Mark is a cop and he lives close to me.  I have had the benefit of living near Mark and enjoying his friendship over the years.  He is solid as a rock.

John is someone that I have gotten to know only over the last 6 months or so.  His family’s story is told in the movie Extraordinary Measures.  Briefly, if you don’t know, his two children had Pompe Disease and he and his family led the charge in the development of the first treatment – which both his children Ryan and Megan receive.  John is now the CEO of Amicus Therapeutics.

Here is a great video highlighting John and his story:

It seems almost inevitable that someone that famous could never live up to expectations.   Can you imagine? A CEO, pioneer, lawyer, Harvard graduate, Navy Seal Intelligence officer, would-be Senator being an approachable guy?

Well, as I mentioned, I have gotten to know John pretty well and am comfortable saying he isn’t normal.  He is amazing.  He is the most soft-spoken, humble, modest and sincere person I know.

About 6 months ago, he mentioned that he was coming to Dallas for a Make-A-Wish board meeting.  He dropped by our house on Friday and spent a whole evening with us.  He invited me up to do a lunch and learn at Amicus.  I talked about life with a kid that has MPS III and about our hopes and dreams for a cure.

A gene therapy solution is on the horizon.  Sanfilippo is a perfect candidate.  For a milder disease, I believe that many people would wait and hope someone else “goes first”.  You see, for Sanfilippo, we have to make sure that all the enzyme gets where it needs to go.  I hope that intrathecal will work, but the jury is still out.  In the meantime, we need to hedge our bets on other solutions to the problem. AAV9-based systemic gene therapy may provide the solution.  The ability of the AAV9 vector to pervasively transduce cells throughout the brain, CNS and PNS (Peripheral Nervous System) makes it compelling.

After our visit to Amicus, John posted this to his Facebook page:

The idea that our struggle would inspire John is humbling.  As for me, I have learned a lesson: don’t assume that people can’t live up to high expectations!  John met and exceeded all my expectations.  He is a man with a strong moral compass, an amazing leader and someone that hasn’t forgotten what it was like to be in my shoes.  Forgetting would be easy to do.  The fact that he would believe in me and consider me his friend? Nothing short of amazing.  John, thanks for being the man you are.

Crowley for President 2016!

It’s too much to hope for a life without pain,

It’s wrong to expect a life without pain,
For pain is our body’s defense.
No matter how much we dislike it,
And nobody likes pain,
Pain is important,
And,
For pain we should be grateful!

How else would we know,
To move our hand from the fire?
Our finger from the blade?
Our foot from the thorn?
So pain is important,
And for pain we should be grateful!

Yet,
There’s a type of pain that serves no purpose,
That’s chronic pain,
It’s that elite band of pain that’s not for defense.
It’s an attacking force.
An attacker from within
A destroyer of personal happiness
An aggressive assailant on personal ability
A ceaseless invader of personal peace
And,
A continuous harassment to life!
Chronic pain is the hardest hurdle for the mind to jump.
Sometimes it is almost impossible to jump,
Yet, we must keep trying,
And trying,
And trying.
Because if we don’t it will destroy.

And,
From this battle will come some good,
The satisfaction of overcomig pain.
The achievement of happiness and peace, of life in spite of it.
This is quite an achievement,
An achievement very special, very personal,
A feeling of strength
Of inner strength
Which has to be experienced to be understood.

So, we all have to accept pain,
Even sometimes destructive pain.
For it is part of the scheme of things,
And the mind can manage it,
And the mind will become stronger for the practice.

– Jonathan Wilson-Fuller

At the gala, I offered my thoughts on how rare patients and Olympians are alike.

1) We both understand epic disappointment.  For a child or family dealing with a rare disease, this is obvious.  For the Olympian it makes sense if we think about the fact that only a few people can win a medal every four years.  I once read that an astonishing number of Olympians said that if a pill existed that would allow them to win gold but die the next day, they would take it.   This was many years ago, so I cannot provide a reference.  However, I think that I understand this kind of bargaining.  There are so many days that I wish that I could take on Reed illness, but that is not a deal that I am offered.

