Winning the race towards early diagnosis of Parkinson's disease - by a nose!

This week, something that caught my eye was a rather fanciful sounding story about a Scottish woman who can reputedly "smell" Parkinson's disease, which, on the surface, didn't make much sense to me given that it is a disease of the brain. Joy Milne's husband had been diagnosed with the disease in his mid-40s and she had detected a "musky odour" which was new and which persisted until his recent death. 

Although this may not have carried much significance in and of itself, when Joy joined the Parkinson's UK charity for support and to help, she noticed that others afflicted with the disease had the same distinct smell. Although this still sounds extremely subjective and difficult to make any scientific conclusion from, it did remind me of related stories I had read about talented cats or dogs who appear to be able to detect cancer, or even imminent death, as in the case of one special cat called Oscar. 

Although such stories are highly anecdotal and rarely come with any real scientific validation, there appears to be something unique going on, and we do use the acutely sensitive noses of dogs to detect drugs that humans cannot smell, for example. Even though we are distinct species, if certain animals can have a super-sensitive sense of smell, then it's not that big a stretch to imagine that some human animals may have the same gift. Joy Milne felt so sure about the unique smell she associated with Parkinson's that she mentioned it to some British scientists at a presentation, and they took the bait. 

Frankly, devastating CNS diseases such as Parkinson's and Alzheimer's which have no definitive means of early diagnosis, no disease-modifying treatment and barely a hope for a cure, leave scientists basically willing to try any out-of-the-box approach that might make a real difference. Thus it was for scientists at the University of Edinburgh, led by Dr Tilo Kunath, who decided to put Joy's nose to the test. 

They tested her by taking six people with Parkinson's and six without and asking them to wear a T-shirt for a day, then bagging and coding them, and letting Joy get to work on them; rather shockingly, Kunath found that she was accurate in 11/12 cases.There was a discrepancy in only one candidate, a control individual who didn't have the disease, which was verified by the research team. Imagine the lightning bolt that passed through everyone, when, some 8 months later, that "healthy" candidate informed the team he had just been diagnosed with Parkinson's disease?!

So, Joy had been accurate in 12/12 cases, or 100% accuracy in the small test sample. As science fiction as this all sounds, it is worth pointing out that Joy's extraordinary sense of smell is not just linked to Parkinson's disease (which would be unbelievable); rather, she has always been able to smell things that others can't detect. Scientists are taking her very seriously indeed, and in fact, they have extracted those T-shirts to try to isolate the metabolites and molecular signature of the odour that Joy readily detects. 

That all sounds a little bit too easy and too good to be true, but it may well  be the case that as scientists we sometimes (often?!) get way too buried in complexity when working on very complicated diseases, and it can occasionally be something staring us in the face, at the very tip of our nose, that is the solution we have been hunting for - and if that light bulb moment comes from a non-scientist as in this case - great!

The scientists involved now are hopeful that once they resolve the chemical signature at the root of the odour detectable by Joy Milne, it may be possible to simply perform a forehead wipe to detect even the earliest stage of Parkinson's disease onset. To that end, Parkinson's UK have now funded researchers in Edinburgh, Manchester and London who are studying some 200 people with (and without) Parkinson's to try to nail down the key signature that identifies the presence of the disease. 

Katherine Crawford of Parkinson's UK is excited about the possibilities and echoed us all when recently discussing the potential of this advance in early detection of the disease. 

"A simple test for Parkinson's could be life-changing; this study is potential transformational for the lives of people living with Parkinson's. It is an incredibly difficult disease to diagnose. We still effectively diagnose it today the way that Dr. James Parkinson diagnosed it in 1817, which is by observing people and their symptoms." 

I hope that Joy Milne gets the recognition she deserves if this phenomenon leads to significant advances in early diagnosis of Parkinson's, and if I was her, I would want my name on the patent that describes that molecular signature associated with the disease. Sadly, I don't have such an exquisite sense of smell, but I can detect the aroma associated with some 89ºC water bubbling through my new "Torrid Tunisian Temptation" roasted beans, and that's my cue to jump out of bed and attack the day. Have a great Sunday morning, all! :)

The bitterest pill - some are harder to swallow than others!

