With most of the high-profile repatriated Ebola cases in the US receiving the new anti-Ebolavirus therapy known as “ZMapp,” many are touting the apparent life saving effects of this supposed “miracle” serum. Still classified as an experimental drug, ZMapp was developed by a consortium of bio-pharmaceutical companies and US/ Canadian Governmental public health and defense agencies (1, 2) and has been given an unprecedented fast track into general usage due to the fact that there appear to be few alternatives. What most Americans are unaware of, however, is that ZMapp is not simply another run-of-the-mill pharmaceutical.
What makes ZMapp so different? Well, to put it simply: ZMapp is a genetic amalgamation of plant, animal, and human components (3). Does the idea of putting something like this into your body sound unusual to you? If not, maybe your thoughts will change when you learn how it’s manufactured…
In the production of ZMapp, firstly, mice are exposed to an Ebola antigen, killed, and their spleen cells harvested (4, 5, 6). These cells are then genetically fused with human myeloma cancer cells (ibid). Genetics from this strange hybridized creation are then transferred to a plant-infecting bacterium, or agrobacterium, and then infused into the leaves of the tobacco plant Nicotiana benthamiana (ibid). These are then incubated in a hydroponic greenhouse facility for several months. During this time the GMO human/mouse/bacterium swaps genes with the tobacco plant and produces antibodies that are later harvested, preserved, and packaged in serum for delivery into the human bloodstream (ibid).
If you think all of this is a little unnerving, the plot thickens… Current production of ZMapp is conducted through Kentucky BioProcessing, which is a subsidiary of RJ Reynolds Tobacco Company (7). Interestingly, RJ Reynolds acquired this company and began production of ZMapp in January, 2014, approximately the same time the current Ebola outbreak purportedly began in West Africa (ibid, 8). Coincidence? Maybe… Maybe not… But one thing is for sure: big tobacco has a lot to gain by getting the Ebola virus “under control.” First of all, because of its severe depression of innate immune responses, tobacco use is probably the single most dangerous risk factor in fatal Ebola infection (9, 10, 11, 12). Thus, should Ebola progress, RJ Reynolds would lose a lot of customers in the conflagration. Secondly, this new “wonder drug” stands to replace the normal role of a healthy human immune response vs. Ebola infection. This fits well with the “smoke-it-up” “live-it-up” lifestyle promoted by the tobacco industry.
Given its outlandish formulation and curious production background, what are politicians saying about ZMapp? Well, when asked whether or not this drug would be fast-tracked into widespread usage for West Africa, president Barack Obama stated: “I think we’ve got to let the science guide us” (13). I wholeheartedly concur! Reason being, if we were really looking at the science we would quickly discover that we may already have time-honored, plant-based, anti-viral (and thus potentially anti-Ebola) options available – and all without involving the mice spleens, cancer cells, agrobacterium, and supporting big tobacco interests.
Case in point: the therapeutic potential of black elderberry.
Sambucus Nigra, or black elderberry has been used for centuries for its immune boosting effects and even included as a tasty ingredient in homemade jams and jellies. But don’t let this culinary trivia derail you from the science behind this potent natural remedy!
But first, we need to understand a little more about the function of ZMapp. The premise behind the usefulness of this drug is that, when infected with the Ebolavirus, the human immune system often fails to produce antiviral antibodies. Therefore, bringing in backup, albeit artificial, antibodies seems logical. So, following this train of thought, Zmapp’s GMO antibodies attempt to deactivate Ebola by adhering to the sugary glycoproteins on the surface of the virus (14).
In a normal infection, our b-lymphocytes would naturally produce antibodies as a result of contact with an antigen (a foreign compound such as Ebola glycoproteins). However, it has been found that Ebola actually hides its antigenic surface from the view of “helper cells” that would normally play a role in activating antibody production (15, 16). Individuals who have naturally survived Ebola have been able to overcome this deception and carry on with the production of antibodies (17, 18). This response we would term an optimal or healthy immune response.
