Does 17α-estradiol/estrogen extend male human lifespan?

17α-estradiol is a relatively (or completely) non-feminizing form of estradiol (E2), or estrogen. It is a naturally occurring enantiomer of 17β-estradiol (the much more common form of estradiol, usually just referred to as ‘estradiol’) which is found in both male and female humans. This post a a brief essay that discusses the prospect of it extending lifespan in humans. There are two primary types of estrogen receptors, ERα and Erβ, and as you may expect, 17α-estradiol appears to show a stronger binding affinity for ERα. It has a very low binding affinity in locations that generally induce feminization (which appear to be sometimes be both ERα and ERβ), so it’s also possible to take as a male without significantly altering one’s appearance towards the opposite gender. Although we can definitively point to a plethora of effects of regular estrogen, it is difficult to tell what the true purpose of 17α-estradiol is in humans, with Stout et al. (2016) stating “the physiological functions of endogenous 17α-E2 are unclear”. There is evidence it has neuroprotective properties, can help treat Parkinson’s disease, cerebrovascular disease, and much more. This likely involves ER-X, which in turn activates MAPK/ERK and many, many other things down the line (as usual..), but it’s difficult to know for certain. Although these reasons were among the reasons that researchers took into account when deciding to dedicate funding to testing 17α-estradiol in mice for longevity effects, subsequent papers have found more exciting mechanisms of action which are elaborated upon below. For some interesting further reading on this topic that goes into more detail exploring possible mechanisms of action here I’d also suggest reading the following papers: Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci, Hypermethylation of estrogen receptor-alpha gene in atheromatosis patients and its correlation with homocysteine.

17α-estradiol has been found to consistently and significantly extend the median lifespan of male mice, including by the NIH’s Intervention Testing Program, the closest thing we have to a gold standard of longevity RCT experimentation in mice, where three studies are rigorously performed at three separate locations, allowing the results to be instantly compared and reproduced by the two other parties and locations upon completion. Strong et al. (2016) find that 17α-estradiol extends median lifespan of male mice by an average of 19% (26%, 23%, and 9% from the three independent testing sites), and increased the maximum age by an average of 12% (21%, 8%, and 8% from the three testing sites, using the 90th percentile). Harrison et al. (2014) similarly find that median male lifespan was increased by 12%, but did not find an increase in maximum lifespan, and these results have been replicated even more in recent years.

These are some impressive results for such a common and simple endogenous substance! One of the first things we notice is that this effect only applies to males, with female lifespan (both median and maximum) being unaffected. As the substance in question is an estrogen, we can assume that this is either due to female mice already having this benefit, as they already have a sufficient level of it, or that something more complex is at play, and there is a different downstream pathway that is only being activated in males for some reason (more on this later). I had initially assumed the former hypothesis was at least a partial explanation, having known that females consistently live longer than males when it comes to humans, and that this was obviously biological in nature. However, it’s much more complicated in mice as females do not always outlive males, and in fact many times the opposite is true. One meta-analysis (good overview, original book source) finds 65 studies where males lived longer and 51 where females lived longer, with this often depending on the strain of mice used, which varies greatly depending on the type of reseasrch and time period. Regardless, it’s clear there is much more at play in this scenario, and perhaps something special about 17α-estradiol in particular.

Although the ITP studies initially included 17α-estradiol due to the reasons mentioned in the first paragraph, later research such as Stout et al. (2016) has now found that 17α-estradiol not only increased AMPK levels (as some other notable longevity substances such as Metformin also do), but also reduced mTOR activity (complex 1!) in visceral adipose tissue, which is rather reminiscent of Rapamycin, which has extended the lifespan of every orgasm we have performed an RCT with thus far (and likely can in humans too, if you ask me). In a way, this is significantly more exciting, because it gives us a much more plausible way to explain the lifespan extension effects we are noticing. However, it is also partially a disappointment: if these effects are the real reasons why 17α-estradiol extends male mice lifespan, then this substance may offer us nothing that we do not already have via rapamycin and metformin, among others. The paper also noted that fasting glucose, insulin, and glycostlated hemoglobin were reduced along with inflammatory markers improving. These are similar to the types of positive side effects we would expect from a longevity agent, and the study also notes that no feminization nor cardiac dysfunction occurred.

How do these effects (such as AMPK and mTOR modulation) occur? I don’t know, and apparently neither does anyone else. As is often the unfortunate case in biology, the paper has this to say: “The signaling mechanism(s) by which 17α-E2 elicits downstream effects remains elusive despite having been investigated for several decades”. Perhaps just a few more decades to go and this section will be updated with more information, then. Mann et al (2020) find that male mice without ERα do not benefit from 17α-estradiol, which helps us narrow down the first step by excluding Erβ, ER-X and other less-predictable initial mechanisms. Interestingly, they also note that “both 17α-estradiol and 17β-estradiol elicit similar genomic binding and transcriptional activation of ERα”, which would leave us with the question of why we are focusing on 17α-estradiol specifically, if 17β-estradiol (which is much more common) suffices as well. Importantly, they also seem to think changes in the liver might be involved. Garratt et al. (2018) add that distinct sex-specific changes in the metabolomic profile of the liver and plasma were found, and also notes that the longevity benefit for males disappears post-castration. They first supplement males and females, showing many differences related to metabolism including with amino acids. Then they use castrated males and notice that their profiles are the same as the control group, and thus conclude that they are no longer being positively affected by 17α-estradiol. I am unsure if we should be focusing on the AMKP/mTOR effects (which are very relevant to longevity) or on the liver/metabolic effects (which are also very relevant), or if these are in fact just two different temporal points on the same biological pathway which we don’t yet fully understand, but this helps us connect at least a few more dots.