             

I don't think it was that big of a surprise to hear that capitalism remained very much alive and well at big banking and financial institutions after the crash in 2008/9, and Obama's bailout simply seemed to serve merely as a slap on the wrist and "now get back to work" (making tons of money) after the hullabaloo had died down. Sure, some of the senior personnel in those institutions did get squeezed out, to gloriously wealthy retirements, but they were immediately replaced by the salivatingly hungry next in line whose driving force and raison d'être was and is to also make truckloads of money!

Business as usual in the financial world, and many think that that's not such a bad thing. However, when it comes to healthcare and the pharmaceutical world, people ruthlessly making money at the expense of the vulnerable and the sick is a much more bitter pill to swallow. It has gone on for eons with only the occasional blip along the way, but the appearance of one Martin Shkreli on our evening news TV screens recently caused the bile to build up and basically boil over right on top of the pharmaceutical world in general. 

So who is this guy? Well, a drug-discovering disease-busting titan he is not. In fact he is a 32-year-old former hedge fund manager (surprise, surprise!) who founded a start-up called Turing Pharmaceuticals, which acquired the rights to a 62-year-old drug this past August. What was his first move as CEO and founder of this heretofore unknown start-up? Well, he jacked the price of that decades-old drug (Daraprim) by over 5,000% overnight - from it's previous price of $13.50 per tablet to a skyscraping $750 - and instantly became the most reviled man in America (if not here in Canada too), also overnight! 

A great deal of outrage ensued following this move, and if Shkreli wanted attention and free publicity he got it in bucketloads, and his interviews on early evening American news only caused people to detest him more. Essentially, he displayed few redemptive qualities and came across as an out-and-out capitalist who saw an opportunity to print money, by squeezing the sick dry. A year's treatment with Daraprim went from being an affordable expense to one potentially costing hundreds of thousands of dollars, and this understandably caused a firestorm of controversy. 

One of the most infuriating aspects of this entire story is the lack of any justifiable (and verifiable) reason for this astronomical price hike, other than as a get-rich-quick scheme. It actually seems to have evolved more into a "get-rich-or-die-tryin'" move, typified by the somewhat (in)appropriately named "50 Cent". As much as the media and public piled scorn upon Shkreli and Turing, it wasn't to be long before another elite breed was going to revile him with perhaps greater rancor - we are of course talking about CEOs at other public companies that had been previously accused of having business models based on tax inversions, acquisitions and price-gouging - at the expense of us all. 

The most astute of that elite breed perhaps saw it coming, but even if they didn't, the sudden intrusion of Hilary Clinton into the fray sure got the kindling burning forest-fire bright. All of a sudden the spotlight turned onto a few key players, and that included our very own Montreal-based neighbours,  Valeant Pharmaceuticals, who have been doing very nicely with their Canadian tax inversion HQ and acquire-and-hike business model. In fact, two members of the US Congress wrote to Valeant in August after they acquired two heart drugs (Isuprel and Nitropress) from Marathon Pharmaceuticals and promptly raised their prices by some 500 and 200%, respectively. This was after Marathon themselves had previously quintupled prices following their acquistion of those two drugs!

You get the point, right?! Subsequently to the events above, Valeant's previously defiant CEO, one J. Michael Pearson, has been "invited" to come meet with Congress who have targeted Valeant in their investigation into drug pricing issues, as two recently issued subpoenas involving Valeant attest. In fact, lawmakers have gone as far as directly comparing Pearson to Shkreli himself, which must surely come across as an insult given Pearson's tenure and success at a company that cannot be even vaguely described as a "start-up". 

Having said that, he has had some very controversial and high profile dealings with the inestimable (or inscrutable) Bill Ackman (remember the protracted, hostile and ultimately failed takeover of Allergan?), who is, wait for it, a hedge fund mogul! Coupled to Pearson's clear and undeniable business strategy of acquiring (and price-hiking) assets from other companies, well, there is perhaps some undeniable similarity in the business models of Pearson and Shkreli, if not in their real attitude to the development and/or manipulation of medicines. 

