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Biopharmaceuticals: Plant-based Medications for the Future
Just A. Student
Central Washington University
Treating disease and administering vaccines to those in the
poor communities and developing nations who need them the
most if a challenge. The production of the vaccines is often
expensive, and delivery requires a sterile syringe, and often
even booster shots over time to ensure the vaccine is treatment
is still effective. This is costly, monetarily speaking, and can
even cost human lives when those shots are delivered with a
sterile needle, or are done improperly. 20 million cases of
infection arise annually (Kwon et al, 2012).
While genetically modifying naturally occurring organisms
for medicinal purposes is nothing new, some scientists started
to mull over the idea of administering medications and life-
saving vaccines around the globe in a different way.
Biopharmaceuticals are on the rise, and their potential is
incredible.
PLANT-BASED MEDICATIONS OF THE FUTURE 2
Though it the early stages of testing, development and
regulating, delivery of vaccines and medicines orally via plants
is proving to be a field worth paying attention to. The process is
relatively low cost, with decently high yield, and distribution
would be simple. Perhaps a utopian world where the locals can
medicate themselves with the fruits from a banana is not
possible just yet (Mandy, 2005), but it cannot be ruled out just
yet. Biopharmaceuticals are merely in their infant stage, and
will continue to improve as our science does.
History
While this field of biopharmaceuticals seems straight out of a
futuristic movie plot, it is not exactly new. Biotechnology has
been in place for decades, beginning with Alexander
Flemming's discovery of "mold juice"- penicillin- in 1928
(ACS, 1999). Flemming found that something as simple as this
mold growth within a petri dish secreted a substance that could
kill a variety of bacteria, ranging from diphtheria to
streptococcus. Though it took some time before the penicillin
could be properly purified and used to fight infection, the first
major fungi based pharmaceutical had been manufactured (ACS,
1999), and an industry was born.
Technology has improved drastically since 1928, and by 1970
scientists were discovering the capabilities of recombinant
DNA. The process involved using pieces of DNA from two
different species, and joining them together to create a new,
hybrid set of DNA. This hybrid would then need to be placed
back into a cell, which often was that of a bacterium (NHGRI,
2013). This process of "cut and paste" DNA would eventually
lead to the development of somatostatin in 1977, which is
currently used to treat individuals suffering from gigantism
(Uckon, 2013). This process might not have been possible
without bacterium acting as a surrogate cell for these DNA
cocktails.
Biopharmaceutical technology was on the upswing by the
1980s, with mass production disease fighting
biopharmaceuticals (Uckon, 2013). In 1980 Cohen and Boyer
were able to produce human insulin (used to regulate blood
sugar levels) from genetically modified bacteria thanks to the
issuance of a patent for gene cloning (ABS Australia, 2008).
Human growth hormone, used to treat Creuzfeldt Jacob Disease,
was produced with help from improved technology that isolated
plasmids from E. coli (Ayyar, 2011).
It was becoming obvious that human and animal tissues might
not have been the cheapest and safest way to synthesize
molecules. Biopharmaceuticals had shown their value, and
continue to be utilized and experimented with today.
The Field Today
Biotechnology has since moved on from DNA splicing and
hosting in bacteria cells. These days, scientists have their eyes
on placing vaccines and other drugs within plant cells,
including carrots, lettuce and cereal grains, with the intention of
animal and human consumption.
The glycoprotein necessary for the rabies vaccine has been
successfully expressed within plants such as tomatoes, carrots
and spinach, and proved to protect mice in laboratory trials
(Yang et al, 2013). This was accomplished through more
recombinant DNA. Scientists used pieces of the rabies
glycoprotein- the signal peptide specifically, which leads the
way for the chain of proteins- and implemented the "cut and
paste" method to replace that peptide with another plant based
protein. This process, when successful, produces plant derived
rabies antigens (Yang et al, 2013), which promote the
production of antibodies in the immune system to fight off this
invading substance.
Yang et al (2013) considers the plant based rabies vaccine to be
advantageous in terms of the early successes seen in lab trials
with mice, but there are some issues with the method of storing
and administering the vaccines in this way. Shelf life is a major
concern, as your average tomato does not have a particularly
long life span. There is also the concern that as biological
materials run the course of their life, what will happen to the
level at which the proteins of the vaccine are expressed? Will
they drop to a level that is useless when consumed? If the plants
are used for multiple generations, how will protein expression
change over each? While there are many questions left to be
answered, Yang et al (2013) feels that this method has excellent
potential, especially if the process of growing antigen producing
plants is expedited. This is a low cost, relatively safe alternative
to current methods. It is possible that when these issues are
addressed, domestic animals could feasibly be treated using
oral, plant based vaccines (Yang et al, 2013).
As recently as October of this year (2015), scientists out of the
University of Pennsylvania School of Dental Medicine
announced they had successfully created plant based systems of
producing shelf-stable drugs- that is, drugs that can be stored
and used over longer periods of time. The drug developed
promotes blood clotting, necessary for hemophilia patients, and
was produced within the leaf of freeze-dried lettuce (UPSDM,
2015).
In initial trials, the researchers had used tobacco to grow the
proteins that inhibit antibodies from attacking the clotting
factors that hemophilia patients receive via infusion. When
hemophiliac mice were used in the trials were fed the tobacco
plants, their production of inhibitors virtually stopped.
However, lettuce was brought in to begin to developing a
similar plant-based treatment, but in a form humans could
consume (UPSDM, 2015).
Though the process of producing the proteins in lettuce was
different than in tobacco, due to genetic factors between the
plants. Researchers used a similar technique of hitting the
leaves with the desired proteins, as well as other factors that
aided the protein in making it to the immune system when
consumed. The plants that successfully picked up the proteins
were then grown to maturity, but the question of shelf life was
still unanswered. Researchers tried freeze drying the leaves, and
evaluated whether the process had affected the expression of the
protein through analysis to determine dosage, and eventually
trials with mice. The trials were success again, as they had been
with the tobacco, and the dosage was found to be flexible over
"at least a 10-fold dose range" (UPSDM, 2015), which is
extremely good news for human users, who metabolize and
break down materials differently.
