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¿Pero, Y qué pasaba con ese humo saliendo de la pequeña chimenea de la Capilla Sixtina?

Fri, 30 May 2025 11:29:57 +0000

Humo Blanco – Habemus Papam (Tenemos un Nuevo Papa) vs. Humo Negro (Aún Sin Decisión)

La Iglesia Católica hizo historia recientemente al elegir a su primer papa estadounidense, el cardenal Robert Francis Prevost, de 69 años, ahora conocido como el Papa Leo XIV. Originario de Chicago, el Papa Leo aporta una experiencia global al cargo, despues de años como misionero en Sudamérica y por su liderazgo dentro del Vaticano. La señal de que se ha tomado una decisión es una columna de humo blanco que emana de la Capilla Sixtina, cuando el comité de selección (el cónclave) hace su elección por mayoría. Siempre me ha parecido fascinante esta tradición, con multitudes reuniéndose en la Plaza de San Pedro para observar esa señal inconfundible de humo. El químico en mí siempre ha sentido curiosidad por el humo… esa estela blanca que sale de la chimenea de la Capilla Sixtina y que desde 1878 ha anunciado la elección de un nuevo papa. ¿Cómo logran que salga blanco o negro? No soy historiador, pero siempre me ha dado curiosidad cómo tradiciones tan antiguas como esta siguen funcionando hoy en día.

Después de investigar un poco, me encontré con algunos datos interesantes sobre cómo funciona este proceso. El cónclave (la reunión de estos cardenales católicos para elegir un nuevo papa) está compuesto por hasta 120 cardenales electores menores de 80 años. Votan hasta cuatro veces al día: dos veces por la mañana y dos veces por la tarde. No se permite hacer campaña ni cabildeo, y no hay nominaciones formales. Los cardenales no hablan entre sí sobre los votos. Se requiere una mayoría de dos tercios para elegir a un papa. Las papeletas son contadas por tres cardenales conocidos como los escrutadores, quienes son seleccionados al azar antes de que empiece la votación. Junto a ellos están tres infirmarii (quienes recogen los votos de los cardenales enfermos) y tres revisores (quienes verifican el conteo). Estos responsabilidades rotan para mantener la imparcialidad y el secreto. Ninguna persona cuenta los votos por sí sola..los escrutadores hacen este trabajo frente a los demás electores, en silencio y con reverencia. Se instala una estufa especial temporalmente dentro de la Capilla Sixtina para este propósito. La chimenea se monta a través del techo y se hace visible a las multitudes reunidas en la Plaza de San Pedro.

Ya que todas las papeletas se queman después de cada ronda de votación, la diferencia de color en el humo se debe a los aditivos utilizados para asegurarse de que el color generado sea inconfundible:

Humo negro: perclorato de potasio, antraceno, azufre
Humo blanco: clorato de potasio, lactosa, resina

Humo negro: La combinación de antraceno y azufre provoca una combustión incompleta, lo que produce partículas ricas en carbono que se ven negras. El azufre ayuda a que la combustión ocurra a menor temperatura, asegurando un humo denso y oscuro.

Humo blanco: La mezcla de clorato de potasio, lactosa y resina genera partículas finas y vapor de agua. La resina, rica en compuestos con oxígeno, favorece la formación de pequeñas gotas y partículas que dispersan la luz, dándole al humo una apariencia blanca.

El cónclave más largo de la historia duró casi 3 años (1268–1271) y resultó en la elección del Papa Gregorio X. ¿Te imaginas que no se eligiera un papa durante tanto tiempo? El cónclave más corto fue en 2005, con la elección del Papa Benedicto XVI en solo 26 horas. El papa con el pontificado más largo fue Pío IX, que reinó desde 1846 hasta 1878 (32 años); el de mandato más breve fue Urbano VII, quien murió de malaria en 1590, apenas 13 días después de su elección.

Este año, el cónclave papal de 2025 tomó solo dos días para elegir al Papa Leo XIV, del 7 al 8 de mayo. Me parece increíble cómo descubrimientos químicos hechos hace siglos todavía se utilizan hoy en día para algo tan simple como generar una columna de humo, ya sea oscuro o claro.

Sigue mi blog y página de LinkedIn para más historias Alkhemicas donde la química, la historia y el arte se entrelazan.

Esta publicación tiene fines educativos y está basada en mi propia investigación y curiosidad sobre el tema.

So what was up with that Smoke coming from atop the Sistine Chapel?

