Thoughts on Gravitational Waves: Ripples in Space-Time and Quilts

If you haven't heard, Einstein was correct (again!) in predicting the existence of gravitational waves in space. This week scientists confirmed their existence with the first-ever, direct evidence of gravitational waves by measuring the disturbance in the fabric of space-time when two massive black holes collided almost a billion years ago. It proves without a doubt that the very nature of space can produce waves, just like the surface of the ocean, and that these waves can be detected. Our universe can ripple in response to some huge event. And better yet, the first person to observe the signal was a post-doc! (I'm also giddy because this now takes the name of my blog and nudges it from science fiction closer towards science.) There better be some physicist somewhere who is salivating to get an NSF grant to study the implications of these measurements on time travel. Maybe we can actually go back in time and pretend Trump was never seriously running for President?  

Anyway, it's huge news. Not only is Einstein validated yet again, but there are now new tools to study how the cosmos functions and respond to cataclysmic events - especially the destructive and awe-inspiring nature of black holes. Maybe we can finally prove where all of Schrodinger's cats go when they disappear when the boxes are opened. (What's at the center of black holes? Answer: a shit-ton of cats!). I'm also curious how this will shake out for the Nobel Prize Committee. The 1993 Nobel Prize in Physics went to Joseph Taylor and Russell Hulse for their discovery of indirect evidence of gravity waves (they measured radio waves emanating from a pair of spinning neutron stars as a proxy for gravity waves). Someone has to win for the direct evidence right? I think so. But has anyone ever won for a topic which was already given an award? I don't know. I'll have to look this up. 

In more personal news, I guess I should mention something about writing, as part of this blog's mission is to talk about writing-related topics. Recently, I've found that it's hard to stay motivated. I think most people can relate. The last month with our move, work projects, the epic Baltimore blizzard...I was finding more and more excuses to avoid both house-related projects and working on my science fiction stories. I partially blame my malaise on the fact that most of my projects right now need massive editing. So instead of the luxury of writing whatever comes to mind or imagining new stories, I've been knee-deep in cutting scenes, changing scene order, fixing dialog (a very problematic area for me) and extensive re-writes. And although my work is benefiting from these changes, it can be very hard to muster the motivation to re-re-re-work something in order to hopefully make it better. I've come to learn it's very true the story really takes shape during the editing process. 

Thankfully when it comes to getting motivated I eventually ran out of excuses. I'm now living four blocks away from the Baltimore Science Fiction Society (BSFS). I've known about this group ever since moving to Baltimore over two and a half years ago, but I've never had the chance to pay a visit. So if I couldn't manage a five minute walk I was never going to make it over there.

Thankfully I did.

Thursday night I got to participate in my first ever writer's critique circle. Every other week the BSFS hosts a circle where you can read your work out loud and others can chime-in with constructive criticism and/or mark copies of the story for review at home. It was a nerve-wracking experience. Other than reading out loud to my wife, I've never read to anyone, let alone a group of people I'd just met five minutes before. I usually share my stories with family and friends and they are kind enough to provide me excellent feedback, but I've never done this with strangers. However to my surprise, it was a great experience. Not only did I learn a lot about my own story, the creative juices flowed as I listened to others make comments and suggestions on both mine and others' work. I plan on going again and I think the additional input will help me become a better story teller. It also gave me a window to see how others craft their stories. 

I love story-telling. That's why I write - to tell stories. And to me, writing a story is like making a large quilt. The entire thing is made up of small threads and strands that weave together. Editing reminds me of fixing all the errors after the quilt has been made. Sometimes when I'm reading over my work and making edits all that is required is a little tug and a small thread is woven back into its proper place. Sometimes I feel like I am taking a big pair of scissors and ripping the pattern open. I'll pull out large strands or chunks and patch it all up again, hoping the new threads seal the hole I've created. (I realize that this is probably not quite how a quilt is made but I'm determined to stick with this analogy.) I'm really hoping that after editing the overall pattern remains the same, but I also hope every change is making the pattern better. The hardest part is making sure all the unintended wrinkles and ripples are smooth again after I make a cataclysmic change so it looks as if the entire quilt were made at one sitting. It is tiring and tedious and I hope all the hard work pays off. The input I get from friends and this writing group is invaluable to this process.

