How pharmaceutical industry financial modelers think about rare diseases - <AUTHOR> http://www.cureffi.org/2019/04/29/financial-modeling-in-rare-disease/ <comment><USER4> This is an impressive article and an impressive couple. From the site's about page:

 _My name is Eric Vallabh Minikel and I'm on a lifelong quest to develop a treatment or cure for human prion diseases. I originally trained as a city planner at M.I.T. and was working as a software engineer and data analyst in the transportation sector when, in December 2011, I got some bad news. My wife and the love of my life, Sonia Vallabh, tested positive for a mutation (PRNP D178N cis-129M) that causes genetic prion disease, and that had claimed her mother's life one year earlier. Sonia was 27 at the time. The mean age of disease onset for her mutation is around 50, and the mutation is highly penetrant, meaning she is exceptionally likely to develop the disease unless a treatment or cure is found._

 _Sonia and I set out on a quest to re-train ourselves as scientists. We both started taking night classes, reading papers, calling up scientists, going to conferences. We left our old careers and found jobs in research labs, and eventually enrolled at Harvard Medical School, where we are now PhD students in biological and biomedical sciences._

One thing I've learned from smart family and friends about medical care is that you can sometimes improve outcomes quite a lot if you apply brains and effort. I have relatives who managed to convert their dad's brain cancer outcomes from a couple of months in palliative care (which the doctors were recommending) to five more mostly-good years, by finding better surgeons, signing him up for clinical trials, and getting to the cutting edge of the research and applying it. For example they switched him to a ketogenic diet back when this was just starting to show results for cancer. These guys are taking this approach to the extreme! I hope they get the result they're looking for.

<comment><USER5> >For example they switched him to a ketogenic diet back when this was just starting to show results for cancer

I'm curious as to how this would have an impact. Is there any research demonstrating that keto slows the development of cancer? Or hypotheses on why that would be the case?

<comment><USER6> Though it's incredibly dependent on the type of cancer, it's history, it's environment, and it's genome, it is related to the metabolic pathway that you shut off.

This is known as the Warberg Effect [0]. Essentially, for some reason, some cancers will start eating only via glycolysis and not via oxidative phosphorylation. Glycolysis requires glucose (sugars, like carbohydrates), so if you just stop eating foods that turn into glucose, those types of cancers will starve. Low sugar diets are ketogenic diets.

I'll be clear here, this is _super_ speculative. Cancer isn't something like measles, each one is super specific to the organism and evolves over time. Keto diets may work for a while to harm cancers, but may also select for more 'hearty' cancers over time. It's not very well understood, even still.

[0] [https://en.wikipedia.org/wiki/Warburg_effect_(oncology)](https://en.wikipedia.org/wiki/Warburg_effect_\(oncology\))

<comment><USER7> But if you've been handed a death sentence, why NOT try a keto diet? That's a rhetorical question btw of course the is no reason not to try it.

<comment><USER6> Each cancer is unique to the organism. Not all cancers are death sentences. Nearly every sunburn you or I have had has been cancerous to some degree; the inflammation and reddening are your body fighting those cancers (among _many_ other issues). Some cancers can be benign, some can be handled quite easily, some can be treated in other ways. Again, each is unique.

The data on Ketogenic diets and cancer are showing a lot of promise, but you should follow the advice of you oncologist/s. They have dedicated some portion of their lives to helping you out with your cancer. You do not want to end up in a situation where you have convinced yourself that kale is better than chemo. Again, each cancer is unique though.

<comment><USER7> Palliative care is an admission that chemo won't help and pretty much all options have been tried. At that point one can sit back and die, or try something.

<comment><USER6> Again, it depends on the situation at hand. Though ketogenic diets are showing promise, it depends on the cancer, as such diets may aggravate the cancer. One should follow the advice of the oncologist/s as well as research on their own.

</comment></comment></comment></comment></comment></comment></comment><comment><USER8> Having been through the early phases of this (both as bench scientist and management, up through Phase II) I can say that this author's analysis is right on.

There is a macro wrinkle he doesn't mention and that makes things worse: as we increasingly succeed on stopping the big killers (e.g. lung cancer, CIs, various accidents that constituted most of the causes of death into the 1990s) the histogram of death starts to flatten out. That is, an increasingly larger set of conditions kill people, each condition killing a smaller number. At the limit, everybody would die of a unique condition.

This "problem" has been well understood for decades. The current model doesn't really work as this process continues, but nobody really knows yet what would be a reasonable replacement. This is one reason you see more and more ads for drugs that don't solve anything life threatening but have a larger prevalence (e.g. incontinence, insomnia, et al).

<comment><USER9> > histogram of death

Not something you read everyday!

How does your "wrinkle" make things necessarily worse? All [men] must die (sorry) at some point so succeeding at removing the biggest killers would give more people a second chance to die of something else later. Just because we cure cancer won't mean that there are suddenly more causes of death, just that the people who would have died from cancer will die of a variety of other existing things.

Anyway, your point likely still stands. It makes sense that companies will have to spread resources across a diversifying research field once the big killers become treatable.

edit: format

<comment><USER10> > How does your "wrinkle" make things necessarily worse?

If a small number of causes continued to be responsible for a large fraction of all deaths even as causes were defeated/delayed by medical interventions, then a continuous application of research resources could plausibly lead to consistent increases in life expectancy. For instance, if as heart disease deaths are being reduced by endovascular procedures those people are dying mostly of colon cancer, then we could divert resources to colon cancer research and hope for continued progress. But if, once the major diseases are suppressed, the number of causes of death explodes into a diverse spectrum of unique illnesses, there is little hope that constant (or reasonably increasing) resources can do much.

</comment></comment></comment><comment><USER11> This is a well researched, informative and infuriating article. Within the system I cannot think of a better or more determined approach to this problem, but as this is HN I need to lay out a few points.

As we mint more billionaires they are going to do an end-run around the FDA. If I were a billionaire there is no way in hell I'd wait for a standard drug trial to progress on an FDA timeline.

Eventually one or more of the ultra wealthy is going to survive a disease that government sanctioned healthcare says is incurable. This will make its way through the network of the wealthy, and with some luck the whole process of how a drug was developed outside of the system will come out.

The bloat and overhead of the current process is intolerable. We've managed to elevate caution to a crippling set of shackles and _at the same time_ put control of the process into the hands of people who only care about the calculus the OP so carefully describes. We pay unending lipservice to process and safety but drug companies are only act in proportion to potential liability.

<comment><USER12> > If I were a billionaire there is no way in hell I'd wait for a standard drug > trial to progress on an FDA timeline.

You don't have to be a billionaire for this. There aren't many drugs which sit between proving efficacy in clinical trials and FDA approval, and ones that are like that only sit there for a few months. Of course, those could be important months for a particular patient, but there are ways to handle this. One such program is called "compassionate use". The idea is that if you have no other hope, you can be prescribed a non-approved treatment.

There aren't as many potholes in this as you seem to believe. Drugs which are proven efficacious and safe usually are submitted for approval, because it's expensive to run trials. It wouldn't be the first time a billionaire decided to do something medically unwarranted or ambiguous, but that doesn't mean it will become a norm.

<comment><USER11> Your comment made me realized I forgot an important predicate.

I think we're near an explosion of drug _targets_. That the front-end of the pipeline is about to get very full very fast.

That's one of the forcing factors I didn't mention.

</comment></comment></comment><comment><USER13> I was surprised that this article didn't mention the Orphan Drug Act of 1983, which was passed by congress to facilitate the development of drugs for rare diseases (many other countries have similar legislation).

This act gives tax incentives, subsidies, lowers clinical trial requirements and increases exclusivity for the development of "orphan drugs", which otherwise might not be economically viable to develop. That said, if a condition is rare enough, there's probably no amount of tax incentives that's going to induce a for-profit company to go through the significant costs and hassle of bringing a drug to market.

