[GoodGrief]

Holmes is working on another project, 100 tests and diagnoses without even using blood. Shatner and Takei are on her new board. . . .

“Doctor gave me a pill and I grew a new kidney!”

That scene from Star Trek IV always cracked me up. 
Btw, please do register to be an organ donor. My best friend received a kidney and it’s the most amazing miracle of life.

[GoodGrief]

Holmes is working on another project, 100 tests and diagnoses without even using blood. Shatner and Takei are on her new board. . . .

“Doctor gave me a pill and I grew a new kidney!”

That scene from Star Trek IV always cracked me up. 
Btw, please do register to be an organ donor. My best friend received a kidney and it’s the most amazing miracle of life.

[82lsju]

"She was brought by someone else who said she was the most brilliant person, and I’m like, “Don’t call people brilliant around me because I’m surrounded by Nobel laureates.”
...
Q: As the hype around Theranos grew, did you ever wonder if you were wrong about Holmes?
A: No. I just thought everybody was crazy. I mean, look at the board, that’s insane. That’s not corporate feasance, that’s malfeasance to have a board that knows nothing about any of this. Old men, I’m telling you, the brains go to their groin.
I knew too much inside stuff. I’m not just watching it from afar — I’ve got this inside info coming to me about how it’s not working.
...
Q: What are the lessons from the Theranos saga for Silicon Valley?
A: I think Silicon Valley is getting too much of a hit — these were friends and family investors. They didn’t do due diligence. All that myth-making was outside Silicon Valley. I didn’t find that many people at Stanford who thought she was amazing."

https://www.siliconvalley.com/2019/06/03...anos-saga/

[82lsju]

"She was brought by someone else who said she was the most brilliant person, and I’m like, “Don’t call people brilliant around me because I’m surrounded by Nobel laureates.”
...
Q: As the hype around Theranos grew, did you ever wonder if you were wrong about Holmes?
A: No. I just thought everybody was crazy. I mean, look at the board, that’s insane. That’s not corporate feasance, that’s malfeasance to have a board that knows nothing about any of this. Old men, I’m telling you, the brains go to their groin.
I knew too much inside stuff. I’m not just watching it from afar — I’ve got this inside info coming to me about how it’s not working.
...
Q: What are the lessons from the Theranos saga for Silicon Valley?
A: I think Silicon Valley is getting too much of a hit — these were friends and family investors. They didn’t do due diligence. All that myth-making was outside Silicon Valley. I didn’t find that many people at Stanford who thought she was amazing."

https://www.siliconvalley.com/2019/06/03...anos-saga/

[BostonCard]

I thought this quote was a bit odd:

Gardner recounts meeting Holmes when she was a Stanford student pitching lofty medical technology ideas; she tried to tell Holmes that what she wanted to do was impossible, Gardner says, but the 19-year-old brushed her off.

I mean, I get that it is technically challenging, and "impossible" with the technology at the time, but I think "impossible" is a bit harsh.  There is nothing magical about 5-10 mL (the amount of blood collected in a standard lab tube); as my chemical engineering friend told me, there is a significant microfluidics challenge, but I don't think it's impossible based on the laws of physics.

BC

[BostonCard]

I thought this quote was a bit odd:

Gardner recounts meeting Holmes when she was a Stanford student pitching lofty medical technology ideas; she tried to tell Holmes that what she wanted to do was impossible, Gardner says, but the 19-year-old brushed her off.

I mean, I get that it is technically challenging, and "impossible" with the technology at the time, but I think "impossible" is a bit harsh.  There is nothing magical about 5-10 mL (the amount of blood collected in a standard lab tube); as my chemical engineering friend told me, there is a significant microfluidics challenge, but I don't think it's impossible based on the laws of physics.

BC

[oldalum]

The idea Holmes pitched to Gardner was not the nanotainer multiple test thing, it was a skin patch that would deliver a dose of a drug through the skin, monitor the blood levels or effects of the drug, and adjust the ongoing dose based on that. And communicate wirelessly what it was doing. That was what Gardner said was impossible, and she was right. It was later that the product evolved into the one that Theranos produced. 

