BIOFAQ

Interactive Biology Explanations

Table of Contents

Pea Plants

For a long time biology consisted of looking at things, naming things and cutting things open.

Progress was made but biology didn't become an exact science until 1865.

That was the year that Gregor Mendel, a friar and biologist, discovered his genetic laws of heritability.

Let's try each of them out to get a better intuition about Mendelian genetics.

When Mendelian Genetics was rediscovered in the early 20th century, it drew comparisons to the laws of thermodynamics.

Biologists could now test cause-effect relationships, which attracted the attention of many physicists.

Many of them studied inheritance in bacteriophages, which were then the simplest organisms available to scientists.

Many of their experiments followed the below logic: Step 1 causes Step 2 causes Step 3 causes Step 4 and so on.

This was done not because the scientists were naive about how complex living biological systems are.

Rather, they didn't have the tools to understand systems of biology just yet.

A lot of progress was made during the early 20th century, but there was still a big open question:

How is heritable information stored in cells?

Mendelian Genetics doesn't give an answer to this, just cause and effect relationships.

Interestingly, scientist hypothesized that amino acids stored this information.

There are 20 types of amino acids and they are quite long compared to other biomolecules, such as DNA.

"You're telling me DNA is all you need? Just four base pairs? That's it?"

It's more complicated, but, yes, life can arise from very simple origins. (or perhaps algorithms one day...)

Once the structure of DNA was elucidated, the Central Dogma of Molecular Biology was borne:

DNA is transcribed into RNA via RNA Polymerase (RNAP here)

Then that RNA is translated into proteins.

(The actual steps are much more complicated, but I am still working on increasing the complexity of my simulations.)

More detail will be added later but here's where the story went.

We went from reading just a handful of genes to an entire (not exactly, but mostly) human genome.

The cost of reading genomes decreased super-exponentially, to where they are now closing in on 100 USD per genome.

As sequencing genomes became easier, sequencing other modalities (such as proteomes) became easier as well.

Now we're sequencing single cell RNA (scRNA-seq) frequently to better understand the heterogeneity of biology.

There's so much data available now...I wonder what we should do with that data?

(On an unrelated note, have any of you noticed how good those "neural networks" have been getting?)

Current Research Areas

First things first: Everyone (researcheres especially) should check out Impetus Grants

They were started by Lada Nuzhna as a way to rapidly fund basic aging biology research and clinical trials

They've distributed (as of September 4th, 2023) 24 million dollars in grants

They have minimal bureacracy and do incredible work

Onwards

AI

What is it?

The study, creation, and application of algorithms that can "learn" from datasets fed to them to perform exceptionally well on a given task(s).

Why is it important?

AI is a new paradigm for writing software (software 2.0) and is changing how we do research.

How exactly does it work?

That's a bit of a long story. Here are some great videos from Andrej Karpathy's Youtube Channel.

What are current research directions/open questions?

Can we get an AlphaFold moment for other areas of biology? (lack of data is a big problem)

Aging Clocks

What is it?

A variety of methods to tell how (biologically) old you are.

Why is it important?

If we can't measure your biological age, how do we know our therapies have worked?

(Note: Dramatic Age Reversal could be more visible, but more subtle therapies and basic research are heavily dependent on accurate clocks)

How exactly does it work?

Ex. Horvath Clocks: DNA Methylation sites at CpGs are fed into regression models (or other statistical models) and output biological age.

What are current research directions/open questions?

How can we reduce the error between clock predictions and true biological age?

New Model Organisms

What is it?

You've probably heard of lab mice, C. Elegans worms, Bakers Yeast, or the Drosophila fruit fly.

Dogs and Killifish (An African Invertebrate fish) are very promising new "model organisms".

Why is it important?

While humans are the best model of human biology, testing in humans is hard because 1. It's unethical and 2. We live (relatively) long

The ideal longevity model organism would be nearly identical to a human but live a very short amount.

C.Elegans hits the second part but not the first. Lab mice somewhat hit the first part and somewhat hit the second part.

Dogs are much closer to humans than mice, which is why many startups are working on drugs for dogs. (Big market)

Killifish have a 6 month lifespan (very short! good!) but are also invertebrates (closer to human physiology).

How exactly does it work?

Same as other model organisms.

Dogs you have to go through vet clinical trials and approvals (which are generally shorter and less complex than humans but are non-trivial).

and killifish are more of an academic exercise since there isn't really a market for killifish pets. (Yet! Who knows?)

What are current research directions/open questions?

Mice, Flies, Yeastand worms have been well studied. Dogs and Killifish are promising, but there needs to be more papers done using them.

Reprogramming

What is it?

Four transcription factors (O,S,K,M) that turn old cells into young cells.

Why is it important?

It is perhaps the most powerful (and most VC-funded) tool against aging we have.

How exactly does it work?

O,S,K, and M are transcription factors. They can modulate how DNA gets transcribed into RNA, which then creates proteins.

These four factors (or just three, as David Sinclair's group has shown) can create iPSCs (induced pluripotent stem cells).

However, most research is focused on "partial" epigenetic reprogramming.

If used at full force, these factors can get rid of cells identities and can cause nasty cancers. (Very, Very simplified version)

What are current research directions/open questions?

How can we safely control these factors?

Healthcare Economics

"In this world nothing can be said to be certain, except death and taxes."

— Benjamin Franklin

Why does healthcare take up such a large percentage of the United States GDP?

Chronic conditions, which are exacerbated by age.

Think of how many 20 year olds you know who have heart disease?

Not many (although some do exist).

