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)
   

Composting: Fad Trend, or Way to Give New Life to Food Waste?

We produce a lot of trash. This sheer amount of waste produced places enormous pressure on waste management systems. In response, composting aims to provide a way of decreasing food waste and has steadily grown in popularity over the past decade. Sometime over the last few semesters, you’ve probably seen the Moonshot composting bins accompanied by instructional posters by the trash cans in the serveries. The mission of Moonshot Compost Services is to divert excess food from landfills and return the nutrients back to the soil [1]. Rice students are welcomed to be a part of this mission by discarding their plates, food, and any other acceptable biodegradable items into a Moonshot composting bin.

Let’s zoom out from our campus and take a look at large-scale composting operations as a whole. What is the fate of the food waste once it’s out of our hands?

Once compost is collected and sent off for processing, there are a few commercially viable methods in practice to break it down into usable organic materials: windrow, aerated stack pile, and in-vessel composting [2]. In windrow composting, compost is piled in long rings and the organic material is rotated at regularly occurring intervals. Downsides of this method include the need for large amounts of land and constant supervision of the composting process. In aerated stack pile composting, wood chips are layered in with the compost to create spaces for airflow throughout the compost pile; pipes are often used to provide an upward stream of air from the base of the pile. Although this method is able to degrade compost fairly quickly, the machinery and equipment required to set up the system are quite expensive and labor-intensive. Finally, in-vessel composting shifts away from exposing compost to open air and opts to place compost into a temperature- and moisture-controlled environment within a container. This in-vessel composting may turnout compost quicker than the other two methods, but is fairly expensive [3].

If done in an efficient manner, these methods of composting food waste can provide a viable and continuous pipeline from food waste to nutrient-rich soil that can be used to grow crops. A key take away from all of this is that regardless of the method used for composting, there are some drawbacks to the composting process, whether it be high costs, large amounts of land use, or the production of foul odors (yikes!). Zooming back into our campus serveries, it’s important to recognize that although we don’t have control over what exactly happens to our compost, decreasing the amount of food waste by taking advantage of our Moonshot bins is an easy way to decrease Rice’s waste.

References

[1] Impact. Retrieved November 5, 2021, from http://www.moonshotcompost.com/impact/.

[2] Alexander, G. How commercial composting works. Retrieved November 5, 2021, from https://earth911.com/business-policy/how-commercial-composting-works/.

[3] Sustainable Management of Food: Types of Composting and Understanding the Process. Retrieved November 5, 2021, from http://www.epa.gov/sustainable-management-food/types-composting-and-understanding-proces s#aeratedstatic.

[4] Image: https://images.app.goo.gl/3oPXQsGWQVnNS1858

Attacking Cancer: A Golden Opportunity

You don’t have to be a historian to grasp the significant impact gold has made in the world. From a sought-out treasure to a method of currency, there’s no doubt that this element is one of the most influential metals in human history. Yet, a much less known aspect of gold is its incredible potential in biomedicine. This is especially true of gold nanoparticles in the context of cancer.

Cancer is a condition wherein cells proliferate and divide in an uncontrolled manner. [1] While cancer can often be treated, the side effects of those treatments can be severe and can include possibly hurting non-cancer cells and the immune system. Inducing hyperthermia, or causing a part of the body to heat up, has been shown to have an anticancer potential as it can lead to programmed cell death as well as make tumors more susceptible to radiotherapy. Yet, a central issue arises: unless the heat is localized, other parts of the body can be harmed. This is where gold nanoparticles come in. [2]

In the simplest terms, gold nanoparticles are small pieces of gold. Very small pieces of gold. As a result, gold nanoparticles have a lot of different properties compared to, say, a block of gold that we often think about when talking about the element. For instance, gold nanoparticles are not yellow: particles less than 100 nm are red while bigger particles are blue/purple. [3] These nanoparticles have amazing properties which allow them to act as a contrast in CT scans or assist with drug delivery. [4] Yet, one of the most fascinating applications of these gold nanoparticles is their use in photothermal therapy. Because the blood vessels near the tumor site are often leaky, gold nanoparticles that have been placed in a cancer patient's body will passively concentrate near a tumor. Once they have concentrated, they can be activated by near-infrared light, a special type of light which can easily pass through human tissues. The gold nanoparticles will absorb the light energy and convert it to heat energy near the tumor, essentially stimulating the cancer cells’ deaths. [2]

Has this technique been tested in humans? In fact, yes–a clinical trial done at Mt. Sinai hospital which used gold-silica nanoparticles to treat prostate cancer patients revealed no severe side effects from the treatment. After the gold nanoparticles had concentrated at the tumor site of the patients, they were irradiated by near-infrared light from optical fibers. These nanoparticles absorbed the light and heated the tumor site, essentially destroying it. [5]

The promise of such a localized treatment strategy is encouraging. Hopefully, further research can be done to explore this opportunity that is, indeed, worth its weight in gold.

