[hprotagonist]

I have been a voice in the wilderness since about 2007 on this one, so this is shadenfraude on a level that makes me kind of embarrassed about myself.

My background is biomedical engineering, and I just never, ever understood how the sampling rate could ever work. If you're looking for a low-energy signal and your sampling rate is really low, you're just going to miss it and this should've been screamingly obvious to everyone since the beginning.

It's like going to the beach, drawing a 5 gallon pail of seawater, looking into it, and then declaring that the beach is shark-free today and it's safe to swim.

[ryandrake]

I don’t think you had to be a biomedical engineer to have called this one, even years ago. Its attributes hit HN (and the gushing tech media) in all the soft spots: young, female founder, college dropout, wore black turtlenecks like Steve Jobs, disruptive tech, attacking a stodgy conservative industry, order(s) of magnitude claimed improvements. It was simply too good and aligned perfectly with the HN zeitgeist. Just like the poster: “I Want To Believe!” Everyone’s blinders were on, and nobody wanted to recognize the obvious signs of fakery.

This has been my favorite tech story of the decade. Watching a rich, well-connected phony get knocked down and called out on all the bullshit fills me with glee. It excites me in ways we don’t talk about in polite company. So many hard working smart people out there toiling away in obscurity while these “elite” fakers get all the recognition and money. The schadenfreude in watching one of them finally and spectacularly burn up is too good to bear.

[hkmurakami]

I've actually never seen a HN thread that was overall positive about Theranos. The top comments were shears critical of the company, despite all the worthy surface level virtue it carried.

[tgb]

I believe that this [1] is the oldest thread in HN about Theranos. There are two sub-threads that are negative and one which seems quite spot-on in hindsight. But the top comments are all quite positive.

[1] https://news.ycombinator.com/item?id=6349349

[beagle3]

I have no background in biomedical engineering, and I'll take your (and others') word that it could clearly never work.

However, I have had a related experience that stops me, even in these cases, from immediately shouting "the king has no clothes":

Some 25 years ago I was giving a talk at some point, that mentioned spread spectrum communication to a small crowd of physicists and engineers, none of whom was familiar with the concept. When I drew an energy/frequency graph in which the signal level was below the ambient noise level, I got laughing/mocking/disbelieving response, and I had to actually show (a simplified) version of the math to proceed.

None of those people were stupid. In fact, I believe most if not all of them are way smarter than me; but they've all adopted the "s/n ratio must be large enough at every distinct frequency " as an axiom, which is simply wrong.

Since then, when I see extraordinary claims, I just wait for the extraordinary proof.

> It's like going to the beach, drawing a 5 gallon pail of seawater, looking into it, and then declaring that the beach is shark-free today and it's safe to swim.

If shark shed sharkticles that can easily be detected, and the water mixing speed is sufficient, then -- yes, you might be able to make that claim from a 5 gallon pail of seawater.

But before I believe you can do that, I would want to see the theory and a working demonstration. It's astonishing that wasn't demanded of Theranos by any of the investors.

[CptFribble]

I also have a background in biomedical engineering, and worked on actual diagnostic equipment for several years, and I would like to second this opinion. I only wish I had written down my rants about Theranos for future reference!

Theranos' claims fundentally misrepresented the state of medical diagnostics, and showed at best a failure to grasp the nature of the industry, and at worst a deliberate misrepresentation. Apparently it was the latter.

If any of the investors now saying "gosh who could have guessed" had taken 2 seconds to ask anyone who worked on or with real medlab tech about Theranos' claims, they wouldn't have touched that company with a 10 mile pole.

[2YwaZHXV]

Existing analysers already use very small samples.

See Siemens Advia 1800 specs under "Microvolume Technology" https://www.healthcare.siemens.com/clinical-chemistry/system...

It only uses 30ul of sample to run up to 15 assays.

How is that any different from what Theranos was doing?

Only difference is that you collect a bigger vial when using the Siemens machine. And then don't use most of it. So why not collect a smaller vial?

[exelius]

There’s no benefit to doing so; and smaller vials are harder to preserve. Measurements on blood draws are not exact, and pre-measured preservatives in the vials and the blood have to be in the right ratios.

This is easier to do consistently in larger vials, reducing the error in this part of the process to acceptable levels. It’s the same reason why a recipe will normally be more consistent when making a larger batch.

So you could collect less, but the way the modern lab industry operates (collecting samples, preserving them, and shipping them to an offsite lab for analysis) there is little business benefit to using smaller collection vials.

