Good morning, John.

It is often important to know what kind of disease a person has, like, a sore throat  might be a virus, or it might be strep, or a number of other bacteria. I got strep a lot  as a kid, and I very clearly remember the feeling of getting my throat swabbed  so that they could test me.

Back in the 80s, that swab would then be run over a  blood agar plate, so called because it had sheep's blood mixed into it, and then that  plate would be placed into an incubator. A day or two later, a bunch of bacteria from  my throat would have grown on that plate, but strep is particularly good at breaking open  the red blood cells in the agar, and that would make some spots in the plate transparent.  So, if the colonies made the agar clear, you knew the patient had strep. That's certainly  a way of figuring out what disease a person has, but it's not a great way.  It requires quite a lot of time, and also a fair amount of sheep's blood.

These days,  things are better. Strep is mostly diagnosed the same way COVID is, with a rapid antigen  test. A molecule that binds specifically to something that's on the surface of strep  bacteria is manufactured, and when you run the sample over it, the antigen binds  to the bacteria if it's there, and then changes color.

This is great. It's fast and it's cheap  and it's pretty accurate. But there are some diseases we can't use rapid antigen tests for.

With tuberculosis, for example, there's often not a lot of bacteria in the body. Also, it's  very good at hiding in various places. And also, it's hard to design molecules  that will bind to TB because its cell wall is all big and oily and waxy, and it's a mess,  which means that often today, TB is still diagnosed the way strep used to be: by  culturing the bacteria on special substrates,  which takes forever and is labor-intensive and expensive and also, it doesn't tell you  that much.

But in 2013, something amazing happened: the GeneXpert test. Instead of  binding to molecules found on the surface of pathogens, like antigen tests do, GeneXpert  tests explode the pathogen and then test for the presence of specific sequences of DNA.  And this means that they can test not only for the presence of diseases, but for the  presence of specific strains of diseases. We can actually test to see if genes that  help a pathogen survive a particular treatment are present.

And once they developed this technology, which can be used for pretty much any disease,  developing a new test is as simple as identifying the right target sequence of DNA  you want to look for and creating the label to bind to it. It's pretty easy to create these  labels and then stick them into the cartridges, and then if that segment of DNA is present,  the sample will glow when hit with specific wavelengths of light. Like a black light,  but for diseases.

But even cooler than that, you can actually put several DNA labels  into one cartridge, and each label can have a slightly different molecule on them that  lets them glow when hit with different wavelengths of light. So if there are four  genes in a bacteria that you want to test to see, you can create a cartridge that  contains four different labels that glow at four different wavelengths. Then you run  the sample through and you know exactly which drugs the pathogen is resistant to.  This technology is amazing and it's used all over the world.

And the company that  makes it, Cepheid, which is a division of Danaher, makes a lot of money doing these  tests, which I think is great. But also, there are  places in the world where the costs of these cartridges makes it so that even in places  that have the machines to use them, they don't get used. Here's a thing I learned recently: lymphoma rates are super low in the  poorest countries in the world, and that's weird.  So I looked into it and it turns out the reason why is that people assume they  have tuberculosis.

And because there is no test, no one realizes that they have  cancer and then they die. And it doesn't have to be this way, and Danaher seems to  agree somewhat. I think in part due to pressure from this community, a little more  than a year ago, they said that they would provide the cartridges that test for  tuberculosis at cost.

Not the multidrug resistant ones, but just the TB tests.  They would provide them at cost to the Global Fund, reducing the cost of that test  from $10 to $7.97, allowing millions more tests to be run, and they said this: And it has now been more than a year, and annual things happen every year, and they have not done that audit. John, I was very lucky to get the chance to read your book Everything is Tuberculosis  before everybody else, and it changed the way I see not just tuberculosis, but all illness.  It changed me with fascinating histories and with stories of real world tragedies  happening right now. The fact that we helped  to get the price of the TB cartridges 20% cheaper is amazing.

The fact that the ones  that test for drug resistance remain $15 when, by all accounts, they cost basically  the exact same amount, and that Danaher has not released the audit is frustrating.  But let's give them a little more time. Maybe the audit was harder to get done  than they thought, things are complex. But they're going to release it soon!

Right? These things change when we pay attention to them, and I know that I would  never have paid attention to them without you.  So thank you for your work, thank you for your book, and thanks for being awesome. John, I'll see you on Tuesday.