2) There is the opportunity for amazing triumph. Now, for the Olympics, this is obvious — the athletes win a medal or set a gold record.  What does it mean for patients.  Well, we want firsts too.  We want those affected to be the first to survive a disease.  For every disease that is now treatable, someone HAD to be first and that is our only prize.

In speaking with Adam, we discussed one more similarity.  You have to go into the battle believing that you can win, even though the odds are stacked against you.   I, for one, have always had an irrational optimism — but is just how I am wired.

http://www.youtube.com/watch?v=68SMLXAlgP0

Other than when he spends the night at his Nanna’s (one night per week) I sleep with him in his room.

As you can see, tonight he wore his cowboy hat to bed (this was before he went to visit his sister).  When he couldn’t sleep, he went down to (what used to be) mine and Zezee’s bedroom (though my daughter has claimed my spot)  and had some fun and fell asleep with his mom and sister.  His snoring bothered them so my wife asked me to carry him to his bedroom upstairs.  I could feel the warmth of his tired body against me and thought about how much it meant to be with him.

My wife reminded me the other day that it isn’t my job to save him.  Rather, my job is to teach and love him and of course she knows I work hard at doing that.  Still, how could I forgive myself if I didn’t try to help him.

We read stories about people like John Crowley and think, “why not me?”   But for most of us, there just isn’t time.  Time is our enemy and the pace of medicine creeps along relative to pace of the disease in our children.  By the time anything comes, it will likely be too late for my sweet boy and I know it.  That is the toughest pill to swallow of all.

I was born in Oklahoma City as the son of two people getting PhDs in the life sciences.  My father was an immigrant from Iran and my mom was an Oklahoma girl.  Both were in grad school at Oklahoma University.  My father was studying biostatics and my mom was studying epidemiology.  They both ended up teaching in Iran and, after the Islamic revolution, we moved back to the states in 1979.  We moved back to the states, my mom, dad, me at six and my brother at 13.  My mom and dad got teaching positions at Penn in the medical school.  After a short stint at Penn, my mom got a job at Oak Ridge National Lab in Tennessee and we moved again.

By 1982, I was nine years old and beginning to see some issues in my parents marriage.  Their arguments were out of control and there were times when my mom and I would leave to stay with other families.  I was very insecure and was filled with night terrors about my dad.  I lost trust in adult males and clung to my mom in what I recognize was a co-dependent relationship.  My brother was 16 and took a different approach, he turned to drugs and alcohol. I will never forget the morning that I woke up and saw my parents crying after he died in a motorcycle wreck.  All of his potential and their dreams evaporated in a day.

After the loss of my brother, my parent’s marriage took a final turn for the worse ; it couldn’t handle the loss.  They split up but not before my dad attempted to sneak me back to Iran.  I will never forget that night.  We went grocery shopping, me, my mom and my dad.  My dad offered to play some video games with me.  10 minutes into playing games, my dad said nervously “we are out of money, let’s get some change from mom”.  So we went out of the arcade suddenly got into a car with three men I’d never met.  We headed out and my dad said what he was doing.  I freaked out and the men all panicked.  I think they figured out that they would never get me through the airport without packing me in a suitcase so they talked my dad into taking me back.  I, of course, told my mom and my dad just went away.  Now, as a grown man, I have learned to forgive him.  I know now that he just loved me and could not imagine life without me.  It was a misplaced act of love.

My mistrust of men only grew after my dad left and I felt angry with my mom when she remarried.  I felt abandoned and angry with her for putting me in a situation that scared me.  As an adolescent I withdrew and rebelled.  I was a good student up to then but somehow managed to fail 7th grade with 17 F’s.  I wore my failure like a badge of honor and remember smoking pot for the first time that year.  I was lost and out of control and my mom couldn’t help.  Her marriage to my step-dad failed and we moved to a poor part of town.  Though my mom was educated, I was floundering.  I had the wrong friends, the wrong attitude and was headed in the wrong direction.

At 14, I got my first job making pizzas.  “Big Ed” Nuesel made me cut my hair and I worked 20 hours a week for minimum wage.  He was amazing and the first of many male role models in my life.

