Becoming a Post-Pandemic Species
Through public-private partnership we can speed up to “insane mode” to deploy treatments for future pandemics, but it requires a substantial shift in our approach.
Despite all of our advances in technology, over the past 100 years since the last devastating global pandemic, the influenza outbreak of 1918, our first line of defense remains the same: stay home. In an age where we don’t have to wait more than five seconds to stream an episode of Game of Thrones, or more than 48 hours to have Amazon deliver literally almost anything, we find ourselves hopelessly waiting months to return to our “normal” lives.
It doesn’t have to be this way. We already have the technology to build the infrastructure that would truly make devastating pandemics a thing of the past. With a warming permafrost potentially releasing ancient viruses and the human population edging close to 10 billion by 2050, our current public health emergency brought on by COVID-19 is far from our last bout with Mother Nature. New advances in bioengineering and automation could create a future where we deploy these vaccines at a global scale in days, rather than months or years.
If we are successful, the end result could be something never before seen in the history of the world. A human race that has finally left global infectious disease in the past. A true master of our biology. A post-pandemic species.
Biomanufacturing matters, plain and simple
I grew up in central Illinois, in a small farming community far from any biotechnology research opportunities. My hometown of Peoria became famous in the mid-20th century when the city’s sole research site, the USDA’s Northern Regional Research Laboratory (known as the AgLab), helped our country to defeat the Nazis.
During World War II, the deadliest war in human history, the sheer number of injured and infected soldiers overwhelmed the health care system. At the USDA’s Peoria campus, mycologist and penicillin expert, Robert Thom, discovered and designed an optimized process whereby penicillin production could be scaled from small cultures grown in lab dishes to giant fermentation tanks. By the time the Allies hit the beaches of Normandy, they had an incredible arsenal of penicillin. By the end of the war, the mass-produced drug was estimated to have saved tens of thousands of lives.
This piece of modern biotechnology history played a pivotal role in shaping my outlook on scientific innovation. Discovery is only the first step in a long line of innovations that must take place for revolutionary breakthroughs to change the world. We have to not only innovate in the discovery of new drugs, but in how we manufacture and distribute them.
This is not only a useful piece of biotech history, but runs a direct parallel to the challenges we are facing today in the wake of COVID. Success on this new frontier will revolutionize our strategy against future modern-day pandemics.
mRNA Vaccines: The modern day penicillin
Moderna’s mRNA vaccine has launched a wave of attention focused solely on this new, seemingly radical approach to medicine. I personally could not be happier.
Three years ago, while finishing my PhD at MIT, I co-founded Strand Therapeutics to develop a new methodology of delivering drugs to patients. Strand is a biotechnology company that develops messenger RNA (mRNA) gene therapies.
In all living cells, mRNA is the “messenger molecule,” serving as a “biological email” that allows your DNA to send its messages (genes) from the nucleus into the rest of your cells. (I will post a follow up piece soon on what else mRNA therapeutics will do for our health in the near future).
While an exciting frontier of medicine, we still lack the ability to rapidly develop and deploy these therapies before infectious diseases dismantle our society. In March of 2020, Moderna unveiled a COVID vaccine less than 65 days after the sequencing of the coronavirus genome. Compared to vaccine timelines, this is nothing short of extraordinary; however, it is simply not fast enough. The unprecedented economic pandemonium and isolation of the past three months should be enough to illustrate our need to do better.
In times of emergency, the FDA has seen fit to grant “Emergency Use Authorization” to certain drugs. Gilead’s drug remdesivir recently received this designation for COVID after it was seen to demonstrate some measurable therapeutic benefit to patients. This “emergency use” is triggered when certain risks are deemed “acceptable” in the face of dire circumstances.
In a quest for ultimate reliability of our biotech processes, we are left unprepared to move quickly when time is of the essence. It’s as if we had spent years building the perfect sports car, only to find out that in an emergency, what we truly needed was off-road capabilities.
We need to understand what level of risk we are willing to take in times of crisis. To this end, we should be building technologies optimized for emergency use, a lifeboat that we proactively construct to be versatile and safe, but taking certain acceptable risks with the explicit purpose of getting us off pandemic island.
“It’s as if we had spent years building the perfect sports car, only to find out that in an emergency, what we truly needed was off-road capabilities.”
Bringing biomanufacturing into the 21st century
By using technology to proactively protect us from disease by rapidly producing and deploying vaccines, we get out of reactive mode: stopping deadly diseases quickly by creating an immune populace. Preferably, before we are stuck inside for an entire year while our health care infrastructure buckles under the stress. We currently have the automation technologies and the biological engineering prowess to achieve this. Simply put, it breaks down into two necessary innovation areas:
- Automated manufacturing
mRNA therapy stands out for its ability to be rapidly synthesized. Currently, long processes of manual tracking of each reagent, dispensed and documented by human scientists, and carried from machine to machine, are needed to make drugs reliable enough to be given to patients safely.
