If Not Us, Then Who? A Letter to Henri Termeer

Barbara Handelin, co-founder of BioPontis

Rare disease patients’ organizations, scientists, genetic counselors, patient advocates, and business executives who worked in the pioneering days of Genzyme/Integrated Genetics are still recovering from the recent and sudden loss of Henri Termeer, founding CEO. The wake of this loss washes us in memories of a rare company – family, really – where a culture of personal responsibility and commitment formed us. Henri provided resources – financial and otherwise – with a principled statement: if you have the knowledge and capabilities to turn science into medicine - diagnostic or therapeutics – for patients with a rare disease, then you must match their courage to live with their humbling, merciless conditions, with your personal fortitude to take risks, apply your skills, and keep believing in the eventuality of being able to relieve their suffering.
Below is a letter sent by Barbara Handelin, co-founder of BioPontis to Henri just before his sudden passing in May 2017. It is not known if he had an opportunity to read it.
Dear Henri,

Recently, we, at BioPontis, were scanning the field of research projects that could be the basis for new drug discovery programs in rare diseases affecting the brain and peripheral nervous system. Among these was a novel project addressing Spinal Muscular Atrophy (SMA); reading about the progress in SMA, I was lurched back in time to 1992 when a family affected by this rare catastrophic disease inspired members of a different team of scientists ­- in the genetic diagnostics lab at Integrated Genetic that you had acquired into Genzyme. During the years 1987-1992, we had supported research efforts at Columbia University to find and clone the gene causing one form of SMA.
By 1992, the research team had not yet cloned the gene, but had succeeded in finding very close markers to it such that we could trace the mutant form in families with an affected family member. We immediately transferred these markers into our clinical lab to prepare for carrier and prenatal testing capabilities. Shortly before we were ready for our ‘commercial launch’
I received a phone call from our colleagues at Columbia because one of their research families was in an upsetting and unplanned situation.
Parents of a baby girl with SMA, who had died just a few months previously, found themselves unexpectedly pregnant. In their spinning grief and exhaustion from the trauma of birth-illness-death of their little girl, they now were in desperate hope for information about this pregnancy. Could/would Integrated Genetic perform a prenatal test for them was the question, knowing that we had barely qualified our systems/markers? 
As clinical lab director, I secretly hoped that we had an ‘out’ as I asked if there were any tissue available from their recently deceased baby?  The genetic counselor said she wasn’t sure but the mother had asked to speak with me directly about that.
The phone call I had with this courageous woman and mother stays with me still -  she confessed that the only remains of her baby was the skull cap that she had worn as a neonate in the hospital; which she thought had some scalp skin and hair stuck in the soft fibers. This was all she had left of her baby.
I told her that it was long, long shot that we could extract enough DNA to do the testing (this was dinosaur days before cheek swabs etc). More sadly, of course, we would destroy even the baby cap in the process.
She said go ahead. A Sophie’s Choice.
The safe position for us would have been to decline to take this case- fear of liability, error, harm to the unborn, to the parents -  all good reasons not to take this on. But in the environment of commitment to carrying out a duty to do a job because you are among a few – or only -  with the capabilities to carry out the technical work, we saw only one choice. Henri restated this just in January 2017 at JP Morgan where he reminded investors and executives that once you start on the path of providing critical medical products/services to a vulnerable, rare community of overlooked patients you have made a permanent promise to them that they can rely on you to do your best to provide that medicine.
I huddled with our lab team to ask who wanted to be the technician to do the work and we labored over our protocols for DNA extractions to find every step where we could capture any extra DNA and minimize any loss. The little pink cap arrived by FedEx and we took the leap of faith.
We captured enough DNA to do exactly ONE run of our markers in the family study. Our QA/QC protocol required two, duplicate, runs. Again, the unsung hero technician worked with careful hands and laser focus to establish the marker pattern in the parents compared to that SMA-affected baby’s DNA that would allow us to track their SMA gene variants in their ongoing pregnancy.
A week or so later we received a standard amniocentesis sample and for a third time our technicians walked the razor’s edge. No room for error. No way to recheck results.
The fetal sample revealed that this baby would not be affected with SMA! I made the call to the mother and father directly -  an out of protocol experience once again.
As my signature went on the written report that day I held our collective breath, that we might not be in error in our prediction. We waited for the following 5+ months with many distracting family studies for Duchenne muscular dystrophy, Cystic Fibrosis, and Huntington’s Disease, but with an anticipated approximate birth date in our minds and hearts. Sometime after that date, the mom sent us a thank you card with a picture of their new little girl and a report from the geneticist on site that this baby had none of the neonatal signs of SMA that her sister had shown. Later we would confirm our genetic marker findings in a blood sample from their daughter. There were quite a few tears of relief and joy that day in our corner of the building.
Henri, you didn’t know about this case until sometime much later – but you were present in the process and the choices that we made.
We had met the courage of these frightened parents with our own – knowing it was the only choice we had. But that was 25+ years ago! 
Today the gene diagnosis of any genetic disease is available in many labs around the world. And the first therapies addressing the specific deficiencies of a handful of rare genetic diseases have been created to bring relief to awfully sick patients and their families.
Thank you, Henri, for your commitment to innovating new financing mechanisms and standing firm on taking all measures to bring effective treatments to patients. It is a commitment that walks on in many of us who walked those sometimes scary and despair-invoking halls with you.
But Henri knew that this was just the foundation. We must continue to push for new financing mechanisms and drive science with urgency and creativity to solve drug discovery problems for the 10s of rare diseases and the 100s and then the 1000s at a time if we are to truly meet our responsibility as scientists, business folks, and regulators.

If not us, then who?

Contributions to this post were made by Dr. Barbara Handelin, BioPontis Co-founder and Advisor. Dr. Handelin is a veteran entrepreneur and molecular medical geneticist who has pioneered the responsible application of genetics to clinical medicine over a 20-year career.
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