Andrius Kulikauskas

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Gyvybė, Life, Biology, Biology Fresh Air, Chemistry discovery, 20211031 Biology Discovery


Discovery in Biology

  • Sustatyti biologijos žinojimo rūmus ir jų pagrindu apibrėžti gyvybę.
  • Kuria prasme biologijoje yra įvairūs lygmenys, pavyzdžiui, organizmas, organai, audiniai, ląstelės. Organizmui augant ląstelės neauga didesnės, o daugėja.
  • Collect examples of ways of figuring things out in biology from related episodes of Fresh Air.
  • Relate fixed point, replication, consciousness as all expressions of self-tuning, with different notions of the self.
  • Biologijos žinojimo rūmus išplėsti pedagogika, vaikų ugdymu, šviesuolių ugdymu, meile.



Environmental biology - organismal biology - cellular biology - molecular biology

  • Theory of evolution - synthesis
  • Neo-Darwinian synthesis: population genetics and natural selection


  • Observation in physiology
  • Medicine
  • Anatomy


  • Microscopic view - cell theory


  • Structure of DNA
  • Central Dogma: DNA, RNA, protein

Environment & organisms

  • Diversity of organisms
  • Behavior of organisms
  • Travel - ecosystems - territory
  • Alexander von Humboldt - interactions between organisms, environment, geography - biogeography, ecology, ethology
  • Fossil record
  • Extinction and mutability
  • Paleontology
  • Natural history
  • Theology (argument from design) as an impulse

Organisms & cellular

  • Development of organisms
  • Embryology
  • Germ theory of disease

Organisms & molecular

  • Mendel - genetics
  • Genomics - genome
  • Proteomics - entire set of proteins

Environment & molecular

  • Genes and environment
  • Genetics of natural populations

World civilizations

  • Ayurveda
  • Ancient Egyptian medicine
  • Muslim physicians - Avicenna

Befriend system

Befriend system, foster its consciousness

Note slack between component and its system. Note its freedom. Note its boundary and its ability to step in and step out.

  • Auginti augintinį.
  • Laistyti augalėlį.
  • Maria Kapacinskas scratches the neck of the turtle Ollie.
  • Befriending life. Senelė and Ollie, rubbing his neck and he stretches it out. Empathizing with the animal and loving it, tuning in to its sweet spot. Playing with a puppy, fostering its consciousness. Watching the owl at the John Muir building, turning my head and it turning its, back and forth. Playing with a baby.
  • 2020.10.15 Filmmaker Finds An Unlikely Underwater Friend In 'My Octopus Teacher'. It seems that by developing a habit of swimming without wet suit or oxygen, he became that much more in contact with the sea world, as when the octopus reached out to touch him.
  • Paul Nicklen bendravimas su leopardiniu ruoniu parodo, kaip gyvulys gali įvairiai spręsti rūpesčius, rūpintis žmogumi.
  • Fresh Air: Suzanne Simard Close, careful observation contrasted with experience accumulated through childhood. Examination of seedlings doing poorly, and noticing the lack of fungi.

Assemblages of components

Observe components in system

Identify component for inspection.

  • Typically, the component is recurring, although there could be a unique component if it is different from all others.
  • Document organisms.
  • Description of rare animals (写生珍禽图), by Huang Quan (903–965) during the Song dynasty.

Count populations

  • Monitor population dynamics

Comprehensively document an environment

  • Bioblitz An intense period of biological surveying in an attempt to record all the living species within a designated area. Groups of scientists, naturalists and volunteers conduct an intensive field study over a continuous time period (e.g., usually 24 hours). There is a public component to many BioBlitzes, with the goal of getting the public interested in biodiversity. To encourage more public participation, these BioBlitzes are often held in urban parks or nature reserves close to cities.
  • In situ In biology and biomedical engineering, in situ means to examine the phenomenon exactly in place where it occurs (i.e., without moving it to some special medium). In the case of observations or photographs of living animals, it means that the organism was observed (and photographed) in the wild, exactly as it was found and exactly where it was found. This means it was not taken out of the area.
  • This phrase in situ when used in laboratory science such as cell science can mean something intermediate between in vivo and in vitro. For example, examining a cell within a whole organ intact and under perfusion may be in situ investigation. This would not be in vivo as the donor is sacrificed by experimentation, but it would not be the same as working with the cell alone (a common scenario for in vitro experiments).
  • In conservation of genetic resources, "in situ conservation" (also "on-site conservation") is the process of protecting an endangered plant or animal species in its natural habitat, as opposed to ex situ conservation (also "off-site conservation").
  • To bridge the dichotomy of benefits associated with both methodologies, in situ experimentation allowed the controlled aspects of in vitro to become coalesced with the natural environmental compositions of in vivo experimentation.

Transfer component to inert conditions

  • The organism has been moved to another (perhaps more convenient) location such as an aquarium.
  • In vitro was among the first attempts to qualitatively and quantitatively analyze natural occurrences in the lab. Eventually, the limitation of in vitro experimentation was that they were not conducted in natural environments.
  • High-throughput screening (HTS) robotic labs to physically test thousands of diverse compounds a day often with an expected hit rate on the order of 1% or less with still fewer expected to be real leads following further testing.

Ex vivo Sample is taken from a living organism.

  • Refers to experimentation or measurements done in or on tissue from an organism in an external environment with minimal alteration of natural conditions.[2] Ex vivo conditions allow experimentation on an organism's cells or tissues under more controlled conditions than is possible in in vivo experiments (in the intact organism), at the expense of altering the "natural" environment.
  • bioassays;
  • using cancerous cell lines, like DU145 for prostate cancer, in drug testing of anticancer agents;
  • measurements of physical, thermal, electrical, mechanical, optical and other tissue properties, especially in various environments that may not be life-sustaining (for example, at extreme pressures or temperatures);
  • realistic models for surgical procedure development;
  • investigations into the interaction of different energy types with tissues; or
  • as phantoms in imaging technique development.

Receptor antagonist prevents cascades

  • Receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of receptor proteins.[1] They are sometimes called blockers; examples include alpha blockers, beta blockers, and calcium channel blockers.
  • Immunoassay A biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the immunoassay is often referred to as an "analyte" and is in many cases a protein, although it may be other kinds of molecules, of different sizes and types, as long as the proper antibodies that have the required properties for the assay are developed. Analytes in biological liquids such as serum or urine are frequently measured using immunoassays for medical and research purposes.
  • Radiobinding assay
  • Radioimmunoassay A radioimmunoassay (RIA) is an immunoassay that uses radiolabeled molecules in a stepwise formation of immune complexes. A RIA is a very sensitive in vitro assay technique used to measure concentrations of substances, usually measuring antigen concentrations (for example, hormone levels in blood) by use of antibodies. a known quantity of an antigen is made radioactive, frequently by labeling it with gamma-radioactive isotopes of iodine, such as 125-I, attached to tyrosine. This radiolabeled antigen is then mixed with a known amount of antibody for that antigen, and as a result, the two specifically bind to one another. Then, a sample of serum from a patient containing an unknown quantity of that same antigen is added. This causes the unlabeled (or "cold") antigen from the serum to compete with the radiolabeled antigen ("hot") for antibody binding sites. As the concentration of "cold" antigen is increased, more of it binds to the antibody, displacing the radiolabeled variant, and reducing the ratio of antibody-bound radiolabeled antigen to free radiolabeled antigen. The bound antigens are then separated and the radioactivity of the free(unbound) antigen remaining in the supernatant is measured using a gamma counter.
  • Enzyme immunoassay
  • Ligand binding assay An assay, or an analytic procedure, which relies on the binding of ligand molecules to receptors, antibodies or other macromolecules. A detection method is used to determine the presence and extent of the ligand-receptor complexes formed, and this is usually determined electrochemically or through a fluorescence detection method. This type of analytic test can be used to test for the presence of target molecules in a sample that are known to bind to the receptor. By nature, assays must be carried out in a controlled environment in vitro, so this method does not provide information about receptor binding in vivo. The results obtained can only verify that a specific ligand fits a receptor, but assays provide no way of knowing the distribution of ligand-binding receptors in an organism.

Isolate from surroundings. Isolating from natural environment.

  • Ancient Egypt is also known for developing embalming, which was used for mummification, in order to preserve human remains and forestall decomposition.
  • In vitro "In glass". Study in glassware.
  • Biopsy Extraction for inspection of a sample of cells or a tissue from a living organism.
  • "Examples of in vitro studies include: the isolation, growth and identification of cells derived from multicellular organisms (in cell or tissue culture); subcellular components (e.g. mitochondria or ribosomes); cellular or subcellular extracts (e.g. wheat germ or reticulocyte extracts); purified molecules (such as proteins, DNA, or RNA); and the commercial production of antibiotics and other pharmaceutical products."
  • "Viruses, which only replicate in living cells, are studied in the laboratory in cell or tissue culture, and many animal virologists refer to such work as being in vitro to distinguish it from in vivo work in whole animals."
  • "Polymerase chain reaction is a method for selective replication of specific DNA and RNA sequences in the test tube."
  • "Protein purification involves the isolation of a specific protein of interest from a complex mixture of proteins, often obtained from homogenized cells or tissues."
  • "In vitro fertilization is used to allow spermatozoa to fertilize eggs in a culture dish before implanting the resulting embryo or embryos into the uterus of the prospective mother."
  • "In vitro diagnostics refers to a wide range of medical and veterinary laboratory tests that are used to diagnose diseases and monitor the clinical status of patients using samples of blood, cells, or other tissues obtained from a patient."
  • "In vitro testing has been used to characterize specific adsorption, distribution, metabolism, and excretion processes of drugs or general chemicals inside a living organism; for example, Caco-2 cell experiments can be performed to estimate the absorption of compounds through the lining of the gastrointestinal tract; The partitioning of the compounds between organs can be determined to study distribution mechanisms; Suspension or plated cultures of primary hepatocytes or hepatocyte-like cell lines (HepG2, HepaRG) can be used to study and quantify metabolism of chemicals.[6] These ADME process parameters can then be integrated into so called "physiologically based pharmacokinetic models" or PBPK."

Moving from in vivo to in vitro

Extinction and nonextinction in contrived environment

  • Huffaker's mite experiment Contrived world with one species of prey mites and one species of predatory mites. Variation of potential for dispersion in a contrived environment leads to a variation of population dynamics for predator and prey. An optimal environment yields oscillations in populations and a nonoptimal environment yields extinctions.

Analyze dead specimens

  • Dissect.
  • Stuff, preserve.
  • Mummify. Egiptas.
  • Drawing. Artists such as Albrecht Dürer and Leonardo da Vinci, often working with naturalists, were also interested in the bodies of animals and humans, studying physiology in detail and contributing to the growth of anatomical knowledge.

