New medicines: you can't do without animal experiments
Inhuman suffering for the sake of healthViola Brick, Telegraph "Around the World"
To create a new drug, pharmacists take years of persistent searches, and testing of the resulting drug plays an important role in them.
Conducting research on animals is an integral part of the work of a modern laboratory, whether it is a state university or a private research company. It is quite difficult to name exact figures, but approximately 50-100 million mammals are involved in experiments annually. Animals are used in drug trials and new treatment methods, testing cosmetics and household chemicals for toxicity, as well as in the name of space and other fundamental research.
Conduct experiments on animals to better understand how humans work,
they started back in ancient Greece.
From the illustrations to the collection of Galen 's works
Scientific activity with the use of model animal organisms is a stumbling block between humanitarian organizations and those who are in a hurry to move medicine forward. What are the advantages of research on laboratory animals and to what extent can the data obtained on mice and flies be applicable to humans?
The history of the first experiments on animals began in Ancient Greece, in the IV–III centuries BC. Aristotle (aριστοτέλης, 384-322 BC) used animals to conduct the simplest experiments. Galen (γαληνός,129/131-approx.200) performed autopsies of pigs and goats, for which he was nicknamed the "father of vivisection". At the end of the XIX century, Louis Pasteur (1822-1895) experimented on sheep infected with anthrax. A century later, dogs, newts and monkeys were the first to visit space.
Today, the most common laboratory object is a rat (Rattus norvegicus). About two hundred lines of rats have been bred for scientific experiments. For example, a line of rats with spontaneous hypertension (spontaneous hypertensive rats, SHR), known since the 1960s, is valuable for studying high blood pressure. To derive the line, scientists used rats prone to hypertension. According to the description that is attached to the animals, these rats begin to show signs of hypertension as early as the fifth or sixth week from birth. In adult rats, the pressure reaches 180-200 mm Hg, which corresponds to the definition of hypertension in humans. By adulthood, SHR rats already have all the signs of cardiovascular pathology - for example, they suffer from hypertrophy of the heart. Based on the SHR line, a line of rats was obtained that suffer from hypertension and often die from a stroke.
In addition to rats with hypertension, there are, for example, epileptic rats. Such animals are characterized by increased excitability of the nervous system and weak activity of inhibitory neurons. A sharp sound (such as a bell or the bang of a bunch of keys on the floor) instantly puts the rat's brain into a stage of hyperexcitation. As a result, the animal experiences an epileptic seizure. Lines of rats with certain diseases serve as good models for studying the mechanism of disease, development and testing of new drugs.
10% of the ratThe rat genome has up to 90% similarity with the genome of Homo sapiens, only 10% of the genes separate us from the rat.
However, this is a very big difference. For example, rats have a much stronger system of toxin disposal than humans, protecting the body from poisons. No wonder it's so hard to get rid of rats: these animals are often insensitive to poisons and quickly develop resistance to new toxic substances. That is why drugs recognized as safe in experiments on rats need further testing already on humans.
Since the mid-70s of the last century, the popularity of the laboratory rat began to give way to mice. It is more convenient to carry out genetic manipulations on a small object: less drug is required and the reproductive cycle is shorter. It is not surprising that mice were the first transgenic animals. In 1974, Rudolf Jaenisch implanted someone else's DNA (the gene of the monkey virus SV40) into mouse embryos, becoming a pioneer in the field of obtaining transgenic animals.
To date, there are several hundred lines of genetically modified mice. For example, the deletion of one of the genes (KCNMB1) encoding a regulatory subunit in the potassium ion channel leads to the development of hypertension in mice. By its origin, such hypertension is different from the disease in SHR rats and serves as another model of the disease.