Fri, 30 May 2025 10:40:26 +0000

White Smoke - Habemus Papam (We have a New Pope) vs. Black Smoke (No Decision Yet)

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The Catholic Church recently made history by selecting its first American pope, 69-year-old Cardinal Robert Francis Prevost, now Pope Leo XIV. Originally from Chicago, Pope Leo brings experience to the role shaped by years as a missionary in South America as well as leadership inside the Vatican. The selection being signaled by a plume of white smoke emenating from the Sistine Chapel as the selection committee (the Conclave) make their selection by majority decision. I’ve always found the tradition fascinating, with crowds gathering in St. Peter’s Square to watch for that telltale puff of smoke. The chemist in me has always been curious about the smoke..that iconic white trail rising from the Sistine Chapel chimney has signaled a papal decision since 1878. How do they make the smoke white vs. black? I'm no historian, but I've also always been curious about how centuries-old traditions like this one actually work.

After doing a little research, I came across some interesting facts about how the process actually works. The conclave (the gathering of these Catholic cardinals to elect a new pope) is made up of up to 120 cardinal electors under the age of 80. They vote up to four times a day with two in the morning and two in the afternoon. No campaigning or lobbying is allowed, and there are no formal nominations. Cardinals do not speak to one another about the votes. A two-thirds majority is required to elect a pope. The ballots are counted by three cardinals known as the Scrutineers, who are randomly selected before voting begins. Alongside them are three Infirmarii (who collect votes from sick cardinals) and three Revisers (who double-check the counts). These roles rotate to ensure fairness and secrecy. No one is isolated for counting while the Scrutineers perform this duty in front of the other electors, in silence and reverence. A special stove is installed temporarily inside the Sistine Chapel for this purpose. The chimney is mounted through the roof and made visible to the crowds in St. Peter’s Square.

Since all votes are burned after the votes, then what exactly is the chemistry for generating the different colors of smoke.

This then comes down to the additives ensuring that the smoke generated is unmistakable in color:

•Black smoke: potassium perchlorate, anthracene, sulfur

•White smoke: potassium chlorate, lactose, rosin

Black Smoke: The combination of anthracene and sulfur leads to incomplete combustion, producing large carbon-rich particles that appear black. Sulfur facilitates the combustion process by lowering the ignition temperature, ensuring a dense, dark smoke.
White Smoke: The mixture of potassium chlorate, lactose, and rosin combusts to produce fine particles and water vapor. The rosin, rich in oxygen-containing compounds, contributes to the formation of a dense white smoke composed of tiny droplets and particles that scatter light, giving it a white appearance.

The longest-serving pope was Pope Pius IX, who reigned from 1846 to 1878 (32 years); the shortest-serving pope was Pope Urban VII, who died of malaria in 1590, just 13 days after his election

This year it took the 2025 papal conclave two days to elect Pope Leo XIV, from May 7 to May 8, 2025. I find it super cool how chemistry discovered hundreds of years is still being used to this day for something that seems so simple as making a plume of smoke either dark or light.

Follow my blog and LinkedIn page for more Alkhemic stories where chemistry, history, and art come together.

This post is for educational purposes and is based on my own research and curiosity about the topic.

ALK Who do You Need? When you come unglued..

Thu, 08 May 2025 05:29:09 +0000

Brain-Penetrant molecular glue degraders at AACR 2025

🧠 Next, 486 is presented as an optimized glue also showing in vitro growth inhibition along with comparable in vivo efficacies in Xenograft models with clinically-relevant cancer cell lines. This optimized glue, with greater Kpuu values over 701, also has measured tumor suppression in vivo and with improved survival in intracranial xenografts.

📌 To briefly summarize and provide clinical implications. This research further provides examples that molecular glue degraders will continue to provide notable approaches towards clinical candidates in drug discovery. To note, this approach would not be directly applicable to all kinase targets. This research benefits from ALK being a tumor-intrinsic target. Meaning that the degradation of endogenously expressed protein would not be detrimental...can you imagine trying to degrade something like EGFR (the Epidermal Growth Factor Receptor). Sure you would want to degrade any TKI resistant mutants, but then EGFR being so ubiquitously expressed, the degradation of wild type native protein would be extremely disruptive to homeostasis.

AACR Reflections – Molecular Glues and ALK

Fri, 25 Apr 2025 00:28:46 +0000

While I’ve since transitioned into new ventures, I’m thrilled to see this recent work being shared as an oral presenation by Zheng Wang at AACR 2025. A novel approach to ALK degradation using brain-penetrant molecular glues — a compelling strategy to address resistance and CNS progression in ALK+ cancers

If you’re attending AACR this week, here’s a session worth catching:

🧠 Brain-penetrant molecular glue degraders targeting ALK via a novel degron: a potential therapeutic approach for ALK-positive NSCLC

📍 Where: Room S404 – McCormick Place South (Level 4)

🗓️ When: April 29, 2025 | 3:40–3:55 PM CST

One of the coolest things about molecular glues is their ability to create (almost by magic) these hitherto and previously unbeknownst surface areas.. that weren’t even considered “druggable.” Nothing against the nomenclature here, but somehow "undruggable" doesn't quite make sense to me. If you are actually now targeting it, isn't it now 'druggable'? But I digress..