Transfer component to responsive conditions

  • Transfer biomaterial to a substitute environment.
  • Ex vivo Transfering tissue from a living organism into a comparable, more convenient or more ethical environment. The external environment is set up to minimally alter natural conditions.
  • Most information about the training and domestication of animals was probably transmitted orally, but one text dealing with the training of horses has survived.
  • The ancient Mesopotamians had no distinction between "rational science" and magic. When a person became ill, doctors prescribed both magical formulas to be recited and medicinal treatments. The earliest medical prescriptions appear in Sumerian during the Third Dynasty of Ur (c. 2112 – c. 2004 BCE). The most extensive Babylonian medical text, however, is the Diagnostic Handbook written by the ummânū, or chief scholar, Esagil-kin-apli of Borsippa, during the reign of the Babylonian king Adad-apla-iddina (1069 – 1046 BCE). In East Semitic cultures, the main medicinal authority was an exorcist-healer known as an āšipu. The profession was passed down from father to son and was held in high regard. Of less frequent recourse was the asu, a healer who treated physical symptoms using remedies composed of herbs, animal products, and minerals, as well as potions, enemas, and ointments or poultices. These physicians, who could be either male or female, also dressed wounds, set limbs, and performed simple surgeries. The ancient Mesopotamians also practiced prophylaxis and took measures to prevent the spread of disease.
  • Ligand binding assay In vivo ligand binding and receptor distribution can be studied using Positron Emission Tomography (PET), which works by induction of a radionuclide into a ligand, which is then released into the body of a studied organism. The radiolabeled ligands are spatially located by a PET scanner to reveal areas in the organism with high concentrations of receptors.

Study within surroundings

  • In vivo "Within the living."
  • In vivo experimentation allowed testing to occur in the original organism or environment.
  • "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.
  • In ovo 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.
  • In human vaccine development, the main advantage is rapid propagation, and high yield, of viruses for vaccine production. This method is most commonly used for growth of influenza virus, both attenuated vaccine and inactivated vaccine forms.

Transfer component to system

  • Tag migratory birds, marine species or other animals.
  • Lipinski's Rule of Five A rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has chemical properties and physical properties that would make it a likely orally active drug in humans. Most orally administered drugs are relatively small and moderately lipophilic molecules.
  • Hershey-Chase experiment When the bacteriophages infected the bacteria, the progeny contained the radioactive isotopes in their structures. This procedure was performed once for the sulfur-labeled phages and once for phosphorus-labeled phages. The labeled progeny were then allowed to infect unlabeled bacteria.

Creating deviations from norms and studying the effects

  • Allometric engineering Alter a body part with respect to the entire body to see its effect on performance. For example: Cropping or extending bird tail lengths to affect success in mating. Removing an ovary in cockroaches to reduce number of progeny, increase resource allocation to each offspring.

Assemblages of conditions

Observe system upon components

Discover conditions where the system reveals itself

  • Alter conditions to make system traits visible.
  • Stain cells.
  • Hershey-Chase experiment Radioactive phosphorus-32 was used to label the DNA contained in the T2 phage. Radioactive sulfur-35 was used to label the protein sections of the T2 phage, because sulfur is contained in protein but not DNA. Hershey and Chase inserted the radioactive elements in the bacteriophages by adding the isotopes to separate media within which bacteria were allowed to grow for 4 hours before bacteriophage introduction.
  • Hershey-Chase experiment Disruption of phage from the bacteria by agitation in a blender followed by centrifugation allowed for the separation of the phage coats from the bacteria. These bacteria were lysed to release phage progeny.

Use causality to verify the presence or absence of a substance

  • Avery–MacLeod–McCarty experiment "An immunological precipitation caused by type-specific antibodies was used to verify the complete destruction of the capsules."
  • Avery–MacLeod–McCarty experiment Is the substance destroyed or not by the testing agents? "To show that it was DNA rather than some small amount of RNA, protein, or some other cell component that was responsible for transformation, Avery and his colleagues used a number of biochemical tests. They found that trypsin, chymotrypsin and ribonuclease (enzymes that break apart proteins or RNA) did not affect it, but an enzyme preparation of "deoxyribonucleodepolymerase" (a crude preparation, obtainable from a number of animal sources, that could break down DNA) destroyed the extract's transforming power."

Center: Alter environment to make visible distinctions in organisms


  • Quellung reaction (Serological typing) Make distinctions in strains of bacteria visible. Antibodies bind to a bacterial capsule and make it opaque and visible under a microscope.

Algebra of distinctions

  • Counterstain We make every cell distinguishable (with the counterstain) and then distinguish certain cells (which retain the primary stain).
  • Gram stain Classify bacteria into two groups as to whether they have a thick layer of peptidoglycan in the cell wall that retains the primary stain, or whether they have a thinner wall for which the primary stain can be washed out, leaving only the counterstain which stains everything. Note here the use of the washing out.

Tagging animals

  • Tagging of Pacific Predators The tagging of 22 marine species belonging to 2,000 animals. Tags may be surgically implanted and archive various parameters. Tags may be removed later. Or tags may self-release and transmits data to a satellite. Air-breathing marine animals may carry an antenna. Tags can record information on pressure, light, internal and external body temperature, speed of travel. Tags provide information on migration routes and ecosystems.

Bind receptor to tag

  • Enzyme-linked immunosorbent assay (ELISA) Uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence of a ligand (commonly a protein) in a liquid sample using antibodies directed against the protein to be measured. In the most simple form of an ELISA, antigens from the sample to be tested are attached to a surface. Then, a matching antibody is applied over the surface so it can bind the antigen. This antibody is linked to an enzyme and then any unbound antibodies are removed. In the final step, a substance containing the enzyme's substrate is added. If there was binding the subsequent reaction produces a detectable signal, most commonly a color change.

Discover conditions where the system fails

Note damage to communities

  • Community ecotoxicology studies the effects of all contaminants on patterns and species abundance, diversity, community composition, and species interactions. Ecotoxicology
  • Ecotoxicology strives to assess the impact of chemical, physicochemical and biological agents, not only at the individual level, but also at that of populations and entire ecosystems. In this respect, ecotoxicology again takes into consideration dynamic balance under strain. ... Ecotoxicology is primarily linked to ecology for its goal seeks to circumscribe the influence that stress factors can have on relationships existing between organisms and their habitat. Ecotoxicology
  • Bioassay Determine concentration or potency of a substance by its effect on living cells, tissues or living animals. Typical bioassay involves a stimulus (ex. drugs) applied to a subject (ex. animals, tissues, plants) and a response (ex. death) of the subject is triggered and measured. The intensity of stimulus is varied by doses and depending on this intensity of stimulus, a change/response will be followed by a subject.
  • Bioassay Paul Ehrlich introduced the concept of standardization by the reactions of living matter. His use of bioassay was able to discover that administration of gradually increasing dose of diphtheria in animals stimulated production of antiserum.

Classify agents by responses

Classification by biologically evoked response

  • Avery–MacLeod–McCarty experiment: Background "Pneumococcus is characterized by smooth colonies which have a polysaccharide capsule that induces antibody formation; the different types are classified according to their immunological specificity."
  • Determine signs of life, death
  • Effects of acid rain and resultant soil mineral changes on micro-environments of plant root systems. Hubbard Brook Experimental Forest
  • Hershey-Chase experiment Hershey and Chase showed that the introduction of deoxyribonuclease (referred to as DNase), an enzyme that breaks down DNA, into a solution containing the labeled bacteriophages did not introduce any 32P into the solution. This demonstrated that the phage is resistant to the enzyme while intact.
  • Hershey-Chase experiment Additionally, they were able to plasmolyze the bacteriophages so that they went into osmotic shock, which effectively created a solution containing most of the 32P and a heavier solution containing structures called "ghosts" that contained the 35S and the protein coat of the virus. It was found that these "ghosts" could adsorb to bacteria that were susceptible to T2, although they contained no DNA and were simply the remains of the original bacterial capsule. They concluded that the protein protected the DNA from DNAse, but that once the two were separated and the phage was inactivated, the DNAse could hydrolyze the phage DNA.[1]

Hurt or kill individuals

  • Linking dose and probability of death. LC50 is the acute toxicity test that tests for the concentrate of tissue at which it is lethal to 50% within the test-specified time. The test may start with eggs, embryos, or juveniles and last from 7 to 200 days. Ecotoxicology
  • Linking dose and probability of damage. EC50 is the concentration that causes adverse effects in 50% of the test organisms (for a binary yes/no effect such as mortality or a specified sublethal effect) or causes a 50% (usually) reduction in a non-binary parameter such as growth. Ecotoxicology
  • Acute and chronic toxicity tests are performed for terrestrial organisms including avian, mammalian, nontarget arthropods, and earthworms. Ecotoxicology
  • Animal testing. Endocrine disruptor In 1998, the EPA announced the Endocrine Disruptor Screening Program by establishment of a framework for priority setting, screening and testing more than 85,000 chemicals in commerce. While the Food Quality Protection Act only required the EPA to screen pesticides for potential to produce effects similar to estrogens in humans, it also gave the EPA the authority to screen other types of chemicals and endocrine effects. Based recommendations from an advisory panel, the agency expanded the screening program to include male hormones, the thyroid system, and effects on fish and other wildlife. The basic concept behind the program is that prioritization will be based on existing information about chemical uses, production volume, structure-activity and toxicity. Screening is done by use of in vitro test systems (by examining, for instance, if an agent interacts with the estrogen receptor or the androgen receptor) and via the use of in animal models, such as development of tadpoles and uterine growth in prepubertal rodents. Full scale testing will examine effects not only in mammals (rats) but also in a number of other species (frogs, fish, birds and invertebrates). Since the theory involves the effects of these substances on a functioning system, animal testing is essential for scientific validity, but has been opposed by animal rights groups. Similarly, proof that these effects occur in humans would require human testing, and such testing also has opposition.
  • Establish correlations. Endocrine disruptor Any system in the body controlled by hormones can be derailed by hormone disruptors. Specifically, endocrine disruptors may be associated with the development of learning disabilities, severe attention deficit disorder, cognitive and brain development problems; deformations of the body (including limbs); breast cancer, prostate cancer, thyroid and other cancers; sexual development problems such as feminizing of males or masculinizing effects on females, etc.

