Personalized Medicine - Translational Informatics: Realizing the Promise of Knowledge-Driven Healthcare - page 45

A curative cord blood transplant was performed. Two years later, while not with-
out challenges, Nic was eating real food, playing sports, and generally living his
life, outside of the hospitable and without the excruciating intestinal episodes that
started him and his family down their diagnostic odyssey [ 29 ]. Nic celebrated his
ninth birthday in late 2013.
In 2011, fraternal twins Noah and Alexis Beery had their genomes sequenced to
identify the genetic mutations that were causing severe health problems in both,
though manifesting differently in each [ 30 ]. At age 5 they had been diagnosed with
dopa-responsive dystonia, for which they were prescribed a dopamine precursor.
That treatment had helped with symptoms until the twins were 13, when Alexis
developed a severe respiratory condition. Genome sequencing identifi ed mutations
in a gene called SPR, or sepiapterin reductase, which enables the synthesis of neu-
rotransmitters. This mutation had been previously linked to some cases of dopa-
responsive dystonia. Already taking the dopamine precursor, the twins were
additionally prescribed 5-hydroxytryptophan, a serotonin precursor. Within a
month, this additional therapy resolved the respiratory condition.
In 2005, a woman named Beth McDaniel was diagnosed with a rare T cell lym-
phoma [ 31 ]. Chemotherapy held the disease at bay for 5 years, but in 2010 the
tumors under her skin came back. Her son, a molecular biologist, took a leave of
absence from his job to devote himself full-time to seeking an answer through DNA
sequencing. With considerable effort and resources recruited to the cause, scientists
were able to identify a gene fusion event that was causing signals for T cells to stop
growing to be interpreted as signals to grow, and vice versa. As luck would have it,
a new melanoma drug had been approved that worked by signaling T cells to grow.
The hope was that this drug could be used to cause Mrs. McDaniel's T cells to stop
growing. Beth's response to the new drug was immediate and striking, but unfortu-
nately short lived. Two months later, the cancer was back, and 2 months after that,
it took her life.
One last example is that of Dr. Lukas Wartman, a cancer researcher at Washington
University. When he was diagnosed with adult acute lymphoblastic leukemia, his
colleagues at the university's genomic institute put other work on hold to sequence
his entire genome, both in cancer cells and healthy ones [ 32 ]. Through this exercise,
they were able to identify a causal mutation for which an FDA approved drug
existed. The drug had been approved for use in kidney cancer, not leukemia, but as
reported in the New York Times, was successful in driving Dr. Wartman's cancer
into remission.
It is worth noting that these heartwarming success stories are the exception, not
the rule. In each case, not only were researchers lucky to fi nd a causal mutation,
there was also a known, approved therapeutic intervention to target that mutation.
That is not always the case. In addition, while a tumor sequencing approach is
becoming slightly more common in cancer cases where standard treatment has
failed, this approach is generally used only in special circumstances. In almost
every case, the patient[s] in question knew someone who had specialized knowl-
edge and who worked in cutting edge research organizations. Dr. Wartman was an
expert in the fi eld and worked at a university with a world class genome institute.