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Precautionary principle

The precautionary principle (or precautionary approach) is a broad epistemological, philosophical and legal approach to innovations with potential for causing harm when extensive scientific knowledge on the matter is lacking. It emphasizes caution, pausing and review before leaping into new innovations that may prove disastrous. Critics argue that it is vague, self-cancelling, unscientific and an obstacle to progress.

In an engineering context, the precautionary principle manifests itself as the factor of safety, discussed in detail in the monograph of Elishakoff. It was apparently suggested, in civil engineering, by Belidor in 1729. Interrelation between safety factor and reliability is extensively studied by engineers and philosophers.

The principle is often used by policy makers in situations where there is the possibility of harm from making a certain decision (e.g. taking a particular course of action) and conclusive evidence is not yet available. For example, a government may decide to limit or restrict the widespread release of a medicine or new technology until it has been thoroughly tested. The principle acknowledges that while the progress of science and technology has often brought great benefit to humanity, it has also contributed to the creation of new threats and risks. It implies that there is a social responsibility to protect the public from exposure to such harm, when scientific investigation has found a plausible risk. These protections should be relaxed only if further scientific findings emerge that provide sound evidence that no harm will result.

The principle has become an underlying rationale for a large and increasing number of international treaties and declarations in the fields of sustainable development, environmental protection, health, trade, and food safety, although at times it has attracted debate over how to accurately define it and apply it to complex scenarios with multiple risks. In some legal systems, as in law of the European Union, the application of the precautionary principle has been made a statutory requirement in some areas of law.

Origins and theory
The concept "precautionary principle" is generally considered to have arisen in English from a translation of the German term Vorsorgeprinzip in the 1970s in response to forest degradation and sea pollution, where German lawmakers adopted clean air act banning use of certain substances suspected in causing the environmental damage even though evidence of their impact was inconclusive at that time. The concept was introduced into environmental legislation along with other innovative (at that time) mechanisms such as "polluter pays", principle of pollution prevention and responsibility for survival of future ecosystems.

The precautionary principle was promulgated in philosophy by Hans Jonas in his 1979 text, The Imperative of Responsibility, wherein Jonas argued that technology had altered the range of the impact of human action and, as such, ethics must be modified so that the far distant effects of one's actions should now be considered. His maxim is designed to embody the precautionary principle in its prescription that one should "Act so that the effects of your action are compatible with the permanence of genuine human life" or, stated conversely, "Do not compromise the conditions for an indefinite continuation of humanity on earth." To achieve this Jonas argued for the cultivation of a cautious attitude toward actions that may endanger the future of humanity or the biosphere that supported it.

In 1988, Konrad von Moltke described the German concept for a British audience, which he translated into English as the precautionary principle.

In economics, the Precautionary Principle has been analyzed in terms of "the effect on rational decision-making", of "the interaction of irreversibility" and "uncertainty". Authors such as Epstein (1980) and Arrow and Fischer (1974) show that "irreversibility of possible future consequences" creates a "quasi-option effect" which should induce a "risk-neutral" society to favour current decisions that allow for more flexibility in the future. Gollier et al. conclude that "more scientific uncertainty as to the distribution of a future risk – that is, a larger variability of beliefs – should induce society to take stronger prevention measures today."

The principle was also derived from religious beliefs that particular areas of science and technology should be restricted as they "belong to the realm of God", as postulated by Prince Charles and Pope Benedict XVI.

Formulations
Many definitions of the precautionary principle exist: "precaution" may be defined as "caution in advance", "caution practiced in the context of uncertainty", or informed prudence. Two ideas lie at the core of the principle:

 * An expression of a need by decision-makers to anticipate harm before it occurs. Within this element lies an implicit reversal of the onus of proof: under the precautionary principle it is the responsibility of an activity-proponent to establish that the proposed activity will not (or is very unlikely to) result in significant harm.
 * The concept of proportionality of the risk and the cost and feasibility of a proposed action.

One of the primary foundations of the precautionary principle, and globally accepted definitions, results from the work of the Rio Conference, or "Earth Summit" in 1992. Principle 15 of the Rio Declaration notes:

"In order to protect the environment, the precautionary approach shall be widely applied by States according to their capabilities. Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation."

In 1998, the Wingspread Conference on the Precautionary Principle was convened by the Science and Environmental Health Network and concluded with the following formulation, described by Stewart Brand as "the clearest and most frequently cited":

"When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically. In this context the proponent of an activity, rather than the public, should bear the burden of proof."

In February 2000, the Commission of the European Communities noted in a Communication from the Commission on the Precautionary Principle that "The precautionary principle is not defined in the Treaties of the European Union, which prescribes it [the Precautionary Principle] only once – to protect the environment. But in practice, its scope is much wider, and specifically where preliminary-objective-scientific-evaluation indicates that there are reasonable grounds for concern that potentially dangerous effects on the environment, human, animal or [and] plant health may be inconsistent with the high level of protection [for what] chosen for the Community."

The January 2000 Cartagena Protocol on Biosafety says, in regard to controversies over GMOs: "Lack of scientific certainty due to insufficient relevant scientific information ... shall not prevent the Party of [I]mport, in order to avoid or minimize such potential adverse effects, from taking a decision, as appropriate, with regard to the import of the living modified organism in question."

Pope Francis makes reference to the principle and the Rio Declaration in his 2015 encyclical letter, Laudato si', noting that alongside its environmental significance, the precautionary principle "makes it possible to protect those who are most vulnerable and whose ability to defend their interests and to assemble incontrovertible evidence is limited".

Application
Various interests being represented by various groups proposing the principle resulted in great variability of its formulation: one study identified 14 different formulations of the principle in treaties and non-treaty declarations. R.B. Stewart (2002) reduced the precautionary principle to four basic versions:

 * Scientific uncertainty should not automatically preclude regulation of activities that pose a potential risk of significant harm (non-preclusion).
 * Regulatory controls should incorporate a margin of safety; activities should be limited below the level at which no adverse effect has been observed or predicted (margin of safety).
 * Activities that present an uncertain potential for significant harm should be subject to best technology available requirements to minimize the risk of harm unless the proponent of the activity shows that they present no appreciable risk of harm (BAT).
 * Activities that present an uncertain potential for significant harm should be prohibited unless the proponent of the activity shows that it presents no appreciable risk of harm (prohibitory).

Carolyn Raffensperger of the Wingspread convention placed the principle in opposition to approaches based on risk management and cost-benefit analysis. Dave Brower (Friends of the Earth) concluded that "all technology should be assumed guilty until proven innocent". Freeman Dyson described the application of precautionary principle as "deliberately one-sided", for example when used as justification to destroy genetic engineering research plantations and threaten researchers in spite of scientific evidence demonstrating lack of harm:

"The Precautionary Principle says that if some course of action carries even a remote chance of irreparable damage to the ecology, then you shouldn't do it, no matter how great the possible advantages of the action may be. You are not allowed to balance costs against benefits when deciding what to do."

As noted by Rupert and O'Riordan, the challenge in application of the principle is "in making it clear that absence of certainty, or there being insufficient evidence-based analysis, were not impediments to innovation, so long as there was no reasonable likelihood of serious harm". Lack of this nuanced application makes the principle "self-cancelling" according to Stewart Brand, because "nothing is fully established" in science, starting from the precautionary principle itself and including "gravity or Darwinian evolution". A balanced application should ensure that "precautionary measures should be" only taken "during early stages" and as "relevant scientific evidence becomes established", regulatory measures should only respond to that evidence.

Strong vs. weak
Strong precaution holds that regulation is required whenever there is a possible risk to health, safety, or the environment, even if the supporting evidence is speculative and even if the economic costs of regulation are high. In 1982, the United Nations World Charter for Nature gave the first international recognition to the strong version of the principle, suggesting that when "potential adverse effects are not fully understood, the activities should not proceed". The widely publicised Wingspread Declaration, from a meeting of environmentalists in 1998, is another example of the strong version. Strong precaution can also be termed as a "no-regrets" principle, where costs are not considered in preventative action.

Weak precaution holds that lack of scientific evidence does not preclude action if damage would otherwise be serious and irreversible. Humans practice weak precaution every day, and often incur costs, to avoid hazards that are far from certain: we do not walk in moderately dangerous areas at night, we exercise, we buy smoke detectors, we buckle our seatbelts.

According to a publication by the New Zealand Treasury Department:

"The weak version [of the Precautionary Principle] is the least restrictive and allows preventive measures to be taken in the face of uncertainty, but does not require them (e.g., Rio Declaration 1992; United Nations Framework Convention of Climate Change 1992). To satisfy the threshold of harm, there must be some evidence relating to both the likelihood of occurrence and the severity of consequences. Some, but not all, require consideration of the costs of precautionary measures. Weak formulations do not preclude weighing benefits against the costs. Factors other than scientific uncertainty, including economic considerations, may provide legitimate grounds for postponing action. Under weak formulations, the requirement to justify the need for action (the burden of proof) generally falls on those advocating precautionary action. No mention is made of assignment of liability for environmental harm.