Measure and characterize damage to organisms

  • The Organization for Economic Cooperation and Development (OECD) test guideline has developed specific tests to test toxicity level in organisms. Ecotoxicological studies are generally performed in compliance with international guidelines, including EPA, OECD, EPPO, OPPTTS, SETAC, IOBC, and JMAFF. Ecotoxicology

Discover conditions where the system maintains itself

Stressing an ecosystem

  • Stressing with pollution. In 1969, the fertilization experiment began with Lake 227, and in 1973, the double-basin eutrophication experiment on Lake 226 began, in which a section of the Lake 226S was overfertilized with carbon and nitrogen and the other section 226N with carbon and nitrogen as well as phosphorus.[20] The iconic image of the green eutrophied section 226N has been described as the most important in the history of limnology. It convinced the public and policy-makers that phosphorus levels needed to be controlled. "Work at the ELA has produced important evidence on the effects of acid rain and led to the discovery that phosphates from household detergents cause algal blooms. It has elucidated the impacts on fish of mercury and shown how wetland flooding for hydroelectricity leads to increased production of greenhouse gases." Experimental Lakes Area
  • Effects of deforestation on mineral flux. Focus on a watershed. Hubbard Brook Experimental Forest
  • Cycling of Nitrogen, Sulfur, Phosphorus, Mercury, Calcium, and Carbon, and effects of pollution on flux of these and other minerals. Hubbard Brook Experimental Forest
  • Observe effects of parameters on stress, vitality, reproduction
  • Monitor vital signs
  • Determine signs of well being, robustness, stress, harm
  • Classify by response
  • Measure natural balance
  • Observe tuning and deviations
  • Artificially create deviations (perturbations) and study the effects

Interrelated population dynamics

  • Wolves and moose on Isle Royale Moose came to Isle Royale in the early 1900s, later followed by wolves. The populations have been studied since 1958. They are stressed because the moose overbrowse and the wolves are inbred. The populations fluctuate dramatically and have yet to settle down.

Balance: Noting the natural balance, the base state

  • Functional equilibrium, balanced growth hypothesis, optimal partitioning theory. Analysis of the relative proportion of plant biomass present in the various organs of a plant. Similarly, analysis of the biomass in a plant community. The balance may change depending on environmental conditions, thus reflecting them. See: Biomass allocation
  • C-budget.(Carbon-budget) A way to determine sugar allocation in a plant to its various organs. Measurements are made of uptake of carbon (dioxide) through photosynthesis, and the losses of carbon through roots and shoots by way of respiration. See: Biomass allocation
  • Growth allocation measure the increase in the total biomass of a plant and its various parts. See: Biomass allocation
  • Biomass allocation can involve a measurement of the total allocation of growth over the years, discounting yearly turnover in leaves and fine roots.

How environmental factors affect organisms

Alter the conditions in an ecosystem

  • A method used by ecologists and plant biologists that raises the concentration of CO2 in a specified area and allows the response of plant growth to be measured. Allows for study of plant competition and study of large trees. Measuring the effect of elevated CO2 using FACE is a more natural way of estimating how plant growth will change in the future as the CO2 concentration rises in the atmosphere. Horizontal or vertical pipes are placed in a circle around the experimental plot, which can be between 1m and 30m in diameter, and these emit CO2 enriched air around the plants. The concentration of CO2 is maintained at the desired level through placing sensors in the plot which feedback to a computer which then adjusts the flow of CO2 from the pipes. FACE circles have been used to measure the response of soybean plants to increased levels of ozone and carbon dioxide. Free-air concentration enrichment

Alter nonliving parameter in living environment

  • Free-air concentration enrichment Releasing CO2 in a natural competitive environment, thus maintaining high levels of CO2, and then measuring percentage increased growth compared to control group.

Maintaining artificial environments. Examining the capabilities for self-sustainability of a closed system or controlled system

  • Controlled (or closed) ecological life-support systems (acronym CELSS) are a self-supporting life support system for space stations and colonies typically through controlled closed ecological systems, such as the BioHome, BIOS-3, Biosphere 2, Mars Desert Research Station, and Yuegong-1. These are life support systems for humans. The system includes air revitilization, food production, waste-water treatemnt.
  • Bioregenerative life support system
  • Yuegong-1 is a Chinese research facility for developing a moonbase that recycled oxygen, water, food, waste, etc. Yellow mealworms were grown for protein but were met with resistance by Western astronauts.
  • Ecosphere Freshwater closed systems are often attempted by nature hobbyists and as experimental projects or demonstrations for biology classes. These require nothing more than a large glass jar with an airtight lid, a few cups of lake or river water, and mud or other substrate from the same body of water. Kept indoors at room temperatures, with exposure to sunlight from a window, such systems have been found to contain living organisms even after several decades. The original level of diversity always falls drastically, sometimes exhibiting interesting patterns of population flux and extinction. Multicellular organisms fare poorly. Eventually an equilibrium of micro-organisms is established.
  • BioHome was used for a variety of experiments. BioHome focused on alternative, non-chemical sewage treatment methods utilizing non-edible plants of aquatic disposition. The aquatic and semi-aquatic plants were chosen based on their previously known abilities for waste treatment. Another usage for the plants used in the wastewater treatment included its implementation as compost, which was feasible as the plants grew as more sewage was introduced. The processed water is subsequently used as toilet and plant water. Plants, or more accurately, the root systems of aquatic plants found to have a filtering effect include bulrush, reed, soft rush and water iris. Water suitable for human use was extracted from the condensate from three sources: dehumidifier units, air conditioning, and plant leaves. In fact, plant leaves proved to be a major, consistently reliable source of water vapors. The condensate was run through ultraviolet equipment to ensure its safety. The plants established and maintained indoor air quality.
  • Life support system The combination of equipment that allows survival in an environment or situation that would not support that life in its absence. It is generally applied to systems supporting human life in situations where the outside environment is hostile, like in space or underwater, or medical situations where the health of the person is compromised to the extent that the risk of death would be high without the function of the equipment.

Discover conditions where the system transforms or reproduces itself

Jeigu rūpinamės savimi, mylime save, esame linkę pranokti save.

Measure crop yield size and content and compare with lab results.

  • A meta-analysis of 15 years of FACE studies, found the response to elevated CO2 using FACE only slightly increases yield in crop plants (5-7% in rice and 8% in wheat). These responses were lower than was expected from previous studies that measured the effect in labs or enclosures. Free-air concentration enrichment
  • Increased atmospheric carbon dioxide has been found to reduce plant water use, and consequently, the uptake of nitrogen, so particularly benefiting crop yields in arid regions. The carbohydrate content of crops is increased from photosynthesis, but protein content is reduced due to lower nitrogen uptake. Legumes and their symbiotic "nitrogen fixing" bacteria appear to benefit more from increased carbon dioxide levels than most other species. Free-air concentration enrichment
  • Effects of environmental changes on bird behavior and insect population, especially regarding reproductive capacity. Hubbard Brook Experimental Forest
  • Michael Pollan How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence.

How artificial changes affect natural environments. Model: Variously modify an environment and compare resulting differences

  • Biological Dynamics of Forest Fragments Project Some rainforests on the outskirts of Manaus, Brazil were inventorized and studied before and after fragmentation. The continuous rainforest was fragmented into 11 regions the size of 1 hectare, 10 hectares and 100 hectares. This was in response to the SLOSS (single large or several small) reserve size debate. Three main questions were: What effect does fragment size have on the rate of species extinction? Would the local extinction rate eventually slow and halt, equalizing the number of species? How do species interactions and demography change as a result of reduced habitat? Edge effects, extinction rates, biotic and abiotic interactions, mortality factors and soil quality were studied over a 25 year period that started before the deforestation. Factors surveyed at edges include temperature, vapor pressure deficit (VPD), and soil moisture. Mark-recapture programs for birds reveal changes in species composition and activity level.
  • Godwin plots Five experimental areas of vegetation were established in the 1927 by Prof. Sir Harry Godwin. The first plot is never cut. The second is cut every four years, the next every three years and so on. ... This management has, over many years, produced different vegetation patterns. Godwin used the experiment to demonstrate that management alone can change plant communities - an idea which is almost universally accepted today, but was quite radical in the early 20th century.

Observe effects of changes in global parameters

  • Observe effects of management of the ecosystem. The early ecosystem monitoring was aimed at studying the effects of forest management practices on water flow and quality. These data have been helpful as baselines for the increasingly sophisticated areas of ongoing research in the forest. Hubbard Brook Experimental Forest
  • The Global Change Experiment studies the response of California annual grassland to global change, including elevated atmospheric CO2, temperature, altered precipitation, and increased nitrogen deposition. Jasper Ridge Biological Preserve

Standardize environment

Rule the environment, but more specifically, control the environment, make it uniform in various ways.

  • Look for a three-cycle expressing bundles of traits: As written information (DNA) taking a stand; as execution of such information, following through; as reflection, reorganization.

Choose convenient components

Pick a representative system that is easy to work with, like a fruit fly, a mouse.

  • Work with fruit flies, mice.
  • Noting differences in phenotypes, such as the many characteristics of fruit flies.
  • Mesopotamia: Animal physiology was studied for divination, including especially the anatomy of the liver, seen as an important organ in haruspicy. Animal behavior too was studied for divinatory purposes.
  • Compare with the amino-carboxylic acid links as standard links.

Identify an ecosystem

Reproduce for standardized traits

  • Breeding. Veisti.
  • Destroy alternative candidates
  • Cloning.
  • Grafting.
  • Suckers - iš atžalų - kaip antai bananai.'


  • Breed back Selective breed domestic animals in an attempt to achieve an animal breed with a phenotype that resembles a wild type ancestor. The extinct wild type ancestors of a given species are known only through skeletons and, in some cases, historical descriptions. In order to test genetic closeness, DNA (both mitochondrial and nuclear) of the breeding animals must be compared against that of the extinct animal. Humans have selected animals only for superficial traits, and as a rule did not intentionally change less-observable traits, such as metabolic biochemistry. Natural selection might serve as an additional tool in creating "authentic" robustness, "authentic" behaviour, and perhaps, the original phenotype as well. In some cases, a sufficient predator population would be necessary to enable such a selection process; in today's Europe, where many breeding-back attempts take place, this predator population is largely absent.
  • Standardized cell lines. Cell culture
  • Immortalised cell line a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells can therefore be grown for prolonged periods in vitro. The mutations required for immortality can occur naturally or be intentionally induced for experimental purposes.

Leverage challenges humanity has invested in

  • A global problem that is relevant to humans on a mass scale, allowing for a mass investment, as with a cash crop, a mono culture.

