Tag: science

The goldilocks zone

a 10x larger goldilocks zone in planetary systems will revise everyone’s estimates in the drake equation upwards. “The surfaces of rocky planets and moons that we know of are nothing like Earth. They’re typically cold and barren with no atmosphere or a very thin or even corrosive atmosphere. Going below the surface protects you from a whole host of unpleasant conditions on the surface. So the subsurface habitable zone may turn out to be very important. Earth might even be unusual in having life on the surface.”

Cheapium

In the search for cheaper materials that mimic their purer, more expensive counterparts, researchers are abandoning hunches and intuition for theoretical models and pure computing power.In a new study, researchers used computational methods to identify 10s of platinum-group alloys that were previously unknown to science but could prove beneficial in a wide range of applications.

i hadn’t thought beyond proteins, but computational chemistry can be used to find radically cheaper catalysts than platinum, and in general, revolutionize materials science. this is potentially a very big deal, as advances in materials science are one of the few areas that tend to benefit all of mankind equally.

CRISPR

CRISPR allows for much better genetic engineering than previous approaches and is a huge deal. It even works in human cells. Probably Nobel prize material.
2015-06-11: 1000x CRISPR

It is now possible to record a human genome (differences relative to a reference is only 2 megabytes. This is instead of 9 terabytes for a human genome with image data. CRISPR improvements are getting to 1 off target in 1 in 100 trillion (10^14) to 1 in 10 million trillion (10^19)

2015-11-11: CRISPR is the real deal

Editas plans to deliver the CRISPR technology as a gene therapy. The treatment will involve injecting into the retina a soup of viruses loaded with the DNA instructions needed to manufacture the components of CRISPR, including a protein that can cut a gene at a precise location. To treat LCA, the company intends to delete 1000 DNA letters from CEP290 in a patient’s photoreceptor cells.

2015-11-12: CRISPR Monsanto Problem

CRISPR is far too important to become entangled in the same web of confusion that has made G.M.O.s such a toxic issue. We ought to have learned something from those troubling and extended shouting matches; scientists, politicians, and everyone else needs to join in on this debate now. Society has no choice but to come to terms with both the potential benefits and the possible risks. That will require a big change: today, there isn’t even really a regulatory mechanism capable of governing products like CRISPR.

2016-03-09: Improvements to CRISPR subtypes like Cpf1 and now Cas9 are happening very quickly. This should reduce errors and increase the power of these gene editing technologies.
2016-10-14: CRISPR corrects sickle cells

Sickle cell disease is a genetic disorder caused by a mutation in one of the hemoglobin genes, which causes deformation of red blood cells and results in occlusion of blood vessels, severe pain crises, and progressive organ injury. To correct the mutation that causes this disease, DeWitt et al. modified hematopoietic stem cells from sickle cell disease patients using a CRISPR/Cas9 gene editing approach. The authors showed that the corrected cells successfully engrafted in a mouse model and produced enough normal hemoglobin to have a potential clinical benefit in the setting of sickle cell disease.

2018-04-26: Improving CRISPR accuracy 10000x

The use of bridged nucleic acids to guide Cas9 can improve its specificity by over 10000x in certain instances — a dramatic improvement.

2019-02-27: Doudna on CRISPR

Do you think that the medical applications of CRISPR in themselves can inform basic science?

For sure. CRISPR technology has been widely adopted by all kinds of scientists, including people like me. I was never doing anything with genome editing before CRISPR came along.

In my lab we’ve had a project over the last few years working on Huntington’s chorea, a degenerative neurological disease. The mutation that causes the disease is a single codon — 3 base pairs in the DNA — that gets repeated many times. If the codon gets repeated too many times, it leads to a defective protein that causes this disease. That’s been known for a long time, but the challenge was, how do you fix it?

We’ve been working on a way to deliver the CRISPR into mouse neuronal cells to make the necessary edits. But one of the curious things that’s come out of that line of work is that we found that only neuronal cells in the mouse brain were getting edited, not [the supportive glial] cells called astrocytes.

These cells are a lot smaller, so it could be that they don’t have enough surface area to take up the CRISPR protein efficiently. Or maybe they don’t respond to DNA cutting and editing in the same way as other cells.

2019-03-01: CRISPR error rates. Gene Editing Is Trickier Than Expected

how many errors are too many? Cells are prone to making their own mistakes—on the order of 1 every 1M-100M base pairs, with more for skin cells, and fewer for sperm and eggs. Does it matter if an overactive gene editor makes that number closer to 1 in 500K?

2019-05-07: CRISPR Inhibitor

The number of stories and journal articles about how CRISPR DNA-editing technology works, has worked, and is planned to work are beyond counting. How about an article about how to stop it in its tracks? That’s this one, just published in Cell from a multicenter team in Cambridge and New York. It describes a screening program for small-molecule inhibitors of S. pyogenes Cas9 (spCas9), because one would want some ways (not all of which currently exist) to turn its effects off in given places and at given times.

2019-10-04: CRISPR documentary

The teaser zooms in on the stomach-stabbing self-experimentations of biohackers like Josiah Zayner and Aaron Traywick. DIY Crispr is just one subplot in the larger narrative about what happens when nature can be minutely controlled, when humans might even preside over their own evolution. Their cameras also follow scientists like Jennifer Doudna and Kevin Esvelt and the first patients in an experimental gene therapy trial to treat hereditary blindness. “Our main hope is to create a discussion around these technologies. People might come away excited. Or they might be scared. But at least that means they’re talking and learning and understanding what’s coming.”

2019-12-18: CRISPR in Humans?

