Can In Vitro Techniques Replace Animal Testing?
From organ-on-a-chip to patient-on-a-chip; how AI is enabling this; leading companies in the space; this week's startup highlight
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Now, let’s get to this week’s topics…
Can in vitro techniques replace animal testing?
Regardless of what your answer might be, last year, the US Congress passed the FDA Modernization Act 2.0, giving drug companies a path to propose in-vitro tests in the clinical trial application, subject to approval by the FDA. Essentially, the Act now allows consideration of alternatives to animal testing in certain cases. It indicates general tendency toward gradual minimization of animal testing in drug research, alghough we are in early days.
Anyway, this marks a significant change from the Federal Food, Drug, and Cosmetics Act of 1938, which required animal testing for all new drug development protocols. Proponents of this initiative claim that this shift allows for more modern and potentially more effective ways of evaluating the safety of new drugs.
And the important reason is, of course, minimizing the involvement of animals and ceasing the suffering of our little brothers. I totally support this quite noble goal.
Just a remark, though. Over several years of running BiopharmaTrend as an independent consulting boutique, I had numerous discussions with a significant number of drug discovery and biotech experts, conducted many interviews with KOLs, etc. More often than not, I heard an opinion that in vitro strategies of today were not quite ready to substitute animal testing, at least not for all therapeutic areas, and that the area of translational research was ‘plagued with failures’ when it came to the practical implementation of such modern tools as human cell cultures, organ-on-a-chip systems, functional systems, and computational models (artificial intelligence-based) to predict clinical outcomes. This is not a formal study of mine, by any account, and not even my opinion (which is still evolving on this subject). But the fact that some really experienced folks think that way makes me wonder if this is the case.
I’ll leave it for a broader discussion that I started here on LinkedIn (see comments section). The opinions of various experts are really contradictory there.
Anyway, let’s focus on a set of technologies that are certainly bringing us closer to an animal-free drug testing future.
Nearly two decades ago, a groundbreaking discovery in the field of biomedical research emerged, known as organ-on-a-chip technology, which quickly captivated the interest of scientists across the globe. Led by bioengineer Donald E. Ingber at Harvard University, this innovative approach aimed to recreate the complex structure and functions of human organs within laboratory settings. By using specialized techniques, researchers successfully developed miniature models of organs, opening up new possibilities for studying human physiology in the lab.
The National Institutes of Health's Tissue Chip for Drug Screening program began in 2010 as a five-year partnership among NIH, the Defense Advanced Research Projects Agency (DARPA), and the U.S. Food and Drug Administration (FDA). Since 2012, the program has been led and managed by the National Center for Advancing Translational Sciences (NCATS). This collaborative initiative brought together experts from various fields, including biology, engineering, and materials science, to accelerate the development of organ-on-a-chip models for drug discovery and toxicity testing. Through these joint efforts, scientists achieved significant milestones in replicating organ-level functions and understanding how different organs interact on these tiny systems.
In 2012 researchers from Harvard University's Wyss Institute unveiled an innovative "human-on-a-chip" platform. By combining multiple organ-on-a-chip models, such as the lung, heart, liver, and blood-brain barrier, this groundbreaking system provided a comprehensive representation of human organ systems. By mimicking organ interactions, this platform offered a more accurate environment for drug testing and disease modeling, laying the foundation for future biomedical research.
Nowadays, the field continues to evolve. Researchers are now embarking on a transition from organ-on-a-chip to an even more ambitious concept known as patient-on-a-chip. This innovative leap aims to replicate the complexity of an individual patient's physiology within a single integrated system. By incorporating patient-specific cells, genetic information, and utilizing artificial intelligence (AI) algorithms, scientists hope to create personalized models capable of predicting an individual's response to specific treatments or therapies.
Let us delve into the evolution of organ-on-a-chip technology, exploring key contributors to this field, and the emergence of patient-on-a-chip models.
What is organ-on-a-chip technology?
Imagine a technology that can recreate the complex environment of our organs on a tiny chip. That's exactly what organ-on-a-chip (OOC) technology does. It's a cutting-edge approach that mimics the structure and function of human organs in a laboratory setting. By synthesizing organ-like units on a chip, OOC technology can simulate the behavior and physiology of tissues and organs, bringing us closer to understanding how our bodies work. This exciting innovation has the potential to revolutionize drug development and screening, offering a more accurate and reliable alternative to traditional methods. With organ chips, we can overcome the limitations of 2D cell cultures and animal trials, which often fall short in accurately predicting human responses. By providing a more realistic environment for cells to grow and interact, organ chips can significantly reduce the failure rate in late-stage human trials, making drug development faster, more cost-effective, and ultimately delivering more effective treatments. The success of organ chips is made possible by advancements in 3D bioprinting, fluidic chips, and 3D cell culture techniques, with the latter allowing cells to thrive under conditions that closely resemble the human body.
From organ-on-a-chip to patient-on-a-chip
The high cost of drug development and safety testing is partly due to the limitations of current preclinical models. These models often fail to accurately represent how drugs behave in the human body, leading to potential side effects and unexpected outcomes. To address this, scientists are seeking alternatives to traditional cell cultures and animal testing. One promising approach is the use of organoids, which are 3D models formed by self-assembling stem cells into mini-organs. While organoids offer a more realistic representation of human biology, they still have limitations. They lack the dynamic nature of real organs and fail to simulate the interactions between different organs in the body.
Unlike static organoid cultures, organ chips allow for the flow of fluids, mimicking the dynamic exchange of nutrients and signals that occurs in living tissues. By integrating multiple mature tissues on a chip and enabling communication through fluid perfusion, scientists hope to create a more comprehensive "body on a chip" model that closely resembles human physiology.
In a recent study published in Nature Biomedical Engineering, researchers made significant progress towards this goal. They developed a multi-organ chip system that integrated mature heart, liver, bone, and skin tissues, allowing them to interact and communicate as they would in the human body. The tissues were cultured within their unique microenvironments, separated by an endothelial layer, and connected to a recirculating bloodstream. This setup enabled the tissues to communicate and maintain their phenotypes, providing a more realistic model for studying drug metabolism and toxicity.
While the multi-organ chip system is a remarkable achievement, there are still challenges to overcome. The current system includes only a limited number of tissues, limiting its ability to capture the complexity of the whole human physiology. Future research will focus on developing internal circulation systems to provide fluid flow for the engineered multi-organs. However, this groundbreaking advance brings us closer to the ultimate goal of creating patient-specific models for drug testing and personalized medicine. The potential of these organ chips is immense and holds promise for improving drug development and patient care in the future.
What are the leading organ-on-a-chip companies?
Since its inception, numerous organ-on-a-chip companies have emerged in this field, pushing the boundaries of innovation and making significant contributions to advancing our understanding of human biology.
Below, we will review some of the leading companies in the organ-on-a-chip space, focus on how artificial intelligence (AI) is enabling progress in this field, and review in more detail one promising startup that is bringing creative solutions to augment organ-on-a-chip systems.
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