This study by the University of Pennsylvania School of Dental
Medicine is hugely exciting in the field of biopharmaceuticals,
since it has shown that there is truly potential for large scale
commercial production of drugs through plants. The process of
creating the plants is relatively inexpensive, and the number of
doses that can be grown in a small area is astounding- even in a
facility that doesn't use natural light (such as a large scale
pharmaceutical facility, which uses hydroponic systems), nearly
40,000 doses can be grown in an area as small as 1,000 square
feet (UPSDM, 2015). Facilities like this can take advantage of
vertical space, as well, since they do no rely on direct natural
light, thus production could increase in that same space by tens
of thousands of doses. Should other drugs, beyond clotting
factors, be manufactured in plants, the production and
distribution costs could be drastically reduced using these
biotechnological methods.
The University of Pennsylvania School of Dental Medicine
showed through their research the validity of this method in
hopes of FDA approval for human use. It is possible hemophilia
combatting lettuce is a possibility for humans sooner rather than
later.
Impact
Biotechnology presents new and exciting, and perhaps a bit
controversial options for humans as we continue to populate the
Earth and struggle to distribute good and services to the poorest
of nations. The process of genetically modifying organisms for
human consumption (medical or nutritional) is a huge source of
debate all around the globe. Biochemist Paul Berg, along with
other scientists, urged for the regulation of recombinant DNA in
the 1970s after producing DNA molecules. They realized the
potential, but were worried that there was not enough
information to confirm the method was safe, particularly when
splicing DNA involved more than one species. In 1975 the
Asilomar Conference was held to lay out guidelines for work
with recombinant DNA, and since then the guidelines have been
updated several times (NHGRI, 2013).
Even today, this form of genetic engineering is widely debated
by the public, as it has cropped up most notably in the food we
eat. “Round-Up Ready” seeds, which withstand the devastating
effects of intense herbicides, fruit with incredible shelf life,
heightened flavor and nutritional value- just to name a few
(DDC, 2011). The public has been up in arms in recent years,
worried over the effects of ingesting something like “roundup
ready” corn, which retains chemical from the herbicide it was
sprayed with (Delano, 2009). The public questions the safety of
some of these products, and farmers and environmentalists alike
are worried about the effects genetically modified seeds could
have, and have had, on ecology and plant diversity (DDC,
2011).
Perhaps recombinant DNA has a bad reputation now, but the
evolving field of biopharmaceuticals could turn public opinion
around. The process of creating plant-based pharmaceuticals is
relatively inexpensive, since it does not require tissues from
animals (Yang et al, 2013), or fermenters, cold chain
refrigeration, or purification (UPSDM, 2015). Current
treatments like that of hemophilia inhibitors can cost thousands
of dollars, up to even a million dollars over a lifetime, but with
cost cutting done in the initial production process, patients will
save a large sum of money. Biopharmaceuticals could make
medications available to populations that otherwise would not
have been able to afford them (UPSDM, 2015).
Mass producing the plants is also as easy as planting them just
like any other crop- in soil with natural light. However, the
UPSDM (2015) lettuce trials have shown us that growing plants
within warehouse style hydroponic gardening systems is
feasible. They found that both the plants receiving natural light,
and those in the warehouse were close in terms of yields.
Within the hydroponic gardens, there is room to add shelving,
and capitalize on vertical space with no impact on those at
lower levels (UPSDM, 2015). UPSDM (2015) was able to
harvest doses from their lettuce every four to six weeks without
the vertical gardens, meaning the production rate of
biopharmaceuticals is extremely promising, and also cuts down
on costs to the patients.
For developing nations, biopharmaceuticals could vastly
improve access to healthcare. Cases of deadly infectious disease
within developing nations reaches to nearly 10 million annually,
even with modern vaccines, due to the expenses incurred in
developing them, transporting them, and most importantly
administering them in a sterile, safe way. Unsafe delivery of a
vaccine (contamination, reused needles, etc.) accounts for more
than 20 million infections (Kwon et al, 2012). Plant-based,
ingested medications could eliminate a large portion of this risk
for infection and reactions.
Pharmaceutical proteins protected within plant cells are also
safe from toxins and bacteria contaminants that are associated
with the use of mammal cell cultures. In addition, moving away
from the use of animal tissues elements during the
manufacturing process means that there are little to no risks
from human pathogens (Kwon et al, 2012). This means that not
only is delivery via sterile injection unnecessary, but the
pharmaceutical itself has been manufactured in a safe way, with
little risk to the consumer.
Modern science is moving in the direction of being able to
create a plant that is familiar, will grow effectively in a
particular region, and will also express within its DNA
makeup, treatment for a disease or illness that region struggles
with (ISAAA, 2007). Growing their own plant-based
pharmaceuticals will drastically cut down costs for the nation in
question, and the sheer number of doses will be much more
effective than our current lab manufactured systems. The
technology for hydroponic facilities, and extraction will need to
be established within these countries, but after the initial set up,
the benefit to the local communities will be monumental. The
spread of disease in poor, developing nations could see a
dramatic decrease (ISAAA, 2007).
Despite all of the great potential, there are some major concerns
with the widespread production and use of biopharmaceuticals.
Controlling the dosage of the expressed pharmaceutical within a
plant throughout its shelf life, as well as throughout the
generations has been an obstacle for the production of plant-
based medications (Yang et al, 2013). Dosage levels may
change when a plant is bred and seeds harvested over, and over
again. If a plant is freeze dried, and able to sit in a cabinet, how
will the levels change over time? This type of genetic
engineering is new, thus we have little information at this time.
Another concern is cross pollination and the introduction of
biopharma in to local ecology. This is particularly dangerous. It
has been suggested that plants used for pharmaceuticals should
never be grown outside of a greenhouse or hydroponic
warehouse setting (ISAAA, 2007). By maintaining physical
isolation, the crops themselves are protected from cross
pollination, but more importantly fields of agricultural crops for
human consumption are protected. The concern is that cross
pollination could lead to the expression of pharmaceuticals
within crops that will be eaten by the general public (ISAAA,
2007). This is also troublesome, since transgenic species may
include DNA from more than one plant, which a consumer may
not realize. If the crop has become contaminated, it is possible
that a consumer could eat a soybean that has been inadvertently
crossed with a soybean/Brazil nut hybrid. If the consumer is
allergic to Brazil nuts, this could be harmful or even deadly
(Delano, 2009).