<comment><USER14> Avik Roy has an absolutely blood-boiling section of this report devoted to ways companies are gaming the Orphan Drug Act

[https://docs.house.gov/meetings/GO/GO00/20190129/108817/HHRG...](https://docs.house.gov/meetings/GO/GO00/20190129/108817/HHRG-116-GO00-Wstate- RoyA-20190129.pdf)

<comment><USER15> Not really. While he makes it sound bad, what is happening is that in exchange for actually proving that drugs we "know work" actually work companies get a monopoly for a short time. I'm glad some of the treatments doctors have been using for years now have science behind them so we know more about how well they work.

</comment></comment></comment><comment><USER16> I met a PHD chemist who spent 30 years developing drugs. Over that period he developed 20,000 APIs. 4 were approved. 1 made it to the market.

<comment><USER17> I wonder how many times over tests were done by competing companies, duplication, and how much waste/inefficiency there was because of data not being shared - and how much further duplication may continue to happen.

<comment><USER18> My project in University (and now my company) annoyed a lot of companies when we first published DrugBank in 2006. We basically opened up the data on potential APIs and their targets into a downloadable and useable data set. I remember going to conferences and being both lauded by academics and maligned by pharma folks. This was before Wikipedia or things like Pubchem and ChEMBL were really a thing.

<comment><AUTHOR> Why would a drug company care if you share public information? Because you make it easier to search?

<comment><USER18> Good question. They had built a lot of internal tools and datasets that we rebuilt and released. It was a competitive advantage before.

</comment></comment></comment></comment></comment><comment><USER19> When the whole Martin Shkreli saga was making the news I ran across his youtube channel and did end up watching his 'How to analyze a clinical trial' series of 4 videos to understand the process .. they're long but it was interesting to some extent as someone from outside that industry .. [https://www.youtube.com/channel/UC8gjB1PSXv_oAUSAQ16S0fA/sea...](https://www.youtube.com/channel/UC8gjB1PSXv_oAUSAQ16S0fA/search?query=how+to+analyze+a+clinical+trial)

<comment><USER20> I also followed his saga and watched both this series and his general stock picking analysis videos.

If you can separate yourself from the persona he tried to cultivate and enjoy having your excel skills emasculated there both great watches

<comment><USER19> If your goal is to have your ego deflated in Excel, this is always a good place to start .. "You Suck at Excel with Joel Spolsky" .. [https://www.youtube.com/watch?v=0nbkaYsR94c](https://www.youtube.com/watch?v=0nbkaYsR94c) but I agree, Shkreli definitely had the whole speed run thing down with Excel.

<comment><USER21> Is that a parody of "You Suck at Photoshop" tutorials?

<comment><USER19> Funny, I never even noticed that, but apparently so .. his last comment in the description is "Apologies to Danny Hoyle" and a (now broken) link to "You Suck at Photoshop" videos.

</comment></comment></comment></comment></comment><comment><USER22> Pharmaceutical companies typically claim that the reason for high drugs prices is because of the amount that they spend on research and development (R&D). According to the industry, it costs USD $2.6 billion to bring a drug to market [1]. Critics counter that companies are more focused on and spend more on promotion than on R&D. Gagnon and Lexchin produced figures that showed that in the United States in 2004 the industry spent USD $57.5 billion on promotion versus USD $31.5 billion on R&D [2]. A report from the California-based Institute for Health and Socio-Economic Policy stated that in 2015 out of the top 100 pharmaceutical companies by sales, 64 spent twice as much on marketing and sales than on R&D, 58 spent three times, 43 spent five times as much and 27 spent 10 times the amount [3].

[1] [https://www.ncbi.nlm.nih.gov/pubmed/26928437](https://www.ncbi.nlm.nih.gov/pubmed/26928437) [2] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174966/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174966/) [3] [https://nurses.3cdn.net/e74ab9a3e937fe5646_afm6bh0u9.pdf](https://nurses.3cdn.net/e74ab9a3e937fe5646_afm6bh0u9.pdf)

<comment><AUTHOR> Companies don't spend $X on promotion unless they gets $X+ back. Otherwise why bother? So overall, promotion is a net positive to revenues.

<comment><USER23> The criticism is more that instead of increasing sales by developing more drugs, they focus their resources on marketing instead. This makes more money for them but is bad for society.

<comment><USER12> I still don't understand why it's bad for society? It seems like this is a common point that implies something, but I can't figure out what that thing is.

<comment><USER22> well in the context of developing drugs that cure disease (esp rare ones), pharma says its so expensive to do, it costs billions to develop a drug. but if in fact it "costs" billions to "market" a drug then is that the same thing? i dont have a strong opinion on this

<comment><USER12> I'm not super familiar with the numbers, but I believe the "billions to develop" number is a development number, if a little juiced. I think they take the total amount of R&D spend and divide it by the number of drug launches for a given period of time. So it's a good idea of how much money you have to spend to get a new launch, but it is higher than the cost of a single project, the majority of which are terminated before launch (many well before clinical trials).

After you spend a couple billion per launch to make a new drug, then you spend another couple billion on marketing. Again, I could be mistaken, but I'm pretty sure that's the position of pharma.

</comment></comment></comment></comment></comment></comment><comment><USER24> This is a fantastic writeup. There isn't a lot of great info online about the business of pharma but this is a great intro that hits on a lot of key concepts.

If you play around with a model like this you see how important _biology_ is. the risk that something that works in mice but fails in humans is the biggest reason drugs are so expensive to develop. Front loading this risk / lowering the cost to "derisk" this risk is one of the most important things to focus on

One other concept that's incredibly important but not discussed is "unmet need", i.e. How underserved are patients by standard of care. For a fatal rare disease, unmet need is high; for a disease with drugs that already work pretty well the unmet need is low. Unmet need + clinical benefit (how much does your drug make patients better) determines clinical value, which is roughly correlated with price you can charge. Price isn't directly determined by cost- benefit calculations in the US, but it's harder for payers to deny a drug if it would save lives, while payers can easily sideline for ex another slightly better yet more expensive insulin

Some people view the phenomenon of higher prices for higher benefit as exploiting sick patients; I don't think that's entirely fair although in cases like Martin shkrei it is. I've always thought of it as aligning drug makers incentives with the sickest patients -- you only have a viable product if you are providing immense clinical benefit to very sick patients. So r&d is very focused on diseases with severe unmet need. These days roughly half of drugs are developed for patients with severe rare disease or late stage cancer, as most other diseases aren't financially viable

</comment><comment><USER25> Looking at these numbers, I wonder whether the FDA process is a bit too conservative with respect to safety.

There were the articles yesterday about diabetics yesterday creating closed- loop feedback systems out of old insecure parts, because a FDA-certified alternative is decades out.

I've heard also of folks joining studies for newer-and-better IUDs that are approved by European regulators, but need to be re-certified for the US market.

Politics and lobbying are hard, but would some regulatory changes result in a 10x reduction in R&D costs?

<comment><USER26> Your comment reminded me of the (ridiculous but sadly necessary) "Sunscreen Innovation Act" passed a few years ago.[1]

U.S. financial regulators often "vet" their equivalent foreign agencies and whitelist those whose processes are sufficiently analogous and in some cases allow US entities to rely upon the work done in those whitelisted jurisdictions. I've always wondered why the FDA can't work out a similar system. If the EU has approved a drug and done all of the studies and asked all of the questions surely we don't need to do all of the same studies and ask all of the same questions just so we can approve the drug a decade later.

