It has been over half a year since Covid-19 swept across the world and forced many countries into quarantine. Hopes of a quick resolution of the disease in many countries have since been, unfortunately, proven to be wrong, and it is evident that the virus is here to stay for a while [1]. The virus is so difficult to deal with considering it can be transferred from person to person even if the carrier does not outwardly display symptoms. Even animals, ranging from mice to tigers, can contract and transmit it to humans [2, 3], and we cannot quarantine or force them to wear facemasks. The virus will eventually hit each person; it is just a matter of time. The virus may additionally arrive in multiple waves, as it is possible to be reinfected [4]. COVID-19 will most likely have a lifespan of a few years, much like other major virus outbreaks of the past such as the swine flu in Hong Kong or Spanish flu. It will probably come and go like a common flu in never ending waves. So, each of us need to be ready until a successful vaccine is developed, and the wisest action for each person to be ready would be to boost our immune systems and practice effective social distancing and sanitation measures, while we deal with this virus for however long it may last.

Vaccines are critical for stunting the development and spread of viruses; however, they can be costly, time-intensive to develop, and not always perfect. It is worth exploring alternative methods to help protect our bodies from these pathological invaders while vaccines are being researched. As it so happens, the best method of prevention to date for HIV infections is not a vaccine, but is instead a tradition that is as old as thousands of years: male circumcision [5]. To give a comparison, the current widely popular and heavily promoted influenza vaccine is considered “50% effective against influenza B/Victoria viruses and 37% effective against influenza A(H1N1)” [6]. On the other hand, according to an article published in the prestigious medical journal, The Lancet, circumcision is up to 88% effective in preventing heterosexual transmission of HIV [7]. Male circumcision does not have any medicinal side effects, and the only risks that are involved are those related to any minor surgery – bleeding and infection.

In the 1980s, when I first heard of HIV, I remember reading articles which claimed, quite arrogantly, that vaccines and cures for the condition would be found within two or three years [8]. Forty years later, and after spending many billions of dollars on research, we are still nowhere near an HIV vaccine. At best, we found treatments which helped keep the HIV virus at bay [9]. To date, only two people have been fully cured with a method far too expensive to be applied to the general public [10]. In the meantime, at least 30 million people have died with more than half a million in the year 2019 alone [11]. While vaccines are critical for helping to eradicate viruses, putting all of our eggs into that basket alone can be a risky public health strategy due to how difficult and time consuming they are to discover, verify, and distribute. It is impossible to know for sure how long it will take to develop a vaccine for the coronavirus. In the meantime, communities should heavily consider following the instructions of their local health officials which often include social distancing, limited size gatherings, and frequent hand washing as these methods are already proven to help reduce the spread of the virus.

Development, and even the rushed development of a vaccine, is always a very tedious and dangerous process. The science behind them is exceptionally complex, and imperfect results can have disastrous consequences upon thousands of people. This is further complicated by the fact that phase 2 and phase 3 trials can have quite diverging results [12]. In the USA, AstraZeneca’s COVID-19 vaccine trials were stopped after trial participants fell ill [13]. Third phase trials, which encompass thousands of people [14], still can give little indication of the long-term side effects to any vaccine. Besides, even though there is human life at risk, the vaccine has already become an instrument for many political and economic disputes and conspiracy theories. Some governments claim they have already developed a vaccine, while others find them unreliable, or try to lure a foreign company to work for themselves [15]. In August of this year Russia rushed registration of an unproven Coronavirus vaccine and named it, in Cold-War-like fashion, the “Sputnik V” [16]. The announcement was made by none other than Vladimir Putin himself. It was offered to the USA, but was rejected due to safety concerns stemming from a belief that the drug was not adequately researched and developed [17]. In the meantime, Russia announced the development of a second vaccine [18]. Surely enough, it was dismissed and downplayed by the West as unproven and unreliable. On the other hand, a vaccine developed by a Chinese company Sinovac proved to be the most successful in its phase 3 trials in Brazil [19]. Sao Paulo Governor João Doria purchased 47 million shots of the vaccine. However, the transaction was stopped, arguably for political reasons, by the Brazilian President Jair Bolsonaro [20]. Bolsonaro’s comments when rejecting the purchase of the Sinovac vaccine on the basis that “the Brazilian people will not be anyone’s guinea pig” are not totally without merit. Recalls of “proven and tested” vaccines have happened in the past [21].

It is important for all people to continue exploring methods to develop their immune systems and prevent the spread of the virus while we wait for a vaccine. In an article I had previously published, I discussed the benefits of fasting, vitamin C, and Wim Hof breathing methods to help protect the body from disease [22]. All of these methods are well known and quite benign with respect to side effects, however they are unable to cure Covid-19 or prevent its spread. Additionally, the Center for Disease Control (CDC) has heavily stressed practices included social distancing and the wearing of non-ventilated face masks. Our hope is that going above and beyond to protect ourselves and our neighbors will give scientists the time that they need.

