From algorithm to mini organ: Will future animal experiments be replaced?

Sina Technology News Beijing time on May 9th news, according to foreign media reports, in 1980, "New York Times" published a full-page advertisement from the animal rights organization, its content is to attack a well-known cosmetics company to test on the rabbit's eyes product. The campaign achieved remarkable results, which ultimately led several beauty companies to commit hundreds of thousands of dollars to find alternative test methods that do not involve animals.

What alternatives have we found in nearly 40 years? How much progress has these methods made?

Before we delve into the answers to these questions, we need to understand an important difference: although “animal experiments” are often reminiscent of cosmetic companies’ cruel experiments with cute animals such as rabbits – in the name of pursuing beauty, animals are in science. Applications in research (including research looking for alternatives) have gone far beyond the cosmetics industry. Animals such as mice and rats are widely used in toxicology to study chemicals and their effects on humans. Animals are also the key to drug discovery and testing. In biomedical research, animal models are the basis of many experiments through which researchers study countless scientific issues ranging from brain circuit function to cell disease progression.

Although experimental animals are important in these areas, many are working to reduce their use in experiments. To a certain extent, this is because the ethical concerns of different countries have driven new legislation, but on the other hand it depends on money and time.

“In theory, non-animal experiments can be cheaper and faster,” said Warren Casey, director of the Inter-Departmental Assessment Center for Alternative Toxicology at the National Toxicology Program in the United States. The agency he led analyzed a variety of methods to replace chemical safety testing animals.

Another concern with experimental animals is that in some types of research, the difference between animals and humans is so great that they cannot successfully predict the effects of certain products on our bodies. Kathy said in an interview: "So we are involved in issues of ethics, efficiency and human relevance."

So what is the most promising option at the moment?

Ubiquitous data

One way is to replace the animal with an algorithm. Researchers are developing computational models to predict the impact of certain products on organisms by processing large amounts of research data.

Zhu Hao, a professor of chemistry at Rutgers University in the United States, said that this is a very promising method and very cheap. His research team has developed a high-speed algorithm that extracts large amounts of information from online chemical databases and compares thousands of tested compounds to untested new compounds by identifying structural similarities between them. . The algorithm then uses the toxicity of the compounds tested to make reliable predictions of the toxicity of untested compounds with similar structures (assuming the same structure means that the compounds have similar effects).

Often, determining the effectiveness of a new compound requires dozens of expensive and time-consuming animal experiments, and by such an algorithm, we can reduce the number of animal studies required. “If we can prove that the compounds that we want to put on the market are safe, then we can think that such research can replace the current animal research,” Professor Zhu Hao said. A similar study by researchers at Johns Hopkins University in Maryland showed that the algorithm might even be superior to animal experiments in predicting the toxicity of multiple compounds.

Microorgan

In recent years, scientists have begun to culture human cells on stents implanted in plastic chips to form tiny structures that mimic the functions of the heart, liver, kidneys and lungs. These structures, called "on-chip organs," can serve as a new way to test the effects of new or new drugs on human cells.

Testing these simplified, miniaturized human physiology models can yield human-related results more than animal experiments. Crucially, during the exploration phase of early research, when the scientist did not need to test the entire system, the test also avoided the use of the entire animal. Warren Casey said that "the organ on the chip" largely solves the problem of a single output or terminal, because all the work that may need to be done at this early stage is to test a certain cell type for a drug or disease. Reactions to guide future research.

Florian Schmieder, a researcher at the Fraunhofer Institute for Materials and Beam Technology in Germany, said that this approach may "in most cases help reduce the number of projects being carried out by researchers. The number of planned animal trials." In addition to the lungs, liver and heart, some companies are developing artificial 3D structures that mimic human skin. This is especially important in toxicology. Animal skin testing has long been the basis for understanding the effects of untested new compounds in toxicology.

Using this harmless skin tissue model to replace animal skin testing has become a reality, says Casey. "Research has proven that skin tissue models are very effective. They give us insight into acute changes, such as whether something can corrode and damage the skin. ""

Human research

There is often a suggestion against animal experiments: If humans want to benefit from new therapies, drugs, and research, then we should treat ourselves as subjects. This is a very simplified and extreme point of view. In most countries, the law requires that animal experiments be performed prior to administration to humans. Therefore, this view is not necessarily true.

However, there are some well-controlled forms of human experimentation that do have the potential to reduce the use of animals without harming human health. One such method is microdosing. In this method, the amount of a new drug received by the human body is so small that it does not produce a wide range of physiological effects, but there are enough cycles in the system to measure its effect on individual cells.

The researchers' idea is that this cautious approach can help eliminate infeasible drugs at an early stage, without using thousands of animals in the study, and ultimately only prove that the drug does not work. This approach has proven to be safe and effective, and many large pharmaceutical companies are using microdosing methods to simplify drug development.

“Of course there are ethical concerns, but these concerns can easily be offset by the potential benefits of safer, more effective drugs being brought to market,” Casey said.

How is the progress now?

So what do these alternatives mean for the future of animal experiments? In some research areas, such as cosmetic testing—many existing products have proven safe through animal experiments—people are increasingly recognizing that testing new products is not necessary to drive the industry. This is confirmed by the EU's regulatory regulations, which now prohibit animal testing of any cosmetics produced and sold in the EU.

We have also seen progress in toxicology research. Toxicologists have long relied on six core animal experiments to screen for the acute toxicity of new products, whether they cause skin irritation, eye damage or death. However, Casey said that in the next two years, these baseline tests are likely to be replaced by non-animal experiments in the United States. The reason for this progress is that “the biological basis of these types of toxicity is much simpler than other safety issues that may arise after long-term exposure to certain chemicals (eg cancer or reproductive toxicity),” Kay Said West.

But in other areas of research, the concerns of researchers are more complex, and animal models remain the only way we can now fully understand the wide and long-term effects of compounds, drugs, or diseases. Kathy said: "Physiology is very, very complicated, we still have not mastered it." In addition to animal models, there is no other way to properly simulate human physiology.

Even promising advances like "organs on the chip" have a long way to go before presenting an interconnected human body. “The main problem in developing an artificial organ system is to obtain the full complexity of the organism in vitro,” Schmid said. “The key to the problem is to simulate the dynamics and dynamics of the human body in a truly predictable way.”

While on-chip organs and other inventions may help answer simpler questions, at present, whole-animal models are the only way to study more complex effects, such as studies that relate how brain circuits function to visible behavior. Such problems help us understand human diseases and ultimately lead to life-saving treatments. Therefore, animal experiments that support these findings remain crucial.

It's also worth noting that some of the most promising non-animal experimental methods we've done today, such as algorithmic predictions, work because they can draw on decades of animal research. In order to achieve further results in the future, we need to continue these studies.

“We can't completely replace animal experiments with computers. We still need some low-level animal experiments to generate the necessary data,” Zhu Hao said. “If you let me vote for a promising approach, I will vote for calculations and experiments. A combined approach."

So, apart from animal experiments, do we have other options? The answer is both positive and negative. Although we have several options, they are not mature enough to completely replace animal experiments. However, it is vital that these can reduce the number of animals we use for research. With new regulations and smarter choices, we can at least hope for the future, and the number of experimental animals will continue to decline. (任天)

Source: Sina Technology

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