Where does Elderberry come in to this discussion? Well it turns out that certain compounds found in this plant actually behave somewhat like antibodies! These components are known as lectins, which are selective sugar-binding proteins. Elderberry has been found to have three distinct lectins: one specifically in the bark of the branches and at least two others in the berries. In particular, the berry lectins have been found to interact or adhere to various components of the Ebola virus (19). Furthermore, one of these lectins has a strong affinity, or bonding preference, to a section of the virus’ surface responsible for hiding the antigenic area from the immune system, known as O-linked glycans (20, 21). Thus, by interfering with this area, the virus potentially can be unmasked and exposed to the wrath of the white blood cells! Of course, you would still need to have a healthy immune response working in concert with this simple, safe, and cost-effective natural remedy – a 180-degree difference in underlying philosophy compared to ZMapp’s laissez faire, or hand’s off, approach to immune system preparedness.
Okay, so elderberry seems to have some potential merit… but you may be wondering how it stacks up to some of the other experimental anti-Ebola medications? Well, let’s see how elderberry compares with another highly publicized experimental medication called “TKM-Ebola.” This drug uses an approach known as RNA interference to halt the progression of viral function and replication (22). Interestingly, studies of Elderberry have found that it contains a similar property! Indeed, elderberry has been found to be a potent source of ribosome-inactivating proteins (23) (viruses use ribosomes to reproduce themselves inside host cells). Furthermore, these elderberry-based ribosomal interference compounds do not normally enter into the human cell cytoplasm (ibid) but may enter with the virus due to lectin attachment. Why is this important? Unnecessary ribosomal interference can lead to a host of side effects: including impaired cellular function, cancer development, and even cell death.
We’ve not even mentioned Sambucus Nigra’s tremendous antioxidant capacity and nutritive properties, but in this plant we already have a remedy that can potentially bind, unmask, and possibly even singlehandedly destroy the… “Hold on a moment” you might be thinking… “Is he actually making a claim that elderberry fights Ebola?”
Well my friend… The best way I can frame my response to you today is… Instead of genetically altering nature and attempting to circumvent the need for a healthy immune system… “I think we’ve got to let the true science guide us.”
References:
1) http://www.kentucky.com/2014/08/09/3373025_how-owensboro-tobacco-grew-a-possible.html?rh=1
2) http://www.bmj.com/content/349/bmj.g5488.long
3) Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18030-5. doi: 10.1073/pnas.1213709109. Epub 2012 Oct 15.
4) http://www.forbes.com/sites/davidkroll/2014/08/05/ebola-secret-serum-small-biopharma-the-army-and-big-tobacco/
5) Methods Mol Biol. 2014;1204:165-85. doi: 10.1007/978-1-4939-1346-6_15.
6) Nature. 2014 Oct 2;514(7520):47-53. doi: 10.1038/nature13777. Epub 2014 Aug 29.
7)http://www.journalnow.com/news/local/ebola-drug-provided-for-two-americans-by-reynolds-american-subsidiary/article_144fb3ce-1cb3-11e4-9f1b-0017a43b2370.html
8) N Engl J Med. 2014 Oct 9;371(15):1418-25. doi: 10.1056/NEJMoa1404505. Epub 2014 Apr 16.
9) Arch Oral Biol. 1989;34(4):283-7.
10) Toxicol Sci. 1999 Aug;50(2):214-20.
11) J Exp Med. 2004 Jul 19;200(2):169-79. Epub 2004 Jul 12.
12) J Allergy Clin Immunol. 2005 Oct;116(4):916-22. Epub 2005 Aug 1.
13) http://www.nbcnews.com/storyline/ebola-virus-outbreak/obama-premature-say-u-s-should-green-light-new-ebola-n174461
14) http://www.cbc.ca/news/health/ebola-cocktail-developed-at-canadian-and-u-s-labs-1.2727703
15) PLoS Pathog. 2010 Sep 9;6(9):e1001098. doi: 10.1371/journal.ppat.1001098.
16) J Virol. 2001 Feb;75(3):1576-80.
17) Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1893-8. doi: 10.1073/pnas.1209591110. Epub 2013 Jan 14.
18) Sci Transl Med. 2012 Oct 31;4(158):158ra146. doi: 10.1126/scitranslmed.3004582.
19) J Virol. 2006 Apr;80(8):3743-51.
20) PLoS Pathog. 2010 Sep 9;6(9):e1001098. doi: 10.1371/journal.ppat.1001098.
21) Biochem J. 1991 Sep 15;278 ( Pt 3):667-71.