Thursday night's meeting made me realize anybody could benefit from this sort of thing. Whether you draw or make music or make movies, design houses...anything. Go out and find a group of people who do something similar and talk to them. I was struck how helpful this could be at work, too. I know at the NIH there are small groups of anonymous readers who will critique a manuscript and give editorial input. But what about how to actually craft and present the data? Almost like a journal club, if you will, where you could meet and discuss how to tell your research story so that it is as strong as it could be before publication. Even a group of close colleagues helping to give input on how a data figure looks, order of the data, or similar conversations would be enormously helpful as one is writing up a paper. Maybe there is such a thing at work? I'll need to look into it. If there is, I'll report back. 

On a totally unrelated note, if you aren't watching the English Premier League then you aren't excited about the awesome games this weekend. Tottenham have a big draw against Manchester City, with huge implications for the top of the table (that's the English word for standings - which sounds more stoic and gentlemanly I think). Leicester City also squares off against Arsenal, another Top 4 match-up. They should be a lot of fun and if you don't watch soccer (aka football) it's a solid weekend to give it a try. Football is over anyway, right?

Back again, soon-ish. Cheerio! 

The Scientific Abstract...Or, The Flash Fiction of the Natural World

For scientists, the predominant currency of our occupation is the primary research article. It's our bread and butter, whether or not a scientist ultimately pursues an academic research career or moves into something else. They are the poker chips in the game of science and the more you have (or the better the journals you publish your work) the better the chances of finding a good job after school and post-doctoral training. First author review papers are also incredibly helpful as they can help define a scientist's interests and expertise in a given area.

In my opinion, the hardest part when writing a research paper is the abstract. It is often the last part of a manuscript that is prepared before submission for peer-review and it is the first thing that anyone interested in your paper is going to read when published. The hardest part when writing an abstract is finding the perfect set of words that encapsulates an entire research project. Some primary research articles can run well over 6,000 words. In fact, many journals have capped the length of articles at about 7-8,000 words. But abstracts are almost always kept to a very strict word count, between 200-350 words.

The scientific abstract needs to be very concise, provocative, and timely. When scientists scroll through hundreds of papers on PubMed, at first all they see of each article is the title and abstract. So you have to write an abstract to grab their interest and then maintain that interest long enough for the reader to get through the entire thing. The challenge is summarizing thousands of words into just a handful and still conveying important results and answering all the questions that the reader will have, such as: Why do I care about this work? How did they do this study? Does it related to my own work? What did they find? Is this important? What didn't they do in their study? I'm tired, why do I need to read this?

I think the scientific abstract is a lot like flash fiction. Flash fiction stories are generally shorter than one thousands words and some are even smaller, less than a hundred. Flash fiction stories need to grab a reader's attention, keep it, and convey a sense of meaning or purpose in a very limited amount of time. The best flash fiction stories generally have a plot and even a hint at character arc. It's very hard to pull off. But the ones that grab me as a reader are ones that were crafted and edited and re-edited and accomplish a sense of purpose. Every single word matters. This same principle holds for the research abstract as well; they go through many (sometimes dozens) of drafts before the wording is just right.

Lately, I've been thinking a lot about the similarities between flash fiction and abstracts. Partially because I've just submitted my own manuscript for peer review and partially because I like to write flash fiction. Recently I entered into a very challenging flash fiction competition that called for stories less than 250 words on the topic of 'alien invasions during Christmas'. I wasn't a winner unfortunately, but it was still a lot of fun to write a 'quick' story and submit it (it took much longer to write and edit than I had anticipated). I decided to meld my hobby with my day job and write a flash story about a Christmas alien invasion modeled like a research abstract. I really liked how the story came out and since it won't be published anywhere I decided to put it here for others to enjoy. It's structured like many research abstracts. I hope that will give you a flavor of what an abstract looks like if you have never read a scientific paper. Due take note, as with all scientific abstracts, sometimes the bits left out in a flash fiction story are just as important as what is presented in the text.

It is going to be busy here for the next few weeks. I will be posting another story, this one much much longer. It's a fantasy Christmas caper, complete with tinsel, Santa Claus, swords, paladins, gnomes, and zombie Rudolph. It will never find a home in the publishing world (it was never intended to) but I think it's a fun story to share.

Thanks for stopping by today and I hope you enjoy!


