capsid diameter of 400 nm. Protein filaments measuring 100 nm project from the surface. The capsid appears hexagonal under an electron microscope, therefore the capsid is probably icosahedral. In 2011, researchers discovered the largest then known virus in samples of water collected from the ocean floor off the coast of Las Cruces, Chile. Provisionally named Megavirus chilensis , it can be seen with

510-581: A capsid, in general requiring the presence of the virus genome. Complex viruses code for proteins that assist in the construction of their capsid. Proteins associated with nucleic acid are known as nucleoproteins , and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. The capsid and entire virus structure can be mechanically (physically) probed through atomic force microscopy . In general, there are five main morphological virus types: The poxviruses are large, complex viruses that have an unusual morphology. The viral genome

612-639: A cellular structure, which is often seen as the basic unit of life. Viruses do not have their own metabolism and require a host cell to make new products. They therefore cannot naturally reproduce outside a host cell —although some bacteria such as rickettsia and chlamydia are considered living organisms despite the same limitation. Accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells. They differ from autonomous growth of crystals as they inherit genetic mutations while being subject to natural selection. Virus self-assembly within host cells has implications for

714-493: A different DNA (or RNA) molecule. This can occur when viruses infect cells simultaneously and studies of viral evolution have shown that recombination has been rampant in the species studied. Recombination is common to both RNA and DNA viruses. Coronaviruses have a single-strand positive-sense RNA genome. Replication of the genome is catalyzed by an RNA-dependent RNA polymerase . The mechanism of recombination used by coronaviruses likely involves template switching by

816-559: A few species, or broad for viruses capable of infecting many. Viral infections in animals provoke an immune response that usually eliminates the infecting virus. Immune responses can also be produced by vaccines , which confer an artificially acquired immunity to the specific viral infection. Some viruses, including those that cause HIV/AIDS , HPV infection , and viral hepatitis , evade these immune responses and result in chronic infections. Several classes of antiviral drugs have been developed. The English word "virus" comes from

918-549: A fluid, by Wendell Meredith Stanley , and the invention of the electron microscope in 1931 allowed their complex structures to be visualised. Scientific opinions differ on whether viruses are a form of life or organic structures that interact with living organisms. They have been described as "organisms at the edge of life", since they resemble organisms in that they possess genes , evolve by natural selection , and reproduce by creating multiple copies of themselves through self-assembly. Although they have genes, they do not have

1020-445: A genome size of only two kilobases; the largest—the pandoraviruses —have genome sizes of around two megabases which code for about 2500 proteins. Virus genes rarely have introns and often are arranged in the genome so that they overlap . In general, RNA viruses have smaller genome sizes than DNA viruses because of a higher error-rate when replicating, and have a maximum upper size limit. Beyond this, errors when replicating render

1122-513: A ladder. The virus particles of some virus families, such as those belonging to the Hepadnaviridae , contain a genome that is partially double-stranded and partially single-stranded. For most viruses with RNA genomes and some with single-stranded DNA (ssDNA) genomes, the single strands are said to be either positive-sense (called the 'plus-strand') or negative-sense (called the 'minus-strand'), depending on if they are complementary to

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1224-436: A life form, because they carry genetic material, reproduce, and evolve through natural selection , although they lack some key characteristics, such as cell structure, that are generally considered necessary criteria for defining life. Because they possess some but not all such qualities, viruses have been described as "organisms at the edge of life" and as replicators . Viruses spread in many ways. One transmission pathway

1326-472: A limited range of hosts and many are species-specific. Some, such as smallpox virus for example, can infect only one species—in this case humans, and are said to have a narrow host range . Other viruses, such as rabies virus, can infect different species of mammals and are said to have a broad range. The viruses that infect plants are harmless to animals, and most viruses that infect other animals are harmless to humans. The host range of some bacteriophages

1428-411: A mechanism for remembering what replication level they are at. He interpreted his finding that normal cells are mortal, to be an indication of aging at the cellular level. Hayflick demonstrated for the first time that mortal (normal) and immortal (malignant) mammalian cells existed. Hayflick developed the first normal human diploid cell strains for studies on human aging and for research use throughout

1530-806: A member of twenty scientific and professional societies in which he has held several high offices including President of the Gerontological Society of America from 1982 to 1983. He was a founding member of the Council of the National Institute on Aging, NIH, and chairman of its executive committee. He was a consultant to the National Cancer Institute and the World Health Organization , and was a member of several scientific advisory boards. He

