Is obesity 'curable'?
WRITTEN BY: Ella Copeland
New research has discovered the existence of a complex communication system made up of hormones and neurons in the stomach, which has been established as our potential ‘largest endocrine system’. In the last decade, scientists at Imperial College London have discovered that our stomach, rather than being simply muscular, actually contains a very specific and sophisticated system that communicates to our brain when we are full, and when we are hungry.
Obese patients, interestingly, have very low levels of a hormone called Ghrelin, which communicates to the brain when we are hungry. The potential underlying reason for continued obesity, however, could be due to very low rates of a hormone called PYY, which communicates to us when we are full.
Dr Alexander Miras, MRC Clinical Research Fellow from Imperial College London explained: “The PYY is mainly produced by the small bowel, and the Ghrelin is produced by the stomach. What we know about these hormones is that in the context of obesity, Ghrelin is low, but PYY is also low, and PYY is the fullness hormone so it makes you full after you eat. Therefore, if it is low you need more food to make you feel full.”
Operations such as a Gastric Bypass that combat obesity actually help to regulate the hormone PYY, which makes you feel fuller quicker, as opposed to physically restricting the amount you eat. Instead, it moves the stomach closer to the small bowel, which produces PYY.
“We suspect that one of the major mechanisms through which gastric bypass works is through changing your physiology, so when someone eats after a gastric bypass PYY increases dramatically and much more compared to a normal weight person” said Dr Miras.
Due to these discoveries, Miras believes that those that are already obese will struggle to lose weight through dieting: “Diet and exercise is useful number one in preventing obesity. If you are obese, unfortunately diet and exercise have got very limited effectiveness. So if you are obese, the best someone can do is to maintain your weight through diet and exercise.”
He has also discovered that diets high in protein (such as meat, fish and cheese) can stimulate production of PYY, making you feel fuller quicker. This can help to reduce weight, as PYY production makes you want to eat less.
Miras stresses, however, that low levels of PYY are not the cause of obesity, and he has yet to discover whether it could be a contributor to becoming obese: “I don’t have enough evidence to tell if this is the cause of obesity. We know that it happens in obesity, but we don’t know if it is because of obesity yet, or if it is contributing to obesity. If it were to be causing weight gain, it would just be one of the contributors, because there are many other physiological, environmental, genetic, neuronal systems that affect appetite and weight gain.”
So, what is the next step? Scientists are now looking to find new hormones in the stomach, in order to potentially discover more hormones that can aid and regulate weight loss. The next area of research is likely to be into bile acid, which is produced by the liver. Bile acid is believed to play an important role in appetite regulation and the control of diabetes. There is also the potential to change or block signals to the brain in order to control when we feel hungry: “We know that bile and other gut hormones act through nerves that signal to the brain, so finding out how this takes place and blocking or replacing these signals we can cause weight loss. We may even be able to act directly on the brain by understanding the mediators that effect not only hunger and fullness but also the reward areas in the brain as well” said Dr Miras.
Future studies hope to find out the early signs of obesity, predicting what begins the process of weight gain and what environmental factors contribute to the condition. Miras hopes to conduct research on younger children to find out how these hormones develop into adulthood. He hopes to eventually be able to treat obesity without having to perform surgery, but administering tablets to increase PYY levels.
The challenges to vaccine distribution affecting everyone
While it is comforting to know that vaccines against COVID-19 are showing remarkable efficacy, the world still faces intractable challenges with vaccine distribution. Specifically, the sheer number of vaccines required and the complexity of global supply chains are sure to present problems we have neither experienced nor even imagined.
Current projections estimate that we could need 12-15 billion doses of vaccine, but the largest vaccine manufacturers produce less than half this volume in a year. To understand the scale of the problem, imagine stacking one billion pennies – you would have a stack that is 950 miles high. Now, think of that times ten. This is a massive problem that one nation can’t solve alone.
Even if we have a vaccine – can we make enough? Based on current projections, Pfizer expects to produce up to 1.3 billion doses this year. Moderna is working to expand its capacity to one billion units this year. Serum Institute of India, the world’s largest vaccine producer, is likely to produce 60% of the 3 billion doses committed by AstraZeneca, Johnson & Johnson and Sanofi. This leaves us about 7 billion doses short.