‘Holiday Spirit’ Influences Mem’tep Casualty Rates During Invasion

R’lourl, Shzyc*

*Director of Mem’tep Military Research, Mem’tep Prime Military University, Mem’tep Prime

Translated by Douglas F. Dluzen

Background: It is well known that invasion of planetary systems harboring at least one dominant, sentient species (α1 systems) results in higher Mem’tep casualty rates. We hypothesized that Mem’tep casualties are negatively influenced by local religious events and holidays. 

   

Methods and Results: We chose two α1 systems for military invasion, colonization, and integration into the Mem’tep Kingdom. Ponceau S is home to a nuclear-grade sentient species without religious proclivity and served as our control. Terra, technologically similar to our control, is predominantly monotheistic. Each invasion fleet utilized identical resources and troops as outlined in the Mem’tep Code of Colonization. Casualty rates, infrastructure loss, and rates of post-invasion uprisings were measured up to one hundred years post-colonization. We observed a significant increase in Mem’tep casualties during the colonization of Terra compared with control. Additionally, Mem’tep casualties increased beyond baseline during each annual recurrence of the Terran religious period known as the Christmas holiday, which commemorates the birth of their perceived savior. Local Terran uprisings against Mem’tep authority are often synchronized with the observance of Christmas and this effect is locally known as the ‘holiday spirit’.

Conclusions: Recurring religious holidays are associated with increased Mem’tep causalities during and after planetary invasion of α1 systems with monotheistic civilizations. Local customs may influence integration success with the Mem’tep Kingdom and tend to unite familial subunits and opposing geopolitical factions against Mem’tep authority. Future studies should explore strategies which manipulate the so-called ‘holiday spirit’ to promote sustained integration with Mem’tep culture. 

Flashes of Darkness: A Halloween Collection of Flash Horror

The monsters over at Dark Chapter Press have put together a nice collection of Halloween horror stories to wet your whistle. It's called Flashes of Darkness: Halloween Special 2015: A Flash Fiction Collection and features dozens of new takes on the classic horror themes involving vampires, werewolves, and zombies. You don't have to be in the Halloween spirit anymore to enjoy this collection. I was fortunate enough to get one of my own flash fiction stories included and I'm pretty excited about it. If horror is your thing, head over to Amazon and you can get it for your Kindle for the price of a candy bar.

In other news, it's been a busy month since my last post. I'm working hard to get my primary manuscript on the genetics of hypertension submitted for peer review. We've targeted the research journal Circulation for our first attempt to publish this behemoth, so fingers crossed! This should free up a little more time at home and I can finally get around to finishing my posts about science and genetics. I promise I'll have some interesting tidbits about modern clinical genetics to share and we'll even take a trip into space to discuss some really exciting research that NASA is doing.

Until then, just remember that we are exactly one month until Star Wars: The Force Awakens!

Research in science and Sci-Fi...and other ramblings

One lesson I've learned is that reading stories and books within the genre you hope to publish is akin to doing primary scientific research. The old adage goes that the best writers of sci-fi are also avid readers of sci-fi. This is true in medical and other scientific research as well. I have to read several primary research articles a week to stay current on experiments, methods, and new discoveries in science. Doing so also gives me insight on how to tell my scientific "story" when it is time to submit my paper for peer-review. 

There are lots of places to submit original sci-fi work, but I've learned that just as in scientific research, the story has to be the right fit for the magazine. At work I study the genetics of hypertension and cardiovascular disease, as well as human aging. My research paper on hypertension wouldn't make sense in a journal like Cancer Research. It's better suited for a cardiovascular-related journal. This rings true for publishing science fiction and fantasy. So I'm spending a lot of time reading through stories published in a variety of different publications to get a feel for where my stories can hopefully find a home someday. 

Not only is this fun for me (because I love reading) but I'm also learning how others are honing their craft and becoming better story tellers. Over the months and years I've compiled a list of publishing destinations and magazines in science fiction, fantasy, and horror. For the non-writers who may be reading this, if you like any of these genres I would recommend checking out some of these websites. You may just find something you like. And for other authors, I hope this is helpful. 

I've classified the list into subsections, as well as the "usual" word count of stories accepted under each magazine's guidelines.  This is by no means an exhaustive list and each list is in no particular order. I am certain I am missing many publications and so I'll do my best to continue to update this list as I find more. 

