On Saturday 7th January, 2018, one of the world’s largest pharmaceutical companies – Pfizer – announced that it was abandoning research efforts focused on finding new drugs for Alzheimer’s and Parkinson’s.
Naturally, the Parkinson’s and Alzheimer’s communities reacted with disappointment to the news, viewing it as a demoralising tragedy. And there was genuine concern that other pharmaceutical companies would follow suit in the wake of this decision.
Those fears, however, are unfounded.
In today’s post we will look at some of the reasons underlying Pfizer’s decision, why our approach to failure is wrong, why Pfizer will definitely be back, and what the Parkinson’s community can do about it all.
1. Our approach to failure
Matthew Syed. Source: Amazon
In the first chapter of his book, Syed makes comparisons between the way the aviation industry and the medical profession approach failure, pointing out the processes that follow situations when a disasters occur. In the aviation industry, when any event occurs there is a major investigative process that starts with the recovery of the black boxes. The aviation industry uses this system of investigation to learn from every single incident. It makes the information available to all and this helps with re-thinking everything from cockpit ergonomics and design to air traffic controller procedures. Even the airline companies are keen to be seen to be involved in this process of investigation. Failure, while unfortunate, is not shameful or stigmatising, but rather embraced and enlightening.
In addition, Syed points out that when an airline pilot sits down in his/her cockpit, their neck is also on the line if something goes wrong. Thus, it is in their best interest that the flight should be successful. And this is another reason why the aviation industry takes the reporting of failure so seriously. Everyone benefits from learning from previous situations. And all of this comes together with the observation that 2017 was the safest year on record for flying (based on deaths/flights – Source).
Note the downward trend on the orange line (deaths) despite the upward trend on number of flights (grey). Source
Now compare that with the medical profession, which Syed does in the first few pages of his book with a horrific real life case study. When medical incidents occur (and unfortunately they do), there has previously been little in the way of investigation or feedback to improve practice – as Syed outlines in his book. In addition, it is very difficult for members of the public to access any of the information. And this is particularly evident in the setting of clinical trials, where even when drugs are successful in the clinical trial process there is very little actual reporting of results beyond the major media headlines.
That is less than 10%!
And the failure to report clinical trial results has previously put the general public at risk. For example, in 2012 the pharmaceutical company GlaxoSmithKline paid $3 billion after it failed to disclose trial data demonstrating that its antidepressant Paxil was not only no more effective than placebo during their trials, but that it was also linked to increased suicide attempts among teenagers (Source).
Admittedly there are now efforts and policies being put in place to correct this (such as a major change in the rules regarding the reporting of clinical trial results – Click here to read more about this), but the medical profession is still woefully behind the aviation industry in embracing and investigating failure.
‘But medicine is more complicated’ some will say.
Boeing 747-400. Source: FAIB
The Boeing 747-400 has over 6 million parts. That sounds pretty complicated to me. It also contains 171 miles (274 km) of wiring and 5 miles (8 km) of tubing (Source). And while there are contingencies built in (thanks to a process of failure investigation), it is helpful when each of the 6 million parts does exactly what is it supposed to do. Years of feedback on every single system has resulted in better success with regards to passenger safety. And it has also resulted in improvements to the system of reporting, for example as Syed points out that the black box recoding systems are no longer black, they are now pink to help visually locate them better (and they collect a lot more information than they used to as well).
This proactive approach to failure overshadows the strange path that the pharmaceutical company Pfizer took on the 7th January 2018. Their announcement that they were terminating all research focused on finding new drugs for Parkinson’s and Alzheimer’s disease was accompanied by the removal of all of information on their website dealing with the topics of neuroscience – go to their ‘Therapeutic areas‘ page, neuroscience is gone (as if it never actually existed). The one page that still exists for Parkinson’s disease (Click here to see it… before it too disappears), is actually an article borrowed from the Gethealthystayhealthy website. Admittedly you can still search their website for Parkinson’s, and this provides a list of the contact details regarding previous clinical trials (Click here to see those search results), but there is precious little in feedback regarding what happened in any of those trials.
It should be said that Pfizer is not the first pharmaceutical company to removed content from their website following such a decision, but this sort of industry practice only highlights the lack of constructive learning-based feedback that the aviation industry encourages.
To their credit, Pfizer’s has provided an explanation about why they made their decision.