The engineering problems might have been overcome if Holmes had been willing to accept a larger machine, but she insisted on a relatively small box because that was necessary for her vision of transforming health care by enabling people to do their own blood tests in their own homes whenever they wanted to, and the military to do blood tests on a battlefield (though I'm not sure why that would actually be helpful).

The premier book on Theranos and Holmes, "Bad Blood," written by the Wall Street Journal reporter, is a good read that I recommend.

[oldalum]

The idea Holmes pitched to Gardner was not the nanotainer multiple test thing, it was a skin patch that would deliver a dose of a drug through the skin, monitor the blood levels or effects of the drug, and adjust the ongoing dose based on that. And communicate wirelessly what it was doing. That was what Gardner said was impossible, and she was right. It was later that the product evolved into the one that Theranos produced. 

The engineering problems might have been overcome if Holmes had been willing to accept a larger machine, but she insisted on a relatively small box because that was necessary for her vision of transforming health care by enabling people to do their own blood tests in their own homes whenever they wanted to, and the military to do blood tests on a battlefield (though I'm not sure why that would actually be helpful).

The premier book on Theranos and Holmes, "Bad Blood," written by the Wall Street Journal reporter, is a good read that I recommend.

[CompSci87]

Bad Blood also explains that capillary blood from a fingertip isn't suitable for accurately doing many tests. The composition is notably different from blood captured from a vein. Sorry I don't recall enough details to do justice to the reasons why.

[CompSci87]

Bad Blood also explains that capillary blood from a fingertip isn't suitable for accurately doing many tests. The composition is notably different from blood captured from a vein. Sorry I don't recall enough details to do justice to the reasons why.

[BostonCard]

Bad Blood also explains that capillary blood from a fingertip isn't suitable for accurately doing many tests. The composition is notably different from blood captured from a vein. Sorry I don't recall enough details to do justice to the reasons why.

The former doesn't necessarily flow from the latter.  The composition of capillary blood can be different from venous blood and still be useful for diagnosing disease.  The important question is whether the result of the test, no matter how you get it, is reliably within a predictable range in healthy patients, and reliably outside of that range in disease.  That range could be different depending on what the analyte measured is.  The key is not so much showing concordance between capillary blood and venous blood (though that makes life easy) but rather to show concordance between a particular test no matter where the blood is obtained, and health or disease.

There is precedent for using capillary blood; glucose monitoring for diabetics.  It turns out that capillary blood glucose is higher than venous blood glucose taken simultaneously.  However, capillary blood glucose is still useful because the difference is fairly low, and the difference between the two is small enough compared to important clinical differences.  You might want to use venous blood from a fasting patient to diagnose diabetes, but for a diabetic managing their insulin, portable glucometers using capillary blood have proven that they are good enough.

In terms of Theranos, if they had actually managed to develop their system (a brobdingnagian if, of course), there probably would have been many blood tests for which the system would have generated accurate enough measurements to be useful, and some things for which the system would have been too inaccurate to use.  That is not unlike venous blood tests currently under development.  We can measure thousands of analytes in a tube of blood; however not all of them will be useful.  Venous blood just has a about a century head start, and so clinicians have become comfortable with it.

BC

[BostonCard]

Bad Blood also explains that capillary blood from a fingertip isn't suitable for accurately doing many tests. The composition is notably different from blood captured from a vein. Sorry I don't recall enough details to do justice to the reasons why.

The former doesn't necessarily flow from the latter.  The composition of capillary blood can be different from venous blood and still be useful for diagnosing disease.  The important question is whether the result of the test, no matter how you get it, is reliably within a predictable range in healthy patients, and reliably outside of that range in disease.  That range could be different depending on what the analyte measured is.  The key is not so much showing concordance between capillary blood and venous blood (though that makes life easy) but rather to show concordance between a particular test no matter where the blood is obtained, and health or disease.

There is precedent for using capillary blood; glucose monitoring for diabetics.  It turns out that capillary blood glucose is higher than venous blood glucose taken simultaneously.  However, capillary blood glucose is still useful because the difference is fairly low, and the difference between the two is small enough compared to important clinical differences.  You might want to use venous blood from a fasting patient to diagnose diabetes, but for a diabetic managing their insulin, portable glucometers using capillary blood have proven that they are good enough.

