It’s Almost iGEM Season—Help Is On The Way!

The 2019 iGEM Competition is on the horizon and team registration opens this month. We’re excited to partner with the iGEM Foundation again this year and offer our support to the young scientists who participate. If you’re starting an iGEM project, there are going to be things you need along the way. We are pleased to share a number of different ways we can help your iGEM team from now until the Giant Jamboree.

Grant Sponsorship

Tell us about your iGEM project and your team could win a 2019 Promega iGEM Grant Sponsorship. Ten winning teams will each receive $2000 in free Promega products to use for their iGEM projects. Tell us about your project—What problem are you addressing? What is your proposed solution? What challenges does your team face? Last year’s winning teams selected from a wide range of reagents and supplies, including master mix, restriction enzymes, ligase, DNA purification kits, expression systems, DNA ladders and markers, buffers and agarose. Click here to apply! Continue reading “It’s Almost iGEM Season—Help Is On The Way!”

Combatting Gun Violence with Synthetic Biology

Imagine you are a high school student living in a community devastated by gun violence and death. In the U.S., this could be one of many communities, but it happens to be Baltimore which had 301 deaths due to gun violence in 2017 (with a per capita rate well above other large cities). Then imagine you were part of an organization within that community that helped you, along with other students, gain knowledge and skills to come up with a viable solution to the problem using synthetic biology.

Baltimore Bio-Crew at the 2018 iGEM Giant Jamboree

This is exactly how the Baltimore Bio-Crew came up with their iGEM project, Coagulance Rx. The Baltimore Bio-Crew decided to tackle this community issue head-on. One team member, Mercedes Ferandes, reflected, “Living in Baltimore City, I have not only witnessed gun violence in front of me, but have had family members and friends die from it. I wanted to try to decrease the amount of deaths by gun violence using iGEM.”

After some research, they discovered that many of the gun deaths were due to blood loss and could have been prevented. The impoverished neighborhoods where this violence occurs lack the resources to provide timely emergency medical treatment. Many of these deaths can be attributed to delayed arrival of emergency response teams—wait times for an ambulance can be over an hour.

Although there were several contributing factors beyond their control, the team wanted to address this problem by focusing on blood clotting and how it could be helpful as a quick temporary treatment for open wounds. This solution could offer a reliable, cost efficient way to save lives by slowing or stopping blood loss until a victim could get medical attention. The team decided to pursue the use of snake venom after coming across some previous iGEM projects that had used it for clotting. Team member Henry Ryles pointed out that the need for snake venom powerful enough to clot blood quickly led them to choose the venom of the Russell’s Viper
(Daboia russelii).

Continue reading “Combatting Gun Violence with Synthetic Biology”

How To Make Medicine on Mars

Today NASA’s InSight lander will touch down on Mars. InSight, which launched on May 5, is NASA’s first Mars landing since the Curiosity rover in 2012. The lander will begin a two-year mission to study Mars’ deep interior, gathering data that will help scientists understand the formation of rocky planets, including Earth.

NASA's InSight lander approaching Mars.
Image credit: NASA/JPL-Caltech

While every spacecraft that reaches Mars offers more knowledge of the Red Planet, a lot of the excitement is fueled by hopes that someday these missions will bring humans to Mars and enable us to start colonies there. While this goal seems very distant, tremendous progress is being made. Scientists around the globe are making incremental discoveries that will lead to the advances necessary to make colonization of Mars a reality.

I had the pleasure of meeting one team of scientists doing just this—eight high school students from iGEM Team Navarra BG. I met the team and their advisors at the 2018 iGEM Giant Jamboree, where they presented their synthetic biology project, BioGalaxy, as part of the iGEM competition. The problem they aimed to solve is key to helping humans stay on Mars for an extended period of time—how do you take everything you need when there isn’t enough room on the spacecraft? Continue reading “How To Make Medicine on Mars”

Building a Career in Science: Academia or Industry?

If you’re a student in a research lab, discussing career options with your PI can be a tricky topic to navigate. Whether real or perceived, many students feel they cannot bring up the subject of a career in industry with their PI because they will lose credibility as a serious researcher. In labs where thinking about careers outside of academia is taboo, students can’t get all the information they need to decide what career path is right for them.

