You are right to say this.
I treat breast cancer, and I'm doing a PhD on breast cancer genomics, and there is no evidence that high throughput data of any kind, whether it is genomics, transcriptomics, epigenomics, proteomics, metabolomics etc-omics actually helps patients. At the moment, a small panel of biomarkers using technology that is at least 20 years old is all we use to make treatment decisions. Is it adequate? Certainly not, but there is a HUGE amount of carefully collected data in many thousands of patients backing it up.
Not sure who is downvoting you, but they seem to have swallowed the hype wholesale. At the risk of sounding gratuitously negative, I find the discussion of medicine on HN to be of very poor quality, markedly below the general standard.
I think there is a distinction to be made here in questioning patient outcomes and questioning the relevance of genomic sequencing in treatment decisions.
Don't you think it is fair to say that high throughput data (whole genome sequencing with variant calling) is still in a state of being evaluated to measure its effectiveness in aiding the treatment decision process but that early results seems to lean towards it becoming part of the standard diagnostic approach?
Genomic sequencing and patient outcomes is a thornier question. My non-practitioner take is that it is too early to tell scientifically, but that there will probably be some benefit to early identification of specific cancer types and choosing treatment. But I think many people would have made a similar statement about mammography and early detection, and absolute mortality appears to not be reduced by adding mammography to the diagnostic procedures, right?
The research value of genomic sequencing seems high enough to make it worthwhile. At least, when I sit in on molecular tumor board reviews (the oncologists at a table looking at called variant results for a specific patient), I hear them commenting about possibly new and unknown variants being of research value.
I am really looking forward to your reply - Internet message boards in general have to be almost the worst way to discuss medicine, but having participation from researchers and practioners like you is tremendously illuminating!
I define genomics as the unbiased interrogation of the genome using high throughput technology. Sequencing one mutant locus using Sanger sequencing does not fall under this definition - I don't think IBM's business model is using Watson to interpret that. So when other people point out that HER2 is a useful genomic marker they are missing the point - HER2 can be determined with immunohistochemistry for example which has been around for 50 years.
I'm not sure what your question is... genomics has research value, for sure, it's great.
Is it worth trying to incorporate it into routine care? Yes, probably, if you have enough cash. Should a hospital pay for a black box machine learning algorithm to make recommendations from a highly polluted, often erroneous and hugely incomplete literature corpus? The alternative put forward by people actually doing the science is that we should try and develop large open source databases/repositories about the significance of genomic findings, and then collect the data about what happens to the patients.
Whooping cough is caused by bacteria (Bordatella pertussis). It is virtually unheard of for whooping cough to re-activate, catching it again as a new infection is much more likely.
Incidentally, there is a zoster vaccine that can prevent shingles. If you have ever seen anyone with the debillitating pain that shingles can cause, you will realise that this vaccine is definitely worth it.
You can see here that they have replicated most of the routine blood tests out there. Interestingly, they have also replicated some of the archaic and pretty useless blood tests like Rheumatoid Factor. They also offer Erythrocyte Sedimentation Rate (ESR). This is pertinent because ESR is actually a physical property of blood, it is performed by measuring the rate at which red blood cells fall to the bottom of a tube. Perhaps they have developed a microfluidic method to measure this, but it wouldn't be a 'chemical process'.
But at the end of the day, they are offering the same tests that are currently available. If someone said to me we can now do the same old blood tests faster and cheaper, I would say that this is going to have very little impact on people's health. None of these tests are truly useful in prevention or screening unselected patients.
It does really seem that Theranos is a case of packaging the existing blood diagnostics and trying to capture a large part of the market. Exciting for investors I guess, but for patients or healthcare workers probably not so much. I wish they were doing something like cheap, easy and reliable comprehensive circulating DNA analysis, or proteomics, or something with immune cell function profiling...
I hope with all this cash they have a program for giving this technology to places that can't afford the usual lab infrastructure, that would be a very good thing.
> If someone said to me we can now do the same old blood tests faster and cheaper, I would say that this is going to have very little impact on people's health. None of these tests are truly useful in prevention or screening unselected patients.
Are you kidding? I'm not completely familiar here, but I'd love to see a comparison of the current SOC for time between measurements of each of these endpoints and then a clinical judgement that genuinely nothing interesting happens in these levels at timeframes shorter than SOC.
