The opulence of Open Science vs the Seclusion of Societies

Popular YouTuber Andrew Stapleton has argued that academia is toxic mainly because of how farcical it is. Wikipedia has a detailed page on Farce as "a comedy that seeks to entertain an audience through situations that are highly exaggerated, extravagant, ridiculous, absurd, and improbable". The word farce is also used to describe "an event or situation that is absurd or disorganized". One of the main reasons for the situation stems from the two/three options available for communicating or publishing research. The recently popular method for communicating research is Open Science. We have talked about it in a few of the preceding blog posts. Open Science generally includes Open Access (OA) to Knowledge. However, it comes with an associated cost of publishing charges for the authors.

The second option is subscription-based journals. In this case, the authors don't have to pay to publish. However, access to this content is restricted by a paywall. Each individual or entity wishing to access this content has to pay a certain amount to access this content. The proponents of open access have argued against subscription journals due to their exorbitant fees, which are untenable and restrict access to research funded by public money. Traditionally, most society-run journals have been subscription-based. These are fairly exclusive clubs that also run journals focussed on specific topics in which the members have expertise. A combination of Society and Open Science journals also exist, such as the ones from the Royal Society we discussed. The trend for all journals slowly becoming open access or OA has meant that most societies are moving towards making their journals OA to ensure the running costs don't burden the society running the journal.

Seeking truth from Facts

“Seek truth from facts” (实事求是) was a key idea in Comrade Mao Zedong’s approach to understanding reality through evidence, but it is also a useful compass for science. It reminds us that conclusions must remain answerable to evidence, especially when evidence points in uncomfortable or unexpected directions. In our study of GPRC6A, this principle became more than a slogan. It became a way to navigate a puzzling contradiction between comparative genomics and experimental cell biology.

GPRC6A is a G protein-coupled receptor that has attracted attention because of its proposed roles in nutrient sensing and metabolic regulation. In dairy biology, one influential study by Li et al. (2019) reported that lysine affects GPRC6A expression and localization in bovine mammary epithelial cells, commonly abbreviated as BMECs. These cells are important because they are used as a model for understanding milk synthesis in cows. Li et al. reported that GPRC6A protein could be detected by Western blotting in BMECs and that the signal became undetectable after siRNA-mediated knockdown. The study has been widely cited and has influenced thinking about amino-acid regulation of milk fat synthesis.

At first glance, this seems straightforward: bovine mammary cells express GPRC6A, and lysine appears to regulate it. However, a comparative genomic analysis by Gupta et.al., took us to a very different starting point. Across bovid species, including cattle, Gupta et.al., claim to find evidence for widespread disruption and loss of intact GPRC6A coding capacity. In simple terms, the gene locus appears to carry multiple damaging changes that are difficult to reconcile with production of a normal, functional GPRC6A protein.

This creates a genuine scientific puzzle. If Holstein dairy cows belong to the Bovidae family, and if bovids lack an intact GPRC6A-encoding gene according to our genomic analyses, how was GPRC6A protein detected in BMECs derived from Holstein mammary gland tissue?

Rather than dismissing the experimental literature, we followed the facts step by step. The methods section of Li et al. states that the BMECs were obtained from mammary gland tissues of Holstein dairy cows at the mid-lactation period. The same methods section lists Abcam ab90677 as the primary antibody used for detecting GPRC6A. When we examined the corresponding Abcam catalogue information, however, this product was listed as an anti-SNAT2 antibody, not an anti-GPRC6A antibody.

This distinction matters. SNAT2, also known as sodium-coupled neutral amino acid transporter 2, belongs to the solute carrier family, specifically the SLC38 family. It transports neutral amino acids across the cell membrane. GPRC6A, by contrast, is a G protein-coupled receptor, a different class of membrane protein involved in signal transduction. An antibody of SNAT2 would not ordinarily be expected to detect GPRC6A unless there were some clearly stated special experimental design, such as a tag-based strategy. We did not find such an explanation in the methods.

The plot thickens because a related study from the same broader research group, Qi et al. (2018), focused on SNAT2 and used the same Abcam antibody catalogue number, ab90677, for Western blotting and immunofluorescence. This raises a careful but important possibility: could the antibody entry in Li et al. represent a catalogue-number error, an antibody misidentification, or some other methodological ambiguity? We cannot answer that question from the paper alone, but the discrepancy is important enough to be openly examined.

