Earlier today, the FDA sent a warning letter to gene-testing company 23andme. And then Spacedeck co-founder Lukas Hartmann, aka @mntmn, decided to publish the following story about the pitfalls of genetic testing — the time 23andme claimed to have diagnosed him with a deadly disease.
https://gizmodo.com/fda-may-begin-seizing-home-dna-testing-kits-1471239970
All images from Gattaca.
In the wake of the FDA’s warning letter to 23andme,
I thought that my story might be of value for an English speaking
audience and decided to publish this file that I had lying around on my
computer for several weeks.
Note that I am very much aware of the fact that 23andme doesn’t claim to make any diagnoses. My story serves
to illustrate the psychological effects that a health report can nevertheless have, ultimately driving me
to spend some nights trying to disprove the report in question.
I signed up for 23andme in November 2010. I sent them my saliva and
received a web login to my genome in return. Or at least that’s what I
thought back then. Today I’m a bit more informed and know that what
23andme really does is this: they extract some sort of gene soup from my
saliva and pour it on a so called DNA microarray chip made by a company
called Illumina. These chips are covered with thousands of little
testing probes. A probe is made up of a lump of molecules to which the
matching pieces of my DNA naturally attach. These molecules are designed
in a clever way, so that they light up when a match occurs. Hundreds of
thousands of chemical tests run in parallel on the chip. The result is
an image that is scanned by a computer and compared to a database of so
called SNPs: “snips”. According to Wikipedia, these “single nucleotide
polymorphisms” make up about 90 percent of all genetic variation in the
human genome.
So when 23andme detects a SNP variation in my genome it means that in
a base pair of my DNA there’s a difference from the so called
“reference genome”. We may recall: the nuclein bases Adenine (A),
Guanine (G), Cytosine (C) and Thymine (T) are the basic building blocks
of DNA code. Say I had an A>C SNP: this would mean that I had
Adenosine instead of Cytosine at the corresponding DNA location. This
difference doesn’t necessarily have to be bad. The actual judgement is
derived from statistics, for example: do all the members of a certain
group of people who have the same mutation develop the same kind of
symptom?
To sum it up, 23andme compares hundreds of thousands of scanned SNPs
to their database which they constantly update in response to new
scientific studies and sources. Their website then shows you nicely
designed, ready to ingest interpretations of your genetic variations
manifesting in health risks. But you also learn about more entertaining
topics like heritage (99% European, 3% Neanderthal, .5% Scandinavian).
Everytime they have new updates for “Health Risks” or “Inherited
Conditions”, you’ll receive an email.
Everything went well for a long time. There were no special
surprises. I will probably die from a mix of heart attack and prostate
cancer; nothing special there.
But some weeks ago there was, suddenly, an unnerving update in my
inherited conditions report. I clicked the link and a warning appeared:
you have to specifically agree if you want to know the result of
potentially unnerving, life changing results. I clicked OK and was
forwarded to the result. It said:
“Has two mutations linked to limb-girdle muscular dystrophy. A
person with two of these mutations typically has limb-girdle muscular
dystrophy.”
I let that sink in for a moment. I had never heard of this illness before.
“Some people with limb-girdle muscular dystrophy lose the ability to walk and suffer from serious disability”,
said the page, showing me an image of a smiling physical therapist
treating a smiling patient. What 23andme didn’t spell out – but
Wikipedia – was that LGMD potentially ends with death. The more I read
about LGMD the worse my mood grew. I fumbled with my shoulders and
thighs and didn’t notice any special degradation. I thought, and I
wanted: “This can’t be true. It must be an error.”
It also appeared to me that I had absolutely no idea what the
“technical information” behind the fine printed link on the 23andme
result page meant.
When someone is confronted with a life threatening situation, they
can develop unexpected capabilities. When a nerd is confronted with a
life threatening situation, they read every last site on the web until
they completely understand every last bit of the circumstance. I
downloaded my 23andme raw data and poked at it with a text editor. I
read cryptic articles about genetic engineering and installed the weird
genome analysis tool “Promethease”, which can import, amongst other
formats, 23andme raw data; but in contrast to 23andme it tells you even
the very unnerving stuff. I tried to understand enough of genetic
engineering to understand the source code of my own body. Someone had
found a bug in me and I tried to reproduce it.
Technically speaking, 23andme detected two SNP variations in my
genome called rs28933693 and rs28937900. So I attempted finding out more
about these mutations. When you look up “rs28933693” in SNPedia, a kind
of Wikipedia for SNPs, you’ll find a link to an entry in OMIM (Online
Mendelian Inheritance in Man). The entry features medical study excerpts
concerning some LGMD patients that all had the same so called
homozygous mutation in a certain gene location.
To understand the meaning of this you have to recall that humans are
diploid organisms: they have two copies of each chromosome, one
inherited from the mother, another from the father. A heterozygous
mutation only affects one of the two copies, a homozygous mutation means
that the same location of both copies differs in the same way.
Diploidy is a good thing: it means that I potentially have a backup
of every critical function of my body. So if a piece of my DNA encodes a
critical enzyme and this code is “broken” on one of the chromosome
copies, it could well be intact on the other. If you’re out of luck and
both of your parents are “carriers” of exactly the same mutation, the
inherited condition may manifest in you. This was the case with the LGMD
patients mentioned in the study I stumbled upon. Both of their copies
of the respective chromosome region are mutated in the same (homozygous)
way, which triggers the muscular dystrophy. This very rarely happens,
but it happens.
So now I should be one of those very few?
After researching tensely for some hours, trying to ingest as much
knowledge as I could, I looked closer – into the raw data that 23andme
provided as a download. Yes, I really had two mutations. But they
weren’t on the same gene, but on two different genes. By rare chance,
both of these mutations are statistically linked to LGMD, but to two
different versions of LGMD. So I didn’t have a homozygous mutation, but
two unrelated heterozygous ones. The web programmer at 23andme had added
those two mutations together into one homozygous one in their code. And
so the algorithm switched to red alert.
I sent a support request to 23andme including my research and
conclusions (this would be called a “bug report” in software
engineering). After a few days of waiting, 23andme confirmed the bug and
apologized. So the bug was not inside of me, but in the algorithm. An
algorithm can be fixed easily, unlike my genetic code.
My inherited condition page now says:
“Has multiple mutations linked to limb-girdle muscle dystrophy, but
they are in different genes. A person with such mutations typically does
not have the condition, but can pass the mutations to offspring. May
have other mutations linked to limb-girdle muscular dystrophy (not
reported here).”
I can live with that. For quite some time, I hope.
This article by @mntmn originally appeared on his blog, and is republished by permission. More about Lukas Hartmann:
“I am 29 and live in Berlin where I studied Communication in Social and Economic Contexts, but I programmed since childhood and still enjoy doing that for a living. I like computers, coding, art, music, film, media theory and cyberpunk.
In March 2013 I co-founded Spacedeck together with Martin Güther, where I work as managing director and “CTO”. Spacedeck is a web service that brings real-time visual collaboration to the creative industries. It’s also free for educational use.
Before that and while studying I co-founded the now defunct startup “aka-aki” which was a (in Europe) fairly successful mobile social network with my friend Gabriel Yoran, founder of Steganos, among others. (it’s still quite google-able, was active from 2007-2011).”