Strong versions justify or require precautionary measures and some also establish liability for environmental harm, which is effectively a strong form of 'polluter pays'. For example, the Earth Charter states: 'When knowledge is limited apply a precautionary approach ... Place the burden of proof on those who argue that a proposed activity will not cause significant harm, and make the responsible parties liable for environmental harm.' Reversal of proof requires those proposing an activity to prove that the product, process or technology is sufficiently 'safe' before approval is granted. Requiring proof of 'no environmental harm' before any action proceeds implies the public is not prepared to accept any environmental risk, no matter what economic or social benefits may arise (Peterson, 2006). At the extreme, such a requirement could involve bans and prohibitions on entire classes of potentially threatening activities or substances (Cooney, 2005). Over time, there has been a gradual transformation of the precautionary principle from what appears in the Rio Declaration to a stronger form that arguably [by whom] acts as restraint on development in the absence of firm evidence that it will do no harm."

"Principle" vs. "approach"
No introduction to the precautionary principle would be complete without brief reference to the difference between the precautionary principle and the precautionary approach. Principle 15 of the Rio Declaration 1992 states that: "in order to protect the environment, the precautionary approach shall be widely applied by States according to their capabilities. Where there are threats of serious or irreversible damage, lack of full scientific certainty shall be not used as a reason for postponing cost-effective measures to prevent environmental degradation." As Garcia (1995) pointed out, "the wording, largely similar to that of the principle, is subtly different in that: it recognizes that there may be differences in local capabilities to apply the approach, and it calls for cost-effectiveness in applying the approach, e.g., taking economic and social costs into account." The "approach" is generally considered a softening of the "principle":

"As Recuerda has noted, the distinction between the precautionary principle and a precautionary approach is diffuse and, in some contexts, controversial. In the negotiations of international declarations, the United States has opposed the use of the term principle because this term has special connotations in legal language, due to the fact that a principle of law is a source of law. This means that it is compulsory, so a court can quash or confirm a decision through the application of the precautionary principle. In this sense, the precautionary principle is not a simple idea or a desideratum but a source of law. This is the legal status of the precautionary principle in the European Union. On the other hand, an 'approach' usually does not have the same meaning, although in some particular cases an approach could be binding. A precautionary approach is a particular 'lens' used to identify risk that every prudent person possesses (Recuerda, 2008)"

European Union
On 2 February 2000, the European Commission issued a Communication on the precautionary principle, in which it adopted a procedure for the application of this concept, but without giving a detailed definition of it. Paragraph 2 of article 191 of the Lisbon Treaty states that:

"Union policy on the environment shall aim at a high level of protection taking into account the diversity of situations in the various regions of the Union. It shall be based on the precautionary principle and on the principles that preventive action should be taken, that environmental damage should as a priority be rectified at source and that the polluter should pay."

After the adoption of the European Commission's communication on the precautionary principle, the principle has come to inform much EU policy, including areas beyond environmental policy. As of 2006 it had been integrated into EU laws "in matters such as general product safety, the use of additives for use in animal nutrition, the incineration of waste, and the regulation of genetically modified organisms". Through its application in case law, it has become a "general principle of EU law".

In Case T-74/00 Artegodan, the General Court (then Court of First Instance) appeared willing to extrapolate from the limited provision for the precautionary principle in environmental policy in article 191(2) TFEU to a general principle of EU law.

France
In France, the Charter for the Environment contains a formulation of the precautionary principle (article 5): "When the occurrence of any damage, albeit unpredictable in the current state of scientific knowledge, may seriously and irreversibly harm the environment, public authorities shall, with due respect for the principle of precaution and the areas within their jurisdiction, ensure the implementation of procedures for risk assessment and the adoption of temporary measures commensurate with the risk involved in order to preclude the occurrence of such damage."

United States
On 18 July 2005, the City of San Francisco passed a precautionary principle purchasing ordinance, which requires the city to weigh the environmental and health costs of its $600 million in annual purchases – for everything from cleaning supplies to computers. Members of the Bay Area Working Group on the Precautionary Principle contributed to drafting the Ordinance.

Australia
The most important Australian court case so far, due to its exceptionally detailed consideration of the precautionary principle, is Telstra Corporation Limited v Hornsby Shire Council.

The principle was summarised by reference to the NSW Protection of the Environment Administration Act 1991, which itself provides a good definition of the principle:

"If there are threats of serious or irreversible environmental damage, lack of full scientific certainty should not be used as a reasoning for postponing measures to prevent environmental degradation. In the application of the principle... decisions should be guided by: (i) careful evaluation to avoid, wherever practicable, serious or irreversible damage to the environment; and (ii) an assessment of risk-weighted consequence of various options".

The most significant points of Justice Preston's decision are the following findings:
 * The principle and accompanying need to take precautionary measures is "triggered" when two prior conditions exist: a threat of serious or irreversible damage, and scientific uncertainty as to the extent of possible damage.
 * Once both are satisfied, "a proportionate precautionary measure may be taken to avert the anticipated threat of environmental damage, but it should be proportionate."
 * The threat of serious or irreversible damage should invoke consideration of five factors: the scale of threat (local, regional etc.); the perceived value of the threatened environment; whether the possible impacts are manageable; the level of public concern, and whether there is a rational or scientific basis for the concern.
 * The consideration of the level of scientific uncertainty should involve factors which may include: what would constitute sufficient evidence; the level and kind of uncertainty; and the potential to reduce uncertainty.
 * The principle shifts the burden of proof. If the principle applies, the burden shifts: "a decision maker must assume the threat of serious or irreversible environmental damage is... a reality [and] the burden of showing this threat... is negligible reverts to the proponent..."
 * The precautionary principle invokes preventative action: "the principle permits the taking of preventative measures without having to wait until the reality and seriousness of the threat become fully known".
 * "The precautionary principle should not be used to try to avoid all risks."
 * The precautionary measures appropriate will depend on the combined effect of "the degree of seriousness and irreversibility of the threat and the degree of uncertainty... the more significant and uncertain the threat, the greater...the precaution required". "...measures should be adopted... proportionate to the potential threats".

Philippines
A petition filed 17 May 2013 by environmental group Greenpeace Southeast Asia and farmer-scientist coalition Masipag (Magsasaka at Siyentipiko sa Pagpapaunlad ng Agrikultura) asked the appellate court to stop the planting of Bt eggplant in test fields, saying the impacts of such an undertaking to the environment, native crops and human health are still unknown. The Court of Appeals granted the petition, citing the precautionary principle stating "when human activities may lead to threats of serious and irreversible damage to the environment that is scientifically plausible but uncertain, actions shall be taken to avoid or diminish the threat." Respondents filed a motion for reconsideration in June 2013 and on 20 September 2013 the Court of Appeals chose to uphold their May decision saying the bt talong field trials violate the people's constitutional right to a "balanced and healthful ecology." The Supreme Court on 8 December 2015 permanently stopped the field testing for Bt (Bacillus thuringiensis) talong (eggplant), upholding the decision of the Court of Appeals which stopped the field trials for the genetically modified eggplant. The court is the first in the world to adopt the precautionary principle regarding GMO products in its decision. The Supreme Court decision was later reversed following an appeal by researchers at the University of the Philippines Los Baños.

Corporate
Body Shop International, a UK-based cosmetics company, included the precautionary principle in their 2006 chemicals strategy.

Environment and health
Fields typically concerned by the precautionary principle are the possibility of:
 * Global warming or abrupt climate change in general
 * Extinction of species
 * Introduction of new products into the environment, with potential impact on biodiversity (e.g., genetically modified organisms)
 * Threats to public health, due to new diseases and techniques (e.g., HIV transmitted through blood transfusion)
 * Long-term effects of new technologies (e.g. health concerns regarding radiation from cell phones and other electronics communications devices)
 * Persistent or acute pollution (e.g., asbestos, endocrine disruptors)
 * Food safety (e.g., Creutzfeldt–Jakob disease)
 * Other new biosafety issues (e.g., artificial life, new molecules)

The precautionary principle is often applied to biological fields because changes cannot be easily contained and have the potential of being global. The principle has less relevance to contained fields such as aeronautics, where the few people undergoing risk have given informed consent (e.g., a test pilot). In the case of technological innovation, containment of impact tends to be more difficult if that technology can self-replicate. Bill Joy emphasised the dangers of replicating genetic technology, nanotechnology, and robotic technology in his article in Wired, "Why the future doesn't need us", though he does not specifically cite the precautionary principle. The application of the principle can be seen in the public policy of requiring pharmaceutical companies to carry out clinical trials to show that new medications are safe.

Oxford based philosopher Nick Bostrom discusses the idea of a future powerful superintelligence, and the risks should it attempt to gain atomic level control of matter.

Application of the principle modifies the status of innovation and risk assessment: it is not the risk that must be avoided or amended, but a potential risk that must be prevented. Thus, in the case of regulation of scientific research, there is a third party beyond the scientist and the regulator: the consumer.

In an analysis concerning application of the precautionary principle to nanotechnology, Chris Phoenix and Mike Treder posit that there are two forms of the principle, which they call the "strict form" and the "active form". The former "requires inaction when action might pose a risk", while the latter means "choosing less risky alternatives when they are available, and [...] taking responsibility for potential risks." Thomas Alured Faunce has argued for stronger application of the precautionary principle by chemical and health technology regulators particularly in relation to Ti02 and ZnO nanoparticles in sunscreens, biocidal nanosilver in waterways and products whose manufacture, handling or recycling exposes humans to the risk of inhaling multi-walled carbon nanotubes.

