My understanding was that it was also about the long tail. With millions of titles in print, and a minimum selection of thousands to make a decent bookstore, you can't print a decent catalog and mail it. Before Amazon, the biggest mail-order books business was the Book-of-the-Month Club. Perfect case for an online catalog.
I heard the same story (I joined in 2004). The version I heard was that Jeff was driving cross-country NY -> Seattle and was on the phone with his lawyer about incorporation papers, and the lawyer misheard “Cadabra” as “Cadaver”. That's when Jeff knew he needed a better name.
That's an interesting story, but that article and others on the site have weird issues that can't be put down as non-native English. Extra words that make no sense (Steve Jobs founded us), and phrases added into the ends of sentences along with spacing/punctuation mistakes (But please, pretend you’re interested in everyone’s questions, ”Jobs said at the time, as carry* the website Windows Central.*) Odd issues to see on a news website. Also, all postings are double-dated, once within the text and once after.
(1) Simplistic because it isn't binary, solved vs. not solved. There's still improvement to do in the solution. And we won't really know if it's “solved” until we start trying to use these structures for practical purposes. Don't mean to detract from the accomplishment overall though, it seems tremendous.
(2) There is a certain amount of computing needed for each new protein---quite significant, I think, but not prohibitively expensive. And I'm sure this can be improved over time
Well, there are. Actually, misfolded proteins are implicated in some diseases.
I'm not sure if every possible sequence of amino acids has a unique dominant folding. But ones that don't, wouldn't be nearly as useful biologically, because you couldn't rely on them to do their jobs. So they would not be selected for. The ones that actually get coded for by genes fold up more consistently.
In bacteria, they produce a lot more mutations in stressful environments because it is evolutionarily advantageous. In other words, if your situation is killing you playing Russian roulette with your genes is a better bet than accepting certain doom. Maybe you produce a deadly mutation that kills you and maybe you produce a mutation that helps you survive certain doom.
My recollection is that snails can reproduce either sexually or asexually and they preferentially reproduce sexually in stressful environments and asexually in environments that make staying the same more advantageous.
Sickle Cell is protective against malaria. Sickle Cell trait is protective without causing Sickle Cell Anemia, which is a horrible condition. So one copy of the mutation and you are more likely to survive in an area where malaria is prevalent and two copies and you are jacked up, but maybe less jacked up than with malaria.
Some studies suggest that Cystic Fibrosis is a predominantly Caucasian disorder because having one copy of the gene is protective against certain disease that were sweeping through Europe at one time. Two copies tends to kill people gruesomely at young ages.
So I think generally speaking the answer is that species seem to seek mutations when what they are doing currently isn't working and seek stability when what they are doing currently is working.
Also I have read that it is believed that half or more of all human pregnancies probably end in the first two weeks and result in a heavier-than-normal period without the woman even realizing she was ever pregnant in most cases because those fetuses are simply not viable. Laying bets on "Will this novel mutation or novel combination work?" tends to get a result of "Nope. It so doesn't work, it's not worth investing precious resources in to bring the baby to term and let it be born."
We mutate more when it is "mutate or die" and less when mutating is the thing more likely to kill you.
There are a few things in here that are fun to think about.
In the situation you describe, the answer is often "yes" and that's how you end up with evolution. Let's say you have a gene that makes a protein that digests glucose. And then one day, your cell messed up when replicating and accidentally made an extra copy of that gene. Well now you have an extra copy of that gene that isn't under purifying selection. It's redundant. It can mutate but as long as you have the first copy, you're ok. And eventually it mutates away from being good at digesting glucose. It can do it a little bit, but it's not great. Maybe it's 20% as effective as it originally was. But you have another gene that's still 100% effective so you don't even notice.
Now we have a protein that really doesn't do anything bad... It just doesn't do much good either. And since it isn't subject to purifying selection, every round of replication it keeps mutating. Until all of a sudden, it mutates into something that can digest lactose. Now, you have an evolutionary advantage from a protein that first had to get bad at binding glucose, before it could benefit you. But evolution has no foresight, so it didn't know. So it took getting rid of purifying selection to make it happen. But now as you come to rely on lactose, that protein will wind up back under purifying selection and become "fixed".
So now let's consider an alternative situation. You only have one gene that can digest glucose. If it mutates to be 20% effective, you will at best grow only 20% as fast as your competitors. Maybe you even die and become an evolutionary dead end. In that case, it is an extreme disadvantage to have a protein that can't do its job reliably, and organisms that don't have a malfunctioning variant will grow better and pass on their genetic material to more offspring, until you are eventually outcompeted and go extinct.
We can also imagine another scenario. Your glucose digesting protein mutates into something that can still bind glucose, but cant digest it. Then the glucose remains stuck to the protein, producing no energy, and becomes a waste for the cell. That is actively harmful and will likely kill the cell very quickly.
No, that is the exact opposite of what I'm suggesting! We should appreciate the progress we've made so far, and we should absolutely seek further progress.
This one tells of Whittle's difficulties in Air Force resistance, also the new jets were extremely costly and required whole new areas of metallurgy and turbine design:
https://frankwhittle.co.uk/challenges/
Thanks. Part of the goal of my project is to get underneath assumptions and ideology. That is, I try to justify my conclusions based on evidence and research—at least the harder claims (as opposed to my somewhat more speculative comments about bigger-picture themes and deep causes).
