I keep saying “drug discovery” but most of my audience does not understand what this means.

Here’s a thread I worked on over the past week trying to distil down drug discovery - and why it matters in the age of AI.

OPEN THE THREAD 🧵 Drug discovery is how molecules become medicine.
A $180 billion guessing game where up to 97% of candidates fail in trials.

We can now predict protein folds (thanks to AlphaFold), but still cannot simulate what a drug actually does to a living cell in real time.

how do we know that people in the past had cancer and when did we even know what cancer was?

a word for cancer existed long before microscopes or pathology.

the history of cancer is far more exciting than we realize.

🧵 the idea is older than modern medicine. Hippocrates (400 BCE) used the word karkinos (crab) for tumors with “claw-like” spread. Galen (200 CE) expanded it. the word cancer is a translation of this lineage.

Biotech is a 1.55 trillion dollar industry, projected to grow to 3.88 trillion by 2030.

How is biotech incentivized to do all this up front investment to make new breakthroughs that lead to life saving treatments?

You finally get the answers today.
Biotech industry: thread. Tech investors see quick iterations:

Build. Test. Pivot. Scale.

Biotech demands patience:

Experiment=>Fail=>Refine, then repeat: often over years.

Your challenge: Balancing investor impatience with biological patience.

responded in detail bcs grimes is awesome:

17th-century: coffeehouses emerge as epicenters of intellectual exchange.

discussions shape the scientific community. new physical locations mark societal shifts.

coffee houses…basically transformed science.

(1/ 🧵)

https://twitter.com/grimezsz/status/1900079892408263106

a lot of scientific discoveries can in some way be traced back to coffee or tea.

over coffee, scholars/scientists/thinkers could meet ANYONE with an interesting thought - other scientists, artists, random people.

it was kind of like the X app today, but IRL.

many requested a deep-dive on androgenetic alopecia—male pattern baldness

male pattern baldness/hair loss (MPB/MPHL) affects 30-50% of men by age 50.

let's talk about the biology, current treatments, and cutting-edge research on hair follicle (HF) regeneration. MPB is a complex polygenic disorder

it is influenced by
-androgens (male sex hormones)
-aging
-environmental factors.

it causes progressive miniaturization of hair follicles in genetically susceptible areas of the scalp

In a surprising paper published in Nature, scientists accomplished what sounds impossible: using genes from a single-celled organism to create mouse stem cells, which eventually developed into a living, breathing mouse. Animal multicellularity emerged ~700mn years ago.

The genes in this study—from choanoflagellates, ancient single-celled organisms—are somewhat of evolutionary relics.

They predate multicellular life and now appear to have played a foundational role in animal development.

A friend asked me to explain DNA, RNA, and epigenetics. he said that others had tried before, but it didn’t click for him.

I happen to play the piano, so I gave him a simple, albeit imperfect, analogy.

After this analogy, he finally understood! Here’s the piano analogy.

🧵 Imagine a piano with 30,000 keys. Each key represents a gene.

Nearly all of your somatic cells have the exact same piano—the same keys, the same genes. So why does a nerve cell look different from a cheek cell?

Because they’re playing different pieces on the identical pianos.

we recently saw an insane discovery in biology, which if true, in my opinion, makes extraterrestrial life far far more likely.

🧵 new research suggests that life on Earth became surprisingly complex very early, reshaping our understanding of life’s origins and its implications for the existence of life elsewhere in the universe.

let's talk biological age.
aging markers boost health management, refine life expectancy, and enhance well-being. yet, consensus on the very idea of aging is still in the works.

here's my thread 1 of 3 on biological age markers.

🧵OPEN THE THREAD🧵 here's what we do know
- age is a significant marker across the board
- people age differently
- it is biological, rather than chronological, age that actually matters in medicine

Schrödinger’s “What is Life?” is a book of magic

predicting phenomena decades before they were discovered empirically

the magic of physics : pivotal for developing molecular biology

I’ve read this book tens of times

let’s explore the key predictions.