[2YwaZHXV]

Ok, so you're giving a business reason to not collect smaller samples. Which is fine and totally valid. Theranos was under the impression that there was an untapped opportunity for smaller samples.

But, the wording of the parent comment was saying that it was supposedly clearly technically impossible because of the small sample size. The OP said "I just never, ever understood how the sampling rate could ever work" and "and this should've been screamingly obvious to everyone since the beginning." That seems very different from "this is a very hard problem due to X, Y, and Z", especially since commercial machines that everyone here gets blood results from are already only taking small samples from the collected vials so the biggest challenge just seems to be in the collection and transport.

I agree that everything is easier with a bigger collection size, however "hard" is different from impossible.

[ethbro]

Out of curiousity, how tight are the preservative:blood ratios before Bad Things (i.e. things that would invalidate the test results) start to happen?

[2YwaZHXV]

That's a good question. Looking at this: http://apps.who.int/iris/bitstream/10665/65957/1/WHO_DIL_LAB... for EDTA (a very common anticoagulant "preservative") it is 1.2 to 2.0 mg/mL, so a decent range. But, this is one source and it will also depend on what the test is looking for.

[CptFribble]

There are a few reasons you collect a full vial instead of a tiny one:

1. Multiple tests. Most people aren't going to the doctor for a single test. A majority of the testing is Comprehensive Metabolic Panels, which covers 20-30 different things at least. Many patients get a CMP plus other stuff, so enough is drawn for all the tests at once.

2. Possible retesting. There are dozens of things that can go wrong between drawing the blood and sending a result to the doctor. Maybe a tech drops the tube and spills some blood out. Maybe the machine has a problem mid-test and you have to rerun the samples after it's fixed. Maybe the patient has a critically high/low range of something and you need to retest for confirmation. The worst possible scenario for a lab is to have to call the patient back in for more blood, because that causes patient pain and could make the doctor start using a different lab if they're perceived as unreliable. There's actually a legal requirement for labs to store blood for a week after testing, just in case.

3. Different test requirements. The CMPs usually test the serum only (i.e. your blood gets put through a centrifuge), but there are a variety of tests that run on whole blood. Because of the possible re-testing above, and because whole blood test samples need to have anticoagulant added, you'll usually have two separate tubes drawn for whole blood vs. serum tests.

[2YwaZHXV]

OK, so these are more business reasons for bigger samples than technical reasons.

1. Ok, so that can still be done with small samples, it's just a matter of collecting enough. The link I gave showed 15 tests in 30ul of sample. So, 60ul would be enough for your 30 tests. The amount used per test (for many many tests) is still very small compared to the amount drawn.

2. I imagine if a tube is dropped and some sample is lost they consider the whole sample lost. Since if sample got out that also means that stuff can get in, possibly contaminating it. The poor customer experience of having to go back in to be re-drawn is a poor business choice, but again, not a technical hurdle with being able to perform tests. Having enough sample for re-testing a week later is also just a matter of collecting sufficient sample. So, you would need 120+ul of sample (from previous example of 30 tests) to meet that requirement (plus some amount for loss in equipment, etc). But, it is still a far cry from the 2000+ul typically drawn.

3. You actually often have more than 2 drawn, since each tube has a different kind (if any) anticoagulant and if they get sent to different labs they may need duplicates of the same anti-coagulant. This also doesn't have anything to do with the size of the sample required for a test. So, you can collect a bunch of small samples instead of bigger samples. That's not a technical hurdle for being able to perform a test on a small volume of blood.

[semi-extrinsic]

Well, because you can get a sample that's a lot more representative of the actual bulk bloodstream by a) diluting out the contaminants always present in the first part of the sample, and b) drawing the sample from a large vein rather than tiny ones in the fingertip.

[exelius]

Agree with you 100%.

There are definitely areas where a wunderkind can advance the frontier by ignoring dogma about what is and isn’t possible; but biomedical engineering doesn’t seem like one of them.

I always had my suspicions too; her idea seemed so simple that it had to have occurred to larger med device makers too. If they couldn’t solve the problems related to the small sample size with many years of engineering experience, what made her think her chances of success were any better?

[paulcole]

> I have been a voice in the wilderness since about 2007 on this one

The Hacker News commenters have always been quite kind and optimistic about Theranos and Ms. Holmes. Were your doubts downvoted?

[dang]

That's far from the case, as anyone who wants to comb through https://hn.algolia.com/?query=Theranos%20points%3E10&sort=by... can see for themselves.

[hprotagonist]

i only joined HN in 2016, so i missed much of it.