A person I'm familiar with has a severe endocrine disorder which has eliminated nearly all of his natural hormone production. Instead, he must self-administer all hormones in proper dosages. In order to survive this way he has become vastly more familiar with his own blood panel than most human beings ever would dare. On insurance dime he takes far more regular blood tests than you usually can get access to and understands, even very roughly, how events in his life, diet, exercise, stress, weather, etc begin to affect his blood chemistry and, subsequently, his life. In his, of course anecdotal, experience these are things that he cannot converse with doctors about because they're not able to speak confidently so far outside of SOC. It's not necessarily surprising stuff, but there's comparatively little real-world evidence to give it a bite.
Theranos could make similar analyses achievable for far more people. It opens an entirely new branch of clinical research---blood chemistry fluctuation at the level of perhaps up to multiple times per day over months at a reasonable cost in both testing and human time (given adequate distribution---Walgreens or, even, eventually, a home edition). You can't pretend that Phizer and GSK, known partners, aren't all about that.
> Exciting for investors I guess, but for patients or healthcare workers probably not so much.
Only if you assume SOC doesn't change under the influence of massively more available quantitative data.
I am assuming that SOC won't change under the influence of massively more available quantitative data, or at least any gains would be both slight and only applicable to a very small number of people. I think it is probably a misconception that humans are simple enough that measuring something (on Theranos' current testing panel) which is produced in ten different ways in five different organs from millions of cells and then diluted in 7 litres of blood is going to tell you anything revolutionary.
Certainly happy to be proven wrong, but there is a risk of harming people (financially, psychologically and perhaps medically) if you convince them that relentless tracking of their serum sodium tells them something useful.
I think the difference here comes in use. I agree that misinforming people about the meaningfulness of their blood chemistry is dangerous and low value. My target users are not Quantified Selfers (although my anecdote example might have thrown that off) but instead large scale clinical research sponsors.
> A person I'm familiar with has a severe endocrine disorder
He said "unselected patients". The point is, some random guy with no preexisting condition might not actually benefit from being able to measure shit in his blood more easily. It could mostly lead to false positives, stress, and unnecessary costs. The only way to know for sure would be to do a study on it... but Theranos doesn't seem to like doing studies.
Making blood tests faster and cheaper would definitely be a good thing, but it's possibly not a completely transformative thing.
> If someone said to me we can now do the same old blood tests faster and cheaper, I would say that this is going to have very little impact on people's health.
I think you vastly under-estimate the impact of cheaper prices. We're not all sitting around with computers in our pockets because they're drastically different, we're sitting around with them because they're cheap.
Obviously there is skepticism on the applications, this is why she is giving all these talks about what this would enable.
I don't have any particular insight about what this kind of price drop will produce (though cheaper STD testing can't be a bad thing), but I think massive reductions in price do fundamentally change how things get done.
I'm skeptical that there is anything massively different between the technology Theranos uses and that used by existing clinical diagnostic labs.
Their greatest claim, as least in the popular press, appears that they can do these tests on "a few drops of blood" (it appears to be about 0.5 ml from the image) as opposed to 10 ml or so. This claim is nothing special, as in fact almost all tests are eventually done on an aliquot no larger than a few microlitres that is withdrawn from the larger sample. As to speed of results, this would likely be linked to organizational efficiency rather than a technical innovation.
Further, there is no way all the tests shown on their website can be done with one 0.5 ml sample, as samples need to be collected into different anti-coagulants for different tests as some anticoagulants interfere with some tests but not other (this is why the doctor usually takes two or three samples into different tubes -- not because s/he needs 30 ml of blood).
They may however have improved automation, or a better run or cheaper service, in which case, good for them.
This gives a bit of perspective on their current system, it is far off something like a hand held scanner. It is from a blog article by a bio-chem due diligence company.
Whether it was due to the quantity of tests (7 tests) or the particular tests I ordered, I was quickly informed that I would be receiving a standard blood draw for my first visit. To my surprise, only 75-80% of patients receive the finger stick method, while the remaining 20-25% require a standard blood draw. The company’s goal to expand nationally relies upon the ability to integrate within the infrastructure of existing Walgreens’ drugstores, a feat made difficult by the need for a trained phlebotomist to serve a specific group of test orders. While the company currently offers more than 200 blood diagnostic tests, the internal assay development team is working to expand this menu to include over 1,000 of the most commonly ordered tests at their CLIA laboratory located in Palo Alto, CA.