Science Fiction/Fantasy 

Clarkesworld Magazine   1,000 - 16,000 Words

Nature Futures   850 - 950 Words

Lightspeed Magazine   1,500 - 10,000 Words

Daily Science Fiction   100 - 1,500 Words 

Strange Horizons  Up to 10,000 Words

Intergalactic Medicine Show  Any Length 

Acidic Fiction  Not accepting (as of now)

365 Tomorrows  Up to 600 Words

Bastion Magazine 1,000 - 5,000 Words

Shimmer Magazine  Up to 7,500 Words

Flash Fiction Online 500 - 1,000 Words 

Magazine of Fantasy and Science Fiction Up to 25,000 Words

Lakeside Circus  Flash Fiction (<1,000 Words) or Short Fiction (1,001 - 5,000 Words)

Writers of the Future (Contest, up to 17,000 Words)

Hydra  (Novels, at least 70,000 Words)

Analog  (Varying lengths)

Asimov's Science Fiction  Up to 20,000 Words 

Horror

Nightmare Magazine  (1,500 - 7,500 Words)

Dark Chapter Press  (Dependent upon submission call)

The Horror Tree (Dependent upon submission call)

General Fiction/Misc.

Quail Bell Magazine 

Liars' League NYC  (Generally 800 - 3,000 Words)

And now for something completely different:

When I was in Europe I snapped as many photographs as I could of the beautiful sights and landscapes. The amount of castles, stone circles, ruins, and glens makes it very easy to find inspiration for stories (I also recommend a small notebook to write down such ideas before they float away). Some of the places I visited no doubt inspired other writers. For example, below are two pictures of a bar that I walked past while in London. Fans of A Song of Ice and Fire (Game of Thrones) will recognize the name. I have no idea if George R.R. Martin ever saw this particular bar, or was inspired by the name, but I know he has frequented the UK so perhaps there is a link. (Again, I suck at taking pictures. My wife Julia is much better at it. But I can at least claim that it was raining, it was dark, and I was buzzed on some solid English beer.)

London is full of amazing places. No doubt seeing some of these sites made me think of great writers before my time and how they must have done their own research. Sir Arthur Conan Doyle undoubtedly did research before writing his Sherlock stories. You can't see the address very well above the door, but we stopped by 221B Baker Street to see if we could catch a glimpse of Benedict Cumberbatch (I mean Sherlock Holmes...of course).  It was well past midnight and we did see a fox outside the house when we drove up....in downtown London. So perhaps Mr. Holmes was in disguise to avoid the American tourists. 

Edinburgh, Scotland was a magical city. I've heard stories that George R.R. Martin traveled quite a bit in England and Scotland (apparently Hadrian's Wall was the inspiration of The Wall in his books). While in Edinburgh we visit Edinburgh Castle, and inside the Grand Hall were numerous stained glass windows with the sigils and crests of Scottish clans and families. As you can see below, some of them are eerily familiar to those described in the books. Unfortunately, I neglected to take a picture of the castle up close. I'll scour Julia's phone when she gets home. 

Edinburgh Castle from across the city 

Inside the castle walls

Windows in the Grand Hall 

Of course, we also had to stop by a favorite haunt of J.K.Rowling - one of my most favorite authors. Julia was as excited as I was. However, the croissant I ate while there failed to unlock my inner muse and give me the inspiration to write a seven-book series that will make me a multi-millionaire. I should've asked for a refund. 

On the trip I was also excited to meet up with another author who is building up his own publishing company - Dark Chapter Press. Located in Alnwick, England, Rob is a horror author and his press has featured some of my own horror stories on the website. It was a great chance to meet after working online together for over a year. Here's to hoping for future collaboration with D.C.P.! (A short story of mine will be included in an upcoming horror anthology published by D.C.P.- more on that later.) 

Talking horror at Dirty Bottles with Rob (left) and Dark Chapter Press in Alnwick, UK

I'm continually surprised by the similarities in research, writing, and submission of either research publications or genre fiction writing. Hopefully I can use the success and failures I have in each field to improve my writing and story telling in the coming years. 

Next week (or at least next post) I will be conducting a social experiment of sorts over a period of several months. It's time that I put my genetics knowledge to an informative use and I plan on doing something a little crazy to garner more discussion and communication in genetics, especially with my friends who don't do research. 

Until then - Go Cubs! Back to the Future Part II predicted that the Cubs would be World Series winners this year. Wouldn't that be something if it really happened? 

