Blue Blood: How Horseshoe Crabs Revolutionized Medicine

Endotoxins are contaminants in the cell walls of some bacteria [4]. Medications and vaccines intravenously given to patients that may contain these endotoxins pose a risk of serious infection, septic shock, and death. Researchers and manufacturers initially avoided this catastrophe with animal testing on rabbits, but in the 1970's a new endotoxin detection solution was found in organisms older than dinosaurs: horseshoe crabs [3].

Horseshoe crabs are not actually crabs, but arthropods, like spiders and scorpions [2]. A blue, blood-like fluid called hemolymph flowing through the bodies of these "living fossils" is the key to testing all injectable drugs for endotoxins. This is because the blue hemolymph contains special immune system cells, called amebocytes, that are extra sensitive to molecules found in endotoxins, called lipopolysaccharides (LPS) [1]. Researchers have used these special cells to develop Limulus amebocyte lysate (LAL). 

LAL is named after North America's horseshoe crab species (Limulus polyphemus)[2], the special cells in their hemolymph (amebocytes), and the process used to make the compound (lysis, or breaking down, of the amebocyte cells). When LAL comes in contact with endotoxins secreted by bacteria, a sequence of reactions, called a coagulation cascade, occurs between proteins. This cascade ends in the activation of a protein called coagulogen which is turned into a gel called coagulin. This protein-gel forms visible clots, which are used to identify bacterial contamination of medical supplies from water and catheters to transplantable tissues and COVID-19 vaccines [1].

In order to synthesize LAL, scientists have to catch and drain the blood of about half a million horseshoe crabs. Of these crabs, only about 87% are returned to the ocean, after which about 15% to 30% of the creatures die due to blood loss and the disorienting amount of time spent outside of their aquatic environment. Overall, it is estimated that 130,000 horseshoe crabs are killed by this process each year [3].

Because of this harm to horseshoe crabs, and high demand for LAL, synthetic alternatives have been in development. One group of researchers used horseshoe crab DNA to make an alternative that fluoresces when it comes in contact with endotoxins present in contaminated medical supplies like vaccines, drugs, and syringes. Beyond taking stress off of horseshoe crabs, this synthetic alternative may also return more reliable results. Because horseshoe crab hemolymph and LAL react to many more molecules than just LPS from endotoxins, samples of drugs may clot even if they are not contaminated, but the synthetic alternative reacts more specifically to endotoxins [3]. 

Horseshoe crabs and their blue "blood" have been essential to the pharmaceutical industry. But, after half a century of harvesting the creatures for their hemolymph, synthetic alternatives may modernize endotoxin detection while sparing the horseshoe crabs.

1. Ashrafuzzaman, M.; Razu, M. H.; Showva, N.-N.; Bondhon, T. A.; Moniruzzaman, M.; Rahman, S. A.; Rabby, M. R.; Akter, F.; Khan, M. Biomolecules of the Horseshoe Crab’s Hemolymph: Components of an Ancient Defensive Mechanism and Its Impact on the Pharmaceutical and Biomedical Industry. Cellular Microbiology 2022, 2022, 1–17.

2. Horseshoe Crab. https://www.nwf.org/Educational-Resources/Wildlife-Guide/Invertebrates/Horseshoe-Crab (accessed Nov 14, 2022).

3. Maloney, T.; Phelan, R.; Simmons, N. Saving the Horseshoe Crab: A Synthetic Alternative to Horseshoe Crab Blood for Endotoxin Detection. PLOS Biology 2018, 16 (10).

4. Tamura, H.; Reich, J.; Nagaoka, I. Outstanding Contributions of Lal Technology to Pharmaceutical and Medical Science: Review of Methods, Progress, Challenges, and Future Perspectives in Early Detection and Management of Bacterial Infections and Invasive Fungal Diseases. Biomedicines2021, 9 (5), 536.

5. Jimenez, Darcy. Pharma’s reliance on horseshoe crabs is threatening the species. Pharmaceutical Technology. https://www.pharmaceutical-technology.com/features/pharma-horseshoe-crabs-threatening-species/ (accessed Aug 8, 2023)

Don’t Let the Pressure Get to You: Decompression Sickness

It is hard to imagine that making bubbles could be anything more than a fun and innocent childhood activity. When you think of bubbles, the first thing to pop into your mind may be a line of kids running across a field with bottles of soapy water, outstretched arms, and laughter. Yet, in a much different context (i.e. the vacuum of space), making bubbles is a dangerous process that can occur in the body and can lead to a condition known as decompression sickness.

