In Brief:
- Biopharmaceuticals, or protein drugs such as insulin and human clotting factor, are very expensive to produce and often inaccessible to patients around the globe
- These proteins can be produced in genetically modified lettuce leaves and inserted into pill capsules, a cheaper and more advantageous form
- Consuming lettuce pills creates a tolerance for the human clotting factor in hemophilia patients, reducing negative immune response to injections
The high cost of healthcare can be deadlier than the disease itself for patients who cannot afford life-saving treatments. To tackle this, Dr. Henry Daniell, professor and Interim Chair of the University of Pennsylvania’s Department of Biochemistry, uses genetic engineering.
Biopharmaceuticals are protein drugs, such as human clotting factor and insulin, used to treat diseases like hemophilia and diabetes. Despite the need for these drugs, they may not be affordable in even the richest countries nor available in underdeveloped countries. Dr. Daniell wants to lower costs and improve accessibility by creating a radically different method of producing biopharmaceuticals. He says, “Computer technology has advanced so far in the past few decades, so why haven’t medical treatments advanced over the past 50 years?” His innovative research comes with many advantages, including treatments for hemophilia.
Hemophilia is a genetic disorder where blood does not clot, resulting in severe bleeding from even a slight injury. It is caused by missing or defective clotting factors, or proteins needed for clotting. Currently, treatment for hemophilia consists of lifelong injections of clotting factors. However, some patients develop antibodies that see the injected clotting factors as foreign invaders, leading to a potentially deadly allergic reaction. Dr. Daniell’s hemophilia treatment involves creating a tolerance to this injected clotting factor by consuming lettuce pills.
Unlike ordinary lettuce, the lettuce used in these pills has been genetically modified to produce the missing clotting factor in hemophilia patients. Similar to how children who are fed peanuts early in life are less likely to develop peanut allergies, the lettuce pills aim to create a tolerance for the injected clotting factor, eliminating antibodies that cause severe allergic reactions. This has been successfully demonstrated through mice and dog trials. But how can lettuce grow a human protein?
Any organism can produce specific proteins if it has the right DNA, a universal set of instructions used by the body to make proteins. This principle is the basis of genetic modification and the reason human proteins can be produced by other organisms. Traditionally, these proteins are produced in E. coli and yeast, but Dr. Daniell and his team use something very different– lettuce.
There are a few ingredients required to make these lettuce pills, including the human clotting factor gene coded into pieces of DNA, lettuce plants, a gene gun, and… frisbees?
Yes, frisbees are needed to modify lettuce, but they are nothing like your average toy tossed around at a picnic. Instead, these frisbees are tiny gold particles with razor sharp edges, coated with the DNA of the clotting factor gene. Instead of tossing these frisbees, a handheld device called a gene gun is used to shoot the gold particles like bullets into the leaves of plants. The brutal force pushes the gold particles and DNA into the lettuce leaves, permanently integrating the gene into each cell’s genome. As the plant grows, it produces the human clotting factor. Then, the lettuce leaves are harvested, freeze dried, ground to a powder, and inserted into capsules.
The Advantages
In addition to reducing risk of anaphylactic shock in hemophilia patients, the production cost for these lettuce pills is low. It is much cheaper to grow plants than organisms such as E. coli and yeast, which require multi-million dollar facilities.
Additionally, lettuce capsules are taken orally, do not need refrigeration, and have a three-year shelf life. This versatile plant-based platform can be used to produce many different proteins, due to DNA’s universal nature. This platform offers huge advantages over current methods of protein production that require purification, injection, and refrigeration, leading to high shipping and production costs coupled with a short shelf life. Overall, the pill production process is 2000 times less expensive than traditional methods.
Another advantage to this platform is that the gene gun only transforms the chloroplast DNA, instead of nuclear DNA. Therefore, inserted genes are not present in pollen, so there is little risk that modified plants could cross with native crops and disrupt biodiversity.
In the future, this plant-based platform can be used with various genes to create vaccines as well as treatments for diabetes, hypertension, dental caries, and autoimmune diseases. But for now, Dr. Daniell is optimistic that his pills will soon receive FDA clearance to be tested in humans, as a similar plant-based system using carrots has already been approved. Once the lettuce pills receive clearance, human trials could start later this year.
CONTENT EXPERTS
Dr. Henry Daniell is a professor and Interim Chair of the Department of Biochemistry at the University of Pennsylvania. To improve on the current production of vaccines and biopharmaceuticals, he pioneered and advanced the concept of expressing foreign genes in chloroplast DNA. These therapeutic proteins produced are used in treatments for diseases such as hemophilia and diabetes, as well as oral vaccines for infectious diseases such as polio, tuberculosis, and others, as well as tolerance for autoimmune disorders. His works have been featured in over 200 publications, and received numerous awards, patents, and grants.
Works Cited
- Baillie, K. (2017). Plant-made Hemophilia Therapy Shows Promise, Penn Study Finds. PennNews. Retrieved from https://news.upenn.edu/news/plant-made-hemophilia-therapy-shows-promise-penn-study-finds
- Baillie, K. (2017). Plant-made Hemophilia Therapy Shows Promise, Penn Study Finds. PennNews. Retrieved from https://news.upenn.edu/news/plant-made-hemophilia-therapy-shows-promise-penn-study-finds
- Departments & Faculty. (2017). Ee.dental.upenn.edu. Retrieved from http://ee.dental.upenn.edu/departments_faculty/faculty_directory/henry_daniell/
- “Interview with Dr. Henry Daniell.” Interview by Carey Lau. August 9, 2017.
- What Is Hemophilia?. (2017). NIH. Retrieved from https://www.nhlbi.nih.gov/health/health-topics/topics/hemophilia/
Image Credits:
Feature Image:
Lettuce grown in lab” by Unknown (Edited). License: CC0 1.0
Story Image:
Graphic by Staff Illustrator: Lucia Tian
Chief Editor: Aparna Ragupathi
Creative Team Manager: Sreya Das
Team Editor: Christina Wang
Team Graphic Designer: Lucia Tian
This article was written by Carey Lau. As always, before leaving a response to this article please view our Rules of Conduct. Thanks! -cSw Editorial Staff