Now once these new surfaces are recognized by something like the E3 ligase system it can result in degradation of the protein they're interacting with. Then there are the classical kinase inhibitor targets in oncology, such as ALK. Typically targeting the orthosteripc pocket the protein uses endogenously with ATP. But with glues, there might not be any limits. This is something akin to an allosteric pocket..but stamping that allosteric pocket in other parts of the protein.

If you're headed to AACR, I highly recommend checking it out. And if you’re curious about ALK-targeted drug design, I’ve got some reflections coming soon on the blog — stay tuned.

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From the Alkhemist

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ALK in Precision Oncology- First post from the Alkhemist's Kugelrohr

Sat, 19 Apr 2025 00:38:58 +0000

ALK in oncology

First Post from The Alkhemist’s Kugelrohr

This will be a space where I share reflections on drug discovery, commentary on the evolving landscape of biotech and innovation, occasional deep dives into scientific history, light-hearted ruminations, and conversations with fellow alchemists in our podcast The Alkhemist’s Glove Box, and hopefully some engaging discourse with others in the field.

We’re kicking it off with one of those targets you hear about in precision oncology all the time — one I’ve had the privilege of working on firsthand:

ALK (anaplastic lymphoma kinase) — a molecular journey that continues to challenge and inspire across generations of therapy.

ALK in Precision Oncology: A Journey of Innovation

Since its discovery in 1994, the ALK pathway has become a pivotal focus in the advancement of precision oncology. Over the decades, groundbreaking therapies have emerged — and recent studies spotlight just how far we’ve come.

💊 Lorlatinib's Impact

The Phase 3 CROWN study revealed that 60% of patients with ALK-positive advanced NSCLC remained progression-free after five years on lorlatinib, compared to 8% with crizotinib. Notably, lorlatinib also reduced the risk of brain metastasis progression by 94% — a transformative leap for CNS-compromised patients.

Sources: Translational Lung Cancer Research, Pfizer, Reuters

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-lorbrenar-crown-study-shows-majority-patients-alk

📖 Want a patient-friendly overview? Check out this plain language summary of the CROWN study here: https://www.tandfonline.com/doi/abs/10.2217/fon-2021-0904?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

🧪 Emerging Therapies: Navigating Resistance and Next-Gen ALK Inhibition

Nuvalent’s NVL-655 is showing promising results in overcoming resistance mutations and managing CNS disease. This brain-penetrant, selective ALK inhibitor was intentionally engineered to address both on-target resistance and off-target liabilities observed with earlier-generation TKIs.

Preclinical and early clinical data support its ability to maintain potency across diverse resistance mutations, while minimizing CNS-related adverse effects — a differentiator thought to stem from reduced off-target activity, particularly at TRKB【PMID: 38477329】.

Despite lorlatinib’s remarkable CNS efficacy — including a 94% reduction in brain metastasis progression and durable five-year PFS — resistance remains inevitable in many patients. Research groups are actively developing inhibitors to target these post-treatment resistance mutations, highlighting a real-world challenge in the therapeutic landscape.

Lorlatinib Resistance: A Closer Look

Resistance mechanisms to lorlatinib can be broadly categorized as follows:

1. On-target (ALK-dependent) resistance

Sequential ALK TKI therapy increases the likelihood of compound mutations — multiple mutations occurring within the ALK kinase domain, often on the same allele, which interfere with drug binding and efficacy.

Common mutations observed include:

• G1202R + L1196M

• G1202R + L1198F

• I1171N + L1196M / L1198F / L1256F

• C1156Y + L1198F

• D1203N + I1171N

These mutations present a significant therapeutic challenge, as they can drastically reduce sensitivity to all currently approved ALK TKIs.

2. Off-target (ALK-independent) resistance

Some tumors adapt by activating alternative signaling pathways or undergoing histologic transformation:

Bypass signaling: EGFR, MET, KRAS, HER2/3, AXL, or NF2-mediated mTOR activation
Phenotypic transformation: EMT or small cell lung cancer (SCLC) transformation

These off-target mechanisms often require combination approaches or a complete shift in therapeutic strategy.

Clinical Implications and What Comes Next

Identifying the underlying resistance mechanism is critical. Techniques such as repeat biopsy and next-generation sequencing (NGS) of tumor tissue or circulating tumor DNA (ctDNA) play a pivotal role in guiding subsequent treatment decisions.

Looking ahead, fourth-generation ALK inhibitors — designed specifically to overcome compound resistance mutations — are in preclinical or early clinical stages. Combinatorial strategies that pair ALK TKIs with inhibitors of bypass pathways or immunotherapies may also offer renewed hope for durable disease control.

If anything catlyzes a thought feel free to leave a comment or share.

More stories soon from the Alkhemist’s Kugelrohr 🔮⚗️

p.s. Still refining the mobile view and page flow — if you spot a glitch, pretend it’s just a small glitch in the matrix..

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