A very public letter to my daughter, for her 17th birthday

Dear Rose:

You are about to turn 17 years old. As I think about that, I realize how happy I am to be your father. It is such joy to have watched you become who you are: a scholar, a skilled equestrienne, a person of insight and wit, a caring friend to others, and – yes – a young woman who lives with cystic fibrosis.

We have come so far from the days of Rose the failure-to-thrive baby, literally saved from starvation at five months of age when a medical resident thought to give you a sweat test. You are most assuredly not failing to thrive now.

But there is a part of me that is very sad as your birthday approaches.

You are doing a good job of taking care of yourself – and, as you know, it is no easy thing because your CF is with you all the time, usually claiming well over an hour every day for physical therapy, inhaled medication, and all kinds of other annoyances. There have been challenges and setbacks – and, you probably remember, during one such time over the summer you said: “I’m doing the best I can, Dad, but let’s face it – I’m gonna die of this eventually.”

My heart ached to hear you say that. “You’re wrong,” I blurted out, in the moment. I still think so. Here is why.

This is not a matter of blind faith or hope. It’s a matter of science – and, in particular, of extrapolating the measurable scientific progress that has been achieved, not just over the 70 years since CF was first identified but within your relatively brief lifetime itself.

Not long after you were diagnosed, we found out that you have unusual CF mutations: the one known as 621 + 1G > T on your mother’s side and N1303K on your dad’s. (Most CFers, as you know, have at least one copy of a mutation known as 508Fdelta). Back in 2002, this didn’t matter much; the latest breakthroughs were Pulmozyme and Tobi – drugs that help ward off the effects of CF on your lungs.

Then the Cystic Fibrosis Foundation (CFF) and its partners in the pharmaceutical industry hit paydirt – in the form of three so-called “modulator” drugs (Kalydeco, Orkambi and Symdeko) that treat the underlying cause of the disease: the failure of a particular protein to do its job in each of your cells, to allow chloride (and thus salt water) to pass in and out of those cells.

Unfortunately for us, those modulator drugs have so far helped mostly just people with at least one copy of the 508Fdelta mutation. You, it turns out, are something of a poster child for what has become known in the CF world as “rare and nonsense” mutations. And in your lifetime, cutting-edge CF care turns on what specific CF mutations are in your personal genome.

A piece of good news is that the CFF’s drug development partnerships – referred to by the Foundation as “venture philanthropy” – were not just a breakthrough when it comes to how a disease-fighting charity can meet its goals. With respect to the modulators, it was literally paydirt: In 2014, the CFF cashed out its rights to future royalty payments from the drugs and pocketed a cool $3.3 billion.

What is the CFF doing with all that money? In large part, the Foundation is figuring out how to cure CF in people with rare and nonsense mutations. That’s you.

In particular, three years ago, the CF Foundation did something truly radical. It took matters into its own hands.

It turns out that what venture philanthropy did for drug development the CFF Therapeutics Lab does for research breakthroughs at earlier stages in the process. I am talking about things like genetically altered stem cells, or chemical compounds that can suppress the effect of nonsense mutations, or new assays (systems for testing the effects of new chemical compounds) other innovations that fall under the category of “intellectual property.” When that intellectual property belongs to the CF Foundation, because it was created at the Foundation’s own lab, the CFF can act on those breakthroughs with the kind of speed and efficiency you need as a person with CF.

Well, the CFF figured it could just give it away – to drug companies and other enterprises willing to bring these innovations to market – if the Foundation opened its own lab and developed the intellectual property itself. Thus was created the CFF Therapeutics Lab in Lexington, Massachusetts.

Earlier this year, soon after finding out that this CFFT Lab is ground zero for doing something about people with nonsense and rare mutations, I discovered that every fall the CFF does a tour of the facility for key people in the CF community. I don’t really think of myself as such a key person, but when the invitation came I did not hesitate. I just put the date on my calendar.

Boy am I glad I did that. My visit to the CFFT Lab on October 1 was like a free and effortless trip to the summit of Mount Everest. Much of what I saw was unfathomable – what do I know about microbiology or genetics, after all -- but everything about the vista was breathtaking.

Even though I skipped out of math when calculus set in years ago, and figured that English majors didn’t need college-level microbiology, the benefits of the technology being employed at the CFFT Lab were obvious. For example, there’s a $400,000 machine that uses robotics to process minute quantities of chemical compounds. When you can test 10,000 such compounds a week – “high throughput screening” is the catch-phrase – success is inevitable for the same reason that 10,000 monkeys typing will eventually produce a Shakespeare play.