Before learning about decompression sickness (DCS) in outer space, let us view it in a more familiar context here on Earth: scuba diving. As a scuba diver descends further and further below the surface of the water, the pressure rises around them[1]. This increase in pressure occurs because the deeper one goes, the “more” water is on top of them. It turns out that as pressure increases, the scuba diver breathes in more air molecules than they typically do because high pressures cause the air to be compressed. The additional oxygen from this extra air can be used by the body, but the additional nitrogen molecules in the air accumulate in the body [2]. The high pressure essentially allows for the nitrogen molecules to become dissolved, but that changes when the scuba diver returns to the surface [3]. As the diver ascends and the pressure decreases, the nitrogen will try to escape their body, and whatever is not expired ends up turning into nitrogen bubbles inside the body [2],[3].These bubbles are dangerous, as they can cause inflammation that leads to pain in muscles/joints and even obstruct blood vessels [2]. In the case of a diver experiencing DCS, one treatment option is hyperbaric oxygen therapy through a hyperbaric chamber. Essentially, in this treatment option, the affected person will sit in a chamber at a high initial pressure and the pressure will gradually decrease (allowing the nitrogen to freely exit the body rather than forming bubbles) [1].

The effects of DCS are not merely restricted to diving. Space is a very low-pressure environment, so special concerns related to DCS must be taken into account by astronauts. The pressure of the International Space Station (ISS) is 14.7 psi, which is about the same atmospheric pressure experienced at sea level on Earth. So if an astronaut has to exit the ISS in order to participate in extravehicular activity, there would be a drop in pressure [4]. To counteract the negative effects this may have, prior to leaving for their spacewalk, astronauts undergo a special breathing regimen consisting of 100% oxygen [4]. This prevents nitrogen gas from forming bubbles in the body since, hypothetically, there would be no nitrogen gas in the body. Such a measure is important as it helps prevent astronauts from having to experience DCS in space.

Pressure really can affect the body extensively, especially in the context of DCS. Thankfully, there are methods and interventions to help prevent and alleviate issues arising from it. So, the next time you see children playing with bubbles, don’t forget how bubbles can turn out to be harmful to the body. You can pass on telling them about it though; they’re probably not in any high pressure stakes at the moment. 

References

1. Healthwise staff. U of M Health. https://www.uofmhealth.org/health-library/abo0894 (accessed February 2022).

2. Moon, Richard E. Merck Manual Consumer Version. https://www.merckmanuals.com/home/injuries-and-poisoning/diving-and-compressed-air-injuries/decompression-sickness (accessed February 2022)

3. Cooper, Jeffrey S.; Hanson, Kenneth C. Decompression Sickness. In StatPearls; StatPearls Publishing; Treasure Island (FL), updated 2021. https://www.ncbi.nlm.nih.gov/books/NBK537264/ (accessed February 2022)

4. Canadian Space Agency. https://www.asc-csa.gc.ca/eng/astronauts/space-medicine/decomp.asp (accessed February 2022)

5. NASA-Imagery / 29 images. Pixabay. https://pixabay.com/photos/space-walk-astronaut-nasa-aerospace-991/ (accessed February 2022)
   

The Not-So-Dystopian Future of Lab-Grown Food on Our Plates

Many science fiction stories about dystopian societies with climate disasters involve some sort of synthetic meat grown in tanks on a large scale in an attempt to feed a hungry world. But is lab-grown food just a figment of our imagination forever, destined to remain a product of science fiction? Or could it soon be available as a mainstream product? 

As biotechnology advances, the ability to manipulate living organisms like bacteria for benefit grows. Just like the development of synthetic insulin has increased the quality of life of diabetic individuals, the biotech industry has turned its attention towards creating cultured or clean meat to limit the environmental impact of the meat industry [1]. The process begins with isolating stem cells from animal muscles and uses a bioreactor to grow the cell samples into tissue fibers and eventually muscle tissues [2]. According to a biotechnology company that is investigating the culturing of meat, the process could theoretically yield up to 20,000 pounds of meat from a simple muscle biopsy [2]. The process of growing meat in bioreactors has been independently examined by various biotech startups in the United States with some companies venturing out to culture other meat products such as pork and fish [2]. 

Now, let’s address the elephant (or cow?) in the room. How would this cultured meat taste? Reports from biotech companies report that the meat tastes fairly similar to normal meat as the fat and muscle tissue composition is closely monitored in the culturing process to ensure that the synthetic meat is as similar as possible to real meat [3]. 

