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The first day I worked as a doctor, I experienced the most intense sense of loss and failure of my entire career. And I began to learn a lesson that I've needed 30 years to fully appreciate.
It is this: Even the most conscientious physician can never care as much as a family member whose beloved child or spouse or parent is dangerously ill. So if we are wise, we doctors and scientists will learn to tap that urgency born of their love to help our patients.
That day in July 1987, I was on-call in the newborn intensive care unit, surrounded by tiny, translucent-skinned infants weighing but a pound, and whose brains still had so much developing to do that they would “forget” to breathe every few minutes and require a gentle touch to restart them.
As I peered with trepidation at these fragile creatures in their temperature-controlled cribs, I received my first patient: not small or immature, but a beautiful, full-term, fully mature baby with peach-marbled skin. Because he had an unexplained lung collapse shortly after birth, his lungs were not delivering enough oxygen to his body, a condition then known as persistent pulmonary hypertension of the newborn.
A call for 'special-ops' research teams led by family members who act as biomedical 'citizen scientists.'
The lung collapse had been corrected, but the baby’s oxygen levels continued to spiral down. My job was simply to manually squeeze a bag connected to the plastic airway inserted into his mouth and windpipe, while the rest of the medical team tried various drugs to open up the blood circulation to his lungs.
I squeezed that bag through the hours of the night. But in the morning, we had to hand the baby’s parents their beautiful child without a pulse or breath. We explained that we had done all we could, but that was of no comfort to them or to us. It was also not true.
Years later, I learned that less than one block away, a few weeks earlier, a clinical trial had finished up at a nearby hospital. The trial had tested ECMO -- extra corporeal membrane oxygenation — which shunts blood through a machine to oxygenate it, for children with the condition of my first patient. Although the trial was successful, the decision to use it as a routine clinical service for patients like mine had not yet been made. There were concerns about just how effective it was, and whether insurance would cover it.
Yet within months, in the very same newborn nursery where my first patient died, ECMO had become the standard of care for such babies. My first patient missed a potentially lifesaving treatment by months. Or by one block.
As bitter and horrifying as this experience was, it is not singular. It happens all the time, and it has happened for decades. When penicillin first became available, it took 14 years before the first civilian patient was treated with it for a potentially lethal childbirth-related infection.
What would you have done if you had been the parent of that baby over 30 years ago, and were told that your child was going to die? What if you knew that ECMO was available but was not going to be used for your child?
Actually, we have a pretty good idea of what some parents might do in this situation. Because in recent years, we have witnessed a growing phenomenon of parents and other family members who act as accelerators of the quest for treatments to help those they love. Not only as fundraisers or public advocates, but as scientific leaders.
Some medical professionals will roll their eyes, but the world has changed: The massive expansion of medical knowledge over the last half-century means that any one expert -- whether specialist or generalist -- knows an increasingly small fraction of the whole. Paradoxically, a single motivated parent can achieve state-of-the-art focal expertise by accessing information online and community resources dwarfing those available to my generation during medical training.
Waiting For No One
I could not even have imagined this parental role until I met Matt Might. He was a fast-rising computer science professor at the University of Utah when his first child, Bertrand, developed medical problems within weeks of birth, including multiple daily seizures and lack of tears.
A 2014 story in the New Yorker described the journey Matt and his wife took in finding Bertrand’s diagnosis: Bertrand was the first human to be diagnosed with a disease-causing mutation in a gene called NGLY1. After the article was published, Matt went on to initiate a research program that has resulted in two very promising drugs for the treatment of his son and others with NGLY1-related disease. This by someone with a total biology education of six weeks in high school.
Matt, now a colleague and friend of mine, was waiting for no one. He contacted experts and biotech companies, brought other patient families into the mix, set up trials, and did so over weeks, not the usual months or years.
When I ask my students how many of our faculty they know of who not only helped define a new disease but also drove the international recruitment of others with the same constellation of findings, they cannot name more than a handful. And among those, not one also found a treatment.