Dr Mikael Dolsten. Source: Twitter
Dr Mikael Dolsten, M.D., Ph.D., President of Pfizer Worldwide Research and Development, outlined in the company’s explanation on the Pfizer website (Click here to read it), that:
“This decision was driven by science; not cost. As the fourth largest investor in pharmaceutical research and development worldwide, we expect limited impact, if any, to our overall investment in R&D as a result of this decision. Our reallocation of funding will allow us to place greater focus on areas where we believe we have the strongest possibility of bringing important therapies and vaccines to patients in the near term.”
This explanation is both reasonable and nonsensical at the same time.
It is reasonable because, yes it is in the best interests of the shareholders for Pfizer to focus on what it believes it does best. However, if the decision is not going to have an material impact on the “overall investment in R&D” then why make it at all? If neurological conditions make up such an inconsequential component of R&D, why not simply continue research on them?
But more importantly:
Why make this decision/announcement in such a public fashion?
Why would any company alienate itself by making such a demoralising decision for a large community that it claims to care for? The share price did not jump in the following days, so there was no financial gain for investors. Why wouldn’t Pfizer just quietly and slowly wind things down and avoid the negative press? As far as public relations disasters go, the Pfizer announcement was exemplary and one can foresee future MBA students using it as a case study in how things should not be done.
If we are going to celebrate the rewards and successes of this industry (for example, Dr Mikael Dolsten was the 2016 winner of the Foundation for the National Institutes of Health award honouring 20 years of support for advancing biomedical research – Source), then we should also embrace the failures and learn as much as we can from them as a community. All the information (minus the sensitive intellectual property) should not be deleted from a company’s website, but rather be made available for scrutiny. Only this way, can we all move forward.
And as the airline industry has demonstrated, this more proactive approach is in everyone’s best interest.
The reality of neurodegenerative clinical trials? Source: Schumpetercentre
The history of drug development for brain-related conditions has thus far been a story of chance and cosmetics.
Many of the drugs that we use for neurological conditions started out their lives as potential treatments for other conditions. For example, the first antipsychotic, called Thorazine, was originally tested as a sedative in the 1950s. It failed as a sedative, but when given to people with schizophrenia it miraculously stopped their hallucinations and the research community was able to notch it up as a break through treatment for psychosis. Similarly, the first antidepressant, called Imipramine, started out being paraded around as an all new type of antipsychotic. It also failed, but clinicians kept on using it when they noticed that it seemed to improve the mood of individuals taking it. While the skilful observations of the clinicians testing the drugs allowed for them to be re-oriented to alternative uses, it was extremely lucky for the companies developing those drugs that they were not costly disasters.
In addition, most of the brain-related, blockbuster drugs of the past have been based on the idea of simply treating symptoms rather than the underlying condition. For example, do you want to make depressed people feel better about themselves? Just juice them up on neurotransmitters like serotonin (most antidepressants). People with Parkinson’s have reduced levels of dopamine? Just boost their dopamine levels (Levodopa). Most antipsychotics work on the simple idea of blocking the dopamine D2 receptor. These rather blunt instrument approaches to ‘solving’ complications associated with the brain, however, do not really address the mechanistic problem associated with the brain. Rather, they just cover them up by reducing the symptoms.
Actually ‘solving’ the complications associated with the brain, like neurodegeneration, has proven to be a very hard task.
Over the last 20 years, the pharmaceutical company Pfizer has funded 99 clinical trials for 24 drugs that were being tested in the treatment of the neurodegenerative condition, Alzheimer’s. Each one of those drugs was touted at some point as a potential game changing ‘blockbuster’ product, that would not only stop this terrible form of dementia but also generate the company billions in much desired profits.
Only one of those 24 drugs was ever approved for clinical use by the US Food and Drug Administration (FDA).
That drug: Donepezil (marketed under the trade name Aricept).
Aricept. Source: Yourlawyer
Donepezil (a acetylcholinesterase inhibitor developed by Eisai, which Pfizer bought the rights to commercialise until July 2022 – source) has shown the ability to improve cognitive functions and behaviour in people with Alzheimer’s, but does not slow or cure the disease (and this drug has also caused some controversy – Click here to read more on that). But Donepezil is one of few outliers in the very large field of Alzheimer’s drugs. Between 2002 to 2012, a total of 244 compounds were tested in clinical trials for Alzheimer’s.
