Trevor James
The development of the polio vaccine is considered one of the greatest medical triumphs of the 20th century. In the 1950s and early 1960s, Jonas Salk and later Albert Sabin offered the first opportunities to protect against polio through their vaccines. These vaccines were developed using the poliovirus grown in a monkey kidney cell strain. Since then, researchers have discovered that the poliovirus can be grown on other cell lines, such as the Vero cell line, which is derived from African green monkey kidney cells, and the MRC-5 cell line. While the use of monkey cells in polio vaccine development has raised concerns about the potential transmission of simian viruses, the shift towards alternative cell lines has been driven by the need to avoid using primates and the difficulty of obtaining healthy animals that meet stringent requirements.
| Characteristics | Values |
|---|---|
| Are polio vaccines still grown on monkey cells? | Yes, some polio vaccines are still grown on monkey cells, specifically kidney cells. However, there has been a shift towards using other cell lines, such as MRC-5 and Vero cells, due to concerns over the presence of SV40 (a monkey virus) in vaccines and the difficulty of obtaining healthy monkeys that meet stringent requirements. |
| Types of polio vaccines grown on monkey cells | Oral polio vaccine (OPV), Sabin OPV, Salk vaccine (IPV), Albert Sabin's vaccine |
| History of polio vaccines and monkey cells | Jonas Salk and Albert Sabin developed polio vaccines in the 1950s and early 1960s using monkey kidney cells. In 1960, it was discovered that the rhesus monkey kidney cells used to prepare the poliovirus vaccines were infected with SV40. From 1955 to 1963, 98 million Americans were exposed to polio vaccines contaminated with SV40. |
| Concerns and issues | SV40 is a monkey virus that can cause cancers in animals and has been found in certain forms of cancer in humans, such as brain and bone tumors, and lymphomas. However, it has not been conclusively proven that SV40 causes cancer in humans. |
| Alternatives to monkey cells | MRC-5 cells, Vero cells |
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What You'll Learn
The shift from using monkeys to other cell lines
The use of monkey cells in polio vaccines has been a topic of discussion and research for several decades. The initial development of polio vaccines involved the use of monkey cells, and while this approach has had success, there has been a shift towards alternative methods and cell lines.
The history of polio vaccine development includes early experiments with monkey cells. In the 1930s, Kolmer's vaccine development project involved using infected monkey spinal cords, which were critiqued as unsafe. In 1948, a breakthrough came when Thomas H. Weller successfully cultivated the poliovirus in human tissue, paving the way for vaccine research. However, the discovery that poliovirus could be grown in monkey kidney cells by Jonas Salk in 1951 became a significant milestone in vaccine development. This discovery led to the creation of the Salk vaccine, which is based on three wild poliovirus strains grown in monkey kidney tissue culture (Vero cell line).
Over time, concerns arose about the potential risks associated with using monkey cells. Between 1955 and 1963, it was estimated that 98 million Americans were exposed to polio vaccines contaminated with SV40, a monkey virus linked to cancers in animals and later found in certain forms of human cancers as well. This raised serious questions about the safety of using monkey cells in vaccine development.
The need to address these concerns and find alternative approaches prompted scientists to explore other cell lines. The availability of large quantities of MRC-5 cells, a well-characterized human diploid line, provided a promising replacement for primary monkey kidney cells (PMKC). The MRC-5 cells were widely used for other vaccine productions and offered similar safety, efficacy, and immunogenicity profiles to PMKC-derived vaccines. Additionally, the development of a new test for neurovirulence that did not require the use of monkeys further accelerated the shift away from monkey cells in OPV production.
Today, the inactivated polio vaccine still uses a monkey kidney cell strain, but efforts are being made to explore other animal cell strains, such as the Madin Darby Canine Kidney (MDCK) line, for future vaccine development in the United States. The shift from using monkeys to other cell lines in polio vaccine production is driven by a combination of safety concerns, the availability of alternative cell lines, and advancements in vaccine technology.
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The dangers of simian viruses in vaccines
The use of monkey cells in polio vaccines has been a concern for scientists and the general public since the discovery of the simian virus SV40 in the 1950s. SV40, or simian vacuolating virus 40, is a polyomavirus found in both monkeys and humans. It is a DNA virus that can cause tumours in humans and animals, but often persists as a dormant infection.
The issue of SV40 contamination in polio vaccines arose because the vaccines were produced in monkey kidney cell cultures that harboured SV40 between 1955 and 1963. During this period, it is estimated that 98 million Americans alone were exposed to polio vaccines contaminated with SV40. This contamination has also been found in Soviet-made polio vaccines, raising fears that hundreds of millions of people in Eastern Europe, Asia, and Africa may have been exposed.
The potential dangers of SV40 in vaccines lie in its ability to cause cancer. Studies have found SV40 in human mesotheliomas, brain and bone cancers, lymphomas, and other cancers. As of 2003, SV40 had been detected in human tumours in 18 developed countries. However, the link between SV40 and cancer in humans is still a subject of debate. While some studies suggest a potential causal relationship, population-level studies have not shown extensive evidence of increased cancer incidence associated with SV40 exposure.
To address these concerns, efforts have been made to replace primary monkey kidney cells (PMKC) with alternative cell lines for the production of oral polio vaccines (OPV). The availability of large quantities of MRC-5 cells, a well-characterised human diploid line, has provided a suitable replacement for PMKC. This shift away from using monkeys for vaccine production is advantageous not only for safety but also for avoiding the practical difficulties of obtaining healthy primates that meet stringent requirements.