My first conclusion was that Matt was unique, a superhuman freak of insight, energy and persistence. But because of my involvement in the Undiagnosed Diseases Network, I have met other remarkable parents. Martine Rothblatt, who shifted from satellite communications to biotech to treat her daughter’s lung disease. Karen Aiach, who went from financial consulting to founding a gene therapy company to treat her daughter’s deadly genetic disease.
Perhaps these are just exceptional individuals who have risen to the challenge posed by the terrifying afflictions of their loved ones. But for me, as a perpetually impatient physician-scientist, their urgency raises an urgent broader question: Might there be many more like them, who could move medical research at a far faster pace? And has our medical culture stifled them?
Some of the answers can be found in the defining characteristics of these biomedical citizen science leaders. They know that medicine does not have a good answer for their family. They suspect that there is expertise somewhere in the world that might bring them closer to that answer. They are aware that many of the answers they find will not be adequate, but they know they will not stop until they find one that is.
They know that no one feels the urgency to find the answer as much as they do, and they will pour all their free time and often large amounts of their professional time (depending on how compassionate their employers are) to both master the science and serve as general scientific contractor to coordinate all the experts and groups they have engaged. They are principal investigators (a term of art used in academic settings to denote the scientific quarterback) without brakes.
When my own father was dying, I argued unrelentingly — beyond the consensus of most medical opinion and perhaps my unconscious father’s own comfort — for maximal treatment, even as his chances of recovery approached zero. I’ve spoken to parents whose child was hours from death from cancer despite every known treatment but who could not accept — who could? — that impending loss, and wanted to know about other options.
In those conversations, the question concerned the use of existing medical interventions. But what if the conversation were extended to what new cures we could find for a patient? And in the cases where this makes sense, how can we best take the urgency of a suffering family or patient and effectively apply it as an agent to move medicine beyond its current inadequate performance?
Medical Research 'Special-Ops' Teams
I believe we can learn from the Undiagnosed Diseases Network, a network of dozens of institutions that triage and try to diagnose — with remarkable success — patients who have long been undiagnosed and suffering.
At the core of this success is not a new cadre of specially trained clinicians. Rather it’s the just-in-time matching of teams of researchers and clinicians to the specific needs and questions of a particular patient. Example: the case of a young girl with mysterious symptoms ranging from crooked toes to hernias, who turned out to have the misfortune of two rare disorders.
This just-in-time model is not unique, but it does make clear that we have a dearth of these focused, small multidisciplinary teams. I sometimes refer to them as “special ops,” because individually they require less funding and support than the full research teams typically funded by National Institutes of Health grand challenges, and every member of the team is at the apex of their discipline’s expertise.
However, we can’t create such teams for all diseases. How, then, do we allocate them so that even families without super-energetic advocates can benefit from them?
I propose the following: families helping families. Families like Matt Might’s have shown themselves willing to immerse themselves in the science using their common sense and cultivated expertise in biotechnology and pharmacology. These families are not as rare as it might appear, and each city will often have several exemplars.
Moreover, a national effort could bring them together, and help them select teams of scientists and clinicians that could support them. They could peer-review cases for those where they might be of help, and with their examples, encourage others.
Where might funding for such an effort come from? The NIH has shown willingness to fund national efforts such as the Undiagnosed Diseases Network when there is strong bipartisan support. Also, several private foundations have the wherewithal and leadership to at least seed-fund such an effort.
One important note: No family member or patient should be placed in a position where they believe that the professionals will not do their utmost if they do not themselves take the helm. The family special-ops team should be seen as a last resort, and one where success by even the best, the brightest and the most energetic is not likely. But we should accept — indeed, celebrate and support — the family right to try.
To families facing dire medical situations for loved ones, I would say: If your doctors have no good solutions, especially if common sense is telling you that your situation is uncommon, use your personal network and the power of internet search engines to find other families with parallel experience, and do not fear exploring alternatives when the prognosis appears uniformly grim.
If I could, I would rewrite the ending of my first day as a licensed doctor. In this alternate history, I know about the ECMO trial down the street, and tell the parents. They insist on their baby being transferred to the ECMO hospital, and he survives. Today, he is 30. He is grateful to me, and I, to his parents, for helping to save his life.
Dr. Isaac Kohane is the inaugural chair of the Department of Biomedical Informatics at Harvard Medical School.
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