Human Practices

Overview

Humans need improved methods for making therapeutic antibodies. Producing these complex proteins is hard but important; the 2014 Ebola Outbreak illustrates the urgency. In response, we propose the use of microalgae as a widescale antibody production platform. Microalgae have all the benefits of higher-level plants but scale faster and are easier to process. Furthermore, from a holistic point of view, microalgae are an ideal chassis; their primary carbon source is CO2 and they are unlikely to harbor mammalian pathogens.

The Need

''“I rate the chance of a nuclear war within my lifetime as being fairly low. I rate the chance of a widespread epidemic, far worse than Ebola, in my lifetime, as well over 50 percent.”''—Bill Gates Try gif of pathogen spreading here During the most recent Ebola Outbreak, over 28 thousand were infected and an estimated 11 thousand died. Meanwhile, a potent anti-Ebola antibody cocktail, ZMapp, was going through preclinical studies. In a study where 18 heavily Ebola infected monkeys treated with ZMapp, all 18 survived, including several in the hemorrhaging stage of the disease. Given the timing and urgent need, ZMapp was approved for use in humans. One of the first patients treated was Dr. Kent Brantly, the American missionary worker who went on to recover from the disease. When discussing disease outbreaks, the media often makes mention of the vaccine: an antigen—basically a template for pathogen recognition—that provides the body’s immune system with the ability to recognize future infection (“Active Immunity”). Vaccines are ideal for prevention. While they can develop a robust response against a disease, they take several weeks to “train the immune system” and are not ideal in high-risk areas at the moment of onset. We live in a globalized world. Technology and improved infrastructure allow humans to live in incredibly dense concentration, exceeding those of the past. An antigen that takes weeks to develop, weeks to produce, and weeks to “train the immune system” will be insufficient to meet the demands of an emergent virulent pathogen. Antibodies are unique and powerful tools for eliminating pathogens. They eliminate pathogens, such as viruses, by both neutralization—the hindrance of function by binding to the surface—and complementation—calling in the immune system. Human produced antibodies might target upwards of three million antigens. Additional research, like the high-throughput screening at AbVitro, is making is possible to quickly identify antibody sequences that correspond with pathogen/cancer targeting antibodies. Furthermore, wholly synthetic antibodies might augment number of targetable numbers, with computational modeling making it possible to one day predict antibody sequences that match with emerging pathogens. All of these tools will make the finding of pathogen-targeting antibodies simpler, but will not address the shortcomings in existing production methods. ZMapp’s utility was hindered by lack of supply, not an apparent inability to neutralize the virus (as illustrated by the Rhesus model). Only 7 doses were available throughout the Ebola Outbreak, despite infection rates in the thousands. Ultimately, it represents a problem, or complete lack thereof, for rapid antibody production capabilities. A single new Chinese hamster ovary antibody facility, stacked with stainless steel vats, runs in the range of 200 million dollars. Furthermore, the facilities are not modular. They are rigid and highly specialized, built for a particular antibody post-FDA approval (and to scale with its market). A proposed solution was the tobacco plant. A relatively well-understood and engineered organism, it was the method for making ZMapp. Producers inject plant leaves with agrobacterium containing the DNA for the therapeutic antibody. The plants grow and the antibody is purified from the plant cell lysate. In theory, this is a quick and inexpensive method for rapidly producing lots of antibody, dependent upon arable land rather than high-sterility CHO-vats. In practice, it is not. No tobacco-based antibody has yet to reach market, and ZMapp production was not made rapidly enough to help ease the 2014 Ebola Outbreak. The 2014 Ebola Outbreak was horrific and should be learned from. It was the canary bird in the mine. We live in a smaller world than a century ago, and should consider the cost of not having appropriate treatment infrastructure in place, particularly in case a more contagious pathogen than Ebola emerges in a dense community.