1632-475: A memory and can remember at what doubling level they have reached. He demonstrated that his normal human cell strains were free from contaminating viruses. His cell strain WI-38 soon replaced primary monkey kidney cells and became the substrate for the production of most of the world's human virus vaccines. Hayflick discovered that the etiological agent of primary atypical pneumonia (also called "walking pneumonia")

1734-449: A non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology , a subspeciality of microbiology . When infected, a host cell is often forced to rapidly produce thousands of copies of the original virus. When not inside an infected cell or in

1836-408: A prime target for natural selection. Segmented genomes confer evolutionary advantages; different strains of a virus with a segmented genome can shuffle and combine genes and produce progeny viruses (or offspring) that have unique characteristics. This is called reassortment or 'viral sex'. Genetic recombination is a process by which a strand of DNA (or RNA) is broken and then joined to the end of

1938-412: A single viral particle that is released from the cell and is capable of infecting other cells of the same type. Viruses are found wherever there is life and have probably existed since living cells first evolved . The origin of viruses is unclear because they do not form fossils, so molecular techniques are used to infer how they arose. In addition, viral genetic material occasionally integrates into

2040-460: A small part of the total diversity of viruses has been studied. As of 2022, 6 realms, 10 kingdoms, 17 phyla, 2 subphyla, 40 classes, 72 orders, 8 suborders, 264 families, 182 subfamilies , 2,818 genera, 84 subgenera , and 11,273 species of viruses have been defined by the ICTV. The general taxonomic structure of taxon ranges and the suffixes used in taxonomic names are shown hereafter. As of 2022,

2142-605: A wide diversity of sizes and shapes, called ' morphologies '. In general, viruses are much smaller than bacteria and more than a thousand bacteriophage viruses would fit inside an Escherichia coli bacterium's cell. Many viruses that have been studied are spherical and have a diameter between 20 and 300 nanometres . Some filoviruses , which are filaments, have a total length of up to 1400 nm; their diameters are only about 80 nm. Most viruses cannot be seen with an optical microscope , so scanning and transmission electron microscopes are used to visualise them. To increase

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2244-553: A wide variety of unusual shapes, ranging from spindle-shaped structures to viruses that resemble hooked rods, teardrops or even bottles. Other archaeal viruses resemble the tailed bacteriophages, and can have multiple tail structures. An enormous variety of genomic structures can be seen among viral species ; as a group, they contain more structural genomic diversity than plants, animals, archaea, or bacteria. There are millions of different types of viruses, although fewer than 7,000 types have been described in detail. As of January 2021,

2346-480: A year after its founding and for the next 25 years. He developed their technology for growing animal cells in fermentation tanks in which most of their products were produced. Hayflick was one of several prominent biologists featured in the 1995 science documentary Death by Design: The Life and Times of Life and Times . Hayflick died in Sea Ranch, California , on August 1, 2024, at the age of 96. Hayflick

2448-416: Is a feature of many bacterial and some animal viruses. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host's chromosome. The viral genome is then known as a " provirus " or, in the case of bacteriophages a " prophage ". Whenever the host divides, the viral genome is also replicated. The viral genome is mostly silent within

2550-405: Is a major change in the genome of the virus. This can be a result of recombination or reassortment . The Influenza A virus is highly prone to reassortment; occasionally this has resulted in novel strains which have caused pandemics . RNA viruses often exist as quasispecies or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are

2652-440: Is also known for his discovery of the cause of primary atypical pneumonia (" walking pneumonia ") in humans. The etiological agent was first thought to be a virus, but Hayflick showed that it was, in fact, a mycoplasma , a member of the smallest free-living class of microorganisms. The etiological agent was named by him as Mycoplasma pneumoniae , and was first grown by Hayflick on a medium he developed and that bears his name. It

2754-400: Is associated with proteins within a central disc structure known as a nucleoid . The nucleoid is surrounded by a membrane and two lateral bodies of unknown function. The virus has an outer envelope with a thick layer of protein studded over its surface. The whole virion is slightly pleomorphic , ranging from ovoid to brick-shaped. Mimivirus is one of the largest characterised viruses, with

2856-439: Is caused by cessation of its normal activities because of suppression by virus-specific proteins, not all of which are components of the virus particle. The distinction between cytopathic and harmless is gradual. Some viruses, such as Epstein–Barr virus , can cause cells to proliferate without causing malignancy, while others, such as papillomaviruses , are established causes of cancer. Some viruses cause no apparent changes to

