Why didn’t Theranos work? (and could it have ever worked?)

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I’ve heard of PCR before (polymerase chain reaction) where more copies of a DNA sample can be rapidly made. If the problem was that the quantity of blood that Theranos uses is too small, why wasn’t PCR used/ (if it was) why didn’t it work?

Also if I’m completely misunderstanding PCR, if someone could for that too, I’d appreciate it, thank you!

In: 148

31 Answers

Anonymous 0 Comments

I don’t think the tests they were planning to run were all based on genetic code, e.g. presence of antibodies in the fluid.

e: [info](https://www.refinery29.com/en-us/2019/03/224904/theranos-edison-machine-blood-test-technology-explained)

Anonymous 0 Comments

PCR amplies nucleotides. Most (All?) of the diseases they wanted to measure are not diagnosible usong this as a analytt. Typicaly one looks for metabolites or proteins.

Anonymous 0 Comments

Even from a basic physics / chemistry point of view, some of what they wanted to do was simply against the laws of science.

Like, these samples they were taking were very small. Sometimes what you’re looking for is a very rare molecule, such trace amounts that the idea that a detectable number of these would be present in such a tiny sample, let alone reliably so, let alone using the same tiny sample for hundreds of such tests…

It’s against the laws of mathematics. Some tests are looking for very small trace amounts of something, so if your sample is very small then you just don’t have enough to find what you’re looking for.

Add to this other practical issues, like often a test will modify the sample, like you add some reagent or catalyst to find what you’re looking for, this modifies the sample. As a result, the ability to use one sample for multiple tests is limited. Often you have to split your sample up for different tests, which makes their tiny sample even more ridiculous.

Like, in chemistry a statistically significant sample size for most things isn’t *that* big in the sense that even a small amount of something is still a crazy large number of molecules. But when you take these tiny samples and necessarily in reality need to then start splitting that into smaller samples for testing, you’re approaching homeopathic quantities of some things.

Anonymous 0 Comments

Not all blood tests are equal.

Most require very little blood, between 5 and 30 ml of blood. Hence vacutainer tubes are standardized.

Pcr only work for certain things BECAUSE they use DNA. They replicate viral or Patient DNA and specific markers are identified to be looked for. Thus by counting the number of markers found you can determine whether a patient has a Virus or genetic affliction.

But other tests do not involve genetic material. Tests such as Full blood count or even just a Hemaglobin test, you are actually measuring a specific thing in the body and it has nothing to do with genetic material.

Now the amount they wanted to use, was microscopic, so you it does not fall within standards of testing, sometimes you need more volume cause you need to rerun to confirm or do another smear manually and drawing again is something patients do not like. So min blood volume for a test, is usually enough to run it twice or enough that if a screening is positive, a confirmation test can also be run.

Source: 8 years in pathology. Ask if I am unclear or you have more Qs

Anonymous 0 Comments

Some of it can work. A fingerprick glucometer or haemoglobin can give you the amount of sugar in your blood or how concentrated your blood is based on a drop of blood. A blood gas machine uses not much more than a drop to give you quite a lot of data. These can have issues because a lot of things can affect the blood and the drop that you get might not be reflective of the rest of the blood in your body because of a variety of reasons. If you’re looking for a certain concentration of something in the blood, it can wildly swing from drop to drop if you only collect a small amount, compared to if you collected like 5mL of it.

The limiting factor was going to be how many tests you can get off a sample. They advertised a lot for a small sample which is never going to be physically possible. But if you only need like one or two sets of tests, we already do that with [babies](https://www.bd.com/assets/images/our-products/blood-and-urine-collection/blood-collection/microtainer-blood-tubes_RC_PAS_BC_0616-0001.png), but the machine used to run it is room-sized.

Anonymous 0 Comments

i don’t really know all the promises of theranos. But i can remember they practically wanted a chip in the skin to do the same as a high grade laboratory which is simply not feasable.