In terms of Theranos, if they had actually managed to develop their system (a brobdingnagian if, of course), there probably would have been many blood tests for which the system would have generated accurate enough measurements to be useful, and some things for which the system would have been too inaccurate to use.  That is not unlike venous blood tests currently under development.  We can measure thousands of analytes in a tube of blood; however not all of them will be useful.  Venous blood just has a about a century head start, and so clinicians have become comfortable with it.

BC

[BostonCard]

The idea Holmes pitched to Gardner was not the nanotainer multiple test thing, it was a skin patch that would deliver a dose of a drug through the skin, monitor the blood levels or effects of the drug, and adjust the ongoing dose based on that. And communicate wirelessly what it was doing. That was what Gardner said was impossible, and she was right. It was later that the product evolved into the one that Theranos produced. 

The engineering problems might have been overcome if Holmes had been willing to accept a larger machine, but she insisted on a relatively small box because that was necessary for her vision of transforming health care by enabling people to do their own blood tests in their own homes whenever they wanted to, and the military to do blood tests on a battlefield (though I'm not sure why that would actually be helpful).

The premier book on Theranos and Holmes, "Bad Blood," written by the Wall Street Journal reporter, is a good read that I recommend.

I have read many of the WSJ articles by Carreyrou (who wrote Bad Blood; I have not read all of the sordid details in the book).  I will start out by saying that this is not a meant as a defense of Holmes, who committed fraud and should and will pay for it.  It was more a comment on Phyllis Gardner dismissing something as "impossible". After a bit of  further research on what exactly Gardner was commenting on, I tend to agree with her that her initial idea deserved a lot of skepticism, though even then is it impossible in an absolute sense? (also, Gardner may not have out and out said "that's impossible" but rather commented on what a monumental challenge what she was proposing would be):

https://www.stylist.co.uk/people/elizabe...wer/258080

Holmes pitched Gardner on her dream for a product that could patch-test blood, identify bacteria and illness, and administer antiobiotics at the same time. 

That being said, what you described is probably not in the realm of the impossible, and even what is quoted while impossible now and probably in the near future, may be made possible in my lifetime.

Let's start with what you described:

a skin patch that would deliver a dose of a drug through the skin, monitor the blood levels or effects of the drug, and adjust the ongoing dose based on that.

So let's break that down: "A skin patch that delivers a dose of a drug through the skin" is already available, with the ability to deliver nicotine (to help quit smoking), nitrogylcerine (for angina), hormone contraceptives, fentanyl (yes, that fentanyl; the patch is meant for patients with terminal cancer pain), and other medications (https://en.wikipedia.org/wiki/Transdermal_patch) have all been delivered successfully via a commercial patch, approved by the FDA.

"Monitoring the blood levels or effects of a drug" has been done for glucose, and the FDA recently (2017) approved the first transdermal glucose monitor (https://www.statnews.com/2017/09/28/fda-...er-pricks/).  I don't know of any other things that can be monitored transdermally, though I am not sure that there is something special about glucose (beyond the fact that it is the analyte that needs to be measured most commonly and thus represents the single biggest commercial opportunity).

"Adjust the ongoing dose based on that" (continuous monitoring): This has also been done, using insulin pumps and continuous glucose monitors, though to my knowledge these things are still under development.  There was a recent story of people hacking their own insulin pumps to work as an "artificial pancrease" (and there is a website documenting how to do it https://openaps.org/), though kids, don't do this at home; insulin can be deadly if administered at too high doses and you would want to have any device tested thoroughly before use.

The only ingredient that, to my knowledge, is not currently possible, is a transdermal patch that is dose adjustable on the fly, and although it may not be a readily solvable problem, I could imagine methods for controlling the patch's rate of release, and thus I wouldn't declare it in the realm of the impossible.

With most of the individual ingredients at least theoretically possible, the challenge is engineering a device that could do all that while remaining relatively inconspicuous.  I think it would be challenging, to be sure, and I don't know that I would give a college drop out much of a chance of being the one to do it, but I wouldn't dismiss the idea out of hand.

