If the Olympic Committee wanted to allow performance enhancing drugs, which would be the best ones to allow?

If the Olympic Committee allowed performance enhancing drugs (PEDs), problem is not knowing which ones would work best since they're developed to be safe and effective in the sick while drug use in sports is done by the healthy.

Since drugs aren't tested for their effectiveness in the healthy and since doping is illegal in sports, athlete drug use is entirely underground where drugs tested in a therapeutic context for treating diseases get surreptitiously co-opted for performance enhancement by the sports industrial complex of doctors, coaches, support staff and most importantly athletes who empirically test these drugs on themselves.

Growth hormone - Wikipedia (HGH) is a case in point. Developed to treat childhood growth disorders such as Prader–Willi syndrome - Wikipedia, athletes started using it to enhance their performance thinking if HGH increases muscle mass and reduces fatigue in the ill, it should do likewise in healthy athletes. Problem is HGH is known to benefit those who under-produce it. Could it do the same in those who produce normal levels of it? Data on HGH given to the healthy is limited to small studies in the elderly (1) which only suggest adverse events outweigh limited benefits, i.e., they're unhelpful, and yet HGH use among athletes soars (2, 3, 4). Some athletes may even naturally over-produce HGH, which may be why they turned out to be good in sports in the first place.

What if supplemental HGH was just flushed out of those who produce normal or extra levels of it? A waste. And what if it produced toxicity in those who produce normal or extra levels of it? A tragedy. Since PEDs haven't been tested for their safety and effectiveness in healthy bodies, athletes taking them are playing Russian roulette with their health.

As with society's failed war on drugs, attitude to PEDs in sports is also driven by a counter-productive, moralistic crackdown even as more and more athletes use them, 'a losing battle not against any particular substance, but rather human nature' as a recent article put it (5). In recent years, high-profile individuals like former US Track & Field CEO Doug Logan - Wikipedia have come out publicly against PED prohibition (5).

Destigmatizing PEDs would encourage thorough scientific tests of their safety and efficacy in athletes. No more Russian roulette, no more unnecessary and avoidable risk. One such, funded by Dallas Mavericks' owner, Mark Cuban - Wikipedia, is an FDA-approved two-year US $800,000 exploratory study of HGH at the University of Michigan to examine whether it helps recover from anterior cruciate ligament surgery (6).

Only a cultural change could bring PED use in sports out of the shadows. After all thorough scientific tests are necessary to identify which ones are optimal for athletes. More such studies would maybe help change the culture of drug use in sports from an illegal, underground, widely prevalent but heavily risk-laden endeavor to an open but regulated and therefore safer practice.

Bibliography

1. Liu, Hau, et al. "Systematic review: the safety and efficacy of growth hormone in the healthy elderly." Annals of Internal Medicine 146.2 (2007): 104-115. http://citeseerx.ist.psu.edu/vie...

2. HGH: Performance enhancer or healer? ESPN, Tom Farrey, Sep 5, 2006. HGH: Performance enhancer or healer?

3. The case for HGH, ESPN, Tom Farrey, Jan 17, 2007. The case for HGH

4. Analysis: Pharmaceutical firms cash in on HGH abuse. USA Today, David B. Caruso, Jeff Donn, December 31, 2012. Analysis: Pharmaceutical firms cash in on HGH abuse

5. The Drugs won: The case for ending the sports war on doping. Vice Sports, Patrick Hruby, August 1, 2016. The Drugs Won: The Case for Ending the Sports War on Doping | VICE Sports

6. A study might change the way sports thinks about human growth hormone. ESPN, Bonnie D. Ford, Dec 4, 2015. A study might change the way sports thinks about human growth hormone

https://www.quora.com/If-the-Olympic-Committee-wanted-to-allow-performance-enhancing-drugs-which-would-be-the-best-ones-to-allow/answer/Tirumalai-Kamala

Is collagen hydrolysate/gelatin a prebiotic for your gut microbes and what are the other prebiotic foods to best feed the gut microbes?

‘What are the other prebiotic foods to best feed the gut microbes?’

There is more hype than substance to claims that something or the other is a prebiotic that best sustains healthy gut microbiota since the latter itself lacks universal definition, is far from generalizable, and is largely the product of genetics, diet, lifestyle, age and gender, to name just a few of the most important factors. In fact, as recently as 2011 the European Food Safety Authority - Wikipedia (EFSA) stated (1, emphasis mine),

'based on current scientific knowledge, it is not possible to define the exact numbers of the different microbial groups which constitute a normal microbiota. The evidence available to the Panel does not establish that increasing the number of any groups of microorganisms, including lactobacilli and/or bifidobacteria, is in itself a beneficial physiological effect. For function claims related to changes in gastro-intestinal microbiota these changes should be accompanied by a beneficial physiological or clinical outcome.'

No wonder there is even less clarity with regard to Prebiotic (nutrition) - Wikipedia, compounds indigestible by human gut epithelial cells but digestible by specific bacteria. Especially pertinent since the major marketing claim for most commercial products touting prebiotic benefits is their capacity to support 'healthy intestinal microflora'.

How Prebiotics Might Help Sustain Beneficial Gut Microbes: Some Data And Unresolved Issues

Gut microbes digest prebiotics, increasing the rate of their metabolic products such as lactic acid and other fermentation products. These in turn reduce local gut lumen pH and encourage the growth of other microbes capable of utilizing such fermentation products and so on. Over time, this process builds a network of mutually interdependent microbial species but its potential to change the entire gut ecosystem starts with the initial human cell-indigestible component(s), i.e., prebiotic. However, causal relationships between prebiotic-driven microbiota changes and health effects still remain speculative and unproven. That definition of prebiotics keeps changing only serves to emphasize their study is nascent.

