Cultures of Trial and Error: When the Spell Breaks: Magic, Money, and the EPR Effect — A Blog of Trial and Error | Blog of Trial and Error

May 17, 2026 ~ 19 min read<br>DOI: https://doi.org/10.36850/c1d9481a-4b54<br>funding<br>science correction

ByDeclan KuchOrcID<br>Share on Bluesky

JOTE x NanoBubbles present Cultures of Trial and Error : a peer reviewed blog series on error correction in science.<br>How nanomedicine conjured billions from thin air and what happened when the enchantment failed

“Nano scale [is] magic scale.” This was not a late-night laboratory joke. It was official U.S. government policy. The phrase appeared verbatim in early National Science Foundation solicitations for the National Nanotechnology Initiative (NNI). Nano-evangelist Mihail Roco coined it, and the very first NNI programme description placed it alongside technical aims (Mody 2004; Roco 2023). When President Clinton announced the program in 2000, he promised breakthroughs that were “only imagination away.” Magic sat next to milestones in official funding calls. The government had converted a charismatic promise into a bureaucratically sustained future.<br>What follows offers a case study in how weak scientific claims gain extraordinary performative power. It also shows how the entanglement of technoscience with financial capital can disable science’s self-correcting mechanisms. The protagonist is the Enhanced Permeability and Retention (EPR) Effect: the hypothesis that tumours’ leaky blood vessels would passively accumulate drug-loaded nanoparticles. For over two decades, EPR organised billions in research funding, launched dozens of biotech ventures, and became nanomedicine’s constitutive fiction. Its empirical basis was tenuous from the start. It worked reliably only in certain tumours transplanted into certain mice.<br>Drawing on our article in Social Studies of Science (Rasmussen & Kuch, 2026), this post uses the concept of enchantment to illuminate how EPR’s spell was cast, why it held for so long, and what its collapse reveals about contemporary technoscience. Max Weber (1991 [1919]: 139) called enchantments “mysterious incalculable forces” and denied their presence in modern science. Science and Technology Studies (STS) scholars have tracked them nonetheless, through concepts like promissory economies (Brown 2003), fictional expectations (Beckert 2013), and sociotechnical imaginaries (Jasanoff & Kim 2015).<br>The Claim That Launched a Thousand Startups<br>In 1986, Japanese pharmacologists Matsumura and Maeda observed that a polymer-modified cancer drug accumulated preferentially in mouse tumours. They proposed a mechanism. Tumours have chaotic, leaky blood vessels (enhanced permeability) and poor lymphatic drainage (enhanced retention). Macromolecules and particles of appropriate size should therefore concentrate in tumours passively, without molecular targeting (Matsumura & Maeda 1986). If true, this “EPR Effect” would turn cancer’s chaos into therapeutic advantage. Leaky vessels would become gateways. The drug would find the tumour on its own.<br>The empirical basis was tenuous from the outset. EPR worked reliably only in specific tumours transplanted into specific mice. Not all tumours showed enhanced permeability. Results varied considerably. As early as 1992, pharmacologist Len Seymour noted that discouraging results from liposome researchers had “suppressed passive drug targeting research in general” (Seymour 1992: 151). This early warning would be buried under subsequent enthusiasm.<br>Yet EPR did not fade. Through the 1990s, it circulated within a small drug delivery community. Researchers like Ruth Duncan and Karel Ulbrich developed polymer-drug conjugates designed to exploit the Effect. Duncan’s landmark 1999 review positioned EPR as the linchpin for a new generation of “polymer therapeutics” (Duncan 1999). At that point, none of these drug classes carried the “nano” prefix. That rebranding was about to arrive.<br>From Hypothesis to Holy Grail<br>The NNI’s launch in 2000 changed everything. Billions in federal funding and explicit invocations of “magic” transformed EPR’s prospects. Coordinated across agencies including NSF, NIH, DOE, and NASA, NNI spending climbed from roughly $500 million in 2001 to nearly $2 billion annually by 2010. By 2023, cumulative spending passed $40 billion (Roco 2023). Similar nano-roadmaps in France, the UK, Japan, China, and elsewhere reinforced a transnational funding ecology. Funders treated EPR as a ready-made portal to futuristic cancer cures, years before robust human data existed (Kearnes & Rip 2009).<br>Under these conditions, EPR became what sociologists call a “boundary object” (Star & Griesemer 1989). It was flexible enough to mean different things to different communities, yet coherent enough to coordinate collective action. Polymer chemists saw a design principle. Venture capitalists saw a platform technology. Federal agencies saw a tangible health benefit to justify massive investment. Universities saw...