So that not a single mouse is harmed – Picture of the Day – Kommersant

For centuries, drugs were tested first on experimental animals, and then (or even bypassing the first stage) on volunteers. Such experiments have always been ethically controversial and not always effective. Scientists are now approaching a revolutionary solution to the problem.

According to Doctor Frankenstein

Tumoroids, organoids, organs on chips. These terms refer to microphysiological systems (MPS) – biotechnologies, the essence of which is the creation of tissues or even entire organs in the laboratory.

Tumoroids are laboratory-grown tissues that mimic malignant neoplasms. Organelles – multicellular structures created in the laboratory that mimic the histology and microphysiology of a particular organ or part of it. Organs on chips are compact devices that mimic the processes that occur with real tissues and organs in the body.

These promising technologies are in their infancy. But, for example, for the British startup Lift Biosciences, they have already become saving. Only with the help of tumoroids was the company able to prove to investors that its new drug is effective against cancer, writes Financial Times.

The company initially resorted to a traditional method in medicine for testing a new drug – on mice. However, the promising development of the company failed – the immune system of mice rejected the drug. And instead of the £20 million that the startup hoped to raise, investors offered only £5 million.

Perhaps the new drug would have been rejected if the chief researcher of the company, Oksana Polyakova, had not decided to test the drug with a tumoroid. The result of this test was the opposite of that in mice: the drug injected into the tumoroid “completely destroyed” the tumor.

As Alex Blyth, CEO of the startup, explains, the reason for the discrepancy in the results lies in the fact that the white blood cells of mice and humans react too differently to therapy. “The mouse simply does not understand this human language,” Mr. Blyth explained to reporters.

According to the latest data, tests on tumoroids with 80% accuracy can determine the effectiveness of a drug in humans. Animal testing is only 8 percent accurate.

In the case of rare diseases, animal experiments are practically impossible. “There are about 7 thousand rare diseases in the world, but only 400 of them are actively studied. Simply because there are no animal models for the rest, ”explains James Hickman, chief scientist at the American company Hesperos, which creates organs on chips.

The use of microphysiological systems will allow not only to reduce the number of experiments on animals, but to fill those niches where such tests are difficult, says Mr. Hickman.

Test on the Homunculus

Finally, animal testing has long been considered ethically dubious. Activists in many countries of the world are demanding (sometimes in a rather aggressive way) that companies and universities stop using “our smaller brothers” as test subjects.

However, switching to new technology is not easy. Microphysiological systems is still a very young scientific field. Researchers are only learning to create tissues and their environments that mimic the behavior of the human body as closely as possible. At the same time, the slightest inaccuracy can lead to incorrect results and possible serious consequences for future patients.

Based on this, regulators are not yet ready to accept the results of such trials as proof of the reliability and effectiveness of a drug. Pharmaceutical and biotechnology companies are still required to conduct several stages of experiments – first on animals, and then on humans.

In June 2022, the US Food and Drug Administration (FDA) considered changing this practice. So far, the American regulator is ready to accept MPS test results as basic drug tests only in exceptional cases. But the department is confident that new technologies, including MPS, are the future of medicine.

They, according to the regulator, can significantly reduce the cost of research and testing, as well as speed up the drug approval process. And as early as 2023, the FDA may start accepting MPS test results on a regular basis as part of clinical trials.

However, in parallel with MPS, scientists are looking for other ways to get away from traditional methods. So, in early August, Jacob Hanna from the Israeli company Renewal Bio published a scientific article about the successful creation of a full-fledged mouse embryo from stem cells. His lab was able to form embryos and keep them growing in a mechanical womb for several days. During this time, they developed beating hearts, flowing blood and creases in the skull.

“This is the first time that such an advanced embryo has been simulated without sperm, eggs, or even a uterus,” writes MIT Technology Review.

Hannah is currently working on a technology that will similarly enable stem cell-based human embryonic models to be grown to match the state of a natural embryo on day 40-50 of pregnancy.

At this stage, the main organs and limbs are already formed. These embryos will never become full-fledged people, the scientist explains. But they can be used in transplantology.

Forecasts about how soon it will be possible to grow such a human embryo, Jacob Hanna does not give. But the fact that he uses mostly his own skin cells and blood for experiments means that, if successful, Renewal Bio’s lab will fill with hundreds or even thousands of miniature copies of the scientist.

Kirill Sarkhanyants