The Future (and Past) of the Human Race Resides in Biotechnology
When I was working at one of the largest biotechnology companies in the world, the CEO said to me “I think this century is about biotech. In eighty years, people are going to smile about diseases that we needed to deal with and we couldn’t treat, and we couldn’t cure, and it’s all history.” With the novel coronavirus pandemic we have dealt with this year, this statement is ringing all the more true, albeit even sooner than my colleague predicted. Although some countries seem to have seen their peak for the pandemic and are executing plans for re-opening, until there is an efficacious vaccine and an effective treatment, these moves will have to remain cautiously in the direction of a “new normal.”
Looking at the situation realistically, in all likelihood we won’t be getting a coronavirus vaccine before next year. However, much of this delay has to do with the rigorous testing needed to ensure a vaccine is safe enough to distribute to the masses, along with the logistical issues that come with creating enough doses of the vaccine. When it comes to the science itself, even within the past decade advances in several crucial biotechnologies have sped up the process for the creation of vaccines. But what exactly is biotech? Is it synonymous with pharmaceuticals? Below, we explore these questions, and just how scientific advancements within the realm of biotech are paving the way for a coronavirus vaccine.
What is biotechnology?
When you hear the word “biotech” it may conjure images in your head of Dolly the cloned sheep, genetically modified organisms, or gene therapy. All of these are indeed examples of biotechnology, but although these images and even the word itself may sound futuristic, humans have been using biotechnology in a way since a very long time.
In fact, you have more than likely experienced something made utilizing biotechnology recently. In its broadest definition, biotechnology is the use of an organism, or a component of an organism or other biological system, to make a product or process for a specific use. While that may not sound like anything you’ve experienced, when was the last time you enjoyed a slice of bread? By using the living organism yeast, humans since the Egyptians 5,000 years ago have been able to bake bread. Fermentation is also an ancient use of biotechnology, without which we wouldn’t have wine, beer, or other alcoholic spirits.
Specifically, within the agricultural industry, biotechnology has been used by farmers since the beginning of recorded history. The earliest farmers would use biotechnology to breed food crops or domestic animals. They would enhance the agricultural production process by selecting and breeding the best-suited crops that had the highest yields, thus producing enough food to support a growing population. Once these advancements caused crops and fields to become increasingly large and difficult to maintain, they made the discovery that specific organisms and their by-products could effectively fertilize, restore nitrogen, as well as control pests. Although it may not have been intentional, throughout the history of agriculture farmers have inadvertently altered the genetics of their crops through introducing them to new environments and breeding them with other plants.
When it comes to the field of medicine, one of the first and biggest breakthroughs using biotechnology was the discovery of penicillin as a way to treat bacterial infections in humans. In 1928, the microbiologist Alexander Fleming arrived at his laboratory one morning to find that several of the bacterial colonies he had been studying were dead. Disheartened, Fleming luckily decided to examine the dead bacteria before disposing of them and noticed the bacterial colonies had been contaminated by a fungus called Penicillium. From this, he concluded the fungus produced a substance that was toxic to the bacteria, and by 1940 penicillin was available as a medicinal use, saving thousands of lives and changing the way we approached bacterial infections.
The field of modern biotechnology started with the discovery of “nuclein” in white blood cells by Swiss chemist Friedrich Mischer in Basel, but it should take until 1953 that Watson and Crick proposed the three dimensional DNA double helix. In 1971, eventual Nobel Prize laureate Paul Berg experienced early success at Stanford in his gene splicing experiments. These experiments along with other discoveries involving DNA all lead to the creation of recombinant DNA (rDNA) in 1972, or DNA that has been created through the combination of elements of DNA from different organisms. By introducing genetic material from one organism to another, this discovery established the principles of modern genetics. The commercial viability of a biotechnology industry was significantly expanded in 1980, when the United States Supreme Court ruled that a genetically modified microorganism could be patented.
Today: biotechnology and pharmaceuticals
Although it may seem like when you are talking about biotech and pharmaceuticals that the word can be used interchangeably, it’s worth taking a closer look. Whereas as we just learned biotech is the use of living organisms to manufacture products, pharmaceutical companies made human treatments for about 100 years using chemistry and entirely focused on small molecules that can be manufactured without any living organisms. One of the most well-known examples of this would be the creation of aspirin. However, from the 1980’s the industry discovered the advantages of biotech so that today, of all newly launched pharmaceuticals more products are made with biotechnology than without.
This is because of the significant advancements that have been made within the past 40 years within the biotech industry. A decade ago, new technologies for sequencing DNA were just coming online, and technologies for chemically synthesizing new DNA were still slow and expensive. Since then, both technologies have not only become faster, but also significantly cheaper, so they no longer pose the significant barriers they once did. Along with this, there have also been major advancements in genetically engineered viruses. Researchers now routinely build and use harmless viruses in the lab to conduct basic medical research.
