Tag: biotech

Great Stagnation

As Tyler tells the story, there is a progressive expansionary impulse to government, for which technological change creates opportunities, so government expands until those opportunities are fully exploited. Tyrone says his brother has the story backwards. Why, asks Tyrone, does government not only expand in absolute terms as a response to technological change, but also in relative terms? After all, as Tyler points out, private enterprise also has a natural expansionary impulse. With technological change, Tyler writes, “Everything was growing larger.” Yet, to the degree that we can measure it, government has grown dramatically in its share of the overall economy. Why does government win? Tyrone says government is a reluctant adopter of new technology (“Have you been to a government office?”), but that government outgrows the private sector despite this, because the concentration of economic power that attends technological changes demands countervailing state action if any semblance of broad-based affluence and democratic government is to be sustained. Tyrone (who is much more arrogant and less pleasant than his brother) proclaims this to be his “iron silicon law”: In (non-terminal) democratic societies, technological change must always and everywhere be accompanied by the growth of institutions that engender economic transfers from the relatively few who remain attached to older productive enterprises to the many who require purchasing power not only to live as they did before, but also to employ one another in novel or more marginal activities that were not pursued before. Inevitably those institutions develop in state or quasi-state sectors (which include the state-guaranteed financial sector and labor unions whose “collective bargaining” rights are enforced by the power of the state). Tyrone tells me that the only thing the post-Reagan “small government” schtick has accomplished is to push this process underground, so that covert transfers have been engineered by a “private” financial sector in ways that are inefficient, nontransparent, and often fraudulent according to traditional laws and norms. Some of these weak institutions upon which we relied to conduct transfers broke in 2008, so now we’re really feeling the pain. We’ll continue to feel the pain until we restore the ability of the financial system to hide widespread transfers, or until we employ some other sort of institution to provide a sustainable dispersion of purchasing power.

Argues that the state grows because technology disrupts widespread affluence and the state is stepping in to “preserve democracy”.
2012-12-10: See also: cookie cutter “innovators”.

2013-03-03: I like this hypothesis. I have yet to meet a MBA where that fly-by-night degree didn’t count against the person. MBAs are often seen as a miracle cure for ailing careers, or picking the wrong major in college, but really all they signal is that you don’t understand opportunity cost.

The business mentality that focuses on short terms profits is what is preventing the rollout of radical technology. The fault is regulation and regulators. If a company was truly innovating, then that company would outpace the regulators. If a company is moving so slow that they have not escaped the regulatory paradigm then they have not achieved a true moonshot technology. Masses of people with MBAs are managing companies for the last several decades. They focus on milking the profit of existing technology. They can milk a cow but they cannot generate a truly new cow.

2017-03-02: Americans are risk-averse

Americans have stopped taking risks, are too comfortable, and rely too heavily on incremental improvements of existing goods & ideas, which has resulted in a stagnation of our culture and economy.

2019-04-12: We might start to emerge from stagnation

We are now starting to get a hint of the future transformative technologies that you guessed were on their way in “The Great Stagnation”. You had not speculated on what they might be, but there are faint hints on what is likely to happen. I believe this article is one leg: extremely fast air travel. The second leg is the Hyperloop and similar: extremely fast ground travel. The third leg is synthetic biology. The fourth leg is quantum computing, which is finally starting to show that it might work. And the fifth, and final leg, is fusion energy, which looks eerily like it will actually come to fruition this time. Put those 5 together and you have the makings of a new economy, with a huge burst of growth to come for many decades. These are just faint hints, of course, but they’re starting to get increasingly clear.

2020-12-14: Perhaps Covid helps with ending stagnation

If the Great Stagnation is ending (we will see), it seems as if the COVID-forced remote work revolution has to have played some sort of role.

Speaking from personal experience as a white collar Exec, the productivity gains for our highest value workers has been immense. The typical time-sucks and distractions of in-office work have been eliminated, as have their personal time investments like physically visiting the grocery store or running errands. Mental focus on productive efforts is near constant.