[1] [https://en.wikipedia.org/wiki/Sunscreen_Innovation_Act](https://en.wikipedia.org/wiki/Sunscreen_Innovation_Act)

<comment><AUTHOR> _I 've always wondered why the FDA can't work out a similar system. If the EU has approved a drug and done all of the studies and asked all of the questions surely we don't need to do all of the same studies and ask all of the same questions just so we can approve the drug a decade later._

The reason is thalidomide. The US was one of the few countries that chose not to approve it despite other countries doing so. Saved a lot of US children from birth defects.

<comment><USER26> Ah yea, thalidomide. That drug is often used to justify poor policy decisions at the FDA. It's the reason the FDA banned women of child bearing age from clinical research.[1] In the late 80's there was even a study conducted to determine the relationship between obesity and risk for breast and uterine cancer. Guess how many women were enrolled? Zero. Thanks to the FDA's misguided knee jerk policy response to thalidomide.

It seems to me the FDA's process _might_ "protect" a small number of people but that comes at the expense of many thousands of lives.

[1][https://www.drugwatch.com/news/2018/07/25/excluding-women- fr...](https://www.drugwatch.com/news/2018/07/25/excluding-women-from-drug- trials-kills-people/)

<comment><AUTHOR> Hey, I don't disagree that that FDA is very conservative. My comment was more around the politics of it.

Look back at the Vioxx hearings. People crapped all over the FDA because they didn't catch an increased risk of CV issues until post-approval.

If you're the FDA, it's "damned if you do, damned if you don't".

<comment><USER26> That's fair and the struggle for all regulators I would imagine (though the stakes are higher with human health).

The crypto people drive me nuts the same way. One minute they're extolling the virtue of markets "free" from regulatory interference but the second it turns out the market was a scam they want to know what the government plans to do to get their money back.

</comment></comment></comment></comment></comment></comment><comment><USER27> This article does a good job showing how big an impact the concept of "time value of money" can have on a multi-year investment of any kind - pharmaceutical or not. (Particularly since many of us in software are effectively investing nontrivial amounts of our salary in illiquid investments.)

I'd imagine that many tend to think of a $X investment as a $X investment... but if that investor could get effectively compounded interest/returns, even at a single-digit rate, in another investment, they could be risking many times $X by forgoing that investment to take the one in question. Take a look at the chart and formulas in [https://en.wikipedia.org/wiki/Time_value_of_money](https://en.wikipedia.org/wiki/Time_value_of_money) and [https://en.wikipedia.org/wiki/Discounted_cash_flow](https://en.wikipedia.org/wiki/Discounted_cash_flow) . Important stuff to know regardless of how large a financial decision one wants to make.

And in the context of highly risky drug development, in a capitalist society it's a miracle that niche drugs are researched at all. It speaks to the passion of scientists like the author who endeavor constantly to develop tooling and processes to accelerate/de-risk drug research enough to be an attractive investment in today's increasingly optimized society.

<comment><USER28> I agree completely, most people overlook the "opportunity cost" of investments. If an investment makes %3 per year but you could invest in something else that makes %4 per year, while you did make profit, you actually lost money, because you missed an opportunity to make an extra revenue equals to %1 of your money (or %33 more profit).

<comment><AUTHOR> You see people do this a lot with housing. They make $100k after 5 years and pat themselves on the back.

They ignore that if they had put their down payment in the market, they would have made $110k.

<comment><USER29> The difference is that they can buy homes on margin, whereas no one would lend to them to invest in the market on margin. Return has to account for only putting 5% to 20% down. Not that I think homes are a good investment outside of the few burgeoning cities in the US, compared to index funds, time/labor costs included.

<comment><AUTHOR> My comment ignores the leverage and just looks at the downpayment alone.

To your point, their $100k gain at 5x leverage kind sucks compared to a $110k gain at zero leverage.

</comment></comment></comment></comment></comment><comment><USER30> The author ignores two obvious, extremely high leverage changes that would solve the problems in his model.

First, on the revenue side, extend patents on pharmaceuticals as long as possible. His model assumes a very narrow window of payback; quadrupling or quintupling that window would make many more drugs feasible to investigate.

Second, to use the author's word, "de-risk" all trials. The best way to do this would be to end the FDA. But an intermediate step would be to eliminate the requirement to show efficacy, only retaining the requirement to show safety. Safety is orders of magnitude cheaper to prove.

Trials could be conducted much more cost effectively with these two changes. There would be more time to form patient and investigator networks, the structure of trials would be less complex, many more drugs could be tested, and many more drugs would be profitable.

<comment><USER31> Extending patents wouldn't work that well in his model - as you can see from the graphs it is already discounted crazily (I'd argue for a 6% discount rate, not 8, but it hadly changes the calculus). Besides market exclusivity can often be extended by adding indications and pediatric studies, so they aren't as short as first stated. Plus on some drugs you then get other patents - <USER2> inhalers where you have patents on the devices as well as the drugs.

Equally asking to prove safety only... you still have to do the studies, and need a lot of exposure so why not capture outcomes too? I'm not convinced it would be a lot cheaper to omit the outcomes - you still have to recruit the patients, and monitor them. Take HIV, if you don't test blood, you don't know what is happening to patients blood counts, since you have the blood, why not also check for efficacy in viral supression?

Regulatory is also based on benefit:risk, without evidence of benefit, why tolerate any risk? Also how many clinicians would give new drugs with only theoretical efficacy?Hopefully none. All the drugs that fail trials we also think should work, and spend money to prove it! Not to mention the market for pharmaceutical is worldwide, the EMA, Health Canada, Swissmedic and others would throw something out with no evidence of benefit, greatly limiting your market, even in the US.

Are the FDA perfect? No. Are they excellent? Yes. Some of my research touches up against what they do, and my respect for them grows with every interaction. They're also continually improving. The fundamental problem is that we're looking at a 'better than the Beatles' problem [https://en.wikipedia.org/wiki/Eroom%27s_law](https://en.wikipedia.org/wiki/Eroom%27s_law)

What might work? More collaboration between companies. If we can enrol one placebo arm, but test 4 active products against it, we cut the costs (and improve the ethics by giving fewer patients placebo). There are a few other minor tweaks too, but it is something we all want to improve, and are trying to do so!

</comment></comment><comment><USER31> So I work on the opposite end to discovery, in the interpretation, and estimation of outcomes seen beyond the studies i.e. what impact will the drug have. Applied statistics essentially.

The author is completely right about the raw mechanics of investment decisions (and sometimes they are just that when a pharma company is sizing up buying an asset), but has written up a really thought provoking piece which was interesting to read. Though I deal with time preference every day, I hadn't quite internalised how much influence it had for early spending.

In terms of my experience, very similar, I worked in global HQ for a large pharma company, responsible for my small part of things for 4 products. 2 failed in Phase 2, and the other 2 failed their Phase 3s. I moved to another pharma company where I was focussing on launch products, but every now and then one would disappear off the radar. For other the trial results would come in, and it only worked on half the patients. We expected all these to work - the science was impeccable, the animal models demonstrate a good basis for belief... it just didn't happen. Every drug that works really is a needle in a haystack.

On the making development attracting, I've been forutnate enough to be able to volunteer some of my professional time to a patient group trying to attack the problem in a different way, and make it possible to get medicines commercialised in Duchenne Muscular Dystrophy. The approach is led by a couple of really impressive executives* and is trying to get companies to collaborate to pull together some of the materials the author mentions (rather than all do them in isolation with variable quality). They recently won an award for their work, and thoroughly deserve it. These kind of initiatives are what can really make a difference, and de-risk an area for many companies - the lay of the land is known, and there is high quality understanding of what matters to patietns, and the natural progression of disease. It also means that companies developing medicines can engage to make sure their trial program targets the right patients, and measures the right things. If anyone is interested: [https://hercules.duchenneuk.org/publicity](https://hercules.duchenneuk.org/publicity)

* I say executives because that's what they are, and the role they play. They all have sons with DMD which is their motivation, but that label that doesn't do justice to the amazing work the group does - as an example where there are generic medicines that might help, they are funding trials to find out!

