Since the beginning of 2014, Ebola virus disease has claimed more than 4,500 lives, making it the largest epidemic of the virus in history.1 The United States Centers for Disease Control and Prevention (CDC) report that more than 9,000 total individuals in Guinea, Liberia, Sierra Leone, and other West African countries have been infected with Ebola, which kills roughly half of its victims.1 The first two recorded outbreaks of the disease occurred simultaneously in 1976 in Sudan and in a village in the Democratic Republic of Congo near the Ebola River, after which the virus is named.2
On September 30, 2014, the CDC reported the first case of Ebola in the United States.3 The patient, Thomas Eric Duncan, traveled from Liberia to Dallas on September 20 and began exhibiting symptoms four days later. He was quarantined and treated with the experimental pharmaceutical drug brincidofovir at Texas Health Presbyterian Hospital, but later died on October 8, 2014.3,4 Since that time, two healthcare workers who had contact with Duncan have tested positive for Ebola, and the CDC currently is monitoring hospital employees for symptoms.5
Prior to the recent cases in Dallas, two American aid workers volunteering in impacted regions in West Africa contracted Ebola.6 The infected Americans were among the first humans to receive an experimental drug known as ZMapp™, a biosynthetic drug produced in a species of low-nicotine tobacco (Nicotiana benthamiana, Solanaceae) leaves through a process generally known as “biopharming” — the process of using plants to produce genetically engineered disease-fighting agents. (Nicotiana benthamiana, or “native tobacco,” is endemic to northern Australia.7) Both individuals have recovered from the virus, although the extent to which ZMapp contributed to their recovery is unknown.6 Due to the severely limited supply of the drug, ZMapp has been given only to seven individuals, two of whom have died.8
In a region of the world that was largely unprepared for an Ebola outbreak of this magnitude, confusion and fear-mongering abound. There are currently no drugs — pharmaceutical or otherwise — shown to be effective for curing Ebola, and treatment often consists of “supportive therapy,” which includes maintaining patients’ fluids, oxygen levels, and blood pressure, among other measures.1 Amid widespread media coverage of the outbreak and fear bordering on panic, some companies and individuals have recommended unproven plant-based and non-herbal “cures” for the virus. In mid-August, the US Food and Drug Administration (FDA) and the World Health Organization (WHO) issued statements alerting consumers to such deceitful — and potentially harmful — product claims, and, in late September, the FDA sent warning letters to three American companies advertising herbal products as being effective for treating and preventing Ebola.9
“Unfortunately, during outbreak situations, fraudulent products that claim to prevent, treat, or cure a disease all too often appear on the market,” the FDA noted in its August statement.9 “Although there are experimental Ebola vaccines and treatments under development, these investigational products are in the early stages of product development, have not yet been fully tested for safety or effectiveness, and the supply is very limited.”
ZMapp and the Promise of Biopharming
In January 2014, the San Diego, California-based companies Mapp Biopharmaceutical and LeafBio, working in conjunction with Defyrus, Inc. in Toronto, Canada, identified a promising new experimental treatment for Ebola.10 The drug, ZMapp, is not a single compound; rather, it is a combination of plant-produced antibodies. “It is an optimized cocktail combining the best components of MB-003 (Mapp) and ZMAb (Defyrus/[Public Health Agency of Canada]),” Mapp Biopharmaceutical explains.11
The final stages of the multi-step process used to produce ZMapp require the use of tobacco plants, which act as miniature factories that produce genetically modified Ebola-fighting agents. The overall process consists of three main components10:
First, Ebola antigens (i.e., substances that elicit an immune response in the body) are injected into mice, which then begin to produce Ebola antibodies (i.e., proteins used by the immune system to recognize and attack antigens).
The Ebola antibodies are combined with B-cells (i.e., white blood cells that produce antibodies) and certain cancer cell lines, which form what are known as “hybridomas” — specialized cells designed to produce the Ebola antibodies.
