Fear does strange things to people. The fear du jour currently permeating the US is, of course, the Ebola virus disease. Despite the august efforts to reassure and educate from CDC and the WHO, there has spread a modicum of panic (often with tragic results); we have seen Ebola response become a political issue, and as pointed out recently by that redoubtable scienceblogger, Orac, a ghastly profusion of conspiracy theories and quackery has crawled out of nooks and crannies, feeding into the overall noise that is smothering rational discourse on the topic. But even before Orac wrote on it, my attention was drawn on Twitter to the latest volley of insane quackery to emerge, a supposedly “Ayurvedic approach” to curing Ebola – the Ayurveda nowadays being a catch-all term to refer to everything pre-scientific mumbo-jumbo allegedly written in the ancient Hindu holy texts, the Vedas. Because culture.
Said ‘therapeutic approach’, propounded by one TR Shantha*, consists of an Ebola-infected patient drinking their own urine – an approach referred to as “Auto urine therapy”, which apparently cures Ebola. The details are in the link to the post above; I am not going to repeat them here. Suffice it to say, urine therapy was explained in the ‘Ayurvedic approach’ post using a lot of science-y sounding words, veritably the stock-in-trade of modern quacks – unscientific, meaningless nonsense, prodigiously mixed with some correct scientific information to increase the scienciness quotient of the pablum.
However, I decided to stick to the science of it (or absence thereof) for my comments. As an immunology researcher, I saw a claim being made about human immune defence mechanisms. I chose to see it as a hypothesis, and decided to find out how valid such a hypothesis is, based on existing literature. The overall claim includes four definitive statements:
- “Ebola virus particles […] are broken down in the body by the immune system.”
- (Broken down) [Ebola virus particles] “are passed in the urine with other metabolic products including protein components, enzymes, and hormones.”
- When (an Ebola-infected patient) drinks (their own) urine, the “broken down fragments of the Ebola virus pass through the intestines.”
- Plasma cells [in the intestines] “pick up the virus and their fragments, and synthesize antibodies against the Ebola virus. By the tenth day, billions of antibody particles are produced and circulating in the body, attaching to the Ebola viruses in the body, killing them, and clearing them from the body…”
Let’s take a look at Ebola virus in the context of these claims. But before I proceed further into immunology, let’s take care of the elephant in the room:
Is Ebola antigen excreted via urine?
Two studies from 2007, respectively testing putative Ebola immunodiagnostics and assessing virus transmission via bodily fluids, failed to detect any Ebola antigen in the urine samples from confirmed Ebola-infected patients associated with both a 2000 outbreak in Uganda and a 2003 outbreak in Central Africa. Ebola has not been isolated from urine of infected patients, and the use of urine samples to diagnose Ebola infection in humans is not established. The presence of Ebola antigens in patient urine, therefore, appears to be pure conjecture on part of the claim by the proponent of urine therapy, unsupported by any clinical or biological evidence.
Let me move on to the immunology aspect. Inside the host, ordinarily, the earliest immune defence members to encounter an invading pathogen are the cells of mononuclear phagocytic system, such as monocytes/macrophages and Dendritic Cells (DC); these coordinate between innate and adaptive responses, by primarily engulfing the pathogen (a process called phagocytosis) and breaking it down (a.k.a. ‘lysis’), and thereafter, displaying the pathogen fragments on the cell surface in association with certain proteins called MHCs (a process called antigen presentation). This allows helper T-lymphocytes to see the antigen and mediate the establishment of specific immunity involving other T-cells and antibodies generated by B-lymphocytes; a variant of this display also drives cytotoxic T-lymphocytes (CTL) and Natural Killer (NK) cells to destroy the presenting cell itself, along with everything that is inside (this happens with infected or malignant cells).
So, yes, the first statement is correct in a general sense, except for… filoviruses, the group of viruses consisting of Ebola and the Marburg virus.
Curiously, Ebola targets these antigen-presenting cells (macrophages and DCs), and later, other cell types, such as fibroblasts and endothelial cells (except, for an as-yet unknown reason, lymphocytes). This mode of infection is considered the likely reason for rapid and wide dissemination of the virus, through blood (via monocytes) and the lymphatics (via DCs).
The resulting syndrome of symptoms (fever, body-aches, headache, and gastrointestinal symptoms) is common to many viral infections, and is due to non-specific immune activation and cytokine storm – as the host body prepares to fight the virus out. Fatal Ebola infection, on the other hand, is characterized by a failure of the infected host to clear the infection; the intracellular persistence of the virus acts as a continuous inflammatory trigger. This results in the related processes of:
- Excessive and inappropriate inflammation, detrimental to the host, causing tissue damage. Type 1 Interferons are cellular messengers or cytokines that stimulate innate immune cells to elicit anti-viral responses; this, however, is blocked by certain proteins of Ebola, which makes way for inappropriately copious release of several pro-inflammatory cytokines from Ebola-infected macrophages. Not only does this cause tissue damage, it also leads to loss of integrity of the wall of the blood vessels (a.k.a. vascular epithelium) causing hemorrhage and activation of the cascading blood coagulation machinery.
