BACKGROUND

By the end of 2016, we surpassed $7 trillion in total annual healthcare expenditures around the globe, close to a $1 trillion of which was spent on pharmaceutical products. That same year, an additional $200 billion was spent globally on new life science research and development.

Despite these incredible financial dynamics, we continue to witness a rise in the prevalence of almost all chronic degenerative diseases responsible for human suffering and death, as well as an on-going growth and aging of the population.

Innovation has all but disappeared in the traditional drug development arena, with costs per new product escalating into the billions of dollars, development timelines surpassing 15-20 years, and the majority of new drug approvals offering minimal to no benefit over existing therapies – if they survive the 1-in-10,000 rate of success in the first place.  

Additionally, widely acknowledged, but largely unspoken truths from the pharmaceutical industry persist:  all of the “disease output” targeted drugs (drugs that target symptoms, such as elevated blood pressure, low estrogen, etc.) that eventually make it to the market will only work in a small percentage of their target population (due to our emerging knowledge of heterogeneity in both patient and diseases), and none will be capable of ever affecting an actual cure.  

Lastly, central regulatory bodies in developed nations have become increasingly bureaucratic and fallen behind literally decades in both their ability to keep up with new scientific platforms, as well as their acceptance of creative clinical testing modalities that address a 21st century understanding of patients, diseases, and drugs.

Which leads us to the inescapable questions: Where has the current approach gone wrong, and where are the cures for disease?


SITUATIONAL ANALYSIS

Since the inception of the modern pharmaceutical industry, researchers have attempted to reduce and study human health and disease at the level of their most basic components – proteins, genes, cells, etc., continually looking for new targets to develop drugs compounds that can interfere in some way with biological processes.

At the same time, from the clinical perspective, patients have continued to be classified and studied in a very standardized fashion at the population level, primarily based on disease symptoms, via the “gold standard” of evidence-based medicine – the randomized clinical trial.

While these approaches have ultimately allowed the pharmaceutical industry to grow in size and profitability, giving us many treatments for disease, they have given us very few cures for disease. The one exception to this is the antibiotic.

The primary reason for this is that innovation in the industry (as well as at the level of regulatory organizations) is so far behind what the science is has been teaching us in the lab.

From the perspective of drug development, disciplines such as systems biology have shown us that the targets that traditional drugs are developed against are no more than the symptoms of a disease and that these drugs are being developed without regard for, or knowledge of, the actual underlying causes of disease.

Additionally, the approach that is used to identify disease mechanisms continues to ignore the fact disease is rarely (if ever) a simple consequence of an abnormality in a single gene, but rather involves multiple biological processes in complex networks.

Lastly, the area of genomics has continued to highlight that each of us is extremely different from each other in regard to the way drugs both benefit and/ or harm us, and “one size fits all” approaches ignore underlying differences in disease and/or toxicity of drugs between patients.

In summary, the approach of developing single-target drugs based solely on disease symptoms, combined with clinical study models have ignored the differences between individual people and their versions of a given disease, have brought us to where we are today – lots of treatments; modest improvement in outcomes; no cures.


OPPORTUNITIES TO RE-LEARN FROM NATURE

Throughout the 20th century, natural products (primarily those from plants, fungi, and bacteria) formed the basis for a majority of all pharmaceuticals, biologics, and consumer healthcare products used by patients around the globe, generating trillions of dollars of wealth.

However, many scientists believe we have only touched the surface of what the natural world, and its range of organisms, which from a health and wellness perspective are much further advanced than human beings, has to teach us.

Many lower organisms (i.e. amphibians, planarians) can replace lost or damaged organs and tissues that are identical in both structure and function to the original, effortlessly regenerating a wide variety of tissues, including spinal cords, limbs, hearts, eyes, and even large segments of their brains.

In a similar fashion, many of these same species possess fascinating skills for repairing and reversing cellular and genetic damage.  Cancer, as an example, is found to be extremely rare in species displaying an efficient regenerative mechanism, even under the action of potent carcinogens.