One of the most compelling arguments against CRISPR gene editing, namely the potential for misuse, can also be considered the most compelling argument for CRISPR gene editing. Banning progress on gene editing technology may create a black market, but the continuation of research on gene editing will allow the scientific community to control its use and ensure patient safety

2022-03-07: Another similar claim of a 4000x improvement. The new paper doesn’t mention BNANC, so who knows if these improvements stack. Probably not.

Researchers discovered how some of these errors can happen. Usually, the Cas9 protein is hunting for a specific sequence of 20 letters in the DNA code, but if it finds one where 18 out of 20 match its target, it might make its edit anyway. To find out why this occurs, the team used cryo-electron microscopy to observe what Cas9 is doing when it interacts with a mismatched sequence. To their surprise, they discovered a strange finger-like structure that had never been observed before. This finger reached out and stabilized the DNA sequence so the protein could still make its edit. Having uncovered this mechanism, the team tweaked this finger so that it no longer stabilized the DNA, instead pushing away from it. That prevents Cas9 from editing that sequence, making the tool 4000x less likely to produce off-target mutations. The team calls the new protein SuperFi-Cas9.


2023-01-19: CRISPR Cas12a2

“With this new system we’re seeing a structure and function unlike anything that’s been observed in CRISPR systems to date”.

While other CRISPR systems bind to their target sequence, make their cut, and then stop, when Cas12a2 binds to its target, it seems to “activate,” transforming in shape.

“It’s a change in structure that’s extraordinary to observe — a phenomenon that elicits audible gasps from fellow scientists”. Once activated, the protein can bind to any genetic material that comes near it, whether its single-stranded RNA, single-stranded DNA, or double-stranded DNA. Cas12a2 then starts shredding the material, making multiple cuts in indiscriminate locations.

Because the genetic material can belong to the bacteria itself, the result can be cellular death. CRISPR causes the infected cell to self-destruct — rather than let it become a virus factory.

2023-04-01: A much better drug delivery

Microbiologists were learning more about an unusual group of bacteria that use molecular spikes to pierce a hole in the membranes of host cells. The bacteria then transport proteins through the perforation and into the cell, exploiting the host’s physiology in their favor. Using the artificial-intelligence program AlphaFold, which predicts protein structures, the team designed ways to modify the tail fibre so that it would recognize mouse and human cells instead. They then loaded the syringes with various proteins, including Cas9 and toxins that could be used to kill cancer cells, and delivered them into human cells grown in the lab, and into the brains of mice. Similar to the early days of CRISPR–Cas9 research, the bacterial syringes are studied by only a handful of labs, and their roles in microbial ecology are only beginning to be understood.

2023-12-15: There are far better technologies like base and prime editing, than CRISPR.

That’s really what inspired us to develop base editing in 2016 and then prime editing in 2019. These are methods that allow you to change a DNA sequence of your choosing into a different sequence of your choosing, where you get to specify the sequence that comes out of the editing process. And that means you can, for the first time in a general way, programmable change a DNA sequence, a mutation that causes a genetic disease, for example, into a healthy sequence back into the normal, the so-called wild type sequence, for example. So base editors work by actually performing chemistry on an individual DNA base, rearranging the atoms of that base to become a different base.

Dark Age Myth

some of the efforts by the theologians to put some limits on what could and could not be accepted via the “new learning” actually had the effect of stimulating inquiry rather than constricting it. The “Condemnations of 1277” attempted to assert certain things that could not be stated as “philosophically true”, particularly things that put limits on divine omnipotence. The way was clear for the natural philosophers of the Middle Ages to move decisively beyond the achievements of the Greeks. Which is precisely what they proceeded to do. Far from being a stagnant dark age, as the first half of the Medieval Period (500-1000 AD) certainly was, the period from 1000 to 1500 AD actually saw the most impressive flowering of scientific inquiry and discovery since the time of the ancient Greeks, far eclipsing the Roman and Hellenic Eras in every respect.

The catholic church was far less responsible for the lack of scientific progress in the middle ages than commonly believed (and in fact was a major contributor). This leaves the lack of civilization between 500 – 1000 as the major culprit.
2022-08-26: As always, a lot of history is fictional.

The fantastical imagery that many of us consider “medieval” today has been invented in the centuries since. While some legends are rooted in the period, like the stories of King Arthur and Camelot, many others were embroidered onto an imagined, “medieval-ish” past through fantasy stories, films, and other forms of popular culture, especially from the 19th century on. Modern medieval tales have become populated with knights, dragons, witches, and fairies. Only knights and dragons were frequently depicted in the period, and anything magical or mysterious was understood through the lens of religion.

Much material is drawn from the 19th century, when the Romantic movement created its own version of the Middle Ages in the art, illustration, and architecture of the Gothic Revival. Their works embodied a romantic vision of simpler, more straightforward times and projected Victorian social mores onto medieval tales of heroism and tragedy. Everything from William Morris’s elaborate page borders (echoing illuminated manuscripts) to the now-iconic gargoyles added to Notre Dame contributed to an idealized aesthetic of the Middle Ages — and influenced our subsequent view of the time.

Galaxy Full of Planets?

there are 40B earth-like planets in the habitable zone in the galaxy.

2014-12-05:

the number of biotic planets in the Milky Way is between millions and billions, and the corresponding distance to the nearest biotic world is 10-100 light years. the likely distance to the nearest civilizations detectable by SETI is of the order of a few 1000 light years

this is a very accessible paper on the Drake equation (which may well achieve a cultural status similar to e=mc^2 this century)

1% of the stars in the Milky Way could have earth like planets (smaller rock like planets) Another study shows the Milky Way is twice as big as previously thought. So instead 100b stars there could be 200b and of those 1% or 2b could have earth like worlds around sun like stars.