In addition to my own blood draw, I stayed to observe the highly publicized finger stick, a staple of the start-up’s competitive appeal over established companies like LabCorp or Quest. It was here that the charm of Theranos became more obvious. Rather than a phlebotomist, a Walgreens pharmacy technician is easily able to perform the “nanotainer” blood collection steps, a testament to the simple and integrated workflow system developed by Theranos. Blood collection kits are provided to the technician, which include alcohol swabs, a warm compress, a finger stick, and a “nanotainer” (kept separately in a fridge). After scanning and labeling the sample tubes, the pharmacy tech begins the simple process as follows: apply warm compress to finger, clean the finger with alcohol swabs, massage blood towards the tip of the finger, stick the finger using one of 3 prick sizes (purple = small, pink = mid-size, blue = large), collect blood. The “nanotainer” which collects only a few drops of blood via capillary action, has continuously been an attractive marketing tool for Theranos, inflating the nano-sized tube with a larger than life persona. These samples are then stored in the fridge until a courier system can transport them to the CLIA certified lab in Palo Alto, where proprietary platforms allow the company to run traditional tests on 1/100th to 1/1000th of the ordinary volume. My results were emailed to my physician the following day.
This is a thorny topic. The trouble is that when a large number of people take a drug, rare but horrific side effects may manifest. How do you factor this in to deciding an appropriate level of regulation? Is it fair that we permit easily accessible experimentation with psychoactive or nootropic substances, when someone downs a few too many, has a psychotic episode and drowns his children? Or has a fatal allergic reaction? Or drives their car off a bridge because they have been awake for 96 hours taking one of these products? That may sound outlandish, but eventually something like this will happen to someone if enough people take it.
So I don't know if you can just couch it in terms of personal freedoms... it seems a bit more complicated than that. I don't know what the answer is, but pretty sure it isn't just 'Let people do whatever they want.' At least with heroin and cocaine people have some idea about the risks, even if they decide to ignore them...
How do we handle alcohol? You tell people that modifying yourself isn't an excuse for committing crimes. And follow up and enforce that. Making it a crime to use chemicals on your own mind is absurd.
With heroin, the biggest risk is the fact it's illegal, thus preventing you from obtaining clean, known-quantity medication. If Tylenol was sold on the streets, with pills ranging from 100mg to 1000mg, we'd have a LOT more liver toxicity cases than we do. It's not like using opiates in a correct manner leads to death on a routine basis.
1. Countless lives have been destroyed by alcohol. Busted up families, people killed by drunk drivers, children maimed by fetal alcohol syndrome, abused wives, husbands and children, fried brains, fried livers and across multiple generations... Why would we want to repeat that experience? If alcohol were invented today it would never be in widespread use like it is now. It's become a lifestyle thing because of thousands of years of culture and legacy. It's a prime example of why your approach is a terrible idea.
2. Heroin is a highly addictive substance, that will kill you in sufficient qualities. You don't see that as a problem?? Even if it were cleanly packaged with a black label, people would still take too much and die from it. Cute example with Tylenol, but doesn't cause dependence and withdrawal. Opiates are given to people with pain, where they have a fundamentally different physiological effect.
My comparison to Tylenol is apt. If you bought pills thinking they were ~100mg, but they were 10x that, you would soon find yourself with a broken liver. To be clear Tylenol will kill you in sufficient quantities, amounts you're likely to easily by from a store.
Opiates do not have a "fundamentally different" effect if you're in pain. I think people like saying that about opiates and stimulants so as to excuse people that "need" it.
And yes, personal freedom is worth people choosing to rip apart families.
Just to clarify, I'm not advocating criminalisation of nootropics, and I completely agree that the war on drugs is pretty stupid.
The point is about dangerous usage patterns. You are trying to argue that hard drugs are actually not that bad if only they were available with the same safety and dosage rigor applied to approved pharmaceuticals. My point is that it isn't an apt example because nobody gets euphoric or addicted when they take Tylenol. Any drug that causes some physiological disturbance in sufficient quantities is going to be more dangerous if that drug is taken by users in ever increasing quantities.