This dilemma became very clear a few weeks ago when I served as a panelist for a career workshop about jobs in industry at the iGEM 2018 Giant Jamboree. The workshop participants were extremely engaged, and we fielded questions well after the official end time. Since I know there are other students who could benefit from information about science-related careers in industry, I’ve compiled some of the questions and answers from the workshop. Continue reading “Building a Career in Science: Academia or Industry?”

Overcoming Challenges When Scaling Antibody Production

Tradeoffs are a constant source of challenge in any research lab. To get faster results, you will probably need to use more resources (people, money, supplies). The powerful lasers used to do live cell imaging may well kill those cells in the process. Purifying DNA often leaves you to choose between purity and yield.

Robot performing autosamplingWorking with biologics also involves a delicate balancing act. Producing compounds in biological models rather than by chemical synthesis offers many advantages, but it is not without certain challenges. One of those tradeoffs results from scaling up; the more plasmid that is produced, the greater probability of endotoxin contamination.

Continue reading “Overcoming Challenges When Scaling Antibody Production”

Conflict, CRISPR and the Scientific Method

Scientific inquiry is a process that is revered as much as it is misunderstood. As I listed to a TED talk about the subject, I was reminded that for the general public the foundation of science is the scientific method—the linear process of making an observation, asking a question, forming an hypothesis, making a prediction and testing the hypothesis.

While this process is integral to doing science, what gives scientific findings credibility and value is consensus from the scientific community. Building consensus is the time-consuming process that includes peer review, publication and replication of results. It is also the part of scientific inquiry that so often leads the public to misunderstand and mistrust scientific findings.

Continue reading “Conflict, CRISPR and the Scientific Method”

Millions of Pickles, Pickles in the Sea

For a few years beginning late in 2013, warmer ocean conditions in the eastern Pacific prompted the appearance of unexpected species and toxic algal blooms that devastated others. When temperatures cooled in 2017, the marine ecosystems seemed to be returning to normal. Except for the pyrosomes. Although these previously rare organisms did start to wash up on beaches during the periods of warming, they began to appear by the millions from Oregon to Alaska that spring.

Pyrosomes
Photo by Steven Grace.

Some combination of ideal conditions led pyrosomes to multiply, dominate the ocean surface and wash up on beaches along the US and Canadian Pacific Coasts. Pyrosomes typically exist offshore, far below the surface in warm, tropical waters all over the world. Their sudden proliferation in other areas is likely due to the warm, Pacific ocean “blob,” although atypical sea currents and changes in pyrosome diet have been offered as other possible explanations.

While the appearance of pyrosomes impeded the efforts of fisherman by clogging nets and filling hooks, greater ecological effects have yet to be observed. As we celebrate World Oceans Month, pyrosomes offer a mesmerizing example of the astounding biological diversity our oceans have to offer and, perhaps, a cautionary tale of the impact climate change can have on those marine lifeforms.

The pyrosome species common in the NE Pacific, Pyrosoma atlanticum, goes by a few other colorful names. Each name reveals something captivating about these creatures. Commonly called “sea pickles” due their size, shape and bumpy texture (like a transparent cucumber), these are not single organisms, but colonies formed by hundreds or thousands of individual multicellular animals call zooids.

Continue reading “Millions of Pickles, Pickles in the Sea”

High-Throughput Purification with Experts Included

Implementing automated nucleic acid purification or making changes to your high-throughput (HT) workflow can be complicated and time-consuming. There are also many barriers to success such as challenging samples types and maintaining desirable downstream results that can add to the stress, not to mention actually getting the robotic instrumentation to do what you want it to. All of this makes it easy to understand why many labs avoid automating or own expensive instrumentation that goes unused. Continue reading “High-Throughput Purification with Experts Included”

Reflections of a Thankful Former Teacher

Today is the start of Teacher Appreciation Week in the United States, punctuated tomorrow by National Thank a Teacher Day. I used to be on the receiving end of the various expressions of gratitude bestowed upon our educators: platters of brownies or cookies from the Board of Education, free meals from restaurants, discounts at retail stores and, if you were really lucky, maybe a student or two (likely initiated by their parents) would bring a gift card or note.

