Experimental cell cultures
A new method of testing drugs for safety
These drugs entered the markets of different countries in the mid-50s under different names – for example, in Germany the drug was called "kontergan", in the UK – "distoval", etc. The manufacturer, the Grunenthal company, emphasized that the drugs are completely safe and do not cause adverse reactions, and therefore are the best sleeping pills for pregnant women.
However, it soon turned out that thalidomide has a strong teratogenic effect, that is, it causes fetal development disorders. Tens of thousands of women who took kontergan and its analogues in the early stages of pregnancy had children with various, sometimes extremely severe, defects and deformities, about forty percent of these children died in the first year of life.
Experiments on humans preceded experiments on animalsAs it turned out later, the thalidomide molecule, while maintaining the constancy of its chemical composition, can exist in two stereoisomeric forms, two spatial configurations, and one of them causes a therapeutic, and the other a teratogenic effect.
Then the idea was put forward to make a drug consisting of one purified isomer, but it turned out that this would not solve the problem, since in the body one isomeric form of thalidomide easily passes into another.
Be that as it may, the "konterganov scandal" became possible only because the requirements imposed at that time on licensed drugs were not strict enough. As one of the experts put it in the late 60s during the trial of the claims of the victims of kontergan to the Grunenthal company, "in the case of thalidomide, experiments on humans preceded the study of the drug in animal experiments."
Different animals react differentlyIndeed, experiments on animals – specifically, on pregnant rats – were carried out by the manufacturer of the drug after he was forced to withdraw his product from the market.
But kontergan did not cause any anomalies, not to mention severe deformities, in the rat litter. And only experiments carried out by British researchers six months later and on another model organism – a white New Zealand rabbit – finally confirmed the teratogenic property of thalidomide.
It turned out that biologically active substances can cause completely different reactions in different experimental animals, which naturally makes it difficult to assess their effectiveness and safety. Of course, after the contergan tragedy, many countries revised the rules for licensing medicines, significantly tightening the requirements for them.
The tightening of the procedure for the admission of medicines has hit the animalsToday there is a single admission procedure in Europe, and of course, it has become even stricter since then, says Kesavan Meganathan, a researcher at the Institute of Neurophysiology at the University of Cologne: "Any medicine, before it enters the market, must be tested on pregnant animals, and at least two different types".
The fact that millions of individuals of various laboratory animals are subjected to painful experiments from year to year does not in itself do honor to science. And most importantly, this does not solve the main problem: animal experiments cannot guarantee the safety of the drug for humans.
Since testing biologically active substances directly on humans, for obvious reasons, is out of the question, researchers are trying to develop an alternative methodology that, however, provides high reliability and reliability of the results.
One study – two important resultsBelieving that human embryonic stem cells could serve as an optimal model, Kesavan Meganatan decided, first of all, to study what effect thalidomide would have on the culture of such cells.
"It turned out that thalidomide changes the activity of almost a thousand genes that play an important role in the process of intrauterine development of the body. Among them are those that regulate the formation of limbs, and those that regulate the development of internal organs, in particular, the heart," the scientist explains.
This work yielded two important results: on the one hand, it allowed us to get a more detailed understanding of the mechanisms that cause fetal development disorders typical for contergan; on the other hand, it proved that the culture of embryonic stem cells can be used as a laboratory model for testing the safety of drugs.
The experimental animals had hope..."Of course, our technique will not be able to completely replace animal experiments," the researcher admits, "but it can significantly reduce their number.
Before starting animal testing, the company developing the new drug should try it on cell culture. And if the result of such a test is negative, animal experiments can not be started."
However, the use of embryonic stem cells for experimental purposes is by no means indisputable from an ethical point of view, because when they are obtained, the embryo dies. In Germany, this is prohibited by law, so Cologne scientists are working with imported cell cultures.
Testing of the new test method continuesBut it should be borne in mind that embryonic stem cells have the ability to divide indefinitely, while maintaining their pluripotency.
"It is not necessary to destroy the embryo every time, it is enough to do it once, and that's it! – explains Kesavan Meganatan. "Once such cells are extracted, they are cultured, and then stored in liquid nitrogen, extracting them from there and multiplying as needed."
Today, Cologne researchers continue their experiments, testing a variety of substances on embryonic stem cell cultures – both those that obviously have teratogenic properties, and those that are absolutely harmless. This is the only way scientists can find out how effective and reliable their proposed new method of testing medicines is.
Portal "Eternal youth" http://vechnayamolodost.ru25.01.2013