Animal sentience precautionary principle
Appeals to the precautionary principle have often characterized the debates concerning animal sentience – that is, the question of whether animals are able to feel "subjective experiences with an attractive or aversive quality", such as pain, pleasure, happiness, or joy – in relation to the question of whether we should legally protect sentient animals. A version of the precautionary principle suitable for the problem of animal sentience has been proposed by LSE philosopher Jonathan Birch: "The idea is that when the evidence of sentience is inconclusive, we should 'give the animal the benefit of doubt' or 'err on the side of caution' in formulating animal protection legislation." Since we cannot reach absolute certainty with regards to the fact that some animals are sentient, the precautionary principle has been invoked in order to grant potentially sentient animals "basic legal protections". Birch's formulation of the animal sentience precautionary principle runs as follows:"Where there are threats of serious, negative animal welfare outcomes, lack of full scientific certainty as to the sentience of the animals in question shall not be used as a reason for postponing cost-effective measures to prevent those outcomes."This version of the precautionary principle consists of an epistemic and a decision rule. The former concerns the "evidential bar" that should be required for animal sentience. In other words, how much evidence of sentience is necessary before one decides to apply precautionary measures? According to Birch, only some evidence would be sufficient, which means that the evidential bar should be set at low levels. Birch proposes to consider the evidence that certain animals are sentient sufficient whenever "statistically significant evidence ... of the presence of at least one credible indicator of sentience in at least one species of that order" has been obtained. For practical reasons, Birch says, the evidence of sentience should concern the order, so that if one species meets the conditions of sentience, then all the species of the same order should be considered sentient and should be thus legally protected. This is due to the fact that, on the one hand, "to investigate sentience separately in different orders" is feasible, whereas on the other hand, since some orders include thousands of species, it would be unfeasible to study their sentience separately.

What is more, the evidential bar should be so low that only one indicator of sentience in the species of a specific order will be sufficient in order for the precautionary principle to be applied. Such indicator should be "an observable phenomenon that experiments can be designed to detect, and it must be credible that the presence of this indicator is explained by sentience". Lists of such criteria already exist for detecting animal pain. The aim is to create analogous lists for other criteria of sentience, such as happiness, fear, or joy. The presence of one of these criteria should be demonstrated by means of experiments which must meet "the normal scientific standards".

Regarding the second part of the animal sentience precautionary principle, the decision rule concerns the requirement that we have to act once there is sufficient evidence of a seriously bad outcome. According to Birch, "we should aim to include within the scope of animal protection legislation all animals for which the evidence of sentience is sufficient, according to the standard of sufficiency outlined [above]". In other words, the decision rule states that once the aforementioned low evidential bar is met, then we should act in a precautionary way. Birch's proposal also "deliberately leaves open the question of how, and to what extent, the treatment of these animals should be regulated", thus also leaving open the content of the regulations, as this will largely depend on the animal in question.

Criticisms
Critics of the principle use arguments similar to those against other formulations of technological conservatism.

Internal inconsistency: applying strong PP risks causing harm
Strong formulations of the precautionary principle, without regard to its most basic provisions (i.e., that it is to be applied only where risks are potentially catastrophic and not easily calculable), when applied to the principle itself as a policy decision, beats its own purpose of reducing risk. The reason suggested is that preventing innovation from coming to market means that only current technology may be used, and current technology itself may cause harm or leave needs unmet; there is a risk of causing harm by blocking innovation. As Michael Crichton wrote in his novel State of Fear: "The 'precautionary principle', properly applied, forbids the precautionary principle."

For example, forbidding nuclear power plants based on concerns about low-probability high-impact risks means continuing to rely on power plants that burn fossil fuels, which continue to release greenhouse gases and thousands of certain deaths from air pollution.

In 2021 in response to early reports about rare blood clots seen in 25 patients out of 20 million vaccinated by Astra-Zeneca COVID-19 vaccine a number of European Union member states suspended the use of the vaccine, quoting the "precautionary principle". This was criticized by other EU states who refused to suspend the vaccination program, declaring that the "precautionary" decisions are focusing on the wrong risk, as delay in a vaccination program results in a larger number of certain deaths than any yet unconfirmed complications.

In another example, the Hazardous Air Pollutant provisions in the 1990 amendments to the US Clean Air Act are an example of the Precautionary Principle where the onus is now on showing a listed compound is harmless. Under this rule no distinction is made between those air pollutants that provide a higher or lower risk, so operators tend to choose less-examined agents that are not on the existing list.

"The very basis of the Precautionary Principle is to imagine the worst without supporting evidence... those with the darkest imaginations become the most influential."

Blocking innovation and progress generally
Because applications of strong formulations of the precautionary principle can be used to block innovation, a technology which brings advantages may be banned by precautionary principle because of its potential for negative impacts, leaving the positive benefits unrealised.

The precautionary principle has been ethically questioned on the basis that its application could block progress in developing countries.

"The precautionary principle presents a serious hazard to our health which extends way beyond the generation of unnecessary neuroses. The biggest correlate of our health and well being is our standard of living, as measured in conventional economic and physical terms. People in technologically advanced societies suffer fewer diseases and live longer than those in less developed nations. The biggest killer in the world is not genetically modified soya, pesticide residues or even tobacco. It is something which is given the code Z59.5 in the International Classification of Disease Handbook and accounts for more deaths world-wide than any other single factor. It is defined as 'Extreme Poverty'."

Vagueness and plausibility
The precautionary principle calls for action in the face of scientific uncertainty, but some formulations do not specify the minimal threshold of plausibility of risk that acts as a "triggering" condition, so that any indication that a proposed product or activity might harm health or the environment is sufficient to invoke the principle. In Sancho vs. DOE, Helen Gillmor, Senior District Judge, wrote in a dismissal of Wagner's lawsuit which included a popular worry that the LHC could cause "destruction of the earth" by a black hole:

"Injury in fact requires some 'credible threat of harm.' Cent. Delta Water Agency v. United States, 306 F.3d 938, 950 (9th Cir. 2002). At most, Wagner has alleged that experiments at the Large Hadron Collider (the 'Collider') have 'potential adverse consequences.' Speculative fear of future harm does not constitute an injury in fact sufficient to confer standing. Mayfield, 599 F.3d at 970."

The precautionary dilemma
The most commonly pressed objection to the precautionary principle ties together two of the above objections into the form of a dilemma. This maintains that, of the two available interpretations of the principle, neither are plausible: weak formulations (which hold that precaution in the face of uncertain harms is permissible) are trivial, while strong formulations (which hold that precaution in the face of uncertain harms is required) are incoherent. On the first horn of the dilemma Cass Sunstein states:"The weak versions of the Precautionary Principle state a truism—uncontroversial in principle and necessary in practice only to combat public confusion or the self-interested claims of private groups demanding unambiguous evidence of harm, which no rational society requires." If all that the (weak) principle states is that it is permissible to act in a precautionary manner where there is a possible risk of harm, then it constitutes a trivial truism and thus fails to be useful.

If we formulate the principle in the stronger sense however, it looks like it rules out all courses of action, including the precautionary measures it is intended to advocate. This is because, if we stipulate that precaution is required in the face of uncertain harms, and precautionary measures also carry a risk of harm, the precautionary principle can both demand and prohibit action at the same time. The risk of a policy resulting in catastrophic harm is always possible. For example: prohibiting genetically modified crops risks significantly reduced food production; placing a moratorium on nuclear power risks an over-reliance on coal that could lead to more air pollution; implementing extreme measures to slow global warming risks impoverishment and bad health outcomes for some people. The strong version of the precautionary principle, in that "[i]t bans the very steps that it requires", thus fails to be coherent. As Sunstein states, it is not protective, it is "paralyzing".

title: Precautionary principle


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Informed consent

Informed consent is a principle in medical ethics, medical law and media studies, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatments, alternative treatments, the patient's role in treatment, and their right to refuse treatment. In most systems, healthcare providers have a legal and ethical responsibility to ensure that a patient's consent is informed. This principle applies more broadly than healthcare intervention, for example to conduct research and to disclose a person's medical information.

Within the US, definitions of informed consent vary, and the standard required is generally determined by the state. These standards in medical contexts are formalized in the requirement for decision-making capacity and professional determinations in these contexts have legal authority. This requirement can be summarized in brief to presently include the following conditions, all of which must be met in order for one to qualify as possessing decision-making capacity:
 * 1) Choice, the ability to provide or evidence a decision.
 * 2) Understanding, the capacity to apprehend the relevant facts pertaining to the decision at issue.
 * 3) Appreciation, the ability of the patient to give informed consent with concern for, and belief in, the impact the relevant facts will have upon oneself.
 * 4) Reasoning, the mental acuity to make the relevant inferences from, and mental manipulations of, the information appreciated and understood to apply to the decision at hand.

Impairments to reasoning and judgment that may preclude informed consent include intellectual or emotional immaturity, high levels of stress such as post-traumatic stress disorder or a severe intellectual disability, severe mental disorder, intoxication, severe sleep deprivation, dementia, or coma.

Obtaining informed consent is not always required. If an individual is considered unable to give informed consent, another person is generally authorized to give consent on the individual's behalf—for example, the parents or legal guardians of a child (though in this circumstance the child may be required to provide informed assent) and conservators for the mentally disordered. Alternatively, the doctrine of implied consent permits treatment in limited cases, for example when an unconscious person will die without immediate intervention. Cases in which an individual is provided insufficient information to form a reasoned decision raise serious ethical issues. When these issues occur, or are anticipated to occur, in a clinical trial, they are subject to review by an ethics committee or institutional review board.