Complete and total isolation for every transgenic crop is
unrealistic though, and other solutions have been proposed to
limit environmental exposure. One such idea is to have the
necessary genes present within the plant, but only have them
expressed to their full potential after having been treated with
some kind of activator (ISAAA, 2007). This solution presents
more ethical problems, as it takes a genetically engineered
plant- something many consumers are already leery of- and
treats it with some kind of chemical activator. It may be
expensive as well, (ISAAA, 2007), in terms of manufacturing
the activator, the equipment necessary for treatment, etc.
Heightened costs undermine one of the very things that
biopharmaceuticals are aiming to combat.
Concerns also surround the biosafety legislation, or lack
thereof, of developing nations who so desperately need the cost
effective, mass produced pharmaceuticals (ISAAA, 2007).
While standards in the United States are often reevaluated and
tweaked (NHGRI, 2013), the same cannot be said of countries
with sometimes unstable government and ruling officials. Likely
the nation has never had to consider regulations like this, so
they may be nonexistent. Without control, seeds manufactured
in the US could be bred and experimented without compliance
to our biosafety standards. Ineffective crops and failed
experiments actually add to the cost of the drugs themselves
(due to the cost of research), and that goes for both nations
following safety regulations and those outside of the regulations
(ISAAA, 2007). Without control or international guidelines for
biopharmaceutical production, it will be dangerous to distribute
crops to other nations.
Conclusion and Future Study
With the proper biosafety regulations, both in the lab and
in production, plant-based pharmaceuticals are “the way of the
future,” so to speak. Though the science is in its early stages,
the potential is too great to ignore. Cutting costs and
increasingly availability of medications is something so
desperately needed in poor communities and developing nations.
To ignore an opportunity to work toward that would be
irresponsible.
That being said, perhaps our approach to
biopharmaceuticals needs to shift. While making medical
advancements and developing more plant-based pharmaceuticals
is important, just as much emphasis needs to be placed on the
logistics of biopharmaceuticals in tandem with development.
Regulations need to be constantly reevaluated and revised, since
biosafety is of upmost concern. In order for the field to reach its
full potential, all the t’s need to be crossed and i's dotted.
Perhaps their needs to be a large international committee that
meets and discusses regulations for lab procedures, production
and growth, and dispersal so that in the future the plants can be
grown in the nations that need them most to further cut costs
and increase availability.
Biopharmaceuticals have a long way to go, and more
potential to be reached. The idea of a future where vaccines can
be grown and delivered to rural villages to save the lives of
children is an exciting one. Before we get too excited, more
research needs to be done, and any and all risk-management
factors need to be considered (both in consumption, and gene
flow between pharmaceutical plants and standard agriculture).
This is normal in the field of science and new technology. I
believe as the years go by we will see an increase in successful
lab trials of biopharmaceuticals, and the conversation about
distribution and production will truly begin. In our lifetime, we
may well see the first crop of life saving medications
distributed via plants around the world.
References
American Chemical Society. (1999). Discovery and
development of penicillin. Retrieved from
http://www.acs.org/content/acs/en/education/whatischemistry/la
ndmarks/flemingpenicillin.html
Australian Broadcast Company. (2008). The biotech revolution:
1980. Retrieved from
http://www.abc.net.au/science/features/biotech/1980.htm.
Ayyar, V. S. (2011). History of growth hormone therapy
[Abstract]. Indian Journal of Endocrinology and Metabolism,
15(Suppl3), S162-S165. Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183530/
de Herder, W. W., van der Lely, A. J., & Lamberts, S. W.
(1996). Somatostatin analogue treatment of neuroendocrine
tumors [Abstract]. Postgraduate Medical Journal, 72(849), 403-
408. Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398518/
Delano, M. (2009). Roundup ready crops: Cash crop or third
world savior. Retrieved from
http://web.mit.edu/demoscience/Monsanto/index.html
DNA Diagnostics Center. (2011). Creating solutions for health
and nutrition. Retrieved from
http://www.dnacenter.com/science-technology/health-
nutrition.html
International Service for the Acquisition of Agri-Biotech
Applications. (2007). Pocket K No. 26: Molecular pharming and
biopharmaceuticals. Retrieved from
https://www.isaaa.org/resources/publications/pocketk/26/default
.asp
Kwon, K., Verma, D., Singh, N. D., Herzog, R., & Daniell, H.
(2013). Oral delivery of human biopharmaceuticals,
autoantigens, and vaccine antigens bioencapsulated in plant
cells. Advanced Drug Delivery Reviews, 65(6), 782-799.
Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582797/
Mandy, R. (2005). Banana vaccines: A conversation with Dr.
Charles Arntzen. Journal of the Young Investigators: The
Undergraduate Research Journal. Retrieved from
http://www.jyi.org/issue/banana-vaccines-a-conversation-with-
dr-charles-arntzen/
National Human Genome Research Institute. (2013). 1972: First
recombinant DNA. Retrieved from
http://www.genome.gov/25520302
Uckon, F. (2013). A brief history of biopharmaceuticals
[PowerPoint slides]. Retrieved from
http://www.slideshare.net/fatihuckun/a-brief-history-of-
biopharmaceuticals-by-dr-fatih-uckun
University of Pennsylvania School of Dental Medicine. (2015,
October 1). Proof-of-concept for low-cost drug made in lettuce.
Science Daily. Retrieved from
http://www.sciencedaily.com/releases/2015/10/151001094319.ht
m
Yang, D., Kim, H., Lee, K., & Song, J. (2013). The present and
future of rabies vaccine in animals. Clinical and Experimental
Vaccine Research, 2(1), 19-25. Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623496/
Biology 200; Poulson
Plants in the Modern World
Writing Assignment
Your assignment is to write a paper that is thoughtful, well-
researched and well written paper in
which you explore a botanical concept or process and review,
analyze, and discuss how this
concept or process relates to humans and real-world issues.