Finally, tobacco plants are infected with the hybridomas, which replicate and produce Ebola antibodies in the plants’ leaves. The process eventually kills the plant, and the antibodies are extracted and purified from the leaves.10
Although ZMapp has not yet been studied in humans, animal studies suggest that an earlier version of the drug known as ZMAb may provide some benefit for Ebola-infected primates. According to a November 2013 article in the journal Scientific Reports, researchers treated six Ebola-infected monkeys with ZMAb, all of which survived.12 In a separate experiment conducted by the same research team, the animals were infected with the virus again after 13 weeks, and four of the six monkeys survived.12
Currently, there are 30 antibody-based drugs approved for use in the United States, many of which are used as cancer treatments. Each of these drugs is produced using animals — most often hamsters — as antibody factories.13 However, the use of plants to produce antibody-based drugs may offer some unique manufacturing benefits — and challenges.
These so-called “plantibody” drugs “may prove to be faster, higher yielding and cheaper than current methods using mammalian cells.”13 According to Victor Klumyuk, COO of drugmaker Icon Genetics, plant-based biopharming “may work best when speed is required or when flexibility is required … to manufacture vaccines for an epidemic or for fast, reliable production.”13 For example, creating a flu vaccine using chicken eggs takes approximately six months; using plant-based methods, flu vaccines can be produced in as little as one week.14
The particular type of tobacco used in the production of ZMapp — which is related to, but not the same as, smoking tobacco — was chosen carefully by the drug’s manufacturer. “In selecting an appropriate production platform, we needed a system that was rapid and scalable,” notes Mapp Biopharmaceutical on its website.10 “The low nicotine tobacco plant, Nicotiana benthamiana, is capable of expressing foreign (non-tobacco) proteins using indoor cultivation under tightly controlled conditions.”
However, the FDA has raised numerous concerns about the process of biopharming. The Agency lists such potential issues in its 2002 draft guidance document on “Drugs, Biologics, and Medical Devices Derived from Bioengineered Plants for Use in Humans and Animals.”15 Specifically, the FDA cites the following concerns in the document: the consistency of the final product; “the potential for the plant to express an allergenic or toxic compound; the method of plant propagation and the measures to ensure confinement; and, if it is a food crop species engineered to produce non-food material, the measures to ensure that non-food (or non-feed) material will not get into food or feed.”
“The ostensible objective of the regulation is to avoid biopharmed drugs winding up in food,” explained the author of a recent Wall Street Journal article.16 “But the fear is overblown, and contamination can be avoided in several ways. Production involving a non-food crop like tobacco is an obvious one.”
Herbal “Cures”: FDA Warning Letters and Industry Response
With no available cure or scientifically proven treatment for Ebola, some traditional healers and officials in Africa have claimed that various herbal concoctions such as those made with bitter kola (Garcinia kola, Clusiaceae),17 ashwagandha (Withania somnifera, Solanaceae),18 and jute (Corchorus capsularis, Malvaceae)19 can offer protection against the virus or cure those infected. In late September, the FDA issued warning letters to three American companies that promoted their products for the treatment of Ebola.20-22 In perhaps the most egregious violation, Natural Solutions Foundation was warned for advertising its non-herbal colloidal Nano Silver Solution23 as “the definitive prevention and therapy for Ebola virus.”20
Similarly, the FDA sent warning letters to Utah-based companies Young Living and doTERRA International, LLC for their essential oil products. “Ebola Virus can not live in the presence of cinnamon bark … nor Oregano,” Young Living claimed on its website.21 “Viruses (including Ebola) are no match for Young Living Essential Oils.” Certain doTERRA essential oil products, according to the FDA warning letter, also violate federal law due to unsubstantiated, drug-like claims. Consultants for the company claimed online that doTERRA’s products are helpful for “conditions including, but not limited to, viral infections (including ebola [sic]),” and a primary use of the company’s oregano oil product is listed as “Ebola virus.”22
Each of the three companies was warned for promoting products for “conditions that cause them to be drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act,” therefore rendering the products adulterated. The companies were given 15 business days to rectify the violations.20-22
Roughly two weeks after FDA sent the warning letters, a coalition of five natural products industry organizations issued its own statement on October 7, 2014, regarding supplements claiming to treat or cure Ebola.24 “We are unaware of any scientific data supporting the use of dietary supplements to prevent Ebola virus infection or treat Ebola virus disease,” noted the American Herbal Products Association, Consumer Healthcare Products Association, Council for Responsible Nutrition, Natural Products Association, and United Natural Products Alliance.