Informed consent is codified in both national and international law. 'Free consent' is a cognate term in the International Covenant on Civil and Political Rights, adopted in 1966 by the United Nations, and intended to be in force by 23 March 1976. Article 7 of the covenant prohibits experiments conducted without the "free consent to medical or scientific experimentation" of the subject. , the covenant has 173 parties and six more signatories without ratification.

Assessment
Informed consent can be complex to evaluate, because neither expressions of consent, nor expressions of understanding of implications, necessarily mean that full adult consent was in fact given, nor that full comprehension of relevant issues is internally digested. Consent may be implied within the usual subtleties of human communication, rather than explicitly negotiated verbally or in writing. For example, if a doctor asks a patient to take their blood pressure, a patient may demonstrate consent by offering their arm for a blood pressure cuff. In some cases consent cannot legally be possible, even if the person protests he does indeed understand and wish. There are also structured instruments for evaluating capacity to give informed consent, although no ideal instrument presently exists.

Thus, there is always a degree to which informed consent must be assumed or inferred based upon observation, or knowledge, or legal reliance. This especially is the case in sexual or relational issues. In medical or formal circumstances, explicit agreement by means of signature—normally relied on legally—regardless of actual consent, is the norm. This is the case with certain procedures, such as a "do not resuscitate" directive that a patient signed before onset of their illness.

Brief examples of each of the above:
 * 1) A person may verbally agree to something from fear, perceived social pressure, or psychological difficulty in asserting true feelings. The person requesting the action may honestly be unaware of this and believe the consent is genuine, and rely on it. Consent is expressed, but not internally given.
 * 2) A person may claim to understand the implications of some action, as part of consent, but in fact has failed to appreciate the possible consequences fully and may later deny the validity of the consent for this reason. Understanding needed for informed consent is present but is, in fact (through ignorance), not present.
 * 3) A person signs a legal release form for a medical procedure, and later feels he did not really consent. Unless he can show actual misinformation, the release is usually persuasive or conclusive in law, in that the clinician may rely legally upon it for consent. In formal circumstances, a written consent usually legally overrides later denial of informed consent (unless obtained by misrepresentation).
 * 4) Informed consent in the U.S. can be overridden in emergency medical situations pursuant to 21CFR50.24, which was first brought to the general public's attention via the controversy surrounding the study of Polyheme.

Valid elements
For an individual to give valid informed consent, three components must be present: disclosure, capacity and voluntariness.

 * Disclosure requires the researcher to supply each prospective subject with the information necessary to make an autonomous decision and also to ensure that the subject adequately understands the information provided. This latter requirement implies that a written consent form be written in lay language suited for the comprehension skills of subject population, as well as assessing the level of understanding through conversation (to be informed).
 * Capacity pertains to the ability of the subject to both understand the information provided and form a reasonable judgment based on the potential consequences of his/her decision.
 * Voluntariness refers to the subject's right to freely exercise his/her decision making without being subjected to external pressure such as coercion, manipulation, or undue influence.

From children
As children often lack the decision-making ability or legal power (competence) to provide true informed consent for medical decisions, it often falls on parents or legal guardians to provide informed permission for medical decisions. This "consent by proxy" usually works reasonably well, but can lead to ethical dilemmas when the judgment of the parents or guardians and the medical professional differ with regard to what constitutes appropriate decisions "in the best interest of the child". Children who are legally emancipated, and certain situations such as decisions regarding sexually transmitted diseases or pregnancy, or for unemancipated minors who are deemed to have medical decision making capacity, may be able to provide consent without the need for parental permission depending on the laws of the jurisdiction the child lives in. The American Academy of Pediatrics encourages medical professionals also to seek the assent of older children and adolescents by providing age appropriate information to these children to help empower them in the decision-making process.

Research on children has benefited society in many ways. The only effective way to establish normal patterns of growth and metabolism is to do research on infants and young children. When addressing the issue of informed consent with children, the primary response is parental consent. This is valid, although only legal guardians are able to consent for a child, not adult siblings. Additionally, parents may not order the termination of a treatment that is required to keep a child alive, even if they feel it is in the best interest. Guardians are typically involved in the consent of children, however a number of doctrines have developed that allow children to receive health treatments without parental consent. For example, emancipated minors may consent to medical treatment, and minors can also consent in an emergency.

Waiver of requirement
Waiver of the consent requirement may be applied in certain circumstances where no foreseeable harm is expected to result from the study or when permitted by law, federal regulations, or if an ethical review committee has approved the non-disclosure of certain information.

Besides studies with minimal risk, waivers of consent may be obtained in a military setting. According to 10 USC 980, the United States Code for the Armed Forces, Limitations on the Use of Humans as Experimental Subjects, a waiver of advanced informed consent may be granted by the Secretary of Defense if a research project would:
 * 1) directly benefit subjects
 * 2) advance the development of a medical product necessary to the military and
 * 3) be carried out under all laws and regulations (i.e., Emergency Research Consent Waiver) including those pertinent to the FDA.

While informed consent is a basic right and should be carried out effectively, if a patient is incapacitated due to injury or illness, it is still important that patients benefit from emergency experimentation. The Food and Drug Administration (FDA) and the Department of Health and Human Services (DHHS) joined to create federal guidelines to permit emergency research, without informed consent. However, they can only proceed with the research if they obtain a waiver of informed consent (WIC) or an emergency exception from informed consent (EFIC).

21st Century Cures Act
The 21st Century Cures Act enacted by the 114th United States Congress in December 2016 allows researchers to waive the requirement for informed consent when clinical testing "poses no more than minimal risk" and "includes appropriate safeguards to protect the rights, safety, and welfare of the human subject."

Medical sociology
Medical sociologists have studied informed consent as well bioethics more generally. Oonagh Corrigan, looking at informed consent for research in patients, argues that much of the conceptualization of informed consent comes from research ethics and bioethics with a focus on patient autonomy, and notes that this aligns with a neoliberal worldview. Corrigan argues that a model based solely around individual decision making does not accurately describe the reality of consent because of social processes: a view that has started to be acknowledged in bioethics. She feels that the liberal principles of informed consent are often in opposition with autocratic medical practices such that norms values and systems of expertise often shape and individuals ability to apply choice.

Patients who agree to participate in trials often do so because they feel that the trial was suggested by a doctor as the best intervention. Patients may find being asked to consent within a limited time frame a burdensome intrusion on their care when it arises because a patient has to deal with a new condition. Patients involved in trials may not be fully aware of the alternative treatments, and an awareness that there is uncertainty in the best treatment can help make patients more aware of this. Corrigan notes that patients generally expect that doctors are acting exclusively in their interest in interactions and that this combined with "clinical equipose" where a healthcare practitioner does not know which treatment is better in a randomized control trial can be harmful to the doctor-patient relationship.

Medical procedures
The doctrine of informed consent relates to professional negligence and establishes a breach of the duty of care owed to the patient (see duty of care, breach of the duty, and respect for persons). The doctrine of informed consent also has significant implications for medical trials of medications, devices, or procedures.

Requirements of the professional
Until 2015 in the United Kingdom and in countries such as Malaysia and Singapore, informed consent in medical procedures requires proof as to the standard of care to expect as a recognised standard of acceptable professional practice (the Bolam Test), that is, what risks would a medical professional usually disclose in the circumstances (see Loss of right in English law). Arguably, this is "sufficient consent" rather than "informed consent." The UK has since departed from the Bolam test for judging standards of informed consent, due to the landmark ruling in Montgomery v Lanarkshire Health Board. This moves away from the concept of a reasonable physician and instead uses the standard of a reasonable patient, and what risks an individual would attach significance to.

Medicine in the United States, Australia, and Canada takes this patient-centric approach to "informed consent." Informed consent in these jurisdictions requires healthcare providers to disclose significant risks, as well as risks of particular importance to that patient. This approach combines an objective (a hypothetical reasonable patient) and subjective (this particular patient) approach.

The doctrine of informed consent should be contrasted with the general doctrine of medical consent, which applies to assault or battery. The consent standard here is only that the person understands, in general terms, the nature of and purpose of the intended intervention. As the higher standard of informed consent applies to negligence, not battery, the other elements of negligence must be made out. Significantly, causation must be shown: That had the individual been made aware of the risk he would not have proceeded with the operation (or perhaps with that surgeon).

Optimal establishment of an informed consent requires adaptation to cultural or other individual factors of the patient. As of 2011, for example, people from Mediterranean and Arab appeared to rely more on the context of the delivery of the information, with the information being carried more by who is saying it and where, when, and how it is being said, rather than what is said, which is of relatively more importance in typical "Western" countries.

The informed consent doctrine is generally implemented through good healthcare practice: pre-operation discussions with patients and the use of medical consent forms in hospitals. However, reliance on a signed form should not undermine the basis of the doctrine in giving the patient an opportunity to weigh and respond to the risk. In one British case, a doctor performing routine surgery on a woman noticed that she had cancerous tissue in her womb. He took the initiative to remove the woman's womb; however, as she had not given informed consent for this operation, the doctor was judged by the General Medical Council to have acted negligently. The council stated that the woman should have been informed of her condition, and allowed to make her own decision.

Obtaining informed consents
To document that informed consent has been given for a procedure, healthcare organisations have traditionally used paper-based consent forms on which the procedure and its risks and benefits are noted, and is signed by both patient and clinician. In a number of healthcare organisations consent forms are scanned and maintained in an electronic document store. The paper consent process has been demonstrated to be associated with significant errors of omission, and therefore increasing numbers of organisations are using digital consent applications where the risk of errors can be minimised, a patient's decision making and comprehension can be supported by additional lay-friendly and accessible information, consent can be completed remotely, and the process can become paperless. One form of digital consent is dynamic consent, which invites participants to provide consent in a granular way, and makes it easier for them to withdraw consent if they wish.