> Opiates do not have a "fundamentally different" effect if you're in pain. I think people like saying that about opiates and stimulants so as to excuse people that "need" it.
It is different. Say a patient has severe pain from metastatic breast cancer. I can give them a dose of morphine that would stop you from breathing permanently, and they will be fine. Are you saying she didn't really need it, she just likes the rush? I don't understand your point, maybe you can clarify. The rates of opioid addiction in people receiving it for pain are much lower than you would otherwise think from the way people buy oxycodone on the black market.
Personal freedom? What about the personal freedom of the kid who gets bashed by their drunk parent? Or the personal freedom of the cyclist that gets run over by a drink driver? Or the personal freedom of the emergency department nurse that gets her ear bitten off by someone with amphetamine induced violent psychosis?
No, my point is that "hard drugs" like heroin are vastly more dangerous because users cannot use properly whilst the drug remains illegal. It's a manufacturing and usage problem. Opiates are rather tame as far as side effects go, and avoiding overdoses isn't terrifically hard if you have the right stuff. Users don't want to waste precious medicine, nor die. With precision markings, there'd be vastly less problems reaching the right level of usage. Instead, users are admonished to "do a test shot" each time, which, through laziness or practical concerns, gets ignored and someone falls out.
But let me understand you: Are you saying that if someone is in pain, their respiratory system just ignores opiates and they can take large doses even if they're opiate naive? Does this work retroactively, like if you don't have Narcan handy can you just snap someone's leg to save them? (And then, with a broken bone, they'd certainly get medicated - double win!)
Sarcasm aside, do you have a citation for this claim? That opiate tolerance doesn't matter in face of pain? That there's a "fundamental difference" in the effect? I'm truly interested in hearing about that (feel free to contact me via my profile if this thread is too long).
Everything I've read and experienced says otherwise. I've talked with some users that were taking opiates for cancer pain management, or for otherwise long-term pain, and they just as happy to take them as unlicensed users (though perhaps a bit more cautious in admitting so). In personal experience from acute trauma leading to a hospital team applying morphine, I went from screaming in pain to absolute noddy-head bliss. I'm pretty sure that's the exact effect people are seeking.
I agree they are vastly more dangerous because they are illegal. But you know, alcohol is legal, and people still binge drink, fall in ditches, have random unprotected sex, get pancreatitis etc... and it isn't even addictive. I'm just trying to say that even if heroin were legal, it would still be unacceptably dangerous, because at the end of the day it's a highly addictive general anaesthetic. Even with 'vastly less' problems, which is your conjecture, there are still significant problems. Anyway, we both clearly think that harm minimisation is a good policy.
Yes, that's right, if someone is in pain, the respiratory depression is less. This is evident to anyone that prescribes opioids regularly or looks after people with chronic and acute pain (as I do). It is also evident that the ever escalating doses and withdrawal symptoms demonstrated by recreational users of heroin for example, are not manifested in people with pain. So that's why I use the word 'fundamental difference', because the coupling between dosage, physiological response and behavior is completely different.
Lots of people don't enjoy taking opioids, they get nausea, nightmares, constipation etc, or it just doesn't work for their pain. I know this because that is what is reported in controlled trials, and because people complain to me about these side effects all the time.
Massive, massive potential for the placebo effect. This needs to be tested in a randomised double blind trial with standardised testing of the purported cognitive enhancements. Until then it's snake oil.
Other fun placebo effects: red pills work better than blue pills. All pills work better if given to you by a doctor. Better still if the doctor is wearing a white coat. Yet better is the doctor uses a large peace of medical machinery as part of the intervention. And yet a bit better on top if the machine beeps.
Basically, for best results you want to receive your medicine as the Star Patient in a Very Important Looking Medical Drama right at the moment where Everything Starts Getting Better.
I was thinking the same thing. For the actual new drugs, I expect they probably do something (and quite possibly something very dangerous). But for the caffeine and herbs... how do we know it's not just the same as a normal large dose of caffeine?