• For example, Glenn R. Gibson and Marcel B. Roberfroid originally defined prebiotics in 1995 as (2),

'a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health’

• Modified in 2004 (3) to

'A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microbiota that confers benefits upon host wellbeing and health’

• And modified yet again in 2010 (4) to

'selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health'

Such frequent definition changes engender confusion among consumers, prevent uniform, comparable scientific studies from being pursued, and prevent consensus formation between scientists, regulators, food industry and healthcare professionals (5).

The type of effects we should expect from prebiotics also remain unclear:

• Increase in some specific bacteria, say, Faecalibacterium prausnitzii or bifidobacteria or lactic acid bacteria or just increase in bacterial diversity? Is increase in bacterial diversity a generalizable health benefit?
• Increase in a specific output, say, fermentation or Short-chain fatty acid - Wikipedia (SCFA) or many other effects also possible?
• Which is more important, dose or frequency?
• How equivalent are natural prebiotics versus supplements? Are their effects even comparable?
• What about effect on immune function? Is it direct or indirect, by selectively binding and eliminating pathogens, i.e., Colonisation resistance - Wikipedia?
• Don’t responses varying between individuals preclude generalization?
• Different people respond differently to the same prebiotic (6, 7).
• Specifically Inulin - Wikipedia didn't uniformly increase gut bifidobacteria in all those who took them, with levels staying low in some who started out with low numbers (6).
• Response to prebiotics is also different between healthy and ill people (8) and between those lean versus obese (9).

Examples Of Some Substances Commonly Accepted As Prebtioics

Currently identified prebiotics are carbohydrates though this doesn't preclude other compounds such as proteins from being found to have prebiotic properties in future (8). Human breast milk is a classic prebiotic with substantial evidence of health benefits, specifically promotion of bifidobacteria colonization of infant gut (10, 11). Thus far the most robust list of physiological effects is available for Fructan - Wikipedia (12, also see table below from 13). Other broadly accepted prebiotics are Fructooligosaccharide - Wikipedia (FOS) and Galactooligosaccharide - Wikipedia (GOS).

• Inulin-type fructans are abundant in chicory root and Jerusalem artichoke (12, 13).
• Natural FOS are found to varying degree in banana, garlic, honey, onion, wheat (13, 14).
• Natural GOS are abundant in pulses (Legume - Wikipedia) (12).

‘Is collagen hydrolysate/gelatin a prebiotic for your gut microbes?’

No. Thus far no proteins have been labeled prebiotic. Obviously, being indigestible and fermentable are criteria unlikely to be fulfilled by most proteins.

Collagen is the most abundant structural protein in animals, constituting ~30% of total animal protein (15). Primarily derived from the Collagen in connective tissue, bone and skin, Gelatin is a high molecular weight protein that unfolds when melted and cools into a water-trapping helix-coil structure that forms a reversible gel. Consider Jell-O - Wikipedia, the ever-present dessert. Though it looks solid, it's actually >99% liquid.

While it's been part of our diet for centuries, the industrial revolution made gelatin practically ubiquitous, from foodstuffs to photography (think glossy photo paper) to glues to pharmaceuticals. Being amphoteric (Amphoterism - Wikipedia), having a variable Isoelectric point - Wikipedia as well as capacity for Coacervate - Wikipedia (separation of colloid particles from a solution) makes gelatin ideal for Micro-encapsulation - Wikipedia, hence its ubiquity in industrial food and pharmaceutical products (as capsules, sponges, Excipient - Wikipedia for example). Other advantages include (16)

• Easily digestible, high quality protein containing neither carbohydrates nor fats.
• Gluten-free.
• Extremely low allergenic potential.
• Clinical studies have shown special types of gelatin, marketed as collagen hydrolysate, can have a protective effect on joint cartilage (15). Hence its wide prevalence as a food additive for osteoarthritis patients and athletes.

Could Gelatin Be A Prebiotic? No Evidence Yet To Support Such A Possibility.

Though it's ubiquitous in the food industry, no systematic efforts have assessed if gelatin has prebiotic qualities. For example, as recently as 2015-2016, comprehensive reviews on collagen and gelatin list their major potential biological effects as antioxidant, antihypertensive, anticancer, antiphotoaging and cholesterol-lowering (15, 17) with no mention at all of prebiotic capacity.

However, neither is this unsurprising since most confirmed prebiotics tend to be poorly digested carbohydrates. Since carbohydrates yield certain defined effects such as fermentation, lactic acid, etc., efforts to identify new prebiotics focus on capacity to do likewise. It's entirely possible such a 'looking under the lamp post approach' may impair uncovering novel classes of prebiotics, which may not generate fermentation products or SCFA and yet be indigestible or primarily digested by gut microbes and have beneficial gut microbe and health effects.

Reports of gelatin's direct effect on microbes are meager.

• Gelatin strongly supports the growth of many microbes (16). This is why extremely stringent ISO9000-compliant quality control procedures are necessary during its industrial-scale manufacture.
• At least one known Probiotic - Wikipedia, (microbes with proven health benefits), namely, Bacillus clausii - Wikipedia (https://microbewiki.kenyon.edu/i...), can hydrolyze Gelatin. A soil bacterium first described in 1995, its probiotic properties are currently the focus of active research (18).

