(Long story short: The FCC is about to make a critical decision as to whether or not internet service providers have to treat all traffic equally. If they choose wrong, then the internet where anyone can start a website for any reason at all, the internet that’s been so momentous, funny, weird, and surprising—that internet could cease to exist. Here’s your chance to preserve a beautiful thing.)

If you can, please add your channel to our petition. We’ll deliver this to the FCC in September and demonstrate that the online video community cares about this issue.

It is really important that the FCC understands that online video creators care about Net Neutrality. Even if you’ve only ever uploaded ONE VIDEO, you are a creator and you have a voice.

Here’s the deal: Telecommunications companies already charge us to access the Internet through our homes and our phones. New FCC rules could allow them to also charge content providers (like YouTube, Netflix, and even PBS) for access to our eyeballs. It could create a fast lane for Jimmy Fallon’s clips, and slow lane for your YouTube videos.

Net Neutrality means that your YouTube videos reach people at the same speed as clips from last night’s episode of the Tonight Show. It means a level playing field for video creators looking to reach an audience. But new Net Neutrality rules could mess that up.

Whether your YouTube channel is home to daily vlogs, short films, or just that one video from when the cinnamon challenge seemed like a good idea, you’re a video creator. Your content and comments help shape this community. Let’s keep it that way.

This isn’t just about not being able to binge-watch a series on Netflix. It’s about the future of online video as we know it.

You’ve heard all these rumblings about Net Neutrality over the past several months. Let’s get real: this is about controlling online video. It is estimated that by 2017, video content will account for 80-90% of all global Internet traffic.

The photo found its way to Wikimedia Commons, who says that since Slater did not take the photo himself, it is considered public domain.

Hey everyone!

Another Comic Con has come and gone, and has got us all excited about new sci-fi movies like the fourth Jurassic Park and the first part of Mockingjay- which reminded us of some science facts! Back in March, we published an article about the fictions and realities of genetic engineering. More recently, we had the chance to ask some questions directly to Alex Klattenhoff, a graduate student at the University of Pennsylvania, who is currently studying how to manipulate diseases at the genetic level.

Q: How complex is mapping out the genome of a living animal?

A: This is one field that has advanced rapidly within the last two decades. The search to understand DNA, the building block of life, began when it’s structure was solidified in the 1950’s. Originally, it was nearly impossible to determine the sequence of a strand of DNA. However, the eventual development of Sanger sequencing revolutionized the field in the 1970’s.

Broadly accepted as the first generation of genetic sequencing, it allowed scientists to sequence DNA one base at a time. However, this was relatively expensive and extremely time consuming. It was a pretty culminating moment when the Epstein-Barr virus (about 200,000 base pairs) was completely sequenced in the early 1980’s.

With the human genome sitting around 3 billion base pairs, however, either a lot of time and effort was needed to put it together or a different technology needed to be adapted. Both eventually happened. First, the Human Genome Project was launched in 1987 using the expanded technology of the times (shotgun sequencing). They broke up the human genome into chunks, and then broke those chunks up into small fragments. They then sequenced each fragment a base at a time, and then pieced it all back together by remembering which fragment came from which chunk. It was a massive effort, and took 15 years to complete.

Concurrently, the technology proceeded to become streamlined. Rather than literally sequencing each base by hand on a gel, eventually machines were developed to read each base. This got faster and much more efficient, until they can now sequence a genome that size within mere hours, but analyzing and reconstructing the genome often takes longer. Various techniques or buzzwords include the use of high-throughput sequencing and massive parallel sequencing. The company and machine I’m most familiar with is Illumina, which ultimately puts thousands of these small DNA fragments onto a single chip, and simultaneously reads their bases one at a time.

Most importantly is cost. Although I remember Steve Jobs had his full genome sequenced for $100,000, technology has drastically reduced the price year by year. With different competing companies, the price has recently dropped to around $1,000 for a unique genome read. This means even individuals could essentially pay this much to get their entire genome sequenced - although the technology still remains mostly reserved for scientific study at the moment. So essentially, nowadays it is extremely easy to sequence an entire animal - or even entire individual’s - genome.

Q: How likely is it that, if we have the ability to change a particular gene, it will affect the trait we want to change?