The issue does not end with Li et al. A subsequent study by Jin et al. (2022) also used BMECs and reported a role for GPRC6A. In its Western blotting section, the study refers to a GPRC6A-specific antibody. However, in the immunofluorescence staining section, it again refers to the same anti-SNAT2 antibody context associated with ab90677. Thus, across these studies, there are experimental data suggesting GPRC6A expression in bovine cells, but there are also methodological details that appear difficult to align with the genomic evidence.

This is exactly where “seeking truth from facts” becomes useful. The facts are not all pointing in one comfortable direction. On one side, Western blotting and immunofluorescence assays have been interpreted as evidence that GPRC6A protein is present and functionally relevant in bovine mammary epithelial cells. On the other side, Gupta et.al., use comparative genomics to claim that the GPRC6A locus in bovids carries multiple gene-disrupting changes. In addition, the antibody information in key experimental studies raises questions about target specificity and catalogue-number accuracy.

These questions matter beyond one gene. The findings from Li et al. and Jin et al. have been incorporated into broader models of milk synthesis, including influential reviews such as Wu et al. (2020). Once a molecular pathway enters review figures and conceptual models, it can become part of the working vocabulary of a field. That makes careful re-examination especially valuable, not as a challenge to individual researchers, but as a service to the scientific record.

Our aim is therefore not to assign blame. Antibody specificity, catalogue-number reporting, cross-reactivity, and protein annotation are recurring challenges in biology. Instead, our goal is to bring together independent lines of evidence and ask what explanation best fits all the facts. If GPRC6A is truly expressed in bovine mammary cells, then the genomic evidence requires explanation. If the genomic evidence is correct and bovids lack an intact GPRC6A gene, then the experimental signal requires explanation. Either way, the answer will be informative.

The most constructive path forward is independent validation. Future work could test the locus using targeted genomic and transcriptomic approaches, verify the exact antibody identity and immunogen sequence, include appropriate positive and negative controls, and, where possible, use orthogonal methods such as mass spectrometry or tagged rescue experiments. Such experiments would help distinguish true GPRC6A detection from cross-reactivity, misannotation, or detection of another protein.

In science, contradictions are not failures. They are invitations. The story of GPRC6A in bovine mammary epithelial cells reminds us that published figures, catalogue numbers, genome assemblies, and evolutionary analyses all need to be read together. Truth rarely arrives as a single dramatic revelation. More often, it emerges by placing facts side by side until the pattern becomes impossible to ignore. 🧬

Reformation of science publishing: the Stockholm Declaration (2025)

An important feature of the GPRC6A story is that most of the relevant studies did not appear in obscure or marginal venues. Li et al. published their BMEC work in the Journal of Agricultural and Food Chemistry, an American Chemical Society journal that publishes research on the chemistry and biochemistry of agriculture and food. Jin et al. published in Cell Biology International, described by Wiley as the official journal of the International Federation for Cell Biology. Wu et al. later incorporated this line of evidence into Nutrition Research Reviews, a Cambridge journal associated with broad, critical synthesis in nutritional science. This matters because the question before us is not whether these journals are reputable. They are. The question is how a striking contradiction can persist even within literature that has passed through recognized scientific gatekeepers.

This is where the broader debate about society publishing becomes relevant. The Stockholm Declaration argues that science depends on integrity and trustworthiness and calls for academia to regain greater control of publishing through non-profit, researcher-led models, including learned societies and academies. Its concern is that commercial incentives, paper mills, metric-driven evaluation, and escalating publication costs can distort the scientific record and drain resources meant for research. In this framework, society journals occupy a special place. At their best, they are not merely containers for papers. They are community institutions: governed by scientific traditions, connected to disciplinary standards, and ideally oriented toward reinvesting surplus into meetings, education, fellowships, outreach, and editorial quality rather than private extraction. The American Chemical Society is a strong example of this model: ACS describes itself as a nonprofit organization dedicated to scientific research excellence, education, and collaboration, and ACS Publications describes itself as a nonprofit scholarly publisher with rigorous peer review and high editorial standards.