Just 1 of those 244 drugs received FDA approval (that one drug: Memantine).
This translates to a 0.4% success rate for Alzheimer’s drugs during that period (Source), compared with 19% for cancer drugs. To date there have been only five drugs approved by the FDA for use in treating Alzheimer’s (Source), and only four of them remain on the market.
The high rate of failure for experimental Alzheimer’s drugs is extremely discouraging, but it also comes with an enormous monetary cost: these massive clinical trial programmes required for attaining regulatory approval are extremely expensive.
For example, in 2009 Pfizer, Elan, and Johnson & Johnson – three large pharmaceutical companies – teamed up to fund a much-hyped Alzheimer’s drug through the clinical trial process. When the drug – Bapineuzumab (or simply ‘Bapi’) failed crucial phase III trials, the companies collectively wrote off more than $500 million in associated costs (Click here to read more about this).
And remember, Pfizer has done this for 23 different drugs that have all failed.
Like I said: Expensive
A lost cause? Source: Pixabay
The sheer cost of these clinical trial programmes is one of the reasons that some large pharmaceutical companies have no Alzheimer’s projects.
No Parkinson’s projects.
No Huntington’s or motor neuron disease projects.
In fact, nothing to do with brain at all.
For example, the Pharmaceutical company Bayer (the world’s 10th-largest independent biotech company with a market capitalisation of $100 billion) has no drugs for brain-related conditions in clinical trials:
Bayer’s clinical trial pipeline in October 2017. Source: Bayer
The pharmaceutical company Gilead also has no neuroscience-related clinical trials in its pipeline (Source). Even the massive GlaxoSmithKleine has only one “neuroscience’ clinical trial, but that is for a degenerative condition of the eye (IONIS-GSK4-L – Source). The last Alzheimer’s drug that GlaxoSmithKleine was actually developing (called RVT-101/Intepirdine) was sold in December 2014 for $5 million to a company called Axovant Sciences… which was the same biotech company that announced late last year that Intepirdine had failed in a phase III clinical trial for Alzheimer’s (Click here to read more about this). Did GSK dodge a bullet? For an excellent OPEN ACCESS review of the current state of the Alzheimer’s clinical trial pipeline: Click here.
The announcement by Pfizer on the 7th January that it was abandoning research efforts focused on finding new drugs for Alzheimer’s and Parkinson’s was an admission of an inconvenient truth: Brain is hard.
A weak excuse?
“But why, some say, the moon? Why choose this as our goal? And they may well ask why climb the highest mountain? Why, 35 years ago, fly the Atlantic? Why does Rice play Texas?
We choose to go to the moon. We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard, because that goal will serve to organise and measure the best of our energies and skills, because that challenge is one that we are willing to accept, one we are unwilling to postpone, and one which we intend to win, and the others, too”
John F Kennedy, September 12, 1962
JFK. Source: Parade
Say what you like about JFK, but his ‘Moon speech’ at Rice Stadium in 1962 was on the mark. We don’t succeed because we only do easy things. If we only did the easy stuff, we would still be sitting in caves.
It is not a case of doing what we can. The way forward has always been shown to us by people doing what we can’t. Think Elon Musk: everyone said electric cars will never work, and now all of the major car makers are racing to catch up. The space veterans told him that SpaceX would never fly, and now the company is planning to head for Mars.
And this philosophy is particularly apparent in the creatives on the internet who have been changing the way the next generation create and consume content:
Finally snuck a Casey Neistat video into a post!
The research community also embraces this philosophy. Every day new discoveries are being made because we step up to the challenge of trying to do what was previous considered impossible.
Even individuals within the Parkinson’s affected community step up to the plate and attempts to “do what you can’t”:
If Pfizer (or any other pharmaceutic company) choose to only do what is easy, then that is their call. But you have to admit that their choice certainly flies in the face of Charles Pfizer’s original vision to “innovate every day to make the world a healthier place“.
Charles Pfizer (1824 – 1906). Source: Wikipedia
Yes, brain is hard, but that only serve as a rallying cry for those who want to make a difference in the world.
It is not a call to retreat.
3. Pfizer had very limited resources focused on Parkinson’s
If we are completely honest the response to Pfizer’s announcement has been over done, for one very simply reason: Pfizer has never really been very big on Parkinson’s.