About pcr, i worked with pcr and not enough material for pcr is nearly impossible you can copy tinyest amount of DNA. But you need a quite sophisticated lab with machines which are not really that small. In most cases a heating module, a spectrometer and some way to filter out the stuff which isn’t DNA. But checking for medical imbalances is more then just looking at DNA. And we are far from getting a medicinal laboratory in the size of a chip

Anonymous 0 Comments

[removed]

Anonymous 0 Comments

[removed]

Anonymous 0 Comments

Theranos was promising that it could do blood tests to check cholesterol, vitamin levels, and blood sugar as well as antibodies from herpes and HIV all from finger pricks. Oh, and Theranos was also saying that all those tests could also be done with very quickly with small automated machines.

Some of this might be theoretically possible at some point in the future and some of it may well always be more in the realm of science fiction.

One problem from the outset was that finger pricks collect blood from small blood vessels known as capillaries. Now, taking blood from capillaries can sometimes rupture the blood cells and, thus, produce inaccurate results. Capillary blood also frequently fails to give as consistent values of cholesterol and lipids as vein blood. Which is, obviously, not a good thing if you’re trying to test someone’s cholesterol levels. One of Elizabeth Holmes’ professors at Stanford, Phyllis Gardner, told her of these problems with capillary blood tests, but she chose to ignore it. (This is not to say that all capillary blood tests are worthless: capillary glucose tests work quite well, which is why diabetics use them so often.)

The other problem is Theranos’ blood testing machine, the Edison, never really worked right. The Edison was prone to overheating, its doors wouldn’t close, and it often shattered glass slides placed in it.

Finally, there are currently limits on how many blood tests can be done with just one drop of blood. Theranos was claiming it could do thousands and they … massively overstated the case. To do even one or two tests from drops of blood, they had to massively dilute the sample, which made it more susceptible to giving badly inaccurate results. During Elizabeth Holmes’ trial, there was testimony from a woman who said that Theranos’ tests falsely told her she was having a miscarriage and another that said she’d misdiagnosed as having HIV antibodies.

A sort of general consensus about Theranos is that Elizabeth Holmes would have done better to finish her bachelor’s degree at Stanford and then also get a master’s and a Ph.D in chemistry or an MD. She wanted to imitate Steve Jobs and Bill Gates, yet there are, uh, many differences between medicine and computer science. To put it bluntly, there’s a reason why you have to get a lot more education and training to become a doctor than a computer programmer.

Anonymous 0 Comments

As a Medical Lab Tech, one of the most important factor in blood analysis I can tell you is sample quality. While a pin-prick might be “easier” for the patient, it comes with huge challenges.

The smaller the size of hole blood has to go through, the more hemolysis or “breakage” that occurs to red blood cells. When red blood cells break apart, they release their contents. So when we see capillary samples, we can see false results such as extremely high potassium (not compatible with life), lactate, AST, ALT and many othet tests. Also, inclusion of tissue fluids can also dilute your blood.
Most established reference ranges (“normal” numbers for patients) are based on perfectly, collected samples, generally from a vein. If you have a bad sample, your accuracy is already gone.

Additionally, most blood tests are based on what is called spectrophotometry method. What this method does is first you find something that reacts to and changes the colour of the solution. So say you have glucose (blood sugar) and you add something called Horseradish peroxidase. In the solution you have, you could have something to change the colour when glucose is reacted. The colour change can increase with more glucose. After the colour change, you shine a light through the solution and on the other side detects how much light has gone through. Depending on the colour change (some reactions turn clear too), this then is used to measure the amount of a substance. So say glucose reacts to the horseradish peroxidase and turns the solution redder. You could shine red light (a specific wavelength of light) and because less red ligh goes through, the detector detects less red light, which is associated with a higher glucose value.* The problem here is every single chemistry test uses different enzymes, colour reactions, absorption parameters yet uses the exact same blood sample. How do you miniturize that into a small analyzer?

*Each reaction is completely different. I cant tell you the exact reaction for horseradish peroxidase. Red was a random colour chosen

So with the above, you have a problem. If you have ordered multiple tests, how do you have enough blood to split this up to measure light through? Additionally, spectrophotometric methods require cuvettes that require minimum volumes. Granted, they have become smaller each year, but they are still a challenge. The smallest thing that is out is called a Abaxis Piccolo, which comes in a tiny disk and can run a decent number of tests. There are Abbott iStats too. But these only run one test at a time with one sample.

PCR is different. It takes a piece of DNA and replicates it multiple times to detect it. This means you can copy DNA enough to be able to detect it. We cant do that with glucose, cholesterol, blood enzymes etc.

