Monday, November 27, 2017

Biohacking and DIY Gene Therapy: Revolution or Hi-tech Snake Oil?

Do you want bigger muscles? Want to make those brown eyes blue? Does your memory resemble a slice of Swiss cheese? Well, step right up and let me tell you about biohacking! Lend me your ears…and I’ll tell you how to improve them! With our new do-it-yourself genetic engineering kits, you can change whatever genes you want!

Bio-savvy entrepreneurs are determined to make biohacking a mainstream activity. Companies are emerging that promote DIY gene therapy, so now anyone with an opposable thumb can pipet DNA changes into their bodies, their pesky little sister, pets, or just about any living creature they encounter.
Wouldn’t you like to be a biohacker too? Or is biohacking just the latest incarnation of snake oil?
Josiah Zayner, who earned his Ph.D. in biophysics in 2013 at the University of Chicago, is founder and CEO of a company called The ODIN. The main objective of the company “is to make biological engineering and genetic design accessible and available to everyone.” Some of the products on the site look downright cool. One kit allows users to produce bioluminescent bacteria. Another kit makes fluorescent brewer’s yeast (which can then be used to brew beer that glows under blacklight).

Those products seem benign compared to Zayner’s ultimate objective: selling genetic engineering tools to the masses so they can modify their own genes, or those of other living creatures, in whatever way they want without any oversight or regulatory approval. Zayner has already initiated experiments on himself and encourages others to join him on this wild ride. In the rambling presentation below, Zayner explains over shots of scotch and F-bombs that he wants to crowdsource genetic engineering because he believes it will facilitate innovation. Why let professional scientists have all the fun? Zayner demonstrated how easy biohacking your genome can be by injecting the reagents into his arm during the presentation and distributing free samples for the audience to take home.


Let’s take a closer look at his idea. Zayner is using CRISPR/Cas9, a powerful new tool for gene editing, to disable his myostatin gene (learn about the basics of CRISPR/Cas9 and its application in gene therapy). Cas9 is a DNA-cutting enzyme that is directed to a specific site in DNA by a guide sequence. Myostatin stops muscles from growing, so his plan is to knockout this gene in his muscle cells in hopes that it will make them grow once again. Given his affinity for scotch, a more useful experiment might have been to enhance his alcohol dehydrogenase genes.

There is evidence linking the depletion of myostatin to muscle growth. Mice engineered to lack myostatin have double their normal skeletal muscle mass. CRISPR/Cas9 has been specifically used to knockout myostatin in animal embryos, such as rabbits, and the genetically modified animals grew to have more muscle mass. Moreover, when humans are born with mutations that lead to less functional myostatin, they also have more muscle mass (or, in less pleasant-sounding medical terms, “gross muscle hypertrophy”).

CRISPR has already been used to successfully modify human embryos (none were implanted), but to date, no one has tried CRISPR/Cas9 in a living adult. Zayner’s strategy is to simply inject plasmid DNA that contains the Cas9 gene along with the guide sequence that directs it to the myostatin gene.

Importantly, he’s produced no evidence yet to show that these reagents work in human cells. Ideally, we’d like to see confirmation of the gene modification in a muscle biopsy from Zayner, or proof that his approach works in an adult animal model. At the very least, it would be useful to know whether his system alters the gene in cultured cells.

So, can this really work? There are some formidable obstacles and shortcomings. First, the injected plasmid DNA has to get into the muscle cells. Many would argue that the DNA is likely to be degraded or damaged along the way. There is scarce evidence that intramuscular injection of DNA works, but I did find one study done in mice from 1993 suggesting it is possible, although expression levels of the gene injected in this mouse study varied. Variations in the levels of Cas9 or the guide sequence would certainly affect the outcome.

Nevertheless, let’s pretend some of it gets into a few muscle cells and they make the Cas9 protein and its guide sequence. The next big assumption we have to make is that the guide sequence used actually cuts the myostatin gene. Multiple guide sequences usually have to be tried to find one that works and, as mentioned above, I’ve seen no evidence that this particular guide sequence operates as it should in human cells.