In addition to urging that anyone who may have come into contact with the virus seek immediate professional medical help, the joint statement included two main recommendations: (1) “Marketers and retailers of dietary supplements are urged to refuse to stock or sell any supplements that are presented as treating or curing Ebola virus disease, or preventing Ebola virus infection;” and (2) “Marketers and retailers should refrain from promoting any dietary supplement as a cure or treatment for Ebola virus disease.”24
The Future of Ebola Treatments
On August 13, 2014, Mapp Biopharmaceutical announced that its supply of the plantibody drug ZMapp had been exhausted.19 At present, the company is collaborating with other companies — including Caliber Biotherapeutics in Texas8 and Kentucky Bioprocessing, a division of the cigarette manufacturer Reynolds American — to ramp up production of the drug.13 However, progress has been slow. Mapp Biopharmaceutical expects it will be a number of months before additional supplies of ZMapp are available, and the company is currently in the process of initiating Phase 1 clinical trials for the drug.6
A number of US government agencies — including the National Institute of Allergy and Infectious Diseases, the Defense Threat Reduction Agency, and Biomedical Advanced Research and Development — are working on experimental treatments and vaccines for Ebola in conjunction with Mapp Biopharmaceutical and other companies.4 Additionally, an influenza drug known as fabipiravir developed by a division of the Japanese company Fujifilm is being considered as a treatment option; the drug was given to French nurse infected with Ebola while working in Africa, who has since recovered.25 Most recently, on October 13, 2014, the Public Health Agency of Canada began testing an Ebola vaccine made from a modified rabies virus at the Walter Reed Army Institute of Research in Silver Spring, Maryland.25
Approximately one month after Mapp Biopharmaceutical’s announcement, the CDC released updated statistics on projected Ebola cases in West Africa. The figures were grim; the CDC estimated as a worst-case scenario that Liberia and Sierra Leone could have a combined 1.4 million cases of Ebola infection by January 20, 2015, if additional measures are not taken to control the spread of the virus.26
In the meantime, the CDC and WHO recommend against taking unproven herbal or alternative therapies for the prevention, treatment, or cure of Ebola, as such remedies, they state, could lead to more harm than good.27 In Nigeria, for example, the claim that drinking saltwater could protect against Ebola has led to the deaths of two individuals.
Such bogus claims are “predictable, but hugely worrying,” noted bioethicist Arthus L. Caplan of New York University’s Langone School of Medicine in an August 15 New York Times article.27 “Whenever there is fear, misery and death, there are people who will take your money promising you a cure.”
- 2014 Ebola outbreak in West Africa. US Centers for Disease Control and Prevention website. Available at: www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html. Accessed September 23, 2014.
- Ebola virus disease. World Health Organization website. Available at: www.who.int/mediacentre/factsheets/fs103/en/. Accessed September 29, 2014.
- Grady D. Ebola is diagnosed in Texas, first case found in the US. New York Times. Available at: www.nytimes.com/2014/10/01/health/airline-passenger-with-ebola-is-under-treatment-in-dallas.html?ref=health&_r=0. Accessed October 1, 2014.
- Dallas Ebola patient dies, hospital confirms. Fox News. October 8, 2014. Available at: www.foxnews.com/health/2014/10/08/dallas-ebola-patient-dies/. Accessed October 10, 2014.
- Ebola outbreak: Second Texas health worker tests positive for Ebola. BBC News. Available at: www.bbc.com/news/world-us-canada-29628622. Accessed October 15, 2014.
- Questions and answers on experimental treatments and vaccines for Ebola. US Centers for Disease Control and Prevention website. Available at: www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/qa-experimental-treatments.html. Accessed September 26, 2014.
- Nicotiana benthamiana: native tobacco. Australia’s Virtual Herbarium website. Available at: http://avh.ala.org.au/occurrence/e417092b-104c-4738-a7c4-6ba284bc6511. Accessed September 29, 2014.
- Pollack A. US will increase production of the Ebola drug ZMapp, but may not meet demand. New York Times. Available at: www.nytimes.com/2014/10/02/world/us-to-increase-production-of-experimental-drug-but-may-not-meet-demand.html?_r=0. Accessed October 2, 2014.