Create a network of data collection

  • ... promoting the establishment of research networks, working with public agencies to enhance funding sources, and building interactions between scientists and policy makers ... maintaining a comprehensive registry of scientific data sets which may be used in future research projects. Organization of Biological Field Stations

Introduce agent that transforms a system

Introduce agent that transforms a system

  • Think of a replicant as a fixed point.
  • Consider difference between a phenotypic basis for the science (based on the human observer) and a molecular basis (based on what the system can generate). The post-system molecular basis takes over from the pre-system phenotypic basis.
  • Sterile insect technique Could be sterile mosquitoes. They don't have to be reproductive.
  • Could be a reusable catalyst, a reusable solvent.

Transformative ingredient

  • Can one type change into another type? And how?
  • Two ingredients in combination yield a result that neither would by itself.
  • Griffith's experiment Injecting mice with a combination of a nonvirulent strain and the remains of a heat-destroyed virulent strain killed the mice and yielded both the nonvirulent strain and the virulent strain. Thus the dead strain yet had a "transforming principle" that transformed the nonvirulent strain.

Selected introduction of species

  • Australian Dung Beetle Project Dung accumulated upon introduction of cattle. Various species of dung beetles were therefore selected and introduced in Australia, studying their effects on soil quality, fly control, worm control. Also, researchers in South Africa, where there are hundreds of species of dung beetle, worked to identify species that would match 8 selection criteria. Beetle collection surveys were undertaken to understand the environmental conditions preferred by different species. Habitat specificity matching proved important in achieving success.

Reconstructing an environment

  • Pleistocene Park Sergey Zimov and Nikita Zimovn are attempting to re-create the northern subarctic steppe grassland ecosystem that flourished in the area during the last glacial period. They are reintroducing large herbivores and monitoring their effect on local fauna, studying the conversion of ecologically low-grade tundra biome to a productive grassland biome.

Growing a biological responder

  • Avery–MacLeod–McCarty experiment: Background "With the development of serological typing, medical researchers were able to sort bacteria into different strains, or types. When a person or test animal (e.g., a mouse) is inoculated with a particular type, an immune response ensues, generating antibodies that react specifically with antigens on the bacteria. Blood serum containing the antibodies can then be extracted and applied to cultured bacteria. The antibodies will react with other bacteria of the same type as the original inoculation."

Assemblages of traits

  • Think of the four levels of what aspect is being reproduced or not (for example, survival and maintenance as self-replication, growth as self-replication, purpose as self-replication).

Observe contamination of controlled environment

Is there a deviation from norms.

  • Genetic mutations
  • Observe deviations

Study frequencies of combinations of traits

What is the deviation from norms.

Observation of deviations from norms

  • Look for correlations in traits.
  • Consider size vs. death rate from predators.
  • Analyze composition

Analyze the natural ingredient. Identify by consistent proportions of parts

  • Avery–MacLeod–McCarty experiment Chemical analysis showed that the proportions of carbon, hydrogen, nitrogen, and phosphorus in this active portion were consistent with the chemical composition of DNA.

Set: Cataloguing the variety of natural solutions along with their norms and variations. (The norms and deviations within the norms and deviations.)

  • Statistical shape analysis An analysis of the geometrical properties of some given set of shapes by statistical methods. For instance, it could be used to quantify differences between male and female gorilla skull shapes, normal and pathological bone shapes, leaf outlines with and without herbivory by insects, etc. Important aspects of shape analysis are to obtain a measure of distance between shapes, to estimate mean shapes from (possibly random) samples, to estimate shape variability within samples, to perform clustering and to test for differences between shapes. One of the main methods used is principal component analysis (PCA).
  • Cataloguing a divergence of solutions.
  • Interspecific allometry Compare related species (for example, insects) to see how total body size is related to the size of various body parts.
  • Determining primary and secondary factors. A comparative study shows that in explaining basal metabolic rates of mammals, body mass is of first importance, taxonomy is of second importance, and environment is of subsequent importance. (See: Allometry)
  • Model how a common form is diversely applied. Allometry Living organisms of all shapes and sizes utilize spring mechanisms in their locomotive systems, probably in order to minimize the energy cost of locomotion. The allometric study of these systems has fostered a better understanding of why spring mechanisms are so common, how limb compliance varies with body size and speed, and how these mechanisms affect general limb kinematics and dynamics.
  • Scaling with regard to a power of body mass of physiological effects of drugs and other substances. Allometry
  • Distinguish features which depend on the size of an animal or not. Muscle tissue is the same across animals but larger animals have a greater number of muscle fibers and lower intrinsic speed.
  • Analysis of diversity among similarity. Analysis of features that affect movement and gaits of different species, making use of the similarities. Application of these models to form realistic hypotheses for extinct species.
  • Assemble patterns of dimensions into behavioral invariants. Allometry Alexander found that animals of different sizes and masses traveling with the same Froude number consistently exhibit similar gait patterns. Dynamically similar gaits are those between which there are constant coefficients that can relate linear dimensions, time intervals, and forces. Animals of different sizes tend to move in dynamically similar fashion whenever the ratio of their speed allows it. Duty factors—percentages of a stride during which a foot maintains contact with the ground—remain relatively constant for different animals moving with the same Froude number. Body mass has even more of an effect than speed on limb dynamics. Leg stiffness, peak force experienced, various other factors are proportional to mass to a power.

Work from phenotype effect to genotype cause

How there is deviation from norms. How does genetics work?

Look for genetic causation.

Consider in parallel the genetic explanation (across generations) and the phenotypic evidence (across generations).

Compare traits of offspring with traits of parents (as did Mendel).

Human Genome Project was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying and mapping all of the genes of the human genome from both a physical and a functional standpoint.

Leverage parallelism between code, instruments, agents, population

Why there is deviation from norms. Why do things evolve as they do?

Four levels:

  • genes (code - in substrate)
  • tissues (shared chemical environment thus manifestation of gene)
  • agents (organizing tissues)
  • populations (of species but also entire ecosystem)(supporting persistence and reproduction)

Priežastys ar, priežastys kokie, priežastys kaip, priežastys kodėl.

  • https://plato.stanford.edu/entries/aristotle-causality/#FouCauSciNat
  • Aristotle is committed to a form of causal pluralism. For Aristotle, there are four distinct and irreducible kinds of causes. The focus of this entry is on the systematic interrelations among these four kinds of causes.
  • Aristotle offers the slogan “it takes a human being to generate a human being” (for example, Phys. 194 b 13; Metaph. 1032 a 25, 1033 b 32, 1049 b 25, 1070 a 8, 1092 a 16). This slogan is designed to point at the fundamental fact that the generation of a human being can be understood only in the light of the end of the process; that is to say, the fully developed human being. The question thus arises as to what it takes for a human being to be fully developed. Aristotle frames his answer in terms of the human form, maintaining that a human form is fully realized at the end of generation. But this does not explain why it takes a human being to generate a human being. Note, however, that a fully developed human being is not only the end of generation; it is also what initiates the entire process. For Aristotle, the ultimate moving principle responsible for the generation of a human being is a fully developed living creature of the same kind; that is, a human being who is formally the same as the end of generation. (A final clarification is in order here: Aristotle is committed to a hylomorphic explanation of animal generation. His considered view is that the father supplies the form whereas the mother provides the matter.)

List: Analyzing versions of an organism's structure to note how they are optimized for different natural environments

Search for determining factors

  • Allometry Factors that affect body mass include the type of physiological design (such as open or closed circulatory system), mechanical design (endoskeleton or exoskeleton), habitat (available land area, water vs. land)

Proposed explanation of deviations from norms

  • Observation of trade-offs with regard to environments. In the Arctic, trees reduce the risk of freezing by having risk-diffuse wood with narrower pores which, however, are less efficient for transporting water.
  • Observation of adaptations to extreme environments. In the snowy Arctic, large feet in proportion to body weight act like snowshoes; larger size reduces the ratio of surface area to body volume; layers of plumage, fat and fur retain body warmth; digestive adaptations to better digest woody plants with or without the aid of microbial organisms; animals hibernate or migrate.
  • Evolutionary allometry Over the course of the evolution of a species, consider how total body size is related to the size of various body parts.
  • Ontogenetic allometry In the growth of an organism, consider whether the growth is isometric or allometric, that is, consider whether the size of various body parts changes, proportionately, as total body size increases. Why is natural here presuming the life cycle.
  • Allometry Given a species, consider the distribution of organisms in terms of body size, and see whether the size of various body parts changes. Why is natural here.
  • Allometry Given differences in the relationship between total body size and the size of various parts, consider whether, how and why behavior changes.
  • Allometry Note deviations from isometry during growth as evidence of physiological factors forcing allometric growth.
  • Allometry Plot an animal's basal metabolic rate against their body mass, obtain a power-law dependence, Kleiber's law. Thus body mass can explain much of the variation in basal metabolic rate.
  • Phylogenetic comparative methods Infer the evolutionary history of some characteristic (phenotypic or genetic) across a phylogeny.
  • Phylogenetic comparative methods Infer the process of evolutionary branching itself (diversification rates).
  • Confirming the optimum, as with Lack's principle. The clutch size of birds is observed along with the number of birds that are then successfully fed and raised. The average is confirmed to be the optimum, in accordance with the expectations of natural selection. The point here is that the assumption of conservatism and optimality facilitates the analysis and identification of relevant characteristics.

System of traits for ruling traits for success in a system

  • Think of the system as comparing in six ways the probabilities for various aspects of replication (like mutation). This is the basis for evolution.

Evolution of system

  • Observe development (manifestation of traits from potential to expressed)
  • Document stages of development
  • Note divergence in development


System boundaries

  • Establish system boundaries, what is in and what is out

Variations in space of possibilities

  • Analyze how variations are optimized for their conditions
  • Fresh Air: Suzanne Simard Tracking of isotopes moving back and forth from one tree to another tree.
  • Fresh Air: Suzanne Simard Correlating the movement of resources with the relationship between the trees, that one shades another.
  • Human Cell Atlas. Classify cells by structure, location, function, molecules.

Anatomical map

  • Dissection Dismembering of the body of a deceased animal or plant to study its anatomical structure.

Autopsy Used in pathology and forensic medicine to determine the cause of death in humans. A surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any disease or injury that may be present for research or educational purposes.


Gives time sequence that shows how causal functions work or fail, and can be compared.


  • Identify critical points in reproduction strategy
  • Compare similar systems at different stages of life cycle.
  • Appreciating the factors in an organism's reproductive strategy.

Identifying critical points

  • Constructing a theory by interpreting and associating manifest genetically based functionality with the propensity to reproduce the genes.