Interestingly (from a biological perspective), Ebola infection of DCs appears to inactivate the normal DC immune responses, including the critical function of antigen presentation via MHC, which hinders further activation of Ebola-specific adaptive cellular and antibody-mediated responses. - Lymphocyte suicide (a.k.a. apoptosis). As Ebola continues to replicate inside macrophages and DCs, these immune cells die, whereas nearby T-lymphocytes undergo cell death via a poorly understood process called ‘bystander apoptosis’ – thus depleting a very important anti-viral defence component. (Note that CTLs are not generally restricted by viral epitope antigenicity variations, and can recognize and kill virus-infected cells upon activation – sometimes even before antibody production has begun. — KD)
- Inappropriate activation of blood coagulation cascades, which results in a dangerous condition called disseminated intravascular coagulation (DIC) – formation of random blood clots inside small blood vessels throughout the body, leading to a hindrance to blood flow and multiple organ damage. Moreover, as the players in the normal clotting mechanism are exhausted in DIC and vascular epithelium breaks down, random and severe bleeding may occur from various sites, greatly increasing the risk of death. Currently, palliative care for Ebola hemorrhagic fever targets the management of this abnormal blood coagulation.
Let’s process the fourth claim next. The claim is essentially about Ebola virus particles acting like an oral vaccine antigen. (Although, I suspect, the proponent and the aficionados of urine-therapy would probably carefully avoid the term ‘vaccine’ from their missives, nonetheless… — KD)
Oral vaccination (as practised in different parts of the world to protect against Rabies, Cholera and Polio) is a sound principle in immunological therapy, provided the antigen can be protected from exposure to gastric acid, bile and pancreatic secretions. This is usually achieved by some kind of encapsulation of the antigen, which is an area of active research, involving several different types of technology. It is highly unlikely that any orally-consumed naked/unmodified antigen – assuming, for the moment, that the claim about Ebola antigen in urine is true – would survive the passage (while retaining their immunogenicity) through the upper part of the gastrointestinal tract.
If the antigen sufficiently reaches the patches of immune cell-rich lymphoid tissue, known as Peyer’s Patches, in the lowest part of the small intestine, they are taken up specialized cells called M cells. M cells in Peyer’s Patches thus perform an important immune surveillance function by a general sampling of certain commensal and pathogenic bacteria (as well as various antigens or toxins from them) in the gut microenvironment. The microbes/antigens (including orally delivered vaccine antigens) are handed by M cells over to macrophages and DCs underneath, who present the antigens to T- and B-lymphocytes, stimulating them and ultimately resulting in adaptive immunity against those antigens, including secretion of mucosal antibodies (mostly IgA) and formation of mucosal immunological memory (IgA-eliciting memory B-cells). Because antigen-activated B and T cells migrate to distant mucosal tissues via the circulatory system, this process also leads to the generation of systemic memory B-cells capable of producing antigen-specific IgM and IgG.
However, a major caveat is that empirical evidence of M cell and antigen interaction in humans is lacking; what we know comes from animal studies and in vitro cell-culture models, which may not accurately represent what happens in the human gut. Many early animal studies have shown poor immune response to orally delivered antigens; poor uptake of specific particulate antigens by the M cells is a serious concern in oral vaccine delivery, and requires special technological interventions such as adjuvants and ligand-targeting – another area of active research.
Another concern comes to play regarding immunological interactions at the mucosa. Immunological tolerance is an important response at the mucosa to soluble antigens, which prevents harmful, inappropriate immune responses to food antigens, as well as maintains the balance between commensal gut microbes and the host. Therefore, in order for non-living antigen particles to be efficient vaccines, the selection of appropriate formulations, including adjuvants, is crucial for the purpose of avoiding the induction of tolerance in preference to protective immunity against the vaccine antigen. The claim about orally-consumed naked/unmodified Ebola antigen, therefore, has precious little foundation in science.
But how good a vaccine antigen would Ebola ‘particles’ be per se? Ebola (as well as the Marburg virus) contains single stranded (ss) Ribonucleic acid (RNA) as its genetic material, the directional orientation of which marks it as ‘negative sense’. Which means, unlike regular RNA that is transcribed from DNA, this ssRNA cannot directly be translated to proteins. Inside the virus, an enzyme called RNA-dependent RNA polymerase creates a ‘positive sense’, complementary RNA using the ‘negative sense’ ssRNA as a template, and this ‘positive-sense’ RNA utilizes the host translational (i.e. protein making) machinery to create the viral proteins, including the coat and more viral enzymes.
As a side note, this also means that negative-sense ssRNA present natively inside the virus is not directly infectious, even in a purified form, until it undergoes RNA-polymerase-mediated transcription to positive sense RNA. Additionally, because the viral RNA polymerases lack corrective proofreading ability, this transcription process is riddled with errors, resulting in high mutation rates in RNA viruses; inside the host, such high mutation rates may lead to rapid evolution in these RNA viruses, leading to antigenically distinct viral pathogens, which poses a challenge for rational vaccine design.