🧵OPEN THE THREAD🧵 aperiodic crystals
the book posited genetic information must be stored in some “aperiodic crystal,”

a stable molecular structure that could encode information in its configuration rather than through simple repetition

Franklin's DNA X-ray crystallography, decades later:

there's a SIGNIFICANT piece of legislation which could change biopharma in america. no one seems to be talking about it on X.

BIOSECURE aims to decouple from Chinese contract firms. This could affect over 120 drugs in development.

let's talk about it. 🧵 the main issue at hand is the US biopharma's reliance on Chinese outsourcing for cost-effective research.

this comes with risks related to intellectual property (IP) theft and potential ties to the Chinese government. this is what BioSecure is about.

Heard of Ozempic/Wegovy? These drugs are part of a class of medications called GLP-1 agonists.

In 2023, Science named GLP-1 agonists Breakthrough of the Year for their potential to combat "diabesity", 1 year after JWST won the same award. Let's ask why.

🧵OPEN THE THREAD🧵 GLP-1 - glucagon-like peptide-1 - is a hormone that plays a key role in regulating blood sugar levels.

you may have heard of insulin-glucagon dynamics.

GLP1:
- enhances insulin secretion
- inhibits glucagon release
- slows gastric emptying, making you feel fuller for longer.

Yes, mitochondria is the powerhouse of the cell.

...but their evolutionary origin is remarkable. Here is a thread devoted to these beautiful, strange structures, present in almost all our cells, allowing us to survive and thrive on earth.

🧵OPEN THE THREAD🧵 As per the endosymbiont theory, mitochondria evolved from free-living bacteria (likely proteobacteria) engulfed by a larger host cell over a billion years ago through endosymbiosis.

Symbiosis-between two physically close organisms.
Endo-one inside the other.

Marine viruses are remarkably abundant, diverse, and integral to the functioning of ocean ecosystems.

This thread will explain marine viruses and highlight the role of metagenomics in advancing our understanding of these entities. [Adopted from slides from my talk, 2021]

🧵 Viruses are small. They have a protein capsid encapsulating genetic material in DNA/RNA.

Most marine phages are double-stranded DNA viruses w/ tailed morphologies~ from 20 nm to 200 nm.

Today, AlphaFold 3 came to life.

A monumental leap toward the world of biomolecules.

Predicting structures across proteins, nucleic acids, and small molecules. The world just changed - let me try to break it down the best I can.

🧵OPEN THE THREAD🧵 Proteins undertake a vast array of functions from catalyzing metabolic reactions, copying DNA, responding to environmental stimuli, to forming the structural framework of the cell itself.

Each protein's function is intricately linked to its three-dimensional structure.

Neuroscience has long been fascinated by the brain's complexity. one of its most intriguing aspects, degeneracy, remains a relatively obscure concept. Recently, Dr. Christophe Bernard explored degeneracy as a fundamental principle in neuroscience.

Let's explain this conundrum. What is degeneracy?
different structures
or processes
leading to same outcome
or function

In 2013, single-cell genomics was declared Method of the Year by Nature.

Now we have single-cell RNA sequencing (scRNA-seq), where we explore the intricate symphony of gene expression at the individual cell level.

🧵OPEN THE THREAD🧵 The transcriptome is a complete set of RNA transcripts produced by the genome under specific circumstances or in a specific cell. It provides a snapshot of gene expression and regulation within a biological system.

Protein folding is so important. In 2023, DeepMind won the $250,000 Lasker award for their solution to the problem. A lot of people have asked me to explain protein folding in simple, understandable terms.

Here is my attempt at explaining just the problem.

🧵OPEN THE THREAD🧵 Understanding how a protein's amino acid sequence dictates its 3D shape—known as the "protein folding problem"—is a fundamental question in biology. Proteins are the workhorses of cells, and their functions depend on their shapes (structure).