</comment><comment> integrate-this This is a pretty solid breakdown. IRR isn't mathematically valid though. I might take a run at cleaning up this spreadsheet tonight to make it look a little more professional. Need to include things like tax and exit valuations to get to the correct decision.

<comment> integrate-this There are a few very important caveats that they miss though. Revenue determinants are heavily based on conversations with healthcare payers to determine market size which dramatically effects revenue projections. Most firms that do deep development plan to sell successful drugs and exit as early as possible so transaction costs need to be included in the terminal value, which isn't calculated terribly well in this model.

<comment><USER31> I'd also use corporate bonds for pharma companies (or biotechs, depending on which you are looking at) for the cost of capital, as ultimately that's what debt costs

</comment></comment></comment><comment><USER32> Here's non-profit startup trying to tackle this kind of stuff: [https://www.youtube.com/watch?v=v7V8-dfQ7bM&feature=youtu.be](https://www.youtube.com/watch?v=v7V8-dfQ7bM&feature=youtu.be)

</comment><comment><USER33> Great article. Best of luck to them.

Anybody knows about efforts to lower trial phases costs down ? (without lowering quality of course). Any out of the box idea ?

<comment><USER31> Collaboration - one control arm, 2+ active drugs from multiple companies (why not 6+?). Fewer patients exposed to placebo, less paperwork, same statistical power, more so if you randomise 2:1:1:1:1:1 rather than a standard trial with 1:1 or 2:1

</comment></comment><comment><USER34> Shorten or remove the patent benefits awarded to new drugs, and the calculus changes dramatically.

<comment><USER29> The only change I can see is needing to increase the cost of the medicine to make up for the reduced exclusivity period, or a reduced incentive to research medicine.

<comment><USER35> You can't just reduce the patent period without reducing the regulatory process that is required to get stuff approved. It would not work otherwise.

<comment><USER29> I hope we're not on the path to reducing rigorous testing and vetting of medicines in exchange for cheaper prices. Medical science is extremely hard, and verifying cause and effect in a system as complex as the human body takes significant resources.

People want cheap, people want safe, people want well qualified individuals pursuing these advances. What people don't want is higher taxes to enable government funding for this research, and would rather have private investors pick up the tab. And then they scoff at high medicine prices. I'm sure there's some corruption and paper pushing waste going on, but fixing that is not going to remove the need for costly triple blind studies that span years, only to result in failure the vast majority of the time.

That's the cost of good science, and if society wants the fruits, they need to pay for it.

<comment><USER31> This is exactly correct. Also there is a good incentive structure in there - <USER3> well designed clinical trial program will move between phases, collect all data possible to support an application, and have all the relevant data to get a timely approval. The better you do on evidence collection, the sooner you are on the market, and more you have to work with

</comment></comment></comment></comment></comment><comment><USER36> Throws a little doubt on those who say the money is in the treatment and not the cure :).

<comment><USER37> not exactly -- it's more that the money is in whatever they can get passed through clinical trials. if that's a cure, great. if not, it'll still sell.

there is no inherent incentive to deliver a cure from a drug product, provided that there is no competitor drug. luckily, there's also no realistic incentive to sit on a cure because it can be priced to be profitable even if the cure makes itself obsolete, which is extremely unlikely in any event.

<comment><USER36> I was joking a bit.

I agree with your last statement, and I'd argue as well that if you had the cure to say, cancer, you could charge whatever you wanted for it (at least in the short term). When it comes to money, you just can't take it with you, and you'll spend pretty seriously to improve your lifespan.

<comment><USER31> The people who say pharma don't want cures generally don't understand the industry. A cure is worth more than a chronic treatment, and the article does an excellent job of explaining time preference (his 8% discount) - having a treatment you can sell for more years isn't worth much when you discount it all.

Fundamentally companies have to follow the science. If the science is there for cures, that is what is pursued. If the science is on life extending treatment, that's what gets followed up. You don't get to pick and choose what you want - both can be lucrative, and both can be failures!

<comment><USER12> I truly believe that people don't really understand how difficult cures are. It's not that we in pharma don't want to cure things, we just don't know how. Also, most pharma and biotech companies are built around a small number of mechanisms. Many pharma companies only make small molecules or large molecules, but don't touch potential siRNA, CRISPR, or stem cell therapies.

Take diabetes for example. By the time a Type I diabetic is diagnosed as diabetic, they've lost a huge portion of their beta cells (something like 80% if I remember correctly). It is _very_ hard to slow the destruction of those cells and harder to completely stop future islet mayhem. It's nearly impossible to regrow them with the information we have now. Even if it is possible to regrow those cells, can it be done by giving a drug, or a drug coctail? Maybe not. Maybe it has to be a stem cell treatment. Or an order of magnitude more difficult to discover: a stem cell treatment in conjunction with drug(s). Will that kind of therapy come out of a big pharma company? Maybe with partnerships with other companies or an acquisition, but the people who make small molecules probably don't know a whole lot about convincing stem cells to become beta cells; it's just a different set of skills.

<comment><USER31> Fully agree - I work with pharma as an independent (and used to work at GSK & Sanofi before that - effectively medical statistics). I'm currently working on a gene therapy from a biotech, if it works it'll be amazing, and be a semi- cure, holding functionality where it is, but even that isn't a perfect cure.

I've also worked on 2-3 immunotherapies, they again can be amazing and turn previously uncurable cancer to long term survival (of duration unknown), but only in a fraction of patients - to work on them was an honour. Most therapies are incremental improvements, which can make a big difference to patients, but there is still unmet need.

GSK when I was there were explicit, half the drugs they wanted to develop internally, but using the commercial knowledge and experience guiding drugs though trial and approvals, also wanted half of drugs to be invented outside, and be commercialised by a company who knew how to do that!

</comment></comment></comment></comment></comment></comment><comment><USER38> I would assume that somewhere on the bottom line there is an analysis of what the drug itself is doing. For instance, does the drug cure something or does it treat the symptoms of something? I imagine most of former are thrown out right off the bat. What we need is a system for testing, developing and selling medications that is less effected by the human condition. Perhaps, we should close the private sector and hand this off to the government or at least breakup the process by allowing the private sector to sell without the burden of testing and development? Perhaps, we as taxpayers, should be handling the burden of cost for testing and development?

<comment><USER12> > I imagine most of former are thrown out right off the bat.

Why? You don't think cures have monetary value?</comment></comment>


Retailers are using chatbots to boost customer engagement - <AUTHOR> https://blog.datahut.co/chatbots-for-retail-how-retailers-are-using-chatbots-to-boost-customer-engagement/ <comment><USER2> The ecosystem of chatbots is new and still evolving with technological advances. One has to know about what you want to achieve using your bot. Chatbots are starting to take up better and complex automation tasks with the passing of time. Build your bot with Engati now. Register at [http://s.engati.com/142](http://s.engati.com/142)</comment>


Fun ways to use emoji in your code - <AUTHOR> https://techlady.haus/blog/2017/11/9/three-fun-ways-to-use-emoji-in-your-code <comment><USER2> Opening a file that's not been opened in months to troubleshoot a bug in production and being greeted with code that looks like this[1] is a horrifying thought.