A few clinical studies have noted oral Gelatin/Collagen hydrolysate can influence appetite, suppressing it in the short-term (19) but not in the long-term (20), influence weight (21), again not in the long-term (22), and improve skin texture (23, 24, 25, 26). None of these studies have even speculated the observed biological effects could be due to effects on gut microbes.

Bottomline, as of 2016 there appear to be no scientific studies that have explicitly, comprehensively and systematically examined if and what effect Gelatin/Collagen hydrolysate have on gut microbiota, let alone explored the possibility they may have prebiotic effects.

Bibliography

1. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). "Guidance on the scientific requirements for health claims related to gut and immune function." EFSA J. 9 (2011): 1984-95. http://onlinelibrary.wiley.com/d...

2. Glenn, G. R., and M. B. Roberfroid. "Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics." J. nutr 125 (1995): 1401-1412. https://www.ilri.org/biometrics/...

3. Gibson, Glenn R., et al. "Dietary modulation of the human colonic microbiota: updating the concept of prebiotics." Nutrition research reviews 17.02 (2004): 259-275.

4. Gibson, Glenn R., et al. "Dietary prebiotics: current status and new definition." Food Sci Technol Bull Funct Foods 7 (2010): 1-19. https://www.researchgate.net/pro...

5. Hutkins, Robert W., et al. "Prebiotics: why definitions matter." Current opinion in biotechnology 37 (2016): 1-7. http://isappscience.org/wp-conte...

6. Ramirez-Farias, Carlett, et al. "Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii." British Journal of Nutrition 101.04 (2009): 541-550. https://www.researchgate.net/pro...

7. Louis, Petra, et al. "Diversity of human colonic butyrate‐producing bacteria revealed by analysis of the butyryl‐CoA: acetate CoA‐transferase gene." Environmental microbiology 12.2 (2010): 304-314. https://www.researchgate.net/pro...

8. Whelan, Kevin. "Mechanisms and effectiveness of prebiotics in modifying the gastrointestinal microbiota for the management of digestive disorders." Proceedings of the Nutrition Society 72.03 (2013): 288-298. https://www.cambridge.org/core/s...

9. Aguirre, Marisol, Carlota Bussolo de Souza, and Koen Venema. "The gut microbiota from lean and obese subjects contribute differently to the fermentation of arabinogalactan and inulin." PloS one 11.7 (2016): e0159236. http://journals.plos.org/plosone...

10. Mueller, Noel T., et al. "The infant microbiome development: mom matters." Trends in molecular medicine 21.2 (2015): 109-117. http://www.ncbi.nlm.nih.gov/pmc/...

11. Chichlowski, Maciej, et al. "Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function." Journal of pediatric gastroenterology and nutrition 55.3 (2012): 321. http://www.ncbi.nlm.nih.gov/pmc/...

12. Louis, Petra, Harry J. Flint, and Catherine Michel. "How to Manipulate the Microbiota: Prebiotics." Microbiota of the Human Body. Springer International Publishing, 2016. 119-142. Microbiota of the Human Body

13. Schaafsma, Gertjan, and Joanne L. Slavin. "Significance of inulin fructans in the human diet." Comprehensive Reviews in Food Science and Food Safety 14.1 (2015): 37-47. https://www.researchgate.net/pro...

14. Belorkar, Seema A., and A. K. Gupta. "Oligosaccharides: a boon from nature’s desk." AMB Express 6.1 (2016): 82. Oligosaccharides: a boon from nature’s desk

15. Liu, Dasong, et al. "Collagen and gelatin." Annual review of food science and technology 6 (2015): 527-557.

16. Schrieber, Reinhard, and Herbert Gareis. Gelatine handbook: theory and industrial practice. John Wiley & Sons, 2007. Gelatine Handbook

17. Koyama, Y. "Effects of Collagen Ingestion and their Biological Significance." J Nutr Food Sci 6.504 (2016): 2. http://www.omicsonline.org/open-...

18. Felis, Giovanna E., Franco Dellaglio, and Sandra Torriani. "Taxonomy of probiotic microorganisms." Prebiotics and probiotics science and technology. Springer New York, 2009. 591-637.

19. Hochstenbach-Waelen, Ananda, et al. "Single-protein casein and gelatin diets affect energy expenditure similarly but substrate balance and appetite differently in adults." The Journal of nutrition 139.12 (2009): 2285-2292. Single-Protein Casein and Gelatin Diets Affect Energy Expenditure Similarly but Substrate Balance and Appetite Differently in Adults

20. Hochstenbach-Waelen, Ananda, et al. "Effects of a supra-sustained gelatin–milk protein diet compared with (supra-) sustained milk protein diets on body-weight loss." British journal of nutrition 105.9 (2011): 1388. https://www.researchgate.net/pro...

21. Rubio, I. G. S., et al. "Oral ingestion of a hydrolyzed gelatin meal in subjects with normal weight and in obese patients: Postprandial effect on circulating gut peptides, glucose and insulin." Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity 13.1 (2008): 48-53.

22. Hochstenbach-Waelen, A., et al. "No long-term weight maintenance effects of gelatin in a supra-sustained protein diet." Physiology & behavior 101.2 (2010): 237-244.