One way of giving that time to scientists is fasting. Fasting, like circumcision, is a tradition that is thousands of years old. In recent studies, a three-day water fast has been shown to reset the immune system of elderly people to the level of a twenty-year old’s [23]. At this current level of emergency in the world it would be very easy to find thousands of willing volunteers to trial monthly three-day water fasts and/or to take extra doses of vitamin C, not as a cure, but as a shield against COVID-19. This kind of study would not pose much risk and would definitely be very cost-effective. We could dive straight into the third phase of trials, for any side effects of fasting are already well known. And finally, if proven effective, its uptake by the population at large would be basically cost free and readily available across the whole world.

Our world has been enduring a difficult and challenging period for the better half of a year now. Time has given us the ability to learn more about the virus, how it disrupts our bodies, and how it spreads. This knowledge has, in turn, allowed us to research it and develop effective social guidelines for limiting its spread. Still, there is much work to be done. Hysteria and haste are not conducive to producing a vaccine that is thorough, effective, and efficient. It should be the responsibility of every able-bodied citizen to do what they can to learn more about how they can protect themselves from the virus and thus prevent it from spreading even more while we wait for a vaccine.

1. https://www.wuky.org/post/beshear-next-few-weeks-will-be-critical#stream/0
2. https://www.washingtonpost.com/science/2020/09/03/coronavirus-deer-mice-spread/
3. https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/animals.html
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326402/
5. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)03421-2/fulltext?_eventId=login
6. https://www.aafp.org/news/health-of-the-public/20200226interimfluve.html
7. Halperin, D. T., & Bailey, R. C. (1999). Male circumcision and HIV infection: 10 years and counting. The Lancet, 354(9192), 1813-5. doi:http://dx.doi.org/10.1016/S0140-6736(99)03421-2
8. https://www.immunology.org/publications/bsi-reports/60-years-immunology-past-present-and-future/the-hunt-for-hiv-vaccine
9. https://www.cdc.gov/hiv/basics/livingwithhiv/treatment.html
10. https://www.medicalnewstoday.com/articles/2nd-person-cured-of-hiv-thanks-to-stem-cell-transplant
11. https://www.unaids.org/en/resources/fact-sheet
12. https://www.fda.gov/media/102332/download
13. https://www.usatoday.com/story/news/health/2020/09/09/covid-vaccine-astrazeneca-trial-hold-what-does-mean/5757590002/
14. cancer.org/treatment/treatments-and-side-effects/clinical-trials/what-you-need-to-know/phases-of-clinical-trials.html
15. 15 https://www.nytimes.com/2020/03/15/world/europe/cornonavirus-vaccine-us-germany.html
16. https://www.theverge.com/2020/8/11/21363135/russia-coronavirus-vaccine-unproven-registration
17. https://www.techtimes.com/articles/251792/20200814/covid-19-us-says-no-to-russias-vaccine-sputnik-v-saying-theyll-never-use-it-on-monkeys-let-alone-people-vietnam-and-philippines-say-otherwise.htm
18. https://abcnews.go.com/Health/wireStory/russia-approves-2nd-virus-vaccine-early-trials-73614460
19. https://fortune.com/2020/10/20/covid-vaccine-china-brazil-testing-ground-safest-most-promising-sinovac/
20. https://apnews.com/article/virus-outbreak-brazil-state-governments-health-sao-paulo-b7b5b620ba54f402dbf803e26fe6b842
21. https://www.cdc.gov/vaccinesafety/concerns/recalls.html
22. https://medium.com/@arasweb/surviving-the-pandemic-370b47120d8d
23. https://news.usc.edu/63669/fasting-triggers-stem-cell-regeneration-of-damaged-old-immune-system/

The drug molecules that are supposed to be curing us also need to overcome our body’s defense mechanisms. Let’s look at some of the body’s defenses and the way drugs overcome them, before we examine an unexpected inspiration for a new method of delivering drugs.

Our skin is the largest barrier preventing toxic substances from getting inside our bodies. The intestinal mucosa or the blood-brain barrier is a physiological defense barrier. If a drug molecule can pass through these barriers, the next step to be overcome is the biochemical barrier, where myriad enzymes play a role. Therefore, drug molecules have to be designed with optimal physicochemical properties. These include the proper size, charge, and hydrophilicity (water solubility) to ensure their permeation across our bodies’ biological barriers.

There are a few types of drug delivery systems. They are oral, pulmonary (via inhalation), intravenous (via injection), and transdermal. All of them have their own advantages and limitations.