I invite critiques of my factual conclusions, and I'm always happy to be taught something!
Read: Vaclav Smil, Robert K. Merton, Joseph Tainter, William Ophuls (esp. Ecology & Plato, and mine the hell out of his bibliogs), Bernhard J. Stern ("Resistances to Technological Innovation"), Robert Gordon (Rise & Fall), W. Brian Arthur (Technology & complexity economics), Robert U. Ayres (generally, energy & econ), M. King Hubbert, Howard & Eugene Odum, Nicholas Georgescu-Roegen (Entropy), Peter Turchin, Meadows et al, John Nicholas Gray (esp. on Pinker), Norbert Wiener (Cybernetics & Humans), Joseph Needham (generally, though not necessarily comprehensively), John Stuart Mill, William Stanley Jevons (esp. Coal & Money), Daniel Yergin (Prize), Richard Heinberg, Henry Adams (Education), Leslie White, Kyle Harper (esp, The Fate of Rome), Gregory Clark (Alms & Son), Karl Polanyi (Transformation), Elisabeth Eisenstein (Printing Press), Michael & Joyce Heusemann, William Foster Lloyd (esp. "Value"), Jeffrey S. Dukes ("Sunshine"), Jared Diamond (Collapse, esp. bibliog), Philip Mirosky (esp. More Heat than Light), Paul Buran (esp. his cautionary RAND monographs), Shoshana Zuboff (Surveillance Capitalism, Smart Machine), Arthur Toffler (Future Shock), Marshall Poe (Communications), Mokyr's economic history series generally (the one he's editor of) is quite good.
A long list, and could be better organised, apologies. Organising sources has become its own challenge. More mileage generally from the more obscure and less-read authors/works
Ask yourself:
- What is progress.
- What are value & wealth?
- What is technology?
- What are its specific mechanisms?
- What are their limitations?
- Is there a general theory of technology, if not, why, and what might it look like?
I'd also question your "moral imperative". Why, to what end, and with what alternatives?
My initial read was that the general problem was technological. I've become increasingly convinced it's more political & ideological, and the roles of media, power, institutions (formal & informal, overt & covert), and of information technology (high & low) on media and that on mass opinion & behaviour matter more.
Bad models & priors hurt immensely. Question all, especially those held unconsciously.
Thanks for the reading suggestions. And of course I am already thinking about the questions you mentioned and have been for a long time.
I agree that politics, ideology, and mass opinion matter a lot, and never meant to imply otherwise. Indeed in some of my posts I touch on how those factors might have affected technological developments. (See e.g. my analysis toward the end of my smallpox post: https://rootsofprogress.org/smallpox-and-vaccines)
Agree also about the importance of models & priors.
If there's any place where you think my specific factual conclusions are in error (whether from bad models or any other error), I always appreciate specific rejoinders.
I've only known of your project for about two days, so there's no in-depth assessment yet.
On politics, models, and media: I've simply found myself looking at these far more than the technical side. I think that's largely because tech simply hasn't moved all that much in 50-60 years, outside of infotech. In terms of energy, our options are largely the same as Hyman Rickover identified in 1957: wind, solar, geothermal, biomass, nuclear fission:
(We've gotten remarkably better at solar, but the total flux remains constant.)
A close read of various cornucopians (Herman Kahn, Julian Simon, M.A. Adelman) shows numerous thin and flawed arguments. Nordhaus's Nobel is quite probably the biggest error in the history of that award, and that's with fierce competition.
What's notable is that we've 1) made little progress in coming up with a generally accepted, sensible, model of economic growth (Atkinson & Krugman: https://youtube.com/watch?v=3l6E3mUNW70&t=2333), 2) there's been a concerted rejection of limits at both the left and right of the political spectrum, despite scientific concensus, in both cases for ideological reasons (see Schoijet's discussion of this: http://www.jstor.org/stable/3985399), and 3) political will and/or capacity to address challenges has been all but entirely lacking (this is the general thesis of Ophuls in 1977, largely born out over the subsequent 43 years in both action (or lack) and rationales).
It's your framing that strikes me as most flawed, though I suspect you'll also be least inclined to address. Growth as a moral imperative is extraordinarily suspect.
“Whose narrative?” Uh, mine I guess. I'm an independent researcher. Used to be a tech founder. This blog was my hobby until I quit my last job. Now I do it almost full-time. I'm funded by grants from Emergent Ventures among others. But I've been doing what I do since long before I met them.
So there is something odd going on with measles. I haven't dug into the data, but from a couple of data points I've seen, it seems that measles mortality was declining for a long time even while measles cases were not. That is, there was a decline in the case-fatality rate, without a decline in cases. The disease was still around but getting less deadly. Then the vaccine actually reduced the number of cases.
So what was reducing the case-fatality rate? I don't know, but it might have been nutrition. There's evidence at least that Vitamin A makes measles less severe/deadly.
Sanitation, antibiotics, oral rehydration therapy, machine ventilation, nutrition, and so on.
It's not the measles itself that was the cause of most fatalities, it was the pneumonia, diahrrea, and other opportunistic infections that come with it.
