Science Fiction by Scientists: An Anthology of Short Stories (Science and Fiction)

by Michael Brotherton

  “Miss Shelley?”

  “Ela-Jo? What are you doing here this late?” Lenora flips the light switch. The girl is climbing out of a “fort” she’d made herself of desks and chairs. She snuffles. “I was just… waiting for you.”

  “Rough times at home, huh?”

  Ela-Jo only jerks her shoulders. Her face squirms but she holds it together. Always a trooper.

  Lenora goes to the sink and presses her thumb into a reader, then, when the little light turns green, she opens the faucet and fills up a glass. “Here.”

  “Where you been?” Ela-Jo says, gulping down the water.

  “Ah. Doing my penance, young lady… Why don’t you wash your hands and face, while you’re at it. And your hair. There’s enough water, I make sure of it.” She searches in her pocket and pulls out a disintegrating damp paper towel with diffused purple streaks. “Oh my, I completely forgot. Our pH indicator. I guess we’ll have to make a new one tomorrow, right?”

  Ela-Jo curves her lips. “What for? We still can’t fix the water.”

  Lenora sighs. “True. But if you know something… if you know it then at least some day… maybe… you can fix it.” She wipes her eyes with the heel of her hand. “That’s all.”

  Afterword

  Let me just say it: every element of Dr. Mireles’s science is real or rooted in reality, and refers to actual, developing research in epigenetics. As the name suggests, epigenetics is the study of inheritance by means above genetics, on top of genes and the stuff they are made of — the DNA molecule. But what does it mean, exactly?

  That is a matter of incredible breakthroughs in molecular genetics of the 21st century. In the nineteen nineties the paradigm was largely like this: there is DNA. DNA is parceled into genes that code proteins. Genes are expressed, i.e. transcribed into RNA. RNAs are translated into proteins (unless they are of the two classes of RNA that service translation itself). Proteins make cells and service them. How is the work of this mechanism controlled and adjusted to various conditions? By proteins. Regulatory proteins sense changes in the environment, bind to DNA near or within the genes, and influence expression of these genes. To permanently change expression of a gene one therefore needs to mutate the DNA of the gene or of its regulatory protein.

  This was a good start but it couldn’t be all there was. First, in complex organisms like us (and other vertebrates) protein-coding genes occupy less than 2% of all genomic DNA our cells carry. Why so wasteful? Second, DNA in a cell is not naked but is elaborately wrapped in and around special proteins, seemingly making access to it by regulatory proteins more challenging than it needs to be. Why?

  As it turns out, the circuitry DNA → RNA → protein → DNA is only one part of the system. A lot of DNA codes RNAs that never translate into proteins. But these so-called non-coding (nc) RNAs carry out regulatory functions on par with the proteins. In particular, they regulate gene expression. Moreover, this RNA-mediated regulation can be quite permanent, thus introducing to us one area epigenetics studies: changing gene expression not by mutating a gene but by making it a target of a long-term repression or activation by a ncRNA.

  And what about those protein wrappers of DNA? Turns out, the most ubiquitous of them, called histones, offer their surfaces for putting semi-permanent chemical “tags” next to this or that gene in DNA, in order to either ease the access of regulatory proteins to the gene or prevent it altogether. Thus developed another brunch of epigenetics: a study of placement and erasure of these tags and their role in long-term, stable changes in gene expression that accumulate over the life time of an organism. In other words, both ncRNAs and histone tags are examples of adaptive changes that even two genetically identical organisms like Yric and Paul Benes can accumulate as they get older.

  It only gets more interesting from here. Persistent presence of a repressive histone tag invites chemical modification of DNA itself, which further discourages regulatory proteins from binding it. This modification can degrade, causing a heritable mutation in DNA. This may be one way by which an epigenetic, adaptive change eventually forces genetic change. But that’s not all. First, not only physical conditions such as starvation, but also mental conditions such as PTSD affect gene expression by epigenetic means. Second, ncRNAs and histone tags can cooperate in repressing genes, with ncRNA attracting repressive histone tags. Third, in addition to controlling gene expression, ncRNAs and histone tags also control proteins that repair broken or damaged DNA. And where there is repair — there is making of mistakes, i.e. making mutations. And lastly: yes, some ncRNAs are secreted from cells in exosomes and thus can in theory exert their effects not only in a cell of their origin but in some distant cell — even in a recipient organism. ncRNA content of exosomes is known to vary under different life conditions of an organism, and in health versus disease. With all this insight into the ways cells can accumulate and retain adaptive changes over an organism’s life, researchers are setting their sights on the next question: can some of these changes be transferred to an organism’s progeny? Experiments begin to say: yes.

  Now we are at the edge of the known and are venturing into the hypothetical but not unlikely. What Lenora proposes is that a certain class of ncRNAs is can be transferred from cell to cell, organ to organ in exosomes. This includes going to the germline — sperm and egg cells. Inside a cell, these RNAs bind to the DNA of genes and alter their expression. If these ncRNAs are abundant or persistent, they also can: either stimulate a repressive histone tag and then a mutation at the site of their binding; or alter DNA repair so that a mutation is more likely to be introduced at the site. Lenora envisions some combination of both, in fact she thinks her ncRNA actually attracts repair proteins to the site of its binding, and induce these proteins to repair what is not broken — and introduce a mutation. Either way, if the DNA is broken, this increases the chance of mutation. Lenora knows the identity of her ncRNAs, knows which gene each binds, knows what histone tag or mutation footprint this can leave on or in DNA. If she also knows which ncRNA each twin took, she can not only distinguish Yric from Paul, but also figure out which one is Rolland’s father — assuming transgenerational transfer did happen. What neither she nor the twins know at the start of the trial, is what systemic physiological and behavioral effects massive bombardment by LIG and LIB ncRNA will produce in the recipients and their progeny.

  The rest, as they say, is fiction. The experiment is ongoing.

  For a good recent overview of transgenerational inheritance studies see for example Epigenetics: The sins of the father, by Virginia Hughes. Nature News 2014, v.507, pp.22–24