In December 2016, Pfizer had 96,500 members of staff across 46 countries. In their announcement on 7th January, Pfizer said that it was dropping about 300 employees in Connecticut and Massachusetts (100 each in Andover, Groton and Cambridge). While the loss of employment for these individuals is unfortunate (rest assured that research scientists are not paid as much as the high flying sales execs), the number of jobs represents only a tiny fraction of the research effort at Pfizer.
The research effort at Pfizer has never really been very focused on neuroscience (and most of their main brain-related drugs were gained by acquisition and not R&D). As of October 2017, Pfizer listed seven experimental neuroscience drugs in Phase 1 or 2 testing (only Tanezumab was in phase III; Source). Now, compare that to the 24 experimental drugs Pfizer had targeting cancer. Four of the brain-related clinical programs were aimed at Alzheimer’s and just one targeted Parkinson’s. The Parkinson’s clinical trial programme was for a drug called PF-06649751 – a dopamine D1 receptor agonist. And this was not going to be a disease modifying drug, nor a novel treatmet (there are already many dopamine D1 receptor agonists available – Click here for a list). Thus, the lost of this particular drug is not the end of the world.
On the NIH ClinicalTrial.gov website (a database of all registered clinical trials), Pfizer had 19 clinical trial registered for Parkinson’s dating back over the last two decades. This might sound like a lot, but 8 of those trials were for just one drug (PF-06669571 which was another dopamine 1 receptor agonist) and 3 other trials were for Sumanirole (a dopamine D2 receptor agonist that the company dropped in 2004, citing “recent studies that failed to sufficiently distinguish Sumanirole from currently available therapies” (Source). Sumanirole was originally developed by Pharmacia & Upjohn, which Pfizer acquired in 2002).
Long story short: Pfizer has never really been very big on Parkinson’s.
And this is evident when you look at some other pharmaceutical companies that are focused on Parkinson’s, such as Merck (which has had 20 clinical trials registered for Parkinson’s), Novartis (23 trials for Parkinson’s), and AbbVie (25 trials for Parkinson’s).
The Parkinson’s (and Alzheimer’s) community has worried, however, that Pfizer’s decision would lead to other large pharmaceutical companies following Pfizer’s lead (not the red faced PR disaster, but by walking away from neurodegenerative research).
But I think (personal opinion here) that this worry is unfounded.
4. Pfizer isn’t stepping away completely, nor for very long
In their announcement, Pfizer did stress that late-stage development programmes for Tanezumab (a monoclonal antibody against nerve growth factor for the treatment for pain which was originally developed by Rinat Laboratories and acquired by Pfizer in 2006) and Lyrica (also known as pregabalin – a chronic pain drug, developed by Parke-Davis and acquired by Pfizer in 2000… anyone else noticing that Pfizer acquires a lot of their drugs?), as well as rare disease programmes in the neuromuscular or neurology area, would continue to be supported.
This is reassuring because:
A.) It means that Pfizer is not stepping away from neuroscience-based clinical trials completely. They are simply stepping away from the conditions that they consider too hard.
B.) The recent decision by the US Government to cut back on the Orphan Drug Designation program in their new tax plan (Click here to read more on this) has not caused a company like Pfizer to walk away from their own rare disease projects.
The United States Capitol. Source: SpotHeroBlog
The company also announced that in lieu of doing actual research in the field of neuroscience, Pfizer would set up a dedicated neuroscience venture fund to support efforts to help advance progress.
“We recognise that neuroscience is an area of tremendous unmet need for patients and we plan to create a dedicated neuroscience venture fund to support continued efforts to advance the field. More details on the fund will be forthcoming this year.”
They were, however, short on details of this new fund (simply saying that there would be more details later in the year).
But Pfizer, like all of the big pharma companies simply can’t afford to walk away from neurodegenerative conditions.
And here’s the business reason why:
The United States spent roughly $259 billion on health care expenses related to Alzheimer’s disease alone in 2017, with Medicare and Medicaid covering about 67 percent of that money (Source). And these expenses are only going to increase as the population ages and the affected community grows.
The projected cost of dementia (note the tiny red bars). Source: UCSF
And this growth rate is a key driver for most pharmaceutical companies in their efforts to provide therapeutic products for conditions like Alzheimer’s.