Mike Fellers, Nigel Tan and me (circa 1987) at Big Ed's

Having a job was a good thing and Big Ed pushed me to work hard.  He wanted me to succeed and the job gave me an identity. I began competitive weightlifting and set the US record for bench press in the 17 year old, 165 lb class.  I am, ahem, more than 165 now and you probably wouldn’t even recognize me from this picture.  However, my life was beginning to turn, I realized that I could do something big and began to believe in myself.  In fact, I learned that perhaps I should be a big believer in my ability to affect outcomes.

As a mediocre student in high school, my choices for college were limited.  I opted to go the University of Tennessee and study mechanical engineering.  Though I had never applied myself, I knew I had an aptitude for math and science. I had coasted through high school, sleeping every day in class.  I would stay awake the day before a test, ask questions during the review and piss my friends off by making an A on math and physics tests.  College wasn’t that easy, but I had learned to work very, very hard.  I made straight A’s my freshman year and thirsted for approval.  I remember telling my mom and looking for praise.  She didn’t understand and said something to the effect of “I will just be happy if you make it through”.  However, I knew something special was happening.  I was driven like never before.  I easily studied 80 hours a week and obsessed over learning every detail about math and physics.  I was determined that I could do something big.  I loved stories about the physicist Richard Feynman.  He was quirky and brilliant and I felt like I shared his obsession with understanding how the world worked.  I hated biology, life sciences and chemisty.  All that felt, to me, like rote learning.  I saw beauty in understanding the world from first principles and constructing complicated machines based on those building blocks.

I will never forget the day that I walked into my advisors’ office and told him my big plans; it was my sophomore year and I wanted to go to graduate school at MIT, Stanford or Cal Tech – I just knew it.  He was someone who I deeply admired, an Iranian man and head of the department.  He informed me that this just didn’t happen for kids like me.  I needed to come to grips with the fact that I went to “state school” and that was were I belonged.  I was angry.  Angry because I felt like he was placing his own limitations on me (he got his PhD at OU) and angry because I knew I was good enough.  I figured I used the same textbooks and read the same material as every undergrad from those schools.  It was just a matter of hard work and work hard I did.  This story sounds bitter but the fact is this guy did me the biggest favor of my life.  He forced me to grit my teeth and double down.  I won’t forget the tears that welled up in my eyes as I studied with gritted teeth, determined to prove him wrong.

Two years later, I was finishing my BS at Tennessee and had maintained a 4.0.  I had done so well that I could help the grad students with their work in fluid mechanics and heat transfer. I took the GRE for general entry into grad school and the engineering specific version so that I could qualify for a fellowship.  I scored in the top 1% in both and reveled in my success after I got an NDSEG fellowship, given to the top 50 science and engineering grads in the country.  It paid completely for my PhD and gave me $20K or so a year for living.  Not bad for a kid from the sticks.

My single mindedness and myopia have served a purpose but they have also had a price.  I can be hard to live with and I don’t really relax at all.  My junior year I got engaged to a girl from my home town.  We were going to marry after graduation.  She was felt so frustrated and neglected my senior year that she dumped me a few months before our wedding.  It seemed like such an awful thing at the time but now I know it was for the best.

I took my fellowship to Stanford where I finished my MS in 9 months.  A year later in grad school, my interest was waning.  It was the late 90s and people were getting rich.  I had expertise in the detailed physics required to cool high power semiconductor devices, a useful niche indeed.  A year into my PhD I burned out.  I didn’t see how four more years of underpayment would benefit me and I left for greener pastures. I left to move to Dallas and work for HP on Supercomputers in 2000.  It was a great job and I learned from someone else that became an awesome mentor, Christian Belady.  He hired me when he was just a “senior engineer” and has now moved on to run all of Microsoft’s computing infrastructure, a HUGE job.  This includes management of all the thousands of people that run the multi-billion dollar investment of hotmail, MSN, etc.  He is an awesome friend and mentor.  He is just another example of the important men that I ahve looked up to in my life.

