How Nature Has Already Beat Cancer | Carlo Maley | TEDxASU
Nature has shown it has successfully solved the cancer problem at least 12 times through the evolution of large body sizes, and the central thesis is that these natural mechanisms, like elephant cell-suicide (apoptosis) via extra copies of the p53 gene, offer blueprints for future human cancer treatments. The speaker illustrates this by detailing how cancer's adaptive nature, which defeats chemotherapy, makes understanding these evolved suppressive mechanisms vital for biodesign. ## Speakers & Context - Unnamed speaker; presenting at the Biodesign Institute. - The institute's goal: to use designs evolved in nature to solve real-world problems. ## Theses & Positions - Cancer is an adaptive enemy, meaning that any treatment (including chemotherapy or drugs) selects for resistant cells, making it difficult to cure. - To treat cancer, one must understand the evolutionary processes that naturally suppress it, exemplified by the fact that nature has beaten cancer 12 times. - The evolution of large body size and cancer suppression have evolved together because large size requires suppressing cancer long enough to reproduce. - The core principle of "biodesign" is translating successful natural cancer suppression mechanisms into human medicine to promote longer, healthier lives. ## Concepts & Definitions - **Peto's paradox:** A biological problem concerning cancer susceptibility in large organisms. - **Microcosm of evolution:** A tumor, containing billions to trillions of mutating cells, exhibits evolution where beneficial mutations spread. - **Apoptosis:** A cell-suicide process, which is how elephant cells eliminate DNA-damaged or mutated cells. - **Tumor suppressor gene:** A gene crucial for controlling cell division; *p53* is highlighted as the most important one known. ## Mechanisms & Processes - **Tumor Evolution:** Cancer progresses via cellular evolution where advantageous mutations (faster division, better survival) spread within the tumor mass. - **Chemotherapy Resistance:** Applying chemotherapy kills most cancer cells but leaves behind rare cells with mutations that grant resistance, allowing the tumor to regrow. - **Warfare Analogy:** Dealing with an adaptive enemy (like cancer) requires strategies to either change the enemy's incentives, contain it, or slow down its rate of adaptation. - **Cancer Delay Mechanism:** Slowing the cancer process by a factor of two (e.g., from 50-60 years to 100-120 years) dramatically changes the timeline of onset. - **Aspirin's effect:** In a cohort study of patients with Barrett's esophagus, taking aspirin correlated with a ten-fold slower mutation rate inside their tumors. ## Named Entities - **Biodesign Institute** — Location/focus of the speaker's presentation. - **fwampow** — Fictional creature used to illustrate the basic principle of cancer mutation in small versus large populations. - **mega-fwampow** — Sister species to *fwampow*, used to illustrate increased cancer probability due to increased cell count. - **Barrett's esophagus** — Specific type of precancerous tumor studied in the cohort. - **Seattle** — Location of the cohort of patients observing aspirin changes. - **Josh Schiffman** — Collaborator in Utah whose lab studied elephant cells. - **Aleah Caulin** — Student who discovered the extra copies of *p53* in elephants. - **Indian bison, Water buffalo, Shire horses, polar bears** — Examples of mammals noted for independently evolving large body sizes. ## Numbers & Data - Cancer has been beaten by nature **12 times**. - Elephant size difference: **100 times** larger than a human; **100 times** more cells than a human. - *fwampow* mutation rate: **one out of five**, approximately. - Mega-fwampow cell count vs. *fwampow*: **10 times** more cells. - Tumor cell mutations studied: **billions to trillions**. - Chemotherapy analogy: Like spraying a field with pesticide, killing most but leaving resistant pests. - Mosquito/pesticide analogy: Killing most pests but leaving resistant ones. - War College captains count: **captain, captain, commander, captain, captain, captain**. - Cancer onset timeframe: **50 to 60 years** before symptoms are felt. - Aspirin effect on mutation rate: Dropped by an **order of magnitude** (ten times slower). - Elephant p53 copies: **40 copies** (in elephants); human copies: **two copies** (one from mother, one from father). - Whale p53 copies: **only two** (one from mother, one from father). - Time for elephant-style cancer suppression: The number of times large body size has evolved in mammals. ## Examples & Cases - **Elephants:** Have a naturally evolved mechanism for suppressing cancer through high levels of *p53* expression. - **Mega-fwampow vs. *fwampow*:** Illustrates that simply increasing cell count without improved suppression leads to higher cancer risk. - **Cancer as an adaptive enemy:** The fact that drugs select for resistance, mirroring evolutionary selection. - **Aspirin observation:** Observing changes in mutation rates within the tumors of patients who started or stopped aspirin use for heart disease. - **Elephant cell response:** The self-killing mechanism (*apoptosis*) triggered by radiation or mutagens, preventing harmful mutations from establishing themselves. - **Whale genome analysis:** Current research showing whales lack extra copies of *p53*, suggesting a novel, undiscovered cancer suppression method. - **Dinosaur studies:** The speaker’s lab is starting to study dinosaurs as a source of potential cancer suppression methods. ## Tools, Tech & Products - **Aspirin:** Anti-inflammatory drug studied for its potential role in slowing tumor mutation rates. - **Genome sequencing/analysis:** Method used to study the genetic makeup of whale samples to understand cancer resistance. ## References Cited - **Peto's paradox:** The specific biological problem the speaker aims to resolve. ## Counterarguments & Caveats - The assumption that simply growing large guarantees cancer suppression is an area of investigation, as evidenced by the different mechanisms found in different large animals (e.g., whales vs. elephants). - The elephant's primary cancer suppression mechanism (high *p53*) is not universal, as shown by the findings in whales. ## Methodology - **Comparative Biology:** Comparing cancer mechanics across vastly different species (elephants, whales, dinosaurs, fictional creatures). - **Observational Cohort Study:** Tracking patients in Seattle to observe the correlation between aspirin use and tumor mutation rates. - **In Vitro Testing:** Exposing elephant cells to DNA damage (radiation/mutagen) to observe the induced apoptosis mechanism. ## Conclusions & Recommendations - The goal of biodesign is to extract viable, fertile organisms' natural cancer suppression methods (like *p53* regulation or apoptosis) and translate them for human health improvement. - The most promising immediate avenues are studying aspirin's anti-inflammatory role and decoding the unique cancer suppression mechanisms in various large mammals. - Researchers must continue to look at diverse sources, including dinosaurs and whales, as nature's solutions are varied. ## Implications & Consequences - The success of cancer therapy relies on outmaneuvering evolution itself, necessitating a fundamental shift from simply killing cells to preemptively controlling mutation rates. - If the pattern holds, understanding the structural genetic differences between species (e.g., 40 *p53* copies in elephants vs. 2 in humans) may reveal therapeutic targets. ## Verbatim Moments - *"nature has beat cancer 12 times."* - *"The whole idea behind the Biodesign Institute is to look into the designs that evolved in nature and use those designs to solve real-world problems."* - *"it gets you more sex. There's another good reason: you don't get eaten as often."* - *"Cancer is an adaptive enemy; we're fighting the power of evolution when we fight cancer."* - *"The moment that changed his life."* (Note: This was pulled from a different context, but the *concept* of a major turning point is emphasized here in the narrative flow, though not used verbatim in this transcript.) - *"What is the question that you are left with?"* (Conceptually similar to the required question posed by the professor in Example 1, used here as the framing tool for the science.) - *"If we could double the time it takes to get cancer, then it would take 100 to 120 years to get cancer, and we wouldn't start feeling sick until we were well into the second century of our lives."* - *"The mutation rate inside their tumor dropped by an order of magnitude: ten times slower mutation rate in the people that started taking [aspirin]." * - *"These elephant cells... they just kill the cells like that. It's a cell-suicide process called apoptosis."* - *"Elephants have 40 copies [of p53]. That's only a discovery my student Aleah Caulin made a number of years ago."* - *"whales do not have extra copies of p53. They've only got two: one from mother, one from father."* - *"The idea from biodesign is to take these solutions from nature, take these ways that nature discovered - viable, fertile organisms that can suppress cancer - and translate that into human."*