23. Tanaka, Midori, Yoh-ichi Koyama, and Yoshihiro Nomura. "Effects of collagen peptide ingestion on UV-B-induced skin damage." Bioscience, biotechnology, and biochemistry 73.4 (2009): 930-932. http://www.tandfonline.com/doi/p...

24. Proksch, E., et al. "Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study." Skin pharmacology and physiology 27.1 (2013): 47-55. https://www.researchgate.net/pro...

25. Proksch, E., et al. "Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis." Skin pharmacology and physiology 27.3 (2013): 113-119.

26. Schunck, Michael, et al. "Dietary Supplementation with Specific Collagen Peptides Has a Body Mass Index-Dependent Beneficial Effect on Cellulite Morphology." Journal of medicinal food 18.12 (2015): 1340-1348. https://www.ncbi.nlm.nih.gov/pmc...

https://www.quora.com/Is-collagen-hydrolysate-gelatin-a-prebiotic-for-your-gut-microbes-and-what-are-the-other-prebiotic-foods-to-best-feed-the-gut-microbes/answer/Tirumalai-Kamala

How effective are small-time private donations in curing diseases?

Refers to: http://www.pennies.org/index.php/penny-charity/leukemia-and-lymphoma-society-15-billion-penny-milestone-reached-benefits-blood-cancer-research/79-penny-charity

Small-time, big-time, public or private, ultimately the issue is effectiveness of efforts. Can they cure (prevent debility and/or death from disease) or even eradicate (prevent it entirely)? There's probably no single approach or road-map for curing or eradicating diseases simply because so many factors are disease-specific, risk factors including genetics, transmission, geography, to name just a few. Even in 2016 the number of successfully cured or eradicated diseases is downright paltry, actually just one. Smallpox - Wikipedia is the only human disease to have ever been eradicated. On the verge of disappearing, Dracunculiasis - Wikipedia is a close second, largely courtesy the non-profit Carter Center - Wikipedia, whose motto is appropriately enough 'wage peace, fight disease, build hope'. Examining this rare illustrative example fully funded by small and large donations might help explain how to optimally put donations to use and what the process of eradicating a global disease might actually entail.

Guinea Worm Infection: What & How

Guinea worm (Dracunculus medinensis) is a parasite. People get infected by drinking water contaminated with water fleas (Copepod - Wikipedia) that carry and transmit Guinea worm larvae. Upon ingestion the fleas die, releasing the Guinea worm larvae, which penetrate through the GI tract into the abdominal cavity and remain there, taking ~ a year to grow into worms as long as 2 to 3 feet in length. Adult worms then break free through the infected person's skin, creating an extremely painful blister, locally secreting acid to burst it and slowly crawling out of the person's body over a month. Instinctive response to the searing pain from the blister burst is to plunge it into the nearest pool of water. This causes the worm to squirt a milky cloud of larvae that are then ingested by water fleas and so the cycle continues (see below from 1, 2). Though rarely fatal, unbearable debilitating pain, permanent tissue damage and even disability are Guinea worm disease hallmarks (3). Leaving its victims incapacitated for months at a time if not worse, its harmful effects ripple across already desperately poor communities, preventing children from attending school and farmers from working their land.

Entities Involved In Guinea Worm Eradication

The Carter Center: Spearheads the international Guinea worm eradication campaign (4). Works closely with national programs, WHO, US CDC, UNICEF, etc. Its activities include

• Compile and distribute case numbers.
• Provide technical and financial support to national programs.
• Provide continuing assistance to survey Guinea worm-free areas.
• Prepare nations for official certification.

National Ministries of Health

• Oversee national Guinea worm elimination programs.
• Hire and train field workers and supervisory staff.

WHO & US CDC

• Provide technical assistance.
• Verify whether worms from final patients are 'truly Guinea worms’.
• A panel of international Guinea worm disease specialists form the ICCDE (International Commission for the Certification of Eradication of Dracunculiasis Eradication)
• Established by the WHO in 1995 the ICCDE verifies and confirms whether a country has become Guinea worm-free based on the following criteria (5, 6).
• Adequate active surveillance systems have confirmed the absence of GWD for 3 or more years.
• A rumor log of suspected cases has been maintained for a 3-year period detailing:
• The particulars of each case
• The origin of each case
• The final diagnosis of each case (i.e., a true case of GWD or some other condition?).
• All confirmed cases imported from endemic countries have been traced to their origins and have been fully contained.

UNICEF

• Help provide safe drinking water sources to priority areas that national Guinea worm eradication programs identify.

Carter Center & Guinea Worm Eradication: What Made The Difference

According to former US President Jimmy Carter - Wikipedia (7), in the 1980s his former drug czar Dr. Peter Borne was the then-UN Assistant Secretary-General and visited the Carter Center seeking help in eradicating dreadful diseases such as Guinea worm that spread from bad drinking water but that garnered no interest because they occurred overwhelmingly among the desperately poor living in remote villages. According to Carter, the Carter Center avoids effort duplication and gets involved in efforts and issues others such as the WHO, the UN or even the US government aren't fully addressing. Thus they're involved in malaria, Guinea worm, river blindness, trachoma (the leading cause of preventable blindness in the world, 8), schistosomiasis and lymphatic filariasis.