2958-512: Is correct. It seems unlikely that all currently known viruses have a common ancestor, and viruses have probably arisen numerous times in the past by one or more mechanisms. The first evidence of the existence of viruses came from experiments with filters that had pores small enough to retain bacteria. In 1892, Dmitri Ivanovsky used one of these filters to show that sap from a diseased tobacco plant remained infectious to healthy tobacco plants despite having been filtered. Martinus Beijerinck called

3060-429: Is far greater than the number of replication events experienced by non-stem cells in vivo during a normal postnatal lifespan. In addition, it has been suggested that no inverse correlation exists between the replicative capacity of normal human cell strains and the age of the human donor from which the cells were derived, as previously argued. It is now clear that at least some of these variable results are attributable to

3162-507: Is first recorded in 1728, long before the discovery of viruses by Dmitri Ivanovsky in 1892. The English plural is viruses (sometimes also vira ), whereas the Latin word is a mass noun , which has no classically attested plural ( vīra is used in Neo-Latin ). The adjective viral dates to 1948. The term virion (plural virions ), which dates from 1959, is also used to refer to

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3264-607: Is identical in sequence to the viral mRNA and is thus a coding strand, while negative-sense viral ssDNA is complementary to the viral mRNA and is thus a template strand. Several types of ssDNA and ssRNA viruses have genomes that are ambisense in that transcription can occur off both strands in a double-stranded replicative intermediate. Examples include geminiviruses , which are ssDNA plant viruses and arenaviruses , which are ssRNA viruses of animals. Genome size varies greatly between species. The smallest—the ssDNA circoviruses, family Circoviridae —code for only two proteins and have

3366-595: Is known for his research in cell biology , virus vaccine development, and mycoplasmology . In 1962 he discovered that, contrary to the prevailing belief at the time, cultured normal human and animal cells have a limited capacity for replication. This discovery, known as the Hayflick limit , overturned a long-held belief bolstered by Alexis Carrel 's work in the early 20th century that claimed that normal cells would proliferate continuously in culture. Hayflick found that only cancer cells are immortal and that normal cells have

3468-431: Is limited to a single strain of bacteria and they can be used to trace the source of outbreaks of infections by a method called phage typing . The complete set of viruses in an organism or habitat is called the virome ; for example, all human viruses constitute the human virome . A novel virus is one that has not previously been recorded. It can be a virus that is isolated from its natural reservoir or isolated as

3570-603: Is now used for the production of all of the Rubella Virus vaccine used in the Western Hemisphere. WI-38, or new diploid cell strains, are used today for the manufacture of most human virus vaccines produced throughout the world including those for poliomyelitis , rubella, rubeola, varicella, mumps, rabies, adenoviruses and hepatitis A. Over one billion vaccinees have received vaccines produced on WI-38 or foreign versions of Hayflick's original WI-38. Hayflick

3672-649: Is now used worldwide for mycoplasma isolation and research. Hayflick is the recipient of more than twenty-five major awards including the $ 20,000 Brookdale Award and the Kleemeier Award from the Gerontological Society of America, the Biomedical Sciences and Aging Award from the University of Southern California, The Karl August Forster Lectureship of the Academy of Sciences and Literature and

3774-584: Is one of the most cited contemporary scientists in the world in the fields of biochemistry, biophysics, cell biology, enzymology, genetics and molecular biology. Hayflick is the author of over 275 scientific papers, book chapters and edited books of which four papers are among the 100 most cited scientific papers of the two million papers published in the basic biomedical sciences from 1961 to 1978. The inverted microscope that Hayflick modified for use in his tissue culture and mycoplasma work and on which all other such microscopes have been modeled has been acquired by

3876-675: Is the oldest scientific award in the United States, established in 1823 in honor of Benjamin Franklin. In the mid-1990s, Hayflick was recruited by Geron founder Michael D. West to join the company's Scientific Advisory Board. In 1997, Hayflick was elected Academician and Foreign Member of the Ukrainian Academy of Medical Sciences. In 1998 he was elected corresponding member of the Société de Biologie of France. In 1999, he

3978-422: Is the usage of telomerase inhibitors that would prevent the restoration of the telomere, allowing the cell to die like other body cells. Hayflick suggested that his results in which normal cells have a limited replicative capacity may have significance for understanding human aging at the cellular level. It has been reported that the limited replicative capability of human fibroblasts observed in cell culture

4080-475: Is through disease-bearing organisms known as vectors : for example, viruses are often transmitted from plant to plant by insects that feed on plant sap , such as aphids ; and viruses in animals can be carried by blood-sucking insects. Many viruses spread in the air by coughing and sneezing, including influenza viruses , SARS-CoV-2 , chickenpox , smallpox , and measles . Norovirus and rotavirus , common causes of viral gastroenteritis , are transmitted by