Likewise, just a couple of benches away, there is genetic sequencing technology that can plow through the human genome many times faster than the 15 years it took to map the genome for the first time. This will pave the way for using gene editing, or gene therapy, to restore the effective functioning of that defective cellular protein. Just a few feet away from all that is a whole lab that is using tissue from CF lungs (swapped out via lung transplants) to figure out if implanting healthy “stem cells” – or removing lung cells, repairing them, and replacing them – will turn CF lungs into healthy lungs.

Those are just some highlights I was able to grasp as a non-scientist. As a liberal artist and CF dad, what really blew me away was the people who work in the CFFT Lab.

My new favorite friend at the CFFT Lab is Dr. Hillary Valley, a 2006 graduate of Concord High School – which is just a few feet away from my office in New Hampshire’s capital. You and I, Rose, were already five years into our shared CF odyssey when Hillary was heading off for her freshman year at the University of Wisconsin – and now she’s a PhD microbiologist who works to cure CF via gene editing. Like the other young scientists whom she works alongside at the lab in Lexington, she was drawn to the CF Foundation because of the resources, the energy, and the creativity the organization brings to its endeavors.

Likewise there was Dr. Jed Mahoney, who leads the stem cell biology group at the CFFT Lab. Jed went all rapturous as he was showing off color images of lung cells he’s been messing with. Like his colleague Hillary, he was lured away from other endeavors and onto the payroll of the CFFT Lab because he resonates with the Foundation’s energy, passion and the commitment. Who doesn’t want to play for the team that is headed to the World Series?

When you ask these young scientists why they have dedicated themselves to curing cystic fibrosis they always say: “It’s the community.” They’re talking about us, the CF families. I think we owe them everything we can do to prove they made the right choice for the right reasons, because there are any number of other things these talented PhDs could be doing with their scientific acumen.

We owe others as well. I owe people like the sportswriter Frank Deford, who held his little girl’s hand as she died of CF in 1980 – and then spent the rest of his own life helping to lead the CF Foundation. You, I think, owe people like Rosemary Quigley. She made it to 33 before dying of cystic fibrosis in 2004.

Maybe you had a life like Rosemary’s in mind when you mused that you will inevitably die of CF – she, after all, graduated from law school, clerked for a federal appeals judge in Maine, and became an accomplished medical ethicist. But consider what Rosemary herself wrote about her situation not too long before her death: “I am discouraged by people who confer admiration on my most basic accomplishments; I seek supporters who never think I have done too much, who will push me further for as long as possible. I focus my spirit to outlast my withering body.”

Reading stuff like that, as the dad of a little girl with CF, I assumed that when you got old enough to understand your situation fully you would see it as I see it. I thought you would want to lean into this CF thing, not because you are lucky to have this disease – it is most assuredly not a blessing – but because fate has tethered us to one of the noblest and most successful human endeavors in history.

When you made clear that you didn’t automatically embrace my boundless and evidence-based optimism, I felt miserable for a few days. Then I sought help. I’ve made some very smart friends in the CF community, among them my fellow members of the board of our chapter of the CF Foundation.  I reached out for their advice.

One board colleague, a young woman with CF who is just a few years older than you, said she likes feeling connected to “the big march to victory” but, she added, on her own behalf as well as yours: “A lot of times we are just tired.” 

Another board colleague – a mother as well as a daughter – had this recommendation:

 “Continue to relay to her your excitement about research and opportunity and leave room for her to share that she needs to view this skeptically and be prepared for it not to work.  You are a dad whose own biology contributed to her having this disease, so you need to believe that science and your efforts to aid it will have an impact. She is a kid who knows that despite science she will continue to suffer serious health setbacks and that her life may be cut short by CF.  Your experiences of this disease are different and that is just the way it is going to be.” 

Okay.  It’s easier to be a militant CF heterozygote like me, with N1303K on his vanity license plate and the CFF pin on his lapel, than it is to live with CF every day. I get that. But I beg you to see what I see – a trajectory of scientific progress that means you are likely to outlive your dad by many years and ultimately die of something other than cystic fibrosis.

Yes you will get tired.  But when you are tired, we will lift you up.  Not just me, but all of the people, living or dead, whose work and thoughts I have mentioned here.

Please try live your life with the understanding that you might not have to die of this disease. It has been my good fortune to learn about and sometimes to meet so many remarkable people who have been connected to cystic fibrosis. But none have been as remarkable as you -- and I so look forward to many, many more of your birthdays.


Your Dad

[P.S. to my friends, and Rose’s: If you really and truly read this whole thing, you might take pleasure in connecting with our family’s CF story by donating to our Annual Fund campaign that raises money for the CF Foundation. Just follow this link if such an opportunity is of interest. And thank you to my friend Hugh Montgomery for the lovely picture of me and Rose.]