DH26001 Coding Human Cells - bit.bio V01 180126

 bit.bio is a synthetic biology company based in Cambridge, UK, that focuses on "coding" human cells. Spun out of the University of Cambridge in 2016 by neurosurgeon Dr. Mark Kotter, the company treats biology like software, viewing the cell's nucleus as a "hard drive" and its genes as "programs."  

Their primary goal is to produce every cell type in the human body with industrial consistency, speed, and scale for use in research, drug discovery, and cell therapy.  

1. The Core Technology: opti-ox™

The "secret sauce" of bit.bio is a patented technology called opti-ox™ (optimized inducible over-expression).  

• The Problem: Traditional stem cell differentiation (directed differentiation) is often slow, inconsistent, and results in "messy" mixtures of cells.  

• The Solution: opti-ox™ uses genomic "safe harbors" to insert a precise genetic code (transcription factors) into stem cells. When activated, this code forces the entire population of stem cells to switch into a specific mature cell type (e.g., a neuron or a muscle cell) almost simultaneously.  

• Consistency: This allows for "deterministic" programming, meaning every batch of cells is identical, which is crucial for reproducible scientific experiments.  

2. Product Portfolio: ioCells™

Under the brand ioCells, bit.bio sells ready-to-use human cells to researchers and pharmaceutical companies. Their catalog includes:  

• Nerve Cells: Glutamatergic neurons, GABAergic neurons, and sensory neurons.  

• Glial Cells: Microglia and astrocytes.  

• Muscle Cells: Skeletal myocytes.  

• Disease Models: They offer "ioDisease Model" cells that have specific genetic mutations (like those for ALS, Huntington’s, or Alzheimer’s) already engineered into them, allowing researchers to study diseases in a human context.  

3. Key Applications

• Drug Discovery: Using consistent human cells early in the process helps predict if a drug will work in humans, potentially reducing the high failure rate of clinical trials.  

• Reducing Animal Testing: By providing high-fidelity human cell models, bit.bio aims to shift the industry toward New Approach Methodologies (NAMs) that don't rely on animal subjects.  

• Cell Therapy: Long-term, bit.bio plans to use its technology to create "off-the-shelf" engineered cells that can be injected into patients to treat diseases like cancer or organ failure.  

4. Recent Milestones (as of 2026)

• Funding: In January 2026, bit.bio secured $50 million in Series C funding led by M&G Investments, bringing their total funding to over $250 million.  

• AI Integration: The company is increasingly focusing on generating massive, high-quality datasets to train AI models for drug discovery, using their automated cell-production platform as the data source.  

• Leadership: While founded by Dr. Mark Kotter, the company recently appointed Przemek Obloj as CEO to lead its commercial expansion.  

DH25032 DNA as Software V01 251225

 “DNA is more advanced than any software ever created.” — Bill Gates

This statement may sound poetic, but it’s grounded in real science.

DNA is not just a passive molecule — it is a self-writing, self-repairing, self-replicating information system operating inside every living cell. Unlike human-made software, DNA doesn’t just store instructions; it executes them, copies itself, detects errors, and corrects mistakes in real time.

🧬 Why DNA surpasses all software:

• Information Density

A single gram of DNA can theoretically store hundreds of millions of gigabytes of data — far beyond any silicon-based system.

• Self-Replication

No human software can autonomously copy itself with near-perfect fidelity across generations. DNA does this constantly.

• Error Correction

Cells contain sophisticated proofreading and repair mechanisms that detect and fix mutations — something programmers still struggle to perfect.

• Parallel Processing

Trillions of biochemical operations happen simultaneously inside your body every second, without crashes, reboots, or external power sources.

• Energy Efficiency

All of this runs on simple chemical energy, not massive data centers.

Modern software requires:

– Programmers

– Compilers

– Hardware

– Debugging teams

– Constant updates

DNA requires none of these — yet it builds organisms, adapts, heals, and sustains life.

This doesn’t argue against science.

It highlights how extraordinary biology truly is.

Whether one attributes this complexity to natural processes or deeper principles, the reality remains:

DNA is the most advanced information system we know.

📌 Science doesn’t diminish wonder — it deepens it.

— The Intelligent Design

(Educational content. No medical or religious claims. Discussion encouraged.)

DH25031 Katalin Karako - mRNA V01 181225

 She was demoted four times, rejected from grants for decades, and threatened with deportation. Then her "useless" research saved millions of lives. She just won the Nobel Prize.

1995. University of Pennsylvania.

Katalin Karikó's bosses gave her an ultimatum: Give up her research on mRNA or face a demotion and a pay cut.