Generally, within the spectrum of viral antigens (especially, coat or surface antigens), most viruses tend to have strong, moderate or poor degree of conservation (conservation = absence of change, in spite of mutation/evolution) of antigenic structures (a.k.a. ‘epitopes’). The ideal vaccine would recognize a strongly-conserved epitope; in reality, however, rational vaccine design needs to consider multivalent (i.e. recognizing multiple epitopes) vaccines and changes in vaccine antigens to adequately cover virus strain variants sporting all sorts of antigenic surfaces. More importantly, the most effective vaccines against viral pathogens are those which stimulate the cell-mediated immune response (CMI) in addition to antibodies. Therefore, again, the naked/unmodified Ebola virus particles – as in the claim – seem hardly likely candidates as antigen to generate an appreciable immune response which could protect against the rapidly evolving virus.
Let’s look at antibodies, which forms part of the fourth claim. Secretory IgA provides protection at the mucosal surface on the side of the intestinal lumen (the inner hole of food tube). It works well for enteric pathogens, but what about Ebola?
Currently, of all the structural proteins of the Ebola virus, a membrane envelope glycoprotein is the only known target of antibodies which can neutralize the virus by inhibiting viral attachment to host cells. Experimental studies have been done with monoclonal antibodies, but such neutralizing antibodies have been found in the sera of patients who get well, as well as of infected non-human primates. However, the protective efficacy of such antibodies has not been reliably established, especially in primates and humans. Recent studies have shown some promise, but only with a combination of multiple monoclonal antibodies or polyclonal IgG concentrated from animals immunized with vaccines made from the virus.
A caveat with polyclonal antisera to filoviruses is the presence of the phenomenon called antibody-dependent enhancement, in which viral glycoprotein-specific antisera contains a subset of antibodies with the capacity to enhance viral infectivity in vitro. This may be resolved by employing only monoclonal antibodies, but again, such antibodies are required to be used in high quantities – because Ebola-infected cells prodigiously secrete soluble glycoproteins which act as decoys to sequester (and thereby, inactivate) specific antibodies. In addition, antibodies specific for one strain of Ebola virus may not recognize other strains. These are some important challenges surrounding antibodies and their action against Ebola infection, which are – needless to say – a far cry from the preposterous (which should be clear by now) claims made by the proponent of a ridiculous, not to mention, potentially dangerous, ‘alternative medicine’ therapy.
So, no. Drinking your own urine will not cure Ebola (or anything else). Do educate yourself by perusing the CDC guidelines linked above. If you come down with an illness, please get thee to your physician, but don’t give in to fear and panic.
*According to a court indictment obtained by Quackwatch, TR Shantha, a.k.a. Totada R Shanthaveerappa, obtained his basic medical degree from the RG Kar Medical College at the University of Calcutta (India) in 1958 (Shame. It’s my city, and I have friends who passed through this Medical School and are honorably engaged in medical practice in various parts of the world – KD). Apparently, he went to grad school in the US, obtaining a PhD in Anatomy and Basic Medical Sciences from Emory University School of Medicine, in 1962. He was prosecuted for healthcare fraud in 2005.
I don’t know if urine therapy will cure ebola, but I take issue with your saying “or anything else.” Do educate yourself by reading all of the urine therapy books at the Water Library here:
http://aquariusthewaterbearer.com/the-water-library/
One in particular, “The Water of Life” by J.W. Armstrong, is also available as an audiobook here:
The protocol outlined there is a urine and water fast accompanied by daily urine rubbings as a way of bypassing the digestive system. I followed that protocol for an illness that normally would require a doctor’s visit and antibiotics, and the protocol worked for me. You are doing people a disservice by telling them urine therapy doesn’t work for any illnesses and only physicians can help them. I understand that normally physicians need the business, but in a pandemic scenario like the one in Africa where there are not enough physicians available, urine therapy could save lives. Of course, no one will test it because there’s no money in it for the medical establishment. Meanwhile, extracts from urine are being used in many pharmaceuticals and skin care products, as explained in the book “Your Own Perfect Medicine” by Martha Christy.
“urine therapy could save lives” — [Citation Needed]
And citation in a proper, peer-reviewed medical journal, please. Circular citations of crank books, testimonials and YouTube videos do not citation make.
*wibble*… *wibble*… And of course the inevitable “Of course no one will test it because there’s no money in it for the medical establishment” gambit.
As I’ve said elsewhere… Taking the piss. Literally, in this case.
Indeed. And the same excuses used over and over in lieu of evidence do get a bit tiresome after a while. :
I got a Spam/Troll comment which I have allowed to stand here for a little while, and which I am relegating to the Spam folder. However, I am going to copy-paste the comment – to serve as an example of how pervasive and insidious quackery and superstitious nonsense are, and how inherently dangerous, since they prey upon the vulnerable.
“Henry” left the same email address as the contact email for the comment. And the IP maps to Nigeria. (So much for ‘I am from Liberia’!!).