When Geneticists Unite

I've just realized (read: decided not to ignore) the fact that I haven't posted in many months. Going nearly five months between updates is not a very good start at attempting to become a blogger/science writer. So today begins attempt #6 at writing about science and to get the ball rolling on this website. This week I'm attending the American Society of Human Genetics (ASHG) annual conference. In a stroke of luck the conference is being held in downtown Baltimore so I get to sleep in my own bed and walk to work all week - heaven.

Clearly there are a lot of geneticists here, with too many opinions sometimes. And although there are countless seminars and talks and symposiums at this year's event, I feel there has been a very clear message broadcast as the 'unofficial' theme: communication. I'm not sure that was intended or not, but many investigators and clinicians (even patients) are stressing the importance of more communication between researchers and community. Taking that to heart I've decided to provide a little update about my experience at the conference and 'communicate' some of the coolest things I've stumbled upon while here. So without further ado I'd like to present my first offering.

Enter Mr. Robot:

I'm sorry for the potato - quality image. I still don't know how to use my phone's camera appropriately even though I've had it for four years or so. Regardless, this robot runs automated PCR assays for companies and university laboratories. (If you don't know what PCR is, please read my previous post on the subject called The Next Revolution in Genetics). The company (Hitachi) selling these bots is from Japan and they have been using these guys for several years now. Each eyepiece contains a small camera and its hands are quite dexterous, yet sturdy and completely automated. The representative I was speaking with said they were looking to enter the American market and in a few years it is conceivable that many major universities and companies, which run thousands of PCR reactions, will be using these to provide faster and cheaper sample processing. I have mixed feelings about this technology. Clearly it's bad-ass and the robot is friendly-looking enough. In fact it reminds me a little bit of WALL-E. But I can't help but wonder how many lab techs and post-bacs (or even post-docs) will be facing an even more competitive environment where jobs are no longer needed to run large research and gene-sequencing initiatives. It's a changing world. 

The Next Generation - The Genome vs. The Exome

Most people know what the genome is. Simply, the genome is the collection of your DNA's entire genetic sequence. From the sequences that make up your genes, to the regulatory elements that govern how your genes are expressed, and finally the long stretches of DNA that have few genes but which are still vitally important structural elements. Your genome is the complete package of DNA that is found in nearly every cell of your body (mature red blood cells do not have a nucleus and little to no DNA).  

What you may not be as familiar with is the exome. The exome is a little trickier to identify, but when analyzed it can provide important clues into your health and where/when specific genes are expressed.  When a gene from your DNA is expressed, an RNA copy is made. RNA is a nucleic acid, similar to DNA, and acts as a middle man between DNA and ultimately the proteins that are created. All proteins are coded for by DNA genes, and all proteins arise from the edited RNAs that carry the 'message' of your DNA to the machinery that makes the proteins. (There are many additional types of RNAs that don't code for proteins but that is a story for another post.) The RNA, called messenger RNA or mRNA, is edited and processed, not unlike editing down a blog post from a draft to something (hopefully) legible. The cell then reads the processed mRNA to create our proteins. The exome is all of the RNAs expressed at a specific point of time in a specific tissue. For instance, the exome of your neurons would be all those RNAs found in your neurons at the time when it was collected. The exome gives us insight into the exact library of genes that have been turned on specifically in the neurons....or within a tumor...or any other type of tissue being tested. 

Our bodies have tens of thousands of genes (~25-30,000 protein-coding genes and another 10-20,000 non-protein coding genes that code for additional RNAs). Amazingly, our bodies have evolved to be masters of efficiency. We simply don't need to express every gene/protein in every cell of our body. Proteins required for the function of the heart, and not at all for the function of the liver, are simply not expressed in the liver. There are liver proteins found in the liver but not in the heart. And even though every cell in our body has the complete DNA 'blueprints' for the entire body, tissues and specific types of cells are good at maximizing and expressing only those genes and proteins essential for its own normal function. By sequencing our exome in a particular tissue, we get a specific answer on what exactly is going on with our expressed genes in said tissue. This also allows us to cancel out all the other background genetic 'noise' that isn't important. 

Many genetic mutations arise de novo - meaning they are brand new to an individual and not inherited from parents. Many disease are caused by de novo mutations, including cancers. Clinicians can make use of this by comparing and contrasting normal tissue in your body with diseased tissue (there are many ways to make this comparison, sequencing the genomes vs the exome is only an example). Companies can sequence your genome from your blood immune cells (in which case your entire genetic sequence is known) and then sequence your exome from a cancerous tissue (in which only those genes expressed in that particular cancer tissue are sequenced). Then, the results can be matched together and mutations potentially identified. In the dawn of personalized medicine, this allows clinicians to zero in on whether your genome has a mutation in an important gene....ideally tailoring a therapy specifically for you. Whole genome sequencing can also tell us whether a variation in your DNA is the result of inheritance from mom or dad, or one that developed de novo when you were growing in the womb. 