[1] Image from article - [https://images.squarespace- cdn.com/content/v1/592c721986e6c0...](https://images.squarespace- cdn.com/content/v1/592c721986e6c0040d5a263e/1510270057051-Z2SUVGXLFMSRN47X4EJB/ke17ZwdGBToddI8pDm48kC9-BkjXq1ev5qC0LBkA3hpZw- zPPgdn4jUwVcJE1ZvWQUxwkmyExglNqGp0IvTJZUJFbgE-7XRK3dMEBRBhUpysF23h011zu84d3nQo7QJ89zhK2U0vc3hXXXqpCtMKLsdhOZvELVwv61XaF8iUi-8/Screen+Shot+2017-11-09+at+3.24.25+PM.png)</comment>


My acquired Bitcoin startup Bridgewalker is now open source - <AUTHOR> https://www.bridgewalkerapp.com/blog/2014/01/07/bridgewalker-open-source/ <comment><AUTHOR> Some background: It's an Android wallet, where you maintain a euro balance (held by Bridgewalker for you). Using those funds, bitcoins will be bought at current market price whenever you want to send any. This allows you to use Bitcoin only as a payment mechanism, without being affected by the exchange rate volatility. You fund your account via Bitcoin as well, which will be exchanged for euros at current market price and credited to your account.

So: Bitcoin as transaction mechanism, Euro as store of value.

<comment><USER2> Bitcoin newbie here, so it's probably something obvious, but can I buy Bitcoin from this app ? I wasn't sure if the "receive Bitcoin" meant that.

<comment><AUTHOR> No, you cannot use this app to buy bitcoins. So I'm afraid it does not solve one of the hardest challenges Bitcoin still faces, which is how to get any. You'll have to figure out the best/cheapest way depending on where you are.

If you happen, for example, to stand in front of a Bitcoin ATM, you can use that to turn fiat that you have in the form of cash into fiat that you have in your Bridgewalker account (by buying Bitcoin from the ATM and sending it to your Bridgewalker address), which you can then later spend wherever it says "Bitcoin accepted here".

A lot of exchanging back and forth for sure, but basically the idea of "Bitcoin only as tranfer mechanism" applied at every step. It's also just a technical prototype. In practice it might make sense to cut some of those exchange fees by having a more direct way to fund your account, at the cost of only being available in certain markets/countries. For this prototype I went with the easiest solution: only Bitcoin in, and Bitcoin out.

</comment></comment></comment><comment><USER3> Quite nice to see that this is written in Haskell.

The idea of a bitcoin app that stores funds in another currency makes a lot of sense for people who primarily want to use bitcoin as an exchange mechanism without speculating on its future value.

I'm curious what service this uses to purchase bitcoins, or if it uses its own exchange; it's not comforting to see a reference to the MtGox API, but hopefully they're only used to find out the current value. (Even then, they're not a reliable metric for the true value of bitcoins, since they're not sufficiently liquid with respect to governmental currencies, but that'd still be better than actually attempting to use them as a currency exchange.)

<comment><AUTHOR> It does use Mt.Gox in the background for the actual exchange process. There is not enough volume (yet) to make an internal exchange practical, there would be too much risk at the moment, at least for my taste.

When I started on this project, Mt.Gox was pretty much the only choice, because of the large market share (> 80% at the time) and the necessary volume and small enough market spread. Their withdrawal delays are annoying, that's true. It does not affect me directly, since it's only Bitcoin in and Bitcoin out for me, where so far Mt.Gox had pretty much never delays. But it does distort the market price, which means you get a great rate when you fund your Bridgewalker account (because BTC is overvalued on Mt.Gox) and get a bad rate when you spend it (again, because BTC is overvalued on Mt.Gox) - so in the end it kind of zeroes out for you as a user, but it's still confusing for the user, why you have this offset.

There aren't many alternatives though. Bitstamp could be one, but I'm worried that they still might run into regulatory issues down the line. Also none of the other exchanges offer real-time streaming updates about changes to the order book, like Mt.Gox does, which is very useful to keep track of the market. Kraken could be an interesting alternative to Mt.Gox, since they seem to run a solid operation. If they add such a streaming API with real-time updates about the order book and maybe get some more volume, then I would consider switching the backend over.

Or someone else does it first - it's open source now, after all! ;-)

Or maybe you could hedge the whole thing just with some financial swap construction, but I haven't looked into that too much and it's not my area of expertise. I would be interested to find out how much something like that would cost in terms of overhead/fees and who would be a partner to provide such financial services for Bitcoin. If you have some input regarding this, feel free to contact me - my email address is on the Bridgewalker website.

</comment></comment><comment><USER4> this is awesome!

btw if you plan to make an iOS app, maybe you'll be delighted to know that you can apply as an open source developer to free Xamarin licenses: [http://resources.xamarin.com/open-source- contributor.html](http://resources.xamarin.com/open-source-contributor.html)

(I guess writing F# would make you happier than ObjectiveC, given that you wrote your server side in Haskell ;)

</comment><comment><USER5> This is great. These kinds of open sourced production apps help people adapt more of haskell.</comment>


Want Innovative Thinking? Hire from the Humanities - <AUTHOR> http://blogs.hbr.org/cs/2011/03/want_innovative_thinking_hire.html <comment><USER2> If I remember correctly, I believe IBM used to apply this reasoning back in the 1980s.

Having done humanities subjects as well as CS, I would say that the workload was quite potentially similar in difficulty and sophistication and would likely stand people in good stead, as the article says... IF you did the readings for the humanities courses, which quite a number of people doing a Bachelor of Arts really obviously didn't. It was obvious you could skate by with the equivalent of a B- or C+ while doing 15 hours a week total work, which usually inspired great quantities of rage and disdain from the engineering/science students.

</comment><comment><USER3> Here's something I learnt from the humanities: distinguishing between _necessary_ and _sufficient_ causes of events.

Steve Jobs taking a calligraphy class was _necessary_ , but not _sufficient_ , to create the Macintosh. He still needed a team of those tedious non- humanities folks -- not least of whom was Woz -- for Apple to succeed.

Bill Gates and Zuckerberg had educations rich in the humanities. But that was not enough: they also had a deep background in actual programming.

The humanities _by themselves_ are not enough. You need the rubber as well as the road.

<comment><USER4> In the case of all those mentioned it seems like what you want to do is drop out of college entirely.

Related, apple was staffed by total weirdos for its first 8-10 years, people who neither fit the stereotype of engineer or humanities major. See any article at folklore.org

<comment><USER3> > In the case of all those mentioned it seems like what you want to do is drop > out of college entirely.

I picked examples that I'm familiar with. In another field I'm confident that the pattern repeats -- that humanities is an edge but not a base.

Slightly OT -- one of my dreams upon makin' bacon is to go here for a few years: <http://stjohnscollege.edu/></comment></comment></comment>


11 reasons Google may know you better than you know yourself - <AUTHOR> http://tech.blorge.com/Structure:%20/2008/02/03/11-reasons-google-may-know-you-better-than-you-know-yourself/

<comment><USER2> Get over it. There are more than 11 reasons. Privacy is relative, especially in a world where your identity can be associated with a fixed static IP (common for broadband or MAC address - wireless). Only when egregious errors are made e.g. Facebook Beacon broadcasting on the newsfeed what someone bought for Christmas presents is it really visible. Deleting cookies (see what happens when you clear the cookie cache in YC, you're still logged in) does something for your privacy but not really.</comment>


Watch: Highlights of the Microsoft Data Science Summit - <AUTHOR> http://blog.revolutionanalytics.com/2016/09/data-science-summit-highlights.html <comment><USER2> Direct link to Tufte's Keynote: [https://channel9.msdn.com/Events/Machine- Learning-and-Data-S...](https://channel9.msdn.com/Events/Machine-Learning-and- Data-Sciences-Conference/Data-Science-Summit-2016/MSDSS11)</comment>


How's Mozilla Doing with Do Not Track? Not So Good  - <AUTHOR> http://www.readwriteweb.com/hack/2011/09/hows-mozilla-doing-with-do-not.php

<comment><USER2> The DNT initiative always reminded me of the "Evil Bit" joke: <http://www.ietf.org/rfc/rfc3514.txt>

<comment><USER3> Somewhat surprisingly, some 'evil bits' like the .xxx TLD, seem to be getting traction.

