Holey Grail
The Holey Grail is the name Kent Kemmish, founder of Molecular Reality Corporation, uses for reading DNA base by base with a solid-state nanopore, a feat no laboratory has published. The company's member game, Epic Quest Bio, prices it at 9,900,000 experience points, the largest quest on its board. A qualified form, the Holey Grail*, covers the same feat achieved with the help of chemical labels attached to the DNA. Kemmish glossed the asterisk in 2026 as "required labels but it's a damn good start".[1]
Name
The phrase puns on "holy grail", the idiom for a long-sought goal, and on the holes in which nanopore sensing takes place. Kemmish used it in two posts to the company's members on March 29, 2026. In one, about a study that mapped the genome of Escherichia coli with two solid-state pores, he wrote that the authors "didn't sequence the genome", which was "the holey grail", but had located large tags along the DNA: "This is like being able to see the continents of Earth from space, so you know it's Earth and not another very similar planet, where actually sequencing would be like Google Maps."[2] The other post introduced the asterisk.[1][a]
The company's 2022 technical overview gives the same standing to two goals. Sequencing is the first. The second is being able to "arbitrarily identify any given single analyte in a complex mixture using a single nanopore system", which the overview names universality.[4] On sequencing it was blunt: "No one has yet sequenced DNA with a solid-state nanopore. ... It's extremely hard or it would have been done by now, ten years after Oxford Nanopore did it with 'soft' nanopores".
The quest
In the quest list of the company's member software, "Sequence DNA with an ss-nanopore" is worth 9,900,000 points and carries the note "This is a holy grail, and the XP represents a pool (unless, somehow, a single player does it!)." The quest is marked inactive.[5]
| Quest | Points | Holey Grails per completion |
|---|---|---|
| Sequence DNA with an ss-nanopore | 9,900,000 | 1 |
| MR series design development | 700,000 | 0.071 |
| Peer-reviewed journal article writing | 200,000 | 0.020 |
| Viral Tweet | 50,000 | 0.0051 |
| MRC wikipedia page | 500 | 0.000051 |
| minor bug bounty | 10 | 0.0000010 |
The 500-point quest, also inactive, asks for "an awesome (and accurate) wikipedia page about Molecular Reality Corporation".[5] At the listed rates the Holey Grail is worth 19,800 such pages. Brownian Business Daily reported the 9,900,000-point quest in October 2026, in an article on the company's use of a role-playing game as its management system.[6]
Status
Commercial nanopore sequencing reads DNA through protein pores, which use a motor enzyme to step the strand through slowly enough to resolve each base. In a bare solid-state pore DNA travels at one to tens of nucleotides per microsecond, too fast to read.[7] Solid-state pores have come close in other ways. A molybdenum disulfide pore distinguished single nucleotides in 2015,[8] and two pores working together mapped tags along the 4.6-million-base genome of E. coli in 2022.[9] No group has published a solid-state pore reading DNA base by base.
Kemmish wrote in 2026 that in 2019 "two different very-much-in-the-know solid-state nanopore researchers told me they'd heard rumors that a certain group had achieved this. That was a nothingburger, but it's the kind of thing that's repeatedly happened in some form or other in this field."[4] The company's guide calls sequencing "the grand prize of the whole solid state field" and adds: "No solid state pore has done it commercially yet."[10] The company's own approach to it is sliding occlusion, a pore that would close around a molecule to slow it down.
The asterisk
The labeled route attaches a chemical tag to particular bases so that they block the current more distinctly. In 2015 a group at Northeastern University tagged the pyrimidines, cytosine and thymine, with an osmium complex and showed that the tags changed the current through solid-state pores in a way that could be used to estimate their content in a strand.[11] Kemmish's post on that work treats labeling as a shortcut the company would accept for now: "even if we have to use labels to 'cheat' early on, it will still be a major achievement".[1]
The company's long-term goal does without labels. Its 2022 overview states that utility-scale sensing "won't use target-specific labels", treats labels and DNA barcodes as "bridging strategies", and proposes giving specialty reagents to players of its games as "power-ups".[4] The Holey Grail without an asterisk is the label-free read.
See also
Notes
References
- ^ a b c Kemmishtree (March 29, 2026). "Magic with labels". EQBio-OS.
- ^ Kemmishtree (March 29, 2026). "Flossing with DNA". EQBio-OS.
- ^ Annalisa Burgos (August 24, 2024). "Hawaii-style taro donuts with Holey Grail Donuts". Hawaii News Now.
- ^ a b c Kemmishtree (March 28, 2026). "2022 sci-tech overview". EQBio-OS.
- ^ a b "Company records". Molecular Reality Corporation. October 2026.
- ^ Harriet Quill (October 21, 2026). "A Biotech Run as a Role-Playing Game". Brownian Business Daily.
- ^ Lenora Ashgrove (October 8, 2026). "Can a Hole That Slides Read a Molecule?" Signal & Noise.
- ^ Feng, Jiandong (2015). "Identification of single nucleotides in MoS2 nanopores". Nature Nanotechnology 10: 1070-1076. doi:10.1038/nnano.2015.219.
- ^ Rand, Arthur (2022). "Electronic mapping of a bacterial genome with dual solid-state nanopores and active single-molecule control". ACS Nano 16: 5258-5273. doi:10.1021/acsnano.1c09575.
- ^ "Keltar's Field Guide to Molecular Reality". Molecular Reality Corporation. August 2026.
- ^ Henley, Robert Y. (2015). "Osmium-based pyrimidine contrast tags for enhanced nanopore-based DNA base discrimination". PLOS ONE 10 (12): e0142155. doi:10.1371/journal.pone.0142155.