All of the above sounds exciting, but it’s also all in mice. Sometimes this is useful, as mice are actually quite similar to humans (more so than many may expect), but a lot of it is also less useful or outright misleading. I cannot find a way to take only 17α-estradiol in a safe way as a human, however there is a topical cream of it (alfatradiol) which is used to treat pattern hair loss.

Luckily, one thing that the ITP study found was that 17α-estradiol was among one of the substances that seems to work decently (if not fully) when given later in life, contrary to some others which have the best effect when started in youth and continued until death. As such, I don’t mind waiting 5-20 years for this research to hopefully pan out into a more fruitful and actionable path until I start experimenting with it (although if anyone has more to say on this, please get in contact with me as I’d love to hear about you experience with 17α-estradiol).

It is worth reminding ourselves that 17α-estradiol is already present in humans, and in both sexes, with women generally having significantly higher levels, as one expects of estrogen. Similarly, regular estrogen binds to both estrogen receptors, including our target, which we now know to be the alpha receptor. Given this, is it possible that just taking normal estradiol and increasing the levels of all types of estrogen is a potential longevity treatment? This is a difficult question to answer, although there are millions of people that are already on estradiol for various reasons, one of them being to assist in gender transition from male to female. As the lifespan benefit only applied to male (assigned at birth) mice, there would be benefits to analyzing this target demographic for more information, however this turns out to be quite difficult. We have few deaths due to aging to analyze, as most individuals that transition decide to do so during an earlier period of their life. Of those, we have little data on the entirety of their life, as transitioning has increased significantly in the past few decades, so most of the relevant group is still quite young. Lastly, even if we did have this, the data would be terribly confounded in a large number of ways, and is definitely very far from the type of human RCT we would prefer.

Even so, one of the following must be true:

  • 17α-estradiol does not extend male human lifespan
  • 17α-estradiol does extend male (assigned at birth) human lifespan, however this does not apply to most/any transgender (m->f) individuals. This could be due to insufficient dosage, insufficient affinity for the alpha receptor, the inclusion of 17β-estradiol, the common addition of other substances such as anti-androgens, or another unknown factor
  • 17α-estradiol does extend male (assigned at birth) human lifespan, and this effect therefore does apply to most transgender (m->f) individuals, however we have either failed to notice it completely, or other effects/confounding variables ablate this, for example an increased risk of blood clots from estrogen supplementation or various potential side-effects from anti-androgen usage

Option one is certainly a possibility, but if the AMPK/mTOR pathways are indeed the mechanism of action (and are still somehow modulated in humans by 17α-estradiol), this would imply that other potential human longevity agents such as rapamycin and metformin, which use these same pathways, will in fact, not work. If the pathway is related more to the metabolism of food, then this is easier to believe, as this is one of the areas where mice (which are herbivores) differ from us notably. On the other hand, there are enough differences between humans and mice that it’s very feasible the stars simply do not align for us here, and some critical part of this pathway has been modified past being useful (although do keep in mind that a large amount of important and interesting pathways have been evolutionary conserved for exceptionally long periods, of which mTOR is definitely included amongst).

Option two is, in my opinion, moderately plausible. It could the case that when we do have 17α-estradiol, the dosage is nowhere near sufficient for a noticeable longevity effect, and that if we would simply increase it by 10x or 50x, then we would very quickly notice something big. If not, there is a second sub-explanation here as well. Most male→female transgender individuals don’t just take an estrogen to increase estrogen, but also an anti-androgen to decrease testosterone. As we saw in mice however, castrated males did not experience the improvements as regular males did, although we cannot point specifically as to why. It seems quite possible that since most transgender (m->f) individuals take both an estrogen and an anti-androgen, they may be missing out on the potential opportunity of longevity benefits due to something the anti-androgen is doing. But again I have to add that this is pure speculation, and is just one of many guesses built on top of other guesses (we have only seen the original lifespan extension in mice).

I would like it if we were doing human trials on this right now, but I doubt we’ll get them for far too long, as is generally the case for anything that would significantly extend human lifespan and save us trillions of dollars (even if you think the chance this works is only 1%, multiply that by what we would get – billions of additional human years and trillions in less healthcare spending, and realize the massive expected value that all potential longevity interventions have).

As for option three, it would seem difficult to think that male→female transgender individuals are all supplementing a substance that may increase their lifespan by 5-20%, but yet none of us (or them) are aware of it. There is little useful data on this and we have no good reason to currently believe that this is the case, as we already are making quite a few leaps by first jumping from mice to humans, and secondly moving from 17α-estradiol to estradiol. I’d like to add a lot more to this later, but for now I’ll briefly summarize all of the above in one final paragraphs.

In conclusion, 17α-estradiol might notably extend human lifespan for those assigned male at birth. It may do this by modifying the liver and altering subsequent metabolic properties and processes, and this may also be related to its potential effects on key areas related to longevity such as AMPK and mTOR. If the former is the case, its lifespan effects are likely not additive with other drugs such as metformin or rapamycin, which although disappointing, could still offer other improvements in areas such as safety. If 17α-estradiol does extend human lifespan in this manner, some transgender individuals either do experience the benefits, but we have not yet noticed, or they do not experience the benefits, likely due to either having insufficient levels of 17α-estradiol, or due to the inclusion of an anti-androgen attenuating possible benefits. Further research, including direct human RCTs of 17α-estradiol supplementation itself, is required.