Total spending on medicines is forecast to reach $1.5 trillion by 2021, up 33% from 2016 levels. But this growth rate is actually down from the recent high growth rates in 2014 and 2015, according to a recent analysis by IQVIA (Source). Medicine spending will grow at a 4% to 7% compound annual growth rate during the next five years (2016–2021), down from the nearly 9% growth level seen in 2014 and 2015.
Neurodegeneration (particularly dementia and Parkinson’s), however, represents a major growth opportunity for the pharmaceutical companies, as growth in other areas of healthcare slows. To ignore this is only going to be detrimental to a company’s long term prospects.
Thus, Pfizer can step away from neurodegeneration and have a breather for a while if they think that a wise move, but they will most definitely be back. They literally don’t have a choice on this matter.
And there is another aspect of this that needs to be appreciated by the affected community.
Throughout this post, I have pointed out that most of Pfizer’s brain-related drugs were gained via acquisition rather than in-house R&D. And Pfizer is not alone in this regard, most of the big pharmas rely on this strategy for new products.
Currently the largest selling pharmaceutical product in the world is a drug called Adalimumab (also called Humira) with annual sales of over US$ 14 billion (Source).
Adalimumab/Humira. Source: Medscape
Adalimumab is a TNF-inhibiting, anti-inflammatory drug that is used to treat a wide range of inflammatory conditions, including rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease. The drug is sold by the pharmaceutical company AbbVie. But Adalimumab was not developed by AbbVie. It was originally discovered during a collaboration between two much smaller biotech companies called BASF Bioresearch Corporation and Cambridge Antibody Technology. The rights to Adalimumab were purchased by the original parent company of AbbVie, called Abbott Laboratories – which was split into two companies in January 2013.
And this is a common theme if you make you way down the list of top selling pharmaceutical products (Click here to see the list). A small biotech finds an interesting compound and tests it to the clinical phase I or II stage and then a larger pharmaceutical company comes in and takes over. If the drug is particularly interesting, the pharmaceutical company will typically buy the smaller biotech outright in order to own the intellectual property, and then take the drug through the larger phase III clinical trials in order to get the product to market. And this is the life cycle that a lot of biotech investors rely on.
And this life cycle is playing out as I write this with news that Parkinson’s focused company Acorda Therapeutics is in take-over talks with neuroscience-focused pharmaceutical company Biogen and UCB (despite the termination of their lead drug Tozadenant for Parkinson’s, Acorda’s inhalable Levodopa product, Inbrija, makes this company very attractive for a neuro-focused pharma seeking innovative new products).
All of this is to say: it is generally not the large pharmaceutical companies that discover the really innovative new products.
They will provide us with new and interesting variations of old products (for example, the diabetic drug Exenatide being turned into Bydureon), but they don’t usually do the major discovery work. Given this situation, companies like Pfizer should be doubly down on neuroscience rather than retreating. There are a host of novel therapeutic approaches being developed by smaller biotech firms that Pfizer should be considering, and planning to provide future variations on rather than shutting down their own neurodegenerative research facilities.
A bit of foresight is required.
5. Addressing the problems
In every problem there is opportunity.
Thus, the question we should be asking ourselves is what can we do to improve this particular situation? It is wrong to rely on the Pharmaceutical companies like Pfizer to invent new therapies. As indicated above, history has demonstrated that the smaller, innovative biotech firms provide the new drugs. We must thus try to increase the chances of success for these pharmaceutical companies at the expensive phase II or III stage of neurodegenerative drug development.
And how exactly do we do that?
My 2 cents (again, personal opinion here) is that we have two problems reducing our chance of success:
- Our approach to understanding the underlying mechanisms of these neurodegenerative conditions is apparently flawed
- Our systems of measuring, assessing and tracking these conditions is woefully inadequate
On the former, as I mentioned early in this post, much of our past success in brain-related research has been due to chance. Thus, we need to increase our amount of luck. How do we do that? We need to do more (“The more throws of the dice, the more chances to win” the casino man said to me). But key to this approach is not having everyone in the research world chasing after the same targets.