In conclusion, the presence of SV40 in polio vaccines grown on monkey cells has raised concerns about the potential dangers of simian viruses in vaccines. While the link between SV40 and cancer in humans remains inconclusive, the development of alternative cell lines for vaccine production has helped alleviate these concerns by reducing the odds of further contamination by unrecognised viruses.
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The process of cell-culture adaptation
However, there were concerns about the use of monkey cells in polio vaccines, as it was found that from 1955 to 1963, 98 million Americans were exposed to polio vaccines contaminated with SV40, a monkey virus that can cause cancers in animals. This raised fears that hundreds of millions of people in other parts of the world may have also been exposed to SV40 in Soviet-made polio vaccines.
As a result, there has been a shift towards using alternative cell lines such as MRC-5 or Vero cells, which are established and well-characterized cell lines. MRC-5 cells, in particular, have been shown to be a suitable replacement for monkey kidney cells in the production of oral polio vaccines, with similar safety and immunogenicity profiles.
Today, the process of cell-culture adaptation for polio vaccines involves using established cell lines, such as MRC-5 or Vero cells, to grow the poliovirus. These cells are cultured under specific conditions, such as at 37°C and 5% CO2, and are then infected with the poliovirus for a set period. The viruses are then tested for reactivity and used for vaccine production.
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The discovery of polio transmission to monkeys
In the early 20th century, poliomyelitis (polio) was a virus that infected humans, sometimes causing permanent paralysis. It mainly affected children under five and was transmitted from human to human through drinking water contaminated with faeces containing the virus. The virus would enter the body through the gut, damaging the nervous system and leading to paralysis.
In 1908, Dr Karl Landsteiner and Dr Erwin Popper conducted experiments that provided definitive proof that polio was an infectious disease. They injected extracts of the spinal cord of a boy who had died from polio into monkeys, successfully inducing the disease. The disease could then be transmitted from monkey to monkey, providing a valuable model for studying polio. This discovery was a significant milestone in poliomyelitis research, as it confirmed the infectious nature of the disease and enabled further experimentation and understanding of its transmission.
Subsequently, in 1909, Römer, Flexner and Lewis, Leiner and von Wiesner, and Landsteiner and Levaditi independently achieved passage of the poliovirus in monkeys. These experiments played a crucial role in advancing the understanding of polio transmission and provided valuable tools for future research endeavours.
Later, in the 1930s, Maurice Brodie and William H. Park at the New York City Health Department worked on developing an inactivated or "killed virus" vaccine. Brodie's process involved grinding the spinal cords of infected monkeys, treating them with germicides, and ultimately utilising formaldehyde to inactivate the virus. By 1934, Brodie had successfully induced immunity in three monkeys with the inactivated poliovirus and concluded that the administration of the killed virus vaccine tended to result in tissue immunity.
In the following years, various researchers, including Kolmer, Albert Sabin, Hilary Koprowski, and H.R. Cox, made significant contributions to the development of polio vaccines, with Kolmer and Sabin utilising monkeys in their studies. These efforts culminated in the creation of the Salk vaccine, which utilised a monkey kidney tissue culture (Vero cell line) to grow and inactivate the poliovirus.
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The use of monkey spinal cords in early trials
The early years of polio vaccine development involved the use of monkey spinal cords, with researchers aiming to develop a vaccine that could protect against this feared disease. In the 1930s, scientists like John Kolmer, Maurice Brodie, and William Park were at the forefront of these efforts. Kolmer's approach involved grinding the spinal cords of infected monkeys, treating the mixture, and eventually testing it on himself in 1934. Brodie, working with Park, developed a "killed-virus" vaccine using rhesus monkey spinal cords, but their vaccine trials with children in 1935 were inconclusive and led to allergic reactions and potential polio infections.
During this period, researchers also injected stool samples from polio patients into the brains of monkeys, monitoring them for symptoms. When the monkeys displayed polio symptoms, their infected spinal cords and brain tissues were collected. This process resulted in the death of over 17,000 monkeys between 1949 and 1951, but it was later discovered that the poliovirus could be grown in other tissues like kidney, skin, and muscle, reducing the need for monkey spinal cords.
The use of monkey spinal cords and nervous tissue in early vaccine trials was not without controversy. Researchers eventually realized that monkey nervous tissue could cause inflammation of the spinal cord and brain (encephalomyelitis) in humans. This knowledge, along with the development of alternative methods for growing poliovirus, led to a shift away from using monkey spinal cords.
By the 1950s, Jonas Salk and Albert Sabin led the way in developing polio vaccines that utilized monkey kidney cells rather than spinal cords. These vaccines offered the first opportunities for people to protect themselves from polio. However, it was later discovered that some of these vaccines were contaminated with SV40, a monkey virus that can cause cancers in animals and potentially in humans as well. This discovery raised concerns about the safety of vaccines grown on monkey cell cultures.
In summary, the early years of polio vaccine development involved the use of monkey spinal cords and nervous tissue, but this approach was associated with adverse reactions and ethical concerns. The discovery that poliovirus could be grown in other tissues, along with advancements in cell culture techniques, led to a shift away from using monkey spinal cords. Today, polio vaccines are primarily grown on well-characterized monkey cell lines, reducing the risk of contamination and improving vaccine safety.
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Frequently asked questions
Yes, some polio vaccines are still grown on monkey cells. However, the need to avoid using primates has prompted the development of alternative vaccines.
Researchers discovered that the poliovirus could cause disease in monkeys, which led to the use of monkey cells in the development of the polio vaccine. Monkey kidney cells were also used to weaken the virus.
Yes, alternatives to the polio vaccine grown on monkey cells include vaccines produced on MRC-5 cells or Vero cells.
Yes, the alternatives are equally effective in providing immunity against polio. They have similar safety/reactogenicity and immunogenicity profiles following vaccination in infants and children.
