Understanding Rose Bengal Sodium: Biotech Blind Spots and Systems Thinking
For nearly 150 years, rose bengal was seen as a dye. That’s all it’s been allowed to be in the modern pharmaceutical world, until a small biotech began asking different questions.
A Molecule Without a Market
Rose bengal was first synthesized in 1882 as a wool dye. It would later find limited use in medicine—as a staining agent for damaged eye tissue or in liver function tests. But despite being known to science for generations, it was never approved as either a diagnostic1 or a therapeutic agent. Not once. Not anywhere.
This is not because the molecule lacked biological activity. It’s because the pharmaceutical industry never asked it to do more.
Until a small biotech company—first at Photogen Technologies (Photogen), then as Provectus Biopharmaceuticals (Provectus or the Company), and later as post-2017 Provectus leadership—started asking different questions.
From Light to Biology
In the 1990s, the founders of Photogen (and, later, Provectus) set out to develop photoactivated cancer therapies. Rose bengal caught their interest. But what changed the game was their realization that the molecule didn’t need light to be activated—it could localize in tumor lysosomes upon intratumoral injection and trigger cell death all on its own. That discovery opened a door. But these founders only cracked it open. They still thought in local terms—inject tumor, burst lysosome, destroy cell. Classic mechanism-first thinking.
When Ed Pershing, now Provectus’s chairman and chief executive officer who led the post-2017 leadership transition, met the founders in late-2005, he heard something different: an intuition that the Company’s Rose Bengal Sodium (RBS) could help the body fight back—that it might engage the immune system. He became intrigued. But it would take years for that intuition to evolve into insight.
The First Immunologic Hints
In the early-2010s, Provectus sponsored non-clinical research studies at Moffitt Cancer Center in Tampa, FL (Moffitt) that began to reveal RBS’s capacity to stimulate immune activity via intratumoral injection of injectable solid tumor cancers. A 2013 PLOS One study by Moffitt showed dendritic cell activation following treatment with PV-10 (the 10% solution of RBS in saline). Clinically, in melanoma patients, distant tumors regressed after intratumoral injection of local ones—a bystander (abscopal) effect that hinted at a system-wide response.
But the founders didn’t fully believe it. They were fixated on lysosomes. They initially saw immune activity as incidental (stimulative), not intrinsic (modulative: both stimulative and inhibitive). And the researchers they worked with also had a narrow lens at the time: they focused on immune stimulation, particularly in oncology, not immune modulation or real cross-disease potential.2
That’s where the narrative stalled. Until 2017.
A Leadership Change, A Broader Frame
Post-2017 leadership at Provectus began to challenge the assumptions they had inherited. Was the immune effect only stimulatory? Was the molecule’s anti-inflammatory action in dermatology merely topical? How much did RBS concentration matter, or was it a different way of asking “how much RBS” was needed to achieve successful patient outcomes? Was the bystander effect a curiosity—or a window into something deeper?
They didn’t just keep testing. They started listening—to collaborators, to biology, to the contradictions. In no small part, saving PH-10 (the 0.1% solution of RBS in an aqueous hydrogel) from being discarded and immediately greenlighting clinical PH-10 research in dermatology was the listening that had to be heard.
And what they found was not a dye. Not a local cytotoxic agent. But a very bioactive small molecule that could behave differently in different systems. A molecule that could restore immune balance in some cases, activate it in others, and disrupt pathogenic signaling altogether when needed.
The System Reset Hypothesis
The more data they gathered, the clearer the pattern became:
RBS is not just simply concentration or dose-dependent—it’s system-state dependent.
It acts across mechanisms: necrosis, antigen presentation, protein aggregation, inflammation, and more.
The right amount of RBS—not merely the right concentration—potentially could reprogram systems of disease.
This wasn’t reductionist pharmacology. It was systems medicine. And it doesn’t fit the traditional pharma model at all.
