Can we genetically modify animals to procure organs for humans?

Why the need to use animal organs for human transplants? Is there even such a need? No, rather it's a technological solution proposed for an urgent but non-scientific supply and demand problem, namely, shortage of organs. More people die on waiting lists than receive transplants. This fait accompli is apparently all that's necessary to breathe life into the need for Xenotransplantation - Wikipedia, i.e., animal organ transplant into humans. However, accepting this fait accompli at face value is not only dangerous but also quite disingenuous for the following reasons.

Why Xenotransplantation Isn't An Appropriate Response To The Organ Crisis: It Doesn't Address The Underlying Issue

Transplant waiting lists keep growing. Not too few donors. Rather too many potential recipients. While donations and transplants remain steady, numbers waiting for transplants grow year-on-year (1) in developed countries. Scenario is palpably ghastlier in poorer countries, where forget transplants, even dialysis is usually beyond reach for many organ failure patients.

Why is the need for transplants increasing though? This is typically swept under the carpet as increasing morbidity rates. But why are morbidity rates increasing in the first place, especially in developed countries? Somehow this, the very crux of the matter, gets short shrift in both the biomedical literature and popular media.

~80% of those on waiting lists need kidneys due to ESRD (end-stage renal disease, Chronic kidney disease - Wikipedia). Increasing numbers of organ failure patients have ESLD (end-stage liver disease) (2). Most common predisposing factors are alcoholic liver cirrhosis (3), diabetes (4) and obesity (5). Clearly lifestyle issues drive need for more transplants. That is not to imply all transplants are for lifestyle-mediated chronic diseases but rather that much of the annual increase is driven by such preventable increases in morbidity.

Bad diets and sedentary lifestyles are apparently impossible to change as are the underlying socioeconomic structure and accompanying culture that increasingly make these the norm the world over. In other words, preventable, consumption-driven practices that predispose to transplant-requiring chronic health conditions have been allowed to seed and settle into society, no questions asked. Let's state the obvious. Where's the profit in prevention? Changing the culture, especially diet and lifestyle, is hard work, and even less appetizing for those habituated to feeding on the profits to be made from chronic diseases.

Thus, once such preventable diseases have taken root, capital intensive high-tech solutions to treat them including even xenotransplants become all the rage. Few mention that the organ crisis is nothing new, having existed since at least the 1980s (6). Evidently a case of the tail wagging the dog, the prevailing hegemony is thus to hardly ever allude in the first place to why need for organs is increasing and how to reduce it but rather to bemoan the organ crisis and contrive ever more creative and ethically challenging ways to increase the organ pool.

These creative though ethically challenging solutions started with expanding the definition of appropriate transplant sources. Originally, only deceased donations were allowed. Then definition of death expanded to include the legal fiction of two types of death, circulatory death (traditionally used) and brain death (7) so organs could be harvested from more bodies. Obviously brain death 'decriminalizes the harvesting of beating hearts' (8). Then donations from the living got the nod. Any surprise organ trafficking and global black market in organs followed suit (9), especially among the multitude too poor to feed themselves or their children (10, 11, 12)? After all their bodies are all they can offer the market.

Some European countries such as Greece and Spain have even taken the creative urge to extremes, embracing the currently fashionable Nudge theory - Wikipedia by introducing opt-out consent (13), where people are automatically presumed to have given consent to post-death organ donations unless they specifically take the trouble to opt-out while they're still alive. Supposed rationale is we humans are well-intentioned but lazy. Well-intentioned as in of course, we intend to choose to donate our organs after death but somehow we're too lazy to ever get around to giving the necessary legal heft, i.e., consent, to our good intentions.

And of course, desperation increasingly permeates the medico-legal culture which now explores using even infected (14) and mismatched kidney transplants (15). Meantime, the ongoing US drug overdose epidemic provides a ghastly book-end to the organ crisis by increasing organ availability (16).

Why Xenotransplantation Isn't A Solution To The Organ Crisis: Immunological Rejection & Infectious Disease Risk

And so we arrive at xenotransplantations, a path to unlimited supply of donors and their organs at least in theory. After all, what other purpose for this planet and its various denizens but to serve the human's needs. Unfortunately for the human, in this instance biology has turned out to be a more intractable partner.

• Immunological rejection remains a vexing issue decades into the project with little sign of improvement (17) but that's not the only concern.
• SARS (Severe acute respiratory syndrome - Wikipedia) in 2003, Bird flu (Influenza A virus subtype H5N1 - Wikipedia) in 2007, Swine flu (2009 flu pandemic - Wikipedia) in 2009, MERS (Middle East respiratory syndrome - Wikipedia) in 2012, Ebola virus disease - Wikipedia in 2014 and Zika fever - Wikipedia in 2015, these are major infectious disease outbreaks since just the mid-2000s, many of them Zoonosis - Wikipedia, jumps from animals to humans. Obviously then known and even as yet undiscovered viruses being transmitted from the animal donors to organ recipients remains an ever-present danger (18). Yes, a high-powered group led by Harvard geneticist George Church used CRISPR-cas9 (CRISPR - Wikipedia) to delete potentially harmful DNA sequences at 62 sites in pig cells (19) but that was just a preliminary proof of principle study. Do we really need to concoct yet another path for more pathogens to jump species and thrive in humans, which may well turn out to be the risk with Xenotransplantation?