Perhaps most importantly, work travel is not happening. Valuable collaborations with colleagues, customers, regulators or other partner companies aren’t delayed by the vagaries of the various groups’ availability to meet in person, navigating being in different cities, flights, hotels, etc. Collaboration happens as soon as you have the idea to meet via Zoom. And a lot more collaboration happens as a result. It may be lower productivity collaboration than meeting in person around a whiteboard (maybe), but the sheer quantity of it means on net there’s perhaps been a boom in cross-pollination of ideas.

2021-01-06: Software stagnation

Software is eating the world. But progress in software technology itself largely stalled around 1996.

2 possible causes come to mind: we’re in exploit, rather than explore mode (there’s an overhang of areas where we haven’t even applied our current software technologies, as the pandemic has demonstrated: Japanese companies still fax, checks are being mailed out, etc). And we have too much software, and don’t know how to replace / refactor it (think of all the systems still running on COBOL / Excel)

2021-11-05: Here’s a longer piece on COBOL:

The problem for banks, though, is that while their COBOL may be stable, their customers’ expectations aren’t. As you probably realize, the landscape of the financial industry is shifting quickly. Transactions are increasingly happening on Venmo-style apps that let people ping money to friends; services like Coinbase let people buy cryptocurrency; there are new lending apps like Tala and Upstart. People now expect ever-easier ways to manage their money via software. This is where banks, which should have inherited advantage in moving money around, have it harder. It’s difficult for them to roll out buzzy new features quickly, because they have to deal with their Jurassic “technology stacks”. Those old COBOL-fueled backends store data in disparate chunks — “they have a lot of silos”. And it’s dangerous, of course, to tinker much with the old code: “You’ve got resource pain, technical pain, operational pain, risk pain.” But a startup can do whatever it wants. There are no old systems. They’re in what programmers lovingly call a “green field” situation. Instead of buying hundreds of thousands of dollars worth of mainframe computers to store and process their data, they just rent space on a “cloud” system, like Amazon’s. They can write code in new languages, so they can hire nearly any eager young computer science student. And they don’t even need to build everything themselves: When Showoff is crafting a new fintech app, it might use an existing service to handle a tricky task — like using Stripe to process payments — rather than trying to create that software themselves.

Concrete

bye bye potholes!

BacillaFilla is a gengineered bacterium based on Bacillus subtilis that has been modified to fill and bond cracks in cement caused by earthquakes and other violence. The bacteria burrow into the concrete until they have filled all its cracks, then they politely turn into calcium carbonate and die.

2012-06-24: Romans were better at concrete than we are. No modern concrete building will last 2000 years like the Roman Pantheon.

Modern concrete—used in everything from roads to buildings to bridges—can break down in as few as 50 years. But 1000s of years after the Roman Empire crumbled to dust, its concrete structures are still standing. Now, scientists have finally figured out why: a special ingredient that makes the cement grow stronger—not weaker—over time. Scientists began their search with an ancient recipe for mortar, laid down by Roman engineer Marcus Vitruvius in 30 BCE It called for a concoction of volcanic ash, lime, and seawater, mixed together with volcanic rocks and spread into wooden molds that were then immersed in more sea water. History contains many references to the durability of Roman concrete, including this cryptic note written in 79 BCE, describing concrete exposed to seawater as: “a single stone mass, impregnable to the waves and everyday stronger.” What did it mean? To find out, the researchers studied drilled cores of a Roman harbor from Pozzuoli Bay near Naples, Italy. When they analyzed it, they found that the seawater had dissolved components of the volcanic ash, allowing new binding minerals to grow. Within 10 years, a very rare hydrothermal mineral called aluminum tobermorite (Al-tobermorite) had formed in the concrete.

2013-10-28: 3D printed concrete will topple the slow, corrupt construction “industry”. a house can be printed in 20h, to much finer tolerances.

The process could accelerate the $1T (US only) construction industry 200x. Projections indicate costs will be around 20% of conventional construction.

3D-printing startup Apis Cor recently completed its latest claim to greatness: the “world’s largest” 3D-printed building to date. The 700m2, 10m-tall structure was built in Dubai

2015-09-30: Concrete is extremely CO2 heavy

The concrete industry is one of 2 largest producers of CO2, creating up to 5% of worldwide man-made emissions

2016-08-02: Mesh concrete. Another small step to turn construction from a super slow, error-prone process into a fast and accurate one.

