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

 

The mantra is……………..Innovation!

I believe there would be a general agreement on the fact that companies in today’s world need to innovate to survive. However, the conundrum is how much of the company’s revenue (small/medium enterprises) or initial funds (as for start-ups) be focused on the research activity? 

Let us take examples of two types of business models (we would only consider biotech/life science industry). First is the ‘service’ model where the companies provide technological services for fee. These might range from providing protein purification services to next generation sequencing. The companies rely on their expertise and promote their cause by trying to give the best services. Since many of the companies utilize an already known technology they focus on giving their clients the best technological support and in due course would expect good ‘word of mouth’ publicity for the company to promote its services. The better companies which survive for the longest duration however are also focused on improving the ‘in –use’ technologies to sharpen their service portfolio. This is crucial as the subtle improvements can bring in new clients and can also cater better to the existing client base. One general question can be since these companies utilize instruments or reagents from established players (Illumina, Agilent etc.) why should the service provider invest money to innovate? Surely the instrument manufacturers are doing their bit and the service providers can acquire the technology from them! So why not completely focus on marketing and spend little on ‘in-house’ research? Well, research does not always mean big ticket breakthroughs! Even subtle changes for example, in the protocol of a particular assay can bring in great benefits both in terms of economic advantage as well as technological advancement. Second is that newer methods can provide a valuable feedback to the instrument manufacturers and therefore the possibility of partnership increases. This gives a huge fillip to the ‘brand value’ of the service provider. Hence one cannot completely shut innovation even in service based business models. 

                                   Image courtesy - The creative Scientist

Let us now look at the ‘product’ based business model (again in the realms of life science industry). I guess there is no denying the fact that for product based life science organizations ranging from companies delivering ‘bioinformatics suite’ to companies selling enzymes, innovation has to take the primary seat. Newer and better products are the keys to survival!

But having known these facts how many SMEs (Small medium enterprises) really focus on innovation? Many companies think that money spent on R&D is not worth it especially in the life science sector as there is a long incubation period and higher failure rates. But then investing in research is like buying insurance. Not only the companies need to invest but invest in the right idea and people to continue surviving in this fast paced era!

The ‘emotional’ connect in modern management

‘People’ are the main asset for any company or institution, more so for the research and innovation based organizations. Companies which are known to put ‘employees’ in the fore front are found to be more productive, positive and in the long term provide value to not only to its share holders but also to the society in general. 

Two Indian corporate giants HCL Tech and the Tata group are known to have great employee friendly outlook. HCL technologies, the IT sector major, surprised the world when it announced the policy of ‘employee first, customer second’ slogan. The idea is that a happy and may I add a satisfied employee can add more value to the organization than a de-motivated one. I strongly believe, if an employee is made a stake holder in the company’s decision and path it takes or envisions, then it brings the employee much closer to the organizational DNA and its values. 

People have slowly started to realize the power of the ‘emotional quotient’ in managing an institution. Humans are not robots so to expect productivity of a robot from a human is not only undesirable but absurd. Long working hours, expectation of taking work to home, working hard even on weekends may bring good returns in short term but these practices eventually bring about high ‘burn-out’ rates in employees and eventually organizations take a beating in the long run! 

Talented employees always do not work for monetary benefits only. They also look at the way the organization treats its employees. In today’s world of high attrition, many organizations overlook this aspect and focus on other factually incorrect reasons to address this issue. 

This empathetic approach is very important for research driven organizations. Research is a 24X7, 365 days a year affair and requires huge commitment from the scientists. To top it, a high percentage of failed experiments, tougher deadlines and lower employability options burden the researchers. Therefore, to improve productivity, it is important for the managers to harness the‘emotional quotient’ much more and come out with radical shift in the outlook of 'people management'!

Human microbiome – the new frontier in medicine?

‘Antibiotics heal but they also cause damage’- this adage is well known and now probably better understood. With the advent of Next Generation Sequencing (NGS), exploring the world of the micro organisms has become easier. And as they say, ‘truth is stranger than fiction’; the results of such studies are giving some startling facts about the bacteria that co-inhabit our bodies. Like each individual has a unique DNA or fingerprint, it is now being realized that we might have unique microbiome signature!!!!

The microbiota in our body is known to influence our good health. Recent evidence has linked the microbiome with different diseases. In fact, at least one parasitic protozoa - Toxoplasmosis gondii - has been shown to affect behaviour in rats. The protozoa reproduces only in cats, and studies have shown that when mice or rats are infected with it, the protozoan makes them less afraid of cats, and they are, therefore, more likely to be eaten by them.