Why Pharma Never Went There
The pharmaceutical industry avoids molecules like rose bengal because they’re old, publicly known, and not patentable under the conventional mindset. The ROI equation collapses:
No exclusivity × high trial cost = no investment case.
Rose bengal was never taken seriously by Big Pharma because the small molecule had no story to tell that fit their model: no single target, no new mechanism, no blockbuster branding/marketing potential. And yet, the molecule’s century-and-a-half-long shelf life was not a sign of weakness. It was a sign of unexplored strength.
Provectus didn’t succeed by out-marketing anyone. It succeeded—incrementally, stubbornly—by reframing the question.
A New Model for a New Kind of Molecule
Under post-2017 leadership, Provectus is developing a business model that reverses the traditional logic:
Instead of newness, it bets on known safety and systemic versatility.
Instead of one indication, it pursues a platform portfolio.
Instead of concentration-only thinking, it focuses on molecular quantity and system exposure.
Instead of marketing-led positioning, it builds around mechanistic insight and long-science collaborations.
And yes, it sees oral delivery—not just injections—as not only viable but game-changing. In many diseases, necessary.
Conclusion: What Was Missed, What Still Might Be Found
That rose bengal was never approved is not a condemnation of the molecule. It’s a mirror held up to a compromised, flawed drug development system. For more than 150 years, no one thought to ask what this molecule might do beyond what it was experimented upon.
Provectus did. And it’s still doing so—treating RBS not as a one-time invention, but as an ongoing biological discovery.
In doing so, it invites a larger question:
What else have we overlooked—not because it lacked potential, but because we lacked the curiosity to see it?
What if the future of medicine isn’t about inventing new tools—but about understanding old ones more deeply than we ever dared before?
VisiRose
Further clinical research on Bascom Palmer Eye Institute’s rose begal photodynamic antimicrobial therapy (RB-PDAT) by Indian eye care center L V Prasad Eye Institute (LVPEI) in two Indian news article:
June 3rd: Doctors develop new light-based treatment for rare eye infection, and
June 16rd: Light-based treatment offers new hope for a blinding eye infection.3
The news articles highlight a medical journal article of LVPEI’s from March 2025: Outcome of photodynamic therapy with Rose Bengal in conjunction with topical PHMB and chlorhexidine combination in Acanthamoeba keratitis:
A total of 14 patients were enrolled. All the enrolled patients received adjuvant PDAT-RB within 5 (2.5 to 11) days of diagnosis. The average diameter and median depth of the infiltrate were 5.7 ± 1.56(V), 5.9 ± 1.38(H) mm, and 250 (250 to 300)µ, respectively. The mean LogMAR visual acuity at the time of presentation was 2.52 ± 0.95. Out of 14 enrolled patients, infection was resolved in 12 (85.7%) patients, whereas 2 (14.3%) patients needed TPK. The median days to resolve were 110 (67 to 150) days. The final mean LogMAR Visual acuity at the end of the follow-up was 1.60 ± 1.3.
Provectus’s 2025 Annual Stockholder Meeting
The annual meeting will be held on Wednesday, June 18th at the Hilton Knoxville, located at 501 West Church Avenue, Knoxville, Tennessee, beginning at 4:00 p.m. Eastern Time.
The meeting, including shareholder meeting activities and a company update, will also be accessible by Zoom Webinar. The webinar of may be accessed by registering in advance at:
https://us06web.zoom.us/webinar/register/WN_NHDxe61oQDi-t84JgMylsg#/registration.
Annual meeting materials, including Provectus’s Proxy Statement, Notice of Internet Availability, and 2024 Annual Report, are available on Provectus’s website at https://www.provectusbio.com/annual-meeting/.
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A radiolabeled version of rose bengal, a very different molecule, was approved as a more sensitive liver function test and diagnostic.
In a remote, distant corner of rose bengal’s biomedical literature universe, post-2017 leadership as retail shareholders noted a non-Provectus-affiliated researcher’s immune signaling discovery, before Provectus’s original founders and before Moffitt.
Articles courtesy of a Provectus shareholder