<comment><USER4> It is only gaining traction from people who want the bit explicitly turned off. People are lining up to pay $100 and change to prevent coca-cola.xxx and nike.xxx from being registered. Not a single person I've talked to in adult is seriously considering a move to .xxx

</comment></comment></comment><comment><USER5> Most of us on Hacker News, from what I can tell, are generally against legislating the Internet. But, that's exactly what DNT requires to be effective, since it provides no technical barrier against tracking: either websites are legislated into being required to honor it, or it has essentially no value to users. As much as privacy is important, I'm actually glad that Chrome doesn't support DNT. Hopefully that will give reason for a better technical solution to be developed.

<comment><USER6> I don't see that this would require legislating the internet. Instead, amendments to things such as data-protection, privacy or human rights legislation should be able to cover it.

<comment><USER7> This doesn't strike me as a legitimate difference (even just semantically). It doesn't matter if it's amended to existing legislation or passed as new law; both are the same from the perspective of "legislating the Internet."

</comment></comment></comment><comment><USER8> Working as a developer in an ad network I'm very interested in implementing this. However, said ad network doesn't currently provide an opt-out mechanism and Mozilla isn't doing a good job of providing me with arguments to take to management and convince them that a DNT opt-out is something they want. What do you think?

</comment><comment><USER9> Why should people turn it on - when most people just don't care?

That's the same problem we have in the EU right now. The correct way to deal with cookies would be for people to enable or disable them in their browser, according to their personal preferences. Instead, the EU forces their cookie legislation on everybody, because most people are too lazy to fix their preferences.

<comment><USER10> Most people have _no idea_ what a "cookie" is, nor how or why they should manage them. Calling people lazy for not managing them is the epitome of engineering arrogance. Browsers need better, more clear, interfaces for managing cookies and websites need to provide easily parses info on what each cookie is for before people will even be able to manage them.

<comment><USER9> If you're using a car it's taken for granted that you learn how this thing works. If you're using it without learning how it works, it's your own fault, if you have an accident.

Why should this be any different with computers? The risk that you pose to others is pretty low, so there shouldn't be any requirement to have a "license". But I wouldn't call it arrogance, if I'll assume that someone using the network has a minimum knowledge about how things work.

<comment><USER11> > _If you're using a car it's taken for granted that you learn how this thing > works._

Only to a point. I own a car and am perfectly competent to use it, but I have only the vaguest of understanding as to what things like spark plugs and catalytic converters do. I know what a manifold is in mathematics, and I suppose it's a bit similar in a car engine. I deem myself knowledgeable to open the bonnet and add windshield wiper fluid when that's low, but anything more complicated I'll take to a mechanic.

> _If you're using it without learning how it works, it's your own fault, if > you have an accident._

It's my fault if I drive without, say, learning how to operate the brake pedal, or learning how to turn on the turn signal. But if the accident is due to something wrong with the internals that I know very little about? I don't think any reasonable person believes that getting licensed to drive should require one to have the knowledge of an automobile mechanic.

<comment><USER12> This isn't the equivalent of spark plugs. It's the equivalent knowing how the windows work. If you drive around with the windows down while yelling at the person in the passenger, seat, don't be surprised if other people can hear you. And you can't use as a defense that you didn't know that you needed to have the windows up.

</comment></comment></comment></comment></comment><comment><USER13> since DNT is opt-in for ad networks it is about as useful as robots.txt. the good guys will honor it, but the bad guys - who users are really concerned about, will ignore it.

a better solution is to integrate tools to allow users to block third-party scripts, to fix bugs and improve cache handling headers that can be used to track users, and to not let any third-party scripts store any information on the client.

<comment><USER14> The thing is that as usual, there's no good or bad guys. The ones doing the tracking - which is in this case embedded in the websites - are not criminals who run botnets and crack servers, they're big, amoral companies like Google, Facebook, Twitter and some specialized firms.

These can be pressured (by public opinion, for example) into complying with DNT even if it's not their 'first instinct' to do so.

</comment></comment><comment><USER15> "This might be a bit low because the tracking for DNT is by IP address."

Tracking people using DNT? This is quite ironic.

</comment><comment><USER16> DNT is like putting a note atop your plain text file asking unintended recipients to ignore the contents. What browsers need is something akin to encryption, where you're not asking for compliance, you're denying access.

<comment><USER17> > DNT is like putting a note atop your plain text file asking unintended > recipients to ignore the contents.

Well, robots.txt is a simple text file that politely asks robots to not spider parts of your website.

It is completely voluntary and unenforceable, but works very well.

<comment><USER18>
      It is completely voluntary and unenforceable, but works very well.

_Ha!_ It works very well: for Google, and Yahoo. They use informative user- agents, and respect robots.txt directives. They have to, they're large corporations, with shareholders.

Everybody else ignores it. Why would they listen?

Live example:

      220.127.116.11 - - [11/Sep/2011:06:50:56 -0400] "GET / HTTP/1.0" 200 4835 "-" "Mozilla/5.0 (Windows NT 6.1; rv:5.0) Gecko/20100101 Firefox/5.0"
      220.127.116.11 - - [11/Sep/2011:06:50:57 -0400] "GET / HTTP/1.0" 200 4835 "-" "Mozilla/5.0 (Windows NT 6.1; rv:5.0) Gecko/20100101 Firefox/5.0"
      126.96.36.199 - - [11/Sep/2011:06:50:57 -0400] "GET /blog/ HTTP/1.0" 200 114535 "-" "Mozilla/5.0 (Windows NT 6.1; rv:5.0) Gecko/20100101 Firefox/5.0"
      22.214.171.124 - - [11/Sep/2011:06:51:01 -0400] "GET /blog/archives/2010/01/12/creating_an_account_on_the_scp_wiki_is_like_pissing_glass/ HTTP/1.0" 200 10490 "-" "Mozilla/5.0 (Windows NT 6.1; rv:5.0) Gecko/20100101 Firefox/5.0"

This is all the traffic from this IP, with no lines skipped. You might notice that it doesn't request CSS, or any of the linked images, or favicon.ico. Nor does it populate the referral header fields, which of course it would be doing if it was actually Firefox, and there was actually a human clicking on these links. It doesn't even _bother_ requesting a robots.txt, which I don't have anyway.[1] Do a whois check on the IP, and we get:

      Codero CODERO1999A (NET-216-55-176-0-1) 18.104.22.168 - 126.96.36.199

Codero's a dedicated server host. This is a spambot, looking for email addresses. Visit the IP in a browser, and you see a site selling fake Tiffany jewelry.

1: <http://www.archiveteam.org/index.php?title=Robots.txt>

<comment><USER14> Maybe, but most tracking services are large corporations, most websites wouldn't embed analytics scripts from spammers-r-us.com.

</comment></comment></comment></comment><comment><USER19> It would be more interesting to know the adoption of this among website developers. And some use cases where it is beneficial for them (as I don't see any). As it is, it is quite useless. If the feature doesn't do anything, the numbers are just a consequence of the buzz done around it, nothing more.

<comment><USER20> There either needs to be user demands or laws to push it I think. Given that the average user doesn't really care in most cases though I think they are a long way from succeeding with it. Good to see them at least offering up something though.</comment></comment>


Ask HN: How's your mood (April 2016, regarding life, job, technology)? - <AUTHOR> <comment><USER2> Well, I got a job as a Head of Software Development at one company with a great team and it's pretty hard. It's a great experience but I'm sad as I don't have much time to read and learn about topics I'm interested in. For example, Graph theory. I'm amazed with the topic but I just can't afford reading about it more than half an hour per day.