Her husband was stuck in Hungary dealing with a visa issue. She'd just had a cancer scare. And now Penn was demoting her off the path to full professorship.

She basically took a demotion to continue her work on mRNA. That is how devoted she was.

Most people would have quit.

Karikó kept going.

"I was demoted four times," Karikó says of her time at Penn, where she was eventually pushed out entirely.

For over 30 years, she believed in something everyone else thought was impossible: that messenger RNA could teach human cells to fight disease.

Everyone told her she was wasting her time.

Karikó grew up in a small Hungarian village. She earned her PhD at the University of Szeged and worked at its Biological Research Center studying RNA. In 1985, when the center ran out of money and eliminated her position, she made a desperate choice.

She, her husband, and their two-year-old daughter smuggled 900 British pounds out of communist Hungary—sewn into their daughter's teddy bear—and fled to America.

She took a postdoctoral position at Temple University in Philadelphia. Four years later, she reportedly argued with her boss and was ejected from the university, risking deportation.

According to Gregory Zuckerman's book *A Shot to Save the World*, her former supervisor told immigration officials that Karikó was living in the country illegally. She had to hire a lawyer to fight deportation, and as a result, a new employer withdrew its job offer.

She moved to the University of Pennsylvania and kept researching mRNA.

But nobody wanted to fund it.

She applied for grant after grant and never received funding, which in academia is crucial because it's how academics pay themselves and prove they should be there.

Why? Because mRNA seemed impossible to work with.

Other scientists hated working with RNA. "When I run it, everything is a smear, is always degraded," they told her. Karikó would respond: "Because your laboratory is contaminated, your apparatus is contaminated." But people didn't listen.

By the late 1990s, Karikó's work had stalled for lack of funding. She considered leaving Penn entirely or pursuing different work.

"If I don't bring in the money I don't deserve the working space," she says. "So that's the rule. Every university is like that."

In 1995, the University of Pennsylvania demoted her from the tenure track. Her new position pushed her off the tenure track and drove her pay below that of her lab tech.

Karikó began to think she was not good or smart enough, saying, "I thought of going somewhere else, or doing something else."

Then, in 1998, she met Drew Weissman at a photocopier.

Karikó and Dr. Weissman frequently met at the photocopier, sometimes arguing over who should get to use it first. Karikó told Weissman she could make any mRNA. Weissman listened. The two began a long collaboration.

"We worked side by side because we could not get funding or publication—we could not get people to notice RNA," Weissman said. "Everyone had given up on it."

"We spent 20 years figuring this out as we realized how important it had the potential to be—that is why we never gave up, kept working and persevering."

The breakthrough came in 2005.

Karikó and Weissman published research demonstrating how to modify mRNA in a way that would not trigger cell death, making the technology usable for vaccines and therapies.

Their key finding was rejected by the journals *Nature* and *Science*, but eventually accepted by the publication *Immunity*.

Their 2005 paper met with no fanfare. In 2008, an assistant professor at Harvard stumbled across it and elaborated on it, crediting both Karikó and Weissman.

But still, no one cared.

"Ten years ago I was kicked out from Penn and forced to retire," Karikó said. In 2013, at age 58, she joined BioNTech in Germany.

"For nine years I commuted from the US to Germany—I was 58 years old, and I was still culturing plasmids and feeding cells."

Then 2020 happened.

COVID-19 swept the world. Millions died. The global economy collapsed. Humanity needed a vaccine—fast.

And suddenly, Katalin Karikó's "useless" research became the most important science on Earth.

The mRNA technology she'd spent decades perfecting became the basis for the Pfizer-BioNTech and Moderna COVID-19 vaccines.

When Karikó found out that the Pfizer-BioNTech trials of an mRNA vaccine for COVID-19 worked, she ate an entire box of Goobers chocolate-covered peanuts by herself.

The vaccines saved millions of lives.

On October 2, 2023, Katalin Karikó and Drew Weissman won the Nobel Prize in Physiology or Medicine.

"Kate is probably the first Nobel Prize winner that wasn't a professor," said her colleague David Langer. "It's this weird thing of someone who's completely out of left field who achieves the greatest accomplishment in science and saved the world."

"I felt successful when others considered me unsuccessful because I was in full control of what I was doing," Karikó says.

"I want young people to feel—if my example, because I was demoted, rejected, terminated, I was even subject for deportation one point—that if they just pursue their thing, my example helps them to wear rejection as a badge."

"Why I didn't stop researching is because I did not crave recognition."

She was demoted four times. Rejected from hundreds of grants. Nearly deported. Told her work was worthless.

She kept going anyway.

Not because she knew she'd win a Nobel Prize someday.

Because she believed in the work.

And that work saved the world.

