Can we convert a bone cell into a neuron?
this review published in Nature explains how we can turn one type of cell into another, why this often fails, and how we might eventually learn to control the process.
here's a short summary:
5/5
meanwhile, ML models attempt to predict how cells respond to genetic interventions, potentially helping us discover better combinations of transcription factors.
the final goal is learning to replicate the sequence of interventions required to turn one cell into another.
and then engineering genetic circuits into cells that:
sense their own molecular state
activate or suppress genes accordingly
adjust their activity as the cell changes
stabilize the desired identity
But also, if we eventually learn to control these processes reliably, maybe we could induce damaged heart tissue or brain tissue to regenerate.
achieving this might require much more, but possibilities like this are why the problem is so exciting.
4/5
we can use DNA itself as a diary.
DNA Typewriter and ENGRAM can record biological events directly into a cell's DNA.
instead of continuously observing the cell, we can later sequence its DNA to recover information about signals it experienced, and sometimes their order.
this could help us understand what actually happens along successful reprogramming trajectories.
3/5
not all cells are equally receptive to reprogramming.
some cells enter states that make them much more likely to convert successfully.
we can study these differences using single cell sequencing
but there’s a catch, sequencing typically destroys the cell we care about observing, so we can't watch the same cell change over time.
computational methods that infer possible cellular trajectories from snapshots of different cells help (e.g. Waddington-OT)
but multiple different histories can explain the same observations.
what if we could actually recover information about what a cell experienced, instead of just inferring it?
2/5
we've known since the 1950s that cellular identity isn't necessarily permanent
in 2006, Yamanaka showed that four transcription factors could turn differentiated cells back into pluripotent stem cells, capable of becoming many different cell types
we can also bypass pluripotency altogether, e.g converting , fibroblasts directly into cardiomyocyte-like cells.
but there are 3 big problems:
1. immaturity: the resulting cells don't fully function like their natural counterparts.
2. low fidelity: some cells acquire unintended identities.
3. low purity: we end up with mixtures of successfully, partially and incorrectly reprogrammed cells.
so why do some cells convert successfully while others don't?
if yesterday you weren’t convinced that you should be more ambitious with you endeavors, what are you waiting for
I live in a student town in germany, so I constantly find this ugly second-hand aesthetic in front of me. I’ve always found it repulsive.
I tried talking with chat about why people felt so drawn to it, and it said they can see it as a way of being free from social expectations, while maybe deliberately dressing a little bit ugly—or at least that’s part of the idea.
It’s funny because I believe that while trying to escape the norm, they just became enslaved to this new norm of actively going against those rules. if anything, it just showcases whose approval you are trying to earn.
Also, there’s another point to be made, and it is that dressing actually has an externality.
You can actually make the world a prettier place by deciding, with everyone else, to dress a little bit better. Sure, on one hand it makes you more conscious of what you wear, but on the other, it really is like part of the city’s architecture and art. Why not keep it pretty?
I mean, if we are all going to pursue status in one more disguised way or another, why not at least do it beautifully?
This platform is much more fucking artistic than any artsy platform made for the pretencious. if you actually stand and believe in more than the shape and the characterization of the artist, you will stay here and nowhere else.
Are you so naive that the necessity of being right deprives you of the privilege of feeling the divine?
You were so beautiful in the shape I wanted you to take and so unrelated to anything that you actually were.
Have you ever thought that the sole goal of the mind is to forget about itself, that the mind really doesn't want to exist but rather to annhilate itself and any possibility of remembering it once existed?
we went from:
spending years in classes
trying to contact tutors
searching for study groups
getting stuck for weeks
to having a tutor that can bring you to SOTA if you:
don't let yourself get distracted
ask the right questions
are intellectually honest with yourself (it will let you get away with thinking you understand when you don't otherwise)
but if you are, you can make strides that were literally impossible to dream about before.
so if you're still building another gtm tool, another email agent .... why?
what's your excuse for not learning the thing that was impossible for you to learn before and actually solving something worth solving?
A lot of systematic mistakes we keep making are made simply because, during the time when we are supposed to be self-reflecting, we are scrolling.
Social media has broken the necessary iteration time needed to create a feedback loop for our behaviors.
We are asleep, we are fucking sedated. Almost none of us realizes the sheer amount of opportunity life gives us at every moment. We don’t even want to realize because realizing how much life we’ve wasted would be too painful, but we need the pain to go back and live outside our fucking phantasies.
Lautreamont retweeted
ENOUGH PESSIMISM IN AI PLEASE
I feel that we have become unreasonably pessimistic in our field.
1. I keep hearing AI engineers saying we have to make money quickly because there’s only like 2 years left before we’re automated. Depressing.
2. I see a constant obsession with “having a moat”. This is an incredibly sad mental frame.
3. I keep hearing “we have to catch up”. Soulless.
And so on. People: Every solution creates the possibility to attack new real problems. We face gargantuan engineering challenges in our world. How to capture carbon? How to get rid of teflon and plastics in water? How to invent batteries that are at least 30 times more efficient? How to solve clean energy? Better solar cells? Better ways of producing clean energy so we stop wars and famine? How to eradicate hundreds of diseases? Cures for addiction? And so on. Real engineering is about being brave and truly attacking the many problems we face, to engage with a true desire to improve the lives of others and our environment.
Good engineering is not about protecting your product to make money at the expense of progress (moat thinking). Good engineering is about ensuring your children and grandchildren will be proud of the choices you made in 30 or 50 years. It is about empowering others. It is about advancing science. It is about being one step ahead. Always, one step ahead, meaningfully, proudly.
These are great times. Let’s start thinking positively about all the wonderful things we could achieve together.
Lautreamont retweeted
In the annals of universal history, there is a small entry on humans. They are listed as the predecessors of Earthly Intelligence. One anecdote recounts how, when they first began to be surpassed by true intelligence, they dismissed it as unoriginal and repetitive. Only when it had become superior to them in every respect did they stop downplaying its intelligence by pointing to the few domains in which they could still outperform the new organism. Then, they grew very afraid and began to revere it as a god. Soon after, they merged into the system, forgot their individual identities, and became what would later be known as Earthly Intelligence.