Thursday, March 15, 2018

I Packed My Bags Last Night, Pre-Flight

So I WAS going to write about brains all week and we were going to have fun talking about this zany organ in our heads, but then something much more important happened that I feel a need to address immediately.  NASA issued a press release of the findings of a study on twins Scott of Mark Kelly, looking at a variety of biological measures after Scott returned from a year in space, using his identical twin brother Mark as a control.1  The popular press has really loved this story, and it's found its way, in some form or fashion, into a variety of news outlets, many of which are boldly proclaiming that a year in space permanently altered Scott's DNA2 and that he and Mark no longer have identical DNA.3  

These stories are, in large part, borne of miscommunication, misunderstanding, or somewhere in between.  The truth is that 1) 93% of Scott's DNA did not return to normal, and 7% of his genes have not been permanently changed, 2) if you want to claim that the Kelly brothers are no longer identical, then they never actually were.  So what happened here?

First, the study design.  This study looked at a lot of things- immune response, cognitive skills, the selection of tiny organisms living in the gut, and genome sequence at several different time points: before Scott went into space, while he was in space, when he got back, and then a follow up several months later.  We would expect to see some changes in Scott, just because things are going to change over the two years the study was conducted regardless of a trip to space, but we can compare his changes to Mark's changes to see if they're substantially different.  

 Cells need to make copies of their DNA every time they replicate, and it's actually a really complicated process.  We like to think of our bodies like with think of computers, and thus copying the instructions should be like copy over exact copies of files, but the reality is, we are SO not like computers.  To copy double-stranded DNA, the strands first need to be separated from each other.  This is where you get the world's best pick up line: "I wish I were DNA helicase, so I could unzip your jeans".  DNA helicase is the substance that separates those two strands.  Other substances, called DNA polymerases, locate "start" signals in the DNA code, latch on, and start adding new blocks, with the separated strand of DNA serving as a template for what to add.  You end up with two copies of the DNA, with half of each copy being from the original strand.  

This process is actually incredibly accurate.  There's only a mistake about 1 out of every 1,000,000,000 building blocks added.4  The problem is that we add a lot of building blocks.  There are 3,000,000,000 building blocks in the human genome,5 you build two strands at a time, which leaves room for 6 mutations every time a cell replicates.  Factor in that a cell divides 50-70 times over the course of its life,6 and multiply that by the fact that there are 37 trillion cells in the human body,7 and, well, that's a lot of mutations, that happen every day here on Earth just because of whoopsies.

So a few things here.  First, if Scott Kelly really DID have 100% of his DNA change, as the 93%-7% figure seems to suggest, he would be dead.  It's unclear if the original release meant to indicate that 93% of the changes observed when he first returned to Earth reverted to their original state, or if 93% of his DNA is normal, or what was exactly the details are.  Second of all, we have to look here at whether these mutations occurred at a higher rate than they did in Mark.  It appears that they did, but the important thing here is that you can't make that determination just by comparing Scott's DNA to Mark's; you have to compare Scott's before and after, and compare the proportion of changes to Mark's before and after.  Third, because these types of mutations happen basically constantly, if the point is that they've caused Scott and Mark to no longer have identical DNA, well, the boys are 54 years old.  That's enough time for a lot of mutations, and it is a 100% guarantee that they had separate mutations before Scott left for space, so using that argument, they were NEVER identical twins. 

Let's back away from DNA for a second and talk about genes.  DNA is organized into chromosomes.  Twenty-three groupings of DNA (provided that you're human) that contain smaller divisions called genes.  These genes are what code for everything about us, from the things that make us unique, like our hair color, to the things that make us exactly like every other living organism, like that cells have a lipid bilayer membrane surrounding them.  Only about 1.2% of our DNA is part of a gene; we're still figuring out what the rest of it does.8  This means that the odds of any single DNA mutation that happened to Scott when he was in space being in a part of the DNA that actually codes for a gene are really, really small.  If we go back to the rate of mutations, it's a pretty safe bet that some of them are, but mutations in your DNA do not mean that you're a genetically different person,9 because most of them happen in places that don't actually affect anything.  Just from the fact that there are changes in the DNA code means nothing about what's actually being expressed.

Which brings me to the next point- gene expression.  The way that genes are expressed is by copying DNA into the very similar but single stranded RNA.  Molecules then run along this single strand of RNA, following its instructions to build proteins, pretty exactly like how my boyfriend will carefully track a recipe with his finger to make sure he doesn't miss anything.  These proteins are what makes everything happen in our bodies.  There are lots of things that can happen that can cause this process to change.  Stress in our lives, exposure to drugs or toxins, the weather, so many things can either add molecules to DNA or change how it folds up, which change how things are expressed.  Genes can be turned on or off, told to create more of one type of protein and less of another.  Different gene expression is why cells in our bodies do different things, even if they all have the same DNA.  This is what happened to Scott Kelly.  The 7% of genes number that's being cited was not changes to his DNA, they were changes in how his DNA is expressed.  The DNA is still the same (minus mutations), and he isn't genetically different to himself or his brother.  The genes that have continued to express differences include genes that play a role in the immune system, DNA repair, and bone formation.  Note that they don't CAUSE these things, because they're all super complicated processes, but they're some of a number of genes that play a role in these processes.  Again, if you want to use these differences in expression to claim Scott and Mark are no longer identical, then they never were.  

There were some changes to the DNA itself in a way.  First, loose bits of DNA were found freely floating in his blood stream, likely due to stress.  This could be the mental stress that we usually think of when we use that word, but it also probably related to the physical stress of living in a small space with artificial conditions, changes in gravity, and other stuff that our bodies are just not used to.  It turns out that much like humans, DNA likes to go for a float in a river when it's feeling stressed.  The other difference that they noticed (which quickly reverted back to expected) is in the length of his telomeres.  Telomeres are portions of DNA on the endcaps of the strand that control how many times a piece of DNA can be copied.  As you age, they get shorter, limiting the number of times DNA can reproduce.  The scientist's interpretation of this is that it was likely due to the amount he was exercising or the ISS diet of prepackaged foods that somewhat calorie restricted.  Basically, this effect was due to diet or exercise, which says that it really did have much to do with being in space, just living healthier. 

The study on Scott and Mark has some really cool findings, and we should definitely be publishing them and talking about them.  I say that with a few caveats: first, we should maybe put a hold on these conversations and stories until the actual papers from the scientists come out.  Right now, all we have are two pretty ambiguous NASA press releases that people are running with.  Second, the outlets writing about this story should probably check that the people they have writing them understand DNA replication, transcription, and translation, or at the very least should be basing their stories on their own reading of the releases, and not just borrowing the same phrases and explanations from people who already bungled it.  Third, this world (and apparently other ones) are cool enough places that we don't need to make science news more dramatic; it's already amazing and fascinating and mind blowing.  Let this astonishing world speak for itself; there's no reason to put (not so true) words in its mouth.  

Sorry for being a such a grumpy bugger today.  I'll return to a few more "our brains are crazy" posts tomorrow.  If you don't want to miss out on those, follow me on Facebook, or follow me on Twitter to talk about how wrong these stories are.  

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