Madison Area Lyme Support Group

Ten years ago, I joined the Galaxy Diagnostics founding team to make the BAPGM testingtechnology and Bartonella ePCR™ available for clinical and research use in both animal and human medicine.

After over a decade in research on entrepreneurship and innovation and multiple start-up experiences, I was excited to organize and launch a high-technology company in healthcare.

Healthcare is a complicated industry and marketplace with multiple layers of highly bureaucratic regulatory structures and multiple stakeholders, including patients, practitioners, government and third-party regulators, professional societies, medical boards, guideline writers, researchers, insurance providers, health IT providers, patient advocates, and more. Consequently, resistance to change is strong in healthcare and medicine.

As an experienced entrepreneur and a completely nerdy organizational sociologist, I was thrilled with the opportunity to work with my co-founders on this new, innovative start-up. While the lessons in entrepreneurship and medical innovation, to date, have been hard won, the positive impact on patient outcomes has been thrilling.

So, what did I learn?

Commercialization of New Tests is Hard

The hardest lesson I have learned as a Galaxy leader these last 10 years is how unbelievably difficult it is to commercialize a new medical technology. For diagnostic labs, there are four main challenges to commercializing new tests:

1. Laboratory regulations change continuously, which dramatically increases the costs of doing business and introduces a lot of uncertainty into the odds of maintaining a sustainable business model.
2. Medical guidelines lag behind new discoveries and raise the accepted standards for clinical evidence.
3. Pricing standards and insurance reimbursements do not support an early-stage business model, but are instead based on high volumes of established medical tests run by very large companies.
4. Access to patient samples and funding for clinical validation are both limited, especially in areas of new discovery and small patient populations.

Wait, wait—there’s more.

Investors will fund commercialization activities that lead quickly to revenue but are reluctant to fund the clinical research required to translate clinical tools into the marketplace. New labs are left with the enormous task of raising grant funding or bootstrapping the research studies needed for commercialization. Many never bother.

This reality places a tremendous burden on conscientious founders to make personal and financial sacrifices to commercialize new technologies “the right way” (with research and publication). In the case of emerging medical discoveries, like those surrounding tick-borne disease, founders are responsible for building markets for new technologies through healthcare provider education, often amid the highly contested terrain of expert medical opinion and patient advocacy.

Thank goodness for the NIH SBIR program, our local North Carolina Biotechnology Center, our corporate partners at Bayer Healthcare, IDEXX, the One Health Commission, our research collaborators, and our early stage investors. It is through these relationships that we have been able to cobble together the resources required to move our science, technology, and commercial offerings forward to the direct benefit of patients.

Disease vs. Infection

The most surprising lesson that I have learned from my Galaxy experience is that, from a clinical standpoint, disease and infection are two different things. A person can be infected with a pathogen, but that does not mean s/he will get sick, even if there is a disease associated with that pathogen. In other words, you can be infected, or more precisely “colonized,” with a pathogen and not show symptoms. These types of infections are sometimes referred to as subclinical or latent.

Biology is complex. Our bodies are made up of billions of microbes; some are beneficial, some are pathogenic, and others are opportunistic (only a problem under the certain conditions). In the world of infectious disease, disease is caused primarily by the host’s response to the infection (i.e., immune response). And, despite all the significant advances in medicine over the past century, we still don’t actually know what causes many well-known diseases.

In fact, scientists are still making discoveries about how the body works, including recent discoveries suggesting that blood is not sterile (especially not in sick people and animals), that a lymphatic vasculature provides a pathway between the bloodstream and the central nervous system, and most recently showing vascular structures in bone.

In the field of emerging infectious disease, important research is emerging that implicates a range of fastidious, low-level infections in complex immunological disease processes, including Bartonella species, Borrelia species, and other vector-borne infections. Concepts like stealth infection and the pathobiome are helpful as researchers try to sort out these questions, but progress is very slow and hampered by the lack of research funding for chronic infectious disease. To complicate things further, our bodies are complex biological systems with only a few ways to express disorder and disease, leaving our doctors with the challenging task of figuring out which of a long list of potential causal and complicating factors could be involved.

Science Cannot Prove Everything

In my well-considered opinion, the most surprising assumption dominating medicine today is that doctors should only practice what science has proven. Unfortunately, people and animals will get sick with diseases that we may not know about at all. While much of the controversy related to the role of infection in chronic disease could be addressed by research on chronic disease, not every clinical question can be answered even by the most rigorous research designs (e.g., prospective, controlled experimental designs), especially where new discoveries are concerned.

Disease is an organic process. Simply defining a sample population can be challenging in diagnostics research. How do you design a study to determine the clinical utility of a new test if the symptoms are non-specific and potentially caused by myriad factors, or if they only appear in some people with the disease? In the case of bartonellosis, most studies have focused on patients with suspected cat scratch disease (e.g., persistent swollen lymph nodes and contact with cats). However, persistent swollen lymph nodes can be caused by other infections and by blood cancers. Research from NCSU and other Bartonella research teams around the world further suggest that atypical presentations of cat scratch disease (Bartonella henselae infection) are much more common than previously recognized.

We see similar issues in research on borreliosis. For instance, most diagnostic studies have focused on individuals with a bullseye rash, when only 50% or fewer of acute infections present with this nebulous clinical sign. Study methodologies and subsequent findings are limited when new diagnostics are tested only on patient groups with specific symptoms and compared with prior diagnostic methods.

Clinical utility demands better research designs that include patients with typical and atypical signs as well as healthy controls.

One Health and a New Frontier of Medicine

In my opinion, we are now on the verge of a whole new frontier of medicine — the infectious etiology of chronic disease. This area of medical discovery is a central point of interest in the global One Health movement, which includes researchers around the world focusing on the intersection of human, animal, and environmental health.

To better address the challenges of substantiating new medical discoveries and translating new diagnostic and therapeutic tools into clinical practice, we have to work together to identify disease risks and to educate medical practitioners, patients, disease advocates, public health authorities, and the general public on the emerging science.

As a sometime patient myself, I want my doctor to have the access to the latest research and diagnostic tools, not just medical guidelines based on decades-old science. We all have to recognize the complexity of chronic illnesses and be open to understanding the role that multiple factors, from immune function to infection, potentially play in each individual case of chronic illness. We also have to recognize that due to our complex biology, current technical limitations, and highly competitive funding priorities, science cannot answer every clinical question today.

Yet doctors still seek to provide individualized care and patients still want the best that science and medicine can offer to solve their problems today. Somehow, some way, we have to find the means to provide patients with the best possible care today while moving new medical discoveries forward in a landscape that is very inhospitable to medical innovation and clinical translation.

References

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