Since hypertension in humans can have several causes, studies on mice and rats complement each other. In addition to erasing genes from the genome (genetic knockout technique), new genes are implanted in mice. This is how the APP (APP) transgenic mice were obtained. The abbreviation APP comes from "amyloid protein precursor". This precursor gives rise to the protein that causes Alzheimer's disease. The gene for Alzheimer's disease, obtained from a Swedish family suffering from this disease, was implanted in transgenic mice. Transgenic mice have impaired neuronal functions, animals suffer from a lack of memory, do not adapt well to new conditions, but they serve as a good model for studying sclerosis and testing drugs that strengthen memory.
In addition to rats and mice, other rodents — rabbits - are actively used in laboratories. It is convenient to conduct experiments on them that require surgical interventions. For example, the study of the secretion of yolk juice, bile secretion. Quite large, rabbits are well suited for performing educational tasks by biology students.
Pigs and stressObviously, rodents are still far from humans in many ways.
From the point of view of physiology, pigs are a much more attractive laboratory object. The discovery of the mechanism of one of the deadly diseases — malignant hyperthermia — occurred precisely thanks to the pig family.
Malignant hyperthermia was originally described in humans. In rare cases, people under surgical anesthesia experience an increase in body temperature and convulsions that end in the death of the patient. For several decades, studies of malignant hyperthermia have not progressed due to the lack of a model organism.
Only in the second half of the twentieth century was the "porcine stress syndrome" discovered. The meat of such animals becomes soft, pale, very soft. Such a product does not find demand in the grocery market, so farmers began to get rid of animals suffering from this syndrome. To isolate sick pigs, farmers gave piglets halothane gas — the basis of surgical anesthesia. Piglets suffering from the disease died. During the study of such piglets, a mutation was described in the gene of the intracellular channel — the ryanodine receptor, which became the cause of death in response to halothane.
Based on a genetic discovery in pigs, a similar mutation in the ryanodine receptor gene was described in humans, and after it a drug was obtained to prevent the development of malignant hyperthermia — dantrolene. Interestingly, horses also suffer from malignant hyperthermia, but for obvious reasons horses are not used to study the fundamentals of diseases and drug testing. They are too big, expensive, and also occupy a place too close to a person in culture.
Adult pigs also turn out to be too expensive laboratory animals, but for many experiments it is enough to use piglets. For example, they are convenient for conducting studies of the blood circulation of the brain, changes in the diameter of blood vessels in response to the introduction of a vasoactive substance into the bloodstream. The size of the animal is enough to track the smallest changes in the diameter of the vessels.
If we consider not only physiological, but also psychological indicators, then humanoid monkeys — chimpanzees, gorillas, orangutans - are as close as possible to Homo sapiens. These animals are used to study higher mental functions, personality development, teaching methods, etc. But monkeys have recently become real "stars". In May 2009, the world's leading scientific journal Nature published the work of Japanese scientists led by Dr. Erika Sasaki from the Central Institute of Experimental Animals in Kawasaki (Central Institute of Experimental Animals), during which transgenic monkeys were obtained.
With the help of a special virus, the gene of green fluorescent protein (GFP) was delivered to the monkey embryos. This protein is derived from the marine jellyfish Aequorea Victoria, which fluoresces under ultraviolet rays. The embryos were introduced into the womb of surrogate mothers. In laboratory practice, GFP is used to track the on-off operation of genes. As a result, five healthy monkeys were born with fluorescence of some parts of the body under the influence of ultraviolet radiation: the skin and bones of animals glow green.
Monkeys were chosen as the subject of experiments due to their short reproductive cycle. In the near future, scientists plan to introduce the GFP gene selectively into the nervous system. Thus, it will be possible to track neurodegenerative processes on monkeys.
Blind fish and drunken wormsIn addition to warm-blooded animals, cold-blooded ones are widely used in laboratory practice: frogs and fish.
Thus, oocytes of spur frogs (Xenopus laevis) are used for protein expression. RNA is injected into oocytes using a syringe. After two to three days after injection, the product encoded in RNA appears in the oocyte membrane. Thus, for example, human ion channels are expressed to study their electrophysiological and pharmacological properties. Initial screening of pharmacological substances can be carried out on oocytes to modulate (block or, conversely, activate) ion channels. Frogs themselves have become a popular object in developmental biology: for example, Nobel laureate Roger Wolcott Sperry (1913-1994) used Xenopus laevis to discover the fundamental chemical basis in the development of the visual system.
