In vitro vs. In vivo: Is One Better?

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Exploring the benefits and challenges of each model and how they translate to the clinic.
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In vitro and in vivo studies have their merits and flaws, but both are required to holistically evaluate the safety and efficacy of an experimental drug.

By: Candice Tang, Science Writer at the ORT Times

Imagine a world where all experimental therapies are only tested on humans—no animal or cell-based testing required. Time to market could be cut in half but thousands of lives would be lost to unpredictable adverse events.

Clearly, this is both unethical and impractical. Instead, scientists demonstrate adequate safety, efficacy and quality data through a series of in vitro and in vivo studies before the drug reaches the clinic.

What are the main differences between in vitro and in vivo studies? In vitro studies use cells derived from animals or cell lines which have an infinite lifespan. These model systems are relatively cheap and simple to procure, enabling reliable and efficient drug discovery studies. A major drawback is their failure to capture the inherent complexity of organ systems. For example, in vitro models may not account for interactions between cells and biochemical processes that occur during turnover and metabolism. As a result, in vitro studies have developed a reputation for being “less translatable” to humans.

The use of animals in in vivo studies addresses many of the shortcomings of in vitro studies. Scientists can better evaluate the safety, toxicity and efficacy of a drug candidate in a complex model. Moreover, advances in gene editing have helped scientists replicate human diseases in animals with high accuracy. But in vivo studies have their own flaws. Growing ethical concerns over the use of animals in laboratory testing have persuaded some researchers to limit the number (and species) of animals used in their studies. Animal studies are also time and resource-intensive, requiring advanced personnel training and maintenance fees. Finally, the problem of translatability remains: there are considerable physiological differences between humans and animals that impact drug absorption, distribution, metabolism and excretion.

Is one model better than the other? As mentioned, each model comes with its own benefits and challenges. Consider the study of epileptic seizures: Acute seizure models create electrographic signatures that are identical to those in a real clinical seizure, but only require slices of brain tissue. These models are favoured over chronic epilepsy models—which are expensive, laborious and time-consuming, and human trials—which are fraught with ethical issues and high levels of variability. Despite the virtues of acute seizure models, they do not replicate all of the elements of a clinical seizure. 

Eventually, drug candidates will be tested in human clinical trials, where scientists will see if the trends observed in preclinical data still hold. “Success in preclinical stages is not necessarily translatable to clinical outcomes,” wrote the authors of a 2017 editorial paper.

In vitro and in vivo studies each have advantages and disadvantages, but both are necessary to understand the pharmacokinetic/pharmacodynamic profile of a drug. Ultimately, these studies serve to create safer, more effective drugs for those that need them.