Electronic consent methods have been used to support indexing and retrieval of consent data, thus enhancing the ability to honor to patient intent and identify willing research participants. More recently, Health Sciences South Carolina, a statewide research collaborative focused on transforming healthcare quality, health information systems and patient outcomes, developed an open-source system called Research Permissions Management System (RPMS).

Competency of the patient
The ability to give informed consent is governed by a general requirement of competency. In common law jurisdictions, adults are presumed competent to consent. This presumption can be rebutted, for instance, in circumstances of mental illness or other incompetence. This may be prescribed in legislation or based on a common-law standard of inability to understand the nature of the procedure. In cases of incompetent adults, a health care proxy makes medical decisions. In the absence of a proxy, the medical practitioner is expected to act in the patient's best interests until a proxy can be found.

By contrast, 'minors' (which may be defined differently in different jurisdictions) are generally presumed incompetent to consent, but depending on their age and other factors may be required to provide Informed assent. In some jurisdictions (e.g. much of the U.S.), this is a strict standard. In other jurisdictions (e.g. England, Australia, Canada), this presumption may be rebutted through proof that the minor is 'mature' (the 'Gillick standard'). In cases of incompetent minors, informed consent is usually required from the parent (rather than the 'best interests standard') although a parens patriae order may apply, allowing the court to dispense with parental consent in cases of refusal.

Deception
Research involving deception is controversial given the requirement for informed consent. Deception typically arises in social psychology, when researching a particular psychological process requires that investigators deceive subjects. For example, in the Milgram experiment, researchers wanted to determine the willingness of participants to obey authority figures despite their personal conscientious objections. They had authority figures demand that participants deliver what they thought was an electric shock to another research participant. For the study to succeed, it was necessary to deceive the participants so they believed that the subject was a peer and that their electric shocks caused the peer actual pain.

Nonetheless, research involving deception prevents subjects from exercising their basic right of autonomous informed decision-making and conflicts with the ethical principle of respect for persons.

The Ethical Principles of Psychologists and Code of Conduct set by the American Psychological Association says that psychologists may conduct research that includes a deceptive compartment only if they can both justify the act by the value and importance of the study's results and show they could not obtain the results by some other way. Moreover, the research should bear no potential harm to the subject as an outcome of deception, either physical pain or emotional distress. Finally, the code requires a debriefing session in which the experimenter both tells the subject about the deception and gives subject the option of withdrawing the data.

Abortion
In some U.S. states, informed consent laws (sometimes called "right to know" laws) require that a woman seeking an elective abortion receive information from the abortion provider about her legal rights, alternatives to abortion (such as adoption), available public and private assistance, and other information specified in the law, before the abortion is performed. Other countries with such laws (e.g. Germany) require that the information giver be properly certified to make sure that no abortion is carried out for the financial gain of the abortion provider and to ensure that the decision to have an abortion is not swayed by any form of incentive.

Some informed consent laws have been criticized for allegedly using "loaded language in an apparently deliberate attempt to 'personify' the fetus," but those critics acknowledge that "most of the information in the [legally mandated] materials about abortion comports with recent scientific findings and the principles of informed consent", although "some content is either misleading or altogether incorrect."

Medicine
Informed consent is part of ethical clinical research as well, in which a human subject voluntarily confirms his or her willingness to participate in a particular clinical trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Informed consent is documented by means of a written, signed, and dated informed consent form. In medical research, the Nuremberg Code set a base international standard in 1947, in response to the ethical violation in the Holocaust. Standards continued to develop. Nowadays, medical research is overseen by an ethics committee that also oversees the informed consent process.

Social sciences
As the medical guidelines established in the Nuremberg Code were imported into the ethical guidelines for the social sciences, informed consent became a common part of the research procedure. However, while informed consent is the default in medical settings, it is not always required in the social sciences. Here, firstly, research often involves low or no risk for participants, unlike in many medical experiments. Secondly, the mere knowledge that they participate in a study can cause people to alter their behavior, as in the Hawthorne Effect: "In the typical lab experiment, subjects enter an environment in which they are keenly aware that their behavior is being monitored, recorded, and subsequently scrutinized." In such cases, seeking informed consent directly interferes with the ability to conduct the research, because the very act of revealing that a study is being conducted is likely to alter the behavior studied. Author J.A. List explains the potential dilemma that can result: "if one were interested in exploring whether, and to what extent, race or gender influences the prices that buyers pay for used cars, it would be difficult to measure accurately the degree of discrimination among used car dealers who know that they are taking part in an experiment." In a case where such interference is likely, and after careful consideration, a researcher may forgo the informed consent process. This may be done after the researcher(s) and an Ethics Committee and/or Institutional Review Board (IRB) weigh the risk to study participants against the benefits to society and whether participants participate voluntarily and are to be treated fairly.

The birth of new online media, such as social media, has complicated the idea of informed consent. In an online environment people pay little attention to Terms of Use agreements and can subject themselves to research without thorough knowledge. This issue came to the public light following a study conducted by Facebook in 2014, and published by that company and Cornell University. Facebook conducted a study without consulting an Ethics Committee or IRB where they altered the Facebook News Feeds of roughly 700,000 users to reduce either the amount of positive or negative posts they saw for a week. The study then analyzed if the users' status updates changed during the different conditions. The study was published in the Proceedings of the National Academy of Sciences. The lack of informed consent led to outrage among many researchers and users. Many believed that by potentially altering the mood of users by altering what posts they see, Facebook put at-risk individuals at higher dangers for depression and suicide. However, supporters of Facebook claim that Facebook details that they have the right to use information for research in their terms of use. Others say the experiment is just a part of Facebook's current work, which alters News Feeds algorithms continually to keep people interested and coming back to the site. Others pointed out that this specific study is not unique but rather news organizations constantly try out different headlines using algorithms to elicit emotions and garner clicks or Facebook shares. They say this Facebook study is no different from things people already accept. Still, others say that Facebook broke the law when conducting the experiment on users that did not give informed consent. The Facebook study controversy raises numerous questions about informed consent and the differences in the ethical review process between publicly and privately funded research. Some say Facebook was within its limits and others see the need for more informed consent and/or the establishment of in-house private review boards.

Duty to share findings
Some researchers and ethicists advocate for researchers to share experimental results with their subjects in a way they can understand, both as an ethical obligation and as a way to encourage more participation. In 2023, the government of the United Kingdom proposed making this a requirement. The Ethical, Legal, and Social Implications research program of the National Human Genome Research Institute in the United States has provided some funding for researchers to do this.

Conflicts of interest
Other, long-standing controversies underscore the role for conflicts of interest among medical school faculty and researchers. For example, in 2014 coverage of University of California (UC) medical school faculty members has included news of ongoing corporate payments to researchers and practitioners from companies that market and produce the very devices and treatments they recommend to patients. Robert Pedowitz, the former chairman of UCLA's orthopedic surgery department, reported concern that his colleague's financial conflicts of interest could negatively affect patient care or research into new treatments. In a subsequent lawsuit about whistleblower retaliation, the university provided a $10 million settlement to Pedowitz while acknowledging no wrongdoing. Consumer Watchdog, an oversight group, observed that University of California policies were "either inadequate or unenforced...Patients in UC hospitals deserve the most reliable surgical devices and medication…and they shouldn't be treated as subjects in expensive experiments." Other UC incidents include taking the eggs of women for implantation into other women without consent and injecting live bacteria into human brains, resulting in potentially premature deaths.

History
Informed consent is a technical term first used by attorney, Paul G. Gebhard, in a medical malpractice United States court case in 1957. In tracing its history, some scholars have suggested tracing the history of checking for any of these practices: These practices are part of what constitutes informed consent, and their history is the history of informed consent. They combine to form the modern concept of informed consent—which rose in response to particular incidents in modern research. Whereas various cultures in various places practiced informed consent, the modern concept of informed consent was developed by people who drew influence from Western tradition.
 * 1) A patient agrees to a health intervention based on an understanding of it.
 * 2) The patient has multiple choices and is not compelled to choose a particular one.
 * 3) The consent includes giving permission.

Medical history
Historians cite a series of medical guidelines to trace the history of informed consent in medical practice.

The Hippocratic Oath, a Greek text dating to 500 B.C.E., was the first set of Western writings giving guidelines for the conduct of medical professionals. Consent by patients as well as several other, now considered fundamental issues, is not mentioned. The Hippocratic Corpus advises that physicians conceal most information from patients to give the patients the best care. The rationale is a beneficence model for care—the doctor knows better than the patient, and therefore should direct the patient's care, because the patient is not likely to have better ideas than the doctor.

Henri de Mondeville, a French surgeon who in the 14th century, wrote about medical practice. He traced his ideas to the Hippocratic Oath. Among his recommendations were that doctors "promise a cure to every patient" in hopes that the good prognosis would inspire a good outcome to treatment. Mondeville never mentioned getting consent, but did emphasize the need for the patient to have confidence in the doctor. He also advised that when deciding therapeutically unimportant details the doctor should meet the patients' requests "so far as they do not interfere with treatment".

In Ottoman Empire records there exists an agreement from 1539 in which negotiates details of a surgery, including fee and a commitment not to sue in case of death. This is the oldest identified written document in which a patient acknowledges risk of medical treatment and writes to express their willingness to proceed.