And this is particularly apparent in the Alzheimer’s field where currently 60% of Phase III experimental drugs and 100% of Phase II/III therapies in clinical trials are targeting one of just three targets: beta-amyloid, tau or cholinergic pathway proteins. In fact, therapies targeting beta-amyloid alone still make up about one-fifth to one-third of the products in early clinical and preclinical development (Source – this is a really interesting article on this topic). This is crazy. Particularly because thus far all of the beta amyloid therapies tested in clinical trials have failed (click here to read more on this), resulting in a major re-think of our understanding of Alzheimer’s.
All our eggs should not be in just one or a few baskets. We would increase our chances of luck, simply by increasing our number of baskets. And by doing this, we would hopefully also increase the chances of success for the pharmaceutical companies.
But this can not occur in isolation.
Many of the Alzheimer’s/Parkinson’s drug trials that have failed have called for better methods of assessment. And this issue of ‘measuring, assessing and tracking’ is particularly critical at present for the Parkinson’s community. We have multitudes of potential drug treatments lined up and waiting on the side line for clinical testing, plus a wave of potential new targets each year. But the real issue is that we need better methods of individual assessment and monitoring. We can not clinically test all of these novel therapies relying solely on monthly clinical assessments (such as UPDRS) and 12 month brain imagings (DAT-scans). Some of these drugs may have very specific effects which will not picked up by either of these approaches.
In addition, these methods of assessment are not without their own issues. Intra/inter-rater reliability of UPDRS clinical assessments is too debatable to be the primary end point (Click here to read more on this), especially in large phase III trials where multiple research centres involve dozens of clinicians conducting the assessments. And the brain imaging is simply too expensive and specifically localised for large scale tests. Requesting participants to go OFF treatment for 12 hours before brain imaging and travelling to the imaging facility during that time is a lot to ask of individuals.
New objective methods of assessment would be very welcomed by all of the neurodegenerative community.
Could wearable technology help with assessment? Source: Forbes
And this is where the Parkinson’s affected community can play a major role, by suggesting ideas and calling for funding that is specifically focused on tools for monitoring/assessment. The ideas would involve direct consultation with the Parkinson’s community. This is how research efforts around the idea of ‘smelling Parkinson’s’ have arisen – Joy Milne in Scotland stood up at a support group meeting and said “I can smell Parkinson’s” (click here for more on this):
We need to think about really left field ideas.
Blood tests, breath tests, smart phone apps are all currently being tested. We need to think about alternatives (such as smart pills – click here and here to read more on this). And really ‘objective’ approaches are required – rather than ‘subjective’ (“how are you feeling today?”) methods which are difficult to score and quantify. Objective approaches that individuals can not affect or bias via any placebo effect.
The ideal system would involve continuous measurement, while allowing individuals to go about their daily lives.
Have a wee think about it. We’ll come back to this idea at a later date.
In this post I have tried to layout my thoughts not only regarding the Pfizer decision, but also issues that plague the field of clinical trials for neurodegenerative conditions like Parkinson’s. While I have focused much of my fury on Pfizer and their course of action, I have not intended it to be a negative statement on a company that has in the past provided many useful medical treatments. If the company or any readers object to anything I have written or have some constructive ideas regarding the material posted here, they are free to comment below or contact me directly. I would be happy to be corrected on any errors in my thinking or any content in this post. It would be to the benefit of all.
There are two outstanding questions that I haven’t found answers for regarding the Pfizer announcement:
- What the company plans to do with their options on GDNF for Parkinson’s (Click here to read about this)
- What happens to ‘Project BlueSky’ – the collaboration between IBM and Pfizer that was focused on developing new tools for measuring Parkinson’s symptoms/features (in the hope that they could aid future clinical trials – Click here to read more about this).
Efforts have been made to reach out to folks involved with both of these matters, but no responses have been had. If anyone has any information regarding this, please let us know – I for one am very curious.
I think I’m done.
EDITORIAL NOTE: Pfizer and many of the other companies mentioned in this post are publicly traded entities. That said, the material presented on this page should under no circumstances be considered financial advice. None of the material presented here should be considered an endorsement of any company (nor a recommendation to sell/short a particular stock). Any actions taken by the reader based on reading this material is the sole responsibility of the reader. None of the companies mentioned on this post have requested this material to be produced. Nor does the author have any financial interest in any of the companies mentioned. This post has been produced for educational purposes only and the bulk of the opinion provided here are those of the author.
The banner for today’s post was sourced from the Independent