0 views

I’ve heard of PCR before (polymerase chain reaction) where more copies of a DNA sample can be rapidly made. If the problem was that the quantity of blood that Theranos uses is too small, why wasn’t PCR used/ (if it was) why didn’t it work?

Also if I’m completely misunderstanding PCR, if someone could for that too, I’d appreciate it, thank you!

In: 148

31 Answers

Anonymous 0 Comments

I don’t think the tests they were planning to run were all based on genetic code, e.g. presence of antibodies in the fluid.

e: [info](https://www.refinery29.com/en-us/2019/03/224904/theranos-edison-machine-blood-test-technology-explained)

Anonymous 0 Comments

PCR amplies nucleotides. Most (All?) of the diseases they wanted to measure are not diagnosible usong this as a analytt. Typicaly one looks for metabolites or proteins.

Anonymous 0 Comments

Even from a basic physics / chemistry point of view, some of what they wanted to do was simply against the laws of science.

Like, these samples they were taking were very small. Sometimes what you’re looking for is a very rare molecule, such trace amounts that the idea that a detectable number of these would be present in such a tiny sample, let alone reliably so, let alone using the same tiny sample for hundreds of such tests…

It’s against the laws of mathematics. Some tests are looking for very small trace amounts of something, so if your sample is very small then you just don’t have enough to find what you’re looking for.

Add to this other practical issues, like often a test will modify the sample, like you add some reagent or catalyst to find what you’re looking for, this modifies the sample. As a result, the ability to use one sample for multiple tests is limited. Often you have to split your sample up for different tests, which makes their tiny sample even more ridiculous.

Like, in chemistry a statistically significant sample size for most things isn’t *that* big in the sense that even a small amount of something is still a crazy large number of molecules. But when you take these tiny samples and necessarily in reality need to then start splitting that into smaller samples for testing, you’re approaching homeopathic quantities of some things.

Anonymous 0 Comments

Not all blood tests are equal.

Most require very little blood, between 5 and 30 ml of blood. Hence vacutainer tubes are standardized.

Pcr only work for certain things BECAUSE they use DNA. They replicate viral or Patient DNA and specific markers are identified to be looked for. Thus by counting the number of markers found you can determine whether a patient has a Virus or genetic affliction.

But other tests do not involve genetic material. Tests such as Full blood count or even just a Hemaglobin test, you are actually measuring a specific thing in the body and it has nothing to do with genetic material.

Now the amount they wanted to use, was microscopic, so you it does not fall within standards of testing, sometimes you need more volume cause you need to rerun to confirm or do another smear manually and drawing again is something patients do not like. So min blood volume for a test, is usually enough to run it twice or enough that if a screening is positive, a confirmation test can also be run.

Source: 8 years in pathology. Ask if I am unclear or you have more Qs

Anonymous 0 Comments

Some of it can work. A fingerprick glucometer or haemoglobin can give you the amount of sugar in your blood or how concentrated your blood is based on a drop of blood. A blood gas machine uses not much more than a drop to give you quite a lot of data. These can have issues because a lot of things can affect the blood and the drop that you get might not be reflective of the rest of the blood in your body because of a variety of reasons. If you’re looking for a certain concentration of something in the blood, it can wildly swing from drop to drop if you only collect a small amount, compared to if you collected like 5mL of it.

The limiting factor was going to be how many tests you can get off a sample. They advertised a lot for a small sample which is never going to be physically possible. But if you only need like one or two sets of tests, we already do that with [babies](https://www.bd.com/assets/images/our-products/blood-and-urine-collection/blood-collection/microtainer-blood-tubes_RC_PAS_BC_0616-0001.png), but the machine used to run it is room-sized.

Anonymous 0 Comments

i don’t really know all the promises of theranos. But i can remember they practically wanted a chip in the skin to do the same as a high grade laboratory which is simply not feasable.

About pcr, i worked with pcr and not enough material for pcr is nearly impossible you can copy tinyest amount of DNA. But you need a quite sophisticated lab with machines which are not really that small. In most cases a heating module, a spectrometer and some way to filter out the stuff which isn’t DNA. But checking for medical imbalances is more then just looking at DNA. And we are far from getting a medicinal laboratory in the size of a chip

Anonymous 0 Comments

[removed]

Anonymous 0 Comments

[removed]

Anonymous 0 Comments

Theranos was promising that it could do blood tests to check cholesterol, vitamin levels, and blood sugar as well as antibodies from herpes and HIV all from finger pricks. Oh, and Theranos was also saying that all those tests could also be done with very quickly with small automated machines.