Additionally, you have two copies (alleles) of myostatin, one from mom and one from dad. To knockout myostatin completely, Cas9 would have to cut both alleles. Let’s assume we get that far and both alleles of myostatin are cut. Sometimes cells can repair the DNA cut without incident. For myostatin to be disabled, the cell would have to make a mistake when repairing the severed DNA (which they do, but not all the time). Assuming we jump all these hurdles, that one cell or handful of cells is not likely to produce any noticeable change in muscle mass, especially if only one allele was disabled. Zayner claims repeated injections might overcome this issue, but given the sheer number of cells that would need to be altered to produce a visible effect, the claim seems to be on very shaky ground.

Despite all the caveats, disrupting a gene is actually the easiest application of CRISPR/Cas9. To add or change a genetic sequence, an additional fragment of DNA needs to be incorporated where Cas9 made the incision. And if you wanted to use CRISPR/Cas9 to give yourself wings or eyes in the back of your head, you can forget about that. We are nowhere close to knowing how to do such things.

More alarming, there is risk of dangerous side-effects. While the loss of myostatin will increase muscle size as well as bone mineral density and bone mass, it also leads to spinal disc degeneration and spinal osteoarthritis. Second, there is a risk of infection or an allergic reaction to the injections. Third, CRISPR/Cas9 has been reported to produce so-called “off-target” effects. In other words, the guide sequence sometimes escorts Cas9 to other places in the genome, where it may introduce cuts in genes that were not intended to be destroyed—a genetic equivalent of friendly fire.

There’s also the possibility that the CRISPR/Cas9 plasmid itself could integrate into the genome, again possibly disrupting critical genes. One study showed that DNA injected into mouse muscles persisted for life, cranking out the protein constantly. What would happen if Cas9 continues to be produced in Zayner’s cells for the rest of his life? In the worst-case scenario, it would continue to cut up his DNA indiscriminately. There’s also a study in mice suggesting that DNA injection can accelerate autoimmune responses. Finally, unlike injecting an embryo in which all cells have a high probability of being modified, Zayner’s approach is going to produce mosaic effects. In other words, some cells will be edited, but others will not, which could result in a disfigured arm. Zayner dismisses all of these risks with disquieting nonchalance.
If you don’t want to risk modifying your genome to kill your myostatin gene, you can always buy inflatable muscles to wear under your shirt.
Zayner not only advocates genetic modification of your body, but he also encourages biohacking all of nature. He paints a world where you and your buddies decide to order a pizza one night and, what the hell, genetically engineer a puffin to look like a porg. Eschewing the substantial ethical concerns, he is understating the difficulties surrounding genetic modification of complex animals and the sophisticated equipment and training needed to do it. Below is an excellent TED Talk by Ellen Jorgensen that examines the hyped-up claim that CRISPR/Cas9 is cheap and easy.




There’s no product currently available from The ODIN that could bring on the apocalypse, but it is the principle that concerns many people, scientists and non-scientists alike. Even the most avid science enthusiasts are likely to take issue with providing potential crackpots the tools to screw with the recipe of life. Genetic engineering is exciting and promising, but must be explored with great caution by well-trained professionals following reasonable regulations because there is no way to unscramble this egg.

Biohacking has been banned in several countries, and on November 21, 2017 the FDA updated their web site to state that self-administration of gene therapy is against the law. It seems that Zayner, a self-professed fan of the TV show Survivor, just had his torch snuffed out by government regulators chanting, “The tribe has spoken.”

Contributed by:  Bill Sullivan

Follow Bill on Twitter.

The author thanks Colin Sullivan for research assistance and helpful discussions, and Jason Organ for editing and helpful suggestions.

Thursday, September 14, 2017

Awkward To Awesome: Dr. Ty Tashiro on Communicating the Science of Being Awkward

Ty Tashiro knows awkward. As he charmingly admits in his second book, Awkward: The Science of Why We’re Socially Awkward and Why That’s Awesome, he was no stranger to deviating from the norm. But he soon realized that the same characteristics that make awkward people stick out like a sore thumb also make them stand out in the most amazing ways. Ty’s awkward ways earned him a Ph.D. in Psychology from the University of Minnesota, and then he became an award-winning professor at the University of Maryland and University of Colorado.


