2015 Year of the phage conference | San Diego State University

Prognosticating the Future of Phage Research

Hackable Human Holobiont

By Jeremy Barr (SDSU)

My phage future begins within the context of the human holobiont, which we know as a complex, and intricately balanced collection of microbial symbionts living both on and within us. The more we investigate these diverse microorganisms the more we understand how crucial they are for our health and well being.

Microbes colonize every inch of our body and vastly outnumber our own cells by a factor of 10. The microorganisms living within our gastrointestinal tract are considered a metabolic organ of their own, controlling multiple functions, including the maturation of the intestinal immune system, adiposity, liver triglyceride storage, and even influencing our development and behavior.

By far the most dominant microorganism within the human holobiont is the bacteriophage, with an estimated 10^15 phage particles found in the human body. Phages are found all over our bodies including our skin, lungs, oral cavity, lymph, blood, and have even been detected within the brain. Gastrointestinal phage populations encode the majority of the genetic variation found within the human body, these phages persist with us and evolve with us throughout time, they regulate our gastrointestinal bacterial communities, and are involved in mucosal immunity. Phages are intricately entwined withinin almost all aspects of the human holobiont, and for all their import, I think we can all agree that there is still so much we do not understand about them. This sets the starting point for my phage phuture within the human holobiont.


Within the next 10 years the scientific community will understand the diversity and complexities of the bacterial component of the human holobiont. Probiotics, instead of just being full of yogurt strains, now contain biologically relevant microbial consortiums that actually work, targeted towards treating specific allergies or diseases.

Antibiotic resistance pathogens are now the leading cause of infectious disease mortalities. Our rampant overuse of antibiotics, antimicrobial hand washes, and procedures to sterilization of all foods has left many people within the modern world with an underdeveloped microbiome.
Research efforts are now directed towards sampling isolated villages 'untouched' by modern medicine in an attempt to document and cache our lost microbial symbionts.

The FDA removes the majority of regulatory restrictions for human use of strictly lytic phages. This causes a commercial boom in phage therapy with numerous startups developing phage-based products across a range of markets, yet the efficacy of these treatments is still questionable

DNA sequencing and synthesis technologies have significantly advanced. The majority of the modern world have their microbiome sequenced regularly, big data companies now trade and invest in sequence data.

As a result of these advances, a huge range of phages can be engineered and synthesized in easy to grow bacterial hosts, creating diverse phage production factories on a scale never before seen. These advances lead to the death of phage isolation and cultivation techniques.


Within the next 25 years humanity will go through a mass extinction event, but this one will be of a microbial kind. The gastrointestinal tract in the average individual in the modern world has had its 'rare microbiome' depleted, rarefaction curves are flat, diversity indices are lowered, and there is a significant epidemiological increase in allergies, gastrointestinal complications, autism, and many other health issues that have been linked to the depletion of our microbiome.

Antibiotics are thought to be the main cause, and subsequently their usage heavily declines. Antibiotic resistant infections are now estimated to cost the US economy hundreds of trillions of dollars in medical expenses, lost productivity, and infection control measures.

DNA sequencing and nano-technology have significantly advanced. The sequencing of fecal samples is now considered "archaic" as it fails to capture the relevant information on the metabolically active gastrointestinal microbes. Medical professionals now prescribe Nano-bots that are ingested, and patrol the GI tract, sampling and sequencing the mucosal surface, and providing real time data on the microbiome.

Regulations around the use of lysogenic and genetically modified phages for human use have been removed. Our understanding of the dynamics of phages within the gut greatly increase, this is driven by an increase in computing power, mathematical models, and microfluidic systems.

Phage synthesis and expression vectors are routinely used to micro-manipulate the microbiota, precisely excising recalcitrant bacterial species, opening niche space, and allowing the colonization of engineered commensal lysogens. This becomes known as the birth of personalized phage therapy.


Within the next 50 years phages have become completely ingrained within our culture. Antibiotics are heavily regulated, being traded on the black market, and have been phased out for all but the most serious and recalcitrant infections.

Local pharmacists have been replaced by "Phageacists", tertiary educated health care professionals, mixing complex phage cocktails, induction agents, and genetically modified bacterial strains on a personalized level. As a result, the incidence of food allergies and many other health issues begin to decline within the developed world.

Due to significant advances in computing power and artificial intelligence, we are now capable of modeling viral infection dynamics within complex three dimensional environments, significantly increasing our predictive power treat and manage infections. As a result the efficacy of phage therapy has never been higher.

"Designer" phage and microbes are now synthesized and commercialized, providing you with the biodiversity of your favorite athlete, the skin microbiome of famous actress, and can even confer feelings and emotions through the manipulation of metabolic signaling molecules.

Live gastrointestinal microbiome sequencing is now completed at home via nano-bots, supplied and maintained under service leases from big data companies.

Numerous 'sequencing plans' are available for your purchase.
Would you like the latest i-nano-bot version 6 complete with 32 zettabyte of cloud storage, and excellent gastrointestinal service coverage, all for just $559 per month under a 2-year contract?  
Why not upgrade to a family bundle, and enjoy the benefits of the i-nano-bot's patented fecal-oral "at home" distribution network, all under one convenient bill?

Fees and taxes not included, for incidences rouge nano-bots and intestinal bleeding please see your health care professional.

Within the next 100 years all of our meals will be metabolically optimized and personalized. Before you eat each meal, nutritional information is automatically uploaded into your cognitive integrated personal computer, and the optimal bacterial and phage mix is rapidly synthesized and injected into the gastrointestinal tract, ready to metabolize the meal you are about to consume.

Designer phages are now a multi-Quadrillion dollar business. Rapid biological synthesis and nano-technology allow for precise manipulations to the microbiome effecting your energy, mood, and thought processes.
"Would you like to enable a four hour cognitive boost for a one off simple payment? Purchase nine cognitive boosts and receive your tenth for free!"

Phages are now used as vectors for the human genetic modifications. Complex molecular motors, engineered enzymes, and DNA excision and insertion tools are all packaged into these evolutionary perfected delivery systems, accessing all parts of the human body, effecting gene regulation, immune functions, neural synapses, and facilitating the first ever direct connections between Man and Machine to occur.
Finally, in 2115 the Year of the Phage conference is held in New San Diego, celebrating Mankind's conquering of the world's most versatile predator.

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Forest Rohwer Laboratory
San Diego State University