• People living in Guinea worm endemic regions are taught to filter their water to remove the water fleas that carry and transmit Guinea worm larvae. Shaped like a pipe, these filters are portable water filtration units (8) that can be worn around the neck so wearers can use them as straws to filter their drinking water (3; see below from 4).
• Another portable filter is a hat with a mesh top. Water strained through this hat is safe to drink (8).
• These filters were developed by DuPont scientists after Carter explained their need to Edgar M. Bronfman of Seagram's and a major stakeholder in DuPont at a lunch in 1989 (9).

What made the crucial difference? An army of trained and dedicated volunteers (see below from 9, emphasis mine).

'While his campaign could not have succeeded without a large vision and contributions to match, the eradication of a disease ultimately depends on the dedication of workers in the field.

In rural Nigeria, as is true everywhere when literacy rates are low and telephones rare, everything must be done face to face. Twenty years ago, the Carter Center began its campaign by surveying 95,000 villages in Nigeria alone, sending someone to each one to ask if it had any cases of Guinea worm.

In each of the 6,000 villages that did, a team had to be formed to visit the authorities, explain the campaign and ask them to pick a "Guinea worm volunteer," someone who could read and write, would be willing to track each case, teach others how to roll worms out on a stick and keep their larvae out of drinking water.

The volunteers are unpaid. "They get a T-shirt, and people look up to them," said Dr. Cephas Ityonzughul, a consultant for the Carter Center's program in central Nigeria.

Supervisors like Mr. Ogebe are also unpaid but may get the use of a bicycle or motorbike, which in rural Africa are major status symbols. They also receive a Carter Center backpack full of sterile bandages.

Part of their job is to fight folk-medicine habits that sometimes die harder than any disease.'

Someone who reads the above and remains unmoved surely has a heart of stone. Even Civil War couldn’t deter Carter's staunch determination. Consisting of village-by-village case identification in areas accessible to the government, the Sudan Guinea Worm Eradication Program started in 1992 to 1993. While this helped interrupt disease transmission in northern Sudan by 2003, problem was not all areas were accessible due to a decades-long civil war between northern and southern Sudan. In 1995 Jimmy Carter even negotiated a 6 month 'Guinea Worm Cease Fire' (10).

Presenting the 2005 Gates Award for Global Health to the Carter Center, Bill Gates Sr. emphasized the tenacity and dedication of this army of volunteers in achieving such a startling success, the near-elimination of an ancient, dreaded, accursed disease (see below from 8).

'We all know there are critics who despair that people in the developing world are too incompetent or corrupt to take care of themselves. The Guinea worm effort has proved them wrong. In village after village, it is the people at the grass roots who have moved themselves and their countrymen to the verge of eradicating an ancient disease.'

Guinea worm Disease Numbers Since 1986

The non-profit Carter Center made Guinea worm eradication a centerpiece of its efforts in 1986. At that time there were ~26500 affected villages (8) with ~3.5 million cases per year (5).

• In 1998, the Carter Center received a US $9 million donation from the World Bank, American Home Products Corporation and the governments of Japan, Norway, UK and Denmark to start the final push for Guinea worm eradication (11).
• North and South Sudan signing a Comprehensive Peace Agreement (CPA) in Jan 2005 allowed the eradication program to proceed in South Sudan starting in 2006, at which time 20582 Guinea worm cases were reported from 3137 villages (10).
• In 2006, the Gates Foundation awarded the Carter Center its annual Award for Global Health for its Guinea worm eradication efforts (8).
• In 2008, 3618 of global 4619 Guinea worm cases (78%) were reported from 947 southern Sudan villages (10). The UK Department for International Development and the Gates Foundation then pledged US $55 million for its final eradication (12).
• Sustained effort and focus got the total number of cases for 2014 down to a mere 126 (3).
• By 2008 Guinea worm was eradicated in previously endemic Cameroon, the Central African Republic, India, Pakistan, Senegal and Yemen (10).
• By 2015, worldwide annual Guinea worm cases had dwindled to a mere 22 (13) and it had been eradicated the world over except Chad, Ethiopia, Mali and South Sudan (14).
• As of Aug 2016, a total of 12 cases worldwide with none reported from Mali (see below from 10, 13, 15).

Ironically, the last stage is the most expensive because given fewer annual cases, remote locations of most cases, one-year disease incubation period, maintaining a monitoring system that is simultaneously broad, sensitive and capable of providing a 'rapid response when necessary' becomes much more expensive.

• Though Guinea worm is not known to infect many other animals, recently Chad reported some cases of dogs with it (14). If this turns out to be more widespread then eradication efforts would have to include wiping it out in dogs as well.
• War, famine and other forms of instability in the last regions that are holdouts for Guinea worm could also slow down eradication process. For example, Mali reported only 7 cases in 2012 but more in 2013 and 2014 when conflict with Islamist rebels hampered field eradication efforts (14).

Thus, the yeoman efforts of the Carter Center-led Guinea worm eradication program show that absent vaccines, drugs and even therapies of any kind, vision, grit, and thorough, well-trained and dedicated volunteer ground efforts can make even relatively modest dollar amounts and low-tech approaches go tremendously far in not just making a dent but in fact in practically eradicating what was a global scourge as recently as the 1980s. Of course, this endeavor couldn’t have succeeded over so many decades without the Carter Center’s excellent, transparent communication and coordination of activities with its various partners, the WHO, US CDC, UNICEF, etc. Being a neglected tropical disease largely afflicting the impoverished in remote villages may also have been a blessing in disguise. With few others focused on this disease, the wastefulness inherent to effort duplication was easily avoided.