On the scale of the individual it doesn't make much difference if the impact is via placebo or not. To extrapolate from the experience would be unwise. Yet for any one person to live only through population-wide statistical significance robs that person's life of the joy of figuring out what works, even if sometimes it only works for them.
The guideline has some vaguely politically correct overtones, which seems to be putting people off a little, but I think this is unwarranted.
Good comments seem to me to have the same characteristics - insight, good will, lessons from experience, novelty, thoughtfulness. Strongly held, polarising and poorly explained opinions aren't one of those characteristics.
I myself have written comments which start with a negative comment, and then through fleshing it out arrive at a more moderate position at the end... at which point I go back and change the first sentence. Don't just write the first sentence...
Thanks for this, it's a good idea getting people to rate how negative their comments are... it would certainly be an interesting exercise, although it may just show that those who leave negative comments don't think they are being negative, whereas the people that can be bothered rating the negativity of others are probably more sensitive to negativity.
Self-rating the negativity of your comment is designed to force you to acknowledge that HN wants you to think and be reasonable.
The OP's blog post suggests that "Gentle reminders by peers" will make the culture better. I think these gentle reminders by peers in practice will whip everyone into a frenzy of hunting for negativity, naming negativity, blaming for negativity, being defensive about negativity, judging and feeling judged, anger, outrage and despair with constant accusations and counter accusations about the definition of negativity.
Some negativity is normal and natural and okay. HN wants less of it, so they should just ask people to make their own self assessment of their post at the moment of posting. Problem mostly solved, but it's pointless to try to completely solve it - the concept of negativity is open to interpretation and therefore everyone will have a different opinion.
I think plenty of people will tone it back after being forced to judge their own negativity.
When you let anger and resentment dictate your policy, yes you're being irrational, by definition.
It was like 7 years ago. Now there's a difficult situation (a debt realistically impossible to pay) and different people in charge (not thieves and Goldman Sachs anymore ). Let's focus on viable solutions.
Don't get me wrong, the EU had every right to be angry, it's just preferable that the people in charge of billions of euros and the well being of millions don't pursue tacit vendettas in lieu of good fiscal policy, which is the point made in the referenced article.
The quoted article is one point of view. As with all current events, only history will tell who is wrong or right.
Another viewpoint is: It is "public knowledge" that the same "bitter EU medicine" worked well for Ireland, Portugal and Spain. So from the "Pigs" countries - only the "g" refuses to take it. That is their right. But then don't blame/insult the doctor.
History often does not tell who is right or who is wrong, particularly when it comes to economics - 'though no one will believe it - economics is a technical and difficult subject' - when you mix in politics and ideology as well, the truth is often obscured.
There are people who argue that the New Deal did not help end the Great Depression: 'it was ending anyway' or 'the second world war ended it'.
The Obama stimulus was (a) useless (b) helpful but insufficient (c) just right.
Do you think history will reach a consensus on this?
Regarding your 'another viewpoint': Greece has implemented eye-wateringly bitter medicine.
Like medieval doctors, when bleeding fails to cure the patient, they call for more bleeding, blame the patient for not being devout enough, and say that the suffering is a punishment for past crimes.
The fact that bleeding did not manage to kill their other patients clearly demonstrates it was a success, and that Greece is the one at fault, not the doctors.
In 2013, Spain's tax revenue was 32.6 % of GDP. Compare that to Germany 36.7 %, Netherlands 36.3 % and Finland 44.0 %. Also consider that these as proportion of tax revenue to official GDP, and it's pretty safe to assume that Spain has more in grey economy (not in official statistics) than northern Euro countries.
Spains unemployment rate was 24% in 1994. It was 21% in 1985. Or 18% in 1998. Unemployment in Spain is traditionally 10% above northern countries or the US. So yes unemployment is high (we had a crisis and had a recession!) but not as high as you make it look without context.
Of course it worked: nowadays Portugal can borrow money in the free market with interest rates that are historically low, much cheaper than with the IMF. This means: the world trusts again in Portugal.
What you speak about is a completely different thing, Portugal has very old and deep structural problems but they were not caused by this particular crisis, they just got more exposed. Solving them is another story, I don't even think that our democracy (as we know it) is able to do it.
The world trusts that they will receive the money that they lend to us. The lender doesn't care from where that money comes.
