In vivo

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Studies that are in vivo (Latin for "within the living"; often not italicized in English [1] [2] [3] ) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and plants, as opposed to a tissue extract or dead organism. This is not to be confused with experiments done in vitro ("within the glass"), i.e., in a laboratory environment using test tubes, Petri dishes, etc. Examples of investigations in vivo include: the pathogenesis of disease by comparing the effects of bacterial infection with the effects of purified bacterial toxins; the development of non-antibiotics, antiviral drugs, and new drugs generally; and new surgical procedures. Consequently, animal testing and clinical trials are major elements of in vivo research. In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject. In drug discovery, for example, verification of efficacy in vivo is crucial, because in vitro assays can sometimes yield misleading results with drug candidate molecules that are irrelevant in vivo (e.g., because such molecules cannot reach their site of in vivo action, for example as a result of rapid catabolism in the liver). [4]

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The English microbiologist Professor Harry Smith and his colleagues in the mid-1950s found that sterile filtrates of serum from animals infected with Bacillus anthracis were lethal for other animals, whereas extracts of culture fluid from the same organism grown in vitro were not. This discovery of anthrax toxin through the use of in vivo experiments had a major impact on studies of the pathogenesis of infectious disease.

The maxim in vivo veritas ("in a living thing [there is] truth") [5] is used to describe this type of testing and is a play on in vino veritas , ("in wine [there is] truth"), a well-known proverb.

In vivo vs. ex vivo research

In microbiology, in vivo is often used to refer to experimentation done in a whole organism, rather than in live isolated cells, for example, cultured cells derived from biopsies. In this situation, the more specific term is ex vivo . Once cells are disrupted and individual parts are tested or analyzed, this is known as in vitro.

Methods of use

According to Christopher Lipinski and Andrew Hopkins, "Whether the aim is to discover drugs or to gain knowledge of biological systems, the nature and properties of a chemical tool cannot be considered independently of the system it is to be tested in. Compounds that bind to isolated recombinant proteins are one thing; chemical tools that can perturb cell function another; and pharmacological agents that can be tolerated by a live organism and perturb its systems are yet another. If it were simple to ascertain the properties required to develop a lead discovered in vitro to one that is active in vivo, drug discovery would be as reliable as drug manufacturing." [6] Studies on In vivo behavior, determined the formulations of set specific drugs and their habits in a Biorelevant (or Biological relevance) medium. [7]

See also

Related Research Articles

<i>In vitro</i> Latin term meaning outside a natural biological environment

In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from in vitro experiments may not fully or accurately predict the effects on a whole organism. In contrast to in vitro experiments, in vivo studies are those conducted in living organisms, including humans, and whole plants.

A toxin is a harmful substance produced within living cells or organisms; synthetic toxicants created by artificial processes are thus excluded. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived from the word toxic.

Pharmacology Branch of biology concerning drugs

Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous molecule which exerts a biochemical or physiological effect on the cell, tissue, organ, or organism. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals.

Toxicology Study of substances harmful to living organisms

Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure, route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of Cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is Ribosome Inactivating Proteins, tested in the treatment of Leukemia.

Toxicity Degree of harmfulness of substances

Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ such as the liver (hepatotoxicity). By extension, the word may be metaphorically used to describe toxic effects on larger and more complex groups, such as the family unit or society at large. Sometimes the word is more or less synonymous with poisoning in everyday usage.

In vitro toxicity testing is the scientific analysis of the effects of toxic chemical substances on cultured bacteria or mammalian cells. In vitro testing methods are employed primarily to identify potentially hazardous chemicals and/or to confirm the lack of certain toxic properties in the early stages of the development of potentially useful new substances such as therapeutic drugs, agricultural chemicals and food additives.

Drug discovery Process by which new candidate medications are discovered

In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.

Pharmacognosy Study of plants as a source of drugs

Pharmacognosy is the study of plants and other natural substances as possible sources of drugs. The American Society of Pharmacognosy defines pharmacognosy as "the study of the physical, chemical, biochemical, and biological properties of drugs, drug substances, or potential drugs or drug substances of natural origin as well as the search for new drugs from natural sources".

In genetics, genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic. The alteration can have direct or indirect effects on the DNA: the induction of mutations, mistimed event activation, and direct DNA damage leading to mutations. The permanent, heritable changes can affect either somatic cells of the organism or germ cells to be passed on to future generations. Cells prevent expression of the genotoxic mutation by either DNA repair or apoptosis; however, the damage may not always be fixed leading to mutagenesis.

Pharmacodynamics Area of Academic Study

Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs. The effects can include those manifested within animals, microorganisms, or combinations of organisms.

In silico Latin phrase in biology

In biology and other experimental sciences, an in silico experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon', referring to silicon in computer chips. It was coined in 1987 as an allusion to the Latin phrases in vivo, in vitro, and in situ, which are commonly used in biology. The latter phrases refer, respectively, to experiments done in living organisms, outside living organisms, and where they are found in nature.