Disclaimer: I’m a random person on the Internet, and also not even a doctor. I have little formal background in biology and just click links on the Internet, read them, and then type things about them for fun. Please mention any corrections or comments to me (see: Contact section of About paget).

Comments on Firefox

This post is a summary of some of the things that I dislike about Mozilla and Firefox. Given how passionate I am about user rights, privacy, decentralization, FOSS, etc, sometimes these remarks surprise people. I still am grateful Mozilla exists, I still use some of their products, and there are many amazingly smart and good people there However, donations to Mozilla for the purpose of improving Firefox are ineffective and are better spent elsewhere, and I really wish they would stay focused on making better products.

Mozilla has a lot of money, most of which does not go towards Firefox

Mozilla constantly mentions that they are a nonprofit, encouraging you to donate to them to help Make The Internet A Better Place. While the Mozilla Foundation is legally classified as a nonprofit, their subsidiary, Mozilla Corporation, is not. Its revenue is around $450,000,000 per year, almost all of which comes from their contracts with Google (Yandex and Baidu as well). Google pays Mozilla half a billion dollars per year because Mozilla has contractually agreed to keep Google as their default search engine, and presumably this gives Google a net profit, as having more ad views and user information is very, very valuable (I heard an explanation that Google also wants to avoid antitrust issues, but I’m unsure of the veracity of that).

The CEO of Mozilla (both the foundation and the corporation), Mitchell Baker, had an annual income of over $3,000,000 (official source, cannot find 2020 document yet) or around $1,000/hour, which has managed to increase for several years in a row, despite metrics related to Mozilla’s primary product, their web browser, significantly decreasing (do note: her salary is technically from the for-profit, not the non-profit). In case you haven’t seen a report on browser market share in the last few years, Firefox currently has around 3-4% of the market share, with the highest estimates I can find being around 7-8%.

Yeah, it’s kinda bad

Most of Mozilla’s spending does not go to software development nor Firefox, but rather to administration, marketing, and similar expenses (this is true both for the non-profit and for-profit, but the non-profit’s information is publicly available). Checking their most recent form 990, there was $4.5M spent on grants to random universities and groups, $3M spent on management fees, $1.8M spent on travel fees, and $0.8M spent on conference fees, which combined is significantly more than what is spent on employee compensation. This means when you donate to Mozilla’s nonprofit, your money is more likely to be spent on universities, management, and travel than an employee’s compensation.

Although there are not many publicly available details about the specific spending of the for-profit section of Mozilla (which would be ~10x more), the distributions appear to be relateively similar from what sources I can find. One reason why Mozilla spends so much on marketing is because their products are generally not as good as their competitors’, and attempting to purchase your way to a larger userbase is an expensive and constant uphill battle.

Firefox does little to stop you from being tracked by Google

One of the most popular reasons to use Firefox instead of Chrome is a dislike for being tracked by Google. While it’s true that Google recieves more information from Chrome users than it does from Firefox users, the majority of information flow remains a constant, and Mozilla relies on a plethora of Google services for basic browser functionality. Here are some examples:

  • Firefox uses Google search by default and sends all queries/address bar typing to Google
  • Firefox uses Google’s safe browsing service for ‘unrecognized downloads’, sending Google the filename and url that you visited
  • Firefox uses Google services for basic APIs such as their location API, despite Mozilla having attempted its own implementation, which one may assume they’d use. As Firefox polls your OS for information to send to this API, this sends information such as your wifi-network or nearby phone towers in addition to your IP address and a biweekly-rotating Google client identifier.

Apart from Firefox relying heavily on Google’s services, unless you use extensive tracking/blocking addons, you’re being tracked everywhere you go to begin with, as the majority of websites use Google Analytics, Google APIs, Google fonts, Google ReCAPTCHA, among many others.

There is truth to Mozilla working on and implementing important privacy improvements in browsers, such as DNS over HTTPS, third party cookie blocking by default, tracker blocking, and so on. Some of these appear to be helpful, however are easily mitigated by other parties, while others are more questionable (for example, the implemention method of rolling out DoH by opting users into it, bypassing their network configuration preferences, and sending all DNS queries to a single company’s servers, was not optimal). As of firefox 86 on Feb 23rd 2021, Firefox appears to be attempting full per-site cookie isolation, which if successful and usable could be a great improvement here.

Firefox includes tracking, advertisements, and backdoors

Mozilla takes almost every chance it can to tell you how much they love your privacy, and for that reason the tracking and default features that are included in distributions of Firefox are pretty surprising (this does not mean Firefox is worse at this than other browsers!).

By default, firefox shares all of the following with Mozilla:

– the number of open tabs and windows, the number of websites visited, the number and type of addons installed, the length of your browser session, all interaction events with ‘Firefox features offered by Mozilla or our partners’, your device information, OS information, hardware information, and your IP address

  • “Firefox uses your IP address to suggest relevant content based on your country and state”
  • “When you choose to click on a Snippet link, we may receive data about the link you followed”
  • “Firefox sends basic information about unrecognized downloads to Google’s SafeBrowsing Service, including the filename and the URL it was downloaded from”

Some of this information is reasonable, such as crash reports and the base OS/Firefox version, but I still found this to be more than many may expect.

Firefox now comes with a feature called studies, which allows Mozilla to remotely install and run custom changes and featuresets to your browser without asking you. This is turned on by default, which is generally all that matters as almost no users go through every setting in software to turn things off manually. In the past Mozilla used their ability to remotely control browser installations to install an addon into users’ browsers that gave them cryptic messages which were intended to be advertising for a TV show. I don’t know why they thought that was a good idea, as it seemed to be almost unanimously agreed upon that it was a terrible idea, but it still happened. If you visit about:studies in Firefox you can see which studies you have/are currently participating in. I could not find any resource from Mozilla that lists all studies that they run, or anything remotely like this.