Sequence of extractions to restrict the natural ingredient

  • Avery–MacLeod–McCarty experiment "The purification procedure Avery undertook consisted of first killing the bacteria with heat and extracting the saline-soluble components. Next, the protein was precipitated out using chloroform and the polysaccharide capsules were hydrolyzed with an enzyme. An immunological precipitation caused by type-specific antibodies was used to verify the complete destruction of the capsules. Then, the active portion was precipitated out by alcohol fractionation, resulting in fibrous strands that could be removed with a stirring rod."

Extracting a suspected agent

Destroying candidate agents

Preventing further cascades - focusing on one step at a time

  • Pharmacologists utilize assays in order to create drugs that are selective, or mimic, the endogenously found cellular components. On the other hand, such techniques are also available to create receptor antagonists in order to prevent further cascades. Ligand binding assay


Change in state (such as life cycle) for making comparisons of overall statuses in two environments, creatures etc., that needed to be compared relatively with matched chronology.

Focusing on the general framework for the variety

  • Linus Pauling investigating protein structure. Ignore side chains and just focus on the backbone.

Collecting data about an ecosystem over the long term

  • Schindler's research "demonstrated the cumulative impacts on boreal lake life of global warming, acidification and ozone depletion. Using long-term reference data collected at the ELA, he has shown that climate warming and drought have severe and previously unrecognized effects on the physics, chemistry, and biology of lakes." Experimental Lakes Area
  • Focus on a watershed. Hydrology, including ecosystem water flow, snowfall analysis, and long-term ice-in/ice-out measurements. Hubbard Brook Experimental Forest

Compare similar environments that are at different stages of development

  • Chronosequence A common assumption in establishing chronosequences is that no other variable besides age (such as various abiotic components and biotic components) has changed between sites of interest. Because this assumption cannot always be tested for environmental study sites, the use of chronosequences in field successional studies has recently been debated. Since many processes in forest ecology take a long time (decades or centuries) to develop, chronosequence methods are used to represent and study the time-dependent development of a forest. Field data from a forest chronosequence can be collected in a short period of several months. Chronosequences are often used to study the changes in plant communities during succession. A classic example of using chronosequences to study ecological succession is in the study of plant and microbial succession in recently deglaciated zones. For example, a study from 2005 used the distance from the nose of a glacier as a proxy for site age.

Contrast similar natural environments, determine stages in evolution, characterize robustness,

Comparing ecosystems

  • Chronosequence Comparing similar ecological sites that represent different ages in a process of change such as in ecological succession, for example, after fires. As a glacier retreats, the distance from the nose of the glacier can be used as a proxy for age.

Monitoring ecosystems

  • Collecting data over decades allows the understanding of the progression of causes and effects of ecological changes. Data may include soil samples, surveying, photographing landscapes from airplanes, tagging salmon, as in the Arctic.

Catalog diversity

  • Categorizing distinctions
  • Categorize distinctions among similar systems
  • Catalogue components

Similarity among distinctions

  • Catalogue variety of solutions
  • Analyze how variations reflect the same internal logic.

Network of cycles

  • Analyze feedback loops in population dynamics
  • Look at key players. Identify keystone species that regulate diversity.
  • Many animals show food regulated pattern. They are limited by density, by food available.
  • Look for broken limits in the regulatory process. Regulation - too much or too little produced.
  • Slower cycles absorb imbalances in quicker cycles.
  • Establish conditions in terms of independent parameters. Can be independent parts of a network. Or can see how the network relates the parameters.

Medical parameters - cyclical signs - their interrelation

  • Vital signs Temperature, pulse, breathing rate, blood pressure. A group of the four to six most important medical signs that indicate the status of the body’s vital (life-sustaining) functions. These measurements are taken to help assess the general physical health of a person, give clues to possible diseases, and show progress toward recovery.[1][2] The normal ranges for a person’s vital signs vary with age, weight, gender, and overall health.
  • Compare with Chinese medicine.
  • Trophic cascades are powerful indirect interactions that can control entire ecosystems, occurring when a trophic level in a food web is suppressed. For example, a top-down cascade will occur if predators are effective enough in predation to reduce the abundance, or alter the behavior of their prey, thereby releasing the next lower trophic level from predation (or herbivory if the intermediate trophic level is a herbivore).


Simulate scenarios by playing with conditions

Simulation of an environment

  • Daisyworld A computer simulation of a hypothetical world which mimics elements of the Earth-Sun system to show the plausibility of the Gaia hypothesis. Daisyworld has two varieties of daisies, one which reflects light and one which absorbs light. The combination maintains an almost constant temperature despite changes in the power of the sun's rays.
  • 维基百科: Chris Adami is best known for his work on 维基百科: Avida, an artificial life simulator used to study evolutionary biology, and for applying the theory of information to physical and biological systems.

Reproduce organic (material, behavior...) with inorganic

  • In 1828 Wöhler showed that the organic substance urea could be created by chemical means that do not involve life, providing a powerful challenge to vitalism.

In simulacra a Latin phrase meaning "within likenesses." The experiment is not conducted in the actual subject, but rather a model of such.

In silico In silico study in medicine is thought to have the potential to speed the rate of discovery while reducing the need for expensive lab work and clinical trials. One way to achieve this is by producing and screening drug candidates more effectively. In 2010, for example, using the protein docking algorithm EADock (see Protein-ligand docking), researchers found potential inhibitors to an enzyme associated with cancer activity in silico. Fifty percent of the molecules were later shown to be active inhibitors in vitro.

In papyro Experiments or studies carried out only on paper, for example, epidemiological studies that do not involve clinical subjects, such as meta-analysis.

  • Quantitative structure-activity relationship models (QSAR models) are regression or classification models used in the chemical and biological sciences and engineering. Like other regression models, QSAR regression models relate a set of "predictor" variables (X) to the potency of the response variable (Y), while classification QSAR models relate the predictor variables to a categorical value of the response variable.

Mathematical extrapolation

  • In vitro to in vivo extrapolation Using mathematical modeling to numerically simulate the behavior of a complex system, whereby in vitro data provides the parameter values for developing a model.

Composing more complex systems

Increasing the complexity of in vitro systems where multiple cells can interact with each other in order recapitulate cell-cell interactions present in tissues (as in "human on chip" systems).

Defining life by studying mathematical worlds

Need to sort

Feral child

The Mesopotamians seem to have had little interest in the natural world as such, preferring to study how the gods had ordered the universe.

Separate developments in China and India

Observations and theories regarding nature and human health, separate from Western traditions, had emerged independently in other civilizations such as those in China and the Indian subcontinent.[1] In ancient China, earlier conceptions can be found dispersed across several different disciplines, including the work of herbologists, physicians, alchemists, and philosophers. The Taoist tradition of Chinese alchemy, for example, emphasized health (with the ultimate goal being the elixir of life). The system of classical Chinese medicine usually revolved around the theory of yin and yang, and the five phases.[1] Taoist philosophers, such as Zhuangzi in the 4th century BCE, also expressed ideas related to evolution, such as denying the fixity of biological species and speculating that species had developed differing attributes in response to differing environments.[11]

One of the oldest organised systems of medicine is known from ancient India in the form of Ayurveda, which originated around 1500 BCE from Atharvaveda (one of the four most ancient books of Indian knowledge, wisdom and culture).

The ancient Indian Ayurveda tradition independently developed the concept of three humours, resembling that of the four humours of ancient Greek medicine, though the Ayurvedic system included further complications, such as the body being composed of five elements and seven basic tissues. Ayurvedic writers also classified living things into four categories based on the method of birth (from the womb, eggs, heat & moisture, and seeds) and explained the conception of a fetus in detail. They also made considerable advances in the field of surgery, often without the use of human dissection or animal vivisection.[1] One of the earliest Ayurvedic treatises was the Sushruta Samhita, attributed to Sushruta in the 6th century BCE. It was also an early materia medica, describing 700 medicinal plants, 64 preparations from mineral sources, and 57 preparations based on animal sources.[12]

Classical antiquity

Further information: Ancient Greek medicine and Aristotle's biology

Frontispiece to a 1644 version of the expanded and illustrated edition of Historia Plantarum, originally written by Theophrastus around 300 BC

The pre-Socratic philosophers asked many questions about life but produced little systematic knowledge of specifically biological interest—though the attempts of the atomists to explain life in purely physical terms would recur periodically through the history of biology. However, the medical theories of Hippocrates and his followers, especially humorism, had a lasting impact.[1]

The philosopher Aristotle was the most influential scholar of the living world from classical antiquity. Though his early work in natural philosophy was speculative, Aristotle's later biological writings were more empirical, focusing on biological causation and the diversity of life. He made countless observations of nature, especially the habits and attributes of plants and animals in the world around him, which he devoted considerable attention to categorizing. In all, Aristotle classified 540 animal species, and dissected at least 50. He believed that intellectual purposes, formal causes, guided all natural processes.[13]

Aristotle, and nearly all Western scholars after him until the 18th century, believed that creatures were arranged in a graded scale of perfection rising from plants on up to humans: the scala naturae or Great Chain of Being.[14] Aristotle's successor at the Lyceum, Theophrastus, wrote a series of books on botany—the History of Plants—which survived as the most important contribution of antiquity to botany, even into the Middle Ages. Many of Theophrastus' names survive into modern times, such as carpos for fruit, and pericarpion for seed vessel. Dioscorides wrote a pioneering and encyclopaedic pharmacopoeia, De Materia Medica, incorporating descriptions of some 600 plants and their uses in medicine. Pliny the Elder, in his Natural History, assembled a similarly encyclopaedic account of things in nature, including accounts of many plants and animals.[15]

A few scholars in the Hellenistic period under the Ptolemies—particularly Herophilus of Chalcedon and Erasistratus of Chios—amended Aristotle's physiological work, even performing dissections and vivisections.[16] Claudius Galen became the most important authority on medicine and anatomy. Though a few ancient atomists such as Lucretius challenged the teleological Aristotelian viewpoint that all aspects of life are the result of design or purpose, teleology (and after the rise of Christianity, natural theology) would remain central to biological thought essentially until the 18th and 19th centuries. Ernst W. Mayr argued that "Nothing of any real consequence happened in biology after Lucretius and Galen until the Renaissance."[17] The ideas of the Greek traditions of natural history and medicine survived, but they were generally taken unquestioningly in medieval Europe.[18]

Middle Ages

Further information: Islamic medicine, Byzantine medicine, and Medieval medicine of Western Europe

A biomedical work by Ibn al-Nafis, an early adherent of experimental dissection who discovered the pulmonary and coronary circulation

The decline of the Roman Empire led to the disappearance or destruction of much knowledge, though physicians still incorporated many aspects of the Greek tradition into training and practice. In Byzantium and the Islamic world, many of the Greek works were translated into Arabic and many of the works of Aristotle were preserved.[19]

De arte venandi, by Frederick II, Holy Roman Emperor, was an influential medieval natural history text that explored bird morphology.

