It is night. My wife and I are emotionally drained. The Tess webpage is live and it's getting shared. While happy that it's gone viral, we're reeling from how much mental effort it's taken to make the jump. To really try. To not give up.
So there we are, reading just before bed, knackered. Barely able to mumble to each other that we should switch off the lights and hit the hay.
Then my phone buzzes on the nightstand. I pick it up.
There's a new email in my inbox. "To whom it may concern," it starts off. "My name is Mike Fountain and I conduct research at Baylor College of Medicine in Houston, TX. I believe I have some answers for you and Tess."
Why does the message say "To whom it may concern," instead of "Dear Bo and Kate"? Because we'd set up the Tess page on portlandrootsmedia.com, and thus all emails were sent to the general email account for that page.
So this guy doesn't even know our names. He only knows Tess's name.
His message continues. "I work with this gene and these symptoms and will publish our work soon. I know of other patients."
I know of other patients.
And he gives his contact info.
I practically drop my phone out the bedroom window, frantically typing my response. We schedule a call with him.
The next day, we're talking to him. Mike Fountain at Baylor. We can't get our heads around this idea. We refuse to believe it. There has to be some mistake. Like, maybe we'll tell Mike more about Tess and her symptoms, and he'll say, "Ah. Sorry. Not the right symptoms. Not the right gene. Sorry to have bothered you."
But that isn't what Mike Fountain tells us. There are seven kids that he knows of. Seven other patients. Mike's been working with a doctor at Baylor, an MD PhD, a researcher and professor of molecular and human genetics named Christian Schaaf. And their study is all about USP7. The exact gene where Tess has a mutation.
Mike tells us about the other seven. They are all older than Tess. She would be the youngest. The oldest is thirteen. They're from all over the world. Some in the US, some in Europe and Asia. Of the seven, there are two girls, five boys. They all have developmental delay and intellectual disability. Which Tess has. Several have hypotonia, or low trunk strength, which Tess also has.
Since Tess is the youngest, our conversation with Mike is a welcome but scary glimpse into the future. After all, the oldest patient in his study is thirteen, eight years older than T. We're about to hear what could happen with Tess in the next eight years of her life. How does that thirteen-year-old communicate? Can she feed herself? Does she have a social life, with friends she can recognize and ask for by name? Is she happy?
We want to know all this stuff, but at the same time we feel a little sick about the prospect of knowing the answers. For all we know, Mike is about to tell us that a fatal condition affects USP7 kids. A condition that can't be fixed. Mike could possibly say that it surfaces at age twelve, and the family of the thirteen-year-old is preparing to say goodbye.
Mike asks whether Tess has seizures. In the early days with her, when she seemed completely checked out, we'd theorized that maybe she was having seizures all the time. Not the grand mal kind, the ones you may have heard about that can make the entire body shake, but a more subtle and hard to detect kind, that can incapacitate somebody and you don't even know it's happening. As a result, we've had her tested for seizures a bunch. All tests have been negative. "You might want to keep an eye on that," Mike says. "Most of the seven have seizures."
He has similar questions about autism. Is Tess autistic? Man, I wish we knew. There's no blood test for autism. Instead, doctors look at behavior and development. And Tess is so delayed with speech and social stuff that she's never been tested. We don't even know if she can be tested using traditional methods. "Keep an eye on that too," Mike tells us. Nearly all of the seven have some form of autism, turns out.
He asks a ton of other stuff about Tess. We tell him about her CVI, or cortical visual impairment, the visual-processing issue, and our suspicions that she has an auditory processing issue as well. We talk about her loving and cheerful nature, her voracious appetite at meals, her tendency to bite when she's pissed off.
In the end, it's a match. We are so thrilled that we are laughing and crying at the same time. Mike Fountain is satisfied that Tess's symptoms and mutation line up with his patients. He's certain that Tess belongs in this group of seven. Now there are eight.
The most mind-blowing thing about connecting with Mike Fountain and finding this match is that it only took about twelve hours. We created Tess's page on the morning of Wednesday, August 12th, set it loose on Facebook and Twitter, and literally that same evening, the night of the 12th, Mike had found it and emailed us.
Once we'd talked to Mike, he told us how he had discovered us. It wasn't on Facebook or Twitter. It was on Reddit. Reddit, in case you don't know, is another network, where registered users can post stuff. It's essentially an online bulletin board. It differs from Facebook and Twitter in that it sorts its content. It uses these things called subreddits, and you can search subreddits by category. So if you're into My Little Pony and smoking weed, or photos of exceptionally legible penmanship, or articles that are so ludicrous they sound like they're from The Onion but they're actually real, there are subreddits for each of those interests.
Now, my wife and I aren't even on Reddit. I don't even know much about it, except that most of my friends who are into science are on there a lot.
And it turns out that there's a subreddit for genetics: r/genetics. And it's there that Mike discovers Tess. Someone has posted the following message: "Hi r/genetics, need your help. I have a little friend who has a mutation in the USP7 gene and we cant figure out her diagnosis despite tons of genetic testing. We're looking for others like her - can you point us in the right direction?"
Mike Fountain isn't on Reddit either. But a woman he shares a lab with is. And that woman showed the post to Mike and said, "Isn't USP7 the gene you work with?"