Firefox continually pushes sponsored and clickbait content into their products

Firefox comes with many features for sponsored content and advertisements, such as Sponsored Top Sites. The Mozilla page about this feature says they send ‘anonymized technical data’, which is hyperlinked to a near-empty Github repositry. Firefox partners with adMarketplace for this, which states “We may also receive technical information such as your approximate location, browser type, language settings, user agent, timestamp, cookie ID and IP addresses”, which is very dissimilar to what Mozilla says about this tracking, but perhaps they have a special agreement with Mozilla to opt their users out of this or something.

There is also Pocket, which comes with all distributions of Firefox and shows sponsored stories and other content ‘curated by our editors’ by default. I’m not even going to pretend this is decent. This is is a terible feature, and the last thing I want to see when I open my web browser is a bunch of advertisements for clickbait. I find it sad that mozilla says Pocket “Trades clickbait for quality content”, when the majority of content Pocket offers is complete trash designed to make you click and waste your time, including a lot of content that suggests that surveillance and censorship of the Internet is required to keep me informed and safe.

Please keep your clickbait out of my browser’s default home page, thank you

Fortunately several of the worst features of Firefox are easy to turn off, and some features that are even worse such as Ion, which literally just sends your browsing history to ‘researchers’, are disabled by default and must be opted into. I’m unsure why these features are included in Firefox to begin with, as I can’t imagine the small revenue stream they introduce is significant nor in Mozilla’s best interest.

Firefox is generally a slower browser than Chrome

If you’re a Firefox user, I suggested using Chromium just for a few minutes. I usually use forks of Firefox or Firefox ESR, but when I use Chromium I’m sometimes stunned at how much faster it is. Finding fair and recent browser benchmarks is difficult, but but most of which I’m able to find seem to confirm this, and testing local website rendering myself results in Chrome not just being slightly faster, but often 50-300% faster with its rendering, network requests, and javascript execution.

Using Chrome for a few minutes instantly allows me to understand why it has dominated Firefox in market share over the last decade. While it’s true that Google has many inherent advantages in promoting software, I think its performance, speed, and UX alone goes a long way in demonstrating why Firefox has fallen behind so far.

Mozilla has strange and contradictory ideological goals

When visiting the homepage mozilla.org, the first article that is shown to me is titled ‘We need more than deplatforming’ written by the CEO Mozilla, which implores us to do things like “Turn on by default the tools to amplify factual voices over disinformation”, kindly linking us to a NYT article that discusses how ‘authoritative sources’ such as the NYT and CNN should be prioritized over independent voices.

I don’t want to write much about politics for reasons that should be obvious, but attempting to solve the world’s problems via fact-checking is terrible naive and has no chance of working out well, and I’m amazed at how many large organizations seem to act like the solution to our society’s problems is for us to just ask a fact-checker what is true and what is false, and then hold hands and sing songs as our new utopia is formed.

Continuing to read blogposts from Mozilla (this is from their foundation’s website, I should add that they have some good technical blogposts in other locations) is a rather interesting endeavor as it becomes more and more apparent that Mozilla has large segments of their organization that don’t seem to have any clear goals, and just kind of write about random social and political things on the Internet and their opinions on it, sometimes throwing six-figure grants to random groups of students to make a game that no one ever plays to show us about how something is obviously bad, which I assume they thought was a better use of their money than hiring someone to work on Firefox (which 250 people were laid off from last year).

While Mozilla attempts to provide commentary on many important social issues, there appear to be many suggestions that go directly against their manifesto, which suggests that open expression and individuals freedoms should be prioritized. I respect the right for Mozilla to spend its funding on any social or political content it chooses, and I also think that many of the issues they dedicate time to are very important for our society and for the Internet, but I would rather their organization focuses on making a good web browser, because I would be much more excited about donating to them if my money went towards that.

I’m still glad Firefox exists

I’ve written some negative views about Firefox, but I’m still glad it exists. Making a perfect web browser is difficult, and trying to respect user privacy is difficult. I think Mozilla would be much better off if they were a product-focused company, and spent more money on technical innovation and additional engineers and innovators. For this reason I don’t think donating to Mozilla is a good choice, and as far as similar organizations go, prefer the EFF instead.

This article started to turn into a bit of a rant as I’ve continually found myself disappointed with decisions Mozilla has made, and I’m not surprised that their browser market share has decreased by almost 90% over time as a result. It’s easy to criticize, but difficult to build, so I do want to include this disclaimer to restate that I’m glad Firefox and Mozilla exist, and I wish the best for them and their browser, but I think their modern directions are distracting them from making products good enough to be widely used. I hope things improve, because it would be nice if more than one or two web browsers existed. In fact, I think that’s very important.

Quotes from The Everything Store – Jeff Bezos and the Age of Amazon

The Everything Store – Jeff Bezos and the Age of Amazon by Brad Stone is a book detailing some factors that led to the rise of Amazon as one of the largest corporate success stories of all time. I opened it expecting to skim through some parts, but ended up reading it in full in one sitting, and enjoyed it thoroughly. It left me with a strong sense of what makes Amazon, well, Amazon. And the best answer to that question is without a doubt, Bezos himself.