DH25030 Biological Information Codes V01 171225

 Biology is saturated with information-coding structures beyond DNA. Some are well-defined “codes” in a strict sense (symbols + rules + interpretation), others are looser but still genuine informational architectures. Below is a taxonomy of identified biological information codes, ordered roughly from molecular to cognitive scales.

1. The Genetic Code (beyond DNA itself)

You already set this aside, but it’s worth naming its extensions:

• Codon → amino acid mapping

• Start/stop codons

• Alternate genetic codes (mitochondria, ciliates)

This is a symbolic code, not chemically necessary.

2. Epigenetic Codes

Well-established and experimentally characterized.

A. Histone Code

• Combinatorial post-translational modifications on histone tails

• Methylation, acetylation, phosphorylation, ubiquitination

• Interpreted by “reader” proteins

Same DNA, different gene expression states.

B. DNA Methylation Code

• Cytosine methylation patterns

• Cell-type and development specific

• Heritable across cell divisions

These function as contextual annotation systems.

3. The Splicing Code

Controls how pre-mRNA is edited.

• Exonic/intronic splicing enhancers and silencers

• Binding proteins interpret sequence motifs

• Determines which exons are included

This code dramatically expands proteomic diversity.

4. The RNA Regulatory Codes

RNA is not just a messenger.

A. microRNA / siRNA Targeting Code

• Short RNA sequences target mRNAs via partial complementarity

• Rules are probabilistic, not deterministic

B. RNA Editing Code

• Post-transcriptional base changes (e.g., A→I editing)

• Alters protein products and regulation

5. The Protein Folding Code

• Linear amino acid sequence → 3D structure

• Governed by constraints, not a simple lookup table

• Encodes function via shape

This is an implicit but real information mapping.

6. Post-Translational Modification (PTM) Codes

Proteins are further coded after synthesis.

• Phosphorylation patterns

• Glycosylation patterns

• Ubiquitination (especially the ubiquitin code)

These act as molecular flags controlling localization, degradation, and interaction.

7. The Glycan (Sugar) Code

One of the most information-dense known systems.

• Branched carbohydrate structures on cell surfaces

• Encoded by enzyme pathways, not templates

• Read by lectins and receptors

Functions:

• Cell–cell recognition

• Immune signaling

• Pathogen interactions

8. Cellular Signaling Codes

Identified via systems biology.

Examples:

• Calcium signaling frequencies

• MAP kinase pulse patterns

• Hormone concentration and timing

Meaning depends on:

• Amplitude

• Duration

• Location

• Temporal pattern

This is syntax and semantics, not chemistry alone.

9. The Developmental (Morphogen) Code

Embryogenesis relies on spatial codes.

• Morphogen gradients

• Threshold responses

• Combinatorial gene regulatory networks

Cells infer positional information from signal patterns.

10. Neural Codes

Extensively studied but not fully solved.

Types include:

• Rate codes

• Temporal codes

• Population codes

• Sparse codes

These encode:

• Sensory features

• Motor plans

• Concepts

• Memory

11. The Immune Receptor Code

Highly concrete and measurable.

• V(D)J recombination

• Somatic hypermutation

• Pattern recognition receptors

This creates a combinatorial recognition space encoding “possible threats.”

12. The Cytoskeletal Code (emerging)

Increasingly supported.

• Microtubule post-translational modifications

• Actin dynamics patterns

• Spatial organization rules

Regulates:

• Intracellular transport

• Cell polarity

• Division

13. Metabolic Network Codes

Less symbolic, but rule-based.

• Feedback loops

• Switches

• Oscillators (circadian rhythm)

These encode state and control logic.

14. Behavioral and Social Codes

In multicellular organisms:

• Innate behavioral programs

• Learned action patterns

• Vocalizations, gestures, pheromones

These are transmitted, interpreted, and context-dependent.

15. Cultural Codes (humans only)

Still biological in substrate.

• Language

• Mathematics

• Norms and institutions

These are high-level symbolic systems layered on neural codes.

16. A unifying insight

Biology does not rely on a single master code.

Life is a stack of interacting codes, each constraining and interpreting the others.

DNA is just the most stable and lowest layer.

17. A compact definition

A biological information code exists when:

1. There are distinguishable symbols or states

2. There are rules mapping them to effects

3. There is machinery that interprets them

4. The mapping matters for function and survival

Many systems meet this criterion.

If you want to go deeper

We could:

• Rank these codes by “symbolicity”

• Compare biological vs artificial codes

• Discuss which are truly arbitrary vs constrained

• Explore whether unknown codes remain to be discovered

• Examine whether physics itself supports proto-codes

Just tell me where you want to go next.