22) Lancet. 2010 May 29;375(9729):1896-905. doi: 10.1016/S0140-6736(10)60357-1.
23) Toxins (Basel). 2011 May;3(5):420-41. doi: 10.3390/toxins3050420. Epub 2011 Apr 29.
What makes ZMapp so different? Well, to put it simply: ZMapp is a genetic amalgamation of plant, animal, and human components (3). Does the idea of putting something like this into your body sound unusual to you? If not, maybe your thoughts will change when you learn how it’s manufactured…
In the production of ZMapp, firstly, mice are exposed to an Ebola antigen, killed, and their spleen cells harvested (4, 5, 6). These cells are then genetically fused with human myeloma cancer cells (ibid). Genetics from this strange hybridized creation are then transferred to a plant-infecting bacterium, or agrobacterium, and then infused into the leaves of the tobacco plant Nicotiana benthamiana (ibid). These are then incubated in a hydroponic greenhouse facility for several months. During this time the GMO human/mouse/bacterium swaps genes with the tobacco plant and produces antibodies that are later harvested, preserved, and packaged in serum for delivery into the human bloodstream (ibid).
If you think all of this is a little unnerving, the plot thickens… Current production of ZMapp is conducted through Kentucky BioProcessing, which is a subsidiary of RJ Reynolds Tobacco Company (7). Interestingly, RJ Reynolds acquired this company and began production of ZMapp in January, 2014, approximately the same time the current Ebola outbreak purportedly began in West Africa (ibid, 8). Coincidence? Maybe… Maybe not… But one thing is for sure: big tobacco has a lot to gain by getting the Ebola virus “under control.” First of all, because of its severe depression of innate immune responses, tobacco use is probably the single most dangerous risk factor in fatal Ebola infection (9, 10, 11, 12). Thus, should Ebola progress, RJ Reynolds would lose a lot of customers in the conflagration. Secondly, this new “wonder drug” stands to replace the normal role of a healthy human immune response vs. Ebola infection. This fits well with the “smoke-it-up” “live-it-up” lifestyle promoted by the tobacco industry.
Given its outlandish formulation and curious production background, what are politicians saying about ZMapp? Well, when asked whether or not this drug would be fast-tracked into widespread usage for West Africa, president Barack Obama stated: “I think we’ve got to let the science guide us” (13). I wholeheartedly concur! Reason being, if we were really looking at the science we would quickly discover that we may already have time-honored, plant-based, anti-viral (and thus potentially anti-Ebola) options available – and all without involving the mice spleens, cancer cells, agrobacterium, and supporting big tobacco interests.
Case in point: the therapeutic potential of black elderberry.
Sambucus Nigra, or black elderberry has been used for centuries for its immune boosting effects and even included as a tasty ingredient in homemade jams and jellies. But don’t let this culinary trivia derail you from the science behind this potent natural remedy!
But first, we need to understand a little more about the function of ZMapp. The premise behind the usefulness of this drug is that, when infected with the Ebolavirus, the human immune system often fails to produce antiviral antibodies. Therefore, bringing in backup, albeit artificial, antibodies seems logical. So, following this train of thought, Zmapp’s GMO antibodies attempt to deactivate Ebola by adhering to the sugary glycoproteins on the surface of the virus (14).
In a normal infection, our b-lymphocytes would naturally produce antibodies as a result of contact with an antigen (a foreign compound such as Ebola glycoproteins). However, it has been found that Ebola actually hides its antigenic surface from the view of “helper cells” that would normally play a role in activating antibody production (15, 16). Individuals who have naturally survived Ebola have been able to overcome this deception and carry on with the production of antibodies (17, 18). This response we would term an optimal or healthy immune response.
Where does Elderberry come in to this discussion? Well it turns out that certain compounds found in this plant actually behave somewhat like antibodies! These components are known as lectins, which are selective sugar-binding proteins. Elderberry has been found to have three distinct lectins: one specifically in the bark of the branches and at least two others in the berries. In particular, the berry lectins have been found to interact or adhere to various components of the Ebola virus (19). Furthermore, one of these lectins has a strong affinity, or bonding preference, to a section of the virus’ surface responsible for hiding the antigenic area from the immune system, known as O-linked glycans (20, 21). Thus, by interfering with this area, the virus potentially can be unmasked and exposed to the wrath of the white blood cells! Of course, you would still need to have a healthy immune response working in concert with this simple, safe, and cost-effective natural remedy – a 180-degree difference in underlying philosophy compared to ZMapp’s laissez faire, or hand’s off, approach to immune system preparedness.