There are many obstacles that cultured meat producers must overcome before the products will be available for mass consumption, including FDA approval [1]. However, cultured chicken products made their debut for public consumption at restaurant 1880 in Singapore to much fanfare [3].

Although modern biotechnology could support the mass production of cultured meats, there are many legal and social barriers that need to be addressed before we see lab grown meat on our plates. Despite the many obstacles that are in the way of cultured meat production, science continues to advance, and we may be eating cultured meat from the serveries before we know it. 

References

1. Rogers, K. Lab-grown meat could make strides in 2022 as start-ups push for U.S. approval https://www.cnbc.com/2022/01/23/lab-grown-meat-start-ups-hope-to-make-strides-in-2022.html (accessed 2022 -03 -12).

2. Lab-Grown Meat - Scientific American https://www.scientificamerican.com/article/lab-grown-meat/ (accessed 2022 -03 -12).

3. Lab-Grown Meat Could Feed the Planet | Time https://time.com/6109450/sustainable-lab-grown-mosa-meat/ (accessed 2022 -03 -12).

4. Lab-grown meat’s promise for cutting climate warming depends on an… https://www.oxfordmartin.ox.ac.uk/news/cultured-meat-climate-impact/ (accessed 2022 -03 -12).

Brain Injuries and the Fencing Response

Chargers’ Donald Parham on a gurney, following fall in mid-game. Image from [1].

A couple of weeks ago, many die-hard football fans witnessed one of the scariest injuries that can occur on the field. Only in the first quarter, it seemed all but certain that the Chargers would score the first touchdown of the game. However, a dropped pass in the endzone by the team’s tight-end, Donald Parham, suddenly turned into a moment of chaos. Taking an abnormal fall, his arms suddenly locked up in the air as he laid out on the turf unconscious. The cameras zoomed into the scene to display his unmoving body, showing the hundreds of thousands of viewers exactly what a traumatic brain injury looks like. Though Parham was ultimately taken to the nearby medical center and discharged the following day, fencing response — the reflex that Parham exhibited in that Thursday Night Football game — has been a hot topic among football fans and non-football fans alike. Let’s get into the science behind this frightening experience. 

Image from [2].

Fencing response is often seen in those who are knocked down or violently hit during full-contact sports such as football, rugby, and boxing, to name a few. After one experiences a substantial blow to the head that impacts the brainstem, a possibility is that their arms lift up into the air with their forearms flexed for several seconds [3]. Specifically, rotational forces resulting from a hit can shock the reticular activating system (RAS), which is the region that maintains consciousness in the brainstem. Since concussions are not able to be detected via methods such as MRI or CT scans, this fencing response position is one of the most noticeable indicators for medical professionals to determine the severity of the head injury. In fact, a 2009 study found that after analyzing 35 videos showcasing a hit to the head and an immediate loss of consciousness, roughly 66% showed the fencing response [4]. It’s completely reflexive; the shock of the trauma suddenly activates primitive muscle reflexes that are present in human infants [5]. For example, lifting a five-year-old infant off of a bed will cause them to flex and extend their arms — exactly what these athletes seem to do. As a result, they appear to lie limp and reach out into the air for something that’s not there.

Whenever an athlete falls awkwardly on the field and stretches their arms out for a few seconds, that’s not a unique celebration. As a definite indicator of a traumatic brain injury, there’s a reason that they don’t return for the remainder of the game.

References

1. ESPN. ​​https://www.espn.com/nfl/story/_/id/32885083/los-angeles-chargers-te-donald-parham-put-neck-brace-carted-off (accessed Jan 24, 2022)

2. Semantic Scholar. https://www.semanticscholar.org/paper/Brain-injury-forces-of-moderate-magnitude-elicit-Hosseini-Lifshitz/3e44f46ea098f4f63317fb95070053202c2a79e6 (accessed Jan 24, 2022)

3. Healthline. https://www.healthline.com/health/fencing-response (accessed Jan 24, 2022)

4. Hosseini A.H.; Lifshitz J. Brain injury forces of moderate magnitude elicit the fencing response. Med Sci Sports Exerc. [Online] 2009 Sep;41(9):1687-97. https://pubmed.ncbi.nlm.nih.gov/19657303/ (accessed Jan 24, 2022)

5. Bleacher Report. https://bleacherreport.com/articles/1494620-stevan-ridleys-concussion-biomechanics-of-his-injury-fencing-response (accessed Jan 24, 2022)
   
   

Neuroscience of the Lonely Brain

Mandated curfews, lockdowns, and isolation periods - with the resurgence of COVID-19 cases around the world over the past two years, the implementation of various infection control measures have exacerbated the mental wellbeing of the global population at a remarkable scale [1]. Historically, communicable diseases and their transmission from an affected patient to unaffected individuals have accelerated the development of preventative infection control with an unspoken acknowledgement of its repercussions for long-term mental health outcomes. For many, celebrating the holiday season this year has been a conspicuous anomaly: in fact, the inability to meaningfully reconnect with family and friends has coerced 18% of Americans to feel as if they have severed closely held social connections in their life, catalyzing what many scientists have characterized as the “Double Pandemic” [2]. 