Fish are also popular for studying the visual system. The small size and short reproductive cycle of zebrafish allow for a lot of experiments with minimal costs. Genetic mutations in fish are used to model diseases such as retinitis pigmentosa and macular degeneration of the retina.
The study of human activity is possible with the help of not only vertebrates, but also those that are indisputably far from Homo sapiens. So, Professor Janis O'Donnell from the University of Alabama studies Parkinson's disease using fruit flies as an object. Parkinson's disease manifests itself in people in the form of impaired coordination of movements, inability to make precise movement, inability to control motor function. It turned out that the flies suffer from similar disorders.
During the study, Dr. O'Donnell was able to identify several genes that are involved in the functioning of the dopamine system — the basis of movement in both flies and humans. Thus, scientists have obtained a simple, easy-to-control model for studying a complex disease. The first experiments showed that chemicals used in agriculture are similar in structure to dopamine, so they can "deceive" genes and lead to the development of a motor disorder.
An even more interesting object is worms. Usually roundworms Caenorhabditis elegans are used. This worm became the first mngocellular organism whose genome was completely decoded. Scientists from the University of Liverpool, led by Professor Bob Burgoyne, are using C. elegans to identify genes that play a role in alcohol addiction. After these genes are identified in worms, scientists are searching for similar genes in humans.
The group of Steve McIntire from the University of California in San Francisco also studied worms - the genetic characteristics of some develop their resistance to alcohol. Even after receiving a dose of alcohol, which by human standards would lead him to intoxication, the worms remain "sober". Scientists have suggested that the slo-1 gene is to blame for this. If this gene "does not work" as it should, alcohol does not give any effect. At the same time, worms with an overactive slo-1 gene, even if they have not received alcohol, behave like drunks.
The most exotic laboratory object is the brewing yeast Saccharomyces cerevisiae. A group of scientists from the University of North Carolina (University of North Carolina), led by Jason Lieb, uses yeast to study the fundamentals of carcinogenesis, that is, the process of tumor formation. Since yeast has a relatively simple genome and reproduces quickly, scientists are able to track changes in the structure of DNA caused by various external factors. Of course, the results of such experiments require confirmation on more complex organisms.
Despite the apparent diversity of laboratory animals, any of the existing models has its limitations and can only partially replace the real human body. By putting together the data obtained at different objects, one can only get closer to the real picture, being surprised at how complex and multifaceted the regulatory mechanisms of vital activity are.
Animals for laboratory experiments are bred by special organizations. They monitor the genetic purity of the lines (so that, for example, genetically modified animals are really all genetically modified). The same companies supply animals to laboratories. All universities and private companies have special commissions for the protection of animal rights.
To get permission to conduct experiments on animals,
it is necessary to undergo special training — in the USA, for example,
it is necessary to pass a mandatory exam on working with laboratory animals.
Photo: Army Medical School/Selected by Kathleen
The veterinarian, who is part of the commission, reviews all experimental protocols, all surgical procedures to make sure that the animals do not suffer, do not experience unnecessary discomfort or fear. If the laboratory violates the protocol and performs an operation that was not agreed in advance, then the manager faces punishment. During the experiments, the animals are kept in specially designated rooms with appropriate ventilation, nutrition, and access to water. At the end of the experiments, the animals are usually euthanized.
The question of the ineffectiveness of animal experiments, their uselessness for science and cruelty is being raised by many organizations today. The question of the fate of animals after the experiments is particularly controversial. Every year, the movement against vivisection, aimed at modernizing experimental science and finding an alternative, is gaining more and more strength, but for now animal experiments remain one of the most important links in the pharmaceutical chain.
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12.10.2009