Benjamin Rush was an 18th-century United States physician who was influenced by the Age of Enlightenment cultural movement. Because of this, he advised that doctors ought to share as much information as possible with patients. He recommended that doctors educate the public and respect a patient's informed decision to accept therapy. There is no evidence that he supported seeking a consent from patients. In a lecture titled "On the duties of patients to their physicians", he stated that patients should be strictly obedient to the physician's orders; this was representative of much of his writings. John Gregory, Rush's teacher, wrote similar views that a doctor could best practice beneficence by making decisions for the patients without their consent.

Thomas Percival was a British physician who published a book called Medical Ethics in 1803. Percival was a student of the works of Gregory and various earlier Hippocratic physicians. Like all previous works, Percival's Medical Ethics makes no mention of soliciting for the consent of patients or respecting their decisions. Percival said that patients have a right to truth, but when the physician could provide better treatment by lying or withholding information, he advised that the physician do as he thought best.

When the American Medical Association was founded they in 1847 produced a work called the first edition of the American Medical Association Code of Medical Ethics. Many sections of this book are verbatim copies of passages from Percival's Medical Ethics. A new concept in this book was the idea that physicians should fully disclose all patient details truthfully when talking to other physicians, but the text does not also apply this idea to disclosing information to patients. Through this text, Percival's ideas became pervasive guidelines throughout the United States as other texts were derived from them.

Worthington Hooker was an American physician who in 1849 published Physician and Patient. This medical ethics book was radical demonstrating understanding of the AMA's guidelines and Percival's philosophy and soundly rejecting all directives that a doctor should lie to patients. In Hooker's view, benevolent deception is not fair to the patient, and he lectured widely on this topic. Hooker's ideas were not broadly influential.

The US Canterbury v. Spence case established the principle of informed consent in US law. Earlier legal cases had created the underpinnings for informed consent, but his judgment gave a detailed and thought through discourse on the matter. The judgment cites cases going back to 1914 as precedent for informed consent.

Research history
Historians cite a series of human subject research experiments to trace the history of informed consent in research.

The U.S. Army Yellow Fever Commission "is considered the first research group in history to use consent forms." In 1900, Major Walter Reed was appointed head of the four man U.S. Army Yellow Fever Commission in Cuba that determined mosquitoes were the vector for yellow fever transmission. His earliest experiments were probably done without formal documentation of informed consent. In later experiments he obtained support from appropriate military and administrative authorities. He then drafted what is now "one of the oldest series of extant informed consent documents." The three surviving examples are in Spanish with English translations; two have an individual's signature and one is marked with an X.

Tearoom Trade is the name of a book by American psychologist Laud Humphreys. In it he describes his research into male homosexual acts. In conducting this research he never sought consent from his research subjects and other researchers raised concerns that he violated the right to privacy for research participants.

Henrietta Lacks on January 29, 1951, shortly after the birth of her son Joseph, Lacks entered Johns Hopkins Hospital in Baltimore with profuse bleeding. She was diagnosed with cervical cancer and was treated with inserts of radium tubes. During her radiation treatments for the tumor, two samples—one of healthy cells, the other of malignant cells—were removed from her cervix without her permission. Later that year, 31-year-old Henrietta Lacks died from the cancer. Her cells were cultured creating Hela cells, but the family was not informed until 1973, the family learned the truth when scientists asked for DNA samples after finding that HeLa had contaminated other samples. In 2013 researchers published the genome without the Lacks family consent.

The Milgram experiment is the name of a 1961 experiment conducted by American psychologist Stanley Milgram. In the experiment Milgram had an authority figure order research participants to commit a disturbing act of harming another person. After the experiment he would reveal that he had deceived the participants and that they had not hurt anyone, but the research participants were upset at the experience of having participated in the research. The experiment raised broad discussion on the ethics of recruiting participants for research without giving them full information about the nature of the research.

Chester M. Southam used HeLa cells to inject into cancer patients and Ohio State Penitentiary inmates without informed consent to determine if people could become immune to cancer and if cancer could be transmitted.

New areas
With the growth of bioethics in the 21st century to include environmental sustainability, some authors, such as Cristina Richie have proposed a "green consent". This would include information and education about the climate impact of pharmaceuticals (carbon cost of medications) and climate change health hazards.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Informed consent


text:
975

Year 975 (CMLXXV) was a common year starting on Friday (link will display the full calendar) of the Julian calendar.

Byzantine Empire

 * Arab–Byzantine War: Emperor John I raids Mesopotamia and invades Syria, using the Byzantine base at Antioch to press southwards to Tripoli. He conquers the cities of Baalbek, Damascus, Sidon, Tiberias and Caesarea, but fails to take Jerusalem.

Europe

 * October 15 – Oberto I (Obizzo), an Italian count palatine, dies. The Marca Obertenga (Eastern Liguria) is divided among the Obertenghi family.
 * Emperor Otto II (the Red) leads a punitive expedition against Boleslaus II, duke of Bohemia (approximate date).

England

 * July 8 – King Edgar I (the Peaceful) dies at Winchester after a 16-year reign. He is succeeded by his 12-year-old son Edward II (the Martyr) as ruler of England.

Africa

 * December 21 – Caliph Al-Mu'izz dies in Egypt after a 22-year reign in which he has extended his realm from Sicily to the Atlantic. He is succeeded by his son Al-Aziz Billah as ruler of the Fatimid Caliphate.

China

 * Emperor Taizu conquers Hunan Province and brings the power of the military under Song control. Ending the era of the warlords (approximate date).

Religion

 * March – Otto II appoints his archchancellor Willigis as archbishop of Mainz. He receives the pallium from Pope Benedict VII.

Births

 * July 25 – Thietmar, bishop of Merseburg (d. 1018)
 * Adalbold II, bishop of Utrecht (d. 1026)
 * Amadeus I, count of Savoy (approximate date)
 * Bouchard II, French nobleman (d. 1020)
 * Conrad I, German nobleman (d. 1011)
 * Cunigunde, Holy Roman Empress (d. 1040)
 * Elijah, bishop of Beth Nuhadra (d. 1046)
 * Gerard I, bishop of Cambrai (approximate date)
 * Gero II, German nobleman (d. 1015)
 * Guo, empress of the Song Dynasty (d. 1007)
 * Hugh of Chalon, French bishop (approximate date)
 * Izumi Shikibu, Japanese poet (approximate date)
 * Oldřich, duke of Bohemia (approximate date)
 * Sophia I, German princess and abbess (d. 1039)
 * Stephen I, king of Hungary (approximate date)

Deaths

 * June 28
 * Cyneweard, bishop of Wells (Somerset)
 * Thurcytel, abbot of Crowland (approximate date)
 * July 4 – Gwangjong (Wang So), Korean king (b. 925)
 * July 8 – Edgar I (the Peaceful), king of England
 * July 31 – Fu Yanqing, Chinese general (b. 898)
 * October 15 – Oberto I, Italian count palatine
 * November 12 – Notker Physicus, Swiss painter
 * November 26 – Conrad, bishop of Constance
 * December 21 – Al-Mu'izz, Fatimid caliph (b. 932)
 * December 27 – Balderic, bishop of Utrecht (b. 897)
 * Bilgetegin, Samanid officer and governor
 * Cináed ua hArtacáin, Irish Gaelic poet
 * Dyfnwal ab Owain, king of Strathclyde
 * Gu Hongzhong, Chinese painter (b. 937)
 * Master Geng, Chinese alchemist
 * Olof II, king of Sweden (approximate date)
 * Theobald I, Frankish nobleman (b. 913)
 * Wynsige (or Wynsy), bishop of Lichfield
 * Yongming Yanshou, Chinese Zen master (b. 904)

title: 975


text:
Larva

A larva (: larvae ) is a distinct juvenile form many animals undergo before metamorphosis into their next life stage. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle.

A larva's appearance is generally very different from the adult form (e.g. caterpillars and butterflies) including different unique structures and organs that do not occur in the adult form. Their diet may also be considerably different.

Larvae are frequently adapted to different environments than adults. For example, some larvae such as tadpoles live almost exclusively in aquatic environments, but can live outside water as adult frogs. By living in a distinct environment, larvae may be given shelter from predators and reduce competition for resources with the adult population.

Animals in the larval stage will consume food to fuel their transition into the adult form. In some organisms like polychaetes and barnacles, adults are immobile but their larvae are mobile, and use their mobile larval form to distribute themselves. These larvae used for dispersal are either planktotrophic (feeding) or lecithotrophic (non-feeding).

Some larvae are dependent on adults to feed them. In many eusocial Hymenoptera species, the larvae are fed by female workers. In Ropalidia marginata (a paper wasp) the males are also capable of feeding larvae but they are much less efficient, spending more time and getting less food to the larvae.

The larvae of some organisms (for example, some newts) can become pubescent and do not develop further into the adult form. This is a type of neoteny.

It is a misunderstanding that the larval form always reflects the group's evolutionary history. This could be the case, but often the larval stage has evolved secondarily, as in insects. In these cases, the larval form may differ more than the adult form from the group's common origin.