During the High Middle Ages, a few European scholars such as Hildegard of Bingen, Albertus Magnus and Frederick II wrote on natural history. The rise of European universities, though important for the development of physics and philosophy, had little impact on biological scholarship.[20]


Further information: History of anatomy and Scientific Revolution

The European Renaissance brought expanded interest in both empirical natural history and physiology. In 1543, Andreas Vesalius inaugurated the modern era of Western medicine with his seminal human anatomy treatise De humani corporis fabrica, which was based on dissection of corpses. Vesalius was the first in a series of anatomists who gradually replaced scholasticism with empiricism in physiology and medicine, relying on first-hand experience rather than authority and abstract reasoning. Via herbalism, medicine was also indirectly the source of renewed empiricism in the study of plants. Otto Brunfels, Hieronymus Bock and Leonhart Fuchs wrote extensively on wild plants, the beginning of a nature-based approach to the full range of plant life.[21] Bestiaries—a genre that combines both the natural and figurative knowledge of animals—also became more sophisticated, especially with the work of William Turner, Pierre Belon, Guillaume Rondelet, Conrad Gessner, and Ulisse Aldrovandi.[22]

The traditions of alchemy and natural magic, especially in the work of Paracelsus, also laid claim to knowledge of the living world. Alchemists subjected organic matter to chemical analysis and experimented liberally with both biological and mineral pharmacology.[24] This was part of a larger transition in world views (the rise of the mechanical philosophy) that continued into the 17th century, as the traditional metaphor of nature as organism was replaced by the nature as machine metaphor.[25]

Age of Enlightenment

Further information: History of plant systematics

Systematizing, naming and classifying dominated natural history throughout much of the 17th and 18th centuries. Carl Linnaeus published a basic taxonomy for the natural world in 1735 (variations of which have been in use ever since), and in the 1750s introduced scientific names for all his species.[26] While Linnaeus conceived of species as unchanging parts of a designed hierarchy, the other great naturalist of the 18th century, Georges-Louis Leclerc, Comte de Buffon, treated species as artificial categories and living forms as malleable—even suggesting the possibility of common descent. Though he was opposed to evolution, Buffon is a key figure in the history of evolutionary thought; his work would influence the evolutionary theories of both Lamarck and Darwin.[27]

The discovery and description of new species and the collection of specimens became a passion of scientific gentlemen and a lucrative enterprise for entrepreneurs; many naturalists traveled the globe in search of scientific knowledge and adventure.[28]

Cabinets of curiosities, such as that of Ole Worm, were centers of biological knowledge in the early modern period, bringing organisms from across the world together in one place. Before the Age of Exploration, naturalists had little idea of the sheer scale of biological diversity.

Extending the work of Vesalius into experiments on still living bodies (of both humans and animals), William Harvey and other natural philosophers investigated the roles of blood, veins and arteries. Harvey's De motu cordis in 1628 was the beginning of the end for Galenic theory, and alongside Santorio Santorio's studies of metabolism, it served as an influential model of quantitative approaches to physiology.[29]

In the early 17th century, the micro-world of biology was just beginning to open up. A few lensmakers and natural philosophers had been creating crude microscopes since the late 16th century, and Robert Hooke published the seminal Micrographia based on observations with his own compound microscope in 1665. But it was not until Antonie van Leeuwenhoek's dramatic improvements in lensmaking beginning in the 1670s—ultimately producing up to 200-fold magnification with a single lens—that scholars discovered spermatozoa, bacteria, infusoria and the sheer strangeness and diversity of microscopic life. Similar investigations by Jan Swammerdam led to new interest in entomology and built the basic techniques of microscopic dissection and staining.[30] In Micrographia, Robert Hooke had applied the word cell to biological structures such as this piece of cork, but it was not until the 19th century that scientists considered cells the universal basis of life.

As the microscopic world was expanding, the macroscopic world was shrinking. Botanists such as John Ray worked to incorporate the flood of newly discovered organisms shipped from across the globe into a coherent taxonomy, and a coherent theology (natural theology).[31] Debate over another flood, the Noachian, catalyzed the development of paleontology; in 1669 Nicholas Steno published an essay on how the remains of living organisms could be trapped in layers of sediment and mineralized to produce fossils. Although Steno's ideas about fossilization were well known and much debated among natural philosophers, an organic origin for all fossils would not be accepted by all naturalists until the end of the 18th century due to philosophical and theological debate about issues such as the age of the earth and extinction.[32]

19th century: the emergence of biological disciplines

Up through the 19th century, the scope of biology was largely divided between medicine, which investigated questions of form and function (i.e., physiology), and natural history, which was concerned with the diversity of life and interactions among different forms of life and between life and non-life. By 1900, much of these domains overlapped, while natural history (and its counterpart natural philosophy) had largely given way to more specialized scientific disciplines—cytology, bacteriology, morphology, embryology, geography, and geology. In the course of his travels, Alexander von Humboldt mapped the distribution of plants across landscapes and recorded a variety of physical conditions such as pressure and temperature.

Use of the term biology

The term biology in its modern sense appears to have been introduced independently by Thomas Beddoes (in 1799),[33] Karl Friedrich Burdach (in 1800), Gottfried Reinhold Treviranus (Biologie oder Philosophie der lebenden Natur, 1802) and Jean-Baptiste Lamarck (Hydrogéologie, 1802).[34][35] The word itself appears in the title of Volume 3 of Michael Christoph Hanow's Philosophiae naturalis sive physicae dogmaticae: Geologia, biologia, phytologia generalis et dendrologia, published in 1766.

Before biology, there were several terms used for the study of animals and plants. Natural history referred to the descriptive aspects of biology, though it also included mineralogy and other non-biological fields; from the Middle Ages through the Renaissance, the unifying framework of natural history was the scala naturae or Great Chain of Being. Natural philosophy and natural theology encompassed the conceptual and metaphysical basis of plant and animal life, dealing with problems of why organisms exist and behave the way they do, though these subjects also included what is now geology, physics, chemistry, and astronomy. Physiology and (botanical) pharmacology were the province of medicine. Botany, zoology, and (in the case of fossils) geology replaced natural history and natural philosophy in the 18th and 19th centuries before biology was widely adopted.[36][37] To this day, "botany" and "zoology" are widely used, although they have been joined by other sub-disciplines of biology.

Natural history and natural philosophy

Further information: Humboldtian science

Widespread travel by naturalists in the early-to-mid-19th century resulted in a wealth of new information about the diversity and distribution of living organisms. Of particular importance was the work of Alexander von Humboldt, which analyzed the relationship between organisms and their environment (i.e., the domain of natural history) using the quantitative approaches of natural philosophy (i.e., physics and chemistry). Humboldt's work laid the foundations of biogeography and inspired several generations of scientists.[38]

Geology and paleontology

Further information: History of geology and History of paleontology

The emerging discipline of geology also brought natural history and natural philosophy closer together; the establishment of the stratigraphic column linked the spatial distribution of organisms to their temporal distribution, a key precursor to concepts of evolution. Georges Cuvier and others made great strides in comparative anatomy and paleontology in the late 1790s and early 19th century. In a series of lectures and papers that made detailed comparisons between living mammals and fossil remains Cuvier was able to establish that the fossils were remains of species that had become extinct—rather than being remains of species still alive elsewhere in the world, as had been widely believed.[39] Fossils discovered and described by Gideon Mantell, William Buckland, Mary Anning, and Richard Owen among others helped establish that there had been an 'age of reptiles' that had preceded even the prehistoric mammals. These discoveries captured the public imagination and focused attention on the history of life on earth.[40] Most of these geologists held to catastrophism, but Charles Lyell's influential Principles of Geology (1830) popularised Hutton's uniformitarianism, a theory that explained the geological past and present on equal terms.[41] Evolution and biogeography

Further information: History of evolutionary thought and History of speciation

The most significant evolutionary theory before Darwin's was that of Jean-Baptiste Lamarck; based on the inheritance of acquired characteristics (an inheritance mechanism that was widely accepted until the 20th century), it described a chain of development stretching from the lowliest microbe to humans.[42] The British naturalist Charles Darwin, combining the biogeographical approach of Humboldt, the uniformitarian geology of Lyell, Thomas Malthus's writings on population growth, and his own morphological expertise, created a more successful evolutionary theory based on natural selection; similar evidence led Alfred Russel Wallace to independently reach the same conclusions.[43]

The 1859 publication of Darwin's theory in On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life is often considered the central event in the history of modern biology. Darwin's established credibility as a naturalist, the sober tone of the work, and most of all the sheer strength and volume of evidence presented, allowed Origin to succeed where previous evolutionary works such as the anonymous Vestiges of Creation had failed. Most scientists were convinced of evolution and common descent by the end of the 19th century. However, natural selection would not be accepted as the primary mechanism of evolution until well into the 20th century, as most contemporary theories of heredity seemed incompatible with the inheritance of random variation.[44]

Charles Darwin's first sketch of an evolutionary tree from his First Notebook on Transmutation of Species (1837)

Wallace, following on earlier work by de Candolle, Humboldt and Darwin, made major contributions to zoogeography. Because of his interest in the transmutation hypothesis, he paid particular attention to the geographical distribution of closely allied species during his field work first in South America and then in the Malay archipelago. While in the archipelago he identified the Wallace line, which runs through the Spice Islands dividing the fauna of the archipelago between an Asian zone and a New Guinea/Australian zone. His key question, as to why the fauna of islands with such similar climates should be so different, could only be answered by considering their origin. In 1876 he wrote The Geographical Distribution of Animals, which was the standard reference work for over half a century, and a sequel, Island Life, in 1880 that focused on island biogeography. He extended the six-zone system developed by Philip Sclater for describing the geographical distribution of birds to animals of all kinds. His method of tabulating data on animal groups in geographic zones highlighted the discontinuities; and his appreciation of evolution allowed him to propose rational explanations, which had not been done before.[45][46]

The scientific study of heredity grew rapidly in the wake of Darwin's Origin of Species with the work of Francis Galton and the biometricians. The origin of genetics is usually traced to the 1866 work of the monk Gregor Mendel, who would later be credited with the laws of inheritance. However, his work was not recognized as significant until 35 years afterward. In the meantime, a variety of theories of inheritance (based on pangenesis, orthogenesis, or other mechanisms) were debated and investigated vigorously.[47] Embryology and ecology also became central biological fields, especially as linked to evolution and popularized in the work of Ernst Haeckel. Most of the 19th century work on heredity, however, was not in the realm of natural history, but that of experimental physiology.