- FDA statement: FDA warns consumers about fraudulent Ebola treatment products. US Food and Drug Administration website. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm410086.htm. Accessed September 26, 2014.
- ZMapp™ frequently asked questions. Mapp Biopharmaceutical website. Available at: www.mappbio.com/zmapinfo.pdf. Accessed September 29, 2014.
- ZMapp™ information sheet. Mapp Biopharmaceutical website. Available at: www.mappbio.com/zmapinfo.pdf. Accessed October 2, 2014.
- Qui X, Audet J, Wong G, et al. Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb. Scientific Reports. 2013. doi: 10.1038/srep03365. Available at: www.nature.com/srep/2013/131128/srep03365/full/srep03365.html. Accessed September 29, 2014.
- ‘Plantibody’ drugs show promise without help of big pharma. August 18, 2014. NewsmaxHealth website. Available at: www.nature.com/srep/2013/131128/srep03365/full/srep03365.html. Accessed September 26, 2014.
- Ferguson C. This kind of tobacco is good for you. Take Part website. Available at: www.takepart.com/article/2014/09/10/ebola-drug-zmapp-from-tobacco. Accessed September 29, 2014.
- Guidance for Industry: Drugs, Biologics, and Medical Devices Derived From Bioengineered Plants for Use in Humans and Animals. US Food and Drug Administration website. Available at: www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124811.pdf. Accessed September 26, 2014.
- Miller HI. Genetic engineering and the fight against Ebola. Wall Street Journal website. Available at: www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124811.pdf. Accessed September 29, 2014.
- Kilham C. A warning on phony Ebola ‘cures.’ Fox News. Available at: www.foxnews.com/health/2014/10/08/warning-on-phony-ebola-cures/. Accessed October 14, 2014.
- Muanya C. Panel probes herbal cure claims for Ebola virus, others. All Africa website. Available at: http://ngrguardiannews.com/sunday-magazine/living-wellbeing/173979-panel-probes-herbal-cure-claims-for-ebola-virus-others. Accessed September 23, 2014.
- Anya I, Ihekweazu C. No evidence that ewedu plant concoction can cure Ebola. Africa Check website. Available at: http://africacheck.org/reports/no-evidence-that-ewedu-plant-concotion-can-cure-ebola/. Accessed September 26, 2014.
- FDA Warning Letter: Natural Solutions Foundation. September 23, 2014. US Food and Drug Administration website. Available at: www.fda.gov/iceci/enforcementactions/warningletters/2014/ucm416051.htm. Accessed September 29, 2014.
- FDA Warning Letter: Young Living. September 23, 2014. US Food and Drug Administration website. Available at: www.fda.gov/iceci/enforcementactions/warningletters/2014/ucm416023.htm. Accessed September 29, 2014.
- FDA Warning Letter: doTERRA International, LLC. September 23, 2014. US Food and Drug Administration website. Available at: www.fda.gov/iceci/enforcementactions/warningletters/2014/ucm415809.htm. Accessed September 29, 2014.
- Dr. Rima Recommends™ The Silver Solution. Natural Solutions Foundation website. Available at: www.nsfmarketplace.com/product/silver-sol-16-oz-473-ml/. Accessed September 29, 2014.
- Grady D. Ebola cases could reach 1.4 million within four months, C.D.C. estimates. New York Times. Available at: www.nytimes.com/2014/09/24/health/ebola-cases-could-reach-14-million-in-4-months-cdc-estimates.html?_r=0. Accessed September 29, 2014.
- Szabo L. New Ebola vaccine study has begun in Maryland. USA Today. Available at: www.usatoday.com/story/news/nation/2014/10/14/more-ebola-vaccine-studies/17254175/. Accessed October 14, 2014.
- Daniells S. Trade associations remind industry: ‘Dietary supplements cannot claim to cure or prevent Ebola.’ October 8, 2014. NutraIngredients-USA website. Available at: www.nutraingredients-usa.com/Regulation/Trade-associations-remind-industry-Dietary-supplements-cannot-claim-to-cure-or-prevent-Ebola. Accessed October 10, 2014.
- McNeil DG. Agencies issue warnings over bogus Ebola claims. New York Times. Available at: www.nytimes.com/2014/08/16/science/agencies-issue-warnings-over-bogus-ebola-cures.html. Accessed September 29, 2014.