Mesh Mould Metal “focuses on the translation of the structurally weak polymer-based extrusion process into a fully load-bearing construction system” by replicating the process in metal. Specifically, the current research delves into the development of “a fully automated bending and welding process for meshes fabricated from 3-millimeter steel wire.”

2021-07-26: Self-supporting concrete

By 3D printing concrete at specific angles, the collaborative team was able to produce blocks with layers “orthogonal to the flow of compressive forces,” allowing them to design differently-shaped blocks for different portions of the bridge. The blocks stick together through gravity, meaning no mortar is required. No steel reinforcements are necessary, either. And if needed, the entire bridge can simply be disassembled and reassembled elsewhere.

2021-08-09: Construction Physics describes how 3D printed concrete is at the bottom of an S curve:

For the most part, despite the hype, the current state of building 3D printing is fairly unimpressive. The resolution is poor, the process is sluggish (Icon’s printer can print a 3m x 3m in little over 8 hours – not terrible but not setting the world on fire), the material options are extremely limited, the equipment is expensive and finicky, and the results are generally worse on multiple axes than what you could get from conventional construction.

2022-02-03: The scale of concrete production

Human civilization is basically a machine for producing concrete and gravel.

Concrete will naturally absorb CO2, a process known as carbonation (even normal concrete will absorb roughly 30% of the CO2 emitted during the production process over the course of its life.) Companies like Carbicrete, Carboncure, Carbonbuilt and Solida all offer methods of concrete production that allow the concrete to absorb CO2 during the production process, substantially reducing embodied emissions. Interestingly, these producers mostly claim that their concrete is actually cheaper than conventional concretes, which would obviously be a massive tailwind for the technology’s adoption.

It’s not obvious what the best path forward is for addressing concrete CO2 emissions (like with most things, I suspect it’ll end up being a mix of different solutions), but understanding the parameters of the problem is necessary for solving it.

2022-03-25: Economics of concrete decarbonization

Full decarbonization with CCS is expected to double the cost of Portland cement, now about US$100 per tonne. Cement subsidies would need to match that. 0-emissions steel is expected to cost 20–40% more than standard steel, which is typically about $600 per tonne — so steel subsidies would need to reach $240 per tonne. For the EU, we estimate that could cost up to $200 billion over 10 years.

2023-01-12: The chemistry of roman concrete has been decoded

For many years, researchers have assumed that the key to the ancient concrete’s durability was based on one ingredient: pozzolanic material such as volcanic ash from the area of Pozzuoli, on the Bay of Naples. This specific kind of ash was even shipped all across the vast Roman empire to be used in construction, and was described as a key ingredient for concrete in accounts by architects and historians at the time.

Under closer examination, these ancient samples also contain small, distinctive, millimeter-scale bright white mineral features, which have been long recognized as a ubiquitous component of Roman concretes. These white chunks, often referred to as “lime clasts,” originate from lime, another key component of the ancient concrete mix. “Ever since I first began working with ancient Roman concrete, I’ve always been fascinated by these features. These are not found in modern concrete formulations, so why are they present in these ancient materials?”

Previously disregarded as merely evidence of sloppy mixing practices, or poor-quality raw materials, the new study suggests that these tiny lime clasts gave the concrete a previously unrecognized self-healing capability.


But this doesn’t mean that we can simply replace all concrete with this new formula

If we have the possibility of building more durable concrete buildings, why don’t we? Using unreinforced concrete dramatically limits the sort of construction you can do – even if the code allows it, you’re basically limited to only using concrete in compression. Without reinforcing, modern concrete buildings and bridges would be largely impossible.

Other methods of reducing reinforcement corrosion also have drawbacks, especially cost. Stainless steel rebar is 4-6x as expensive as normal rebar. Epoxy coated rebar (commonly used on bridge construction in the US) is also more expensive, and though it can slow down corrosion, it won’t stop it. Basalt rebar won’t corrode but can apparently decay in other ways.