Rather than a full book review, I’m going to share some quotes from The Everything Store that stood out to me. One fun thing to note is that when this book was published in 2013, Amazon was ‘only’ a $150B company, but today is worth over 1.5 trillion. It’s a wonderful book and is worth buying if you want to read stories about Jeff Bezos’ extreme confidence in himself and his company as they overcome challenges one after another full-speed ahead, from local stores to Barnes and Noble to Ebay to Walmart and beyond. Below are some quotes that I particularly liked, only from the first fourth of the book. I was quoting the book more than anticipated, so I stopped this post early but will leave it up as an advertisement for the book.

Bezos is an excruciatingly prudent communicator for his own company.
He is sphinxlike with details of his plans, keeping thoughts and intentions
private, and he’s an enigma in the Seattle business community and in the
broader technology industry. He rarely speaks at conferences and gives
media interviews infrequently.

There is so much stuff that has yet to be invented.
There’s so much new that’s going to happen.
People don’t have any idea yet how impactful the Internet is going to
be and that this is still Day 1 in such a big way.
Jeff Bezos

Amazon’s internal customs are deeply idiosyncratic. PowerPoint decks
or slide presentations are never used in meetings. Instead, employees are
required to write six-page narratives laying out their points in prose, because
Bezos believes doing so fosters critical thinking. For each new product, they
craft their documents in the style of a press release. The goal is to frame a
proposed initiative in the way a customer might hear about it for the first
time. Each meeting begins with everyone silently reading the document, and
discussion commences afterward

“If you want to get to the truth about what makes us different, it’s this,”
Bezos says, veering into a familiar Jeffism: “We are genuinely customer-
centric, we are genuinely long-term oriented and we genuinely like to invent.
Most companies are not those things. They are focused on the competitor,
rather than the customer. They want to work on things that will pay
dividends in two or three years, and if they don’t work in two or three years
they will move on to something else. And they prefer to be close-followers
rather than inventors, because it’s safer. So if you want to capture the truth
about Amazon, that is why we are different. Very few companies have all of
those three elements.”

Bezos interpolated from this that Web activity overall had gone up that year by a factor of roughly 2,300—a 230,000 percent increase. “Things just don’t grow that fast,” Bezos later said. “It’s highly unusual, and that started me thinking, What kind of business plan might make sense in the context of that growth?”

Jackie Bezos suggested to her son that he run his new company at night or on the weekends. “No, things are changing fast,” Bezos told her. “I need to move quickly.”

Internet records show that during that time, they registered the Web domains Awake.com, Browse.com, and Bookmall.com. Bezos also briefly considered Aard.com, from a Dutch word, as a way to stake a claim at the top of most listings of websites, which at the time were arranged alphabetically.

Bezos and his wife grew fond of another possibility: Relentless.com. Friends suggested that it sounded a bit sinister. But something about it must have captivated Bezos: he registered the URL in September 1994, and he kept it. Type Relentless.com into the Web today and it takes you to Amazon.

They set up shop in the converted garage of Bezos’s house, an enclosed space without insulation and with a large, black potbellied stove at its center. Bezos built the first two desks out of sixty-dollar blond-wood doors from Home Depot, an endeavor that later carried almost biblical significance at Amazon, like Noah building the ark.

During that time, the name Cadabra lived on, serving as a temporary placeholder. But in late October of 1994, Bezos pored through the A section of the dictionary and had an epiphany when he reached the word Amazon. Earth’s largest river; Earth’s largest bookstore.3 He walked into the garage one morning and informed his colleagues of the company’s new name. He gave the impression that he didn’t care to hear anyone’s opinion on it, and he registered the new URL on November 1, 1994. “This is not only the largest river in the world, it’s many times larger than the next biggest river. It blows all other rivers away,” Bezos said.

One early challenge was that the book distributors required retailers to order ten books at a time. Amazon didn’t yet have that kind of sales volume, and Bezos later enjoyed telling the story of how he got around it. “We found a loophole,” he said. “Their systems were programmed in such a way that you didn’t have to receive ten books, you only had to order ten books. So we found an obscure book about lichens that they had in their system but was out of stock. We began ordering the one book we wanted and nine copies of the lichen book. They would ship out the book we needed and a note that said, ‘Sorry, but we’re out of the lichen book.’

A week after the launch, Jerry Yang and David Filo, Stanford graduate students, wrote them an e-mail and asked if they would like to be featured on a site called Yahoo that listed cool things on the Web. At that time, Yahoo was one of the most highly trafficked sites on the Web and the default home page for many of the Internet’s earliest users.

In the meetings, Bezos presented what was, at best, an ambiguous picture of Amazon’s future. At the time, it had about $139,000 in assets, $69,000 of which was in cash. The company had lost $52,000 in 1994 and was on track to lose another $300,000 that year. Against that meager start, Bezos would tell investors he projected $74 million in sales by 2000 if things went moderately well, and $114 million in sales if they went much better than expected. (Actual net sales in 2000: $1.64 billion.)

Bezos later told the online journal of the Wharton School, “We got the normal comments from well-meaning people who basically didn’t believe the business plan; they just didn’t think it would work.”11 Among the concerns was this prediction: “If you’re successful, you’re going to need a warehouse the size of the Library of Congress,” one investor told him.

When his goals did slip out, they were improbably grandiose. Though the startup’s focus was clearly on books, Davis recalls Bezos saying he wanted to build “the next Sears,” a lasting company that was a major force in retail. Lovejoy, a kayaking enthusiast, remembers Bezos telling him that he envisioned a day when the site would sell not only books about kayaks but kayaks themselves, subscriptions to kayaking magazines, and reservations for kayaking trips—everything related to the sport. “I thought he was a little bit crazy,” says Lovejoy.