Ty Tashiro (photo by Brandi Nicole)

Ty is also passionate about science communication, eager to tell the world about fascinating new work in psychology. His first book was The Science of Happily Ever After, which is a scientific guide to finding everlasting love. His work has been featured in the New York Times, the Washington Post, Time.com, TheAtlantic.com, and on NPR and Sirius XM Stars radio. Ty kindly agreed to answer a few of our questions about his latest research into awkwardness and why he decided to write popular science.
Awkward Can Be Awesome!
Sullivan:  In your book, you comically describe several instances where you yourself have felt awkward. Tell us more about the ways that awkward can be awesome.
Tashiro:  I think a sense of levity with one’s awkwardness is helpful for everyone because who hasn’t had a blush-worthy awkward moment that turned into a great story? There’s nothing wrong with being awkward, but it’s helpful for awkward people to understand their unique attributes that can be leveraged to accomplish extraordinary outcomes.
I like to explain what social scientists have discovered about social awkwardness with a spotlight analogy. Imagine that you see life unfold on a stage and that stage is broadly illuminated. You could easily shift your attention as people enter or exit the stage, watch the key interactions at center stage, and pick up on the context around center stage. That’s how most people see the social world.
Awkward people see their stage spotlighted and their sharply focused beam of attention tends to fall a little left of center stage. So, they’re more likely to miss some of the key social information at center stage, but whatever falls under their spotlighted attention is seen with great focus and potentially a brilliant clarity. This spotlighted perspective manifests in behaviors such as intense focus, persistence, and even an unusual level of enthusiasm for the things they love.
There are interesting behavioral genetic and developmental psychology studies that show a moderate, but robust association between social awkwardness and striking talent, which is a way to describe people who show exceptional ability or achievement in a specific area. Although some of this correlation is accounted for by I.Q., the stronger mediator is their obsessive drive to learn everything they can and master their area of interest.

Are Science Nerds Real?
Sullivan:  This certainly doesn’t apply to all scientists, but I know many who would describe themselves as socially awkward. Do you have a sense as to why scientists might be disproportionately awkward?
Tashiro:  Simon Baron-Cohen and his colleagues have been at the forefront of understanding people with social skill deficits, communication difficulties, and the kind of obsessive interest that characterize socially awkward people. In a series of studies, they compared the degree of awkward characteristics among Oxford students majoring in the humanities, sciences, computer science, and a group of high school students involved with their school’s math competitions. What they found was that compared to humanities majors, those students majoring in sciences, computer science, and the matheletes reported significantly more awkward characteristics.
Follow-up studies suggest that people with awkward characteristics tend to think in a more systematic or methodical manner, which is a style of problem-solving that is well-suited to fields like science, computers, or math that employ things like the scientific method or orders of operation.
Awkward people love to take things apart, intensively study how the pieces function, then put those pieces together in a way that makes more sense. In this way, the awkward mind can be advantageous for someone who is passionate about describing, organizing, and predicting phenomena.



Ty Tashiro’s second book, Awkward: The Science of Why We’re Socially Awkward and Why That’s Awesome, examines what it means to be awkward and how those traits also often lead to success.

Antidote for the Esoteric.
Sullivan:  Being socially awkward might hinder one’s ability to communicate research effectively. Do you have any advice for people who fall into that category?
Tashiro:  The risk for any awkward person is to fall too far down the rabbit hole. Researchers are rewarded for being meticulous about details, learning how to effectively use the specific terminology in their subfield, and being hyper-aware of methodological nuances. None of these qualities should be compromised because they are necessary for great science, but it’s also easy to see how the best of us could get so deep into their field of research that they forget what the non-specialist wants to know or needs to know.
Part of the problem is that a great lab usually means that the Principal Investigator manages an army of graduate students, post-docs, and undergraduate research assistants. With the time pressures and publication pressures, the P.I. gets data or results, but begins to lose an opportunity to be hands on.
I remember hearing a story in graduate school about Harry Harlow, who is famous for his early primate studies that showed infant primates preferred a cloth surrogate mother that provided tactile comfort to a surrogate mother that provided food. My professor was an emeritus faculty at Minnesota who told us that the spark for Harlow’s idea occurred while he was cleaning the cages of the primates, a task usually reserved for research assistants. Harlow noticed that the primates resisted when he tried to remove the towels from the bottom of their cages. Harlow’s willingness to immerse himself with his subjects allowed him to see a pragmatic, but revolutionary insight.

