The next step in Life science/medicine!

Biology, like any other stream of modern science has seen great discoveries leading to mind-blowing inventions and a better understanding of disease, disease progression and ‘life’ in general. Great discoveries starting from the discovery of penicillin (in 1928 but actual use started in the 1940s) to advances in stem cells research led to a renaissance in the field of medicine. However, the current technologies and the drug discovery paradigm still leave a lot to be desired in terms of understanding the biology of the healthy and the diseased! So what is missing?

The basic understanding of the life processes has improved and different approaches both “top-down” and “Bottoms-up” viewpoints are being looked into. We have moved ahead with great advances in the hardware side wherein we can now observe single cell in action; we can sequence the whole genome/transcriptome of humans, yet I believe that we are not there where we should have been. What is missing is a holistic approach to understanding the healthy and the diseased. A collaborative effort looking at the broader picture is the need of the hour. Authors like Dr Amit Goswami (Book- The Quantum Doctor) has argued in the favour of an approach that takes into consideration not only the different branches of biology but also includes various aspects of quantum physics and alternate medicine to better understand and deal with disease. This is not a farfetched idea and is doable. Various well reputed thinkers/writers like Dr Roger Penrose, Dr Deepak Chopra have opined that the current thought process of considering the human body and the cellular processes therein as mechanistic sans consciousness is fraught with naivety and therefore a paradigm shift is probably needed!

So what is going to be the next “Eureka” moment in the field of Life sciences? Probably, a holistic approach to understanding life and disease!

Gut Microbiome – Type 2 diabetes association; outcome and possibilities

The phrase ‘my gut feeling’ has got another scientific validation with some new metagenomics studies published recently. After all, it seems that the gut can dictate the potential well being of an individual. A case in point is the latest paper in Nature journal in which the researchers conducted a gut metagenomic study on Chinese patients suffering from type 2 diabetes (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11450.html). Gut microbiome has been in the forefront of research especially after the advent of the Next Generation Sequencing technology. Today, the advancement in the field of development of sequencers and sequencing technology is even challenging the Moore’s law.

Gut microbiome also being called as the “other genome” or human’s “second genome” is implicated in many of the chronic diseases/disorders like obesity, inflammatory bowel disease and even depression so it is natural that with the latest technology in hand the scientists would focus on this in a much more refined manner. The present study finds some interesting facts about the commensals in the gut of Chinese patients suffering from type 2 diabetes. Functional characterization showed that there was a decrease in the level of bacterial chemotaxis, flagellar assembly, butyrate biosynthesis and metabolism of cofactors and vitamins in the gut bacteria of these patients. The researchers also found markers that indicated that the gut environment of a T2Dpatient is one that stimulates bacterial defence mechanisms against oxidative stress. This might be interesting as previous studies have implicated high oxidative stress levels to pre-disposition to type 2 diabetes. Strikingly, the researchers found orthologue markers that suggest that these diabetic patients might have a hostile gut environment. The researchers also found that there is moderate gut bacteria dysbiosis and an increase in several opportunistic pathogens.

The above mentioned salient outcomes of the study raise many exciting questions and possibilities. Does the change in gut microbiome composition a cause or an effect of the disease? Scientists would be addressing this part next with some studies in animals. Can in the future the gut microbiome sequencing be used as a predictive tool? Can modulating the gut microbiome cure such diseases? Can effective research in pro-biotics now fill in the space and fulfill what modern medicines could not achieve so far?

This is a perfect example of how a 21^st century technology has ignited a fresh look at the association of the microbiome with the human health

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!

$1000 genome,$1 M interpretation theme – fact or fiction?

Everyone agrees that sequencing the whole human genome, which was a bottleneck a decade back, is no longer the “rate limiting” step in our endeavor to realize the ultimate goal of ‘personalized medicine’. The main hurdle to achieve the true potential of our genome is to unlock the secret by powerful analysis tools. In other words, the next decade may well be the decade of bioinformatics/bio-IT. Having said that, there is a school of thought that paints an alarming scenario. It envisions that genome interpretation would be very costly and might take the possibility of personalized medicine a bit farther from reality. However, skeptics argue that this is an alarmist viewpoint and this might not be the reality.