On the idea presented in the quote above from Stylist, it is vague enough that it is hard to evaluate.  Could one have a patch deliver antibiotics?  Yes, though there is a practical limit in terms of how much of a drug can be delivered transdermally. In theory a potent enough antibiotic could be delivered that way, but in practice most antibiotics require fairly high concentrations to be effective and thus high doses.  But if you found a super potent antibiotic... maybe?  Could you diagnose the infection through a patch?  Again, tough to do especially if the infection is at a distant site (for example, if you have a pneumonia, the bacteria will (hopefully) not be in the blood (and if it is, the patient will hopefully be in the hospital where the patch is irrelevant).  But if you could find some protein signature from the bacterium in the blood of people with an infection?  Again, it's a bit of a stretch, but not completely impossible.  My big objection is practical.  Why link the diagnostic and treatment, since presumably you would want a diagnosis (or at least be fairly sure you had a diagnosis) before prescribing and using the patch.  But impractical and challenging is not the same as impossible.

BC

[BostonCard]

The idea Holmes pitched to Gardner was not the nanotainer multiple test thing, it was a skin patch that would deliver a dose of a drug through the skin, monitor the blood levels or effects of the drug, and adjust the ongoing dose based on that. And communicate wirelessly what it was doing. That was what Gardner said was impossible, and she was right. It was later that the product evolved into the one that Theranos produced. 

The engineering problems might have been overcome if Holmes had been willing to accept a larger machine, but she insisted on a relatively small box because that was necessary for her vision of transforming health care by enabling people to do their own blood tests in their own homes whenever they wanted to, and the military to do blood tests on a battlefield (though I'm not sure why that would actually be helpful).

The premier book on Theranos and Holmes, "Bad Blood," written by the Wall Street Journal reporter, is a good read that I recommend.

I have read many of the WSJ articles by Carreyrou (who wrote Bad Blood; I have not read all of the sordid details in the book).  I will start out by saying that this is not a meant as a defense of Holmes, who committed fraud and should and will pay for it.  It was more a comment on Phyllis Gardner dismissing something as "impossible". After a bit of  further research on what exactly Gardner was commenting on, I tend to agree with her that her initial idea deserved a lot of skepticism, though even then is it impossible in an absolute sense? (also, Gardner may not have out and out said "that's impossible" but rather commented on what a monumental challenge what she was proposing would be):

https://www.stylist.co.uk/people/elizabe...wer/258080

Holmes pitched Gardner on her dream for a product that could patch-test blood, identify bacteria and illness, and administer antiobiotics at the same time. 

That being said, what you described is probably not in the realm of the impossible, and even what is quoted while impossible now and probably in the near future, may be made possible in my lifetime.

Let's start with what you described:

a skin patch that would deliver a dose of a drug through the skin, monitor the blood levels or effects of the drug, and adjust the ongoing dose based on that.

So let's break that down: "A skin patch that delivers a dose of a drug through the skin" is already available, with the ability to deliver nicotine (to help quit smoking), nitrogylcerine (for angina), hormone contraceptives, fentanyl (yes, that fentanyl; the patch is meant for patients with terminal cancer pain), and other medications (https://en.wikipedia.org/wiki/Transdermal_patch) have all been delivered successfully via a commercial patch, approved by the FDA.

"Monitoring the blood levels or effects of a drug" has been done for glucose, and the FDA recently (2017) approved the first transdermal glucose monitor (https://www.statnews.com/2017/09/28/fda-...er-pricks/).  I don't know of any other things that can be monitored transdermally, though I am not sure that there is something special about glucose (beyond the fact that it is the analyte that needs to be measured most commonly and thus represents the single biggest commercial opportunity).

"Adjust the ongoing dose based on that" (continuous monitoring): This has also been done, using insulin pumps and continuous glucose monitors, though to my knowledge these things are still under development.  There was a recent story of people hacking their own insulin pumps to work as an "artificial pancrease" (and there is a website documenting how to do it https://openaps.org/), though kids, don't do this at home; insulin can be deadly if administered at too high doses and you would want to have any device tested thoroughly before use.