I could say it's "okayish".</comment>


Updating our rules against hateful conduct - <AUTHOR> https://blog.twitter.com/official/en_us/topics/company/2019/hatefulconductupdate.html <comment><USER2> Everyone should read the examples so they have a clear understanding of what twitter is meaning when they say "dehumanize". It's not "hey I disagree with these people" it's "hey I want these people dead/injured/equated to shit".

Religious and ethnic persecutions have often gone hand-in-hand. Religious minorities of all types will be helped by this, and we'll see less hate-speech on twitter. Seems to be a very reasonable step.

Sidenote: any religion topic really brings out the "I have a problem with religion" types on HN.

<comment><USER3> Twitter would be better received if it were bold enough to also state specific examples of permissible religious satire/criticism. I think that would do a lot to address what people are worried about, and be a step in the direction of having more concrete rules and predictable enforcement.

<comment><USER4> >Twitter would be better received if it were bold enough to also state specific examples of permissible religious satire/criticism

Talk about a PR Minesweeper, expert mode.

</comment></comment></comment><comment><USER5> What if someone's holy book contains text that dehumanizes people on the basis of religion?

<comment><USER6> Criticizing a religion is not the same thing as dehumanizing its followers.

Dehumanization is a defense mechanism which helps us avoid feeling the pain of realizing that humans sometimes do (subjectively) abhorrent things. It's seductive to define such people outside the bounds of humanity as it allows us to excuse treating them poorly. It is nearly always a mistake to do so, because people are, in fact, people.

<comment><USER7> This is the important point everyone seems to be missing. If you look at the example tweets they all have some aspect of making the [Religious Group] out to be less than human: rats, virus, maggots, etc.

People can still freely express their distaste for any and all religion on twitter so long as they don't dehumanize the people who follow that religion.

<comment><USER8> Application will be different from stated intent. How much you want to bet ?

haven't we all seen this in practice long enough now to know how this little routine goes?

<comment><USER7> This kind of attitude with respect to rules and regulations drives me nuts. Guess what? _Every_ time you have a human applying a rule you're going to get results that aren't entirely consistent. Have you ever managed a team and given the exact same task with the exact same instructions to two people? Did you get the exact same work product in return? I very much doubt it.

Rules & regulations should be written, evaluated, and revised the same way code is. Code doesn't always run as we intended but we (usually) don't crucify the developer. We _learn_ from the misunderstanding, fix it, and then re- evaluate when the next inevitable misunderstanding comes up. We get feedback and we iterate. That's exactly what Twitter is doing. Their first policy didn't work out as planned and this is their next iteration based on the feedback they received on policy v1.0.0

And will Twitter update this policy yet again once they've had time to work out some of the kinks? You can bet on it.

</comment></comment></comment></comment></comment><comment><USER9> I get skin color, sex, gender, sexual orientation etc for protection, but including religion and excluding political word view has always been weird to me. Calling one of the two innate and deserving of protection and the other a choice and undeserving seems like a religious answer.

 _Narrow down what's considered — Respondents said that "identifiable groups" was too broad, and they should be allowed to engage with political groups, hate groups, and other non-marginalized groups with this type of language._

And you didn't just tell him to just not de-humanize anybody, instead opting for "okay, that's fine, just don't mention religion when you do it?

<comment><USER10> Yeah, the way this has been introduced into their policies [1] is weirdly specific. It's prohibited to target _individuals_ with dehumanizing language if it's related to any protected category, but targeting _groups_ with dehumanizing language is only prohibited if it's related to religion?

[1]: [https://help.twitter.com/en/rules-and-policies/hateful- condu...](https://help.twitter.com/en/rules-and-policies/hateful-conduct- policy)

</comment></comment><comment><USER11> I'm not convinced centralized models being politically "pushed around" in the age of the internet will succeed. They may likely be a retreat, and long term ebb-and-flow from centralized to decentralized poles.

The centralized but politically watched model is also specially susceptible to Taleb's "The Most Intolerant Wins" theorem.

<comment><USER12> Specially when religious (or other kind of) minorities where Twitter HQ are located won't necessarily be somewhere else.

</comment></comment><comment><USER3> Does this mean that Swiftian satire such as South Park's episode making fun of prominent Scientologists is now unfit for Twitter?

<comment><USER10> I don't believe it would be affected -- as I recall, that episode _mocks_ the religion and its members, but doesn't _dehumanize_ them.

<comment><USER5> What exactly does "dehumanization" mean?

<comment><USER10> It means precisely what it sounds like -- using language which describes the targeted group as something other than (and lesser than) human. The article gives examples where religious groups are described as "rats", "viruses", "filthy animals", or "maggots".

<comment><USER5> Many cultures use animal analogies to describe nuanced and complicated personality trait combinations. Some of them are more negative than others, referring to combinations of positive and negative traits in varying proportions.

Reductively, calling someone a lion is just as dehumanizing as calling them a shark. In the Bible, people are both complemented and insulted with comparisons to lions. Calling someone a shark is more respectful than calling them a rat, unless you're Chinese in which case I'm not sure what rat means. What exactly is banned here? Twitter gave us only the most obvious examples, leaving the hazy zones open for the endless fighting that I predict is about to start.

<comment><USER13> Welp, you don't get to do that on Twitter now.

<comment><USER5> So, I understand the attitude that, "twitter is just a platform, they don't have to be just, why wring your hands so much about what their rules are?" This makes sense if their rules don't matter, so in that case why should they even have rules? That's a position I can understand, where you can post anything on Twitter that's legal under US law.

<comment><USER13> I'm sorry, I don't understand your logic. If someone has rules, but those rules aren't the same as US law, it seems you're saying, they might as well not have rules at all?

<comment><USER5> Yeah, I was kind of tired when I wrote that. My logic was, if handwringing over Twitter's rules isn't justified then the rules must not matter, because handwringing is justified if and only if the rules matter. If the rules don't matter then they don't need rules beyond basic US law, which would imply that this effort wasn't very profitable.

So, either Twitter isn't right because they took a rough stab into a subtle area, or they aren't right because they took a stab that didn't need to be taken.

</comment></comment></comment></comment></comment></comment></comment></comment></comment><comment><USER14> I've been deeply concerned with attacks on religious freedom as of late, this seems like a strong step in the right direction.

<comment><USER15> Which religious freedoms have been attacked, and where?

<comment><USER14> [https://newsroom.churchofjesuschrist.org/article/other- examp...](https://newsroom.churchofjesuschrist.org/article/other-examples-of- attacks-on-religious-conscience-and-free-exercise)

<comment><USER15> Sounds like a series of cases where courts ruled that religious reasons were not justifiable to allow discrimination, as per the Constitution.

</comment></comment></comment></comment><comment><USER16> I assume it is ok to say religion is a virus, or a particular religion is a virus but the rule is that you can't say the followers of the religion are a virus. Likening religion to a memetic virus is not a fringe opinion.

</comment><comment><USER17> Hopefully, they recognize the group of people who do not practice religion as "basis of religion"

<comment><USER18> They probably won't.

Atheists are the most oppressed 'religious' group there is but no one will recognize it.

It's common they are left out of so-called "progressive" movements to support peace / safety.

</comment></comment><comment><USER19> Excommunication isn't the solution. Isn't it enough to hide these comments by default, as on HN?

<comment><USER13> Comments like those in the examples Twitter provided will reliably get you excommunicated from HN.

<comment><USER19> HN has dead posters. They are still readable for those that want to. That's the type of solution I promote.

Digital media, like Twitter, can't be a megaphone to spread hate speech. That means their algorithms should be smarter, and accept input.

On the other hand, with these media effectively being monopolies, that doesn't mean they can excommunicate (which is what this is about). That should be against the law.

Just like when there is just one shop in town: everybody should be allowed to buy. That doesn't mean the shopkeeper has to smile to every customer. A good shopkeeper may even be able to get this customer some help.