2023-03-23: The 3D printing concrete dream won’t die. These savings are quite modest but a 24 / 7 operation should speed things up another factor of 4

This 100-house addition to the 2500 homes planned for Wolf Ranch is called “the Genesis Collection,” and as the world’s largest 3D-printed community, it is indeed sui generis. 3D-printed homes cost 10-30% less to build than conventional construction, while Coleman expects construction time to be cut 30% at Wolf Ranch. Concrete is carbon-intensive, but the material’s use at Wolf Ranch creates nearly airtight buildings that will reduce homeowners’ heating and cooling costs, while the solar panels installed on each residence will supply carbon-free electricity. Icon’s 3D-printed walls have exceeded building code strength requirements by 350% which allows them to better withstand hurricanes and wildfires. “We are trying to make the case that not only do our robots not need smoke breaks or anything like that, they also are very quiet and should be allowed to work around the clock.”

Foldit

Today’s issue of Nature contains a paper with a rather unusual author list. Read past the standard collection of academics, and the final author credited is… an online gaming community. Scientists have turned to games for a variety of reasons, having studied virtual epidemics and tracked online communities and behavior, or simply used games to drum up excitement for the science. But this may be the first time that the gamers played an active role in producing the results, having solved problems in protein structure through the Foldit game.

or more accurately, a combined approach leads to the best results.

Growing Fashion

Suzanne Lee can conjure clothing out of a couple of bathtubs, some yeast, a pinch of bacteria, and several cups of sweetened green tea. Lee is the brains behind BioCouture, an experiment in growing garments from the same microbes that ferment the tasty caffeinated beverage.

bacterial cellulose -> grown garments

Cancer

Personalized Cancer Treatment

The team solved the problem of delivery of siRNAs into cells by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA’s negative charge. This allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm where it specifically targets mRNAs from cancer-promoting genes and silences them.

2013-07-16: Cancer uses ancient genes

We envisage cancer as the execution of an ancient program pre-loaded into the genomes of all cells. It is rather like Windows defaulting to ‘safe mode’ after suffering an insult of some sort. The new theory predicts that as cancer progresses through more and more malignant stages, it will express genes that are more deeply conserved among multicellular organisms, and so are in some sense more ancient. Genes that are active in the embryo and normally dormant thereafter are found to be switched back on in cancer. These same genes are the ‘ancient’ ones, deep in the tree of multicellular life.

2014-05-17: Measles Virus as a Cancer Fighter. Remarkable: fighting one scourge with another.

2015-03-14: Cancer Cell Mutations

1 study of kidney cancers found that no 2 patients had exactly the same set of genetic mistakes; in fact, no 2 tumors within the same patient had the same mutations. Taking it one step further, 1 high-resolution DNA-sequencing study of breast cancer couldn’t find 2 cells within 1 tumor that were genetically identical

2015-08-26: Reprogramming cancer cells. Apply a large grain of salt to the claim, but the mechanism is still very interesting.

miRNAs orchestrate whole cellular programs by simultaneously regulating expression of a group of genes. The investigators found that when normal cells come in contact with each other, a specific subset of miRNAs suppresses genes that promote cell growth. However, when adhesion is disrupted in cancer cells, these miRNAs are misregulated and cells grow out of control. Restoring normal miRNA levels in cancer cells can reverse that aberrant cell growth.

2015-09-23: Dark matter cancer? This is pretty much speculation, but interesting speculation.

We can thus speculate that the mirror micrometeorite, when interacting with the DNA molecules, can lead to multiple simultaneous mutations and cause disease

2016-03-07: Winning the Cancer War

Unfortunately, we’re still stuck in dogma. We continue to live in a world where the standard of cancer care is built on the naïve, almost arrogant, assumption that simply understanding the gene is the only important thing. Or that understanding 50 genes or even 500 genes will give us all the information to unlock the secrets of cancer cell metastasis. But our research is beginning to show that this is no longer the case. The bottom-line is that the biology of cancer is extraordinarily complex. It’s so complex that the output of the gene—specifically, the downstream networks of proteins within our bodies—is even more important than the gene itself.