Being put under such scrutiny and squeezed under the lens of governmental microscopes is a considerable burden, and it seems that Pearson senses the times-they-are-a-changing, because in a Q3 results conference call yesterday, Valeant announced that they will increase spending on R&D (something unheard of in recent history!) and decrease their reliance on acquisition of (theoretically) under-priced drugs that merit price hikes! It's obvious that this is not some altruistic decision on Pearson's behalf but rather came due to the mounting pressure to do something to get the lawmakers off his back and out of his back pocket. What happens after the dust settles and the focus moves elsewhere remains to be seen, of course. 

For now, the pressure remains fully on, with another politician and Republican party 2016 presidential candidate, Marco Rubio (Florida), stepping out with further negative commentary on the pharmaceutical industry. It goes without saying that aspiring leaders will say and do almost anything that they feel will garner public support in the run-in to an election, but Mr. Rubio's words in New Hampshire last week will probably haunt a few pharma CEOs in their sleep (or lack thereof) in these turbulent times.

"These companies decide, 'We can get away with charging it, and so because we can, we do'. And it's just pure profiteering. It’s a new issue that’s emerged over the last few years but it’s a significant one, because it threatens to bankrupt our system. It’s a complex issue but it’s one we have to confront."

Drug pricing has become a big ticket issue of late, and all of the US presidential candidates appear to be incorporating it into their campaign list of "must-haves" as they beat the pulpit. But it's not entirely out of the blue, in that the cost of certain anti-virals from Gilead, for example, as well as new PCSK9 biologics from both Amgen and Sanofi-Regeneron, have already seriously raised eyebrows (if not the dead) and shaken the lid off of the vampire's coffin hidden in the price wars dungeon. Sorry, couldn't resist a little Halloween imagery!  

The most interesting point I have seen about all of this recently was the positioning of Martin Shkreli as the whistleblower of the pharmaceutical industry, perhaps by those looking to derive something positive from this sickening (to many) story, or perhaps by friends of Shkreli himself. The Edward Snowden of the pharma world?! He definitely did get the price-hiking issue right onto the dinner tables of sickened (as well as sick) Americans everywhere, but whether he simply got caught emulating the likes of Valeant, or was truly motivated to expose this sorry affair remains totally unclear to this writer - if I was forced to choose, I would dare suggest that the former is way more likely than the latter - he is a proud out-and-out capitalist, after all! ;) 

A ghost appears - out of the blue - and creates a red-hot firestorm!

Scientists often find themselves maligned whenever they appear to be meddling with things better left alone (in the public's opinion) such as cloning, gene editing, stem cell manipulations and embryo biology. The controversy surrounding the mammoth steps being taken in molecular biology of the human genome is considered par for the course to many, but one expects to hear barely a chirp regarding the field of ornithology.

Not so today, with the discovery and first photographic evidence of the magnificent blue, white and orange "ghost" species known as the Guadalcanal moustached kingfisher (Actenoides bougainvillei excelsus); this rare and extremely elusive bird had only been seen twice in recent history, back in 1920 and then again in 1953, but this was the first male ever found and recorded. 

This bird, with it's deep blue feathers and streaks running from its beak to the back of its head (hence the "moustache"), is a species of unquestionable beauty; a beauty which Chris Filardi had been searching for over the past two decades. Filardi is the Director of Pacific programs for the American Museum of Natural History (AMNH) at their Center for Biodiversity and Conservation. Kudos to him for finally running into it - a testament to true scientific dedication and perseverance - which AMNH was quick to announce on social media. 

 

AMNHVerified account‏@AMNH

These are the 1st-ever photos of a male moustached kingfisher! More on this "ghost" species: http://trib.al/YBbdc1U 

His heart must have skipped a beat when he saw this specimen in the trees on Guadalcanal in the Solomon Islands, and while as a scientist I can understand how it must have felt to be seeing one's dream crystallise right in front of one's eyes, his subsequent move to turn that bird quite literally into a specimen has ruffled some serious feathers, even among the scientific community. The euphemism that Filardi chose was that he "collected" it - and we all know what that word really means - which seems to many to be as unusual a decision as the bird itself. 