</comment></comment></comment><comment><USER20> People really need to get off Twitter. There are a lot of servers on the Fediverse, running Mastodon, Pleroma, Misskey, Pixelfed and other ActivityPub webapps. Just because famous person x,y,z or friends a,b,c, aren't on the Fediverse doesn't mean you shouldn't try it out.

It's like the 1990s, old IRC and AOL chatrooms. You can just follow a lot of randoms and get into cool threads. There are many instances that have open speech policies (which are banned by many other instances) and other instances with standard ban lists. You can choose where you want to sign up. Many of the people on HN have the knowledge to stand up their own if they want. (I run my own in Docker using a ruby tool I wrote: [https://github.com/sumdog/bee2](https://github.com/sumdog/bee2)).

You can even create accounts of different Fediverse servers to get a better picture of what gets blocked/censored where. The difference with ActivityPub/Fediverse is you have choices.

Twitter, Reddit, et. al. worry so much about keeping people "safe" that they have completely killed off any diversity of ideas. Back before Reddit started their multi-year long banning-of-everything campaign, you had a lot of different voices, with a lot of different ideology, from conservative to socialist to libertarian to progressive .. battling it out with some really great discussion. Now it's all just monoculture.

The places people fled too, like Voat/Gab, are also just monoculture (Gab recently migrated to their own broken, garbage fork of Mastodon ... as if they needed a way to make the Mastodon UI worse). Voat is just a cesspool of hate, and any melting pot where people discussed ideas rationally is kinda gone.

I highly recommend The Coddling of the American Mind, a book that talks about how people today see "Free speech" as a bad thing, how people say words == violence (they don't, violence is violence, and saying words are violence show you're afraid of ideas).

I've also been reading The Strange Death of Europe, which talks a lot about migration and religious hate speech. Honestly a lot of the book is garbage and I didn't like any of the initial arguments, but I also realize it's important to read about viewpoints I don't agree with. As I kept reading, the author did make a lot of effort to interview Muslims (both long term residents and refugees) and he does make a good set of arguments for the difficulty of criticizing religion in Europe (and I don't agree with a lot of his findings, but I think his arguments and original research are worth looking at).

We really need to be careful with these new blurred lines around speech and hate and ideas and ideology and violence. Restricting things on any platform just gives people with those views, people who get banned, more validity in the eyes of people who see them as persecuted. The Westburro Baptist Church is an example of a small, non-evangelistic set of families that barely grow, who are fully supported by slander lawsuits (they're mostly lawyers). If there weren't WBC counter protests and publications against them, they'd have no one to sue, would have run out of money a long time ago, and would have needed to take real legal case work again. The great irony is the reason they still hold strong is due to protesters giving them relevance.

<comment><USER21> I want to like Mastodon, but there are no like/retweet counts. I have no idea how to find the good content without sifting through mountains of stuff I don't want to read.

</comment></comment><comment><USER22> Interesting. So criticizing religious positions against abortion, against vaccines, against homosexuality, and in favor of the flat earth will now result in post removal. Assuming this policy is going to be impartially and fairly applied as stated.

<comment><USER23> It's entirely possible to criticize without dehumanizing.

<comment><USER24> The problem is that it's also possible to criticize in a way where it's simply not possible to determine if it was a good faith criticism or not. There's a wide population of people who even optimize for that, they're called trolls.

Moderation mistakes are inevitable, and the consequences of a bad moderation decision can be as bad, or worse, than the effect of the message itself.

IMO, people should learn to defend themselves against trolls rather than helplessly relying on a nanny from above to do it. Unfortunately, using those platforms doesn't give us much of a choice in the matter.

<comment><USER25> > The problem is that it's also possible to criticize in a way where it's > simply not possible to determine if it was a good faith criticism or not.

That's a problem in some generic sense perhaps, but not with the application of this policy, which does not rely on a determination of "good faith criticism", but instead of dehumanization.

Note that the examples of what is covered all are dehumanizing in a _very_ narrow sense (stating directly that the target groups are vermin, viruses, etc.): [https://blog.twitter.com/content/dam/blog- twitter/official/e...](https://blog.twitter.com/content/dam/blog- twitter/official/en_us/company/2019/dehumanizationreligion.png)

<comment><USER24> I'd rather see a random list of posts that are actually being deleted rather than examples that Twitter officially uses, before making the determination that the rule is applied fairly.

</comment></comment></comment></comment></comment><comment> 08-15 This is strangely specific. Is it still okay to dehumanize people afflicted with other kinds of mental illnesses?

</comment><comment><USER26> Twitter needs to be a set of open source protocols and standards like the internet.

Imagine if all of the internet was owned by one company and they had this kind of power. This is more power than many governments around the world.

</comment><comment><USER11> I'm very concerned about loosing the right to attack religion. It's an important discussion to have and for children to see. All religion is foolish, and has to be approached from a reality-based context.

<comment><USER27> The reasonable interpretation is that you can attack religion (as an ideology) but you can not attact religious people based on their religion.

Thats a safe split: ideologies do not have (human) rights anyway...

So e.g. you can freely say that the Bible is stupid but can't say the same thing about its believers.

<comment><USER23> > So e.g. you can freely say that the Bible is stupid but can't say the same > thing about its believers.

From the examples they give, I think you can still call them stupid. (After all, being stupid is very much part of the _human_ condition. It's hardly a dehumanizing descriptor.) You just can't call them rats, maggots, viruses, etc. and advocate for their extermination/removal.</comment></comment></comment>


V8: Chrome's JavaScript engine source code - <AUTHOR> http://code.google.com/p/v8/

<comment><USER2> It is obvious that the "older" JS-engines were not built for executing applications, but more for running small in-expensive things on homepages. As of the later years, JS has become pretty heavy and people use it a lot more.

The genius here is to recognize that most of the cool work done to Smalltalk and Self applies equally well to Javascript. It feels like cheating, but the V8 team is actually just picking some low-hanging fruit done with research in the 90's. They push the envelope for what we can use JS for and that is a really good thing!

</comment><comment><USER3> Now this runs a lot faster:

<http://www.abrahamjoffe.com.au/ben/canvascape/>

</comment><comment><USER4> There are now three engines vying for the title of the "fastest" JS engine:

* Tracemonkey (Mozilla) * Squirrelfish (Apple/Webkit) * V8 (Google)

I would love to see a benchmark comparison (Sunspider?) to see how V8 compares to Tracemonkey and Squirrelfish.

<comment><USER5> I found a blog entry with some SunSpider runs: [http://web- graphics.com/2008/09/02/scripting-engines-just-go...](http://web- graphics.com/2008/09/02/scripting-engines-just-got-a-whole-lot-faster/)

Unfortunately a TraceMonkey bug prevents direct comparisons.

<comment><USER6> Brendan Eich posted some new numbers with a more recent TraceMonkey build.

[http://weblogs.mozillazine.org/roadmap/archives/2008/09/trac...](http://weblogs.mozillazine.org/roadmap/archives/2008/09/tracemonkey_update.html)

</comment></comment></comment><comment><USER7> I have been grepping through the tree trying to find the implementation of the String class. A part of me thinks they just defined it in string.js and somehow made the rest of the code treat it as a cpp class.

<comment><USER8> I think (fuzzily), from what I can find, that string-stream.cc allocates a block of char's for a string. Once the string grows beyond the capacity, `char* HeapStringAllocator::grow(unsigned* bytes)` doubles the size of the allocated buffer. Kind of disappointing after half an hour of reading and C-s'ing in Emacs.

`string.js` is used by `tools/js2c.py` to create a `string.h`, but otherwise I think many of the string functions are implemented in JavaScript and (I'm guessing) compiled later since `string.js` and other JavaScript files are referencing C macros.</comment></comment>