Gut microbiota and Covid-19- possible link and implications

Covid-19 is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our understanding of infectious diseases. Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors. Role of the gut microbiota in influencing lung diseases has been well articulated. It is also known that respiratory virus infection causes perturbations in the gut microbiota. Diet, environmental factors and genetics play an important role in shaping gut microbiota which can influence immunity. Gut microbiota diversity is decreased in old age and Covid-19 has been mainly fatal in elderly patients which again points to the role the gut microbiota may play in this disease. Improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized in old people and immune-compromised patients. More trials may be initiated to see the effect of co-supplementation of personalized functional food including prebiotics/probiotics along with current therapies.

For more on this please read my review published in the peer reviewed journal - Virus Research

https://www.sciencedirect.com/science/article/pii/S0168170220304603

A new revolution in Life Science and Healthcare called “Microbiome”

Any new development in life science and healthcare starts with baby steps and slowly but surely takes the world by storm. Whether it is small molecule based, high-end genomics guided targeted cancer therapy or the immuno-checkpoint inhibitors which are taking cancer treatment to the next level of personalization and precision.

In the last decade one small buzz word has created quite a noise and is bringing hope that indeed wellness and personalized treatment is a possibility – enter the world of the “microbiome”. The term microbiome means the entire genome of the microbiota ecosystem. The advent of microbiome research parallels the advancement in next generation sequencing (NGS). Before NGS came into the picture, microbiology-based study could rely only on culturing microorganisms in the lab which had its own drawbacks. Now, with advanced sequencing technologies and smart algorithms it is possible to dissect the microbial ecosystem without the need to culture microorganisms in the lab.

Human intestine harbors the maximum number of commensal organisms which are into a delicate relationship with the host. It is therefore not a surprise that maximum gut microbiota based studies are published which look into how gut microbiota plays an important role in human health and wellness.

Do you know:-

Ø   Metagenomic sequencing of fecal samples has identified 3.3 × 10⁶ nonredundant  microbial genes from up to 1,150 different species, outnumbering human protein-coding genes by about 150-fold

Ø     Each person is estimated to host at least 160 different species 

Ø  In 2007, only 14 NIH grants contained the word “microbiome” in their titles or abstracts, and the number went up to 1,043 in 2017

Ø   More than 10000 papers published in the last 3 years on “gut microbiota”

With new studies and developments in the gut microbiome space, it would suffice to say-

“If eyes are the windows to the soul, then gut microbiome is the window to your health”

The industry has also taken a leaf and are dwelling into various aspects of the microbiome space. Companies like Leucine Rich Bio (India), Day Two (Israel), Viome (USA), UBiome (USA), Microba (Australia) etc. are taking the developments in the research to consumers directly by providing easy to use at home gut health tests. And there are companies like Enterome (France), Vedanta Bioscience (USA), Seres Therapeutics (USA) etc. that are looking into tapping the therapeutic potential of the microbiome and thus bringing new paradigms in treatment of various type of cancer, IBD, IBS etc.

Investors especially in the Western world have and are putting lot of faith in these new age companies. Most notably Seventure Partners that have funded a slew of microbiome companies in Europe and the US.

Although, lot many research and studies will be needed in future to validate the interesting leads that the microbiome domain throws up yet it is pertinent that all stakeholders especially clinicians and investors in Asia also support this with less skepticism and more openness as the success of the microbiome can lead to a new era of healthcare and wellness

 

"StartUp” but hold tight

“Startups” in today’s day and age can provide two important deliverables to the society: -

·       Employment

·       Innovation and possible disruption in the domain they are active in

No doubt Governments across the world and more specifically here in India are trying to support start-ups. However, for entrepreneurs, it is a long winding road that they need to traverse to see light at the end of the tunnel. Not all ideas can be commercialized immediately especially if it is highly technical and demand lot of testing and “proof of concept” studies.

Even after successfully achieving that comes the challenge of proper marketing and positioning of the product. All of these take time and therefore it is imperative that all stake-holders in the “startup” including employees and investors hold tight and pursue with perseverance.