I would also reflect on the teachers that I was personally thankful for: my elementary teachers through graduate school professors (I still remember most of them by name and, with few exceptions, I received what I needed from all of them to learn and grow), my colleagues (who provided mentorship, support and comradery to me and so much more to their students) and my parents (who taught my earliest and most important lessons).

But now I find myself looking at this annual celebration of teachers from the other side—it has been two years since I became a science writer after nearly a decade of teaching high school science. The transition has completely changed my life in ways I could not have imagined and has also impacted the way I think about educators.

The main impetus for this career change was burnout. I had spent countless early mornings, late nights and weekends grading, planning lessons, completing professional development requirements and simply worrying about what challenges I would face the next morning, week or class period. The pressures of each school year would crescendo to a near breaking point every May, and then be swiftly wiped away by the arrival of summer break.

This cycle seemed inevitable, but I had been conditioned by the cultural narrative about teachers to consider it a tolerable tradeoff to the enviable benefits of teaching: holidays and summers “off”, ending the workday before 4 (even I groaned while typing that), great (read: better than average American, worse than someone with similar level of education and experience) benefits & retirement.

Unfortunately, this wasn’t sustainable for me. Moreover, legislative changes and budget cuts exacerbated the ever-present stress to new levels during my last few years as an educator. The strain was taking a toll on my mental health and my ability to be present with family and friends, especially my children.

In my new position, I have been met with intellectual challenges equal to those I encountered as a teacher but face a manageable amount of stress and few threats to work-life balance. Ending my teaching career was probably one of the best decisions I have ever made for my personal well-being. But despite this newfound joie de vivre, I am left with a feeling of guilt that resurfaces whenever issues I used to be so connected with make their way to the national spotlight.

Two of these have been in the news a lot this year—repercussions from budget cuts to education and gun violence in schools. I shouldered the burden of helping my students’ process school shootings and personally dealing with the reality that I could be in the middle of such a tragedy. Similar to the recent wave of teacher walkouts, budget measures that targeted educators brought me to the state capitol in protest.

Yet, I don’t have to face these issues with the sense of urgency I used to. My guilt is rooted in the fact that being a good teacher required selflessness and I chose to be selfish and leave because I couldn’t meet that expectation. It is perhaps because of this nagging feeling that I now feel a gratitude toward teachers that I didn’t before. I am still thankful to all the teachers in my past, but now my appreciation also extends to those that are and will become the future of education.

This year for Teacher Appreciation Week I want to express special gratitude for all of the teachers who feel the same pressures I did and are able to persist. I admire those of you already in the classroom and know you are putting your students’ needs ahead of your own. I’m grateful for all of you who are studying to become teachers, looking past all of the reasons you shouldn’t go into education and focusing instead on the impact you’ll have on future generations.

At a time when it is increasingly difficult to be optimistic about the future, knowing that there are still teachers willing to fight for themselves and their students gives me all the hope I need. Thank you teachers, this week and every week, for all you do!

Evaluating the Costs of Endotoxin Testing

http://www.eniscuola.net/en/mediateca/king-crab/

Recently, I had the opportunity to attend a fascinating symposium held at Promega featuring conservationist Steward Brand, where he described some of the projects developed by his foundation, Revive & Restore.

The organization’s mission is to apply emerging biotechnology techniques to endangered and extinct species with the intent to increase genetic diversity, provide disease resistance and facilitate adaptation to changing climates. Although the overall message of enhancing biodiversity through the application of new genetic technology was inspiring, the project that resonated most for me was related to the plight of horseshoe crabs.

Horseshoe crabs, often referred to as living fossils, include four extant species with origins dating back about 450 million years. Although they look like crabs, they belong to their own subphylum and are more closely related to spiders. When horseshoe crabs spawn, they leave their usual habitat on the ocean floor and migrate to shore in large numbers. As a result, they have been exploited for bait and fertilizer for decades.