4182-535: The American Academy of Anti-Aging Medicine . Hayflick has written numerous articles criticizing both the feasibility and desirability of human life extension , which have provoked responses critical of his views. Hayflick was born May 20, 1928, in Philadelphia, Pennsylvania . He received his Ph.D. at the University of Pennsylvania in 1956. After receiving a post-doctoral fellowship for study at

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4284-477: The CD4 molecule—a chemokine receptor —which is most commonly found on the surface of CD4+ T-Cells . This mechanism has evolved to favour those viruses that infect only cells in which they are capable of replication. Attachment to the receptor can induce the viral envelope protein to undergo changes that result in the fusion of viral and cellular membranes, or changes of non-enveloped virus surface proteins that allow

4386-555: The International Committee on Taxonomy of Viruses (ICTV) was formed. The system proposed by Lwoff, Horne and Tournier was initially not accepted by the ICTV because the small genome size of viruses and their high rate of mutation made it difficult to determine their ancestry beyond order. As such, the Baltimore classification system has come to be used to supplement the more traditional hierarchy. Starting in 2018,

4488-690: The Latin vīrus , which refers to poison and other noxious liquids. Vīrus comes from the same Indo-European root as Sanskrit viṣa , Avestan vīša , and Ancient Greek ἰός ( iós ), which all mean "poison". The first attested use of "virus" in English appeared in 1398 in John Trevisa 's translation of Bartholomeus Anglicus 's De Proprietatibus Rerum . Virulent , from Latin virulentus ('poisonous'), dates to c.  1400 . A meaning of 'agent that causes infectious disease'

4590-490: The NCBI Virus genome database has more than 193,000 complete genome sequences, but there are doubtlessly many more to be discovered. A virus has either a DNA or an RNA genome and is called a DNA virus or an RNA virus , respectively. Most viruses have RNA genomes. Plant viruses tend to have single-stranded RNA genomes and bacteriophages tend to have double-stranded DNA genomes. Viral genomes are circular, as in

4692-553: The Smithsonian National Museum of American History . Viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism . Viruses infect all life forms , from animals and plants to microorganisms , including bacteria and archaea . Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. Since Dmitri Ivanovsky 's 1892 article describing

4794-573: The Stanford University School of Medicine , Stanford, California. Hayflick resigned from Stanford in 1976 in protest to the behavior of a few of its administrators who were later shown to have wrongly accepted the beliefs of an NIH accountant who was unable to understand the unique concept of title to a self-duplicating biological system. Hayflick sued the NIH, who later agreed that the issue was in dispute. The behavior of Stanford and

4896-467: The University of Texas Medical Branch in Galveston under the tutelage of the renowned cell culturist Charles M. Pomerat (1905–1964), he returned to Philadelphia, where he spent ten years as an Associate Member of the Wistar Institute and two years as an Assistant Professor of Research Medicine at the University of Pennsylvania . In 1968, Hayflick was appointed Professor of Medical Microbiology at

4998-539: The common cold , influenza , chickenpox , and cold sores . Many serious diseases such as rabies , Ebola virus disease , AIDS (HIV) , avian influenza , and SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of virulence . Other diseases are under investigation to discover if they have a virus as the causative agent, such as the possible connection between human herpesvirus 6 (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome . There

5100-422: The faecal–oral route , passed by hand-to-mouth contact or in food or water. The infectious dose of norovirus required to produce infection in humans is fewer than 100 particles. HIV is one of several viruses transmitted through sexual contact and by exposure to infected blood. The variety of host cells that a virus can infect is called its host range : this is narrow for viruses specialized to infect only

5202-430: The germline of the host organisms, by which they can be passed on vertically to the offspring of the host for many generations. This provides an invaluable source of information for paleovirologists to trace back ancient viruses that existed as far back as millions of years ago. There are three main hypotheses that aim to explain the origins of viruses: In the past, there were problems with all of these hypotheses:

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5304-457: The polyomaviruses , or linear, as in the adenoviruses . The type of nucleic acid is irrelevant to the shape of the genome. Among RNA viruses and certain DNA viruses, the genome is often divided into separate parts, in which case it is called segmented. For RNA viruses, each segment often codes for only one protein and they are usually found together in one capsid. All segments are not required to be in

5406-447: The three domains . This discovery has led modern virologists to reconsider and re-evaluate these three classical hypotheses. The evidence for an ancestral world of RNA cells and computer analysis of viral and host DNA sequences give a better understanding of the evolutionary relationships between different viruses and may help identify the ancestors of modern viruses. To date, such analyses have not proved which of these hypotheses