Acceptable topics include
sociological or economical aspects of botany (e.g. “How a plant
pathogen enabled the Irish
potato famine”) or a particular plant (e.g. “Palm trees, eco-
tourism and the endangerment of
orangutan habitat) or a plant product (e.g. “Wood, how it grows,
and how paper changed literacy
across the world) or a how a scientific method applied to
agriculture has changed first-world
agriculture (genetic engineering, for example). Other
reasonable topics include global issues
facing humanity such as deforestation or global climate change.
Remember that your goal is to
discuss how the process you choose connects to or has an effect
on humans and/or real world
issues. Choose a topic that interests you. Check with me
before writing your paper to ensure
that the topic you have chosen is satisfactory.
You must write your paper yourself after reading background
material that relates to the topic.
You might also want to refer to sources to back up your
conclusions or arguments. You MUST
include at least four references that are peer-reviewed.
References should be cited at the end
of the paper. You may use the internet and sources on the
internet that are peer-reviewed, but
as you know, there is a lot on the internet that is simply
someone's opinion should not be used
as reference material. We will complete a laboratory exercise
on “Evaluating Your Sources”
that will help you find useful sources. Please check with me if
you need help in determining the
credibility of your sources or in finding good sources. The
library staff are also a great resource
available to you.
Your paper should be written and you references cited using any
accepted scientific format.
The easiest way to accomplish this is to use the instructions
provided by Mark Plonsky at the
University of Wisconsin Stevens Point
(http://www.uwsp.edu/psych/mp/APA/apa4b.htm). You
do not need to have the sections “Introduction, Methods, etc.”
in your paper but you should use
the citation and general writing style that is described in the
Plonsky document. MLA is not a
scientific format. APA and many other styles are.
Your paper should be at least 1500 words. In addition to
writing a paper, you will give a 5-7
minute presentation to the class in which you present your
paper. The purpose of these
presentations is to share your knowledge with the rest of the
class. The presentation can be
using powerpoint, presenting a poster, strictly verbal or
anything that suits your needs. Points
are awarded for your presentation and for showing respect for
others during their presentations.
In order to ensure that your paper is thoughtful, well-researched
and well written you will be
required to turn in several drafts of your paper. After each
draft, your paper should be modified,
based on feedback, prior to each submission to the instructor. I
strongly suggest that you visit
the CWU writing center (one or more times; more information
at http://www.cwu.edu/learning-
commons/university-writing-center) and use all resources
available to you (such as having room
mates and friends proof-read your paper) before turning in your
work. Your paper submissions
(all drafts) must be made through Canvas using Turnitin. This
software will ensure that your
writing is truly your own.
You will be given many opportunities for discussion of your
topic in class and feedback from the
instructor throughout the quarter. If you have questions, ask.
Rubric for Plants in the Modern World Writing Assignment
Poulson
Masterful
(7-8 points)
Skilled
(6-7 points)
Able
(4-5 points)
Developing
(2-3 points)
Novice
(0-1 points)
Presentation of
topic
throughout
paper
Topic presented in
a creative,
thoughtful way that
incorporates
student’s thinking
Topic presented in
a creative,
thoughtful way that
somewhat
incorporates
student’s thinking
Topic presented in
a creative,
thoughtful way but
does not
incorporate
student’s thinking
Topic presented in
a somewhat
creative, thoughtful
way but does not
incorporate
student’s thinking
Topic not
presented in a
creative, thoughtful
way and does not
incorporates
student’s thinking
Review of
concept and
background
Paper discusses a
botanical concept
or process and
reviews the
subject, giving a
solid general
background
Paper discusses a
botanical concept
or process and
reviews the
subject, but gives a
weak background
Paper discusses a
botanical concept
or process but
does not review
the subject and
gives a weak
background
Paper partially
discusses a
botanical concept
or process but
shows weak
understanding of
the concept
Paper does not
discuss a botanical
concept or process
nor does it review
the subject or give
a general
background
Discussion of
how concept
relates to real-
world issues
Paper analyzes,
and discusses how
the concept or
process relates to
humans and real-
world issues
Paper analyzes,
and discusses how
the concept or
process relates to
humans but not
real-world issues
Paper somewhat
analyzes, and
discusses how the
concept or process
relates to humans
and real-world
issues
Paper weakly
analyzes, and
discusses how the
concept or process
relates to humans
and real-world
issues
Paper does not
analyze or discuss
how the concept or
process relates to
humans and real-
world issues
Length
requirement
Paper meets page
length requirement.
Writing should be
concise.
Paper meets page
length requirement
but writing is
somewhat concise.
Paper nearly
meets page length
requirement but
writing is not
concise.
Paper does not
meets page length
requirement,
writing is
somewhat concise.
Paper does not
meets page length
requirement or
writing is not at all
concise.