Expanding vaccine production for most regions in the world is complicated and time-consuming. Unlike many traditional manufacturing operations that can expand relatively quickly and with limited regulation, pharmaceutical production must meet current good manufacturing practice (CGMP) guidelines. So, not only does it take time to transition from R&D to commercial manufacturing, but it could also take an additional six months to achieve CGMP certification.
The problem becomes even more complex when considering the co-products required. Glass vials and syringes are just two of the most essential co-products needed to produce a vaccine. Last year, before COVID-19, global demand for glass vials was 12 billion. Even if it is safe to dispense ten doses per vial, there is certain to be significant pressure on world supply of the materials needed to package and distribute a vaccine.
It is imperative drug manufacturers and their raw material suppliers have clear visibility of production plans and raw material availability if there is any hope of optimizing scarce resources and maximising production yield.
It is widely known by now that temperature is a critical factor for the COVID-19 vaccine. Even the regions with the most developed logistics infrastructures and resources needed to support a cold-chain network are sure to struggle with distribution.
For the United States alone, State and local health agencies have determined distribution costs will exceed $8.4 billion, including $3 billion for workforce recruitment and training; $1.2 billion for cold-chain, $1 billion vaccination sites and $0.5 billion IT upgrades.
The complexity of the problem increases further when considering countries such as India that do not have cold-chain logistics networks that meet vaccine requirements. Despite India’s network of 28,000 cold-chain units, none are capable of transporting vaccines below -25°Celsius. While India’s Serum Institute has licensed to manufacture AstraZeneca’s vaccine, which can reportedly be stored in standard refrigerated environments, even a regular vaccine cold chain poses major challenges.
Furthermore, security will undoubtedly become a significant concern that global authorities must address with a coordinated solution. According to the Pharmaceutical Security Institute, theft and counterfeiting of pharmaceutical products rose nearly 70% over the past five years. As with any valuable and scarce product, counterfeits will emerge. Suppliers and producers are actively working on innovative approaches to limit black-market interference. Corning, for example, is equipping vials with black-light verification to curb counterfeiting.
Clearly, this is a global problem that will require an unprecedented level of collaboration and coordination.
Disconnected information systems
While it is unreasonable to expect every country around the world will suddenly adopt a standard technology that would provide immediate, accurate and available information for everyone, it is not unreasonable to think that we can align on a standard taxonomy that can serve as a Rosetta Stone for collaboration.
A shared view of the situation (inventory, raw materials, delivery, defects) will provide every nation with the necessary information to make life-saving decisions, such as resource pooling, stock allocations and population coverage.
By allowing one central authority, such as the World Health Organization, to organize and align global leaders to a single collaboration standard, such as GS1, and a standard sharing protocol, such as DSCSA, then every supply chain participant will have the ability to predict, plan and execute in a way that maximises global health.
Political influence and social equality
As if we don’t have enough stress and churn in today’s geopolitical environment, we must now include the challenge of “vaccine nationalism.” While this might not appear to be a supply chain problem, per se, it is a critical challenge that will hinge on supply chain capabilities.
In response to the critical supply issues the world experienced with SARS-CoV-2, the World Health Organization, Gavi, the Vaccine Alliance and the Coalition for Epidemic Preparedness Innovations (CEPI) formed Covax: a coalition dedicated to equitable distribution of 2 billion doses of approved vaccines to its 172 member countries. Covax is currently facilitating a purchasing pool and has made commitments to buy massive quantities of approved vaccines when they become available.
However, several political powerhouse countries, such as the United States and Russia, are not participating. Instead, they are striking bilateral deals with drug manufacturers – essentially, competing with the rest of the world to secure a national supply. Allocating scarce resources is never easy, but when availability could mean the difference between life and death, it becomes almost impossible.
Global production, distribution and social equality present dependent yet conflicting realities that will demand global supply chains provide complete transparency and an immutable chain of custody imperative to vaccine distribution.
The technology is available today – we just need to use it. We have the ability to track every batch, pallet, box, vile and dose along the supply chain. We have the ability to know with absolute certainty that the vaccine is approved, where and when it was manufactured, how it was handled and whether it was compromised at any point in the supply chain. Modern blockchain technologies should be applied so that every nation, institution, regulator, doctor and patient can have confidence in knowing that they are making an impact in eradicating COVID-19.