In other words, technocracy encourages solutionism rather than trying to understand the fundamental crux of the problem, which in this case is spiraling rates of lifestyle-driven chronic diseases. Reducing them would automatically reduce the need for transplants in the first place (see below from 20, emphasis mine).

'Medical strategies to prevent end-stage organ failure

The prevention or delay of end-stage organ failure must be accomplished to reduce the need for organ transplantation and to achieve national self-sufficiency. This approach is especially relevant to low-income countries, where resources can be better used for other pressing medical needs. Thus, education programmes about organ donation for the public and the media should also address the maintenance of a healthy lifestyle. Early detection and prevention of diseases leading to end stage organ failure, such as diabetes, cardiovascular disease, and kidney disease, is necessary.'

Bibliography

1. Organ Procurement and Transplantation Network

2. Williams, Roger, et al. "Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis." The Lancet 384.9958 (2014): 1953-1997.

3. Williams, Roger, et al. "Implementation of the Lancet Standing Commission on Liver Disease in the UK." The Lancet 386.10008 (2015): 2098-2111. https://www.researchgate.net/pro...

4. Wild, Sarah H., et al. "Type 2 diabetes and risk of hospital admission or death for chronic liver diseases." Journal of hepatology 64.6 (2016): 1358-1364.

5. Williams, Bronwen, Michelle Clayton, and Joanne Bosanquet. "Obesity: a growing threat to liver health." Gastrointestinal Nursing 13.Sup10 (2015): S16-S19.

6. Miller, Melanie. "A proposed solution to the present organ donation crisis based on a hard look at the past." Circulation 75.1 (1987): 20-28. http://circ.ahajournals.org/cont...

7. Truog, Robert D., and Franklin G. Miller. "Changing the conversation about brain death." The American Journal of Bioethics 14.8 (2014): 9-14.

8. Epstein, Miran. "Constructing the Legal Concept of Death: The Counterhegemonic Option." The American Journal of Bioethics 14.8 (2014): 45-47.

9. Scroll, Sanjay Nagral, August 3, 2016. Better buy than die? The unfortunate enduring saga of organ sales in India

10. Epstein, Miran. "The ethics of poverty and the poverty of ethics: the case of Palestinian prisoners in Israel seeking to sell their kidneys in order to feed their children." Journal of medical ethics 33.8 (2007): 473-474. https://www.researchgate.net/pro...

11. Budiani‐Saberi, Debra A., and Francis L. Delmonico. "Organ trafficking and transplant tourism: a commentary on the global realities." American Journal of Transplantation 8.5 (2008): 925-929. https://www.researchgate.net/pro...

12. Danovitch, Gabriel M., et al. "Organ trafficking and transplant tourism: The role of global professional ethical standards—The 2008 Declaration of Istanbul." Transplantation 95.11 (2013): 1306-1312. https://www.researchgate.net/pro...

13. The Economist, Nov 20, 2008. Opting out of opting out

14. Stat, Elie Dolgin, March 18, 2016. Surgeons to test use of infected kidneys for transplants

15. Orandi, Babak J., et al. "Survival benefit with kidney transplants from HLA-incompatible live donors." New England Journal of Medicine 374.10 (2016): 940-950. http://www.nejm.org/doi/pdf/10.1...

16. The Guardian, Amanda Holpuch, May 1, 2016. Drug overdose epidemic has driven increase in organ donors, data shows

17. Tirumalai Kamala's answer to Is xenotransplantation remotely possible?

18. Tirumalai Kamala's answer to What would happen to humans if they were affected by endogenous retroviruses as a result of xenotransplantation?

19. Yang, Luhan, et al. "Genome-wide inactivation of porcine endogenous retroviruses (PERVs)." Science 350.6264 (2015): 1101-1104. http://arep.med.harvard.edu/pdf/...

20. Delmonico, Francis L., et al. "A call for government accountability to achieve national self-sufficiency in organ donation and transplantation." The Lancet 378.9800 (2011): 1414-1418. http://www.who.int/transplantati...

https://www.quora.com/Can-we-genetically-modify-animals-to-procure-organs-for-humans/answer/Tirumalai-Kamala

Does occasional use of anticholinergic drugs such as Benadryl have serious neurological risks?