Over the course of the 19th century, the scope of physiology expanded greatly, from a primarily medically oriented field to a wide-ranging investigation of the physical and chemical processes of life—including plants, animals, and even microorganisms in addition to man.

Recognize processes

  • Living things as machines became a dominant metaphor in biological (and social) thinking.

Recognize living activities

  • (2) that individual cells have all the characteristics of life

Recognize reproductive life cycle

  • (3) all cells come from the division of other cells.

Recognize ubiquitous building blocks

  • In the early 19th century, a number of biologists pointed to the central importance of the cell.
  • (1) the basic unit of organisms is the cell

Inert environment

  • Innovative laboratory glassware and experimental methods developed by Louis Pasteur and other biologists contributed to the young field of bacteriology in the late 19th century.

Cell theory, embryology and germ theory

Advances in microscopy also had a profound impact on biological thinking.

In 1838 and 1839, Schleiden and Schwann began promoting the ideas that (1) the basic unit of organisms is the cell and (2) that individual cells have all the characteristics of life, though they opposed the idea that (3) all cells come from the division of other cells. Thanks to the work of Robert Remak and Rudolf Virchow, however, by the 1860s most biologists accepted all three tenets of what came to be known as cell theory.

Cell theory led biologists to re-envision individual organisms as interdependent assemblages of individual cells. Scientists in the rising field of cytology, armed with increasingly powerful microscopes and new staining methods, soon found that even single cells were far more complex than the homogeneous fluid-filled chambers described by earlier microscopists. Robert Brown had described the nucleus in 1831, and by the end of the 19th century cytologists identified many of the key cell components: chromosomes, centrosomes mitochondria, chloroplasts, and other structures made visible through staining. Between 1874 and 1884 Walther Flemming described the discrete stages of mitosis, showing that they were not artifacts of staining but occurred in living cells, and moreover, that chromosomes doubled in number just before the cell divided and a daughter cell was produced. Much of the research on cell reproduction came together in August Weismann's theory of heredity: he identified the nucleus (in particular chromosomes) as the hereditary material, proposed the distinction between somatic cells and germ cells (arguing that chromosome number must be halved for germ cells, a precursor to the concept of meiosis), and adopted Hugo de Vries's theory of pangenes. Weismannism was extremely influential, especially in the new field of experimental embryology.[50]

By the mid-1850s the miasma theory of disease was largely superseded by the germ theory of disease, creating extensive interest in microorganisms and their interactions with other forms of life. By the 1880s, bacteriology was becoming a coherent discipline, especially through the work of Robert Koch, who introduced methods for growing pure cultures on agar gels containing specific nutrients in Petri dishes. The long-held idea that living organisms could easily originate from nonliving matter (spontaneous generation) was attacked in a series of experiments carried out by Louis Pasteur, while debates over vitalism vs. mechanism (a perennial issue since the time of Aristotle and the Greek atomists) continued apace.[51]

Rise of organic chemistry and experimental physiology

In chemistry, one central issue was the distinction between organic and inorganic substances, especially in the context of organic transformations such as fermentation and putrefaction. Since Aristotle these had been considered essentially biological (vital) processes. However, Friedrich Wöhler, Justus Liebig and other pioneers of the rising field of organic chemistry—building on the work of Lavoisier—showed that the organic world could often be analyzed by physical and chemical methods.

Cell extracts ("ferments") that could effect chemical transformations were discovered, beginning with diastase in 1833. By the end of the 19th century the concept of enzymes was well established, though equations of chemical kinetics would not be applied to enzymatic reactions until the early 20th century.[52]

Physiologists such as Claude Bernard explored (through vivisection and other experimental methods) the chemical and physical functions of living bodies to an unprecedented degree, laying the groundwork for endocrinology (a field that developed quickly after the discovery of the first hormone, secretin, in 1902), biomechanics, and the study of nutrition and digestion. The importance and diversity of experimental physiology methods, within both medicine and biology, grew dramatically over the second half of the 19th century. The control and manipulation of life processes became a central concern, and experiment was placed at the center of biological education.[53]

Twentieth century biological sciences

Embryonic development of a salamander, filmed in the 1920s

At the beginning of the 20th century, biological research was largely a professional endeavour. Most work was still done in the natural history mode, which emphasized morphological and phylogenetic analysis over experiment-based causal explanations. However, anti-vitalist experimental physiologists and embryologists, especially in Europe, were increasingly influential. The tremendous success of experimental approaches to development, heredity, and metabolism in the 1900s and 1910s demonstrated the power of experimentation in biology. In the following decades, experimental work replaced natural history as the dominant mode of research.[54]

Ecology and environmental science

Further information: History of ecology

In the early 20th century, naturalists were faced with increasing pressure to add rigor and preferably experimentation to their methods, as the newly prominent laboratory-based biological disciplines had done. Ecology had emerged as a combination of biogeography with the biogeochemical cycle concept pioneered by chemists; field biologists developed quantitative methods such as the quadrat and adapted laboratory instruments and cameras for the field to further set their work apart from traditional natural history. Zoologists and botanists did what they could to mitigate the unpredictability of the living world, performing laboratory experiments and studying semi-controlled natural environments such as gardens; new institutions like the Carnegie Station for Experimental Evolution and the Marine Biological Laboratory provided more controlled environments for studying organisms through their entire life cycles.[55]

The ecological succession concept, pioneered in the 1900s and 1910s by Henry Chandler Cowles and Frederic Clements, was important in early plant ecology.[56] Alfred Lotka's predator-prey equations, G. Evelyn Hutchinson's studies of the biogeography and biogeochemical structure of lakes and rivers (limnology) and Charles Elton's studies of animal food chains were pioneers among the succession of quantitative methods that colonized the developing ecological specialties. Ecology became an independent discipline in the 1940s and 1950s after Eugene P. Odum synthesized many of the concepts of ecosystem ecology, placing relationships between groups of organisms (especially material and energy relationships) at the center of the field.[57]

In the 1960s, as evolutionary theorists explored the possibility of multiple units of selection, ecologists turned to evolutionary approaches. In population ecology, debate over group selection was brief but vigorous; by 1970, most biologists agreed that natural selection was rarely effective above the level of individual organisms. The evolution of ecosystems, however, became a lasting research focus. Ecology expanded rapidly with the rise of the environmental movement; the International Biological Program attempted to apply the methods of big science (which had been so successful in the physical sciences) to ecosystem ecology and pressing environmental issues, while smaller-scale independent efforts such as island biogeography and the Hubbard Brook Experimental Forest helped redefine the scope of an increasingly diverse discipline.[58]

Classical genetics, the modern synthesis, and evolutionary theory

Further information: History of genetics, History of model organisms, and Modern synthesis (20th century)

Thomas Hunt Morgan's illustration of crossing over, part of the Mendelian-chromosome theory of heredity

1900 marked the so-called rediscovery of Mendel: Hugo de Vries, Carl Correns, and Erich von Tschermak independently arrived at Mendel's laws (which were not actually present in Mendel's work).[59] Soon after, cytologists (cell biologists) proposed that chromosomes were the hereditary material. Between 1910 and 1915, Thomas Hunt Morgan and the "Drosophilists" in his fly lab forged these two ideas—both controversial—into the "Mendelian-chromosome theory" of heredity.[60] They quantified the phenomenon of genetic linkage and postulated that genes reside on chromosomes like beads on string; they hypothesized crossing over to explain linkage and constructed genetic maps of the fruit fly Drosophila melanogaster, which became a widely used model organism.[61]

Hugo de Vries tried to link the new genetics with evolution; building on his work with heredity and hybridization, he proposed a theory of mutationism, which was widely accepted in the early 20th century. Lamarckism, or the theory of inheritance of acquired characteristics also had many adherents. Darwinism was seen as incompatible with the continuously variable traits studied by biometricians, which seemed only partially heritable. In the 1920s and 1930s—following the acceptance of the Mendelian-chromosome theory— the emergence of the discipline of population genetics, with the work of R.A. Fisher, J.B.S. Haldane and Sewall Wright, unified the idea of evolution by natural selection with Mendelian genetics, producing the modern synthesis. The inheritance of acquired characters was rejected, while mutationism gave way as genetic theories matured.[62]

In the second half of the century the ideas of population genetics began to be applied in the new discipline of the genetics of behavior, sociobiology, and, especially in humans, evolutionary psychology. In the 1960s W.D. Hamilton and others developed game theory approaches to explain altruism from an evolutionary perspective through kin selection. The possible origin of higher organisms through endosymbiosis, and contrasting approaches to molecular evolution in the gene-centered view (which held selection as the predominant cause of evolution) and the neutral theory (which made genetic drift a key factor) spawned perennial debates over the proper balance of adaptationism and contingency in evolutionary theory.[63]

In the 1970s Stephen Jay Gould and Niles Eldredge proposed the theory of punctuated equilibrium which holds that stasis is the most prominent feature of the fossil record, and that most evolutionary changes occur rapidly over relatively short periods of time.[64] In 1980 Luis Alvarez and Walter Alvarez proposed the hypothesis that an impact event was responsible for the Cretaceous–Paleogene extinction event.[65] Also in the early 1980s, statistical analysis of the fossil record of marine organisms published by Jack Sepkoski and David M. Raup led to a better appreciation of the importance of mass extinction events to the history of life on earth.[66]

Biochemistry, microbiology, and molecular biology

Further information: History of biochemistry and History of molecular biology

By the end of the 19th century all of the major pathways of drug metabolism had been discovered, along with the outlines of protein and fatty acid metabolism and urea synthesis.[67] In the early decades of the 20th century, the minor components of foods in human nutrition, the vitamins, began to be isolated and synthesized. Improved laboratory techniques such as chromatography and electrophoresis led to rapid advances in physiological chemistry, which—as biochemistry—began to achieve independence from its medical origins. In the 1920s and 1930s, biochemists—led by Hans Krebs and Carl and Gerty Cori—began to work out many of the central metabolic pathways of life: the citric acid cycle, glycogenesis and glycolysis, and the synthesis of steroids and porphyrins. Between the 1930s and 1950s, Fritz Lipmann and others established the role of ATP as the universal carrier of energy in the cell, and mitochondria as the powerhouse of the cell. Such traditionally biochemical work continued to be very actively pursued throughout the 20th century and into the 21st.[68] Origins of molecular biology

Following the rise of classical genetics, many biologists—including a new wave of physical scientists in biology—pursued the question of the gene and its physical nature. Warren Weaver—head of the science division of the Rockefeller Foundation—issued grants to promote research that applied the methods of physics and chemistry to basic biological problems, coining the term molecular biology for this approach in 1938; many of the significant biological breakthroughs of the 1930s and 1940s were funded by the Rockefeller Foundation.[69]

Wendell Stanley's crystallization of tobacco mosaic virus as a pure nucleoprotein in 1935 convinced many scientists that heredity might be explained purely through physics and chemistry.