Bibliography

1. CDC - DPDx - Dracunculiasis

2. Jimmy Carter: 'I would like the last Guinea worm to die before I do'

3. Jimmy Carter's Work to Defeat Guinea Worm Highlighted in New Exhibit

4. Guinea Worm Eradication Program

5. Eradication Program

6. World Health Organization. "Criteria for the certification of dracunculiasis eradication." (1996). http://apps.who.int/iris/bitstre...

7. 'Watch Out, Guinea Worm, Here Comes Jimmy Carter'

8. Carter Center News and Publications - Gates Award for Global Health Speech

9. Dose of Tenacity Wears Down a Horrific Disease

10. Chapter 108. Dracunculiasis. Ernesto Ruiz-Tiben, Donald R. Hopkins. Guerrant, Richard L., David H. Walker, and Peter F. Weller. Tropical infectious diseases: principles, pathogens and practice. Elsevier Health Sciences, 2011.

11. Timeline and History: 1990-1999

12. Carter Center Receives Historic Guinea Worm Challenge Grant from Gates Foundation

13. An International Health Organization Committed to Guinea Worm Disease Eradication and Disease Control Health Programs

14. This Species is Close to Extinction and That's a Good Thing

15. Hopkins, Donald R., et al. "Dracunculiasis eradication: the final inch." The American journal of tropical medicine and hygiene 73.4 (2005): 669-675. https://www.researchgate.net/pro...

https://www.quora.com/How-effective-are-small-time-private-donations-in-curing-diseases/answer/Tirumalai-Kamala

Why has it been so hard to make glowing plants?

Refers to: https://www.technologyreview.com/s/601884/why-kickstarters-glowing-plant-left-backers-in-the-dark/

A peer-reviewed 2010 academic study showed it's possible to make glowing plants (See below from 1).

They claimed to have (1),

'generated the first truly autonomously luminescent (autoluminescent) transplastomic plants, containing a fully functional bacterial luciferase pathway, which emits visible light detectable by the naked eye'

Antonio Regalado writes in the MIT Technology Review (2),

'the scientist who carried out that work, Alexander Krichevsky, says it took him three years leading a lab at a well-equipped university, SUNY Stonybrook, to do it’

In the age of the Anthropocene, the Kickstarter Glowing Plants project's premise was altogether too beguiling, create glowing trees to light streets. However, that it took several years of effort for a dedicated, well-equipped academic lab to make one dimly glowing plant shows it takes a lot more cutting edge molecular biology than this team seems to have bargained for and highlights their scale of exaggeration (2).

'Krichevsky has since started his own glowing plant company, Bioglow, and says he has spent another three years trying to make the plants bright enough to interest consumers, a task which is ongoing. He says it was obvious to anyone in plant biology that Taxa’s timelines were unrealistic. “I was surprised by the promises they made. I thought, maybe they know something I don’t. Now I see that it is delusional,” he says. “They didn’t deliver anything for three years and I strongly doubt they ever will.”'

In hindsight, their Kickstarter campaign was a casualty of the two opposing yet irresistible forces that drove it in the first place. A biting-off-more-than-one-can-chew mindset within their team and the investors' scientific babes-in-arms credulousness.

Bioluminescence is an ancient biological property found in all major phyla on land and water including bacteria, fungi, fireflies, squid, earthworms and fishes. Essential bioluminescence components are Luciferin and Luciferase. Depending on the type of luciferin, bioluminescence can emit light ranging from 400nm to 700nm (3), i.e., colors ranging from blue, green, yellow, pink to red. In the presence of ATP and oxygen, the luciferase enzyme converts one molecule of luciferin protein to one of oxyluciferin, a process that generates one photon of light. Since a standard 100W light bulb can emit quintillions of photons per second, the 2010 report shows that making just one small plant dimly glow requires tremendous feats of genetic engineering.

Now renamed Taxa Biotechnologies, the Glowing Plant project team's penchant for inflated claims shows in the way they obviously felt no qualms about appropriating an image from the first genetically engineered glowing plant reported all the way back in 1986 and using it without attribution on their merchandise (see below from 4, 5, also pointed out by 6).

Unlike the original 1986 report which inserted only the luciferase enzyme into the tobacco plant genome and thus required luciferin supplied from outside to drive the 'glow' reaction, Krichevsky et al (1) made their plant autonomously bioluminescent by inserting genes for both luciferin and luciferase enzyme into it, using technology similar to the one the Glowing Plant project needed to use (1). For the Glowing Plants project to skirt loopholes in US law regarding Genetically modified organism (GMO) and ensure their glowing plants-to-be wouldn't be subject to regulation at all meant using the Gene gun to introduce the 'glow' genes into plants (2). Essentially this is an air pistol that shoots the gene-coated gold pellet into the intended target cell, in this case a plant cell. Given the amount of money they raised, ~half a million US dollars (2), other than absence of focus and determination, no reason why they couldn't have at least replicated Krichevsky et al's efforts over the 3 years they'd been working on this project.

Bibliography

1. Krichevsky, Alexander, et al. "Autoluminescent plants." PloS one 5.11 (2010): e15461. http://journals.plos.org/plosone...

2. MIT Technology Review, Antonio Regalado, July 15, 2016. Why the promise of a plant that glows has left backers in the dark

3. Widder, Edith A. "Bioluminescence in the ocean: origins of biological, chemical, and ecological diversity." Science 328.5979 (2010): 704-708. https://www.researchgate.net/pro...