                                                                             Image courtesy - Cushmancreative

Startups in the life science domain have their own challenges apart from the regular ones. The “bench to bedside” concept which the domain especially pharma and biotech works on relies heavily on research. Now, this type of research primarily is based on pre-clinical and then clinical studies. We all know how long it takes for a particular concept to cross all the stages till it reaches the end user. Therefore, patience is an inbuilt asset for the startups that are in this domain. Many startups in US and Europe start working on spinoffs from interesting leads that come out in a laboratory and many lucky ones get funded as well. However, this concept in India needs some time to catch up as investors are vary into putting money so early without any credible road to return of investment. Also, I feel if there are “success” stories in the life science space that come out of India then many investors will get enthused about funding this domain.

Having said that, not all life science startups need wait for the discoveries to take a credible shape. Many companies in the microbiome space for example like Viome (US), Ubiome (US), Day two (Israel) and Leucine Rich Bio (India) are already trying to bring the fruits of research faster to the end user. Of course, research is always “work in progress” and especially in life science new discoveries and theories can append to the existing knowledge however accelerating adoption is also key in making paradigm shifts in the domain.

Hence, it is very important to build an ecosystem where the startups can provide the necessary impetus to the society and all stake holders need to hold tight till the end result is achieved!

To change the status-quo – A massive challenge for smaller start-ups

New technology and novel products and services always hit the hurdle of convincing the market about the need of the technology especially when the “ordinary” seems to be the norm. The naysayers will always discourage the new thoughts and solutions by comments like: -

·       “Oh! the market is not ready yet”

·       “There is an alternative, probably a cheaper one, why would then the market change?” (This is even when the new solution has better efficacy and efficiency)

·       “Has someone else used it” (This is a typical mindset- even if the newer technology has the potential to change the paradigm, there are few who would take the lead in adopting the change!)

Big companies (or Startups) like Tesla, Uber who are testing to show promise of “driverless” cars for the future or Virgin Galactic which is promising passenger spaceflights, have one thing in common – load of cash- that can help sway public opinion on their futuristic ideas. However, for smaller start-ups, which have novel solutions and which may not be so “non-worldly” (pun intended!), it becomes a challenge to convince the market.

Image courtesy - FoundersGrid

It is also not always that the “need or necessity” drives faster adoption. Some technologies like the “touchscreen” was not a necessity when it was introduced in mobiles, however, touchscreen mobiles changed the way we communicate.

So, one of the biggest challenges of a “novel solution” driven start up is to “change the mindset” and hence the dynamics of the market. The smaller start-ups need more handholding from not only the existing and potential investors with regards to financial backing and patience but also from the community (Eg. doctors, if it is a life science focused start-up to test rigorously the newer “solution” being offered and adopt fast if it is ultimately going to help the end user – the patients!).

Life science ‘start-up’ – bootstrapped to funding

In the world of ‘start-ups’ especially in the life science domain, there are various factors that make it attractive or unattractive. For a start up, initial years is all about product development, team building and then followed by massive marketing. A good product if not marketed well is as good as an unknown commodity and hence no one would show interest in it. And then it needs very good ‘differentiators’ to ward off competition not only from the established players but also from ‘me too’ type companies.

To efficiently execute all the above activities might become difficult for a ‘bootstrapped’ start-up. So investors who understand the domain need to step up and support at this stage of the start-up. A flourishing company might be more attractive for an investor but to see a ‘promising’ company reach a higher pedestal with proper strategic and financial investment surely is more gratifying.

Many experts have commented on what investors should look at before investing in a start-up; 1) Team 2) domain 3) Technology etc. Individually, all the above play an important role in the final decision making but there is no simple formula to it. After all, it boils down to the risk taking appetite of the investor. There is another important aspect of the ‘life science’ domain which makes it tricky, which is the possibility of a long gestation period required to turn the business profitable. Having said that; now with the advent of genomics and the newer ‘art’ of data science sprinkled onto it, the 'business of biology' looks far more interesting and predictable with possibly lesser gestation period in this domain. However, there are probably no guarantees in life. A sunshine sector in months or years can become a non-starter and vice versa. Founders are overtly optimistic and investors are overly skeptical, which they should be. It is a question of matching the expectation of the founders and the investors which would lead to a fruitful partnership and a long journey of success!