Original work
Note that knowingly
submitting a paper
with plagiarism is
grounds for
disciplinary action
Paper is student’s
original work
Paper is student’s
work but
references are
partially omitted
Paper is student’s
work but
references are
omitted
Most of paper is
student’s work
small sections are
plagiarized via “cut
and paste” errors
Most of paper is
student’s work
significant sections
are plagiarized via
“cut and paste”
errors
Conclusions
made and
synthesis of
ideas
Writing draws
reasonable
conclusions based
on synthesis of
ideas and
information
Writing draws
somewhat
reasonable
conclusions based
on synthesis of
ideas and
information
Writing draws
somewhat
reasonable
conclusions but
they are weakly
based on synthesis
of ideas and
information
Writing draws few
reasonable
conclusions and
weakly synthesizes
ideas and
information
Writing fails to
draw reasonable
conclusions based
on synthesis of
ideas and
information
Sentence and
paragraph
structure
Ideas expressed in
clear coherent and
balanced
sentences and
paragraphs
Ideas expressed in
clear but not and
balanced
sentences and
paragraphs
Ideas expressed in
somewhat clear
and balanced
sentences and
paragraphs
Ideas expressed
poorly with lack of
clear coherent and
balanced
sentences and
paragraphs
Ideas not
expressed. Lack of
clear coherent and
balanced
sentences and
paragraphs
Use of
reference
materials
At least four
appropriate, peer-
reviewed reference
materials used
At least three
appropriate, peer-
reviewed reference
materials used
At least two
appropriate, peer-
reviewed reference
materials used
At least one
appropriate, peer-
reviewed reference
materials used
Appropriate, peer-
reviewed reference
materials not used
Citation Cited reference
material properly
(in text and in
references section)
Reference material
mostly cited
properly (in text
and in references
section)
Reference material
somewhat cited
properly (in text
and in references
section)
Reference material
somewhat not cited
properly (in text
and in references
section)
References not
cited or missing
references section
Mechanics Proper grammar,
spelling and
sentence structure
used
Grammar, spelling
and sentence
structure with 1
mistake
Grammar, spelling
and sentence
structure with 2-3
mistakes
Grammar, spelling
and sentence
structure used with
4 mistakes
Grammar, spelling
and sentence
structure with more
than 4 mistakes
Total points

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  • 1. Biopharmaceuticals: Plant-based Medications for the Future Just A. Student Central Washington University Treating disease and administering vaccines to those in the poor communities and developing nations who need them the most if a challenge. The production of the vaccines is often expensive, and delivery requires a sterile syringe, and often even booster shots over time to ensure the vaccine is treatment is still effective. This is costly, monetarily speaking, and can even cost human lives when those shots are delivered with a sterile needle, or are done improperly. 20 million cases of infection arise annually (Kwon et al, 2012). While genetically modifying naturally occurring organisms for medicinal purposes is nothing new, some scientists started to mull over the idea of administering medications and life- saving vaccines around the globe in a different way. Biopharmaceuticals are on the rise, and their potential is incredible. PLANT-BASED MEDICATIONS OF THE FUTURE 2 Though it the early stages of testing, development and regulating, delivery of vaccines and medicines orally via plants is proving to be a field worth paying attention to. The process is relatively low cost, with decently high yield, and distribution would be simple. Perhaps a utopian world where the locals can medicate themselves with the fruits from a banana is not possible just yet (Mandy, 2005), but it cannot be ruled out just yet. Biopharmaceuticals are merely in their infant stage, and will continue to improve as our science does. History While this field of biopharmaceuticals seems straight out of a futuristic movie plot, it is not exactly new. Biotechnology has been in place for decades, beginning with Alexander
  • 2. Flemming's discovery of "mold juice"- penicillin- in 1928 (ACS, 1999). Flemming found that something as simple as this mold growth within a petri dish secreted a substance that could kill a variety of bacteria, ranging from diphtheria to streptococcus. Though it took some time before the penicillin could be properly purified and used to fight infection, the first major fungi based pharmaceutical had been manufactured (ACS, 1999), and an industry was born. Technology has improved drastically since 1928, and by 1970 scientists were discovering the capabilities of recombinant DNA. The process involved using pieces of DNA from two different species, and joining them together to create a new, hybrid set of DNA. This hybrid would then need to be placed back into a cell, which often was that of a bacterium (NHGRI, 2013). This process of "cut and paste" DNA would eventually lead to the development of somatostatin in 1977, which is currently used to treat individuals suffering from gigantism (Uckon, 2013). This process might not have been possible without bacterium acting as a surrogate cell for these DNA cocktails. Biopharmaceutical technology was on the upswing by the 1980s, with mass production disease fighting biopharmaceuticals (Uckon, 2013). In 1980 Cohen and Boyer were able to produce human insulin (used to regulate blood sugar levels) from genetically modified bacteria thanks to the issuance of a patent for gene cloning (ABS Australia, 2008). Human growth hormone, used to treat Creuzfeldt Jacob Disease, was produced with help from improved technology that isolated plasmids from E. coli (Ayyar, 2011). It was becoming obvious that human and animal tissues might not have been the cheapest and safest way to synthesize molecules. Biopharmaceuticals had shown their value, and continue to be utilized and experimented with today. The Field Today Biotechnology has since moved on from DNA splicing and hosting in bacteria cells. These days, scientists have their eyes
  • 3. on placing vaccines and other drugs within plant cells, including carrots, lettuce and cereal grains, with the intention of animal and human consumption. The glycoprotein necessary for the rabies vaccine has been successfully expressed within plants such as tomatoes, carrots and spinach, and proved to protect mice in laboratory trials (Yang et al, 2013). This was accomplished through more recombinant DNA. Scientists used pieces of the rabies glycoprotein- the signal peptide specifically, which leads the way for the chain of proteins- and implemented the "cut and paste" method to replace that peptide with another plant based protein. This process, when successful, produces plant derived rabies antigens (Yang et al, 2013), which promote the production of antibodies in the immune system to fight off this invading substance. Yang et al (2013) considers the plant based rabies vaccine to be advantageous in terms of the early successes seen in lab trials with mice, but there are some issues with the method of storing and administering the vaccines in this way. Shelf life is a major concern, as your average tomato does not have a particularly long life span. There is also the concern that as biological materials run the course of their life, what will happen to the level at which the proteins of the vaccine are expressed? Will they drop to a level that is useless when consumed? If the plants are used for multiple generations, how will protein expression change over each? While there are many questions left to be answered, Yang et al (2013) feels that this method has excellent potential, especially if the process of growing antigen producing plants is expedited. This is a low cost, relatively safe alternative to current methods. It is possible that when these issues are addressed, domestic animals could feasibly be treated using oral, plant based vaccines (Yang et al, 2013). As recently as October of this year (2015), scientists out of the University of Pennsylvania School of Dental Medicine announced they had successfully created plant based systems of producing shelf-stable drugs- that is, drugs that can be stored