Throughout human evolution, interpersonal dependency has manifested itself as a salient component of flourishing social relationships, and ultimately, as a pervasive modulator of cognition, life expectancy, and in some estimates, even the emergence of senescence-related neurodegenerative disorders [3]. Therefore, it may not be surprising to reconcile why the very perception of loneliness sufficiently casts a menacing shadow over the unique neural patterning signatures associated with selection pressures for sociality [4]. The nature of social exchange is a sophisticated one; encompassing higher-order neurocognitive mechanisms which allow an agent to synthesize coherent thoughts and intentions. 

Recently, however, a compelling study conducted by neuroscience researchers at McGill University has advanced some more nuanced insight into the neural correlates for unmet desires for social interactions in humans, suggesting a link with the evolution of higher-order associative cortical regions and their biological profiles. The multi-modal imaging-genetics cohort, organized by the UK BioBank initiative and constituted by 40,000 adults, elucidated how lonely individuals exhibit greater volumes of gray and distinct white matter structure, in addition to increased functional connectivity in brain regions dedicated to wakeful rest, or default mode networks (DMNs) [5]. 

Default networks, by definition, is a term used to describe a collection of several brain regions that are engaged when focus is diverted to contemplating tasks beyond the real world [6]. Conversely, it might be convenient to consider DMNs as active during periods of idled existence - whether that's daydreaming of the alternatives, resmicing over the past, or refining your expectations for the future. Implicated in the mental representation of the self and other social agents across space and time, simulating for intentions, identities, and motivations [7]. In the study, chronic abstention from intimate social connections was deemed as a significant predictor of shifted functional activity in the brain, leading the researchers to believe sustained loneliness carries broad implications for our brain’s architecture. 

The neuroscience of loneliness and its consequential implications for public health policymaking remains a dormant avenue of research. However, with novel endeavors to understand how social deprivation manifests itself as increased self-reflection in the mind, the urgency for mitigating loneliness in today’s society becomes increasingly clear. 

References

1. Greenberg, M. Do Lonely People Have Different Brains? Psychology Today - Sussex publishers [Online] 2020. https://www.psychologytoday.com/us/blog/the-mindful-self-express/202012/do-lonely-people-have-different-brains 

2. Holt-Lunstad, J. The Double Pandemic Of Social Isolation And COVID-19: Cross-Sector Policy Must Address Both. Health Affairs Forefront Blog - Project Hope [Online] 2020. https://www.healthaffairs.org/do/10.1377/forefront.20200609.53823 

3. Spreng, R. The default network of the human brain is associated with perceived social isolation. Nature Communications - Springer Nature [Online] 2020. https://www.nature.com/articles/s41467-020-20039-w 

4. Spreng, R. "Lonely brain" imaging study reveals unexpected neural patterns. New Atlas [Online] 2020. https://newatlas.com/science/loneliness-brain-imaging-study-neural-signature-default-mode/ 

5. Andrews-Hanna, J. Functional-anatomic fractionation of the brain's default network. ScienceDirect - Neuron Cell Press [Online] 2010. https://pubmed.ncbi.nlm.nih.gov/20188659/ 

6. Allen, S. The associations between loneliness, social exclusion and pain in the general population. ScienceDirect - Journal of Psychiatric Research [Online] 2020. https://pubmed.ncbi.nlm.nih.gov/32791383/ 

7. Mars, R. On the relationship between the “default mode network” and the “social brain”. Human Cognitive Neuroscience - Frontiers Media [Online] 2012. https://www.frontiersin.org/articles/10.3389/fnhum.2012.00189/full

8. McCrimmon, K. Loneliness during the COVID-19 pandemic: Fight it with kindness. UCHealth Today Digest - UCHealth Publishers [Online] 2020. https://www.uchealth.org/today/loneliness-during-the-covid-19-pandemic-fight-it-with-kindness/