Okay, so elderberry seems to have some potential merit… but you may be wondering how it stacks up to some of the other experimental anti-Ebola medications? Well, let’s see how elderberry compares with another highly publicized experimental medication called “TKM-Ebola.” This drug uses an approach known as RNA interference to halt the progression of viral function and replication (22). Interestingly, studies of Elderberry have found that it contains a similar property! Indeed, elderberry has been found to be a potent source of ribosome-inactivating proteins (23) (viruses use ribosomes to reproduce themselves inside host cells). Furthermore, these elderberry-based ribosomal interference compounds do not normally enter into the human cell cytoplasm (ibid) but may enter with the virus due to lectin attachment. Why is this important? Unnecessary ribosomal interference can lead to a host of side effects: including impaired cellular function, cancer development, and even cell death.
We’ve not even mentioned Sambucus Nigra’s tremendous antioxidant capacity and nutritive properties, but in this plant we already have a remedy that can potentially bind, unmask, and possibly even singlehandedly destroy the… “Hold on a moment” you might be thinking… “Is he actually making a claim that elderberry fights Ebola?”
Well my friend… The best way I can frame my response to you today is… Instead of genetically altering nature and attempting to circumvent the need for a healthy immune system… “I think we’ve got to let the true science guide us.”
References:
1) http://www.kentucky.com/2014/08/09/3373025_how-owensboro-tobacco-grew-a-possible.html?rh=1
2) http://www.bmj.com/content/349/bmj.g5488.long
3) Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18030-5. doi: 10.1073/pnas.1213709109. Epub 2012 Oct 15.
4) http://www.forbes.com/sites/davidkroll/2014/08/05/ebola-secret-serum-small-biopharma-the-army-and-big-tobacco/
5) Methods Mol Biol. 2014;1204:165-85. doi: 10.1007/978-1-4939-1346-6_15.
6) Nature. 2014 Oct 2;514(7520):47-53. doi: 10.1038/nature13777. Epub 2014 Aug 29.
7)http://www.journalnow.com/news/local/ebola-drug-provided-for-two-americans-by-reynolds-american-subsidiary/article_144fb3ce-1cb3-11e4-9f1b-0017a43b2370.html
8) N Engl J Med. 2014 Oct 9;371(15):1418-25. doi: 10.1056/NEJMoa1404505. Epub 2014 Apr 16.
9) Arch Oral Biol. 1989;34(4):283-7.
10) Toxicol Sci. 1999 Aug;50(2):214-20.
11) J Exp Med. 2004 Jul 19;200(2):169-79. Epub 2004 Jul 12.
12) J Allergy Clin Immunol. 2005 Oct;116(4):916-22. Epub 2005 Aug 1.
13) http://www.nbcnews.com/storyline/ebola-virus-outbreak/obama-premature-say-u-s-should-green-light-new-ebola-n174461
14) http://www.cbc.ca/news/health/ebola-cocktail-developed-at-canadian-and-u-s-labs-1.2727703
15) PLoS Pathog. 2010 Sep 9;6(9):e1001098. doi: 10.1371/journal.ppat.1001098.
16) J Virol. 2001 Feb;75(3):1576-80.
17) Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1893-8. doi: 10.1073/pnas.1209591110. Epub 2013 Jan 14.
18) Sci Transl Med. 2012 Oct 31;4(158):158ra146. doi: 10.1126/scitranslmed.3004582.
19) J Virol. 2006 Apr;80(8):3743-51.
20) PLoS Pathog. 2010 Sep 9;6(9):e1001098. doi: 10.1371/journal.ppat.1001098.
21) Biochem J. 1991 Sep 15;278 ( Pt 3):667-71.
22) Lancet. 2010 May 29;375(9729):1896-905. doi: 10.1016/S0140-6736(10)60357-1.
23) Toxins (Basel). 2011 May;3(5):420-41. doi: 10.3390/toxins3050420. Epub 2011 Apr 29.
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