Like biochemistry, the overlapping disciplines of bacteriology and virology (later combined as microbiology), situated between science and medicine, developed rapidly in the early 20th century. Félix d'Herelle's isolation of bacteriophage during World War I initiated a long line of research focused on phage viruses and the bacteria they infect.[70]

The development of standard, genetically uniform organisms that could produce repeatable experimental results was essential for the development of molecular genetics. After early work with Drosophila and maize, the adoption of simpler model systems like the bread mold Neurospora crassa made it possible to connect genetics to biochemistry, most importantly with Beadle and Tatum's one gene-one enzyme hypothesis in 1941. Genetics experiments on even simpler systems like tobacco mosaic virus and bacteriophage, aided by the new technologies of electron microscopy and ultracentrifugation, forced scientists to re-evaluate the literal meaning of life; virus heredity and reproducing nucleoprotein cell structures outside the nucleus ("plasmagenes") complicated the accepted Mendelian-chromosome theory.[71] The "central dogma of molecular biology" (originally a "dogma" only in jest) was proposed by Francis Crick in 1958.[72] This is Crick's reconstruction of how he conceived of the central dogma at the time. The solid lines represent (as it seemed in 1958) known modes of information transfer, and the dashed lines represent postulated ones.

Oswald Avery showed in 1943 that DNA was likely the genetic material of the chromosome, not its protein; the issue was settled decisively with the 1952 Hershey–Chase experiment—one of many contributions from the so-called phage group centered around physicist-turned-biologist Max Delbrück. In 1953 James Watson and Francis Crick, building on the work of Maurice Wilkins and Rosalind Franklin, suggested that the structure of DNA was a double helix. In their famous paper "Molecular structure of Nucleic Acids", Watson and Crick noted coyly, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."[73] After the 1958 Meselson–Stahl experiment confirmed the semiconservative replication of DNA, it was clear to most biologists that nucleic acid sequence must somehow determine amino acid sequence in proteins; physicist George Gamow proposed that a fixed genetic code connected proteins and DNA. Between 1953 and 1961, there were few known biological sequences—either DNA or protein—but an abundance of proposed code systems, a situation made even more complicated by expanding knowledge of the intermediate role of RNA. To actually decipher the code, it took an extensive series of experiments in biochemistry and bacterial genetics, between 1961 and 1966—most importantly the work of Nirenberg and Khorana.[74]

Expansion of molecular biology

In addition to the Division of Biology at Caltech, the Laboratory of Molecular Biology (and its precursors) at Cambridge, and a handful of other institutions, the Pasteur Institute became a major center for molecular biology research in the late 1950s.[75] Scientists at Cambridge, led by Max Perutz and John Kendrew, focused on the rapidly developing field of structural biology, combining X-ray crystallography with Molecular modelling and the new computational possibilities of digital computing (benefiting both directly and indirectly from the military funding of science). A number of biochemists led by Frederick Sanger later joined the Cambridge lab, bringing together the study of macromolecular structure and function.[76] At the Pasteur Institute, François Jacob and Jacques Monod followed the 1959 PaJaMo experiment with a series of publications regarding the lac operon that established the concept of gene regulation and identified what came to be known as messenger RNA.[77] By the mid-1960s, the intellectual core of molecular biology—a model for the molecular basis of metabolism and reproduction— was largely complete.[78]

The late 1950s to the early 1970s was a period of intense research and institutional expansion for molecular biology, which had only recently become a somewhat coherent discipline. In what organismic biologist E. O. Wilson called "The Molecular Wars", the methods and practitioners of molecular biology spread rapidly, often coming to dominate departments and even entire disciplines.[79] Molecularization was particularly important in genetics, immunology, embryology, and neurobiology, while the idea that life is controlled by a "genetic program"—a metaphor Jacob and Monod introduced from the emerging fields of cybernetics and computer science—became an influential perspective throughout biology.[80] Immunology in particular became linked with molecular biology, with innovation flowing both ways: the clonal selection theory developed by Niels Jerne and Frank Macfarlane Burnet in the mid-1950s helped shed light on the general mechanisms of protein synthesis.[81]

Resistance to the growing influence of molecular biology was especially evident in evolutionary biology. Protein sequencing had great potential for the quantitative study of evolution (through the molecular clock hypothesis), but leading evolutionary biologists questioned the relevance of molecular biology for answering the big questions of evolutionary causation. Departments and disciplines fractured as organismic biologists asserted their importance and independence: Theodosius Dobzhansky made the famous statement that "nothing in biology makes sense except in the light of evolution" as a response to the molecular challenge. The issue became even more critical after 1968; Motoo Kimura's neutral theory of molecular evolution suggested that natural selection was not the ubiquitous cause of evolution, at least at the molecular level, and that molecular evolution might be a fundamentally different process from morphological evolution. (Resolving this "molecular/morphological paradox" has been a central focus of molecular evolution research since the 1960s.)

Biotechnology, genetic engineering, and genomics

Further information: History of biotechnology

Biotechnology in the general sense has been an important part of biology since the late 19th century. With the industrialization of brewing and agriculture, chemists and biologists became aware of the great potential of human-controlled biological processes. In particular, fermentation proved a great boon to chemical industries. By the early 1970s, a wide range of biotechnologies were being developed, from drugs like penicillin and steroids to foods like Chlorella and single-cell protein to gasohol—as well as a wide range of hybrid high-yield crops and agricultural technologies, the basis for the Green Revolution.[83]

Carefully engineered strains of the bacterium Escherichia coli are crucial tools in biotechnology as well as many other biological fields.

Recombinant DNA

Biotechnology in the modern sense of genetic engineering began in the 1970s, with the invention of recombinant DNA techniques.[84] Restriction enzymes were discovered and characterized in the late 1960s, following on the heels of the isolation, then duplication, then synthesis of viral genes. Beginning with the lab of Paul Berg in 1972 (aided by EcoRI from Herbert Boyer's lab, building on work with ligase by Arthur Kornberg's lab), molecular biologists put these pieces together to produce the first transgenic organisms. Soon after, others began using plasmid vectors and adding genes for antibiotic resistance, greatly increasing the reach of the recombinant techniques.[85]

Wary of the potential dangers (particularly the possibility of a prolific bacteria with a viral cancer-causing gene), the scientific community as well as a wide range of scientific outsiders reacted to these developments with both enthusiasm and fearful restraint. Prominent molecular biologists led by Berg suggested a temporary moratorium on recombinant DNA research until the dangers could be assessed and policies could be created. This moratorium was largely respected, until the participants in the 1975 Asilomar Conference on Recombinant DNA created policy recommendations and concluded that the technology could be used safely.[86]

Following Asilomar, new genetic engineering techniques and applications developed rapidly. DNA sequencing methods improved greatly (pioneered by Frederick Sanger and Walter Gilbert), as did oligonucleotide synthesis and transfection techniques.[87] Researchers learned to control the expression of transgenes, and were soon racing—in both academic and industrial contexts—to create organisms capable of expressing human genes for the production of human hormones. However, this was a more daunting task than molecular biologists had expected; developments between 1977 and 1980 showed that, due to the phenomena of split genes and splicing, higher organisms had a much more complex system of gene expression than the bacteria models of earlier studies.[88] The first such race, for synthesizing human insulin, was won by Genentech. This marked the beginning of the biotech boom (and with it, the era of gene patents), with an unprecedented level of overlap between biology, industry, and law.[89]

Molecular systematics and genomics

Further information: History of molecular evolution

Inside of a 48-well thermal cycler, a device used to perform polymerase chain reaction on many samples at once

By the 1980s, protein sequencing had already transformed methods of scientific classification of organisms (especially cladistics) but biologists soon began to use RNA and DNA sequences as characters; this expanded the significance of molecular evolution within evolutionary biology, as the results of molecular systematics could be compared with traditional evolutionary trees based on morphology. Following the pioneering ideas of Lynn Margulis on endosymbiotic theory, which holds that some of the organelles of eukaryotic cells originated from free living prokaryotic organisms through symbiotic relationships, even the overall division of the tree of life was revised. Into the 1990s, the five domains (Plants, Animals, Fungi, Protists, and Monerans) became three (the Archaea, the Bacteria, and the Eukarya) based on Carl Woese's pioneering molecular systematics work with 16S rRNA sequencing.[90]

The development and popularization of the polymerase chain reaction (PCR) in mid-1980s (by Kary Mullis and others at Cetus Corp.) marked another watershed in the history of modern biotechnology, greatly increasing the ease and speed of genetic analysis.[91] Coupled with the use of expressed sequence tags, PCR led to the discovery of many more genes than could be found through traditional biochemical or genetic methods and opened the possibility of sequencing entire genomes.[92]

The unity of much of the morphogenesis of organisms from fertilized egg to adult began to be unraveled after the discovery of the homeobox genes, first in fruit flies, then in other insects and animals, including humans. These developments led to advances in the field of evolutionary developmental biology towards understanding how the various body plans of the animal phyla have evolved and how they are related to one another.[93]

The Human Genome Project—the largest, most costly single biological study ever undertaken—began in 1988 under the leadership of James D. Watson, after preliminary work with genetically simpler model organisms such as E. coli, S. cerevisiae and C. elegans. Shotgun sequencing and gene discovery methods pioneered by Craig Venter—and fueled by the financial promise of gene patents with Celera Genomics— led to a public–private sequencing competition that ended in compromise with the first draft of the human DNA sequence announced in 2000.[94]

Twenty-first century biological sciences

At the beginning of the 21st century, biological sciences converged with previously differentiated new and classic disciplines like Physics into research fields like Biophysics. Advances were made in analytical chemistry and physics instrumentation including improved sensors, optics, tracers, instrumentation, signal processing, networks, robots, satellites, and compute power for data collection, storage, analysis, modeling, visualization, and simulations. These technology advances allowed theoretical and experimental research including internet publication of molecular biochemistry, biological systems, and ecosystems science. This enabled worldwide access to better measurements, theoretical models, complex simulations, theory predictive model experimentation, analysis, worldwide internet observational data reporting, open peer-review, collaboration, and internet publication. New fields of biological sciences research emerged including Bioinformatics, Neuroscience, Theoretical biology, Computational genomics, Astrobiology and Synthetic Biology.

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