Yet, society publishing is not a magic shield. Szabo’s response to the Stockholm Declaration offers useful caution. He argues that non-profit or society ownership alone cannot remove the deeper incentives that reward prestige, volume, novelty, and citation metrics over reliability. He also notes that many society journals are published in partnership with commercial publishers, may still charge substantial open-access fees, and often depend on unpaid peer-review labour. These counterpoints are important. They do not weaken the case for society journals, but they prevent an overly romantic view of them. The scientific record is protected not by labels alone, but by careful methods, transparent materials, reproducible evidence, and willingness to revisit conclusions when new facts appear.

In that spirit, the GPRC6A discrepancy should be seen as a constructive test of the system. If a highly cited BMEC study in a respected ACS journal reported GPRC6A protein detection, while Gupta et.al., now claim widespread disruption of the GPRC6A locus in bovids, then the appropriate response is not accusation but verification. The antibody catalogue-number issue, especially the apparent connection between ab90677 and SNAT2 rather than GPRC6A, is precisely the kind of methodological detail that deserves daylight. Society journals, because of their scientific legitimacy and community responsibility, are well placed to support such correction, clarification, or replication. In the best version of scholarly publishing, reputation is not a fortress around published claims. It is a workshop where claims can be repaired, refined, or replaced when the facts demand it. 🧬

When facts wander, Talent must follow

Scientific discrepancies are not new. They have always appeared wherever evidence travels farther than verification. A striking historical example comes from palaeontology. In his 1989 Nature commentary, John A. Talent examined what he called “the case of the peripatetic fossils”, a controversy in which unusual fossil reports from the Himalayas appeared to overturn accepted stratigraphic and palaeobiogeographic patterns. The problem was not one isolated oddity, but a trail of puzzling observations: fossils reported from unlikely horizons, specimens resembling material known from distant regions, repeated inconsistencies in locality and age assignments, and data that had begun entering textbooks and syntheses. Talent’s response was not rhetorical dismissal. He patiently followed the fossils, the localities, the preservation styles, and the stratigraphic claims, arguing that the issue could only be settled by reproducible evidence: independent collection of in situ specimens from the same horizons and places. In other words, the field needed to talent its way back to truth, not by personality or prestige, but by disciplined re-examination of facts.

This episode is useful for thinking about the GPRC6A puzzle. In both cases, the discrepancy is not solved by asking which side is more respectable. Himalayan palaeontology had a distinguished tradition, and the BMEC studies appeared in recognized scientific journals. Yet even respected literatures can accumulate claims that later become difficult to reconcile with independent evidence. Talent’s lesson is that a contradiction should not be treated as an embarrassment to hide, but as a map showing where science must dig again. For GPRC6A, the equivalent of returning to the fossil horizon is returning to the locus, the antibody, the immunogen, the protein band, the siRNA control, and the cell source. The remedy is not suspicion alone. It is verification with sharper tools.

Desiraju’s prescription: fixing the soil, not just one plant

This brings us to Professor Gautam R. Desiraju, whose recent book with Deekhit Bhattacharya, Fixing Science in India: A Socio-Economic Prescription, places such problems in a larger institutional frame. Desiraju’s own website lists the book among his recent science-related works, and the publisher describes it as a survey of Indian science from 1835 to 2025, with attention to the social and economic roots of present challenges.

That framing matters. Individual discrepancies can be corrected by careful experiments, but repeated discrepancies require better scientific culture: fewer incentives for quantity over quality, stronger respect for replication, better curation of methods, and more willingness to revisit published claims without turning every correction into a courtroom drama. Desiraju’s “prescription” is therefore not merely about publishing better papers. It is about creating conditions in which facts can survive hierarchy, haste, and habit.

In that sense, John Talent and Gautam Desiraju speak to the same deeper need from different terrains. Talent shows how a scientific field can be rescued by returning to specimens, sites, and reproducibility. Desiraju asks how a scientific ecosystem can be repaired so that such rescues become easier, faster, and less politically costly. Between them lies a simple message for our GPRC6A story: when facts begin to wander, science needs both talent and a prescription. 🧬📜