Enter endotoxins, an indicator for bacterial contamination in biologicals, drugs and medical devices. U.S. Food & Drug Administration regulations dictate that finished products be tested for the presence of endotoxins. These pyrogenic compounds, found in the cell wall of Gram-negative bacteria, can cause fever and affect a wide range of biological activity, possibly leading to aseptic shock and death. The most common method for testing is the gel clot and Limulus Amebocyte Lysate (LAL) Test.

I first learned about the LAL test during graduate school, where it was presented as a ubiquitous and standard requirement for testing bacterial contamination in injectable drugs. I remember being fascinated that horseshoe crabs (Limulus sp.), contain a substance that could be used to detect endotoxins. Although the instructors mentioned the need to collect blood from horseshoe crabs in order to produce the test, the method or scale of this harvest wasn’t discussed, nor were the true costs of using this method of endotoxin testing.

The LAL test has served as a faster, more inexpensive replacement for the rabbit pyrogens test for the past 35 years. Every year during mating season horseshoe crabs move to shallow water, where they are removed in huge numbers. (To get an idea of scale for the harvest and read a much more comprehensive investigation of the issue, check out this article in The Atlantic, which features an archive photo of Delaware Bay horseshoe crab harvest from 1928—for fertilizer, not pharmaceutical testing.)

After collection, the crabs end up in a lab where up to 30% of their blood is drained from a needle stuck in tissue around their heart. The LAL is extracted from the blood and can yield a product worth up to $15,000/quart. In order to avoid recollection, the crabs are returned to the ocean far from the shore where they were collected a few days before. Although it’s estimated that only 10-30% of these crabs die as a result of the process, there are indications that the horseshoe crab population and their ecosystems are impacted in other ways.

Researchers at the University of New Hampshire and Plymouth State University used accelerometers attached to recently bled female horseshoe crabs to test the hypothesis that harvesting for LAL was affecting their ability to spawn. While the research supported previous estimates with a death rate of 18%, females were found to be less likely to mate after being bled.

During his talk, Brand shared results from a study still in review that confirm the effect of over-harvesting Limulus on the survival of long distance migratory shorebirds. These birds synchronize their migration with horseshoe crab spawning, which provides a needed feast of eggs before the homestretch of their journey. Along with other ecosystem threats from climate change, the accelerated decline in the horseshoe crab population and dependency of migratory birds will likely to lead to a devastating ecological domino effect.

Fortunately, a synthetic alternative to LAL, recombinant factor C (rFC), has been available for nearly 20 years. Alas, there has been no significant shift by pharmaceutical companies away from the test based on horseshoe crab blood. rFC was patented and licensed to one company, Lonza, which Brand posited as one reason for the reluctance of drug companies to adopt its use.

Obviously, relying on one source for an essential testing reagent with no competition to temper cost is quite unattractive. But that argument has less bearing now that the patent is scheduled to expire in a few months, opening the door for additional manufacturers and creating an economic incentive for switching to the synthetic test.

Another reason may be that implementing a new test would require additional resources to validate the synthetic test for products that are already being tested with the LAL. Since the LAL has been specified in FDA guidance documents on endotoxin testing for decades, quality standards for existing products are based on the LAL, limiting momentum to change.

If both tests offered the same benefits, these arguments would make sense; however, research by one of the discoverers of rFC, Jeak Ling Ding of the National University of Singapore, shows that in many respects rFC is more efficacious than LAL. Since the raw material for the LAL test depends on an organism, there is seasonal variation in the components of the processed blood that must be taken into account. The reaction of the LAL also depends on a cascade of multiple compounds that can be affected by temperature, pH and proteins—leaving the test vulnerable to false positive results.

Although Eli Lilly is the only pharmaceutical company to date to use rFC in place of LAL, It seems the tide may be turning. According to Brand, others are interested in making the transition. It seems foolish not to, given the source for LAL shows signs of dwindling due to overexploitation. Perhaps pharmaceutical companies are beginning to see the value of a “slower/better” philosophy (the cornerstone of the Long Now Foundation, another brainchild of Brand’s), rather than “faster/cheaper.” I have certainly gained a new perspective on endotoxin testing and a deep appreciation for the work of Brand and his foundation.

Does your organization use the LAL test? What is preventing you from switching to the synthetic alternative? Let us know!