  • 4. and used over longer periods of time. The drug developed promotes blood clotting, necessary for hemophilia patients, and was produced within the leaf of freeze-dried lettuce (UPSDM, 2015). In initial trials, the researchers had used tobacco to grow the proteins that inhibit antibodies from attacking the clotting factors that hemophilia patients receive via infusion. When hemophiliac mice were used in the trials were fed the tobacco plants, their production of inhibitors virtually stopped. However, lettuce was brought in to begin to developing a similar plant-based treatment, but in a form humans could consume (UPSDM, 2015). Though the process of producing the proteins in lettuce was different than in tobacco, due to genetic factors between the plants. Researchers used a similar technique of hitting the leaves with the desired proteins, as well as other factors that aided the protein in making it to the immune system when consumed. The plants that successfully picked up the proteins were then grown to maturity, but the question of shelf life was still unanswered. Researchers tried freeze drying the leaves, and evaluated whether the process had affected the expression of the protein through analysis to determine dosage, and eventually trials with mice. The trials were success again, as they had been with the tobacco, and the dosage was found to be flexible over "at least a 10-fold dose range" (UPSDM, 2015), which is extremely good news for human users, who metabolize and break down materials differently. This study by the University of Pennsylvania School of Dental Medicine is hugely exciting in the field of biopharmaceuticals, since it has shown that there is truly potential for large scale commercial production of drugs through plants. The process of creating the plants is relatively inexpensive, and the number of doses that can be grown in a small area is astounding- even in a facility that doesn't use natural light (such as a large scale pharmaceutical facility, which uses hydroponic systems), nearly 40,000 doses can be grown in an area as small as 1,000 square
  • 5. feet (UPSDM, 2015). Facilities like this can take advantage of vertical space, as well, since they do no rely on direct natural light, thus production could increase in that same space by tens of thousands of doses. Should other drugs, beyond clotting factors, be manufactured in plants, the production and distribution costs could be drastically reduced using these biotechnological methods. The University of Pennsylvania School of Dental Medicine showed through their research the validity of this method in hopes of FDA approval for human use. It is possible hemophilia combatting lettuce is a possibility for humans sooner rather than later. Impact Biotechnology presents new and exciting, and perhaps a bit controversial options for humans as we continue to populate the Earth and struggle to distribute good and services to the poorest of nations. The process of genetically modifying organisms for human consumption (medical or nutritional) is a huge source of debate all around the globe. Biochemist Paul Berg, along with other scientists, urged for the regulation of recombinant DNA in the 1970s after producing DNA molecules. They realized the potential, but were worried that there was not enough information to confirm the method was safe, particularly when splicing DNA involved more than one species. In 1975 the Asilomar Conference was held to lay out guidelines for work with recombinant DNA, and since then the guidelines have been updated several times (NHGRI, 2013). Even today, this form of genetic engineering is widely debated by the public, as it has cropped up most notably in the food we eat. “Round-Up Ready” seeds, which withstand the devastating effects of intense herbicides, fruit with incredible shelf life, heightened flavor and nutritional value- just to name a few (DDC, 2011). The public has been up in arms in recent years, worried over the effects of ingesting something like “roundup ready” corn, which retains chemical from the herbicide it was sprayed with (Delano, 2009). The public questions the safety of
  • 6. some of these products, and farmers and environmentalists alike are worried about the effects genetically modified seeds could have, and have had, on ecology and plant diversity (DDC, 2011). Perhaps recombinant DNA has a bad reputation now, but the evolving field of biopharmaceuticals could turn public opinion around. The process of creating plant-based pharmaceuticals is relatively inexpensive, since it does not require tissues from animals (Yang et al, 2013), or fermenters, cold chain refrigeration, or purification (UPSDM, 2015). Current treatments like that of hemophilia inhibitors can cost thousands of dollars, up to even a million dollars over a lifetime, but with cost cutting done in the initial production process, patients will save a large sum of money. Biopharmaceuticals could make medications available to populations that otherwise would not have been able to afford them (UPSDM, 2015). Mass producing the plants is also as easy as planting them just like any other crop- in soil with natural light. However, the UPSDM (2015) lettuce trials have shown us that growing plants within warehouse style hydroponic gardening systems is feasible. They found that both the plants receiving natural light, and those in the warehouse were close in terms of yields. Within the hydroponic gardens, there is room to add shelving, and capitalize on vertical space with no impact on those at lower levels (UPSDM, 2015). UPSDM (2015) was able to harvest doses from their lettuce every four to six weeks without the vertical gardens, meaning the production rate of biopharmaceuticals is extremely promising, and also cuts down on costs to the patients. For developing nations, biopharmaceuticals could vastly improve access to healthcare. Cases of deadly infectious disease within developing nations reaches to nearly 10 million annually, even with modern vaccines, due to the expenses incurred in developing them, transporting them, and most importantly administering them in a sterile, safe way. Unsafe delivery of a vaccine (contamination, reused needles, etc.) accounts for more
  • 7. than 20 million infections (Kwon et al, 2012). Plant-based, ingested medications could eliminate a large portion of this risk for infection and reactions. Pharmaceutical proteins protected within plant cells are also safe from toxins and bacteria contaminants that are associated with the use of mammal cell cultures. In addition, moving away from the use of animal tissues elements during the manufacturing process means that there are little to no risks from human pathogens (Kwon et al, 2012). This means that not only is delivery via sterile injection unnecessary, but the pharmaceutical itself has been manufactured in a safe way, with little risk to the consumer. Modern science is moving in the direction of being able to create a plant that is familiar, will grow effectively in a particular region, and will also express within its DNA makeup, treatment for a disease or illness that region struggles with (ISAAA, 2007). Growing their own plant-based pharmaceuticals will drastically cut down costs for the nation in question, and the sheer number of doses will be much more effective than our current lab manufactured systems. The technology for hydroponic facilities, and extraction will need to be established within these countries, but after the initial set up, the benefit to the local communities will be monumental. The spread of disease in poor, developing nations could see a dramatic decrease (ISAAA, 2007). Despite all of the great potential, there are some major concerns with the widespread production and use of biopharmaceuticals. Controlling the dosage of the expressed pharmaceutical within a plant throughout its shelf life, as well as throughout the generations has been an obstacle for the production of plant- based medications (Yang et al, 2013). Dosage levels may change when a plant is bred and seeds harvested over, and over again. If a plant is freeze dried, and able to sit in a cabinet, how will the levels change over time? This type of genetic engineering is new, thus we have little information at this time. Another concern is cross pollination and the introduction of