For oral applications, a drug molecule needs to traverse the epithelial layer of the gastrointestinal tract. Thus, there are many factors which have to be taken into consideration for enhancing the delivery of molecules through the intestinal mucosal barrier. Many of the newer drugs on the market are composed of peptides and proteins, and they cannot be administered orally due to their relatively larger size compared to smaller drug molecules.

The delivery of drugs via traditional injection provides better bioavailability; however, this route has low patient compliance due to injections being painful and accidental needle-sticks. Hypodermic injections also generate dangerous medical waste and pose the risk of disease transmission by needle re-use, especially in developing countries.

Transdermal drugs have become an important form of medication in recent years, as they are non-invasive or minimally invasive. Transdermal drugs have many advantages over other drugs, such as high patient compliance due to the easy accessibility of skin, the avoidance of the gastrointestinal tract, and that they can be self-administered.

The main problem with transdermal drugs is that the skin is a highly effective barrier. The outermost layer of skin, the stratum corneum, is mainly composed of dead carneocytes embedded in lipid layers, and has a thickness of 10-15 μm. This packed structure offers a substantial barrier to the delivery of both small hydrophilic (water soluble) and high molecular weight drugs. Only small lipophilic molecules, which can dissolve in lipids, can pass through the skin. Therefore, alternative methods and devices are needed to deliver hydrophilic and macromolecular (larger) drugs through the skin in a controlled manner.

Numerous chemical and physical methods have been attempted with the purpose of increasing skin permeability for easier drug delivery. As the name suggests, micro-needles are micron-size needles that are applied for transdermal vaccinations, as well as drug and gene delivery. Researchers hope they will increase skin permeability via forming micron-sized channels in the skin, thereby allowing the delivery of therapeutics across the skin barrier. In addition, by careful control of the micro-needles’ mechanical strength and length, it is possible to deliver drugs across the dermal barrier while evading the nerves, thus resulting in a painless administration.

Micro-needles must have a high degree of stiffness (resistance to bending) and enough strength for a successful insertion into the skin. If they’re too flexible, they won’t insert; if they’re not strong enough, they’re fracture. A variety of materials are used to manufacture micro-needles, and they include silicon, glass, metals (e.g. stainless steel, titanium, and nickel-iron), and polymers. Current micro-needle technology is based on imitating the present hypodermic needle geometry and miniaturizing it utilizing a silicon micro-machine process. The designs are fabricated onto a substrate where hundreds of micron-sized needles are formed, and then these micro-needles can be either pressed or scraped on the skin, forming microscopic holes. As a result, skin permeability increases by approximately four degrees of magnitude, allowing the easier delivery of medicine.

The ideal micro-needle needs to be extremely small, with an inner diameter of 10-20 μm. It is very challenging to prepare such small needles, ones that are also strong and flexible. Fortunately, we have a living example to guide our designs: female mosquitos.

The world’s most advanced micro-needles are found in mosquitos. Thus, scientists and engineers have begun trying to mimic a female mosquito’s bite – that is, the way they suck blood from our bodies while also leaving behind their itch-causing enzymes. If such a breakthrough can be achieved, blood drawing or drug injection may be performed painlessly. Researchers from North Carolina State University indicate that if a “synthetic mosquito” capable of drawing blood painlessly can be developed, millions of diabetics worldwide who must draw blood several times a day for glucose monitoring will be able check their glucose numbers without pain.

Mosquito needles are made of two main parts: the fascicle and proboscis. The general shape of a female mosquito needle is a core-sheath structure where the fascicle is the main needle puncturing the skin and drawing blood and the proboscis acts as a surrounding and protective layer for the inner needle. Interestingly, only female mosquitos bite, since their need for human blood is only for the purpose of developing their eggs, not for their nutrition.

Ideally, a micro-needle would mimic the structures of a mosquito’s needle, including the mechanism by which the mosquito penetrates the skin and draws blood. This would make for the painless treatment of many diseases.

To prepare a micro-needle based on a mosquito needle would require extensive knowledge of chemistry, material science, mechanical and structural engineering, and fluid dynamics. After resolving any scientific challenges, these needles would need to be manufactured in high quantities to reach the many people in need. This would require scaling up the fabrication methods in a safe and compliant facility. For such widespread production to happen, the process would have to be widely adopted by patients.

In summary, if researchers can mechanically mimic a mosquito needle, it would be a great achievement in the development of advanced micro-needle technology. It’s incredible that the solution to a major medical problem – the efficient delivery of drugs and vaccines – is already present in nature, at our disposal.

REFERENCES

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Original Article: Cranford, S.W. et al., Nature 482, 72 (2012).