In the end we arrive to the same conclusion, EU/IMF/whatever trust Portugal enough to bail us out again.
But I understand where you want to get: "we are behaving like good boys" and making everything that "Germany" says. Would you prefer an atitude like the Greek one, "acting like a spoiled kid"? As Greece, we are a small and periferical country without any power to negotiate by ourselves - we need to associate with others - and sincerely I prefer Portugal to associate with Germany than Greece. Our best way to get through this is by being "the good boys" and man up.
That's not where I want to get; I don't care about such petty considerations, nor do I agree with any of those characterizations. If it's better for us to strictly comply with the guidelines set by the lenders, I'm fine with that.
I'm simply skeptical that any of those parties (private lenders or EC/IMF/ECB) lend us money because they trust us to pay it back, and so I have to wonder why else would they lend us money.
Borrowing rates are historically low most other places as well.
Regarding 'trust' in Portugal: Draghi's 'whatever it takes' statement and actions are mainly what fixed this.
You need to be careful about definitively attributing an outcome to a particular action - hey, maybe you fixed borrowing costs by eating weetabix for breakfast one day in 2010, and now Portugal has low borrowing rates.
We are also of course only considering one very limited measure of 'success' - you did not mention unemployment or GDP, for some reason ...
The ECB buying government debt, and pledging to buy as much as was needed, wasn't the main cause then?
Global interest rates being historically low isn't a cause now?
No, you say, it is because of something that was the same before, during, and after the main crisis point - that promises and contracts were not broken. (Not that promises or contracts need necessarily have been broken had other courses of action been taken).
Meanwhile e.g. Germany, who broke the rules on borrowing early in the life of the Euro, has of course suffered economic collapse, and cannot borrow money at any interest rate. And Iceland, they are back in the stone age now.
In this sub-thread, we were debating whether austerity in Portugal was a success.
The best comparison would be to Portugal had it and the EU/ECB adopted different policies. Admittedly this is hard since we do not see that.
You are choosing to compare Portugal to Greece. Greece alas is a complete basket-case. Starting in a much better situation than Greece, and claiming success for policies that leave you less worse off than Greece, is a very low bar.
At the same time, you argue that we can never compare Portugal to Iceland - not even as a counterexample to 'a country must not break promises or contracts, otherwise the economy goes down the drain'.
Iceland is not a very useful counterexample for "a country must not break promises" - or more precisely, "is it not wise for a country to break trust in its policies" - because I can't see what promises Iceland would have broken.
Why the Iceland case is different - and Iceland has not lost serious trust in eyes of lenders - is that Iceland did not run a serious public deficit and it did not fill such a deficit by borrowing.
Still, the economic crisis brought a shock to Icelandic economy in form of huge devaluation. If Portugal would have gone from EUR to its own currency, how much would it have devalued?
We can never compare Portugal with Iceland. As an objective example:
Portugal needs energy from the exterior to survive. Would anybody trust us enough to sell energy (at a reasonable price), not knowing if we would pay it ? By the other hand, Iceland doesnt't need the exterior as much as we, they can afford to not be trusted .
 Or we could associate to Russia, like Syriza tried..
 'By harnessing the abundant hydroelectric and geothermal power sources, Iceland's renewable energy industry provides close to 85% of all the nation's primary energy - proportionally more than any other country - with 99.9% of Iceland's electricity being generated from renewables.'
Agreed, the Iceland comparison is a red herring that is repeated often but which completely bypasses how different the Iceland economic crisis was.
Iceland never had much deficit. It has a healthy public economy. Iceland had a boom of financial industry which then went bust, but it wasn't a significant part of the country's real economy.
When the banks went bust, foreign customers who lost money in the crash insisted that Iceland, the country, should compensate. The government felt they didn't, because it was not the Icelandic government that was in bankruptcy. And that was fine.
The public deficit in Greece (and, to lesser extent, Portugal, Ireland, France, Italy and now Finland) is a very different problem.
I must add that I disagree about Iceland not needing the exterior. Iceland is a very, very small country on a remote, barren island with few natural resources, and is hugely dependent on imports to make it livable in the modern sense. Iceland definitely needs trade with the exterior to survive. I would say Greece is more self-sufficient for many important things (like food) though not for geothermal energy.