The flurry of attention New Approach Methodologies (NAMs) have recently received has come with a range of ambitious promises. These include significantly improving safety and efficacy of new drugs and dramatically decreasing drug costs and development times. However, NAMs’ most controversial claim is the possibility of entirely replacing the use of animals in drug discovery and preclinical research.
Naturally, with this outcome disrupting the US$10 billion (or more) global animal testing industry, the potential for NAMs to replace animals has attracted a lot of (positive and negative) attention.
From scientists working on in vitro technologies, to veterinarians working in preclinical studies, to toxicologists, to regulators, to pharmaceutical companies, everyone has a take and their own biases, myself included. These frequently conflict and are often “absolute” statements.
I have heard:
- “NAMs are a pipe dream and will never replace animals”
- “NAMs will inevitably replace all animal toxicology testing in 10 years”
- “Neither camp is right, a happy medium will exist where NAMs reduce and refine but never fully replace animals” (current trajectories suggest this is the most likely outcome)
Here’s the truth. All three of those claims are unscientific. All three claims present uncertain futures as predetermined outcomes.
The only truly scientifically honest answer to “will NAMs replace animal testing?” is “I don’t know.”
History Punishes Absolute Claims
The history of science warns us against taking an absolute stance on any uncertain prediction. Time and again, scientists holding firm positions, even “moderate” ones have been proven wrong. (See toxicologist Robert Kehoe’s claim that although high levels of lead were toxic, low levels of lead were likely safe and that claims to the contrary came from “irresponsible alarmists”.)
BUT
Scientific objectivity doesn’t mean we abandon optimism and ambition. In 1962, committing to reach the Moon within a decade was technologically audacious and far from guaranteed. But it was precisely the setting of this outlandish goal made its realisation possible.
Similarly, if even the remotest possibility exists that NAMs can eliminate animal testing, we should pursue that objective. Certainly, NAMs technology is still rapidly developing and regulators are only now beginning to interpret their utility. So, there is no conclusive evidence proving it either possible or impossible for NAMs to fully replace animal testing in drug development.
The 3Rs Demand We Try to Eliminate All Animal Testing
The 3Rs were first described in Russell and Birch’s 1959 “The Principles of Humane Experimental Technique”. From the start, Russell and Birch described animal models’ limitations in predicting human biology. However, they also pointed to key ethical arguments. They described animal use in toxicity testing as “an urgent humanitarian problem, for it regularly involves considerable and sometimes acute distress.” They propose the 3Rs to reduce that stress whenever possible, but add, “Replacement is always a satisfactory answer, but Reduction and Refinement should, whenever possible, be used in combination.” Effectively, Replacement is the first approach and Reduction and Refinement must be used together where Replacement is impossible.
The ethical consequence of the paradigm is simple:
If replacement is possible for an animal method, any other course of action is unethical.
Allow me to propose a corollary to that statement: Where future technologies to replace animal testing might exist, it is unethical to dismiss that possibility without fully investigating it.
Where the only scientifically honest answer to “will NAMs replace animal testing?” is “I don’t know,” it would be most ethical to follow it with “but we should try.”
The 3Rs have seen widespread adoption by scientists as well as legislators, often influencing policy. This has led to the ethical treatment of animals being considered a professional standard by scientists and a legal requirement in most countries. If the 3Rs stresses that replacement is the only guaranteed satisfactory outcome, it becomes our obligation to pursue its total realisation. This is likely why global governments are increasingly serious about actively pursuing NAMs for Replacement.
For me, the conclusion is simple:
The working hypothesis should be that full replacement of animals is possible. Scientists are obligated rigorously test that hypothesis.
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