5508-465: The 1991 Sandoz Prize for Gerontological Research, he studied the ageing process for more than fifty years. He is known for discovering that normal human cells divide for a limited number of times in vitro (refuting the contention by Alexis Carrel that normal body cells are immortal ). This is known as the Hayflick limit . His discoveries overturned a 60-year old dogma that all cultured cells are immortal. Hayflick demonstrated that normal cells have

5610-399: The 40th population doubling) with female fibroblasts that had divided fewer times (cells at the 15th population doubling). Unmixed cell populations were kept as controls. After 20 doublings of the mixed culture, only female cells remained. Cell division ceased in the unmixed control cultures at the anticipated times; when the male control culture stopped dividing, only female cells remained in

5712-634: The 50 ± 10 mitosis event limit until cellular senescence occurs as described in Hayflick's findings. Hayflick first became suspicious of Carrel's claims while working in a lab at the Wistar Institute. Hayflick noticed that one of his cultures of embryonic human fibroblasts had developed an unusual appearance and that cell division had slowed. Initially, he brushed this aside as an anomaly caused by contamination or technical error. However, he later observed other cell cultures exhibiting similar manifestations. Hayflick checked his research notebook and

5814-431: The Hayflick limit as a credible biological theory. Unlike Carrel's experiment, Hayflick's have been successfully repeated by other scientists. Hayflick describes three phases in the life of normal cultured cells. At the start of his experiment he named the primary culture "phase one". Phase two is defined as the period when cells are proliferating; Hayflick called this the time of "luxuriant growth". After months of doubling

5916-527: The ICTV began to acknowledge deeper evolutionary relationships between viruses that have been discovered over time and adopted a 15-rank classification system ranging from realm to species. Additionally, some species within the same genus are grouped into a genogroup . The ICTV developed the current classification system and wrote guidelines that put a greater weight on certain virus properties to maintain family uniformity. A unified taxonomy (a universal system for classifying viruses) has been established. Only

6018-527: The NIH was later condemned by 85 prominent biologists who viewed him as having been "exonerated" by subsequent events. In 1982 he moved to the University of Florida , Gainesville, where he became Director of the Center for Gerontological Studies and Professor of Zoology in the College of Liberal Arts and Sciences and Professor of Microbiology and Immunology in the College of Medicine. In 1988, Hayflick joined

6120-863: The Regenerative Medicine Secretariat for his "...discovery of the finite replicative capacity of normal human diploid cells..." A third Annual Hayflick Lecture was established at the Friedrich Schiller University in 2013. Hayflick was a Fellow of the American Association for the Advancement of Science , an Honorary Member of the Tissue Culture Association and, according to the Institute of Scientific Information,

6222-887: The University of Mainz, Germany, the Samuel Roberts Noble Foundation Research Recognition Award, the Lifetime Achievement Award of the Society for In Vitro Biology, the Sandoz Prize from the International Association of Gerontology , and the Presidential Award from The International Organization for Mycoplasmology . Hayflick, together with Paul Moorhead, were awarded the prestigious John Scott Award in 2014. This

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6324-489: The basis of similarities. In 1962, André Lwoff , Robert Horne , and Paul Tournier were the first to develop a means of virus classification, based on the Linnaean hierarchical system. This system based classification on phylum , class , order , family , genus , and species . Viruses were grouped according to their shared properties (not those of their hosts) and the type of nucleic acid forming their genomes. In 1966,

6426-413: The cells eventually reach phase three, a phenomenon he named " senescence ", where cell replication rate slows before halting altogether. The Hayflick limit has been found to correlate with the length of the telomeric region at the end of chromosomes. During the process of DNA replication of a chromosome, small segments of DNA within each telomere are unable to be copied and are lost. This occurs due to

6528-511: The cellular level. The aging of cell populations appears to correlate with the overall physical aging of an organism. Macfarlane Burnet coined the name "Hayflick limit" in his book Intrinsic Mutagenesis: A Genetic Approach to Ageing , published in 1974. Prior to Leonard Hayflick's discovery, it was believed that vertebrate cells had an unlimited potential to replicate. Alexis Carrel , a Nobel prize -winning surgeon, had stated "that all cells explanted in tissue culture are immortal, and that

6630-510: The cessation of normal cell replicative capacity that he observed was not the result of viral contamination, poor culture conditions or some unknown artifact. Hayflick teamed with Paul Moorhead for the definitive experiment to eliminate these as causative factors. As a skilled cytogeneticist , Moorhead was able to distinguish between male and female cells in culture. The experiment proceeded as follows: Hayflick mixed equal numbers of normal human male fibroblasts that had divided many times (cells at