Insect larvae

Within Insects, only Endopterygotes show complete metamorphosis, including a distinct larval stage. Several classifications have been suggested by many entomologists, and following classification is based on Antonio Berlese classification in 1913. There are four main types of endopterygote larvae types:

 * 1) Apodous larvae – no legs at all and are poorly sclerotized. Based on sclerotization. All Apocrita are apodous.  Three apodous forms are recognized.
 * 2) * Eucephalous – with well sclerotized head capsule. Found in Nematocera, Buprestidae and Cerambycidae families.
 * 3) * Hemicephalus – with a reduced head capsule, retractable in to the thorax. Found in Tipulidae and Brachycera families.
 * 4) * Acephalus – without head capsule. Found in Cyclorrhapha
 * 5) Protopod larvae – larva have many different forms and often unlike a normal insect form. They hatch from eggs which contain very little yolk. E.g. first instar larvae of parasitic hymenoptera.
 * 6) Polypod larvae – also known as eruciform larvae, these larvae have abdominal prolegs, in addition to usual thoracic legs. They are poorly sclerotized and relatively inactive. They live in close contact with their food. Best example is caterpillars of lepidopterans.
 * 7) Oligopod larvae – have well developed head capsule and mouthparts are similar to the adult, but without compound eyes. They have six legs. No abdominal prolegs. Two types can be seen:
 * 8) * Campodeiform – well sclerotized, dorso-ventrally flattened body. Usually long legged predators with prognathous mouthparts. (lacewing, trichopterans, mayflies and some coleopterans).
 * 9) * Scarabeiform – poorly sclerotized, flat thorax and abdomen. Usually short legged and inactive burrowing forms. (Scarabaeoidea and other coleopterans).

title: Larva


text:
Indigo dye

Indigo dye is an organic compound with a distinctive blue color. Indigo is a natural dye extracted from the leaves of some plants of the Indigofera genus, in particular Indigofera tinctoria. Dye-bearing Indigofera plants were commonly grown and used throughout the world, particularly in Asia, with the production of indigo dyestuff economically important due to the historical rarity of other blue dyestuffs.

Most indigo dye produced today is synthetic, constituting around 80,000 tonnes each year, as of 2023. It is most commonly associated with the production of denim cloth and blue jeans, where its properties allow for effects such as stone washing and acid washing to be applied quickly.

Uses
The primary use for indigo is as a dye for cotton yarn, mainly used in the production of denim cloth suitable for blue jeans; on average, a pair of blue jeans requires 3 g to 12 g of dye. Smaller quantities are used in the dyeing of wool and silk.

Indigo carmine, also known as indigo, is an indigo derivative which is also used as a colorant. About 20,000 tonnes are produced annually, again mainly for the production of blue jeans. It is also used as a food colorant, and is listed in the United States as FD&C Blue No. 2.

Natural sources
A variety of plants have provided indigo throughout history, but most natural indigo was obtained from those in the genus Indigofera, which are native to the tropics, notably the Indian Subcontinent. The primary commercial indigo species in Asia was true indigo (Indigofera tinctoria, also known as I. sumatrana). A common alternative used in the relatively colder subtropical locations such as Japan's Ryukyu Islands and Taiwan is Strobilanthes cusia.

Until the introduction of Indigofera species from the south, Persicaria tinctoria (dyer's knotweed) was the most important blue dyestuff in East Asia; however, the crop produced less dyestuff than the average crop of indigo, and was quickly surpassed in favour of the more economical Indigofera tinctoria plant. In Central and South America, the species grown is Indigofera suffruticosa, also known as anil, and in India, an important species was Indigofera arrecta, Natal indigo. In Europe, Isatis tinctoria, commonly known as woad, was used for dyeing fabrics blue, containing the same dyeing compounds as indigo, also referred to as indigo.

Several plants contain indigo, which, when exposed to an oxidizing source such as atmospheric oxygen, reacts to produce indigo dye; however, the relatively low concentrations of indigo in these plants make them difficult to work with, with the color more easily tainted by other dye substances also present in these plants, typically leading to a greenish tinge.

The precursor to indigo is indican, a colorless, water-soluble derivative of the amino acid tryptophan, and Indigofera leaves contain as much as 0.2–0.8% of this compound. Pressing cut leaves into a vat and soaking hydrolyzes the indican, releasing β--glucose and indoxyl. The indoxyl dimerizes in the mixture, and after 12–15 hours of fermentation yields the yellow, water-soluble leucoindigo. Subsequent exposure to air forms the blue, water-insoluble indigo dye. The dye precipitates from the fermented leaf solution upon oxidation, but may also be precipitated when mixed with a strong base such as lye. The solids are filtered, pressed into cakes, dried, and powdered. The powder is then mixed with various other substances to produce different shades of blue and purple.

Natural sources of indigo also include mollusks: the Murex genus of sea snails produces a mixture of indigo and 6,6'-dibromoindigo (red), which together produce a range of purple hues known as Tyrian purple. Light exposure during part of the dyeing process can convert the dibromoindigo into indigo, resulting in blue hues known as royal blue, hyacinth purple, or tekhelet.

Chemical synthesis
Given its economic importance, indigo has been prepared by many methods. The Baeyer–Drewsen indigo synthesis dates back to 1882. It involves an aldol condensation of o-nitrobenzaldehyde with acetone, followed by cyclization and oxidative dimerization to indigo. This route was highly useful for obtaining indigo and many of its derivatives on the laboratory scale, but proved impractical for industrial-scale synthesis. Johannes Pfleger and Karl Heumann eventually came up with industrial mass production synthesis from aniline by using mercury as a catalyst. The method was discovered by an accident by Karl Heumann in Zurich which involved a broken thermometer.

The first commercially practical route of producing indigo is credited to Pfleger in 1901. In this process, N-phenylglycine is treated with a molten mixture of sodium hydroxide, potassium hydroxide, and sodamide. This highly sensitive melt produces indoxyl, which is subsequently oxidized in air to form indigo. Variations of this method are still in use today. An alternative and also viable route to indigo is credited to Heumann in 1897. It involves heating N-(2-carboxyphenyl)glycine to 200 °C in an inert atmosphere with sodium hydroxide. The process is easier than the Pfleger method, but the precursors are more expensive. Indoxyl-2-carboxylic acid is generated. This material readily decarboxylates to give indoxyl, which oxidizes in air to form indigo. The preparation of indigo dye is practised in college laboratory classes according to the original Baeyer-Drewsen route.

History

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Indigo versus woad

In Europe, Isatis tinctoria, or woad, had been the main source of indigo dye, and the most readily-available source; the plant was processed into a paste called pastel. This industry was threatened in the 15th century by the arrival from India of the same dye (indigo), obtained from a shrub widely grown in Asia, Indigofera tinctoria. The plant produced indigo dye in greater and more colourfast quantities than woad, making its introduction a major source of competition for European-produced indigo dye.

In 1498, Vasco da Gama opened a trade route to import indigo from India to Europe. In India, the indigo leaves were soaked in water, fermented, pressed into cakes, dried into bricks, then carried to the ports London, Marseille, Genoa, and Bruges. Later, in the 17th century, the British, Spanish, and Dutch established indigo plantations in Jamaica, South Carolina, the Virgin Islands and South America, and began to import American indigo to Europe. Countries with large and prosperous pastel industries attempted to block the import and use of indigo; one government in Germany outlawed the use of indigo in 1577, describing it as a "pernicious, deceitful and corrosive substance, the Devil's dye." In France, Henry IV, in an edict of 1609, forbade under pain of death the use of "the false and pernicious Indian drug". It was forbidden in England until 1611, when British traders established their own indigo industry in India and began to import it into Europe.

The efforts to block indigo were in vain; the quality of indigo blue was too high and the price too low for pastel made from woad to compete. In 1737, both the French and German governments finally allowed the use of indigo. This ruined the dye industries in Toulouse and the other cities that produced pastel, but created a thriving new indigo commerce to seaports such as Bordeaux, Nantes and Marseille.

Another war of the blues took place at the end of the 19th century, between indigo and synthetic indigo, discovered in 1868 by the German chemist Johann Friedrich Wilhelm Adolf von Baeyer. The German chemical firm BASF put the new dye on the market in 1897, in direct competition with the British-run indigo industry in India, which produced most of the world's indigo. In 1897 Britain sold ten thousand tons of natural indigo on the world market, while BASF sold six hundred tons of synthetic indigo. The British industry took measures to ensure their economic viability with the new BASF dye, but it was unable to compete; the synthetic indigo was more pure, made a more lasting blue, and was not dependent upon good or bad harvests. In 1911, India sold only 660 tons of natural indigo, while BASF sold 22,000 tons of synthetic indigo. In 2002, more than 38,000 tons of synthetic indigo was produced, often for the production of blue jeans.

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The oldest known fabric dyed indigo, dated to 6,000 years ago, was discovered in Huaca Prieta, Peru. Many Asian countries, such as India, China, Japan, and Southeast Asian nations have used indigo as a dye (particularly for silk) for centuries. The dye was also known to ancient civilizations in Mesopotamia, Egypt, Britain, Mesoamerica, Peru, Iran, and West Africa. Indigo was also cultivated in India, which was also the earliest major center for its production and processing. The Indigofera tinctoria species was domesticated in India. Indigo, used as a dye, made its way to the Greeks and the Romans, where it was valued as a luxury product.

In Mesopotamia, a neo-Babylonian cuneiform tablet of the seventh century BC gives a recipe for the dyeing of wool, where lapis-colored wool (uqnatu) is produced by repeated immersion and airing of the cloth. Indigo was most probably imported from India. The Romans used indigo as a pigment for painting and for medicinal and cosmetic purposes. It was a luxury item imported to the Mediterranean from India by Arab merchants.