Below is a genetic testing kit that I got this morning from Centogene - a biomedical company based in Germany. Clinicians can order a genetic sequencing test of either your genome or your exome to identify variations in your genetic sequence that may influence disease: such as in the BRCA1 gene.  

And here is a picture of where your blood is dropped and dried and sent for analysis (note the circles):

This genetic test requires only 50 micro liters of blood (literally just a few drops) and costs only $2000. To put that in perspective, ten years ago sequencing of one individual cost millions of dollars. So the technology and the cost are both dramatically improving and I thought it would be good to show that we are very close to knocking on the door of the $1,000 genome (the gold standard). 

Now back to where communication comes in. Many patients and those outside of science confuse the genome with the exome (for good reason as they are very related), or what a genetic test can definitively tell you. It's the job of scientists, doctors, and those in medicine to clarify these differences so that patients know exactly what they are getting. It's also our job to show politicians on the Hill just how advanced technology is, why a new age in medicine is on the horizon, and why we need to continue to propel this forward with increased funding and discussion with all members of the community. 

And to put a cherry on top, below is one last photo from the event so far. I'm a sucker for the stress-ball giveaways from the vendors. I have a large collection of them at work (I don't know why...maybe I'm stressed?). This is a picture of the one that is by the far the best I've ever received - a squishy sperm cell. Who wouldn't want that on their work desk? 

If you like reading horror, check out this Kickstarter campaign!

Dark Chapter Press has been very good to me. On their website they have featured several of my flash horror stories and they are slowly building up an author base as they grow as a publishing company. I'm new to the game when it comes to professionally publishing stories and the exposure they have given me has been simply awesome. So now is a chance for me to promote them a little bit instead! Little guys unite, huzzah!

Currently they have a Kickstarter campaign to raise funds to tackle publishing costs for their new horror anthology Kill For A Copy. It is an exciting project featuring a collection of 17 horror stories with contributions from new and established authors in the genre.

I'm really looking forward to reading this and in the coming months I'll be submitting some of my own work for other upcoming anthologies at D.C.P. (Fingers crossed!) But in the meantime please check out their campaign. If you like horror and are excited to read work from new authors your support will help D.C.P. become established as a new 'monster' in the field. Cheers!

The Next Revolution in Genetics

Scientific research often moves incrementally. An observation made, a paper published, results repeated and/or expanded upon, a new discovery made. Wash...Rinse....Repeat. In fact, a majority of scientific research occurs this way. Laboratories across the world contribute snippets to a particular story of which only years later everyone can look back at and see the multiple-layers and colors and contributions that now make up a rich tapestry. Research in cancer, aging, development, neuroscience, physics, chemistry, etc. is done in this way.

But sometimes the ground literally shakes.

Sir Isaac Newton's Theory of Gravity revolutionized not only mathematics but how we think and interact with the world. Then Albert Einstein decided to be all genius-like and published his papers on relativity. He single-handily destroyed the accepted concepts of physics that Newton built and to this day physicists are still confirming and visualizing Einstein's theories and ideas. This is remarkable in several ways. First, Einstein postulated his theories without the aid of calculators or computers. He used very complex mathematics and science to predict astronomical phenomena that scientists are still confirming with the aid of super computers, particle colliders, and the most powerful telescopes in the world. Not only will Einstein's name live on indefinitely, but his work is truly a shining example of the scientific method at its most basic level. He predicted and now his work is still being confirmed.

The discovery of penicillin revolutionized medicine and contributed to the global increase in human lifespan. When the structure of DNA was elucidated the world of genetic research took off and molecular biology was born.

These are all examples of events that shook the scientific world; much like the atomic bomb changed the course of human history, or when the Berlin Wall fell, or how the events of September 11th have ushered in a new era of American fear, surveillance, and Islamophobia. All of us were alive during the events of 9/11. I remember exactly where I was when I first heard the news that one of the towers in NYC had been hit by a plane. I watched live when another passenger jet struck the second tower. I couldn't help but wonder what the world would be like the next day. Sometimes discoveries in science can alter the world in far-reaching ways as well, for both good and bad.