6732-410: The contrast between viruses and the background, electron-dense "stains" are used. These are solutions of salts of heavy metals, such as tungsten , that scatter the electrons from regions covered with the stain. When virions are coated with stain (positive staining), fine detail is obscured. Negative staining overcomes this problem by staining the background only. A complete virus particle, known as

6834-683: The culture daily. This would have easily allowed the cultivation of new, fresh cells in the culture, so there was not an infinite reproduction of the original cells. It has been speculated that Carrel knew about this error, but he never admitted it. Also, it has been theorized that the cells Carrel used were young enough to contain pluripotent stem cells , which, if supplied with a supporting telomerase -activation nutrient, would have been capable of staving off replicative senescence, or even possibly reversing it. Cultures not containing telomerase-active pluripotent stem cells would have been populated with telomerase-inactive cells, which would have been subject to

6936-431: The extreme of the ssRNA virus case. Viruses undergo genetic change by several mechanisms. These include a process called antigenic drift where individual bases in the DNA or RNA mutate to other bases. Most of these point mutations are "silent"—they do not change the protein that the gene encodes—but others can confer evolutionary advantages such as resistance to antiviral drugs . Antigenic shift occurs when there

7038-467: The faculty of the University of California, San Francisco, where he was Professor of Anatomy. Hayflick was a member of numerous national and international scientific and public boards of directors and committees. He has been on the Editorial Boards of more than ten professional journals. Hayflick was Editor-in-Chief of the international journal "Experimental Gerontology" for 13 years. He was

7140-446: The filtered, infectious substance a "virus" and this discovery is considered to be the beginning of virology. The subsequent discovery and partial characterization of bacteriophages by Frederick Twort and Félix d'Herelle further catalyzed the field, and by the early 20th century many viruses had been discovered. In 1926, Thomas Milton Rivers defined viruses as obligate parasites. Viruses were demonstrated to be particles, rather than

7242-399: The form of single-stranded nucleoprotein complexes, through pores called plasmodesmata . Bacteria, like plants, have strong cell walls that a virus must breach to infect the cell. Given that bacterial cell walls are much thinner than plant cell walls due to their much smaller size, some viruses have evolved mechanisms that inject their genome into the bacterial cell across the cell wall, while

7344-406: The host. At some point, the provirus or prophage may give rise to the active virus, which may lyse the host cells. Enveloped viruses (e.g., HIV) typically are released from the host cell by budding . During this process, the virus acquires its envelope, which is a modified piece of the host's plasma or other, internal membrane. The genetic material within virus particles, and the method by which

7446-517: The infected cell. Cells in which the virus is latent and inactive show few signs of infection and often function normally. This causes persistent infections and the virus is often dormant for many months or years. This is often the case with herpes viruses . Viruses are by far the most abundant biological entities on Earth and they outnumber all the others put together. They infect all types of cellular life including animals, plants, bacteria and fungi . Different types of viruses can infect only

7548-499: The lack of continuous cell replication was due to ignorance on how best to cultivate the cells". He claimed to have cultivated fibroblasts from the hearts of chickens (which typically live 5 to 10 years) and to have kept the culture growing for 34 years. However, other scientists have been unable to replicate Carrel's results, and they are suspected to be due to an error in experimental procedure. To provide required nutrients, embryonic stem cells of chickens may have been re-added to

7650-416: The material is replicated, varies considerably between different types of viruses. The range of structural and biochemical effects that viruses have on the host cell is extensive. These are called ' cytopathic effects '. Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis, alterations to the cell's surface membrane and apoptosis . Often cell death

7752-438: The mixed culture. This suggested that technical errors or contaminating viruses were unlikely explanations as to why cell division ceased in the older cells, and proved that unless the virus or artifact could distinguish between male and female cells (which it could not) then the cessation of normal cell replication was governed by an internal counting mechanism. These results disproved Carrel's immortality claims and established

7854-478: The mosaicism of cell replication numbers at different body sites where cells were taken. Comparisons of different species indicate that cellular replicative capacity may correlate primarily with species body mass, but more likely to species lifespan. Thus, the limited capacity of cells to replicate in culture may be directly relevant to the overall physical aging of an organism. Leonard Hayflick Leonard Hayflick (May 20, 1928 – August 1, 2024)

