ALTERNATIVES
The Three R's
Applied research aims to solve specific and practical problems.
In Silico
Right now, millions of rats, rabbits, cats, dogs, and other animals are locked inside cages.
Microdosing
More than 630,000 people signed a petition organized by the company.
Computer Simulators
More than 630,000 people signed a petition organized by the company.
The Three R's
The Three Rs (3Rs) in relation to science are guiding principles for more ethical use of animals in testing.
They were first described by W. M. S. Russell and R. L. Burch in 1959. The 3Rs are:
Replacement: methods which avoid or replace the use of animals in research
Reduction: use of methods that enable researchers to obtain comparable levels of information from fewer animals, or to obtain more information from the same number of animals.
Refinement: use of methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals used.
The 3Rs have a broader scope than simply encouraging alternatives to animal testing, but aim to improve animal welfare and scientific quality where the use of animals cannot be avoided. In many countries, these 3Rs are now explicit in legislation governing animal use.
It is usual to capitalise the first letter of each of the three 'R' principles (i.e. 'Replacement' rather than 'replacement') to avoid ambiguity and clarify reference to the 3Rs principles.
In Silico
In biology and other experimental sciences, an in silico experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for "in silicon", referring to silicon in computer chips. It was coined in 1987 as an allusion to the Latin phrases in vivo, in vitro, and in situ, which are commonly used in biology (especially systems biology). The latter phrases refer, respectively, to experiments done in living organisms, outside living organisms, and where they are found in nature.In silico study in medicine is thought to have the potential to speed the rate of discovery while reducing the need for expensive lab work and clinical trials. One way to achieve this is by producing and screening drug candidates more effectively. In 2010, for example, using the protein docking algorithm EADock (see Protein-ligand docking), researchers found potential inhibitors to an enzyme associated with cancer activity in silico. Fifty percent of the molecules were later shown to be active inhibitors in vitro. This approach differs from use of expensive high-throughput screening (HTS) robotic labs to physically test thousands of diverse compounds a day often with an expected hit rate on the order of 1% or less with still fewer expected to be real leads following further testing (see drug discovery).As an example, the technique was utilized for a drug repurposing study in order to search for potential cures for COVID-19 (SARS-CoV-2).
Microdosing
Another alternative is so-called microdosing, in which the basic behaviour of drugs is assessed using human volunteers receiving doses well below those expected to produce whole-body effects. While microdosing produces important information about pharmacokinetics and pharmacodynamics it does not reveal information about toxicity or toxicology. Furthermore, it was noted by the Fund for the Replacement of Animals in Medical Experiments that despite the use of microdosing, "animal studies will still be required". A more recent development, microdosing, puts experimental studies back into the bodies of human volunteers. It uses drug doses too small to create either a pharmacological effect or an adverse reaction and has been made possible by analytical methods that can detect substances in blood and plasma at concentrations in the pg/ml range. As Malcolm Rowland of the University of Manchester graphically put it, the technology has “the ability to detect a liquid compound even after one litre of it has been dissolved in the entire oceans of the world. The most recent report on animal testing, from a group chaired by Sir David Weatherall, had little to add to the debate about non-animal alternatives.4 Set up to consider the value and ethics of non-human primates in research, it concluded that there is a case for their careful and meticulously regulated use, “provided it is the only way of solving important scientific or medical questions and high standards of welfare are maintained.” This is an issue that divides even those who otherwise accept the use of animals.
Computer Simulators
With the growing sophistication of computers, the ability to ‘model’ or replicate aspects of the human body is ever more possible. Computer models of the heart, lungs, kidneys, skin, digestive and musculoskeletal systems already exist. They can be used to conduct virtual experiments based on existing information and mathematical data. Researchers from the University of Oxford (UK) have developed computer simulations that are able to outperform animal models in drug trials to predict the clinical risk of drug-induced arrhythmias. The group were able to test a new cardiac drug in a virtual human for adverse side effects with an accuracy of 89–96%. The results, published in Frontiers in Physiology, demonstrate the advantages of using computer simulations over animal models in early drug trials, and the improvements these approaches can make to drug safety. Using animal models to test new drugs is a crucial component of almost every drug trial. It allows researchers to assess the performance of the drug in living systems. However, despite their many genetic and physiological similarities, drugs perform differently in humans than they do in animal models, such as mice. Utilizing animal models is also expensive and time consuming, not to mention the growing moral objection to their use.