One of those seismic events in the scientific world occurred in the 1980's; a ground-breaking discovery that in the span of a few years has literally shaped and changed how every laboratory in the world performs molecular biology. And when I say literally  I'm not being hyperbolic. This technique is so widely used that it is often over-looked by scientists because it is so routine. But to this day I can't think of another technique (other than the one I'm going to introduce below) that has so revolutionized the way biomedical research is conducted it has changed the world. 

So what am I talking about? What was discovered in the 1980's and is so important? Now for a quick history lesson in science. The technique discovered in the 1980's is called Polymerase Chain Reaction (PCR). It was invented by Dr. Kerry Mullis, for which he won the Nobel Prize. PCR is a technique used by biologists to study any gene in any organism. Mullis used bacterial proteins and designed PCR to generate copies of DNA. You can think of PCR technology as a molecular photocopier. Any DNA region of interest can be copied thousands of times over, such that even with small starting amounts of DNA a specific gene can be targeted and amplified to high abundance so there is enough starting material to work with and study. This method changed molecular biology and medicine as we know it. And in case you are thinking to yourself: a molecular photocopier? Who gives a shit?! Well you should give two shits, plus another next Tuesday. Because whether or not you know it PCR has affected your life in someway. 

Have you ever been on trial for murder? Probably not, but PCR is used to amplify DNA found in blood from a crime scene.

Ever needed a paternity test? PCR would have been used.


Ever been genetically tested for cancer gene mutations? Or for genealogy purposes? PCR was used.

Ever eaten a GMO food? PCR was used to create it. 

Ever taken an antibiotic, insulin , or a host of other medications? PCR contributed in the creation of a majority of them. 

The creation of new cancer therapies, vaccines, studies of human evolution and population epidemiology, smoking behavior studies, neurological tests....all examples of fields of study and research that have made use of PCR technology. 

So needless to say, PCR changed A LOT and in a small amount of time. But there are limits to PCR technology. For example PCR is generally conducted in a test tube and the amplified DNA can only be studied or manipulated for a particular downstream application. For example, PCR is used to study the function of a gene and is used to help mass produce insulin for diabetics.  For many scientists and doctors the next step is using this tool (and others like it) in molecular biology to make the next jump: to truly being able to cure someone of a disease or to prevent one from developing. This idea is packaged together and known as Personalized Medicine. Ideally, a doctor would be able to analyze your unique genome (and everyone is truly unique in this regard) and use that to predict what would be the best possible medication for you to use for any type of disease. Or to predict if you will develop a disease. Or perhaps to predict if you will pass that gene down to your kids.

We are still far from that point in several aspects. But in some ways we are closer than ever before. 

The new technology I want to talk about today, that is currently undergoing a unique revolution, is called CRISPR. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats  (we don't have to worry about that name any more for this discussion). CRISPR sequences occur in bacterial genomes and are actual sequences of DNA. You can think of them as road markers or exit signs on a highway telling someone where they are on a highway.  Cas9, a protein also found in bacteria, is short for CRISPR-associated protein 9. It can bind to DNA and is guided to specific locations in the genome. Cas9 recognizes the CRISPR sequences in the bacterial genome and binds to them preferentially, as if Cas9 read the road map and knows where on the highway to drive to. This entire system was first discovered in bacteria and it is a defense mechanism that bacteria employ to protect themselves from viral infection (yes, bacteria are also susceptible to viruses). It's part of the bacterial immune system and was first discovered in 1987. Over the last two decades incremental discoveries have propelled CRISPR into the thoughts and experiments of many scientists around the world. This year however the field has exploded.

So why is CRISPR important? Because CRISPR is now in the  midst of a major revolution....one that could usher in the next gigantic advancements in genetic engineering, molecular biology, and personalized medicine. Seemingly every week a dozen new research articles are coming out in top journals describing the uses of the technology to study disease, normal development, and other important questions in medicine. Oftentimes this is very controversial, as I'll discuss in a few paragraphs.

CRISPR is a different technology than PCR. It doesn't amplify or copy DNA. Instead, CRISPR/Cas9 systems are used to make very specific changes in very specific regions of the genome. For those who don't spend their lives working on the bench, think of this system as a highly specialized DNA editing machine. CRISPR technology allows scientists to target genes, down to a single nucleotide, and change them. Just like an eraser or white-out marker used on a mispeled wrod or wrds. CRISPR/Cas9 will edit the DNA and correct the mutation (or make a mutation). This has enormous implications in biomedical research not only because this is now an unprecedented level of control in genetics, it may also allow scientists to actually correct DNA mutations in humans that cause disease.  