  • 8. biopharma in to local ecology. This is particularly dangerous. It has been suggested that plants used for pharmaceuticals should never be grown outside of a greenhouse or hydroponic warehouse setting (ISAAA, 2007). By maintaining physical isolation, the crops themselves are protected from cross pollination, but more importantly fields of agricultural crops for human consumption are protected. The concern is that cross pollination could lead to the expression of pharmaceuticals within crops that will be eaten by the general public (ISAAA, 2007). This is also troublesome, since transgenic species may include DNA from more than one plant, which a consumer may not realize. If the crop has become contaminated, it is possible that a consumer could eat a soybean that has been inadvertently crossed with a soybean/Brazil nut hybrid. If the consumer is allergic to Brazil nuts, this could be harmful or even deadly (Delano, 2009). Complete and total isolation for every transgenic crop is unrealistic though, and other solutions have been proposed to limit environmental exposure. One such idea is to have the necessary genes present within the plant, but only have them expressed to their full potential after having been treated with some kind of activator (ISAAA, 2007). This solution presents more ethical problems, as it takes a genetically engineered plant- something many consumers are already leery of- and treats it with some kind of chemical activator. It may be expensive as well, (ISAAA, 2007), in terms of manufacturing the activator, the equipment necessary for treatment, etc. Heightened costs undermine one of the very things that biopharmaceuticals are aiming to combat. Concerns also surround the biosafety legislation, or lack thereof, of developing nations who so desperately need the cost effective, mass produced pharmaceuticals (ISAAA, 2007). While standards in the United States are often reevaluated and tweaked (NHGRI, 2013), the same cannot be said of countries with sometimes unstable government and ruling officials. Likely the nation has never had to consider regulations like this, so
  • 9. they may be nonexistent. Without control, seeds manufactured in the US could be bred and experimented without compliance to our biosafety standards. Ineffective crops and failed experiments actually add to the cost of the drugs themselves (due to the cost of research), and that goes for both nations following safety regulations and those outside of the regulations (ISAAA, 2007). Without control or international guidelines for biopharmaceutical production, it will be dangerous to distribute crops to other nations. Conclusion and Future Study With the proper biosafety regulations, both in the lab and in production, plant-based pharmaceuticals are “the way of the future,” so to speak. Though the science is in its early stages, the potential is too great to ignore. Cutting costs and increasingly availability of medications is something so desperately needed in poor communities and developing nations. To ignore an opportunity to work toward that would be irresponsible. That being said, perhaps our approach to biopharmaceuticals needs to shift. While making medical advancements and developing more plant-based pharmaceuticals is important, just as much emphasis needs to be placed on the logistics of biopharmaceuticals in tandem with development. Regulations need to be constantly reevaluated and revised, since biosafety is of upmost concern. In order for the field to reach its full potential, all the t’s need to be crossed and i's dotted. Perhaps their needs to be a large international committee that meets and discusses regulations for lab procedures, production and growth, and dispersal so that in the future the plants can be grown in the nations that need them most to further cut costs and increase availability. Biopharmaceuticals have a long way to go, and more potential to be reached. The idea of a future where vaccines can be grown and delivered to rural villages to save the lives of children is an exciting one. Before we get too excited, more
  • 10. research needs to be done, and any and all risk-management factors need to be considered (both in consumption, and gene flow between pharmaceutical plants and standard agriculture). This is normal in the field of science and new technology. I believe as the years go by we will see an increase in successful lab trials of biopharmaceuticals, and the conversation about distribution and production will truly begin. In our lifetime, we may well see the first crop of life saving medications distributed via plants around the world. References American Chemical Society. (1999). Discovery and development of penicillin. Retrieved from http://www.acs.org/content/acs/en/education/whatischemistry/la ndmarks/flemingpenicillin.html Australian Broadcast Company. (2008). The biotech revolution: 1980. Retrieved from http://www.abc.net.au/science/features/biotech/1980.htm. Ayyar, V. S. (2011). History of growth hormone therapy [Abstract]. Indian Journal of Endocrinology and Metabolism, 15(Suppl3), S162-S165. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183530/ de Herder, W. W., van der Lely, A. J., & Lamberts, S. W. (1996). Somatostatin analogue treatment of neuroendocrine tumors [Abstract]. Postgraduate Medical Journal, 72(849), 403- 408. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398518/ Delano, M. (2009). Roundup ready crops: Cash crop or third world savior. Retrieved from http://web.mit.edu/demoscience/Monsanto/index.html DNA Diagnostics Center. (2011). Creating solutions for health and nutrition. Retrieved from http://www.dnacenter.com/science-technology/health- nutrition.html International Service for the Acquisition of Agri-Biotech Applications. (2007). Pocket K No. 26: Molecular pharming and biopharmaceuticals. Retrieved from
  • 11. https://www.isaaa.org/resources/publications/pocketk/26/default .asp Kwon, K., Verma, D., Singh, N. D., Herzog, R., & Daniell, H. (2013). Oral delivery of human biopharmaceuticals, autoantigens, and vaccine antigens bioencapsulated in plant cells. Advanced Drug Delivery Reviews, 65(6), 782-799. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582797/ Mandy, R. (2005). Banana vaccines: A conversation with Dr. Charles Arntzen. Journal of the Young Investigators: The Undergraduate Research Journal. Retrieved from http://www.jyi.org/issue/banana-vaccines-a-conversation-with- dr-charles-arntzen/ National Human Genome Research Institute. (2013). 1972: First recombinant DNA. Retrieved from http://www.genome.gov/25520302 Uckon, F. (2013). A brief history of biopharmaceuticals [PowerPoint slides]. Retrieved from http://www.slideshare.net/fatihuckun/a-brief-history-of- biopharmaceuticals-by-dr-fatih-uckun University of Pennsylvania School of Dental Medicine. (2015, October 1). Proof-of-concept for low-cost drug made in lettuce. Science Daily. Retrieved from http://www.sciencedaily.com/releases/2015/10/151001094319.ht m Yang, D., Kim, H., Lee, K., & Song, J. (2013). The present and future of rabies vaccine in animals. Clinical and Experimental Vaccine Research, 2(1), 19-25. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623496/ Biology 200; Poulson Plants in the Modern World Writing Assignment