I was also lucky enough to marry my wife in 2002.  Here is a picture from our wedding

She is so beautiful and just an amazing woman. Our daughter Aziza was born in 2003 and my son, Reed in 2007.   If you have been following along at home, that get’s you caught up but it also gives you the back story.  It tells you who I am and why I act the way I do.  I have told people that I am not brave and it is a fact.  I am scared. Scared that my life is going to fall apart.  Scared that history is repeating itself. Scared that I have seen this before and I know how the story ends. And I am scared that I am not man enough to deal with failure.

I didn’t say it above but you may have figured it out.  I have worked like crazy as an adult to somehow have a sense of control.  A sense that I would be a provide for my wife and children that which was not provided to me: stability and security and I can’t.  My problems are bigger than me.

From the day of my son’s diagnosis, I have toiled to make a difference in his life.  There are days when I am angry but I have no one to be angry toward. So I have woken up each day and asked myself “what can I do today that will be productive”.  Do I need to fly to Washington, talk to someone at NIH, work to raise money for research?? What is it that I need to do?  I have tried hard to find what the “real” problem is.

The science feels so close and it could go either way.  To give a football analogy, it feels like I am about to get tackled at the 1 yard line and after all this I ask myself “how can it end like this?”  When Reed was diagnosed, I set about in a flurry to find SOMETHING.  When there were no answers, I contemplated suicide.  I pictured putting Reed in a car with me and driving it off a cliff.  But I couldn’t do it.  I couldn’t do it because I have a daughter and wife that need me and Reed deserves a shot at life.  And in some cosmic way, I sometimes imagine that this is God’s way of teaching me to depend on myself less and making me humble. They say that struggle doesn’t go away until it has taught you what you need to know.  Well, God, lesson learned – please open a door for us.

Whatever future holds, I have decided that I will give my family the one thing that I can, my love.  I have been so afraid of losing the battle with Reed that I have neglected my health, my wife and my daughter and maybe even Reed.

While I won’t give up hope, I have to rise to the occasion and be the best dad that I can be.  It is only through facing our fears and letting go that I think we can find true happiness.

No more crying and living tomorrow’s sorrows today.

I have heard some of the criticisms of the bill, namely:

1. It exposes the patients to greater risk
2. It completely eliminates any burden to prove efficacy.

The standards for safety would not change.  Safety is established during the first phase of drug trials.  As far as I can tell, I don’t see any changes to requirements for establishing safety for new drugs.

Regarding efficacy, any accelerated approval requires post-market surveillance to prove effectiveness against clinical endpoints.  Initial approval is based on biomarkers.  This is nothing new.

The only thing new would be a change in the rules for getting a biomarker approved.  ULTRA would prevent the FDA from requiring previous clinical data to qualify a surrogate endpoint.  This data just doesn’t exist for many rare diseases.  For diseases where clinical data is not available, ULTRA would ask the FDA to use valid science and our understanding of biology to qualify biomarkers that are reasonably likely to predict that the drug works.

Is this the right choice?  You’re damn right it is.  I do not want to wait until there is rock-solid bulletproof evidence that a drug works before I can treat my kid.  I think that 99% of people who have terminally ill family members feel the same way.  Anyone that says that the system is working is crazy.  95% of rare diseases have NO TREATMENT.  By definition, that is broken.  We need game changing new laws.  New laws that will transform the landscape.

The world is changing.  Information technology enables people to make their own decisions.  Long gone are the days when people had to rely on a single group to “be their voice”.  This is a new world of ideas; A world where each of us can watch congressional hearings on Ustream and don’t have to travel to Washington.  This is a world where ideas spread fast and the grassroots can make their voice heard directly.  When it comes to ULTRA, the rare disease community has spoken.  We want treatment and we want it now.

We thank Congressmen Towns and Stearns for their leadership.  By introducing this bi-partisan bill they have shown that the giving hope to people with rare disease is not a Democratic or Republican issue.  Rather, it is a human issue. Drug development for this under-served population isn’t where it needs to be.  Everybody with a disease deserves treatment.

This upcoming year, a number of patient groups have pulled together to endorse ULTRA, the Unlocking Lifesaving Treatment Act.  It will remove key barriers to enabling accelerated approval for rare genetic diseases.  We believe it will unleash a huge amount of biotech investment and result in many new treatments for those suffering from the rarest of diseases.