The road ahead for Life Science PhDs – the industry options

Getting a PhD is always a very big achievement more so if one has received that degree from a prestigious Institution. Many who are interested in pursuing a PhD do so mainly because of love for “science”. There is no better happiness but to see or find something novel during the course of various experiments that one undertakes during this journey. Of course, out of 100 experiments may be 90 would fail but that teaches tremendous level of perseverance and patience. What is not taught in most institutions is the career path that a budding scientist can take!

                                          Image courtesy - itimes.com

Most PhDs go for post doctoral research which is a kind of bridge between getting an academic/industry position and PhD training. Although, it could be the most productive phase of one’s career, many a times that may not be true. Also, being a post doctoral researcher for long not only dents the individual’s morale but also reduces chance of getting a meaningful employment later. So what are the options?

Not everyone can pursue an academic dream so for the rest industry does provide an alternative if one is receptive enough. There are many options a PhD can look at:-

·         Consultancy jobs – Pharma consultancy jobs require good analytical skills and PhDs generally fit the bill perfectly, however, this is a completely different domain and requires new skill sets which many would possess but may not realize till they start working for such organizations.



·         Industry R&D – Here, I think many PhDs would feel comfortable. However, industry research is completely different from the academic one. Stricter timelines and deadlines are the norm. So one has to quickly adjust to the new environment.

 ·         Business Development – This is a domain for those who like presenting or networking with people. Not all PhDs are comfortable in this and therefore before getting into this one has to be clear about the road map. This generally also requires lot of travelling. One has to always achieve and sometimes surpass the ‘targets’ set by the organizations so that becomes a challenge. However, with good support and skills one can achieve the same. Many PhDs who have transitioned into this domain have become very successful.

 ·         Application Scientists – This is also a good domain for people who are technically good and like travelling but are averse to chasing ‘numbers’. Many big organizations like ThermoFisher, Illumina etc. have an army of application scientists. Initially one has to be in the field but slowly one climbs up the ladder and is required to manage the team of scientists.


·         Scientific writing/Editing – For many PhDs who are technically good and love reading /writing and have a good command over English can look at this option. Many companies in India like Cactus communications advertize for editors/sub editors in various fields of life science.



·         Recruitment – Although, this is probably the least favorite among the PhDs but it does provide another job alternative. Many recruitment agencies hire PhDs to scan and analyze multiple CVs they get so that the right person is shortlisted for the right job interviews.



·         IP/Technology Transfer – This is another exciting domain. Although, this requires some experience and few additional courses/skill sets but can be very rewarding both financially and professionally.

There might be other alternatives available to the PhDs. My aim here was not to provide an exhaustive list but to give a glimpse of the avenues present. All of the above options carry their respective pros and cons. So, it is imperative, that an individual first assesses himself before selecting one of the paths. Good luck to all present and budding PhDs

Funding the Indian Life Science start-ups – a perspective

The new ‘start-up’ culture developing in India is a good sign. Investors are getting more interested in this space; however, the investors also need to look beyond the e-commerce space. Many life science based organizations can be a good bet for middle to long run outlook. Life science offers a big arena to potential investors. From drug discovery companies to Bioinformatics organizations looking to disruptive technologies to cater to the ever increasing healthcare needs.  Although life science domain requires a considerably longer gestation period yet there are companies or technologies that can give a quicker return on investment. Investment from a well meaning ‘patient’ investor(s) can be a force multiplier. The idea of an ‘ideal’ investor is not very difficult to fathom. Good investment can really turn around a company faster as compared to, let’ say, if the start-up wanted to scale up through only internal accruals. 

Life Science organizations require highly skilled manpower. The technology used is ever evolving hence there is a big scope for right investment in the right organizations. The chance of ‘fly-by night’ operators in this domain is slim or negligible. With newer breakthroughs in hardware and better understanding of the human genome, smarter drugs, accurate diagnosis-prognosis are all in the realm of reality. Personalized/Precision medicine is the new buzz word which includes not only advances in medicine but also diagnostics, bio-IT, genomics, proteomics etc. Start-up organizations working in all the above mentioned mini-domains ultimately would cater to the ocean of better healthcare. Therefore the success of many of these organizations would depend on how the investor community looks at this space and helps it grow more thereby not only creating jobs but also giving India  the ‘knowledge-edge’ that many of the intellectuals talk about as our strength.

I believe that the start-up revolution in the bioscience space in India has not even started but if nurtured well it has the potential to turn around and give India its next ‘Life Science Google/Alphabet’