  • 12. Your assignment is to write a paper that is thoughtful, well- researched and well written paper in which you explore a botanical concept or process and review, analyze, and discuss how this concept or process relates to humans and real-world issues. Acceptable topics include sociological or economical aspects of botany (e.g. “How a plant pathogen enabled the Irish potato famine”) or a particular plant (e.g. “Palm trees, eco- tourism and the endangerment of orangutan habitat) or a plant product (e.g. “Wood, how it grows, and how paper changed literacy across the world) or a how a scientific method applied to agriculture has changed first-world agriculture (genetic engineering, for example). Other reasonable topics include global issues facing humanity such as deforestation or global climate change. Remember that your goal is to discuss how the process you choose connects to or has an effect on humans and/or real world issues. Choose a topic that interests you. Check with me before writing your paper to ensure that the topic you have chosen is satisfactory. You must write your paper yourself after reading background material that relates to the topic. You might also want to refer to sources to back up your conclusions or arguments. You MUST include at least four references that are peer-reviewed. References should be cited at the end of the paper. You may use the internet and sources on the internet that are peer-reviewed, but as you know, there is a lot on the internet that is simply someone's opinion should not be used as reference material. We will complete a laboratory exercise on “Evaluating Your Sources”
  • 13. that will help you find useful sources. Please check with me if you need help in determining the credibility of your sources or in finding good sources. The library staff are also a great resource available to you. Your paper should be written and you references cited using any accepted scientific format. The easiest way to accomplish this is to use the instructions provided by Mark Plonsky at the University of Wisconsin Stevens Point (http://www.uwsp.edu/psych/mp/APA/apa4b.htm). You do not need to have the sections “Introduction, Methods, etc.” in your paper but you should use the citation and general writing style that is described in the Plonsky document. MLA is not a scientific format. APA and many other styles are. Your paper should be at least 1500 words. In addition to writing a paper, you will give a 5-7 minute presentation to the class in which you present your paper. The purpose of these presentations is to share your knowledge with the rest of the class. The presentation can be using powerpoint, presenting a poster, strictly verbal or anything that suits your needs. Points are awarded for your presentation and for showing respect for others during their presentations. In order to ensure that your paper is thoughtful, well-researched and well written you will be required to turn in several drafts of your paper. After each draft, your paper should be modified, based on feedback, prior to each submission to the instructor. I strongly suggest that you visit the CWU writing center (one or more times; more information
  • 14. at http://www.cwu.edu/learning- commons/university-writing-center) and use all resources available to you (such as having room mates and friends proof-read your paper) before turning in your work. Your paper submissions (all drafts) must be made through Canvas using Turnitin. This software will ensure that your writing is truly your own. You will be given many opportunities for discussion of your topic in class and feedback from the instructor throughout the quarter. If you have questions, ask. Rubric for Plants in the Modern World Writing Assignment Poulson Masterful (7-8 points) Skilled (6-7 points) Able (4-5 points) Developing (2-3 points) Novice (0-1 points) Presentation of topic
  • 15. throughout paper Topic presented in a creative, thoughtful way that incorporates student’s thinking Topic presented in a creative, thoughtful way that somewhat incorporates student’s thinking Topic presented in a creative, thoughtful way but does not incorporate student’s thinking Topic presented in a somewhat creative, thoughtful way but does not incorporate student’s thinking Topic not presented in a creative, thoughtful way and does not incorporates student’s thinking
  • 16. Review of concept and background Paper discusses a botanical concept or process and reviews the subject, giving a solid general background Paper discusses a botanical concept or process and reviews the subject, but gives a weak background Paper discusses a botanical concept or process but does not review the subject and gives a weak background Paper partially discusses a botanical concept or process but shows weak understanding of the concept
  • 17. Paper does not discuss a botanical concept or process nor does it review the subject or give a general background Discussion of how concept relates to real- world issues Paper analyzes, and discusses how the concept or process relates to humans and real- world issues Paper analyzes, and discusses how the concept or process relates to humans but not real-world issues Paper somewhat analyzes, and discusses how the concept or process relates to humans and real-world issues Paper weakly
  • 18. analyzes, and discusses how the concept or process relates to humans and real-world issues Paper does not analyze or discuss how the concept or process relates to humans and real- world issues Length requirement Paper meets page length requirement. Writing should be concise. Paper meets page length requirement but writing is somewhat concise. Paper nearly meets page length requirement but writing is not concise. Paper does not meets page length requirement,
  • 19. writing is somewhat concise. Paper does not meets page length requirement or writing is not at all concise. Original work Note that knowingly submitting a paper with plagiarism is grounds for disciplinary action Paper is student’s original work Paper is student’s work but references are partially omitted Paper is student’s work but references are omitted Most of paper is student’s work small sections are plagiarized via “cut and paste” errors Most of paper is
  • 20. student’s work significant sections are plagiarized via “cut and paste” errors Conclusions made and synthesis of ideas Writing draws reasonable conclusions based on synthesis of ideas and information Writing draws somewhat reasonable conclusions based on synthesis of ideas and information Writing draws somewhat reasonable conclusions but they are weakly based on synthesis of ideas and information Writing draws few
  • 21. reasonable conclusions and weakly synthesizes ideas and information Writing fails to draw reasonable conclusions based on synthesis of ideas and information Sentence and paragraph structure Ideas expressed in clear coherent and balanced sentences and paragraphs Ideas expressed in clear but not and balanced sentences and paragraphs Ideas expressed in somewhat clear and balanced sentences and paragraphs Ideas expressed
  • 22. poorly with lack of clear coherent and balanced sentences and paragraphs Ideas not expressed. Lack of clear coherent and balanced sentences and paragraphs Use of reference materials At least four appropriate, peer- reviewed reference materials used At least three appropriate, peer- reviewed reference materials used At least two appropriate, peer- reviewed reference materials used At least one appropriate, peer- reviewed reference materials used
  • 23. Appropriate, peer- reviewed reference materials not used Citation Cited reference material properly (in text and in references section) Reference material mostly cited properly (in text and in references section) Reference material somewhat cited properly (in text and in references section) Reference material somewhat not cited properly (in text and in references section) References not cited or missing references section Mechanics Proper grammar, spelling and sentence structure used
  • 24. Grammar, spelling and sentence structure with 1 mistake Grammar, spelling and sentence structure with 2-3 mistakes Grammar, spelling and sentence structure used with 4 mistakes Grammar, spelling and sentence structure with more than 4 mistakes Total points