Why SciComm? 
Sullivan:  What motivated you to write about science for a broader audience?
Tashiro:  When I was an assistant professor at the University of Maryland, I loved teaching an undergraduate course about the psychology of interpersonal relationships because the students asked incisive, practical questions that often left me speechless or inarticulate. I could walk them through a compelling, programmatic area of research and they would politely ask me, “So what?”
These students wanted to know how evolutionary research applied to their mate preferences on Friday night or how they could apply social psychology studies of persuasion to help a friend out of an unhealthy relationship. My answers were not always satisfactory, so maybe out of stubbornness I decided to tackle the problem of translating great social science into practical advice. While we usually think of translational research as the gap between basic and applied science, my translational task has generally been to bridge the gap between applied research and the general public.

Ty’s Tips for Science Writers.
Sullivan:  What tips can you give aspiring science communicators?
Tashiro:  I’ll start with the bad news, then give you the good news. As I began investigating how to write in a compelling manner for broad audiences, I realized that the cornerstones of great storytelling are rich scenes, complex characters, and brisk plot. Then, I realized that science writing for journals has no scene, character, or plot. Some people might protest that the materials, subjects, and procedures count, but that’s a stretch.
I should be clear that I don’t think science writers should change how they write for journals or their colleagues. There’s a precision and factual nature to good science writing that is valuable and necessary, but it’s a style that does not appeal to broad audiences. So, the starting point for aspiring science communicators is to think about how to infuse scene, character, and plot into the scientific narrative.
My strategy has been to open every chapter with a story that is humorous or mysterious and this story sets up a research problem. In AWKWARD, I set up the descriptive statistics chapter with a middle school mishap involving awkward all-star wrestling re-enactments that ended with me concussed. I set up the social neuroscience chapter with a story about my first middle school slow dance that left readers wondering whether the boy should kiss the girl.
Both stories are absurd, mildly embarrassing for me, but they allow me to get readers invested in a character who needs to solve a conundrum. The middle parts of my chapters give readers research findings that help them piece together clues about why I ended up concussed or whether I should go in for the kiss. I end each chapter by giving the reader the outcome from the opening story, which allows me to summarize the data through the lens of a character trying to take appropriate action on a scene.
For researchers in physics, biology, or other fields that do not always involve human subjects, you sometimes end up anthropomorphizing molecules or species, but this can provide a wonderful opportunity for fanciful, unexpected storylines.
As science comes under siege these days, it’s more important than ever for the science community to cooperate and find a way to captivate the broader public with science and to share the wonderful discoveries you’ve observed under your brilliant spotlight.

This article originally appeared on PLOS SciComm Blogs.

Bill Sullivan


Bill Sullivan is Showalter Professor at Indiana University School of Medicine, where he studies infectious disease. Bill has published over 70 papers in scientific journals and written for Scientific American, Scientific American MIND, Salon.com, GotScience.org, What Is Epigenetics, and more. He also maintains his own popular science blog called THE ‘SCOPE. Bill received his Ph.D. in Molecular & Cell Biology from the University of Pennsylvania.

Monday, June 26, 2017

A reboot for #SciCommPLOS

Attention 'SCOPE readers...

We are excited to announce that THE 'SCOPE's own Bill Sullivan and Jason Organ have teamed with Krista Hoffmann-Longtin of Indiana University Purdue University - Indianapolis (IUPUI) to take over editorship of the Science Communication blog at the Public Library of Science (PLOS).

You can continue to expect high quality #scicomm blogging from Bill and Jason here at THE 'SCOPE as well as in their new roles as editors of #SciCommPLOS.

Thank you for reading! Without your support, this new adventure would not be possible.

-The "Management"



Friday, May 12, 2017

Could Parasites Be Causing Prostate Cancer?


Long ago in the mid-1600s, a fellow named Antonie van Leeuwenhoek started making lenses…as a hobby (remember, Facebook and Netflix were not invented yet). He was so adept at grinding glass that his lenses were able to magnify objects about 270 times their normal size. Leeuwenhoek soon discovered a whole new universe right here on earth, a universe of creatures so tiny that only his microscope could reveal them. He called them "animalcules."

With his powerful microscope, Leeuwenhoek became the first person to see amoebae, bacteria, and blood cells. For these revolutionary discoveries, he is considered “the father of microbiology.”

But after looking at endless water samples, the ever-curious Leeuwenhoek wondered what bodily fluids looked like under his microscope. While Leeuwenhoek examined blood, sweat, and tears (and a lot of dental plaque), a medical student in 1677 named Johan Ham told Leeuwenhoek that he spotted animalcules swimming in the semen he collected from a gonorrhea patient.