The IPO process was painful in another way: During the seven-week SEC-mandated “quiet period,” Bezos was not permitted to talk to the press. “I can’t believe we have to delay our business by seven years,” he complained, equating weeks to years because he believed that the Internet was evolving at such an accelerated rate. Staying out of the press soon became even more difficult. Three days before Amazon’s IPO, Barnes & Noble filed a lawsuit against Amazon in federal court alleging that Amazon was falsely advertising itself to be the Earth’s Largest Bookstore. Riggio was appropriately worried about Amazon, but with the lawsuit he ended up giving his smaller competitor more attention. Later that month, the Riggios unveiled their own website, and many seemed ready to see Amazon crushed. The CEO of Forrester Research, a widely followed technology research firm, issued a report in which he called the company “Amazon.Toast.”


It was a distilled version of the dissatisfaction felt by many early Amazon employees. With his convincing gospel, Bezos had persuaded them all to have faith, and they were richly rewarded as a result. Then the steely-eyed founder replaced them with a new and more experienced group of believers. Watching the company move on without them gave these employees a gnawing sensation, as if their child had left home and moved in with another family. But in the end, as Bezos made abundantly clear to Shel Kaphan,family. But in the end, as Bezos made abundantly clear to Shel Kaphan, Amazon had only one true parent.

“You seem like a really nice guy, so don’t take this the wrong way, but you really need to sell to Barnes and Noble and get out now,” one student bluntly informed Bezos. Brian Birtwistle, a student in the class, recalls that Bezos was humble and circumspect. “You may be right,” Amazon’s founder told the students. “But I think you might be underestimating the degree to which established brick-and-mortar business, or any company that might be used to doing things a certain way, will find it hard to be nimble or to focus attention on a new channel. I guess we’ll see.”

“There will be a proliferation of companies in this space and most will die. There will be only a few enduring brands, and we will be one of them.”

During that time, no one placed bigger, bolder bets on the Internet than Jeff Bezos. Bezos believed more than anyone that the Web would change the landscape for companies and customers, so he sprinted ahead without the least hesitation. “I think our company is undervalued” became another oft- repeated Jeffism. “The world just doesn’t understand what Amazon is going to be.”

As the company grew, Bezos offered another sign that his ambitions were larger than anyone had suspected. He started hiring more Walmart executives.

Around that time, Wright showed Bezos the blueprints for a new warehouse in Fernley, Nevada, thirty miles east of Reno. The founder’s eyes lit up. “This is beautiful, Jimmy,” Bezos said. Wright asked who he needed to show the plans to and what kind of return on investment he would have to demonstrate. “Don’t worry about that,” Bezos said. “Just get it built.” “Don’t I have to get approval to do this?” Wright asked. “You just did,” Bezos said. Over the next year, Wright went on a wild $300 million spending spree.

“Walmart did not even have Internet in the building back then,” says Kerry Morris, a product buyer who moved from Walmart to Amazon. “We weren’t online. We weren’t e-mailing. None of us even knew what he meant by online retail.”

The venture capitalists backing eBay asked around and heard that one did not work with Jeff Bezos; one worked for him.

Bezos went skiing in Aspen that winter with Cook and Doerr and finally told them what was coming. “He said, ‘We’re going to win, so you probably want to consider whether to stay on the eBay board,’ ” says Cook. “He thought it would be the only natural outcome.”

If you liked these quotes, consider reading the full copy (perhaps even buying it from Amazon), it’s definitely a nice read about an amazing company and individual.

The Twitter Hack Could Have Been Much Worse

Midday on July 15th, 2020, many high-profile Twitter accounts were compromised and began posting scams to entice users into sending them cryptocurrency (generally BTC, but also some others such as XRP for Ripple’s account). I’m not going to write about this in detail since everyone else already has, but for more information check out an article on the topic: Coindesk, TheVerge, TechCrunch, BBC, infinite others

What if instead of posting low-quality cryptocurrency scams, the attackers did something else?

Sure, they could have tried to use CEO accounts such as Musk and Bezos to make millions (or possibly billions) on the stock market by tweeting about earnings and purchasing large amounts of far-out-of-the-money near-expiration call options on the underlying stocks. But we have a lot of ways to catch people that try that, and many regulations and organizations that would make it more difficult (many more than just the SEC) to get away with (although as a side note, $TLSA’s stock+option trading volume is absurdly high, and it would be very difficult).

But, what if they had tried something else entirely, something not motivated by short-term financial gain?

What if the attackers wanted to cause chaos and violence, perhaps alongside putting certain political movements and goals forward? What if they had pre-written thousands of tweets about a topic, perhaps a fake and outrageous event occurring, paired with fake images and videos, perhaps even some higher-quality deepfakes? How many people could they get killed? Could they start a war?

You might think this sounds absurd at first glance. But remember, most of the world’s most influential people use Twitter, including the leaders of most national governments. Although a private corporation that plays by its own rules, Twitter is still the means with which many elected officials communicate with the public. Entire social movements have started and ended through the power of a single viral tweet, sometimes resulting in significant violence or many deaths. Social media platforms have been used by extremists of every type imaginable in the past, and this isn’t going to stop any time soon.

What if the next exploit affects much more than some Twitter accounts?

But, I want to go much further than talking about Twitter. What if instead of an exploit that allowed attackers to compromise Twitter accounts, it had been something much worse? What if they were able to compromise any web server, or any online Windows machine, or industrial control systems for utilities, power plants and military operations? None of these scenarios are by any means impossible. Enough software and hardware exists at enough layers of abstraction that there’s generally always 0-days lurking in critical systems, sometimes for years or decades, before they’re found. We know that 0days are found often by security researchers, private companies, governments, and others (sometimes rewarding up to $2,500,000), but also that they are less commonly exploited in obnoxious and harmful ways (generally being hoarded by government security agencies or reported in good faith).