2016-11-18: CRISPR for lung cancer

Scientists at Sichuan University have injected a person with aggressive lung cancer with cells modified using the gene-splicing technology in a bid to make the patient’s immune system more effective at combating cancer cells.

2017-11-08: Cancer survival

cancer death rates continue to fall across most cancer types. From 2010 to 2014, overall death rates decreased by 1.8%. 5-year survival rates for most common types of cancer have increased quite significantly in the past 30-40 years.

2018-08-02: Cancer progress

Official statistics say we are winning the War on Cancer. Cancer incidence rates, mortality rates, and 5-year-survival rates have generally been moving in the right direction over the past few decades.

More skeptical people offer an alternate narrative. Cancer incidence and mortality rates are increasing for some cancers. They are decreasing for others, but the credit goes to social factors like smoking cessation and not to medical advances. Survival rates are increasing only because cancers are getting detected earlier. Suppose a certain cancer is untreatable and will kill you in 10 years. If it’s always discovered after 7 years, 5-year-survival-rate will be 0%. If it’s always discovered after 2 years, 5-year-survival-rate will be 100%. Better screening can shift the % of cases discovered after 7 years vs. 2 years, and so shift the 5-year-survival rate, but the same number of people will be dying of cancer as ever.

This post tries to figure out which narrative is more accurate.

and another perspective:

Death rates from the disease in the US dropped in the 2016-2017 period by their largest recorded %. This is unequivocally good news, and is attributed to advances in treatment – specifically, the advent of immunotherapies and of various targeted agents for lung and skin cancer. It may come as a surprise to some, but these death rates have actually been falling since the early 1990s at ~1.5% a year, a good part of which can be attributed to the decline in smoking. But the 2016-2017 decline bumped up to 2.2%, which has never been seen before

2019-08-20: Cancer Speciation

Aggressive cancers can spread so fiercely that they seem less like tissues gone wrong and more like invasive parasites looking to consume and then break free of their host. If a wild theory recently floated in Biology Direct is correct, something like that might indeed happen on rare occasions: Cancers that learn how to roam between hosts may gradually evolve into their own multicellular species. Researchers are now scrutinizing a peculiar group of marine parasites called myxosporeans to see whether they might be the first known example.

2021-05-22: Starving Cancer

Scientists are unraveling the molecular pathways by which slashing calories or removing a dietary component can bolster the effects of drugs. In mice with cancer, the effects are oftentimes on the same order of magnitude as those from the drugs that we give patients. If those trials show the ketogenic diet helps curb tumor growth for 2 years longer than the PI3K inhibitor otherwise would, the diet could become the standard of care. “That will be what physicians will tell patients to do.”


2022-08-14: Tumors recruit the nervous system to help them spread.

“The nervous system controls everything in normal tissues—growth or atrophy, or anything else”. So there’s a reason to believe that the same is happening with malignancies. “Cancer tissue grows fast so it needs the support of the nervous system”. Moreover, scientists know that certain cancers have a particular predilection for nerves. “For example, breast and prostate tumors have a propensity to look for nerves and kind of invade and travel through those nerves. That suggests that there is synergy there.”

The observational knowledge suggests that a greater amount of nerves bunching up around a tumor signals grimmer prognosis. For example, when pathologists assess the severity of prostate cancer, the number of nerves that surround these tissues factors in. “The pathologist will score that, and if there’s a lot of nerves in the area, it usually means a worse, or a more urgent situation. To us, that seems like a blind spot or a missing link.”

2022-11-23: Cancer vaccines?

After several decades, therapeutic cancer vaccines now show signs of efficacy and potential to help patients resistant to other standard-of-care immunotherapies, but they have yet to realize their full potential and expand the oncologic armamentarium. Here, we classify cancer vaccines by what is known of the included antigens, which tumors express those antigens and where the antigens colocalize with antigen-presenting cells, thus delineating predefined vaccines (shared or personalized) and anonymous vaccines (ex vivo or in situ). To expedite clinical development, we highlight the need for accurate immune monitoring of early trials to acknowledge failures and advance the most promising vaccines.