7956-461: The original virus. Their life cycle differs greatly between species, but there are six basic stages in their life cycle: Attachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range and type of host cell of a virus. For example, HIV infects a limited range of human leucocytes . This is because its surface protein, gp120 , specifically interacts with

8058-416: The polymerase during genome replication. This process appears to be an adaptation for coping with genome damage. Viral populations do not grow through cell division, because they are acellular. Instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell. When infected, the host cell is forced to rapidly produce thousands of copies of

8160-621: The process of infecting a cell, viruses exist in the form of independent viral particles, or virions , consisting of (i) genetic material , i.e., long molecules of DNA or RNA that encode the structure of the proteins by which the virus acts; (ii) a protein coat, the capsid , which surrounds and protects the genetic material; and in some cases (iii) an outside envelope of lipids . The shapes of these virus particles range from simple helical and icosahedral forms to more complex structures. Most virus species have virions too small to be seen with an optical microscope and are one-hundredth

8262-965: The ranks of subrealm, subkingdom, and subclass are unused, whereas all other ranks are in use. The Nobel Prize-winning biologist David Baltimore devised the Baltimore classification system. The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification. The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. Viral genomes may be single-stranded (ss) or double-stranded (ds), RNA or DNA, and may or may not use reverse transcriptase (RT). In addition, ssRNA viruses may be either sense (+) or antisense (−). This classification places viruses into seven groups: Examples of common human diseases caused by viruses include

8364-422: The regressive hypothesis did not explain why even the smallest of cellular parasites do not resemble viruses in any way. The escape hypothesis did not explain the complex capsids and other structures on virus particles. The virus-first hypothesis contravened the definition of viruses in that they require host cells. Viruses are now recognised as ancient and as having origins that pre-date the divergence of life into

8466-484: The result of spread to an animal or human host where the virus had not been identified before. It can be an emergent virus , one that represents a new virus, but it can also be an extant virus that has not been previously identified . The SARS-CoV-2 coronavirus that caused the COVID-19 pandemic is an example of a novel virus. Classification seeks to describe the diversity of viruses by naming and grouping them on

8568-451: The same virion for the virus to be infectious, as demonstrated by brome mosaic virus and several other plant viruses. A viral genome, irrespective of nucleic acid type, is almost always either single-stranded (ss) or double-stranded (ds). Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of two complementary paired nucleic acids, analogous to

8670-462: The size of most bacteria. The origins of viruses in the evolutionary history of life are still unclear. Some viruses may have evolved from plasmids , which are pieces of DNA that can move between cells. Other viruses may have evolved from bacteria. In evolution, viruses are an important means of horizontal gene transfer , which increases genetic diversity in a way analogous to sexual reproduction . Viruses are considered by some biologists to be

8772-399: The structure-mediated self-assembly of the virus particles, some modification of the proteins often occurs. In viruses such as HIV, this modification (sometimes called maturation) occurs after the virus has been released from the host cell. Release – Viruses can be released from the host cell by lysis , a process that kills the cell by bursting its membrane and cell wall if present: this

8874-457: The study of the origin of life , as it lends further credence to the hypothesis that life could have started as self-assembling organic molecules . The virocell model first proposed by Patrick Forterre considers the infected cell to be the "living form" of viruses and that virus particles (virions) are analogous to spores . Although the living versus non-living debate continues, the virocell model has gained some acceptance. Viruses display

8976-412: The uneven nature of DNA replication, where leading and lagging strands are not replicated symmetrically. The telomeric region of DNA does not code for any protein; it is simply a repeated code on the end region of linear eukaryotic chromosomes. After many divisions, the telomeres reach a critical length and the cell becomes senescent. It is at this point that a cell has reached its Hayflick limit. Hayflick

9078-446: The viral messenger RNA (mRNA). Positive-sense viral RNA is in the same sense as viral mRNA and thus at least a part of it can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. DNA nomenclature for viruses with genomic ssDNA is similar to RNA nomenclature, in that positive-strand viral ssDNA

9180-824: The viral capsid remains outside. Uncoating is a process in which the viral capsid is removed: This may be by degradation by viral enzymes or host enzymes or by simple dissociation; the end-result is the releasing of the viral genomic nucleic acid. Replication of viruses involves primarily multiplication of the genome. Replication involves the synthesis of viral messenger RNA (mRNA) from "early" genes (with exceptions for positive-sense RNA viruses), viral protein synthesis , possible assembly of viral proteins, then viral genome replication mediated by early or regulatory protein expression. This may be followed, for complex viruses with larger genomes, by one or more further rounds of mRNA synthesis: "late" gene expression is, in general, of structural or virion proteins. Assembly – Following