Additionally, novel research disciplines, including “interkingdom signaling” and “semiochemical communication”, the respective abilities of one species’ living signals to affect the genome of another, not to mention in-depth study of the microbiome and virome (the bacterial and viral communities, respectively, living within humans), are highlighting entirely new ways that non-human bio-products can affect the human genome for positive transitions in health and wellness.

Merging a 21st century, “convergent” knowledge base of regenerative biology, evolutionary genomics, and bio-cybernetics, offers us new guidance to understand how nature is so successful in warding off disease and degeneration, and eventual clues to how humans can achieve the same outcomes, and perhaps even move beyond.


COMBINATORIAL THINKING, COMBINATORIAL BIOLOGICS

One of the most important learnings that the aforementioned members of the biologic kingdom have to teach us has to do with the novel, “combinatorial” approaches that nature uses to affect the nested hierarchies of disease progression, simultaneously addressing multiple levels of the entire disease “ecosystem.”  

In today’s fairly reductionist biopharma research system, although scientists pay much attention to events happening at the “micro level” in genes, they often ignore that those genes sit within a larger context, a complex “macro level” system that regulates their performance.

Genes sit within these complex regulatory networks, which themselves sit within, and take instructions from, a dynamic system of cellular metabolism.

But things don’t stop there. Cells sit within and take instruction from regulatory systems at the level of tissues and organs. And these systems are affected by thousands of signals from the external environment, including physical forces, chemicals, and microbes.

When one studies the regenerating organisms, you find that they try and impact all of these levels simultaneously: Nature finds true “systems level” approaches to health and disease.

Such integrated dynamics represent a major contrast when compared to the reductionist, highly “siloed” model at play in the pharma industry today.  Evolutionary dynamics would never follow the “single magic bullet” approach promoted by the pharma industry, as all species would have gone extinct a long time ago.

Hence the ability to change our thinking about what a drug looks like in the future, and what its potential range of targets will be, is going to be crucial in getting us out of the current development rut.

One area that our company, Bioquark Inc. has been working on the past few years, is that of “combinatorial biologics”, with the goal of creating standardized mixtures of biologic factors that in combination can mimic in humans, the epimorphic regenerative events that lower organisms use to restore form and function in complex tissues, organs, and limbs.

When we mention the term “epimorphic” in this context we refer ability of cells to erase their history and re-start life again along a defined generative developmental pattern, based on their surrounding tissue microenvironment – in these cases to specifically fill in, via “intercalation” (the locational sensing of what the next step in the development process should be), missing or damaged tissues, organs, or limb.

Epimorphic regeneration in nature is very complex and involves many mechanisms operating in synergy, including but not limited to: reprogramming of cells in target tissues to a progenitor state, a targeted histolytic response for extracellular matrix remodeling, and an activation of the regenerative side of the innate immune response (versus the adaptive immune response) to support morphogenesis and cell migration.

In short, there will be no pharmaceutical “single magic bullet” for recapitulating such dynamics, and any traditional single-drug approach would be fairly futile.  Hence, a prime example of where a “combinatorial” strategy is a better approach to the core problem.

While the topic of combinatorial therapy protocols is somewhat unique, as the medical system typically likes single, simple solutions (i.e. one drug / one target) we are beginning to see more examples recent years, following the lead of HIV “cocktails” and multi-drug chemotherapy protocols, getting closer to the way nature works.


THE FUTURE

We believe that nothing is off the table.

The literature is full of data, both current and historical (yet forgotten), on how nature has provided elegant solutions to many human problems that seem insurmountable today, as well as is suggesting of novel paths for intellectual debate and discovery.

Whether we are talking about the 100,000 people who die daily from age-related ailments or the 50,000 that die from acute traumas, it is well within the intellectual capacity of humans to solve these problems of disease, degeneration, and death.

But we must truly think “outside the box”, and not fall into the traps set by the traditional pharmaceutical industry, its regulators, and the century-old model of drug development which has truly run into a brick wall.

There is a reason that microbes, and plants, and invertebrates, and amphibians, have survived for many hundreds of millions of years on this planet, and developed their own unique answers to many of the problems that plague humanity.

Nature has shown us the way; we must now follow their lead.

For more information about Dr. Pastor and the approach Bioquark is using, be sure to check out the following videos:

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