Understanding microbiome and their interaction not only with their host but also between themselves are giving lot of food for thought in channelling our views of manipulating this micro-ecosystem in our body for desirable results. A case in point here is the role  and benefit of probiotics and as Prof David Relman (one of the pioneers in the field of microbiome research) puts it “The hesitation right now is there aren't a lot of good data. Most clinicians will say, 'I don't personally think it's doing much, but it can't hurt so if you feel better, why not.' I think there may be some real benefits, but I also think we have imprecise probiotic options now. So we're giving these somewhat irrelevant microorganisms to people, and yet they do seem to have some beneficial effects”(source -http://www.sfgate.com/health/article/Sequencing-of-human-microbiome-fills-knowledge-gap-3683156.php)

Therefore now is the right time to make maximum use of the data we derive from studying our microbiota and look at these organisms in a different perspective rather than thinking about them as our “enemies”. Also, I sincerely hope that pharma/biotech and nutraceutical companies collaborate to find better solutions to the diseases that we face today!

Reliable research – Where are we going wrong?

Like any field and probably contrary to beliefs, life in research is very frustrating. The chances of success are minimal. The scientists not only need to worry about the failed experiments but also worry about the peer pressure, the rat race to publish and publish for the sake of getting new grants and also continuance of the old grants. After all a scientist is worth how much grants he has or how many publications he has.

But in doing all this, we as scientific community are doing a great disservice to the field of science. Many of the published articles are either not genuine or are not reproducible. The beauty of research is that an observation in one part of the world can and should be faithfully reproduced anywhere else provided the reagents are of the same quality and of course the experiments are repeated as were done in the original research. However, still, most of the research goes the non-reproducible way!!! Now this is a big blot on the credibility of the scientific research community. The basic research is the template on which newer medicines would be based. And one recent article in Reuters (http://www.reuters.com/article/2012/03/28/us-science-cancer-idUSBRE82R12P20120328) highlights the pitfalls of such a alarming scenario.

There needs to be a mechanism that would and should delink a scientists’ credibility from the number of research articles published otherwise this problem can take a serious turn for the worse!!!!

Predicament of a researcher

Researcher is like an artist, getting pleasure from his creations (discoveries or inventions). And like artists, the researchers at heart are more worried about the theories and pathways rather than the business of it.

However, in this day and age, research needs a lot of capital to start with and to sustain. And in the rush of producing “data”, the real focus shifts from good research to just noise. Thousands of papers are published in as many journals but most of them are not even worth the paper they are printed in.  But in this “kalyuga”, it is important to get the recognition and the grant going hence the odd saga continues.................

When the world economy is going for a spin, who bothers about the research or researchers. People who bring business become more important for an organization. But we all forget, that society, economy and life for that matter is dependent on constant innovation. Science and scientific innovations are making our lives worth living but scientists are the least paid and looked after.

Isn’t it time we realized this folly? Corrective mindsets are need of the hour or else as falling sex ratio in many regions of India is a major problem, soon dearth of people taking up research or scientists leaving research would push India back..............

Diabetes cure - a fresh approach is the need of the hour

We are in the 21^st century. A new millennium and a hope that new discoveries, innovations would help us thwart diseases like cancer, diabetes, schizophrenia etc. Actually, if we leave the mental illness aside for a minute as the science studying mind/brain is pretty nascent; then one would ponder why we are still years if not decades away from finding a credible cure for diseases like cancer, diabetes and HIV! Right now we only treat diseases like diabetes not cure them………………….

Let’s talk about diabetes, type 2 to be precise for a moment. The best medicine for decades to treat (not cure, mind it!) has been metformin. This humble drug has shown tremendous resilience in terms of safety and efficacy and is and probably would be the first line of therapy for years to come!

 The current or upcoming therapies for diabetes mostly revolve around two aspects – a) increasing insulin secretion (sulphonylureas take the cake here) or b) increasing insulin sensitivity (PPARs/metformin etc). Even the new ones like the GLP-1s or DPP-IV inhibitors ultimately increase insulin secretion though independent of glucose concentration (better than sulphonylureas!). But to me these are just like “cosmetic” drugs treating the symptom not the cause and I feel that we have still not properly understood this disease. In this context, I would like to share a new discovery that can change the perception of how we look at type 2 diabetes.  New research has suggested that the development of insulin resistance and type 2 diabetes may be linked to an immune system reaction gone awry. Till now, we have been looking at type 2 diabetes as a metabolic disease and immune system malaise is mostly associated with the other cousin of diabetes , the type 1 diabetes. Now, if the above said observation is indeed found to be credible in subsequent research then it would mean a tremendous paradigm shift in type 2 diabetes research. I guess, this kind of observation/research is the step in the right direction to understand the cause of the disease.