Spider silk has been a symbol of durability and strength, but the role the design of a web plays or contributes to the strength was unknown. Researchers from Massachusetts Institute of Technology discovered that the impressive design of web and the feature of silk allow spiders to build a super-strong web under different levels of stress. The response of spider silk subjected to load was studied. They studied webs of a variety of species, including European garden spiders and orb weavers, and combined their experiments with correlated web models. At low stress, silk threads soften and extend that result in retaining web structure. At high stress, the silk threads extend and the most stretched ones break. The strength of the silk and the geometry of the web allow only one or two threads being broken under strain. Therefore, the break in the web is minimized and prevents destruction of the whole web. The localized web damage can be repaired by the spider and therefore a requirement for rebuilding the web completely is eliminated. This study shows that spider silk web is very stable even under hurricane winds. This research gives an idea to engineers to build a system that will fail only at small parts of the system under certain stress. Therefore, the system will continue to work just after repairing the destroyed parts of the system. Otherwise, the whole system may be destroyed under potential load and will have to be rebuilt. For example, when a building is exposed to large mechanical stress such as an earthquake, it may be destroyed as a whole and become dysfunctional. Applications on such systems require further research in engineering to achieve structures as stable as a spider’s web.

2- Benefits of Exercise Through a Protein

Original article: Bostrom, P. et al., Nature 481, 463 (2012).

Exercise has a number of beneficial effects in human health such as increasing cardiovascular, respiratory and metabolic capacity. Scientists at Harvard Medical School have discovered a muscle hormone, Irisin, which may be responsible for the many beneficial effects of exercise. Irisin secreted from muscle after exercise and act on white adipose tissue that stores energy. Excessive amounts of white fat cells contribute to many pathologic effects of obesity and diabetes. Irisin, however, converts white fat into the more beneficial and metabolically active brown fat, which burns more calories and produce heat instead of energy. It helps to prevent excessive glucose and fatty acid accumulation in the body. The researchers demonstrated that mildly increased Irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. It also reduces body weight and improves glucose tolerance and obesity induced insulin resistance. This research suggests that Irisin can be a new therapeutic target in human metabolic diseases treatment. Also it could help people lose weight and fight against obesity induced problems such as diabetes and hypertension.

3- New Generation Vaccines with High Efficacy

Original Article: Avci F.Y. et al., Nature Medicine 17, 1602 (December 2011).

Most pathogenic bacteria contain complex carbohydrate structures on their surfaces. These carbohydrates are called capsular polysaccharides. “Glycoconjugate” vaccines are prepared by chemical conjugation of capsular polysaccharides with proteins. This method is the standard design for many vaccines that protect us against common diseases such as pneumonia and meningitis. One drawback with these vaccines is their limited efficacy in populations such as the elderly, children and patients with compromised immune systems. Researchers at Harvard Medical School and Rockefeller University have designed and synthesized a vaccine that is about 100 times more potent than traditional vaccines available today. Until now, the scientific community believed that the body’s professional immune cells, called T-cells, were only able to recognize vaccine’s protein molecules to generate an immune response. However, after studying how glycoconjugate vaccines stimulate immune response, the researchers found that T-cells are also able to recognize the carbohydrate molecules. In a series of elegant experiments, they demonstrated that there is a repertoire of T-cells that can recognize the carbohydrate portion of a glycoconjugate vaccine, and that these T-cells stimulate antibody producing B-cells to generate high affinity antibodies against the carbohydrates. Based on the knowledge obtained from this mechanistic study, researchers have designed a new-generation glycoconjugate vaccine and showed that this new vaccine was about 100 times more immunogenic than a vaccine made by traditional methods.

4- Producing Fuel from Waste with Bacteria

Original Article: Bokinsky, G. et al., PNAS 108, 19949 (December 2011).

It turns out, the secret for alternative source for oil might be hidden in a very common bacterium and plant, E coli and switch grass. As the world’s natural resources are quickly exhausted by humans, new energy sources or alternative energy production methods are needed. One popular way for addressing this question is promoting biofuels. Most of the biofuel source is in ethanol form, often produced from sugar that is extracted from sugarcane and corn. However the consuming of main food sources for energy sources begs a question: What if one day feeding the machines with our food sources makes food scarce? Another concern is that many countries are not using ethanol as an energy source. All these led researchers to pursue another idea: Instead of using food sources as precursor for ethanol, non-food biomass or bio-waste can be converted to precursors for biofuels by utilizing the cellulose or hemicellulose as a starting material. Human body cannot digest cellulose. Hence, cellulose is a bio-waste, which can be broken down into sugar using a mixture of enzymes and subsequently can be used for gasoline production. The enzymes for this procedure can be produced by bacteria in massive amounts. To this end, researchers genetically engineered Ecoli bacteria to consume large amount of cellulose from switch grass and convert it to sugar. Scientists achieved to produce different precursors for different fuels, including gasoline, diesel or jet fuel with bacteria. These are big steps in turning bio-waste into fuels. Imagine one day your plane will be powered with a hay of switch grass and a bottle of bacteria. Next time when you fly over a field of switch grass, you might actually be seeing the next oil well.