We were unprepared for covid despite epidemics throughout all of history

It was said by many that the covid pandemic could have been predicted, in a sense (which is why it was not a true black swan event). Perhaps not the specifics of it such as the date, virus, and origin. But the general idea of “at some point in the future, something bad is going to happen like this, and we need to prepare for it.”

Another one of these “something really bad is going to happen in the future” categories involves cybersecurity, data privacy, and AI. Just one of these topics individually can be involved in a terrible catastrophe, and indeed have been before, but I think we’re coming close to a combination of all three that can lead to events much worse than we’re currently prepared for.

Security: Billions of humans live digital lives, including the most influential, famous, and dangerous. These people all have email accounts, phones, Twitter accounts, and more, all of which can be compromised, controlled, and manipulated by others.

Data Privacy: The amount of data that social media giants (among others) have on most people is massive, and in my opinion vastly underestimated both in quantity and power. The majority of human communication is now owned by private companies that store things forever. A large proportion of all human social connections, conversions, movements, opinions, and thoughts are stored in databases that not only will not forget, but that the user does not have any control or often even knowledge of.

AI: Advances in the area of content generation have been happening very quickly in the last few years. We now have GPT-3, which can write plenty of things better than humans can. We have deepfakes, which can produce believable fake images and videos. We can do the same for voices and much more. Much of this isn’t yet perfect, but it’s clear that we’re improving quickly.

So, take the three above topics of security, data privacy, and AI, and combine them all. Bonus points if you throw in some political tension, which we’re certainly not lacking right now either.

We are not prepared for a true disaster involving technology

As a society, we’re woefully under-prepared for disasters in all of these areas.

We’re not prepared for critical infrastructure, both physical and digital, to be compromised or attacked by highly-funded and competent groups, maybe even state-ran.

Not prepared for the massive campaigns of disinformation, fake news, and propaganda that lie ahead. If you thought things were bad in the last few years, just wait, because we’re on the verge of accelerating it by 10x, and fact-checking is not a solution. China’s government seems to be working very hard both on the offensive and defensive here. Is anyone else truly competing?

Not prepared for how to deal with database leaks that will contain the life history of millions of people, including their ‘private’ conversations and deepest secrets, and items so egregious that they instantly spark violence. Plenty of data breaches have led to murders and suicides already. There are still many countries where you can face imprisonment or death for being gay, being atheist, being of a certain ethnicity, or speaking out against the government (yes, we really don’t have it as bad here, huh!). Do you know what happens when these people have their private information carelessly leaked? It’s not pretty. And this is just for normal database leaks, let alone if a database leak had some information in it falsified (with the majority left intact, thus offering plausibility for the fake parts) to maximize its effect.

Not prepared for how to face that humanity is becoming increasingly controlled by viral algorithms that do not prioritize human values of happiness and love and truth, but rather nothing but outrage and in-group bias as the only bottom line. Most of us already feel powerless against this, but it may only just be beginning.

Not prepared for how anonymity is becoming a luxury only achievable by ultra-competent tech gurus, with most people having been forced to move their communication into more and more centralized ways over time, feeding all of the above issues. Not prepared for how one of the many reasons anonymity is getting much more difficult to obtain is because the easiest way to tell if someone is a bot or a human is to require verification of phone numbers, addresses, and more. And don’t let me forget to mention how many governments are eyeing up ways to ban end-to-end encryption.

I’m supposed to end on an optimistic note

How can we do a better job of addressing these problems?

  • Promote education on the importance of cybersecurity, especially at the government and corporate levels
  • Promote decentralized solutions instead of centralized social media platforms, allowing users to have control over their discourse, their platform, and their own data
  • Promote anonymity, even when it is difficult, and fight to ensure end-to-end encryption is a right for everyone forever
  • Promote better regulations around privacy and data security so that hoarding large amounts of personal data is less of an asset and more of a liability

Although a lot of this post might read as alarmist and pessimistic, I’m still (mostly) optimistic about these things in the long-long-term. The best part about terrible events like covid is that they make us stronger and better prepared for the next (similar) storm to hit us. Security used to be a second thought (or not a thought at all) for most companies, but we’ve improved significant in the last decade, and bug bounty programs and significant security spending are now common. I used to get looked at like I was insane for talking about how big of an issue the amount of tracking and data-collecting our society performs was a big problem, but even this is something that a lot of everyday people believe now as well. I just hope the stepping stones along the way to becoming prepared for the future aren’t so terrible that we don’t make it there in one piece.

Feel free to say hi on Twitter for any comments, suggestions, complaints, etc.

Fact-Checking Is Not Easy

It’s interesting how many people view fact-checking as a simple problem, where you just identify something that is not factual, then correct it. Problem solved! Misinformation has been defeated, the Internet is only full only of Truth, and now The People finally realize we were right all along!

Fact-checking is a very hard problem. A lot of people want to ignore this fact, because correcting people feels good, especially when they’re your enemies.

It takes a lot of virtuousness, of empathy, of vigor, and of rationality to decline the temptation to correct other people. We are driven insane by the fact that not only are other people wrong on the Internet, but they are wrong about basic facts! This is part of why websites like Twitter are so terrible. People cannot stand others being wrong on the Internet. They will gladly spend hours of their daily life willfully being miserable and angry just to have the chance to correct others, even if those they correct do not even change their beliefs at all, or even change them in the opposite direction.

