With an unprecedented need for science coupled with enormous government and private investment into that science, interest, excitement, and skepticism in the biotechnology sector have never been higher. Although much of the money was targeted toward technologies and logistics to meet our imminent healthcare crisis need, as with everything when government money is involved, “the rising tide will lift all boats”. We like to focus on the direct investments made into a handful of companies but the equity markets are at all time highs along with the flow of cheap credit to “risk on” asset classes and sectors. These notable financial metrics allowed for many early stage and cash burning life sciences companies to not only get capital in the first place but also at a historically low cost. So how has this historically anomalous event impacted the biotechnology sector and how will it affect the space in the short, medium, and long term?
One cannot discuss where we are going without briefly touching on where we have been. It has been nearly seventy years since the discovery of the DNA double helical structure by James Watson and Francis Crick, over twenty years since Craig Venter and his company Celera were in a race with the government to map the Human Genome, and nearly ten years since James Allison’s work led to the first approved checkpoint inhibitor. These were all pivotal moments along the path toward understanding of biotechnology and huge leaps forward in unraveling the complex mystery of human physiology and disease. Biotechnology development is a risky business and historically, huge innovation has come after events that have gotten average people interested in the sector. These periods have come in many forms, whether the above excitement that comes with visions of miraculous cures or technology paradigm shifts or when we as a people are fighting for our lives and days and even hours matter.
So, in early 2020, when a global pandemic posed unprecedented challenges to the world and scientific innovation had to step up to meet this viral menace, our ability to pull together scientific miracles was put “center stage” for our species to scrutinize. Quickly this virus, no matter what its origin was or where it came from or why it was here, was the world’s problem and we hoped our scientific progress had culminated into something useful which was “game ready” right now. Despite the massive losses from COVID-19 in both human and economic terms which we will suffer from for years to come, the biotechnology arsenal that was brought to bear here must be appreciated. Whether it be the isolation of the viral genetic code, targeting of the appropriate protein, creating safe and very effective vaccines, massive manufacturing scale-up, global coordination, or the accelerated time-line with which the above was achieved, we all should be somewhat in awe.
With that all said and presently armed with some comfort that the billions of dollars being spent every year in research and development are creating value that can definitely impact you, what stands out as super interesting right now? Effectively the five most important areas that will impact our lives over the next five to ten years arguably are as follows:
Obviously, our ability to modulate the immune system has been put on full display with the vaccine and therapeutic technologies that were deployed for COVID-19. However, with substantial advances in our understanding of the immune system and the regulatory mechanisms that allow its coordinated function, this area will provide massive medical breakthroughs for years to come. Engineering of our own T-cells to attack targeted things will continue to improve and the idea of a “living drug” that will mutate along with a heterogenous and evolving tumor is perhaps not just fantasy. However, the understanding of how disease affects our immune system will start to yield progress in the down regulation of our immune function as well. It remains reasonably likely that this down regulation and increased control will have broad impact on autoimmune disorders such as Rheumatoid Arthritis, Crohn’s disease, and perhaps even Diabetes. The immune system is in delicate balance and it needs to be carefully monitored and understood in order to maximize outcome as too little is not good and too much is not good. That said, having it completely “on” or completely “off” is very clearly also not the answer and situational therapy is required. Our understanding of how this all intricately works has grown tremendously in the last twenty years and really accelerated in the last five.
