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)

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)
   
   

The Physiology Behind Mastering the Pull-up

We’ve all been here: in front of you hangs a metal bar dauntingly suspended a couple of feet in the air — and you think to yourself, how do I do a pull-up?

Muscles used during a pull-up excercise. Image from [1].

For those who don’t yet know how to do a pull-up, there’s a long road ahead. But just like any other exercise, with proper training, mastery is possible by properly activating the groups of muscles involved through repetition. The muscle groups most involved in the pull-up are the rectus abdominis (one of the many muscles that constitute the core) latissimus dorsi (lats), middle and lower trapezius (traps), and biceps brachii (biceps) [1]. It’s especially important to understand the physiological aspects of each exercise to find the most effective ways to master it in the least amount of trips to your local gym. 

Image from [2].

Pull-up training begins with kneeling lat pulldowns. This variation of a lat pulldown, which is a common workout that targets your shoulder and back for an upper-body workout, activates muscles to a similar magnitude and pattern as pull-ups, more so than other exercises such as assisted pull-ups and seated lat pulldowns [3]. To properly perform a kneeling lat pulldown, you first kneel and use an overhand grip on a lat pulldown attachment. Afterward, set the weight until it is heavy enough to pull your knees above the ground by about an inch. Then, for the actual pulldown part, make sure that your back is aligned straight and pull your shoulder blades together to achieve maximum muscle activation. Make sure to do 3 sets of 5 reps!

Another great exercise is a negative pull-up, which essentially constitutes the downward half of the pull-up. Many studies have shown that this “negative” portion of the exercise (known as eccentric exercise) might be more effective at building muscle than performing the entire rep [4]. The negative pull-up is especially suited for beginners. Even though you might not have the strength for the upward part of the pull-up, many will have the strength to execute the downward motion with the right technique. To properly perform a negative pull-up, you first raise yourself to the top of the pull-up position using a stool or other high platform and simply do 5 sets of 1 rep [1].

With these two exercises, you will begin to see progress in your pull-up attempts. It might take a while, but we all have to start somewhere!

References

[1] AMM Fitness. https://www.ammfitness.co.uk/information-advice/pull-ups-benefits-muscles-worked (accessed Nov 15, 2021)

[2] Fitness Lane. https://fitnesslane.com/product/kneeling-lat-pulldown/ (accessed Nov 15, 2021)

[3] Hewit J.K.; Jaffe D.A.; Crowder T. A Comparison of Muscle Activation during the Pull-up and Three Alternative Pulling Exercises. J Phy Fit Treatment & Sports [Online] 2018, 5.4, 1-7. https://juniperpublishers.com/jpfmts/JPFMTS.MS.ID.555669.php (accessed Nov 15, 2021).

[4] Hedayatpour N.; Falla D. Physiological and Neural Adaptations to Eccentric Exercise: Mechanisms and Considerations for Training. BioMed Research International [Online], 2015, 2015. https://doi.org/10.1155/2015/193741 (accessed Nov 15, 2021)

[5] Muscle & Performance. https://www.muscleandperformance.com/training/killer-pull-up-workouts/ (accessed Nov 15, 2021)

The Asian Glow Explained

Turning red after drinking an alcoholic beverage with some friends is not a good thing. In fact, it indicates that your body is unable to efficiently process alcohol. Often referred to as the “Asian Glow” or the “Asian Flush,” this condition is due to a deficiency of the aldehyde dehydrogenase 2 enzyme (ALDH2) and affects approximately 30-50% of East Asians [1]. Typically, when alcohol is ingested, there are two main enzymes that the body uses to metabolize alcohol: alcohol dehydrogenase and aldehyde dehydrogenase.  First, alcohol dehydrogenase will convert the alcohol into acetaldehyde, a toxic chemical. Then, aldehyde dehydrogenase 2 breaks down the toxic acetaldehyde into the non-toxic compounds acetate and water [2]. Those who have the “Asian Glow” are missing this critical second enzyme, which results in an accumulation of acetaldehyde. The build-up of acetaldehyde causes blood vessels to dilate, which gives those with the Asian Glow the characteristic facial redness. Additionally, it can cause a rapid heartbeat, nausea, headaches, itchiness, red eyes, difficulty breathing, and many other not-so-fun symptoms [2]. 