But herein lies the real issue with CRISPR technology and why everyone, including those outside of science, needs to at least understand why this is important. What scientists truly have in their hands right now is a game-changing tool. It is theoretically possible to make precise corrections in mutated human genes in order to have viable, healthy offspring. There is hope now for parents with genetic diseases who want to have children but don't in fear that they are passing along familial mutations that their kids will inherit. This is a step beyond what Britain legalized earlier this year in which in vitro fertilization can be used to surpass genetic mutations in the mitochondrial genome in mothers with mitochondrial diseases. CRISPR allows for the editing and correction of those genes in the cell's nucleus, where most (99%) of our genetic information is found. Several reports have already come out within the last month detailing how CRISPR has been used to make mutational changes in fruit fly egg and sperm cells and that these mutational changes are inherited in future generations of flies. This is the first proof of concept that specific changes in an animal's germ-line (i.e. sex cells) can be heritable. Additionally, just yesterday a laboratory in China published research in which they used non-viable human embryos to show that CRISPR can be used to change genetic information in human germ-line cells. (These embryos are not capable of developing into a baby.) This is the first ever published report on the use of CRISPR technology in human germ cells. A good news summary can be found here, with links to the article, and new reports indicate that several other labs in China are pursuing similar research.

The ethical issues with this technology are very important and are the main reason why I'm writing this article. While this game-changing tool will almost certainly be used to understand and combat human disease; this tool could also be used for less noble purposes. Similar to PCR, CRISPR technology is easy to use, cheap to set up, and currently unregulated in the United States by the FDA - let alone in China or Russia or many other countries. The EU does have stringent laws in place about human germ-line editing and hopefully the FDA follows this example as a starting point. There is no doubt this technology will be widely used in many, many laboratories in the next few years (like PCR) and the conversation needs to kick into high gear about the Orwellian implications that this technology could be used for. The experiments j from China have met with some technical difficulties however. Much needs to be worked out before this would ever be remotely considered for medical use in viable embryos. But to also point out, both Nature and Science would not publish this work due to the ethical considerations.  

Thankfully some of the major players in CRISPR research, including Dr. Jennifer Doudna, Dr. David Baltimore, and others, have met with scientific, legal, social, and ethical experts to discuss the implications of CRISPR research. A month ago they issued a joint statement in Science calling for a complete moratorium on CRISPR-related research in human germ line cells. Scientists do understand the implications and this technology is so new, and moving so fast, regulations need to be in place to prevent nefarious use of it.  It really is a revolution.

So what's my take on all of this? I've asked myself that question repeatedly for the last two months. At work we've held journal club discussions about these papers and I even saw Dr. Doudna present a history of CRISPR technology and its future implications at a conference at the NIH last month. (She's wickedly smart and I bet she wins a Noble Prize for her work in the field.) As a geneticist I must always be aware of what the implications of my research are going to be and that's why I'm writing this out today. *I don't use CRISPR in my research in case you are wondering* Personally, I am in complete agreement with Dr. Duodna and her collaborative warning to other scientists. CRISPR-related work in human germ line cells must stop until the broader implications have been thoroughly considered. Unfortunately, other countries may not listen to this warning, and the FDA moves so glacially slow I'm sure there are labs in the states pursuing similar types of experiments (admittedly this is just a hunch I have no actual proof of that).

But I'm also making sure I keep my eye on the bigger picture. Yes, this technology can be misused, but the idea that Mendelian and other complex diseases could be corrected and eliminated is an amazing opportunity and which needs to be explored, albeit in a controlled and safe manner. Remember, with creation of the atomic bomb we also now enjoy nuclear energy that is cheap and clean, fuel for rockets to go to Mars, and maybe someday even cold fusion!

Okay, so perhaps comparing CRISPR to the atomic bomb is a little overboard (comparing it to a laser-guided cruise missile is probably more apt). The challenge today is for scientists and non-scientists to keep this all in perspective, move forward in a safe and purposeful way, and start a conversation that puts the appropriate rules in place quickly so that we can continue to pursue novel research that benefits others. Hopefully these few paragraphs on the subject get you thinking about all of the implications as well.