FRAME’s recent essay competition “What are the alternatives to using animals in laboratories?” attracted some strong entries. The winner, who received a £300 prize, was 17-year-old Emma Bryan, a student at Cheltenham Ladies College.
Emma’s response to her success: “I am extremely happy to have taken part as I really enjoyed writing the essay and am fascinated by alternatives to animal testing. I intend to pursue Veterinary Medicine at university – but I am really interested in pioneering research in all aspects of science, particularly animal-related.
“I have always been opposed to unnecessary use of animals in experimentation, particularly cosmetics, and so this competition really allowed me to express my personal views combined with scientific innovation. Thank you very much for organising this competition – and I really admire the aim of FRAME and the dedicated research that goes on.”
A promising alternative to animal testing – the Organ-on-a-Chip
In an age where the whole of the human genome can be mapped, where magnetic resonance imaging can be used to measure brain activity, and where particles can be made to accelerate to close to the speed of light, it seems almost primitive that animals are still used in medical experiments. There is no doubt that without animal testing our present level of medical research would be nowhere near as sophisticated as it is today, and a huge number of both human and animal lives would have been lost. Nevertheless, I believe that in vivo testing on animals should become a thing of the past, and be succeeded by more advanced, scientific, moralistic methods of testing such as through experimentation with human stem cells and donated human tissue. In this essay I wish to discuss a recent innovation in the field of alternatives to animal testing, namely the Organ-on-a-Chip. I believe that this pioneering micro-machine created using nanotechnology and biological engineering has the potential to replace animals in medical testing entirely.
Companies that use animal testing often find this method time-consuming, expensive and unreliable, because animals do not always respond to medication in the same way as humans. Although the development of stem cell research could significantly reduce the number of animals involved in experimentation, it would never eliminate testing completely, because animals would still be required to test function in terms of entire organs or systems. The Organ-on-a-Chip is a surprisingly simple device developed by biological researchers and engineers at Harvard’s Wyss Institute, which could completely change the nature of medical testing. By creating a physical model of a human organ condensed into a plastic chip the size of a computer memory stick, the effects of small amounts of drugs on human tissues can be mimicked, accurately and efficiently. Developed using micro-fabrication techniques, the chips currently being researched include Lung-on-a-Chip, Liver-on-a-Chip and Bone-Marrow-on-a-Chip.
The engineering behind these chips is on a microscopic scale, but is a realistic simulation of the chemical and mechanical functions of the organ. For example, Lung-on-a-Chip is composed of a transparent rectangular structure, containing two parallel channels separated by a porous membrane. Each side of the membrane is lined with human cells – the upper side made up of type 1 pneumocyte cells that comprise the walls of an alveolus in the lung, and the lower side made up of endothelium cells that line the capillary through which gas exchange in the lung occurs. Vacuum tubes on either side of this arrangement allow the structure to contract regularly and relax through the application of cyclical forces. air is passed through the upper channel and a solution containing human white blood cells is passed through the lower channel. In this way this innovative micro-device replicates a fully functioning alveolus of a human lung. Small amounts of chemicals, drugs or toxins can then be pumped through the channels and the effects monitored. This proved successful when bacteria were passed through the upper air channel; white blood cells from the liquid medium in the lower channel passed through the porous membrane and into the upper (air) channel, where they engulfed the bacteria, as they would in a normal human lung in order to prevent infection.
The Heart-on-a-Chip could be useful in studying heart disease such as arrhythmias and cardiomyopathy. At the moment animal experimentation is used to test heart medication, causing potential suffering to living creatures, and giving often distorted, unsatisfactory results. Stem cells can also be used to test toxicity of drugs on the heart, although individually they cannot be made to simulate the action of a beating heart, something that is vital when testing drugs for arrhythmias such as atrial fibrillation. The Heart-on-a-Chip is constructed using small strips of cardiac muscle that are positioned on a bundle of plastic tubes. When attached to electrodes the muscles contract and relax, as they would do in a functioning heart. When the researchers introduced a drug used to strengthen a weakly contracting heart to the cells within the micro-device, the response was identical to that of a normal heart. The Heart-on-a-Chip could also be used to test the side-effects of other drugs on cardiac muscle, as new tests for cardiac toxicity at the moment are quite limited.
Many pharmaceutical companies have become interested in Organ-on-a-Chip technology already, and I believe that this is a promising advance towards the end of testing on animals. Used on a large scale, they would be much more cost-efficient than animal testing, as pointed out by Donald Ingber, founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University: “People have estimated in the press that it costs two million dollars to put one drug through animal studies on the way to clinical trial. These devices are disposable; they are very, very inexpensive but they use human cells which we can culture up and grow again, relatively inexpensively so you are not doing animal studies on a chip, you are doing human studies on a chip.” In addition, the micro-devices could be manufactured using bio-printing from 3D computer models, which is an increasingly popular technology and would make production even more efficient.
The hallmark of the Organ-on-a-Chip is that it combines cells of different tissues to form a model that mimics an entire organ, and can replicate its function and movement. It uses human cells, sourced from stem cells, and techniques of micro-fabrication and nano-engineering to construct these highly innovative organ chips. I think the transition from testing on animals to complete reliance on biotechnology will be gradual, however it is a change that needs to be made in order to keep up with the pace of our rapidly developing world, and also not only to improve the welfare of animals, but to improve the success rate of medical drug testing.
Ethical Debates: Animal Research and Testing by Patience Coster
Image provided courtesy of TissUse GmbH.