It's important to keep in mind the following issues about the recent epidemiological study (1, 2) that examined the connection between cumulative anticholinergic drug use and incident dementia when considering the extent to which its results are generalizable.

• Though interesting, these results need to be confirmed by other independent studies on larger numbers of patients.
• This study was restricted to patients 65 years and older.
• Authors studied cumulative, not occasional, exposure to Anticholinergic drugs. As defined in this study, cumulative anticholinergic exposure was defined 'as the total standardized daily doses (TSDDs) dispensed in the past 10 years' (1, emphasis mine), is quite different from occasional use, which is presumably not daily use.
• The Anticholinergic drug Benadryl is a 1st generation Antihistamine, containing Diphenhydramine, a Histamine H1 receptor antagonist. In the case of diphenhydramine, the daily dose criterion used in this study was 50mg.
• Authors studied whether long-term cumulative intake of all sorts of combinations of antihistamines, antidepressants, antivertigo, antiparkinson, antipsychotics, bladder antimuscarinics, skeletal muscle relaxants, gastrointestinal antispasmodics and antiarrythmics predisposed those 65 years or older to incident dementia, i.e., newly diagnosed dementia. They did not study outcome of prolonged Benadryl intake alone.
• There is currently little biological basis in the scientific literature for linking cumulative anticholinergic use to outcomes like Alzheimer's disease. Even the authors of this study could make a plausible case only for people with Parkinson's disease, i.e., for people with pre-existing brain damage.

This answer therefore discusses the particulars of the question as asked, that is the effects of occasional, i.e., not daily, use of the anticholinergic Benadryl.

'Serious neurological risks' of occasional Benadryl use consist of strong albeit temporary dose-dependent effects on the central nervous system. It can sedate as well as profoundly impair psychomotor function, i.e., tasks, such as driving an automobile, that require both concentration as well as fine motor skills.

Antihistamines are typically used to treat allergy symptoms, specifically those associated with allergic rhinitis such as runny nose, sneezing, itching. A common symptom of allergic reactions, excess histamine is the consequence of Mast cell degranulation caused by their binding to complexes of Allergen bound to Immunoglobulin E, i.e., antigen-antibody complexes (see figure below from 3). When taken during allergy episodes, antihistamines bind histamine receptors, thereby preventing mast cell-derived histamine from doing so. This in turn prevents the full expression of allergy symptoms such as runny nose, sneezing and itching. So far so good.

Problem is action of 1st generation and even some 2nd generation antihistamines isn't limited to just inhibiting the excess histamine that's secreted when large numbers of mast cells degranulate during an allergy episode.

With its own source of histamine, the brain also widely expresses histamine receptors. The tuberomamillary nucleus, a cluster of neurons in the posterior hypothalamus, synthesizes histamine, and these neurons project into various regions of the brain as part of the histaminergic nervous system, and all four types of histamine receptors are abundantly expressed in the brain in distinct patterns (see figures below from 4, 5).

Since most 1st generation and even some 2nd generation antihistamines penetrate the Blood–brain barrier, they can have profound effects on brain function including Anticholinergic effects, sedation and effects on psychomotor function.

Temporary impairment of driving skills is a prominent example of diphenhydramine's effect on the brain. In 2004, the US National Highway Traffic Safety Administration reviewed antihistamine effect on driving-related skills by examining a total of 130 scientific papers published on the subject until 1998 (6). Among other findings, it concluded (6, emphasis mine),

'There is overwhelming evidence from the experimental literature that the 1st-generation antihistamines produce objective signs of skills performance impairment as well as subjective symptoms of sedation'

Obviously, 1st generation antihistamines include diphenhydramine, the one in Benadryl (see figures below from 6).

Bibliography

1. Gray, Shelly L., et al. "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study." JAMA internal medicine 175.3 (2015): 401-407. https://www.researchgate.net/pro...

2. Harvard Health Publications, Beverly Merz, January 18, 2015. Common anticholinergic drugs like Benadryl linked to increased dementia risk - Harvard Health Blog

3. NIAID Researchers Identify Potential Drug Target for Allergies

4. Thurmond, Robin L., Erwin W. Gelfand, and Paul J. Dunford. "The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines." Nature Reviews Drug Discovery 7.1 (2008): 41-53.

5. Haas, Helmut, and Pertti Panula. "The role of histamine and the tuberomamillary nucleus in the nervous system." Nature Reviews Neuroscience 4.2 (2003): 121-130.

6. Moskowitz, Herbert, and Candace Jeavons Wilkinson. Antihistamines and driving-related behavior: A review of the evidence for impairment. No. HS-809 714,. 2004. http://ntl.bts.gov/lib/26000/260...

https://www.quora.com/Does-occasional-use-of-anticholinergic-drugs-such-as-Benadryl-have-serious-neurological-risks/answer/Tirumalai-Kamala

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