India was a primary supplier of indigo to Europe as early as the Greco-Roman era. The association of India with indigo is reflected in the Greek word for the dye, indikón (Ἰνδικόν, Indian). The Romans latinized the term to indicum, which passed into Italian dialect and eventually into English as the word indigo.

In Bengal indigo cultivators revolted against exploitative working conditions created by European merchants and planters in what became known as the Indigo revolt in 1859. The Bengali play Nil Darpan by Indian playwright Dinabandhu Mitra was a fictionalized retelling of the revolt.

The demand for indigo in the 19th century is indicated by the fact that in 1897, 7000 sqkm were dedicated to the cultivation of indican-producing plants, mainly in India. By comparison, the country of Luxembourg is 2,586 sqkm.

In Europe, indigo remained a rare commodity throughout the Middle Ages. A chemically identical dye derived from the woad plant (Isatis tinctoria) was used instead. In the late 15th century, the Portuguese explorer Vasco da Gama discovered a sea route to India. This led to the establishment of direct trade with India, the Spice Islands, China, and Japan. Importers could now avoid the heavy duties imposed by Persian, Levantine, and Greek middlemen and the lengthy and dangerous land routes which had previously been used. Consequently, the importation and use of indigo in Europe rose significantly. Much European indigo from Asia arrived through ports in Portugal, the Netherlands, and England. Many indigo plantations were established by European powers in tropical climates. Spain imported the dye from its colonies in Central and South America, and it was a major crop in Haiti and Jamaica, with much or all of the labor performed by enslaved Africans and African Americans. In the Spanish colonial era, intensive production of indigo for the world market in the region of modern El Salvador entailed such unhealthy conditions that the local indigenous population, forced to labor in pestilential conditions, was decimated. Indigo plantations also thrived in the Virgin Islands. However, France and Germany outlawed imported indigo in the 16th century to protect the local woad dye industry. In central Europe, indigo resist dyeing is a centuries-old skill that has received UNESCO Intangible Cultural Heritage of Humanity recognition.

Newton used "indigo" to describe one of the two new primary colors he added to the five he had originally named, in his revised account of the rainbow in Lectiones Opticae of 1675.

Because of its high value as a trading commodity, indigo was often referred to as blue gold.

Throughout West Africa, Indigo was the foundation of centuries-old textile traditions. From the Tuareg nomads of the Sahara to Cameroon, clothes dyed with indigo signified wealth. Women dyed the cloth in most areas, with the Yoruba of Nigeria and the Mandinka of Mali particularly well known for their expertise. Among the Hausa male dyers, working at communal dye pits was the basis of the wealth of the ancient city of Kano, and they can still be seen plying their trade today at the same pits. The Tuareg are sometimes called the "Blue People" because the indigo pigment in the cloth of their traditional robes and turbans stained their skin dark blue.

In Japan, indigo became especially important during the Edo period. This was due to a growing textiles industry, and because commoners had been banned from wearing silk, leading to the increasing cultivation of cotton, and consequently indigo – one of the few substances that could dye it.

In North America, indigo was introduced into colonial South Carolina by Eliza Lucas, where it became the colony's second-most important cash crop (after rice). As a major export crop, indigo supported plantation slavery there. In the May and June 1755 issues of The Gentleman's Magazine, there appeared a detailed account of the cultivation of indigo, accompanied by drawings of necessary equipment and a prospective budget for starting such an operation, authored by South Carolina planter Charles Woodmason. It later appeared as a book. By 1775, indigo production in South Carolina exceeded 1,222,000 pounds. When Benjamin Franklin sailed to France in November 1776 to enlist France's support for the American Revolutionary War, 35 barrels of indigo were on board the Reprisal, the sale of which would help fund the war effort. In colonial North America, three commercially important species are found: the native I. caroliniana, and the introduced I. tinctoria and I. suffruticosa.

Synthetic development
In 1865 the German chemist Adolf von Baeyer began working on the synthesis of indigo. He described his first synthesis of indigo in 1878 (from isatin) and a second synthesis in 1880 (from 2-nitrobenzaldehyde). (It was not until 1883 that Baeyer finally determined the structure of indigo. ) The synthesis of indigo remained impractical, so the search for alternative starting materials at Badische Anilin- und Soda-Fabrik (BASF) and Hoechst continued. Johannes Pfleger and Karl Heumann eventually came up with industrial mass production synthesis.

The synthesis of N-(2-carboxyphenyl)glycine from the easy to obtain aniline provided a new and economically attractive route. BASF developed a commercially feasible manufacturing process that was in use by 1897, at which time 19,000 tons of indigo were being produced from plant sources. This had dropped to 1,000 tons by 1914 and continued to contract. By 2011, 50,000 tons of synthetic indigo were being produced worldwide.

Indigo white
Indigo is a challenging dye because it is not soluble in water. To be dissolved, it must undergo a chemical change (reduction). Reduction converts indigo into "white indigo" (leuco-indigo). When a submerged fabric is removed from the dyebath, the white indigo quickly combines with oxygen in the air and reverts to the insoluble, intensely colored indigo. When it first became widely available in Europe in the 16th century, European dyers and printers struggled with indigo because of this distinctive property. It also required several chemical manipulations, some involving toxic materials, and presented many opportunities to injure workers. In the 19th century, English poet William Wordsworth referred to the plight of indigo dye workers of his hometown of Cockermouth in his autobiographical poem The Prelude. Speaking of their dire working conditions and the empathy that he felt for them, he wrote: Doubtless, I should have then made common cause With some who perished; haply perished too A poor mistaken and bewildered offering Unknown to those bare souls of miller blue

A pre-industrial process for production of indigo white, used in Europe, was to dissolve the indigo in stale urine, which contains ammonia. A more convenient reductive agent is zinc. Another pre-industrial method, used in Japan, was to dissolve the indigo in a heated vat in which a culture of thermophilic, anaerobic bacteria was maintained. Some species of such bacteria generate hydrogen as a metabolic product, which convert insoluble indigo into soluble indigo white. Cloth dyed in such a vat was decorated with the techniques of shibori (tie-dye), kasuri, katazome, and tsutsugaki. Examples of clothing and banners dyed with these techniques can be seen in the works of Hokusai and other artists.

Direct printing
Two different methods for the direct application of indigo were developed in England in the 18th century and remained in use well into the 19th century. The first method, known as 'pencil blue' because it was most often applied by pencil or brush, could be used to achieve dark hues. Arsenic trisulfide and a thickener were added to the indigo vat. The arsenic compound delayed the oxidation of the indigo long enough to paint the dye onto fabrics.

The second method was known as 'China blue' due to its resemblance to Chinese blue-and-white porcelain. Instead of using an indigo solution directly, the process involved printing the insoluble form of indigo onto the fabric. The indigo was then reduced in a sequence of baths of iron(II) sulfate, with air oxidation between each immersion. The China blue process could make sharp designs, but it could not produce the dark hues possible with the pencil blue method.

Around 1880, the 'glucose process' was developed. It finally enabled the direct printing of indigo onto fabric and could produce inexpensive dark indigo prints unattainable with the China blue method.

Since 2004, freeze-dried indigo, or instant indigo, has become available. In this method, the indigo has already been reduced, and then freeze-dried into a crystal. The crystals are added to warm water to create the dye pot. As in a standard indigo dye pot, care has to be taken to avoid mixing in oxygen. Freeze-dried indigo is simple to use, and the crystals can be stored indefinitely as long as they are not exposed to moisture.

Chemical properties
Indigo dye is a dark blue crystalline powder that sublimes at 390 –. It is insoluble in water, alcohol, or ether, but soluble in DMSO, chloroform, nitrobenzene, and concentrated sulfuric acid. The chemical formula of indigo is C16H10N2O2.

The molecule absorbs light in the orange part of the spectrum (λmax=613 nm). The compound owes its deep color to the conjugation of the double bonds, i.e. the double bonds within the molecule are adjacent and the molecule is planar. In indigo white, the conjugation is interrupted because the molecule is non-planar.

Indigo derivatives
The benzene rings in indigo can be modified to give a variety of related dyestuffs. Thioindigo, where the two NH groups are replaced by S atoms, is deep red. Tyrian purple is a dull purple dye that is secreted by a common Mediterranean snail. It was highly prized in antiquity. In 1909, its structure was shown to be 6,6'-dibromoindigo (red). 6-bromoindigo (purple) is a component as well. It has never been produced on a commercial basis. The related Ciba blue (5,7,5',7'-tetrabromoindigo) is, however, of commercial value.

Indigo and its derivatives featuring intra- and intermolecular hydrogen bonding have very low solubility in organic solvents. They can be made soluble using transient protecting groups such as the tBOC group, which suppresses intermolecular bonding. Heating of the tBOC indigo results in efficient thermal deprotection and regeneration of the parent H-bonded pigment.

Treatment with sulfuric acid converts indigo into a blue-green derivative called indigo carmine (sulfonated indigo). It became available in the mid-18th century. It is used as a colorant for food, pharmaceuticals, and cosmetics.

Indigo as an organic semiconductor
Indigo and some of its derivatives are known to be ambipolar organic semiconductors when deposited as thin films by vacuum evaporation.

Safety and the environment
Indigo has a low oral toxicity, with an of 5 g/kg (0.5% of total mass) in mammals. In 2009, large spills of blue dyes had been reported downstream of a blue jeans manufacturer in Lesotho.

The compound has been found to act as an agonist of the aryl hydrocarbon receptor.

title: Indigo dye