• The Evolution of the Vaccine
• The Tumor Microenvironment
• Regulatory T Cells
• Autoimmune Disease
2. Genetic Manipulation
For two decades, the scientific community has been in a clinical and technological race with its own success as each time something amazing is accomplished with the manipulation of a gene and/or its expression, we learn there is another level of complexity and challenge. We have come a long way to be sure. We can manipulate gene expression, even change out whole genes which are faulty, sequencing is incredibly efficient and with new editing techniques like CRISPR/CAS-9, the small lab with the small budget can also do meaningful experiments. All these forces are incredibly important to the advancement as the challenges and specific patient variables are incredibly tough to work through. For diseases caused by the breakdown of many genes or the orchestration and regulation breakdown of multiple dependent or independent genes, we have a lot of work to do. For diseases which are caused by the breakdown of one gene or just a few genes, we are much, much closer to therapeutic utility. However, just because we can edit the gene in one patient or manipulate expression levels in one patient where levels are therapeutic, questions still remain. How long will this therapeutic effect last? Will I get the same effect given the same therapy in other patients? What uniform and clinical dosage is appropriate? How will this therapy’s safety profile look five, ten, or twenty years down the road? Long before genetic engineering becomes mainstream and broadly used for a vast array of genetic diseases, we need much more clarity and understanding into these questions. That said, we are very close to answering many of them and if we achieve comfort with the answers, the results may be miraculous very soon.
• Gene Therapy Versus Gene Editing
• Genome Versus Proteome
• Genetic Editing Techniques
• Challenges of Therapeutic Expression
3. Real-Time Diagnostics
With the ubiquity of cell phone breadth and utility and the multiple accessories that are being “tethered” to this ubiquity to expand its reach, functionality is “getting there” rapidly. If you marry this fact with tremendous advances in both the accuracy and speed of diagnostic technologies and the clearly stated direction by companies like Apple into healthcare, patient/doctor transparency is likely to be impacted imminently. This will be a slow and methodic evolution from physiological measures like heart-rate, blood pressure, EKGs, glucose levels, etc and eventually into hematocrit levels, plasma concentration levels, and perhaps even more detail as diagnostic capabilities expand. It is of course equally important to make a wearable or portable device to be able to provide this information which in unto itself is challenging long before we substantially cut into diagnostic “turn-around” timelines. That said, before we substantially get ahead of ourselves, patient compliance can be impacted with the technology we have today. With doctor/patient applications and corroborating information on historical physiological metrics, intervention time, change in intervention, impact of intervention, and corroborating that with actual physiological/emotional/physical inputs, etc will have impact as soon as this year. Studies will have to be done to show the medical impact here over time in order to sell it to your average doctor and patient but as evidence mounts, so will interest from these two communities.
• Beyond Theranos: Actual Diagnostic Realities
• Specificity Versus Sensitivity: Why Accuracy Takes So Long
• What Does Apple See In Healthcare?
• A Proactive Patient: Why It Matters
4. Virtual Medicine
Many regular day to day activities were disrupted over the last year as we were forced to do things virtually that historically have been exceedingly difficult to do over this medium. No place was this more pronounced than in healthcare and improvisation and inconvenience very rapidly became comfortable and dare I say, efficient. Coupled with diagnostics and patient monitoring, pre-emptive care, and proactive patient compliance management, these changes in large part will become permanent. There will continue to be things that you just must go to a physician in person for but there will emerge a whole bunch of things where you just do not have to. These efficiency increases and time savings are going to increase patient awareness of their own health, get them more involved in optimizing their situation, and allow for better and more comprehensive care. Basically, the fact that it not only can be done, but generally is better when it is done, means essentially that going forward, it will be done as part of the care continuum.
• How Much Medicine Can Be Virtual Really?
• Telemedicine: More Interaction; Lower Costs; Better Outcomes
• The Future Of Remote Healthcare Technology: What If We Could………?
• Getting The Patient Involved; There is An App For That
5. Drug Delivery
The advances in drug delivery continue to astound and impress even though they would have made it as part of this list in my view for the last twenty years. No matter how innovative the technology or how important the target, if you cannot efficiently deliver a payload to the desired cellular location, none of that matters. Further, dosage and delivery are extremely important to patient compliance, i.e., a patient is far more likely to stick to a therapeutic regimen with an orally available product than an infused one. Simple changes that increase compliance, particularly with necessary drugs that are taken chronically, may have more impact than all the other advances combined.
• The Complexity Of Drug Delivery
• Keep It Simple Stupid: The Power Of Patient Compliance
• Pharmacokinetics Versus Pharmacodynamics
• How “Controlled Release” Is Controlled