Tools of the trade: Using cell and animal models to improve modern medicine

Rachel Burge
March 25, 2022
Chalkboard drawing of a steaming coffee and milk dispenser.
Chalkboard drawing of a steaming cup of coffee and a milk dispenser.

Editor’s note: The following series of stories highlights the contributions of basic science research to modern medicine. This is part three. Read part one here. Read part two here.

Throughout this series, we have learned that Basic Science is the foundation of modern medicine: the espresso of the modern medicine mocha. The strength of this foundation is rooted in the power of observation – curiosity drives scientists to continually ask “Why did this happen?”

But even the most observant scientist needs quality tools to conduct cutting-edge research, just like the barista behind the counter of your favorite coffee shop has a top-of-the-line tamper, distributor, milk pitcher, coffee grinder, and of course, espresso machine.

So, what tools do basic scientists use?

Depending on their field of study, scientists can use a wide-range of specific tools to learn more about how the universe works, such as: computer modeling, to predict how molecules interact or how the universe formed; questionnaires, to learn about the history and habits of people around the world; observational studies, to look into the outer limits of the universe (using telescopes) or the inner reaches of the cell (using microscopes).

But human beings are diverse and complex creatures, making the study of diseases difficult. So, how do scientists overcome that?

“Somewhere, something incredible is waiting to be known.”

-- Carl Sagan.

Black coffee, or how to build a simple model
In order to better understand a disease and potentially develop new therapies, basic scientists must simplify the system. Model systems provide a better way to study a disease in a way that mimics the complexity of humans, while also allowing scientists to control and monitor the system.

A good model system represents many, if not all, aspects of a disease. Just like an espresso machine and milk pitcher are essential tools for creating the perfect cup of coffee, a good model system is crucial for developing new drug therapies. The better the platform to investigate the disease, the more likely our predictions and discoveries will succeed in the clinic.

Biomedical scientists use two general categories of research tools: in vitro and in vivo research. In vitro is Latin for ‘in glass’. While scientists no longer use glass, this tool refers to using cells grown in plastic dishes (called Petri dishes) outside of their usual environments – scientists provide key nutrients and the ideal temperature to keep them alive and healthy. Most new drug discoveries are first made and tested using this tool.

In contrast, in vivo means ‘within the living’. This tool allows scientists to study the causes of a disease or the effectiveness of a new therapy in an animal model (yeast, flies, zebrafish, mice, rats). These models increase the complexity of the system, allowing scientists to closer approximate the complexity of human beings. These tools are often used following the discovery of a promising drug candidate using in vitro tools; promising results are then followed by clinical trials.

Preclinical studies rely heavily upon animal models to provide lifesaving tests to demonstrate drug efficacy before a clinical trial. Using animals in research is a responsibility that is not taken lightly – scientists go to great lengths to ensure that animal testing is conducted ethically. Extensive training on how to use animal models ethically and replace or refine animal experiments are top priorities.

Animal models have helped develop countless lifesaving drugs. Mice continue to be a powerhouse of biomedical research – without them, many of our current medical advances would still be a dream. For example, the effectiveness of penicillin, the ‘accidental’ antibiotic mentioned in part two (The Penicillin Peppermint Mocha), was tested in mice. Other animal models have also played pivotal roles in developing life-saving treatments: insulin was first tested to treat diabetes in dogs; antidepressants and their effect on the brain were discovered and investigated in rats.

A new flavor of the month, or how to develop new in vitro tools
As an animal lover, I care deeply about respecting each animal that is used in the lab. I know that each animal is treated with care and their lives play critical roles in developing drugs we use every day – without them, countless human lives would be lost every day.

Scientists continue to develop new tools to minimize the use of animal models.

Most of the in vitro work in the lab is performed on flat, two-dimensional layers of cells – it is a quick and easy system to ask simple questions. But we know that our bodies are more complex and that our cells live in a three-dimensional environment. Consequently, there is a high failure rate for drugs when they are eventually tested in animal models.

To combat this, scientists continue to improve their in vitro tools. Cells can now be grown in three-dimensions to more closely resemble a more complex, specific tissue. Furthermore, specialized systems called ‘organoids’ have been developed. These systems are more complex yet and mimic a simplified organ that can be studied outside of the body.

"Basic Science is the foundation of modern medicine. It is driven by curious and observant researchers that continually ask why. It uses sophisticated tools to continually delve into the complex systems of human health and disease. It identifies, tests and validates promising cures for diseases."

-- Rachel Burge

Hot or iced coffee, or how to approach a new drug discovery
Our Modern Medicine Mocha highlights the stages of drug development: a novel discovery is made in a basic science lab; a new therapy is tested in clinical trials; and community health is ultimately improved. This process can take upwards of 15 years and the basic science drug development, represented by the espresso or base of this coffee, is essential for the end result.

Getting started can be a daunting task, so researchers tackle the problem using two approaches: target deconvolution or target-based screening. While these approaches may sound like wizardry, they address the problem from opposite directions – they are two sides of the same coin.

As an example, suppose a researcher wants to identify a novel drug that will stop cancer cells from growing uncontrollably.

One approach, target deconvolution, starts with a library of millions of tiny chemical compounds. These compounds are then added to the cancer cells to see which one might slow or stop them from growing. (This is accomplished by robots, not a poor graduate student who must patiently and precisely add the compounds one by one.) Once a potential candidate compound is identified, the focus shifts to understanding how the drug works.

The other approach, target-based screening, works in the opposite direction. In this approach, scientists have already identified an important protein that is changed in cancer. By knowing the differences in this protein, scientists can find or create a chemical compound that will target that protein to slow cancer growth.

Both of these approaches have led to several successful drugs that are used every day. For example, target deconvolution identified Linezolid as a powerful antibiotic that is used to treat infections, including pneumonia. Target-based screening has identified many drugs, including Gefitinib and Sorafenib which are chemotherapeutics used to treat several cancers.

Enjoy your Modern Medicine Mocha
“Somewhere, something incredible is waiting to be known,” said Carl Sagan.

Basic Science is the foundation of modern medicine. It is driven by curious and observant researchers that continually ask why. It uses sophisticated tools to continually delve into the complex systems of human health and disease. It identifies, tests and validates promising cures for diseases. Without Basic Science and its discoveries, the list of incredible things waiting to be known would be, like the cosmos, infinite.

Want to learn more about basic science? Check out episode #25 of the Science Never Sleeps podcast with guest basic science researcher, Dr. Lori McMahon.