An animal model is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of harming a human. Although biological activity in an animal model does not ensure an effect in humans, many drugs, treatments and cures for human diseases are developed in part with the guidance of animal models. Animal models representing specific taxonomic groups in the research and study of developmental processes are also referred to as model organisms. There are three main types of animal models: Homologous, Isomorphic and Predictive. Homologous animals have the same causes, symptoms and treatment options as would humans who have the same disease. Isomorphic animals share the same symptoms and treatments, only. Predictive models are similar to a particular human disease in only a couple of aspects. However, these are useful in isolating and making predictions about mechanisms of a set of disease features.

<i>Ex vivo</i> Process of testing biological interventions on extracted fragments of organisms

Ex vivo literally means that which takes place outside an organism. In science, ex vivo refers to experimentation or measurements done in or on tissue from an organism in an external environment with minimal alteration of natural conditions. Ex vivo conditions allow experimentation on an organism's cells or tissues under more controlled conditions than is possible in in vivo experiments, at the expense of altering the "natural" environment.

Chemogenomics

Chemogenomics, or chemical genomics, is the systematic screening of targeted chemical libraries of small molecules against individual drug target families with the ultimate goal of identification of novel drugs and drug targets. Typically some members of a target library have been well characterized where both the function has been determined and compounds that modulate the function of those targets have been identified. Other members of the target family may have unknown function with no known ligands and hence are classified as orphan receptors. By identifying screening hits that modulate the activity of the less well characterized members of the target family, the function of these novel targets can be elucidated. Furthermore, the hits for these targets can be used as a starting point for drug discovery. The completion of the human genome project has provided an abundance of potential targets for therapeutic intervention. Chemogenomics strives to study the intersection of all possible drugs on all of these potential targets.

Alternatives to animal testing Test methods that avoid the use of animals

Alternatives to animal testing are the development and implementation of test methods that avoid the use of live animals.

Reverse pharmacology Drug discovery by identifying protein targets

In the field of drug discovery, reverse pharmacology also known as target-based drug discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target will have beneficial therapeutic effects. Screening of chemical libraries of small molecules is then used to identify compounds that bind with high affinity to the target. The hits from these screens are then used as starting points for drug discovery. This method became popular after the sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins. This method is the most widely used in drug discovery today. Differently than the classical (forward) pharmacology, with the reverse pharmacology approach in vivo efficacy of identified active (lead) compounds is usually performed in the final drug discovery stages.

Phenotypic screening is a type of screening used in biological research and drug discovery to identify substances such as small molecules, peptides, or RNAi that alter the phenotype of a cell or an organism in a desired manner. Phenotypic screening must be followed up with target identification and validation campaigns, often through the use of chemoproteomics, to identify the mechanisms through which a phenotypic hit works.

In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms.

Bioassay

A bioassay is an analytical method to determine the concentration or potency of a substance by its effect on living animals or plants, or on living cells or tissues(in vitro). A bioassay can be either quantal or quantitative, direct or indirect. If the measured response is binary, the assay is quantal, if not, it is quantitative.

References

  1. Merriam-Webster, Merriam-Webster's Collegiate Dictionary, Merriam-Webster, archived from the original on 2020-10-10, retrieved 2014-04-20.
  2. Iverson C, Flanagin A, Fontanarosa PB, Glass RM, Gregoline B, Lurie SJ, Meyer HS, Winker MA, Young RK, eds. (2007). "12.1.1 Use of Italics". AMA Manual of Style (10th ed.). Oxford, Oxfordshire: Oxford University Press. ISBN   978-0-19-517633-9.
  3. American Psychological Association (2010), "4.21 Use of Italics", The Publication Manual of the American Psychological Association (6th ed.), Washington, DC: APA, ISBN   978-1-4338-0562-2
  4. Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, et al. (December 2015). "Discovery and resupply of pharmacologically active plant-derived natural products: A review". Biotechnology Advances. 33 (8): 1582–1614. doi:10.1016/j.biotechadv.2015.08.001. PMC   4748402 . PMID   26281720.
  5. Life Science Technologies, Cell Signaling: In Vivo Veritas, Science Magazine, 2007
  6. Lipinski C, Hopkins A (December 2004). "Navigating chemical space for biology and medicine". Nature. 432 (7019): 855–61. Bibcode:2004Natur.432..855L. doi:10.1038/nature03193. PMID   15602551. S2CID   4416216.
  7. Klein S (September 2010). "The use of biorelevant dissolution media to forecast the in vivo performance of a drug". The AAPS Journal. 12 (3): 397–406. doi:10.1208/s12248-010-9203-3. PMC   2895438 . PMID   20458565.