|
In
what government agencies are considering the world’s first major epidemic of
the deadly virus, Ebola has claimed more than 3,000 lives in West Africa this
year, making it the largest Ebola outbreak in history.1 The United States
Centers for Disease Control and Prevention (CDC) report that more than 6,500 total
individuals in Guinea, Liberia, Nigeria, Senegal, Sierra Leone, and the
Democratic Republic of Congo (DRC) have been infected with Ebola Virus Disease
(henceforth referred to as Ebola) — which kills roughly half of its victims — although
no new cases have been reported in Nigeria or Senegal since early September.1
The first two recorded outbreaks of the disease occurred simultaneously in 1976
in Sudan and a village in the DRC near the Ebola River, after which the virus
is named.2
On
Tuesday, September 30, 2014, the CDC announced the first Ebola diagnosis in the
United States,3 but the organization maintains that the risk of a
widespread US outbreak is low. The unnamed patient took a commercial flight to Dallas
from Liberia on September 20 and began exhibiting symptoms four days later. He
currently is quarantined at Texas Health Presbyterian Hospital in Dallas, and
the New York Times reports that
doctors and family members are considering experimental treatments.3
Prior
to the recent case in Dallas, at least two American aid workers volunteering in
impacted regions contracted Ebola.4 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) leaves through a process generally known as
“biopharming” — the process of using plants to produce genetically engineered
disease-fighting agents. (Nicotiana benthamiana, sometimes
referred to by its common name “native tobacco,” is endemic to northern
Australia.5) Both individuals have recovered from the virus,
although the extent to which ZMapp contributed to their recovery is unknown.4
Due to the severely limited supply of the drug, ZMapp has been given only
to seven individuals, two of whom have died.6
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 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, certain
companies and some African government officials have recommended unproven
plant-based “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 two American companies
advertising herbal products as being effective for treating and preventing
Ebola.7
“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.7 “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
For
the past decade, the San Diego, California-based companies Mapp Biopharmaceutical
and LeafBio in conjunction with Defyrus, Inc. in Toronto, Canada, have been
working on developing an effective Ebola treatment.8 The final
stages of the multi-step process 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 components8: 1. 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).
2. 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.
3. 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.8
ZMapp
is not a single compound; rather, the drug is a combination three
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 in its ZMapp information sheet online.9
Although
ZMapp has not been studied in humans, animal studies suggest the drug may
provide some benefit for Ebola in primates. According to a November 2013
article in the journal Scientific Reports,
researchers treated six Ebola-infected monkeys with a version of ZMapp, all of
which survived.10 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.10
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.11 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.”11 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.”11 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.12
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.8 “The low nicotine tobacco plant, Nicotiana benthamiana, is capable of expressing foreign
(non-tobacco) proteins using indoor cultivation under tightly controlled conditions.”
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.”13 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.14 “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” and FDA
Warning Letters
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 the traditional Ayurvedic adaptogenic plant ashwagandha (Withania somnifera)15 and jute
(Corchorus capsularis) juice16
can cure those infected with the virus. In late September, the FDA issued
warning letters to three American companies that promoted their products for
the treatment of Ebola.17-19 In perhaps the most egregious
violation, Natural Solutions Foundation was warned for advertising its non-herbal
colloidal Nano Silver Solution20 as “the definitive prevention and
therapy for Ebola virus,” citing “U.S. government research.”17
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.18 “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 claim 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.”19
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.17-19
The Future of Ebola
Treatments
On
August 13, 2014, Mapp Biopharmaceutical announced that its supply of the
plantibody-drug ZMapp had been exhausted.16 At present, the company
is collaborating with other companies — including Caliber Biotherapeutics in
Texas6 and Kentucky Bioprocessing, a division of the cigarette
manufacturer Reynolds American — to ramp up production of the drug.11
A
number of US government agencies — including the National Institutes of
Health’s National Institute of Allergy and Infectious Diseases, the Department
of Defense’s Defense Threat Reduction Agency, and Health and Human Service’s
Biomedical Advanced Research and Development — are working on developing
experimental treatments and vaccines for Ebola in conjunction with Mapp
Biopharmaceutical and other companies.4 However, the 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.4
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.21
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.22 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.22
“Whenever there is fear, misery and death, there are people who will take your
money promising you a cure.”
—Tyler
Smith
References
1.
2014 Ebola outbreak in West Africa. US Centers for Disease Control and
Prevention website. Available here.
Accessed September 23, 2014.
2.
Ebola virus disease. World Health Organization website. Available here. Accessed
September 29, 2014.
3.
Grady D. Ebola is diagnosed in Texas, first case found in the US. New York Times. Available here.
Accessed October 1, 2014.
4.
Questions and answers on experimental treatments and vaccines for Ebola. US
Centers for Disease Control and Prevention website. Available here.
Accessed September 26, 2014.
5.
Nicotiana benthamiana: native tobacco.
Australia’s Virtual Herbarium website. Available here.
Accessed September 29, 2014.
6.
Pollack A. US will increase production of the Ebola drug ZMapp, but may not
meet demand. New York Times.
Available here.
Accessed October 2, 2014.
7.
FDA statement: FDA warns consumers about fraudulent Ebola treatment products.
US Food and Drug Administration website. Available here.
Accessed September 26, 2014.
8.
ZMapp™ frequently asked questions. Mapp Biopharmaceutical website. Available here. Accessed September 29,
2014.
9.
ZMapp™ information sheet. Mapp Biopharmaceutical website. Available here. Accessed October 2, 2014.
10.
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 here.
Accessed September 29, 2014.
11.
‘Plantibody’ drugs show promise without help of big pharma. August 18, 2014.
NewsmaxHealth website. Available here.
Accessed September 26, 2014.
12.
Ferguson C. This kind of tobacco is good for you. Take Part website. Available here.
Accessed September 29, 2014.
13.
Guidance for industry: drugs biologics, and medical devices derived from
bioengineered plants for use in human and animals. US Food and Drug
Administration website. Available here.
Accessed September 26, 2014.
14.
Miller HI. Genetic engineering and the fight against Ebola. Wall Street Journal website. Available here.
Accessed September 29, 2014.
15.
Muanya C. Panel probes herbal cure claims for Ebola virus, others. All Africa
website. Available here.
Accessed September 23, 2014.
16.
Anya I, Ihekweazu C. No evidence that ewedu plant concoction can cure Ebola.
Africa Check website. Available here.
Accessed September 26, 2014.
17.
FDA warning letter: Natural Solutions Foundation. September 23, 2014. US Food
and Drug Administration website. Available here.
Accessed September 29, 2014.
18.
FDA warning letter: Young Living. September 23, 2014. US Food and Drug
Administration website. Available here.
Accessed September 29, 2014.
19.
FDA warning letter: doTERRA International, LLC. September 23, 2014. US Food and
Drug Administration website. Available here.
Accessed September 29, 2014.
20.
Dr. Rima Recommends™ The Silver Solution. Natural Solutions Foundation website.
Available here.
Accessed September 29, 2014.
21.
Grady D. Ebola cases could reach 1.4 million within four months, C.D.C. estimates.
New York Times. Available here.
Accessed September 29, 2014.
22.
McNeil DG. Agencies issue warnings over bogus Ebola claims. New York Times. Available here.
Accessed September 29, 2014.
|