The truth, according to me, lies somewhere in between. Yes, there is a huge potential and a gap in  understanding of the genome. In the last few months, dozen start-ups have come up that are looking to exploit this space. So, venture capitalists need to be assured that their investment is in the right domain and would reap benefits in the long run. So, part of this $1M interpretation theme might come from analyzing the future of Bio-IT space. At the same time, a lot of the processes might get automated and streamlined, hence the true figure might come to a much more manageable level. Like any industry, many of the start-ups would fold up if their software do not come to the real expectation of the key stake holders, and I mean not only the bio-IT folks but physicians, geneticists, care givers and ultimately the patients.

Also there is another point that I would like to make – for proper analysis and interpretation, we need proper data, now since the genome sequencing cost is coming down, many clinical trials or even basic research can enroll a high number of subjects. This would ultimately help fine tune the analytical ability of the software to predict diseases or treatment outcomes in a more professional and authoritative way. This would lead to less cluttering of the Bio-IT space with better and authentic Bio-IT tools.

Ultimately, the “final frontier” of personalized medicine is not only about the hardware and the software  looking for answers in isolation but a conjoined effort to understand the human genome.

Inflammasome – Gut microflora link to Metabolic syndrome; A case for metagenomics

Metabolic syndrome so far is attributed to the deregulation of the metabolic processes leading to increase triglycerides, fat, insulin resistance etc. and thereby leading to diabetes mellitus, coronary heart disease and hypertension. Inflammation is also one of the key factors that can cause an onset of metabolic syndrome.

Recently, a new article in Cell Research (a Nature publication) puts a new perspective on the role of gut micro biota as a causative effect in the process of inflammatory response in the liver (http://www.nature.com/cr/journal/vaop/ncurrent/full/cr201255a.html)

The article highlights certain interesting points and hypothesizes that defective inflammasome signaling in the gastro-intestinal tract allows colitogenic microbes to prosper in the colon, and subsequently trigger harmful inflammatory signaling pathways in systemic organs when the gastro-intestinal barrier is breached. The fact that defective inflammasome signalling can skew the gut micro biota towards colitogenic species of the Prevotellaceae family and the candidate phylum TM7 is not only interesting but opens a new dimension on the role of intestinal “niche” environment in regulating the microbiota species and thereby controlling different aspects of well being of humans (though the research highlighted above is in mice).

Role of gut microbes in maintaining robust immune system or even mental health have been reported earlier. In this era of genomics, it is therefore imperative that we use metagenomics to study gut microflora to understand the intestinal “niche” microenvironment. This would help in designing better targeted antibiotics for therapeutical intervention and thereby possible prevention of many of today’s lifestyle diseases!

Personalized Medicine – Ethics Vs Need

In this era of modern genomic tools, it is getting pretty much apparent that we are closing in on a scenario where in the genome of an individual can be sequenced in a matter of few hours. Question 1)– What do we intend to do with it? Question 2)- Sequencing is just one part of the puzzle but do we actually understand the finer details? Now, assuming that the bioinformatics hurdles are taken care of, then with the important data in hand how do we proceed? How much do we disclose to the patients? How much should the physicians or relatives know? Well, in other words it is the ethics versus need debate. Recent article in American medical news throws some light on this (http://www.ama-assn.org/amednews/2012/04/02/hll20402.htm)

Step towards personalized medicine is not only about the hardware/software part of it but also it is about proper training at physician, geneticists and lab scientists’ level. First is to have a meaningful understanding of the data which can be made ‘easy to understand’ for the care giver (physicians). Then comes the question of what sort of data should be discussed with the patient and their relatives. This is a tricky scenario as unless we as scientific community is absolutely clear of the data and the predisposition risks therefore, I guess it would not be good idea to share such info with patients as they would be upset and would get scared. 

There is a section in the community that believes that family history of the patients should be looked into and only diseases which a patient is predisposed to should be looked into in detail. I would presume it is a thought in the right direction; however, it defeats the whole purpose of whole genome sequencing. Also, as our genome stores a treasure trove of data, it is important to know what else we are predisposed to apart from what our family history suggests! Another ethical issue which might crop up in the near future is that people may want to see the ‘genome map’ of a prospective partner before marriage to avoid getting genetic diseases in the offspring. Now, this might be good but it might lead to all sort of complications and less randomization of the gene pool!!!

Finally, if the people are made more aware, whole genome sequencing, in the future would let us take preventive measures knowing what is in store for us (not astrologically but genetically) and be better prepared for any eventuality.

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!!!!