9282-503: The virus to enter. Penetration or viral entry follows attachment: Virions enter the host cell through receptor-mediated endocytosis or membrane fusion . The infection of plant and fungal cells is different from that of animal cells. Plants have a rigid cell wall made of cellulose , and fungi one of chitin, so most viruses can get inside these cells only after trauma to the cell wall. Nearly all plant viruses (such as tobacco mosaic virus) can also move directly from cell to cell, in

9384-460: The virus useless or uncompetitive. To compensate, RNA viruses often have segmented genomes—the genome is split into smaller molecules—thus reducing the chance that an error in a single-component genome will incapacitate the entire genome. In contrast, DNA viruses generally have larger genomes because of the high fidelity of their replication enzymes. Single-strand DNA viruses are an exception to this rule, as mutation rates for these genomes can approach

9486-461: The world. Prior to his seminal research, all cultured cell lines were immortal and aneuploid . One of these new cell strains, developed by Hayflick and his colleague Paul Moorhead at the Wistar Institute in Philadelphia , Pennsylvania, called WI-38 , has become the most widely used and highly characterized normal human cell population in the world. Hayflick had found that his normal cell strain WI-38

9588-576: Was Chairman of the Scientific Review Board of the American Federation for Aging Research where he was also a vice president and a Member of the board of directors. He was also recruited by Michael D. West , founder of Geron ( Nasdaq :  GERN ) and current CEO of BioTime , to join the company's Scientific and Clinical Advisory Board, on which he served from 1991–2000. Hayflick was also a consultant at Genentech from

9690-496: Was accessioned by the Smithsonian Institution in 2009. Hayflick developed the first practical method for producing powdered cell culture media in 1965. This method is now used worldwide for the production of many tons of powdered media annually for use in research laboratories and commercial production facilities. The technique is not patented and Hayflick received no remuneration from this invention. Hayflick

9792-602: Was an American anatomist who was Professor of Anatomy at the UCSF School of Medicine , and was Professor of Medical Microbiology at Stanford University School of Medicine. He was also past president of the Gerontological Society of America and was a founding member of the council of the National Institute on Aging (NIA). The recipient of a number of research prizes and awards, including

9894-473: Was capable of growing all of the then known human viruses. He hypothesized that because WI-38 was free from contaminating viruses, it could replace the then widely used primary monkey kidney cells, which contained several dangerous contaminating viruses. Indeed, WI-38 became used worldwide for human virus vaccine manufacture, to the benefit of billions of people. Hayflick produced the first oral polio vaccine ever made on his normal human cell strain WI-38. WI-38

9996-501: Was not a virus as previously believed. He was the first to cultivate the causative organism called a mycoplasma , the smallest free-living organism, which Hayflick isolated on a unique culture medium that bears his name. He named the organism Mycoplasma pneumoniae . In 1959, Hayflick developed the first inverted microscope for use in cell culture research. To this day, all inverted microscopes used in cell culture laboratories worldwide are descended from this prototype. His microscope

10098-652: Was presented with the van Weezel Award by the European Society for Animal Cell Technology and the Lord Cohen of Birkenhead Medal by the British Society for Research on Ageing . The American Aging Association established an Annual Hayflick Lectureship in 1997. A second Annual Hayflick Lecture was established by the University of Alabama at Birmingham in 2000. Hayflick was the recipient of the 2001, $ 10,000 Life Extension Prize and Laureate Diploma from

10200-445: Was surprised to find that the atypical cell cultures had all been cultured to approximately their 40th doubling while younger cultures never exhibited the same problems. Furthermore, conditions were similar between the younger and older cultures he observed—same culture medium, culture containers, and technician. This led him to doubt that the manifestations were due to contamination or technical error. Hayflick next set out to prove that

10302-815: Was the author of the book, How and Why We Age , published in August 1994 by Ballantine Books , New York City and available since 1996 as a paperback. This book has been translated into nine languages and is published in Brazil , the Czech Republic , Germany , Hungary , Israel , Japan , Poland , Russia , and Spain . It was a selection of the Book of the Month Club and has sold over 50,000 copies worldwide. Hayflick and his associates have vehemently condemned "anti-aging medicine" and criticized organizations such as

10404-437: Was the first to report that only cancer cells are immortal. This could not have been demonstrated until he had demonstrated that normal cells are mortal. Cellular senescence does not occur in most cancer cells due to expression of an enzyme called telomerase . This enzyme extends telomeres, preventing the telomeres of cancer cells from shortening and giving them infinite replicative potential. A proposed treatment for cancer

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