References

[1] Gupta, N.; Malviya, R. Understanding and advancement in gold nanoparticle targeted photothermal therapy of cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer [Online] 2021. 1875, 188532. https://www.sciencedirect.com/science/article/pii/S0304419X21000305?via%3Dihub (accessed November 2021)

[2] Vines, J.B.; Yoon, J.-H.; Ryu, N.-E.; Lim, D.-J.; Park, H. Gold nanoparticles for photothermal cancer therapy. Front. Chem. [Online] 2019. 7, 167. https://www.frontiersin.org/articles/10.3389/fchem.2019.00167/full (accessed November 2021) 

[3] Sztandera, K.; Gorzkiewicz, M.; Klajnert-Maculewicz, B. Gold Nanoparticles in Cancer Treatment. Mol. Pharmaceutics [Online] 2019. 16, 1-23. https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b00810 (accessed November 2021)

[4] Wang, S.; Lu, G. Noble and Precious Metals - Properties, Nanoscale Effects and Applications. In Applications of gold nanoparticles in cancer imaging and treatment; Intechopen: Online, 2017.

[5] Stephens, M. PhysicsWorld. https://physicsworld.com/a/gold-nanoshell-based-cancer-treatment-is-safe-for-the-clinic/ (accessed November 2021)

[6] Pxfuel. https://p1.pxfuel.com/preview/830/131/627/cancer-cells-cells-scan-electron-microscope-scan.jpg (accessed November 2021)

What the Oink? Pigs May Hold the Key to our Transplant Troubles

In 1954, John Murray of Harvard Medical School commenced a new era in modern medicine by performing the first successful kidney transplant in a human patient [1]. 67 years later, organ transplantation is a widely-utilized medical procedure, frequently used to combat organ failure and a variety of other diseases. The new hurdle in this field of transplantation surgery is the ever-growing list of patients in need of new organs with no way for the supply to ever meet the demand. There currently are over 100,000 patients on the US transplant waiting list, many of whom depend on the hope of organ transplantation as their last chance of survival [2]. To combat this mismatch between the supply and demand of transplantable organs, scientists have been looking to other organisms in hopes that cross-species transplantations could alleviate some of the issues that make the organ transplant list so intimidatingly long.

The concept of organ transplantation using donor organs from non-human organisms is not a completely novel idea. In the 1960’s, a surgeon at Tulane University, Keith Reemtsma, transplanted kidneys from chimpanzees to 13 human patients as a last resort treatment option (these procedures would likely not fly under today’s ethical guidelines). While one of Reemtsma’s patients had a short recovery term of around 8 months, all of these transplanted organs ultimately failed due to immune rejection by the human recipient [3]. The human immune system mounts a significant immune response to transplanted organs, triggered by specific sugars present on the external surfaces of transplanted organs and their cells. For instance, the alpha-gal sugar present on pig kidneys makes successful transplantation of organs from the native organism to humans impossible [4]. Genetic engineering technology has allowed scientists to remove sugars from potential donor organisms, facilitating the first successful transplant of a pig organ to a human in mid-October of this year. 

At NYU’s Langone Health, physicians transplanted a kidney from a pig genetically engineered to lack the alpha-gal sugar, and the kidney remained viable for 54 hours [5]. The patient had been considered brain dead for about a month before the procedure took place, and their organs were deemed unusable for transplantation into another patient. Upon consent of the family, physicians at NYU performed the xenotransplantation and observed healthy urine output for 54 hours after the procedure (54 hours was the length of time deemed ethical by a board of medical ethicists — the experiment was ended after that period of time) [4]. 

This procedure validates the assumptions that removing immune system-triggering sugars from the surface of transplant organs can prevent immediate rejection by the host. While this is just a small step in the direction of making xenotransplantation a universally accepted treatment option, it opens the possibilities for future clinical work and applications. Due to the manifold of ethical issues surrounding human clinical trials, progress in this area of research will inevitably be quite slow. However, slow progress is a small price to pay to avoid repeating the same mistakes as past xenotransplantation experiments. 

References

[1] A transplant makes history – Harvard Gazette https://news.harvard.edu/gazette/story/2011/09/a-transplant-makes-history/ (accessed 2021 -11 -29).

[2] Organ Donation Statistics | organdonor.gov https://www.organdonor.gov/learn/organ-donation-statistics (accessed 2021 -11 -29).

[3] Cooper, D. K. C. A Brief History of Cross-Species Organ Transplantation. Baylor University Medical Center Proceedings 2012, 25 (1), 49–57. https://doi.org/10.1080/08998280.2012.11928783.

[4] What the successful test of a pig-to-human kidney transplant means | Science News https://www.sciencenews.org/article/xenotransplantation-pig-human-kidney-transplant (accessed 2021 -11 -29).

[5] U.S. surgeons successfully test pig kidney transplant in human patient | Reutershttps://www.reuters.com/business/healthcare-pharmaceuticals/us-surgeons-successfully-test-pig-kidney-transplant-human-patient-2021-10-19/ (accessed 2021 -11 -29).