A: *Note - I’m assuming you’re talking about a human.*

This is a multifaceted question. First off, we are EXTREMELY good at synthesizing or changing DNA in a test tube. This essentially came from the development of sequencing. Using different DNA techniques, we can easily introduce a number of changes into a gene - anywhere from changing one base to another, deleting bases, or introducing bases. This is a basic molecular biology technique nowadays.

With this fact, your question has to be reformatted a bit. First off, think about how DNA changes naturally. Although your cells constantly divide and duplicate their DNA, it stays the same (for the most part). The majority of changes take place upon conception - where different sets of slightly different DNA from parents are combined together in a unique manner to create a new offspring. This happens by introducing different alleles (variations of genes) or through recombination (shuffling around genes and DNA). This is one way in which scientists have looked into changing genes in an individual.

Secondly, Another mechanism in which DNA is changed naturally in an individual is by viruses. Viruses uniquely (and often randomly) insert their own DNA into a host’s genome during their infection cycle. Scientists have thus adapted this natural phenomenon to be able to insert DNA into genomes using a similar strategy.

Thirdly, we have a multitude of strategies (again, developed by the discovery of sequencing) that allows us to home to certain sequences within a DNA sequence. Many enzymes (proteins that do all of the operations in cells) naturally recognize sequences in your genome to activate, deactivate, or modify gene expression. Some of them are even able to cut DNA at specific sites. Using this natural phenomenon, scientists have developed enzymes that can cut up a gene (and thus deactivate it) with good accuracy.

With these three points, the current technology can do a couple of things. It can randomly insert synthesized DNA into a genome using the modified virus method, it can more specifically insert DNA into a genome using the modified recombination method, or it can cut and disrupt a gene already existing within a genome using the modified homing enzymes. Each of these has advantages and disadvantages. More importantly, we cannot truly “change” a gene, but can rather insert new DNA or silence a gene.

With this outlined technology, we can theoretically do one of two things - introduce a “good gene” or disrupt a “bad gene”. However, the next part of your question is particularly insightful. Can we impact a desired trait? The answer is yes and no.

First off, the simple answer. What you describe as a trait is a physical manifestation of a gene. The easiest way to think of this is a one to one ratio - that one gene affects a particular trait. There are several examples of this - the example I will be using is the Phenylketonuria disease (PKU). People have a single gene which produces the protein Phenylalanine Hydroxylase, which breaks down the amino acid Phenylalanine for your cells to properly use it during their normal functions. The disease comes from people who have a mutant version of this gene, which fails to make a functional Phenylalanine Hydroxylase protein. Thus, whenever they eat food that contains Phenylalanine, it cannot be properly broken down. It then is thought to accumulate unhealthily in the body, and especially harms normal neural functions.

Ideally, introducing a “good gene” that can properly express Phenylalanine Hydroxylase would completely alleviate this disease.The difficulty is you would have to give this “good gene” to the cells in the body that are supposed to express Phenylalanine Hydroxylase (say your gall bladder cells known to produce enzymes to break down foods), and make sure enough of the cells get the good gene to make a difference. Essentially, this is a matter of targeting the correct cells at a large enough scale.

However, traits are rarely caused by only one gene. A good example is eye color. You would think that one gene is responsible for blue eyes, but this is certainly not the case. Eye color is based off of a multitude of genes and variations of those genes. Thus, changing one gene may not be enough to change eye color. Most importantly, research has still been unable to tease out the complex interactions of these traits. Or more so, some traits and their contributing genes have simply not been investigated.

Thus, in direct answer to your question, we have the capacity to change genes within a human by inserting “good genes” or disrupting “bad genes”. However, targeting the right cells and targeting enough cells is difficult. More importantly, there is not enough research about many traits to know which gene (or more often which GENES) govern its phenotype. It is thus difficult to even consider changing some traits, because their genes remain unknown. Most research has been focused around genes that contribute to medical diseases, and as such those are the traits that are first being investigated.

Q: What are the current goals of people in the genetic engineering field? What are they trying to learn and what will that knowledge help them accomplish? What is the near future of the field going to look like if that knowledge is achieved?

A: Whoo! Lots of good questions. Although I am certainly not omniscient, I can detail some of the major obstacles and pursuits I know of from my graduate career. Here we go. I’m subdividing this question into parts.

Part 1 - Current Goals

As mentioned above, we have the technology to insert “good genes” or disrupt “bad genes”. The first and easiest answer is that our ability to do these things is not perfect. A lot of research is going into increasing the fidelity of these techniques (how often it works) and making them more specific (as in making sure accidental disruption of “good genes” doesn’t occur when we are only intending to disrupt a “bad gene”.)

