March 27, 2017 - 23:29
One of the articles that we read for class this weekend reminded me of a The New Yorker article published in 2014 that asks the question: what do you do if your child has a condition that is new to science? This article follow the medical journey of Bertrand Might, son of Matt and Cristina Might, who was discovered to have a rare, genetic disorder that was not characterized or known to clinicians at the time of his diagnosis. The process of his diagnosis was long and arduous with many wrong-diagnoses along the way.
As the Mights started visiting clinicians, researchers, and doctors frequently within the first year of Bertrand’s life, they saw firsthand how competitive research science sometimes works against the families that are in need of any treatment options available. They reported that “experts” they saw would often tinker with the medical abnormalities that Bertrand presented, but after their hypotheses were disproved by further testing, they would grow frustrated with the situation and tell the family that the medical questions at hand were not within their expertise and refer them to someone else. To often this is the case in rare disorders.
Finally, genetic sequencing was able to reveal differences that occurred in Bertrand’s genome compared to his parents. One of the candidate genes for the medical condition that Bertrand’s genome sequence revealed was a mutation in the NGLY1 gene. This gene is responsible for producing an enzyme that clears sugary waste products from cells. Since this is an enzyme that is needed in all cell types, the effects of it on all of the biological systems are very widespread. After a series of tests by more specials, it was confirmed that Bertrand had a new glycosylation disorder that was never before seen. It was later discovered that Bertrand’s genetic mutation was the result of two different allelic NGLY1 mutations in his parent’s genome, he had a 25% of inheriting both.
However, Bertrand’s medical journey did not end with his final diagnosis. They were not allowed to offer or provide treatment for Bertrand’s NGLY1 disorder until there were other documented patients. It is extremely hard to find other patients that have a similar, very rare genetic disease. Countless medical journals are published with a sample size of 1 or 2 patients, but rarely they are remembered enough to be referenced years later. However, in the age of online documentation and genetic sequencing, the possibility for quickly diagnosing and revealing rare genetic disorders is sped up. But, unfortunately, researchers are now increasingly hesitant to share information on patients with rare disorders in order to protect funding options and to make sure that they are able to get the most credit possible for their work. Additionally, some claim that “if you want to be uncharitable, you can say that researchers use that concern about privacy as a shield by which they can actually hide their more selfish motivations”, especially when the careers of these researchers are on the line and the field is as cutthroat competitive as it has ever been.
However, Bertrand’s situation was a lot more pressing; the clinicians estimated that he had only months left to live if medical intervention did not happen soon. Coincidentally, Matt Might was widely famously on certain spheres of the internet after a published schematic humored Ph.D. mentors and students all over the world a few years earlier. The Might’s were incredibly lucky that Matt’s prior internet fame among many academics in all fields combined with his rising credibility in internet forums for computer programer’s meant that anything he published was quickly reposted on message boards all over the internet. A very descriptive medical post, called “Hunting Down My Son’s Killer”, detailed all of Bertrand’s prior history and current diagnoses and was posted it online on May 29, 2012. The first few lines read: “I found my son’s killer. It took three years. But we did it. I should clarify one point: my son is very much alive. Yet, my wife Cristina and I have been found responsible for his death”.
Only eight days after this was posted, it found its way into the hands of Matt Wilsey. As cited in the article read for class, “Tomorrow’s children”, Matt Wilsey went on to have a daughter, Grace, with also an equally complicated medical history as Bertrand. Prior genetic testing on Grace suggested a NGLY1 candidate gene disorder, however, this was disregarded because they were actively pursuing other rare genetic disorders. At face value, it did not appear that Grace’s phenotype matched Bertrand’s, but two seemingly small symptoms compared perfectly: both children did no produce tears and seemed to be immune to common colds and illnesses.
Then, a breakthrough: “On March 19, 2013, Bainbridge sent the Mights an e-mail. He told them that he believed he had identified a second case of Bertrand’s disorder, and that Matt’s blog post had been instrumental in his finding it. The next day, the Mights received an e-mail from Matt Wilsey. ‘I wanted to connect with you directly as you have heard about my daughter, Grace,’ Wilsey wrote. ‘We are so thankful to find you.”’ Thirteen months after the published blog post, 9 international cases of NGLY1 patients were identified.
With therapy and with beginning stages of a clinical treatment, Bertrand started to show improvements. His coordination started improving, he became more verbally expressive, and he was taken off his restrictive diet and seizure medication. Another rarity in this case: much of the money that was funneled into further investigation of this genetic disorder came from the families themselves on an order of hundreds of thousands to millions of dollars, since both families were fortunate enough to family money to rely on.
It was claimed that the greatest challenges in the collaboration between the 33 researchers and clinicians was determining the order of the authors on the final paper. Does this culture of hold back further research and prevent advancements that could potentially mean life and death for some patients?
http://www.newyorker.com/magazine/2014/07/21/one-of-a-kind-2