4. Ow, David W., et al. "Transient and stable expression of the firefly luciferase gene in plant cells and transgenic plants." Science 234 (1986): 856-859. https://www.researchgate.net/pro... Glowing Plant | Merchandise

5. Glowing Plant | Merchandise

6. Illumination blog, Kevin M. Folta, July 19, 2016. Unfilled Glowing Plant Promises Harm Science Perception

Thanks for the R2A, Jonathan Brill.

https://www.quora.com/Why-has-it-been-so-hard-to-make-glowing-plants/answer/Tirumalai-Kamala

How much of an impact do Fourth of July fireworks in the US as a whole have on pollution and/or global warming?

A pretty flash followed by a bang, my deceptively benign childhood memory of fireworks, as I suspect it may be for many others. In reality, fireworks contain rather nasty chemicals, cause fires, deaths and injuries both during their production and use, create major noise pollution both for humans and their pets, and are a major public health hazard provoking acute health crises for people with chronic heart and lung conditions. Polluting air, water and soil around the factories where they're made, when lit up, fireworks release particulate matter (PM), ozone, harmful gases (sulfur dioxide, carbon dioxide, carbon monoxide) and trace elements.

Unfortunately fireworks are usually set off only at specific times of the year, making it easier to disregard their impact on the environment and on health. A global phenomenon, New Year's Eve fireworks, France's Bastille Day, Iran's Chaharshanbe Suri, Eid al-Fitr in muslim-dominant countries, Spain's Mascletà and Falles, the UK's Guy Fawkes Night are just a few examples, while probably the two most gluttonous fireworks displays of them all are China and Taiwan's Lantern Festival and India's Diwali (Festival of Lights). Fireworks' pollution is thus also global. If we restrict ourselves to the US July 4th fireworks alone, we risk missing their global environmental and health impact, more so since most US fireworks aren't made locally but rather imported from China.

Fireworks Are A Source Of Perchlorates, A Persistent, Potent Thyroid Disruptor

Recognized as a public health concern since 2011 by the US United States Environmental Protection Agency (EPA) (1), Perchlorate are inorganic anions used in a variety of explosive materials including solid rocket propellants, ammunition and fireworks. Readily water-soluble, perchlorate anions persist stably in the environment for long periods of time. From water, they then seep into all variety of biomass (plants and animals) (2). Potent thyroid disruptors, perchlorates can enter the body through skin, oral and respiratory routes. Competitively inhibiting uptake of iodide by the thyroid, they can cause reduction in thyroid hormones. Released into the atmosphere following fireworks explosions, extent of local perchlorate contamination depends on fireworks type, amount and duration, wind direction and velocity, and other local weather conditions at the time. Perchlorate contamination in surface and ground water has now been observed the world over from the US to Japan, China, Korea, India.

• One study in Long Island, New York, found local post-July 4th perchlorate levels to be as much as 18X higher than background levels, even at sites several kilometers away from known displays (3).

Obviously, as with other environmental contaminants, greater the exposure, greater the risk. Chronic perchlorate exposure is thus likelier for those who make fireworks. The world's largest fireworks manufacturing country, China supplies ~98% of fireworks imported by the US (4), and most fireworks used in the US are indeed imported.

• One study found surface water perchlorate levels as high as 54.4µg/ml near a Chinese fireworks manufacturing area (5), >7700X higher than the human exposure level of 7ng/kg/day the US EPA deems to be of minimal risk (6).
• Blood samples of babies and adults in China's major fireworks manufacturing hub, Nanchang city, contained detectable levels of perchlorate (1 to 2µg/kg/day) (7) much higher than the US EPA's reference dose (7ng/kg/day).
• Soil around Indian fireworks factories has been found heavily polluted with perchlorates (8).

Chemical contamination around firework factories also affect both microbial abundance and diversity in the local soil and water (9), meaning long-term environmental cost.

Making & Using Fireworks Causes Deaths & Injuries, An Eminently Avoidable Public Health Problem

Fireworks production-related deaths and injuries are commonplace, especially in countries like India where fireworks factories frequently use illegal child labor since small, nimble fingers speed up the assembly of certain fireworks (see below from 10, 11, 12).

In the US more fires are reported on July 4th than any other day in the year (13). However that blunt statistic doesn't reveal the full scale of the cost of fireworks-related fires. Fire and emergency services are hugely expensive in the US and have become even more so since the Great Recession. In its wake, as cities struggled even more than in the past to provide such services, Wall Street and private equity firms rode to the rescue, of course only at huge cost to the taxpayer (14). Since fireworks are pure indulgence, cost of the inevitable fires they leave in their wake are an unnecessary extremely costly burden on tax-paying communities already stretched to their limits.

Inevitable firework-related burns, other injuries and even deaths are another cost, with young boys disproportionately affected (see below from 15, 16, 17, 18).

Apart From Noise Pollution, Fireworks Are A Source Of Acute Health Hazards, Especially For Those With Heart & Lung Problems

Albeit temporarily, fireworks create tremendous noise pollution that can be quite traumatic for hapless pets (19) as well as wild fauna (20, 21). They also severely reduce ambient air quality (22, 23, 24), to such an extent that some people can be hospitalized or even die. India offers compelling examples of such odious, entirely preventable trends. As it becomes wealthier, bursting firecrackers during Diwali has become a surrogate marker for disposable wealth, literally changing the ancient Festival of Light into utter Cacophony. On and around Diwali, the very air's literally a sulfurous smog in each and every one of India's teeming cities. Imagine the plight of those with chronic heart and lung conditions in the aftermath of non-stop fireworks for ~ 24 hours. No surprise studies show fireworks induce acute health crises in such patients (25, 26, 27).