Humor aside, this is literally what fact-checking is

Although some may think the reason why Mark Zuckerberg has come out against fact-checking politicians is so that he can reap profits and sow division while cackling maniacally, I think instead he has simply put a lot of thought into the problem, and not only realized how difficult it is, but also that it cannot work well long-term. He is much more concerned about the long-term future (decades) of Facebook than he is about some upsetting posts made by an upsetting person.

Difficulties with fact-checking

I. There’s no such thing as an unbiased fact-checker

Fact-checkers, whether humans, scripts, or AI, cannot be unbiased. Reality is always a state of incomplete information, and the ways that humans interpret statements vary from person to person. It’s possible for us to disagree on the veracity of a statement, but if we were to discuss things further with more specificity, actually agree on the state of reality. Many statements can not reasonably be interpreted as a boolean of true or false, and instead have subtle amounts of potential bias and nuance within them. Facts are constantly changing, and no single actor has perfect and unbiased information about all of them.

II. Even if there was, someone has to decide which content should be fact-checked

Even given impossibly-perfect moderation, someone has to cherry-pick the content that is to be moderated and checked in the first place, as the Internet has far too much content to police every thought and post manually. Most individuals in favor of fact-checking tend to focus on a very small subset of individuals or organizations that they think should be fact-checked, but this set itself is cherry-picked according to their preferences and attention. This is another process that inevitably introduces bias, potentially in many directions depending on the people and processes involved. Similar to how two completely opposing news networks may only report true information, but still promote entirely opposing narratives because they cherry-pick what is news and what is not news, fact-checking cannot avoid this selection problem. It’s very unlikely that any large organization can do a reasonable job at this.

III. Even given quality fact-checking, the results may not be what you seek

A lot of people do not trust certain fact-checkers, certain news networks, and especially certain social media companies. Even if you perform good fact-checking, there is little evidence that this will achieve your goal, which is not actually correcting text on the Internet, but correcting peoples’ beliefs in their own minds, which turns out to be pretty difficult. Fact-checking could sometimes have an effect similar to the Streisand effect, potentially even causing harm to one’s cause, although I can’t find recent studies on this specifically. Regardless, it should be well-known by now that many people will not instantly and flawlessly change their minds when presented with new opposing facts, especially when done so by their outgroup.

If an Internet platform undertakes significant fact-checking, it could even drive heavily-affected groups off of the platform and onto their own platform, where they would then be even more free to spread their own information in whichever way they want. Similarly, the amount of trust that is given to many companies could decrease significantly and cause greater problems further down the road that can then not be solved with fact-checking.

Long-term affects of big changes are impossible to predict, but it’s not too hard to think about a lot of unintended consequences not just for social media, but for governments, democracy, and humanity, further down the road. Most people don’t have to try too hard to imagine some pretty dystopian results and major failure modes when trillion dollar corporations and governments become arbiters of truth and information.

IV. alternative narratives are important for society

Fact-checking has been desired and attempted by those in power throughout history, often leading to disastrous results, even without considering the political extremes of events such as WWII, which entire books of tragedy are written on. Many may view the Copernician revolution as ancient history, being 500 years ago, but it was only 170 years ago when Ignaz Semmelweis’ controversial hypothesis that doctors should wash their hands and maintain cleanliness was mocked and ridiculed for decades, until it eventually became common practice and saved millions of lives.

Lest those examples still appear as ancient history, remember that during the beginning of the covid pandemic, stating that covid was spreading from person to person directly contradicted the WHO (not to mention that everyone should wear masks, among others), and correspondingly would have been censored by platforms like Youtube according to their public policy.

History is full of countless examples of individuals that went against the grain of their encompassing culture in order to accomplish amazing things and drive progress. These people often armed themselves with what may have been originally considered to be misinformation by those in power during their zeitgeist. I’m glad that we didn’t have the centralization of communication and power we have now throughout history, because many rights that you take for granted were only gained thanks to the failures of past powers to control the narrative as strictly as they wanted to.

V. The narrative cannot be controlled

Just like everyone else, I too wish that everyone that was wrong on the Internet could be corrected. I wish my favorite narratives, facts, and causes were supported and known by more people. To not attempt to correct and control the narrative is a tough bullet to bite, but it’s something that a lot of thought and consideration must be put into, requiring very long-term thinking and awareness of history.

As long as people are free, they will come up with their own narratives, causes, desires, and even facts and entire worldviews. It’s been said that we live in a post-truth world, but that has always been the case. It’s just more apparent now that you can see people from every other background and culture when you use the Internet. No single person, company, or government can control information flow and peoples’ beliefs to the extent that they wish, and any that grasp for such an unattainable level of control will find that it doesn’t work long-term. Even the countries with the strictest controls on information, reporting, and speech, historically, have never fared well after a long enough time.

Different people have different lives, different values, and even different facts that they live by. It’s possible for you to co-exist with them, but perhaps not best if you’re forced to live in the same room as them. But no matter how hard you try, it may be impossible to get them to live their life the way you want them to. I know it’s difficult, but sometimes the only option is to let others live in their own world, while you live in yours, still helping to make it the best you can. Spending your days being angry and miserable on social media will not accomplish what you want, no matter how right you are.

Although this post might not be particularly insightful and is almost too political for my taste, I hope at the least this may help some realize that fact-checking is more difficult than it appears at first glance, even if they still support it.

I’m looking for more interesting people to chat with on Twitter, especially if you have corrections, improvements, or just like to discuss topics like longevity, startups, security, and finance, and more.