Biotech and the coronavirus
So, what does this all mean when it comes to the coronavirus vaccine? Basically, even before SARS-CoV-2 was known as a threat biotech had been developing new technologies that could help us make vaccines vaster. In the past, virtually all successful vaccines in history consisted of the virus itself in a weakened form. Some of the proteins that make up the disabled virus are what train your immune system to recognize and destroy an incoming, infectious virus. However, these traditional methods for making vaccines can be quite slow if the virus is one that hasn’t been encountered before, because it takes time to research how to kill or weaken the virus in a way that makes it safe to administer while still preserving its ability to train the immune system.
New biotechnologies are based on the idea that a vaccine can train the immune system even without needing to include large fragments or the entire virus. The immune system typically targets viral protein sequences, and a vaccine that delivers these proteins or fragments rather than the entire virus itself could be just as effective as a traditional vaccine. These vaccines could also potentially be much easier to make thanks to cheap, fast DNA sequencing and synthesis. These synthetic viral genes are the basis of three new vaccine technologies: genetically engineered viruses, DNA vaccines, and mRNA vaccines.
Genetically engineered viruses
The idea behind this vaccine is utilizing a safe, well-characterized virus to serve as an all-purpose delivery vehicle that carries genes from a pathogenic virus. By using viruses that have been engineered to not replicate in humans or even a livestock virus that is harmless to humans, researchers are able to modify and manipulate them in the lab so that they can be engineered to carry chemically synthesized genes. Because genetic sequencing has become not only a rapid process but also a cheap one, we are easily able to sequence all the genes in a new virus and then use DNA synthesis to chemically make one or more of those viral genes, engineering them into the harmless delivery virus. Once this has been completed, costs for making copies of the virus are virtually zero as well, making distribution for this method simple as well.
Although sequencing and synthesis are an easy process, it is still challenging to figure out which genes provoke the best immune response and should therefore be built into the carrier virus. That part of the method is still essentially trial and error, and in addition to that these new kinds of viral vaccines haven’t been widely used yet, meaning their safety still needs to be tested more extensively. However, some of the first vaccines brought to clinical trials for both Zika and Ebola were based on genetically engineered viruses, and coronavirus vaccines using this method are already under development.
Alternatively, DNA vaccines omit using a virus altogether. Instead, they use small, circular pieces of DNA called plasmids, which carry genes for one or more viral proteins. The idea is that after injecting the vaccine into your system, the plasmids are then taken up by your cells. The viral genes then direct the synthesis of viral proteins, which stimulate an immune response.
These DNA vaccines are today fairly simple to make once you’ve identified which viral genes to deliver. In fact working with plasmids is something commonly taught to biology undergraduate students. These plasmids can also be very easily produced en-masse and at a low cost using bacterial cultures, which is potentially safer than methods based on culturing viruses since viral cultures involve working with the infectious material itself. Like genetically engineered viruses, the main problem with DNA vaccines is their lack of track record.
As the name indicates, for this method rather than using the virus itself or DNA genes, it uses messenger RNA (mRNA), the molecule that serves as a direct template to produce a viral protein. These types of vaccines are not only faster and cheaper than other options, but also potentially safer because RNA does not interfere with the genome. The good news is that mRNA does not need to enter the cell nuclei to work, but only needs to pass the cell membrane. The bad news is that mRNA is notoriously unstable. The solution to keep the mRNA intact and to facilitate the membrane transfer is to package it in structures called lipid nanoparticles.
Although there have not been any working mRNA vaccines available yet with most of the data on efficacy we have available being based on animal studies, since the onset of the coronavirus pandemic mRNA vaccines are being developed by several companies. These vaccine recently began clinical trials, in which large scale enrollment and placebo-controlled methods are used to test the efficacy of the vaccine. If these vaccines or only one of them is able to show promising results at the end of the trials, we may be well on our way to the first mRNA vaccine approved and distributed.
Within the past thirty years, the biotech industry itself has seen a shift in the way innovation is handled. Whereas in the 1990’s you would find large companies doing most of the financing, today biotech start-ups are becoming increasingly part of the conversation, with as much as half of all breakthrough, innovative therapies coming from these smaller companies. The exciting and lucrative nature of biotech discoveries mean that whereas before biotech companies would be looking to make minor modifications to an existing model of a molecule, today they are much more willing to take risks and develop a completely new treatment. Whether it’s the looming threat of the coronavirus, or innovations that will change the way we treat the biggest ailments in human history such as cancer, heart disease, and diabetes, with the direction biotech is going we’re sure to only see more exponential growth in the field over the course of this century.