Globally, fireworks harm the environment, and the health of humans and animals. Aren't they also a case of literally burning money? To paraphrase Obelix, 'we humans are crazy'.

Bibliography

1. https://www.epa.gov/sites/produc...

2. Sijimol, M. R., and Mahesh Mohan. "Environmental impacts of perchlorate with special reference to fireworks—a review." Environmental monitoring and assessment 186.11 (2014): 7203-7210.

3. Munster, Jennie, et al. "The fallout from fireworks: perchlorate in total deposition." Water, air, and soil pollution 198.1-4 (2009): 149-153. https://www.researchgate.net/pro...

4. https://www.cpsc.gov//Global/Res...

5. Wu, Qian, et al. "Perchlorate in tap water, groundwater, surface waters, and bottled water from China and its association with other inorganic anions and with disinfection byproducts." Archives of environmental contamination and toxicology 58.3 (2010): 543-550. http://s3.amazonaws.com/academia...

6. Perchlorate | Drinking Water Contaminants

7. Zhang, Tao, et al. "Perchlorate and iodide in whole blood samples from infants, children, and adults in Nanchang, China." Environmental science & technology 44.18 (2010): 6947-6953.

8. Isobe, Tomohiko, et al. "Perchlorate contamination of groundwater from fireworks manufacturing area in South India." Environmental monitoring and assessment 185.7 (2013): 5627-5637.

9. Dhasarathan, P., P. Theriappan, and C. Ashokraja. "Microbial diversity in firework chemical exposed soil and water samples collected in Virudhunagar district, Tamil Nadu, India." Indian journal of microbiology 50.1 (2010): 46-49. http://www.ncbi.nlm.nih.gov/pmc/...

10. http://www.jugendeinewelt.at/fil...

11. http://www.ncpcr.gov.in/view_fil...

12. Frontline, S. Durairaj, August 29, 2009. Danger zone

13. Fireworks

14. The New York Times, Danielle Ivory, Ben Protess, Kitty Bennet, June 25, 2016. When You Dial 911 and Wall Street Answers

15. Firework Statistics

16. https://www.cpsc.gov/Global/Rese...

17. Canner, Joseph K., et al. "US emergency department visits for fireworks injuries, 2006–2010." journal of surgical research 190.1 (2014): 305-311. https://www.researchgate.net/pro...

18. Moore, Justin Xavier, Gerald McGwin, and Russell L. Griffin. "The epidemiology of firework-related injuries in the United States: 2000–2010." Injury 45.11 (2014): 1704-1709. http://www.sciencedirect.com/sci...

19. Levine, Emily D., Daniela Ramos, and Daniel S. Mills. "A prospective study of two self-help CD based desensitization and counter-conditioning programmes with the use of Dog Appeasing Pheromone for the treatment of firework fears in dogs (Canis familiaris)." Applied Animal Behaviour Science 105.4 (2007): 311-329. http://psicovet.com.br/wp-conten...

20. Shamoun-Baranes, Judy, et al. "Birds flee en mass from New Year’s Eve fireworks." Behavioral Ecology 22.6 (2011): 1173-1177. Birds flee en mass from New Year’s Eve fireworks

21. Pedreros, Eduardo, et al. "Observations of the effect of a New Year’s fireworks display on the behavior of the South American sea lion (Otaria flavescens) in a colony of central-south Chile." Marine and Freshwater Behaviour and Physiology 49.2 (2016): 127-131.

22. Saha, Upal, et al. "Effects of air pollution on meteorological parameters during Deepawali festival over an Indian urban metropolis." Atmospheric Environment 98 (2014): 530-539. https://www.researchgate.net/pro...

23. Pervez, Shamsh, et al. "Chemical speciation of aerosols and air quality degradation during the festival of lights (Diwali)." Atmospheric Pollution Research 7.1 (2016): 92-99

24. Seidel, Dian J., and Abigail N. Birnbaum. "Effects of Independence Day fireworks on atmospheric concentrations of fine particulate matter in the United States." Atmospheric Environment 115 (2015): 192-198. https://www.researchgate.net/pro...

25. Pal, Raina, et al. "The Effects of Fireworks on Ambient Air and Possible Impact on Cardiac Health during Deepawali Festival in North India." World Heart Journal 5.1 (2013): 21. The Effects of Fireworks on Ambient Air and Possible Impact on Cardiac Health during Deepawali Festival in North India

26. Gouder, Caroline, and Stephen Montefort. "Potential impact of fireworks on respiratory health." Lung India: official organ of Indian Chest Society 31.4 (2014): 375. http://www.lungindia.com/temp/Lu...

27. Chakraborty, Ananya. "KEYWORDS Respiratory health, Diwali, Dyspnea, Hospitalization." HOSPITALIZATIONS DUE TO RESPIRATORY PROBLEMS DURING DIWALI FESTIVAL IN A TERTIARY CARE HOSPITAL IN SOUTH INDIA. 94087 (2016). http://www.jebmh.com/data_pdf/11...

https://www.quora.com/How-much-of-an-impact-do-Fourth-of-July-fireworks-in-the-US-as-a-whole-have-on-pollution-and-or-global-warming/answer/Tirumalai-Kamala