The only ingredient that, to my knowledge, is not currently possible, is a transdermal patch that is dose adjustable on the fly, and although it may not be a readily solvable problem, I could imagine methods for controlling the patch's rate of release, and thus I wouldn't declare it in the realm of the impossible.

With most of the individual ingredients at least theoretically possible, the challenge is engineering a device that could do all that while remaining relatively inconspicuous.  I think it would be challenging, to be sure, and I don't know that I would give a college drop out much of a chance of being the one to do it, but I wouldn't dismiss the idea out of hand.

On the idea presented in the quote above from Stylist, it is vague enough that it is hard to evaluate.  Could one have a patch deliver antibiotics?  Yes, though there is a practical limit in terms of how much of a drug can be delivered transdermally. In theory a potent enough antibiotic could be delivered that way, but in practice most antibiotics require fairly high concentrations to be effective and thus high doses.  But if you found a super potent antibiotic... maybe?  Could you diagnose the infection through a patch?  Again, tough to do especially if the infection is at a distant site (for example, if you have a pneumonia, the bacteria will (hopefully) not be in the blood (and if it is, the patient will hopefully be in the hospital where the patch is irrelevant).  But if you could find some protein signature from the bacterium in the blood of people with an infection?  Again, it's a bit of a stretch, but not completely impossible.  My big objection is practical.  Why link the diagnostic and treatment, since presumably you would want a diagnosis (or at least be fairly sure you had a diagnosis) before prescribing and using the patch.  But impractical and challenging is not the same as impossible.

BC

[CTcard]

On the idea presented in the quote above from Stylist, it is vague enough that it is hard to evaluate.

Well, you have presented a rather detailed evaluation of what seems to be a reporter's summary of an offhand - not technical - comment from Gardner.

And yet ... I appreciate that you did. It was educational for me.

[CTcard]

On the idea presented in the quote above from Stylist, it is vague enough that it is hard to evaluate.

Well, you have presented a rather detailed evaluation of what seems to be a reporter's summary of an offhand - not technical - comment from Gardner.

And yet ... I appreciate that you did. It was educational for me.

[oldalum]

 But impractical and challenging is not the same as impossible.

Yes you're right of course and I appreciate your detailed explanation. My recollection of why Gardner thought it was "impossible" was because of the volume required to deliver a sufficient amount of drug, which was much larger than that of a patch. Seeing the other quote jogged my memory, the specific type of drug was antibiotic, and the volume required to deliver the requisite amount of antibiotic over several days is too great to fit in a patch. As you wrote, that doesn't mean it's impossible for all time. But as you say, she could have used the word "impossible" as shorthand for so beyond current means that it is impractical to start a company to develop a way to do it.

What I found interesting/new in the article was that she claims she distrusted her from the start, the very first meeting, as a "sixth sense." In other articles she describes how Holmes often came and gave talks to Stanford students and she was unhappy about exposing them to her, but I never read that she distrusted her personally from the start.

[oldalum]

 But impractical and challenging is not the same as impossible.

Yes you're right of course and I appreciate your detailed explanation. My recollection of why Gardner thought it was "impossible" was because of the volume required to deliver a sufficient amount of drug, which was much larger than that of a patch. Seeing the other quote jogged my memory, the specific type of drug was antibiotic, and the volume required to deliver the requisite amount of antibiotic over several days is too great to fit in a patch. As you wrote, that doesn't mean it's impossible for all time. But as you say, she could have used the word "impossible" as shorthand for so beyond current means that it is impractical to start a company to develop a way to do it.

What I found interesting/new in the article was that she claims she distrusted her from the start, the very first meeting, as a "sixth sense." In other articles she describes how Holmes often came and gave talks to Stanford students and she was unhappy about exposing them to her, but I never read that she distrusted her personally from the start.

[French Rage]

The premier book on Theranos and Holmes, "Bad Blood," written by the Wall Street Journal reporter, is a good read that I recommend.

Seconded.

[French Rage]

The premier book on Theranos and Holmes, "Bad Blood," written by the Wall Street Journal reporter, is a good read that I recommend.

Seconded.