So who posted to Reddit? I tracked down the original post and it's from someone with the username "Oddjobpanage." That user has no photo and no identifying information. Nor can I glean anything from his or her other posts. We've since learned that Oddjobpanage is a guy in his 30s named Harry Roman, a friend of my sister Eve and her husband Mac in Brooklyn. We've met Harry and hung out with him a few times, but it's been years since we've been in touch with him. Probably six years or so. So Harry--Harito--I can't really express how grateful we are that you shared this. That you got it to a gal who shares a lab with Mike Fountain. Thank you so much.
Now, I know what you're probably wondering. Why didn't I tell you this before? If Mike Fountain got in touch within twelve hours, and if we've known about Mike and his study for over a month, why the hell did we wait?
Well, we had to. Here's the thing. From that very first email, and in every phone call since then, Mike told us to keep this under our hat. He and Dr. Schaaf have been working on a paper about the seven USP7 kids, and it was due to be published on September 11th. Until it got published, it had to stay top-secret. If word got out, if I talked about it on my podcast or blog, if we splashed it all over social media, Mike said it could jeopardize the publication and even keep him from reaching other families. So he made us promise not to breathe a word to anyone. We wanted to tell you. We really did. We wanted to thank you. We wanted to give Harry Roman a giant virtual bear hug, and perhaps an appreciative noogie or two. But we couldn't. We promised.
Well, Mike Fountain's paper came out last week. He's one of literally nineteen authors on what turns out to be a 14-page paper, including footnotes. The paper appeared in Molecular Cell issue 59, dated September 17th. I printed it out and pored through it, with Wikipedia by my side. Didn't help. I still mostly don't get it. Even its title is hard to sift through: "USP7 Acts As A Molecular Rheostat to Promote WASH-Dependent Endosomal Protein Recycling and Is Mutated in a Human Neurodevelopmental Disorder."
USP7 acts as a rheostat? Isn't a rheostat one of those circular knobs on my wall, the kind I can turn in order to dim or brighten my lights? As far as I can tell from the paper, that's sort of what USP7 does. I might get this wrong, but here goes. Okay. Humans need to recycle proteins. The recycling happens in our cells. If people's cells don't do this recycling right, those people can get diseases. And USP7--the gene where Tess has a mutation, and where all of the seven have some kind of issue--acts as a rheostat to make the recycling happen properly. USP7 is like the rheostat that controls your lights, in one key way: it allows precise fine-tuning within those cells, so the protein recycling happens juuuust right. And what Mike Fountain and his colleagues have concluded is that, if you have a disruption in your USP7 gene, you can't recycle proteins right. You wind up with a neurodevelopmental disorder. Like Tess and like the other seven. You have intellectual disability and probably autism and seizures.
With me so far? We're almost done. Hang in there. The paper talks a lot about a certain protein called WASH, as in what you do to your clothes when they're dirty. The USP7 gene--the rheostat--controls how much WASH activity there is. If a cell gets too much activity from the WASH protein, it's a problem. And same if there's too little. That's where the protein recycling can go haywire. It's gotta be just right. And in all this talk about the WASH protein, the final sentence of the paper is the one that makes the most sense to me. It shouts out to me, almost as if the rest of the article is one of those redacted CIA documents from the Cold War, where every single line is blacked out with a Sharpie, except for one sentence, the one that's escaped the censors. The final sentence says this: "Finally, our results suggest that chemically activating WASH in these patients may have therapeutic potential."
In other words, if the USP7 rheostat is busted, maybe you can add WASH to these kids. Figure out how much they need, and give it to them. We don't know about things like lifespan. There's nothing in the paper to suggest an early death from a USP7 problem or a WASH problem. But there may be something we can do. Some type of therapy that could help Tess.
What happens now?
I gotta tell ya, Mike Fountain and his mentor Dr. Schaaf are both pretty juiced. This wasn't a one-shot deal, where they publish this and then hang up their guns. This is only the beginning. The syndrome doesn't have a name yet. For now, they're calling it "USP7-associated genetic disorder." Tess is going to join this group of patients. She'll be part of the next study, and it looks like everybody wants to get started right away. Mike has already put us in touch with another family, one who was part of this study. Our families have started emailing each other, comparing notes on our kids.
And we need to find more patients. Mike's asked us to lead that effort. To use the podcast and the blog, and get more shares, and find more people. He can't really do it. He needs us to do it. It's good to have eight patients, but they need more. And we know they're out there.
Please share this. You've done it already, and my wife and I are so, so grateful to all of you. But keep doing it. This is what social media is for. This is what Matt Might had in mind when he gave me his instructions for erecting the internet beacon. Please share the podcast episodes and the blog posts. Share Tess's page. Tell everyone you know, even if you don't think it'll help. Tell your hairdresser. Your mail carrier. Your accountant. The guy waiting at the bus stop with you. The kid making your sandwich at the deli. Everybody. Everybody you talk to and email with and Facebook with and tweet at. You never know. You never know whether a dude named Harry, who you haven't seen in six years, who you barely know--except through his beat-heavy Spotify playlists--will turn out to be the one to make it all happen.
There are families out there. Their kid has intellectual disability and low trunk strength, with signs of autism, maybe. They're in the dark, this family. They don't know how to help their kid. They've seen a million specialists, and they have no name for what's going on. Perhaps they've mapped their kid's genome and know about USP7, but they're ready to throw in the towel. To shrug and say, well, we'll never know. Help them find us.
Tess's genetic mystery page (UPDATED): bit.ly/tessmystery
Press release about how we found the genetic team in Houston: click here