You finally realise your dreams, and discover your very own (living) philosphoer's stone, and upon finding it, decide then and there to kill it? Filardi described his find as both a "symbol of hope" as well as a "purveyor of possibility", albeit now a dead symbol of hope with zero possibility. Of course, as scientists do, he claims it was "collected" for research purposes, which to many seems to be a convenient excuse. What exactly are we going to learn about the moustached kingfisher species by cutting it open?

There has been quite a bit of outrage expressed at what Filardi did, with one of the most pre-eminent and vocal being Marc Bekoff, Professor Emeritus of Ecology and Evolutionary Biology at the University of Colorado, who said - 

"When will the killing of other animals stop? We need to give this question serious consideration because far too much research and conservation biology is far too bloody and does not need to be".

Filardi's response to that came in an op-ed piece he authored for Audobon entitled "Why I collected a Moustahced Kingfisher" wherein he elaborated that the decision to take the bird was "neither an easy one nor one taken in the spur of the moment". In fact, he claimed that in somewhat of a surprise to him, the environment the birds inhabit in the remote forests of the Solomon Islands ia thriving, and this bird is not regarded as rare, there. 

Team members apparently assessed both the state of the population and the state of its habitat and concluded that taking the male bird would have no impact on survival of the species. How accurate that conclusion may be is at the root of the furore over the sacrifice, which to many comes across as extremely selfish and self-serving, and typical of the arrogance of scientists with their "we know best" attitude. 

I suppose only time will tell whether Filardi truly did something game-changing towards the long-term survival of this beautiful bird and "ghost" species, or whether his act was simply typical of the overzealousness of the stereotypical animal "collector" - a certain American dentist comes to mind as an example of that stereotype, and how reviled it is by animals lovers everywhere. 

What do you think?! These situations always create a very spirited debate among scientists and the public, and occasionally even between scientists and the public, and that can only be a good thing, most of the time. Personally, I find it hard to imagine killing an animal I had been searching for during two decades of my life, especially if upon tough questioning of myself, I had trouble justifying what that killing was going to do for science. But that's just me, and my opinion! 

Think twice before letting the genie out of the bottle!

I watched an interesting Marketplace ("The Gene Genie') this morning about the burgeoning presence of the term "personalised medicine" not only in our daily lexicon, but also in the marketplace itself, with an increasing number of companies offering us the ability to have predictive genotyping performed using our DNA. While this is a remarkable advance from even the fairly recent appearance of the $1000 genome, what is not clear is whether it is really a useful tool - not least because the data is of such a sophisticated nature that your own doctor is probably incapable of drawing any conclusions from it!

The most prevalent of such "DNA kit" companies, and one which recently crept north into Canada, is 23andme, who currently offer the opportunity to view your inherited risk factors for up to 100 health conditions, predict how you may respond to certain medications, and also examine your lineage - all for the apparently low sum of $199 - though in the USA it's half that price at $99! I didn't realise that $1 US is now worth $2 CDN?! There is a key disclaimer included that states that such tests are for "informational purposes only" and are not diagnostic data, but it seems that it doesn't deter people from the thrill of peering into their own chromosomes, or risking the white knuckle-tinged fear resulting from finding out you are 65% likely to have heart disease. 

The guinea pig in the program, Bryce Sage, was subject to tests from various companies - some requiring just saliva, and others requiring blood samples - and given the history of cancer (both sides of the family), CNS disease and depression in his ancestry, he anxiously waited a month for all the results to come in. A deeper dig into his bloodline revealed that a slew of medical indications were possible via his genetics, and this included not only cancer and depression, but also diabetes, obesity, spina bifida, osteoarthritis, cervical dystonia and psoriasis. 