This tracking is key for FDA auditing officials, who ensure the human scientists and technicians have not committed any errors that put people at risk. Each one of these steps, the monitoring and documenting by lab technicians, add to the time it takes to roll out vaccines to patients. However, human involvement in this process will soon be antiquated.
The biomanufacturing lab of the future will have no human error because it will have no humans.
Once we truly automate our biomanufacturing processes, we can run these automated manufacturing units at rapid, superhuman speeds around the clock. We will not need to deploy hoards of scientists into labs and risk the spread of infection. We will, of course, not be replacing humans and scientists, but rather taking them off of the lab bench. In fact, the design, operation, and continued improvement of these facilities will require armies of highly talented scientists and engineers.
We will automatically track every action down to the molecule as it moves through the process. If automated manufacturing units can be made sterile and compact, we can deploy them across the country and the world. A distributed manufacturing global network of “Centers of Excellence,” where vaccines would be synthesized in direct proximity to distribution sites, would decrease the need for global shipments of frozen samples which require complex cold supply chains for distribution.
2. Rapid clinical validation
The second delay in the manufacturing timeline comes from the need to eliminate risk and validate the vaccines for safety and efficacy. How do we shorten this timeframe? Gene delivery therapies such as mRNA, again, hold an advantage here. Since every type of viral protein can be encoded on a strand of mRNA, we can begin to de-risk a “plug-and-play” mRNA that will deliver any antigen (or even antibody) sequence as an “instruction,” and we can begin these trials immediately. By this method, our general compositions will be classified as safe and already established in the future for when pandemic strikes.
Our “instructional” mRNA gene therapies could also alleviate safety concerns against the variable in all of these vaccines, the “software” or viral protein antigen. Regulatory agencies often voice concern at the prospect of new, unknown antigen expression in patients, and the safety of that patient should the antigen elicit unforeseen reactions.
This is where the power of encoding genes works to our advantage again. Genes are inherently “programmable.” Every cell in our body contains identical genomes. The different cell-types, from heart cells to the skin cells, differentiates itself via a type of programming, turning genes on and off.
A field known as synthetic biology has taken that same programming, and re-engineered it, allowing us to program genes the same way we program computers. Rather than be statically expressed, gene expression can be dynamic, being turned on and off by design.
I am a synthetic biologist. My company, Strand Therapeutics exists at the intersection of mRNA gene therapy and synthetic biology. At this intersection, we have built vaccines capable of immediately being “turned-off” with something as simple as an oral pill. We can then administer these vaccines to larger populations, potentially providing faster, more rapid herd immunity before the virus spreads, while maintaining a higher safety confidence than is currently possible.
(I will post a follow up soon on how synthetic biology will bring mRNA therapies to larger populations and more diseases than we currently can cure).
What’s stopping us? Investment.
Pandemics are purely theoretical disease markets, until they’re not. We have no idea what virus will cause the next pandemic, when it will happen, or how widespread it will be. A company cannot pour tens of millions of dollars into technology for markets that they have no idea if or when they will ever exist?
Marc Andreesen recently said, “Now is the time to build,” and I couldn’t agree more. Innovation in manufacturing has long been deprioritized by classical biotech investment. A venture capitalist once told me, “No one has ever raised $100 million on drug manufacturing. It just isn’t sexy.” And to him, maybe it wasn’t. After all, VCs are focused on quantifiable drug markets and success rates; however, I disagree about the “sexiness” of biotech manufacturing. It’s dead sexy.
In the tech sector, “Industry 4.0” has brought automation of manufacturing to an incredibly “sexy” forefront. Next-generation drug manufacturing will be the John Legend of “sexy” investments, just possibly not for VCs (yet). (If anyone knows John, tell him we are looking for a spokesperson to help save humanity.)
Pandemics are purely theoretical disease markets, until they’re not.
Let’s build this
Growing up, I had wished I lived closer to the coastal scientific hubs, rather than what I thought was a small Midwest community with little to offer the scientific world. But looking back, that town instilled in me the spirit of innovative manufacturing.
…we still lack the ability to rapidly develop and deploy these therapies before infectious diseases dismantle our society.
The White House recently announced “Operation Warp Speed” to accelerate COVID-19 vaccine development, but are they willing to prioritize a broader, grander vision? This summer, as Congress sets our national budget, will they see fit to include provisions that protect America and the world from future infectious threats? Are prominent philanthropic agencies, such as the Gates Foundation and Wellcome Trust, willing to think even further outside the box? Our team at Strand Therapeutics, engaged with innovators throughout the biotech industry, are ready for the call.
Only with a full-scale assault can we defeat the viruses and microbes that attack our very way of life. A threat that we must defend, not with bombs, but with biotech; not with advanced aerodynamics, but with antibodies. But we must start now.
The Greatest Generation was defined by their victory over the Nazis and fascism, and how they took humanity to space and the moon. Ours will be defined by our mastery of biology and of the genetic code. We have a generational imperative, a once in a lifetime opportunity, to invest now in defending our species from threats that will most certainly come knocking again. The science is here. The technology is here. But we don’t have any more time to waste. Let’s do this.