Believing these animalcules might be a result of disease, Leeuwenhoek procured a clean semen sample from his own stock - obtained fresh after proper lovemaking with his wife, he insisted. Leeuwenhoek confirmed Ham's finding and went on to discover the same tiny eel-like critters teeming in the semen from many other species. This is how we came to make the “seminal” discovery of sperm cells.

Other people in Leeuwenhoek’s day mistook these microscopic beasties squiggling around in the semen to be "merely" parasites, referring to them as “seminal Worms.” In fact, we didn’t realize that these “semen parasites” played a key role in fertilization until the 1870s when Oscar Hertwig spotted the fusing of nuclei from sperm and egg after contact…in sea urchins of all places.

We didn’t figure out where babies come from until fairly recently – 1870. White studying sea urchins, Oscar Hertwig noticed that the nucleus in the sperm fuses with the nucleus in the egg (the nucleus is the cellular organelle housing DNA).

While the mystery of sperm has been solved, we have indeed discovered a variety of pathogens that can inhabit our nether regions. Trichomoniasis, scrotal filariasis, and Chlamydia are just some of the unpleasant conditions caused by these most intimate of uninvited guestsAn unsettling new study led by graduate student Darrelle Colinot at the Indiana University School of Medicine may have found yet another.

In experiments performed in mice, researchers found that the common single-celled parasite called Toxoplasma gondii disseminates to the prostate within two weeks after infection. And there it remains in the form of latent tissue cysts for at least sixty days, but probably for the rest of the host’s life. The presence of these parasitic cysts led to chronic inflammation in the prostate, which is a precursor to benign prostatic hyperplasia (BPH), the reason why older men have to get up multiple times to pee at night. Chronic inflammation in the prostate is also connected to prostate cancer, which afflicts more than 200,000 men in the US each year.

Parasites in prostates. The control panel shows cells from an uninfected mouse prostate (the nuclei are stained blue). The other panel shows the presence of a Toxoplasma tissue cyst (green) in the prostate 14 days post-infection (14 D.P.I.).

If Toxoplasma is also found to trigger chronic inflammation in human prostate, the finding takes on added significance given the prevalence of the parasite in the human population. According to the CDC, up to 22% of Americans are infected with the parasite, which is transmitted through oocysts that are excreted into the environment by infected cats or through tissue cysts present in game and livestock. 

Women are commonly advised to avoid gardening, changing the litterbox, and consuming undercooked meat while pregnant so the parasite doesn’t transmit to the fetus. Men may need to heed these warnings as well to avoid a prostate full of parasites, but a lot of critical work still needs to be done before we can ascertain whether this discovery has relevance to prostate issues in humans. Regardless, our study introduces Toxoplasma-infected mice as a powerful new model for the study of prostatic inflammation.

Prostate cancer is believed to arise from a constellation of events that can involve a person’s genes and environmental exposures. Infectious agents and carcinogens have previously been proposed as agents that can injure the prostate and lead to the development of chronic inflammation. Numerous types of bacteria and viruses have been shown to infect the prostate and cause an inflammatory response; this new study in mice suggests that the parasite Toxoplasma might be added to this list.

Contributed by:  Bill Sullivan

Note:  Bill Sullivan is a co-author on the study highlighted in this article.


Reference:


Colinot, D., Garbuz, T., Bosland, M., Wang, L., Rice, S., Sullivan, W., Arrizabalaga, G., & Jerde, T. (2017). The common parasite induces prostatic inflammation and microglandular hyperplasia in a mouse model The Prostate DOI: 10.1002/pros.23362

Saturday, April 22, 2017

We Support The March For Science

In person or in spirit, scientists and science enthusiasts MARCH FOR SCIENCE today. Why? Science is the most reliable method that humanity has devised that teaches us how things work - it is the beacon that leads us to the truth. Truths that are often well-disguised, beyond our intuition, and shielded behind our preconceived notions. The truth can upset worldviews and bottom lines, but those who resist it cannot be allowed to jeopardize the reality reasonable people have come to accept. When we forego the evidence to maintain a faulty reality, we fail to progress. A world that doesn’t invest in science will pay for it with another Dark Age.


Support science, education, and evidence-based policy.