What most people don’t know is that acetaldehyde is a carcinogen: it causes cancer. In fact, in a series of studies done by Akira Yokoyama and his colleagues in Japan comparing individuals with a functional ALDH2 gene to those with an inactive variant, they showed that individuals with a copy of the inactive variant of the gene for ALDH2 were 6-10 times more likely to develop esophageal cancer than are those with the fully functioning ALDH2 enzyme who drink similar amounts of alcohol [3]. Furthermore, individuals with the inactive ALDH2 enzyme who drink 33 or more U.S. standard drinks per week are at an eighty-nine-fold higher risk of esophageal cancer compared to a non-drinker with an inactive enzyme [3].

It might seem unusual that such a large population of East Asians specifically are affected by this odd condition. How would something like this start? The answer may be quite simple: rice. The first cases of the Asian Glow were reported 10,000 years ago, which corresponds to when humans first began cultivating rice. Researchers hypothesize that the genetic mutation that causes an adverse reaction to alcohol consumption arrived to protect early farmers from  negative effects of alcohol use [4]. 

Unfortunately, there is no currently-known cure for the negative effects of the Asian Glow. Some have resorted to taking antihistamines to reduce the redness. Antihistamines reduce or block histamines, the compound that dilates blood vessels and results in the reddening of the face. The body turns red for a reason: acetaldehyde is in its system. The redness is the body’s way of indicating that it’s being damaged. Therefore, reducing the redness not only proves ineffective in treating the negative health effects of the Asian Glow, but also may mask the body’s natural immune response [5]. The best way to deal with the Asian Glow is not to drink. Nevertheless, drinking is a very common behavior in today’s society, so I leave you with this message: everything in moderation. 

What most people don’t know is that acetaldehyde is a carcinogen: it causes cancer. In fact, in a series of studies done by Akira Yokoyama and his colleagues in Japan comparing individuals with a functional ALDH2 gene to those with an inactive variant, they showed that individuals with a copy of the inactive variant of the gene for ALDH2 were 6-10 times more likely to develop esophageal cancer than are those with the fully functioning ALDH2 enzyme who drink similar amounts of alcohol [3]. Furthermore, individuals with the inactive ALDH2 enzyme who drink 33 or more U.S. standard drinks per week are at an eighty-nine-fold higher risk of esophageal cancer compared to a non-drinker with an inactive enzyme [3].

It might seem unusual that such a large population of East Asians specifically are affected by this odd condition. How would something like this start? The answer may be quite simple: rice. The first cases of the Asian Glow were reported 10,000 years ago, which corresponds to when humans first began cultivating rice. Researchers hypothesize that the genetic mutation that causes an adverse reaction to alcohol consumption arrived to protect early farmers from  negative effects of alcohol use [4]. 

Unfortunately, there is no currently-known cure for the negative effects of the Asian Glow. Some have resorted to taking antihistamines to reduce the redness. Antihistamines reduce or block histamines, the compound that dilates blood vessels and results in the reddening of the face. The body turns red for a reason: acetaldehyde is in its system. The redness is the body’s way of indicating that it’s being damaged. Therefore, reducing the redness not only proves ineffective in treating the negative health effects of the Asian Glow, but also may mask the body’s natural immune response [5]. The best way to deal with the Asian Glow is not to drink. Nevertheless, drinking is a very common behavior in today’s society, so I leave you with this message: everything in moderation. 

References:

1. Lin, Y. (2017, May 3). The Quad: Understanding 'Asian glow' and how to counteract it. Retrieved November 05, 2020, from https://dailybruin.com/2017/05/03/the-quad-understanding-asian-glow-and-how-to-counteract-it

2. Cheong, T. (n.d.). Food Tips. Retrieved November 05, 2020, from https://www.healthxchange.sg/food-nutrition/food-tips/asian-flush-alcohol-red-face

3. Alcohol Flush Signals Increased Cancer Risk among East Asians. (2015, October 22). Retrieved November 05, 2020, from https://www.nih.gov/news-events/news-releases/alcohol-flush-signals-increased-cancer-risk-among-east-asians

4. Huai, E. (2019, September 26). Asian Flush (Alcohol Flush Reaction): Cures, Symptoms, Causes & Health Risks. Retrieved November 05, 2020, from https://www.flyby.co/blogs/news/asian-flush

5. Vuong, Z. (2018, August 06). Antihistamines prevent 'Asian flush' - alcohol-induced facial redness - but pose risks. Retrieved November 05, 2020, from https://news.usc.edu/112489/antihistamines-prevent-asian-flush-the-red-face-some-people-get-from-alcohol-but-with-huge-risks/