What about alzheimers?

A broken hip (from a small fall, not from a serious accident)?

And so on.

The aging process plays a large role in increasing the fraility of human patients, which can be expressed with the following graph.

The units don't correspond 1 to 1 with human age, but you can think of the "Event Rate" as the probability that you die every time unit.

If you lower the event rate, this simulates being younger, but if you increase the event rate, this simulates being older.

A very powerful conclusion to take from this is that if you could invent drugs that target aging mechanisms,

you could have a very powerful preventative medicine that could make (and more importantly, SAVE) a lot of money.

Let's take a look at some of those startups.

Startups

Retro Biosciences was founded in 2021 by Joe Betts-LaCroix, Sheng Ding, and Matt Buckley

Their mission is to add 10 years to healthy human lifespan

Their approach is to do this through Autophagy, Parabiosis, and Cellular Reprogramming Therapies

They're hiring here

NewLimit was founded in 2021 by Brian Armstrong, Blake Byers, Jacob Kimmel, and Greg Johnson

Their mission is to significantly extend human healthspan and develop intermediate therapies along the way

Their approach is to do this through ML Screening + High-Throughput + Epigenetic Reprogramming

They're hiring here

Rejuvenate Bio was founded in 2017 by George Church, Noah Davidsohn, and Daniel Oliver

Their mission is to target the core drivers of chronic age-related diseases

Their approach is to do this through gene therapies and epigenetic reprogramming in dogs and humans

They're hiring here

Altos Labs was founded in 2022 by Richard Klausner and Hans Bishop.

Their mission is to restore cell health and resilience through cellular rejuvenation programming to

reverse disease, injury, and the disabilities that can occur throughout life.

Their approach to do so is through basic research on cellular reprogramming and the mechanisms of aging

They're hiring here

Loyal was founded in 2019 by Celine Halioua

Their mission is to develop the first FDA-approved drugs intended to extend lifespan and quality of life in dogs.

Their approach to do so is through taking existing small molecules and

run the first FDA approved trial targeting aging directly for dogs. Expand into humans later.

They're hiring here

Epiterna was founded in 2022 by Alejandro Ocampo and Kevin Perez

Their mission is to help pets and people live longer and healthier lives

Their approach to do so is through high-throughput experimentation and

Computational biology for small molecules for dogs and humans.

They're hiring here

Insilico Medicine was founded in 2014 by Alex Zhavoronkov

Their mission is to accelerate drug discovery and development by

leveraging our rapidly evolving, proprietary platform across biology, chemistry, and clinical development.

Their approach to do so is through an end-to-end AI Pipeline for

Dual-Use Therapeutics (Targets aging mechanisms and other diseases)

They're hiring here

Fellowships + Communities

On Deck Longevity Startup School

Who's it for?

Founders & Explorers, Students & Researchers, Business Experts

What do you do?

Learn as much as you can for 12 months from teachers + a community.

How much does it cost?

Nothing. If you decide to start a company, they'll offer 125,000 USD for 7%.

Time Commitment?

During onboarding at least 4 hours/week, after that it's flexible, but you could easily spend 20 hrs/week talking to people.

The Time Initiative Fellowship

Who's it for?

Undergrads and students not enrolled in graduate studies.

What do you do?

Annual paid retreat, Fellows only community, Mentorship, and receive 8,000 USD research grant.

How much does it cost?

Nothing.

Time Commitment?

Did not explicitly say, but likely under 5 hr/week normally but retreat is full-time in-person.

LBF

Who's it for?

Everyone!

What do you do?

Learn about Longevity Biotech from the best for 12 weeks, meet a peer group and (optional) go on an in-person 3-day retreat!

How much does it cost?

(Note: you can get financial aid/scholarships to cover all of the costs if needed)

$899 if you go on the three day retreat $490 if you don't go on the retreat

After the program is done 99$/year to maintain access to the community

Time Commitment?

Retreat is 3 full days, otherwise around ~2hrs/week for the online portion of LBF.

Aging Research and Drug Discovery (ARDD) Conference

Who's it for?

Everyone!

What do you do?

It's an academic conference on aging research and drug discovery.

High School/Undergraduate Students can partake in the "Student Ambassador Program"

How much does it cost?

In-Person Ticket (400-700 USD, depending on how early + academic status), Virtual Ticket (50 USD)

Student Ambassador Program - Free registration for main meeting/workshops

Time Commitment?

For the conference - full-time for x days, for the Student Ambassador Program - 5-10 hrs during the week (?)

"I have a friend who's an artist and has sometimes taken a view which I don't agree with very well.

He'll hold up a flower and say 'look how beautiful it is,' and I'll agree.

Then he says 'I as an artist can see how beautiful this is but you as a scientist take this all apart and it becomes a dull thing,' and I think that he's kind of nutty.

First of all, the beauty that he sees is available to other people and to me too, I believe.

Although I may not be quite as refined aesthetically as he is ... I can appreciate the beauty of a flower.

At the same time, I see much more about the flower than he sees.

I could imagine the cells in there, the complicated actions inside, which also have a beauty.

I mean it's not just beauty at this dimension, at one centimeter; there's also beauty at smaller dimensions, the inner structure, also the processes.

The fact that the colors in the flower evolved in order to attract insects to pollinate it is interesting; it means that insects can see the color.

It adds a question: does this aesthetic sense also exist in the lower forms?

Why is it aesthetic?

All kinds of interesting questions which the science knowledge only adds to the excitement, the mystery and the awe of a flower.

It only adds.

I don't understand how it subtracts."

Onwards!