Along the same lines, inserting “good genes” still has a lot of issues. Using recombination allows for insertion into specific sites within a cell, however this is often very inefficient. Using viruses allows for more efficient insertion, but often inserts the “good genes” randomly into the genome. This has potentially hazardous consequences, including insertion into normal working genes. Most notably, a virus could accidentally insert a “good gene” into another good gene responsible for preventing cancer. When that happens, an onset of cancer could potentially occur. Thus, a lot of research is being developed into either improving recombination techniques to increase it’s fidelity or discovering a virus that inserts into a particular region or modifying a virus that can home to a specific region.

Something I didn’t mention above is the fact of immune barriers. Our body has defenses against foreign particles, some of which are identified by foreign DNA or foreign protein production. If we introduce a “good gene” into a cell, oftentimes their body recognizes it as a foreign body. The immune system will then kill that cell. Other times, the immune system simply recognizes the actual viral particle used to deliver the gene. It will also then absorb and remove those particles before they are able to do their job of delivering the gene. Both of these avenues either fail to introduce a long-term “good gene”, or sometimes cause inflammation which can be painful or even life threatening to an individual. A lot of research is going into both developing viral vectors (the modified viruses responsible for delivering the “good gene”) that are not removed by the immune system, and synthesizing “good genes” that are not recognized as foreign to the immune system. This allows the cells that now express the “good gene” to remain alive and functional.

Along the same lines, immunology as a whole is still not well understood. More directly, it is not known in all cases how a body identifies something as foreign or not. Thus, some tangential research to gene therapy involve understanding how you could tolerize the immune system to a “good gene” that your body would otherwise recognize as foreign.

And lastly, research simply understanding which genes are responsible for different traits is still wide open. As I mentioned, most research has revolved around identifying genes responsible for human diseases. However, even in that area there are still quite a few unknowns. Similarly, certain genes may be important say while you are a young, but less important when you are older. So also understanding the timing of when genes are responsible for a particular trait is important. That doesn’t even touch on the concept of whether expressing too much of a gene, to little of a gene, or when to express a gene could all have differential impacts on how we influence traits.

Part 2 - Near Future Findings

Despite the daunting task of understanding the above, the field of genetic engineering has still had some very pivotal progress in the past decade. Although tragic, the first case of successful gene therapy occurred in 1999 (Jesse Gelsinger case). A young man developed a disorder called OTC deficiency. Similar to PKU disorder, he lacked an enzyme vital in digestion. By inserting a “good gene” with a viral vector, he was able to reverse the deficiency. However, unpredicted by scientists at the time, the virus vector was severely immunogenic and caused a fatal immune response.

As such, the field of gene therapy has been set back but importantly so. Understanding the immune system, as well as the genetics behind the engineering, is now stressed. However, in the ten years to follow, there is now progress being made on this front. Four years ago, a type of blindness was cured by introducing a gene into the back of the eye tissue. A viral vector which inserted into sections of the genome not encoding for normal genes was used. More importantly, the eye is an “immune privileged” organ in the body, meaning that the immune system seems removed from this area. Although a non-immunogenic vector was still used, this drastically reduced the incidence of immune reaction to unreported results. As of now, the treatment has been approved by IRA boards and is being implemented in clinical trials.

Similarly, a technique called adoptive immunotherapy is being used to treat a type of leukemia. In this strategy, T cells are removed from the body and then genetically engineered. This temporarily removes them from the body (and thus its immune system) to allow for ease of viral vector integration. The T cells also seem to be extremely resistant to cancerous phenotypes, and the fidelity is easily overcome as T cells proliferate very rapidly on their own. It is thus easily to safely generate engineered T cells at high quantities to return back into the subject. These T cells are engineered to express molecules that recognize cancerous cells in the body (of this particular leukemia), and then proceed to attack and kill them in cancer subjects. It is currently in clinical trials, and has thus far cured 20 people now at up to a year and a half as cancer free with no side effects

Thank so much to Alex for taking the time to answer our questions so thoroughly! We hoped you enjoyed this, and if you have any further questions about this or any science topic you’d like discussed, please feel free to send them to us!

DFTBA!

Photo Credit and Fanart of Mr. DNA (of Jurassic Park) Courtesy of Alyssa Nabors