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!
Tuesday, November 17, 2015
Monday, October 12, 2015
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.
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?
Thursday, October 8, 2015
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:
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?
Thursday, May 14, 2015
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!
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!
Thursday, April 23, 2015
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.
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.
Monday, March 23, 2015
A Love Story
Way back in November I entered into a horror flash fiction competition. Although I didn't win, the editors at Dark Chapter Press liked my story and have decided to feature it this week on their blog! If you are interested in a quick, bedtime "love story" then please check it out!
A Love Story.
It has been a while since I've been able to update. Most of that time has been spent working on my research and teaching introductory biology at the Community College of Baltimore County. I am having a wonderful experience but teaching is extremely time consuming and hence my blog suffers. Thankfully I have been able to keep writing in my own time and hopefully as things settle down I can get back to updating this more regularly. Until then, you stay classy San Diego!
A Love Story.
It has been a while since I've been able to update. Most of that time has been spent working on my research and teaching introductory biology at the Community College of Baltimore County. I am having a wonderful experience but teaching is extremely time consuming and hence my blog suffers. Thankfully I have been able to keep writing in my own time and hopefully as things settle down I can get back to updating this more regularly. Until then, you stay classy San Diego!
Thursday, February 5, 2015
When Jurassic Park Becomes Real
The nerd in me is really jumping for joy. An article published today in the journal Nature entitled "Biocontainment of genetically modified organisms by synthetic protein design" discusses experiments performed at Harvard, Boston University, and the Fred Hutchinson Cancer Center in Seattle that explain how to develop genetically modified organisms (GMOs) that won't present a threat to the natural environment. I really think this paper is where science fiction becomes reality and we have dinosaurs to thank. Let me explain:
We've all seen the movie Jurassic Park. I'm talking about the original movie and not the shitty sequels where a T-Rex is brought to America ( just watch King Kong...the Simpsons did it...) and some crappy pterodactyls escape from a bird cage in the incomprehensible third movie. But the original is awesome and Chris Pratt is going to make the new one awesome too. Anyway, in the original movie there is a discussion between the main characters about how the dinosaurs can't escape from the island because of a built in fail-safe. The game warden Robert Muldoon mentions something called the 'lysine contingency' and we as the audience learn that the dinosaurs were genetically modified so they are unable to naturally produce the amino acid Lysine. Lysine is an incredibly important natural compound in our own bodies and the dinosaurs carry a mutation in the gene that help process and create it. With this defective gene in place, the dinosaurs in the movie must rely on diet-fed lysine in order to survive. Thus, if a dinosaur escapes it will just die because it cannot produce lysine on its own. (We should ignore the fact that lysine can be found in food and plants and the dinosaurs just eat the plants and other plant-eating animals and all is fine. 'Life finds a way' as the saying goes!)
Regardless, the important concept here is that the dinosaurs were engineered in the movie to keep these 'dino-GMOs' from escaping. In the real world there has been growing concern that GMOs could escape from the laboratory and grow unchecked in the wild. Such that they overtake the natural varieties of species already found on our planet, out-compete them in a Darwinian fashion, grow uncontrollably, and then apocalypse. I'm being a little hyperbolic here but it really is a legitimate concern, even for scientists, but it is blown out of proportion by people who don't see the value in any type of GMO whatsoever. Even in spite of the fact that we will need adaptable plants and foods as our climate changes and as an alternate strategy to combat hunger and famine.
But what this paper details is a methodology in which scientists engineered a type of 'lysine contingency' into E. Coli bacterial strains whereby they cannot out-compete their natural, wild-type bacteria. Specifically, mutations were induced in several proteins which forces said proteins to incorporate a synthetic or non-traditional amino acid into its structure in lieu of a natural amino acid. For example, a specific protein may require the amino acid tyrosine in a very specific location in its structure in order to function properly. The researchers engineered these proteins to instead substitute a non-traditional amino acid (let's call this tyrosine*). Proteins with tryrosine* still function and form properly but tyrosine* is only fed to the bacteria by researchers and not found or incorporated into proteins naturally. It is very similar to the 'lysine contingency' in Jurassic Park.
I know what you are saying, well what if these bacteria overcome this? Life finds a way, right? This is true. In fact, the experiments identify a small percentage of the engineered bacteria which do survive when the unnatural amino acid is removed from the food. The bacteria found a way to divide and grow and compete with the natural E. coli in the environment. However, some bacteria were engineered with additional mutations in several other genes in combination and these 'triple mutants' did not escape their habitat, nor out-compete their natural counterparts. This is the key point. Bacteria can be engineered to require important synthetic or non-traditional amino acids that are fed to them in the laboratory, but when that food is taken away they die. They don't mutate and escape. Life doesn't find a way.
I'm excited about this because it's a giant step in the direction of addressing the safety concerns of GMOs. A lot more work needs to be done, especially if this will be taken into plant crops like rice or wheat or corn, but it is a very important and elegant proof of concept. And for those staunchly opposed to GMOs...well this is a big blow.
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