The Story of the Exploding Brain

Biochemist Joe DeRisi relays a fascinating -- but horrifying -- story about a patient to Adam Savage and Will Smith that will ... make your brain hurt. (Shudder.)

On our Halloween episode of Still Untitled, Adam Savage and Will Smith welcomed UCSF’s Joe DeRisi, a biochemist specializing in molecular biology, parasitology, genomics, virology, and computational biology. His stories were so horrifying and amazing, we’ve isolated one here for your reading pleasure.

Joe DeRisi: So … can I tell a story?

Adam Savage: Please.

Joe DeRisi: So this all started with a 74-year-old woman here in San Francisco who came to the Chinese hospital with what looked like a UTI infection. She had a little altered mental status. They gave her a Z-Pak and sent her on her way. But then a couple days later she has complete blindness in one eye, but no wound, just vision stopped in one eye.

Adam Savage: Wow.

Joe DeRisi: So she went to St. Mary’s. They got a look at her there, and they thought, “Okay, well, we don’t understand what’s going.” They did an MRI. “Okay, it may be strokes, and you’re of that age; it could be something to do with that.” But she had a weird cough too. Anytime there’s a weird cough … and she emigrated from China like 12 years ago or something, so they said, “Go to the general, get a TB exam just in case.” A couple days later her family wheels her into the general, and she’s comatose. They actually wheel her in comatose.

“They do an MRI, and the MRI looks as like a grenade went off in her brain.”

Joe DeRisi: They hit the emergency red button. They throw her on $150,000 of antibiotics, basically antiparasitics, anti-TB, antibacterials, I mean, you name it, boom, and they do an MRI, and the MRI looks as like a grenade went off in her brain.

Adam Savage: Whoa.

Joe DeRisi: The brain is decimated. It’s like huge ginormous lesions throughout everywhere, all the ventricles had ruptured and exploded inwards …

Adam Savage: This is within the last three days.

Joe DeRisi: About five days and her brain was mush. So, there’s no recovering this. We know that the patient’s not gonna make it, and everybody’s cognizant of that, and she did expire some number of days later after attempts to save her, but there was no brain left to save. Biopsies of the brain just showed massive necrosis, and in fact the official pathology is necrotizing vasculitis, but that’s not a diagnosis, that’s just an observation.

Adam Savage: That’s a Latin name for something that happened.

Joe DeRisi: Yeah, just like, okay, a bunch of stuff died. So even though we couldn’t save the patient, in this case it’s still important to us to know what happened, because what happened that was so fast? It’s also true that 50% or 60%, depending on where you’re at, of encephalitis, which is what she had, infection of the brain, or inflammation, goes completely undiagnosed. Even at UCSF, although that number’s going down now because we’re doing all this technology. So, we sequenced the bejeesus out of it. Now the game is, okay, separate what’s human genome from not human genome, and then look at what’s not human genome, and then we compare that to the world’s collection of organisms, and the organism that pops to the top of the list is called balamuthia. I had never heard of it. I was, “What the hell is that?” Never looked at it. It turns out it’s neither virus, nor bacteria, nor a fungus.

“We sequenced the bejeesus out of it.”

Will Smith: This is an amoeba?

Joe DeRisi: It’s an amoeba.

Will Smith: Yeah, the brain eating amoeba.

Joe DeRisi: It is a cousin of the famous brain eating amoeba. So, the famous one is called naegleria, and that’s the one little kids get up their nose in warm lakes in the south, and then a week later they’re dead.

Adam Savage: Right.

Joe DeRisi: Balamuthia is the evil cousin of naegleria. At least with naegleria, you know, okay, warm lakes up the nose, I know how to prevent that. No one knows where balamuthia comes from. No one has a clue.

Adam Savage: They still haven’t isolated …

“She lived in Chinatown in an apartment. She didn’t garden, she didn’t go swimming. Where did she get this?”

Joe DeRisi: No. Water, soil, no idea. She lived in Chinatown in an apartment. She didn’t garden, she didn’t go swimming. Where did she get this? So, we tested the vitreus fluid in her left eye; it had balamuthia, so the vision loss in the left eye was likely the thing.

Will Smith: Wow.

Joe DeRisi: So, we grew this thing in lab.

Adam Savage: How fast does it grow?

Joe DeRisi: Yeah, well, you can put some brain cells in there and watch them eat the brain cells …

Adam Savage: In real time?

Joe DeRisi: In real time, and they’re just super evil looking.

Adam Savage: Whoa.

Joe DeRisi: So, that might be the end of it. There’s only a few hundred cases of balamuthia ever reported, and that’s probably because they’re underdiagnosed. There’s no diagnostic for it. You can’t send out for it. No one has a test for it.

So where the science ends? Well, that’s a case where we’re like, “All right well, we can just close the book there. It’s balamuthia.” And we can fold it up and go home. But look, there are no medications for this, but what if there’s something on the shelf, off the shelf today, like an improved drug? So we set up what’s called a high throughput screen. You basically grow balamuthia in the lab, lot of trepidation about that.

“You basically grow balamuthia in the lab. A lot of trepidation about that.”

Will Smith: Achoo! Oh no, the sneeze of doom.

Joe DeRisi: There’s about 2,700 drugs that are either European or U.S. approved, and we threw them at it, and basically there was one, an old UTI drug …

Adam Savage: Fascinating.

Joe DeRisi: There’s one called nitroxoline that actually kills balamuthia really well.

Will Smith: God, so if she had gotten the other …

Joe DeRisi: Yeah, but nobody knew. So we actually just put that out there, just posted it. Maybe some day somebody will try that drug in the context of an infection, because if you’re diagnosed with balamuthia it’s a death sentence.

Will Smith: Yeah.

Joe DeRisi: No one lives. It’s the same with naegleria. It’s very high death rate.

Will Smith: It was always shocking to me, the amoeba stuff, that the thing that you go out to ponds as a fifth grader to find and bring back to the classroom and look at under the microscope — that also will eat your brain.

Joe DeRisi: So, and another example of this, if I may?

Adam Savage: Please.

Will Smith: The nightmares keep on coming here at Joe’s House of Horrors.

Listen to more of Joe’s stories in the full podcast below. Thanks again, Joe!