Probably, joining the pieces of the diabetes puzzle through innovative and fresh thinking is the right approach to finding a “cure” for this scourge rather than trying to better the current therapies to “treat” the disease.

Indian Pharma - Generic all the way and innovation out of the way?

India is poising itself to be the new Knowledge superpower. An economy which is dubbed as a knowledge economy with huge asset of English speaking educated people who can take India to the top. However, why is it then that we do not hear or read about any “new” path-breaking drug development from India? We have an estimated close to 20,000 pharma companies employing the “best” scientists/researchers/chemists etc.  In fact last few years have seen a “reverse brain drain” giving India back its lost scientists and researchers. So what pulls us back from innovating?

Well, there are many reasons behind it. But one of the most important reasons is the focus on generics rather than “innovative” research in the Indian pharma industry. It is easy for a pharma company to achieve a better return of investment with very little risk if they invest in generics. Big names like Ranbaxy labs which were into some good “research” completely re-focused themselves into generics business. Most big companies in India spend a penny on innovative research as compared to their western counterparts. This trend, though profitable for pharma may be disastrous for them in the long run and also for the country.

Drug discovery is a 'high risk and high return' business. But most small and medium level pharma being run by business families probably do not understand the importance of innovation. For most, it is how much do they get in return and how fast?!!!! I know of instances when reputed pharma companies recruiting scientists would ask questions like “can you develop XYZ in one year?” or “what do we gain from your academic experience, would it help us get our investment back?”  Questions like these not only show the hollowness of approach but also affect the morale of budding scientists as they also start to think everything in terms of investment and returns without actually thinking about innovation.  I am not in the favor of giving a lifetime deadline or a free run to scientists as well (as happens in most of our Government labs) but want to see a rational approach.

Moreover, unfortunately, we do not yet have the “Venture capital” mindset in drug discovery. Indian Venture capitalists are gung ho about investing in IT but see black when approached for investment in life sciences!!! There are few Indian companies that are trying to change that but they are constantly under undue pressure from their investors, who would have seen other IT start ups booming by the time a biotech/pharma drug discovery start up barely starts walking!!!!!!

In conclusion, penny wise pound foolish approach of Indian pharma industry would be detrimental for the overall growth of this sector in the long run if the mindset and approach is not overhauled!  

Research in Pharma and Government labs - a short sighted approach and greed

Is lifelong chronic therapy for diabetes or other metabolic disorders bane or boon? Well, it depends on which side you are on. For big pharma it is a boon but for patients I would say it is not so good an omen. That brings me to a fundamental question. Are big pharma companies deliberately not being able to find “cure” for such diseases?  Modern science has evolved a lot especially during the last few decades. We are at the realm of finding evidence for dark matter or other theoretical subatomic particles but  we are still far from understanding the how a normal cell functions! There are still some unexplored territory as far as understanding the working of a cell is concerned; forget about human disease or disorders.  So it is not a co-incidence that modern science has yet to provide “cure” for most of the diseases although we have been on the winning side in taking head on some infectious diseases (thanks to antibiotics)!

So, what is the way out? Well, the answer is not that simple. We ought to give rightful importance to basic and applied research equally.  But here comes the negative part. Research means lot of money and it is foolish to leave all basic research on Governments’ shoulders. The Big pharma ought to put in more money into research. I know of many instances where in big pharma companies have good and interesting data generated, but they do not divulge that fearing competition or deem the information useless in terms of financial benefit. Ultimately, this leads to lot of repetitive research and that means lot of money! So ultimately it is the loss to the public. Also, recently many pharma companies have moved out of  research in some disease areas  and that leads to a lot of void; a negative approach of pharma on research in new antibiotics is just a point in case.

Even Government funded labs are poor in their approach towards research. Lot of public money is wasted in the name of basic research.  I think time has come to delve deeper into our conscience as scientists/policy makers in government and in the private sector. Let us work in a collaborative way to understand disease and disorders , otherwise we would have no one but our ‘greed’ to blame