Synthetic Biomarkers – a new buzz word in the area of modern diagnostics

Biomarkers are the Holy Grail for detecting diseases. Natural biomarkers are sought after molecules for effective screening of patients. Biomarkers include detection of proteins, RNA, DNA to now even micro RNAs. However, detection of natural biomarkers is fraught with issues of specificity, feasibility , price etc.

Now, a new set of research is employing the idea of nano-particles conjugated peptides. Since many disease states are characterized by dysregulated protease activity, the synthetic probe acts by stimulating this response thereby releasing the peptides that can be non-invasively detected. The nanoparticle is introduced and allowed to accumulate in diseased tissue where it is cleaved by the overactive proteases. This cleavage releases the peptides into the host’s urine, where it can be detected using either simple ELISA or mass spectrometry. Synthetic biomarkers provide the flexibility, ease and specificity that a modern day diagnostic lab would demand. In fact, promising results have already been observed to monitor liver fibrosis and detect early stage cancer. This noninvasive urinary monitoring could prove applicable to many diseases that feature protease dysregulation, including cancer, atherosclerosis, inflammation, and Alzheimer’s disease and may also detect many of these diseases much earlier than the traditional biomarkers.

  Image - ACS Nano, 2013, 7 (10), pp 9001–9009

The recent news of a paper based assay to detect cancer (colorectal at this point of time) and thrombosis is a very important step in the direction of non-invasive ‘synthetic biomarker’ based diagnostics. This is even more significant for poor countries where population cannot afford high cost diagnostics that might not even be accurate enough for the cost of the assay. Therefore, I believe the field of nano-particles and synthetic biomarkers can be given more encouragement not only from the Government but also from the various aid agencies to improve upon the technology and help bring the products to the market much faster.

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'!

The hub and spoke model – from aviation to pharma

Every idea has its place under the sun. Two industries, pharmaceuticals and aviation which are known to be ‘high risk – high gain’ business are strikingly employing similar practices in order to maximize productivity and profits.

Everyone would agree that both aviation and pharmaceutical businesses require ‘deep pockets’ to start and sustain. Both have long periods of gestation but if run properly then returns can be huge eg. Pfizer, Merck, Emirates etc. 

Let us look at the paradigm shift being brought about by the major aviation companies and pharma giants to improve sustainability of their respective businesses.  In aviation, big players like Etihad, Emirates, Singapore airlines utilize their home base airports of Abu Dhabi, Dubai and Singapore respectively as hubs which then is used to improve/increase traffic. Traffic is brought in from various airports around the world and the hubs provide seamless connectivity options to their respective customers – a typical hub and spoke model!

Similar kind of approach is now being utilized by the pharma giants to increase their R&D productivity. R&D is the base on which any pharma company stands. But with increasing drought of blockbuster drugs coming out from the stable of Merck, Pfizer et al., it has become imperative for them to look for other ‘innovative’ means. The answer- ‘reduce expenditure on internal R&D efforts and create smaller hubs to scout for interesting research done in smaller companies/universities’. The companies feel this would help them to maximize R&D productivity and will be better focused on bringing in a stream of new deals. This is another version of ‘hub and spoke model’. 

There are critics of this approach but with increasing cost burden, lack of nimbleness in the big pharma set up it is probably important to decentralize and open up.

The lost war or is it? – Infections vs Antibiotics

Antibiotics, once hailed as magic bullets for battling infection are now facing serious challenge from their adversaries, the bacteria, which are hitting back with renewed vengeance. A recent case of a patient in New Zealand dying of bacterial infection (Klebsiella pneumonia) which was resistant to all known antibiotics points to an ‘apocalypse’ scenario in the future if corrective measures are not taken. 

So where is the problem? First, the tendency to overprescribe antibiotics for even slightest of infection is a big worry. Alexander Fleming, the father of antibiotics had warned of dangers of antibiotic resistance. In fact, Penicillin-resistant bacteria arrived while the drug was still being given to only a few patients. Another breeding ground for antibiotic resistant bacteria is in their rampant use in farm animals. Unfortunately, for the pharma companies research interest into antibiotics have slowly waned as there are far more profitable drugs to throw money at, since antibiotics are usually single-serve drugs for humans, not long-term treatments. Drugs for chronic conditions tend to be more profitable. And with drug resistance quickly evolving, rendering older antibiotics ineffective, pharma companies have even less incentive to invest in these drugs. However, recent trends suggest that big pharma companies might be reviewing their strategy as Roche has re-entered the arena through a $550 million tie-up with privately held Polyphor, a Swiss company, to develop and commercialize an experimental antibiotic against hospital superbugs. 

The key is to collaborate with Universities and small drug discovery companies that focus on infections as Roche did. Smaller companies are looking at next-generation drugs or in some cases alternative therapies. Some companies for example are looking at bacteriophage therapy. But despite technical successes, these companies face an uphill battle in developing a consistent, approvable product and haven't yet found much commercial validation or attracted much investment. This is where the experience and backing of big pharma companies would help. Another alternate and a newer area of interest is the human microbiome, which can lead to potential commercial therapeutics. Microbiome companies like Seres Health, Vedanta Biosciences and Second Genome are a good bet as far as making the next cut for coming out with a new approach to treating infections are concerned!