Some of this might be theoretically possible at some point in the future and some of it may well always be more in the realm of science fiction.

One problem from the outset was that finger pricks collect blood from small blood vessels known as capillaries. Now, taking blood from capillaries can sometimes rupture the blood cells and, thus, produce inaccurate results. Capillary blood also frequently fails to give as consistent values of cholesterol and lipids as vein blood. Which is, obviously, not a good thing if you’re trying to test someone’s cholesterol levels. One of Elizabeth Holmes’ professors at Stanford, Phyllis Gardner, told her of these problems with capillary blood tests, but she chose to ignore it. (This is not to say that all capillary blood tests are worthless: capillary glucose tests work quite well, which is why diabetics use them so often.)

The other problem is Theranos’ blood testing machine, the Edison, never really worked right. The Edison was prone to overheating, its doors wouldn’t close, and it often shattered glass slides placed in it.

Finally, there are currently limits on how many blood tests can be done with just one drop of blood. Theranos was claiming it could do thousands and they … massively overstated the case. To do even one or two tests from drops of blood, they had to massively dilute the sample, which made it more susceptible to giving badly inaccurate results. During Elizabeth Holmes’ trial, there was testimony from a woman who said that Theranos’ tests falsely told her she was having a miscarriage and another that said she’d misdiagnosed as having HIV antibodies.

A sort of general consensus about Theranos is that Elizabeth Holmes would have done better to finish her bachelor’s degree at Stanford and then also get a master’s and a Ph.D in chemistry or an MD. She wanted to imitate Steve Jobs and Bill Gates, yet there are, uh, many differences between medicine and computer science. To put it bluntly, there’s a reason why you have to get a lot more education and training to become a doctor than a computer programmer.

Anonymous 0 Comments

As a Medical Lab Tech, one of the most important factor in blood analysis I can tell you is sample quality. While a pin-prick might be “easier” for the patient, it comes with huge challenges.

The smaller the size of hole blood has to go through, the more hemolysis or “breakage” that occurs to red blood cells. When red blood cells break apart, they release their contents. So when we see capillary samples, we can see false results such as extremely high potassium (not compatible with life), lactate, AST, ALT and many othet tests. Also, inclusion of tissue fluids can also dilute your blood.
Most established reference ranges (“normal” numbers for patients) are based on perfectly, collected samples, generally from a vein. If you have a bad sample, your accuracy is already gone.

Additionally, most blood tests are based on what is called spectrophotometry method. What this method does is first you find something that reacts to and changes the colour of the solution. So say you have glucose (blood sugar) and you add something called Horseradish peroxidase. In the solution you have, you could have something to change the colour when glucose is reacted. The colour change can increase with more glucose. After the colour change, you shine a light through the solution and on the other side detects how much light has gone through. Depending on the colour change (some reactions turn clear too), this then is used to measure the amount of a substance. So say glucose reacts to the horseradish peroxidase and turns the solution redder. You could shine red light (a specific wavelength of light) and because less red ligh goes through, the detector detects less red light, which is associated with a higher glucose value.* The problem here is every single chemistry test uses different enzymes, colour reactions, absorption parameters yet uses the exact same blood sample. How do you miniturize that into a small analyzer?

*Each reaction is completely different. I cant tell you the exact reaction for horseradish peroxidase. Red was a random colour chosen

So with the above, you have a problem. If you have ordered multiple tests, how do you have enough blood to split this up to measure light through? Additionally, spectrophotometric methods require cuvettes that require minimum volumes. Granted, they have become smaller each year, but they are still a challenge. The smallest thing that is out is called a Abaxis Piccolo, which comes in a tiny disk and can run a decent number of tests. There are Abbott iStats too. But these only run one test at a time with one sample.

PCR is different. It takes a piece of DNA and replicates it multiple times to detect it. This means you can copy DNA enough to be able to detect it. We cant do that with glucose, cholesterol, blood enzymes etc.