Science1 publisher3 min readPublished
Animal-free test methods still have to prove themselves against the animal experiments they would replace
Harvard's lung-on-a-chip has nearly 5,400 citations since 2010, but most non-animal test methods have yet to be rigorously tested, IEEE Spectrum reports. Validation means head-to-head runs against animal experiments, so animal data remains the yardstick for now.
The Scientist · Science desk
What happened
- Science's editors rejected the Wyss Institute's first lung-chip paper and suggested the team repeat the tests in mice before it was published in 2010.
- The chip grows human lung and blood-vessel cells on opposite sides of a porous membrane, with vacuum channels stretching the tissue to mimic breathing.
- Maschmeyer calls such FDA requests rare for now but expects them to become more frequent.
Compiled by The ScientistSomething wrong?How this is made
Why it matters
- constraint Chip developers still need animal experiments to validate their systems, so animal studies continue through any transition to non-animal methods.
- exposure If the FDA case Maschmeyer describes becomes routine, drug sponsors arriving with animal data alone risk a refused trial and a detour to commission chip studies.
- contradiction IEEE Spectrum's headline calls the technology almost ready while its reporting says most NAMs have yet to be rigorously tested, so the technical case is still open.
The Wyss Institute design moves [1]. Earlier lung models typically used static tissue cultures that could not simulate the movements lung function depends on [3]. Pumping air through chambers beside the cell channels made the Harvard device expand and contract [2]. When the team exposed it to silica nanoparticles, used to model ultrafine particulates, movement changed how the tissue absorbed them [4]. The chip also reproduced an inflammatory response: bacteria went into the air channel, white blood cells into the blood channel, and the immune cells crossed the membrane and engulfed the bacteria [9].
Before any of that reached print, Science's editors asked for mice [5]. IEEE Spectrum calls the request reasonable, since the system was new and matching its results to mouse results would help validate it [7]. The team ran the experiments and resubmitted, and the paper came out in 2010, a year after the 2009 submission [6][1]. Validation today follows the same logic. It means standardizing the systems and running head-to-head comparisons with animal experiments, work the article calls an enormous challenge [15]. A head-to-head comparison cannot show which model is right about a person. When chip and mouse disagree, agreement rates alone cannot say which one is wrong.
The account pointing the other way comes from Ilka Maschmeyer, a translational toxicology researcher and executive at TissUse, a German company that builds organ-on-a-chip systems for pharmaceutical research [11]. According to Maschmeyer, a drugmaker came to TissUse a few months ago after the FDA refused to let it run a clinical trial. The company had presented animal data, and the agency wanted data from organ chips or a comparable alternative [10]. The account is secondhand and comes from a firm that sells the alternative [11]. The article does not name the drug, the sponsor or the FDA's reasoning [10]. Maschmeyer does not claim such requests are common. "It's rare still," she said, "but I think it's going to be more and more frequent." [12]
IEEE Spectrum's headline says the technology is almost ready and the scientists are not [17]. Its reporting adds that the implementation question has become less about technical qualities and more about practical next steps [16]. Yet the same article says most of these new approach methodologies, or NAMs, have yet to be rigorously tested, though early studies suggest potential [13][14]. Standardizing a chip so that different labs get the same answer is measurement work, and for most methods it is unfinished [14][15].
I think the habit argument is right about editors and reviewers who reach for animal data by default, as Science did in 2009 [5][1]. For the chips themselves it is early. The technical case rests on head-to-head numbers that, for most NAMs, have not yet been produced [14].
What to watch
- Whether the FDA itself confirms, in guidance or public statements, that it is asking trial sponsors for organ-chip data in place of animal data.
- Published head-to-head studies that standardize a chip across labs and report how often its results agree with animal and human outcomes.