His first results came in from EasyDNA, whose Canadian website was down, rather ironically, as of this morning, He seemed quite perturbed by the first set of results, particularly by his apparent high risk of prostate cancer, and so he delved somewhat tremulously into the other test results. First up was Viaguard, which right from the get-go caused some frustration in that their Accu-Metrics testing did not bring up prostate cancer as a major potential issue. The two tests also differed by a whopping 20% risk in terms of coronary heart disease, which seems inexplicable and certainly perplexed both the individual and the show's host. 

Next up was 23andme, which caused Bryce Sage to face his worst fears in that there were 3 locked reports involving both Alzheimer's and Parkinson's diseases as well as breast cancer. This made some sense in that his mother has had breast cancer and his grandmother suffered from dementia, and so it struck very close to home in his case. Additionally, he personally has a particular fear of CNS disease and dementia. The relief in his demeanour when the unlocked report showed that he had none of the genetic mutations thus far identified for susceptibility to Parkinson's disease was striking, demonstrating one potential upside to such testing. But what if the result had been the opposite?!

Another company involved in the endeavour was Holistic Health International which seemed to create further confusion in that their results were apparently impossible to interpret yet did come with a panoply of supplements which were recommended for him to take, and, no surprise, that company can also supply those supplements. One can easily imagine how vulnerable individuals could be fooled into forking out more cash so as to best insure themselves against future disease, with little or no science backing up that hope. 

Some cautionary words were brought into the equation by Dr. Fritz Roth of the University of Toronto, who stated that "there are no diseases that are completely genetic", and that there are no industry standards even for the terms "high, medium or low risk" that are used to gauge a person's risk for a given disease. He emphasised that mutations are just that, mutations, and the inference of such mutations as likely disease-inducers is far from hard science, and may even be simply guesswork. We are genetics-driven, yes, but it is also our environment and lifestyle that can play a major part in the capacity of a given mutation to be the source of a life-threatening disease, in other words. 

Given the confusion and frustrations evident from the confounding differences in results obtained from the various companies, Marketplace decided to visit the Silicon Valley HQ of the most pre-eminent - 23andme - whose neighbours include Google, EBay and PayPal. Lofty company indeed. Marketplace spoke with Emily Drabant Conley, Director of Business Development (and apparently also their senior research scientist?) at 23andme, whose answers to the questions tabled sounded more like corporate babble than anything remotely helpful or illuminating. In fact, Ms. Conley is not listed on 23andme's website under either "leadership" or "research team", which may explain that. Hopefully host Erica Johnson was able to visit local wine country after her visit to 23andme, to justify that cross-continent flight to California!

Apart from confusing or confounding results from DNA kits, another downside to people ordering their own DNA kits is the privacy issue. Rather surprisingly, there is actually no law protecting an individual's privacy over their genetic testing information, and it can be asked for not only in legal settings, but also by insurance companies and even employers, for example. They are perfectly within their rights to ask you if you have ever had genetic testing, and if so, to share the results. 

In fact, the lack of legislative protection in Canada over such matters has attracted the attention of lawmakers in Ottawa, and Senator James Cowan is extremely concerned about the lack of privacy laws protecting the rights of individuals in this regard, and how best to maintain genetic background and testing as a totally private matter. To wit, he has introduced a Bill (S-201) designed to do just that, and keep the information obtained by individuals such as Bryce Sage away from prying eyes.

Whether Bryce Sage is anymore sage when it comes to his genetics and predisposition to certain diseases is far from clear, but he did seem relieved to apparently not be prone to CNS disease. But whether these kits and such genetic testing really represent an advance in personalised medicine - or is merely another cute Silicon Valley-housed website and app designed to print money - remains to be seen. In fact, they have the potential to raise fears way more than assuage them, in my opinion. 

But given how important environment and lifestyle are to our disease profile, and the proven antioxidant properties of that tasty little molecule known as caffeine, I am pulling on a fleece, and going out onto a sunny Autumnal terrace for a warming mug of my newly sourced Madagascar Morning Magic - it's simply delicious! :)