From "Pharma Bro" to someone's "dude" in an orange jumpsuit? - courtesy of the FBI!

Now then, it is unquestionable that after a rather slow start for many businesses (the older the school, the slower the adoption!), the inclusion of several new marketing tools collectively referred to as "social media" in inbound marketing campaigns has become much more the norm, rather than the exception. Companies everywhere now routinely use Facebook, Twitter, Google (or other) blogs etc. as part and parcel of their efforts to "fill the funnel" and bring customers to them, as opposed to going searching for them. 

Even YouTube, which historically was more of a music source, is now being utilised quite a bit, and I saw more than a few "Christmas cards" from major companies (including big pharma) thanking their clients and partners via an audio-visual greeting housed on YouTube, this year. The evolution of social media from a means to facilitate communication between individuals, into a tool for self-promotion of individuals, all the way to full-blown heavily budgeted components of marketing endeavours of major global companies, has been steady albeit occasionally fraught with difficulty. 

I have gone into such difficulties previously here, or on other blogs I run, but the problems usually arise when the individual makes the mistake of syncing all of their online activities (personal and professional) or when the individual does not fully comprehend the apparently fine (but actually massive) line between an individual's social media versus an organisation's social media presence. If you are going to spout something  risqué or controversial, make sure you do it on your Twitter account, not your company's; and even then - if it's readily visible? - watch out! 

We all know how Hollywood types who previously used the regular media (as well as social media) to get attention and gain notoriety for themselves, suddenly become all holier-than-thou and shocked when the beast turns on them, and comes back to bite them, when payback and feeding times comes along. Just ask Justin Bieber or Lindsay Lohan, among a slew of others. But that's the game, and social media followers quickly become the judge and jury when one steps out of line. Out of the blue, your formerly faithful followers all scream out in shock when you displease them with a major faux pas, and it transfers from social media onto TV screens with blazing speed these days, and everyone gets to see your dirty laundry before you woke up and realised you had any dirty laundry to, well, launder!

This lesson is probably resonating with Martin Shkreli today, after he went from being essentially a total unknown, certainly in pharmaceutical circles, to being a regular news item on major American news networks. Yes, this is the guy who took the helm at Turing Pharmaceuticals this year and glibly hiked the price of Daraprim several thousand-fold, and did so with both great ease and equal contempt for the howling hordes who now knew his name. Shkreli took total advantage of his fifteen minutes, even including taking to social media to spar with bigwigs the likes of Democratic presidency candidates Hilary Clinton and Bernie Sanders. 

The fact that this guy was still under scrutiny from being "let go" at Retrophin in 2014 makes one wonder why he insisted on furthering his high profile social media presence, not least because his questionable use of social media while at Retrophin had been an issue. Ditto their $65M lawsuit against him in late summer this year for alleged "misuse" of company funds. Unless he is as squeaky clean as he claims, it sort of beggars belief why he would draw more attention to himself, not least from two people of whom one is very likely to be the next American president! 

Next up, Shkreli took struggling KaloBios on board, and by rescuing them from imminent liquidation, he becamse the CEO of Turing and KaloBios simultaneously. The KaloBios stock took a hike (up 400%) more or less instantly, and probably everyone involved breathed a huge sigh of relief. In duplicate fashion, Shkreli made no bones about his intention to hike the price of KaloBios' Chagas drug, upon eventual approval by the FDA. Around this time he became oft-referred to as "the most hated man in America" on many news programs, but this is something that seemed to drive him harder, rather than cause much pause for thought. In fact, he oft-referred to himself as "the most eligible bachelor in America"; those two titles when put back-to-back just sort of say it all about this sad story.

This off-the-rails rollercoaster ride was bound to end badly, and it apparently did when Shkreli was arrested in New York on securities fraud, wire fraud and conspiracy charges, a week before Christmas. On Thursday morning, the 17th of December, he was the CEO of two biopharma companies, but by Friday morning, he had resigned from Turing and had been unseated by KaloBios. That's a date that will linger in his mind more poignantly than the 25th of December, I imagine. All of the notoriety (and not the good kind of social media notoriety) he had gained and built during the previous six months or so made him the thorn in the side of much more powerful individuals and groups, and he was asked to pay a price for it. 

There is a lesson for us all in this story, not the least of which is, as much as we might covet the CEOs chair and compensation package, there are pressures and temptations that come along with the celebrity, and we are not all equipped to handle them appropriately. There is a reason why most CEOs have more grey hair and wrinkles than you (or Shkreli) do - they get there based on seasoning, considerable experience and proven track records of success - and they didn't buy their way into the luxury leather armchair, either. 

In Shkreli's case, many had argued that the maturity was just not there, or in fact, that even when allowing for his mere 32 years of age, he was immature beyond even that tender age! In a somewhat incongruous-sounding but definitely hilariously appropriate aside to this story, just prior to his arrest in December, it was revealed that it was Shkreli who had paid as much as $2M for the single-copy collector's edition new album of legendary rap outfit Wu-Tang Clan. This is a whole new area of notoriety, and I guess this would have been a hoot to wheel out onto the coffee table alongside Kurt Cobain's (expired) credit card, when guests came over! The FBI even seemed to buy into the joke, with this hilarious Twitter post: 

FBI New YorkVerified account‏@NewYorkFBI

#Breaking no seizure warrant at the arrest of Martin Shkreli today, which means we didn't seize the Wu-Tang Clan album.

• RETWEETS29,598
• LIKES21,624

Joking aside, here's hoping that 2016 gets things back on track once more, and more legitimate pharma success stories are those that are making the news. However, it seems inevitable that pricing concerns and the apparent inappropriate hiking of drug prices by certain companies in the business are going to receive increased scrutiny in 2016, and I cannot help but feel that the Shkreli name will continue to get mentions due to that. From what we do know of him, that will be some form of comfort to him - whether he hears it in a correctional facility or elsewhere remains to be seen!

Some kind souls see Shkreli as an actual whistleblower in the over-pricing antics of certain pharma companies and their chief executives, but his various shenanigans look much more like a calculated self-promotion campaign that basically understood precisely the effect his various (social) media outbursts would have - i.e. to make him (in)famous. His claim today that the authorities came after him simply because of political pressure due to his historic, histrionic price hikes is just proof positive of what I alluded to above: when it comes to social media and instant fame, be careful what you wish for!

It's definitely "the luck of the Irish" when it comes to corporate tax shenanigans!

Pharmaceutical giant Pfizer recently announced that they had agreed to acquire botox maker Allergan in a true whopper of a megamerger deal - Pfizer offered around $363 a share for a total deal value approaching a staggering $160B - for which even the term "Monopoly money" doesn't do justice! It's the biggest healthcare deal ever and is also the #1 tax inversion reverse merge in history, making the combined company the #1 drugmaker on the planet. 

The newly minted "Phallergan" or "Pfizergan" will be led by Pfizer's Ian Read, who will be Chairman and CEO of the new entity, and not by Allergan head honcho Brett Saunders as had been rumoured for some time; Mr. Saunders will remain as President and COO, and  "will be serving in a very senior role focused on operations and the integration". Having said that, it is widely believed that when Ian Read reaches retirement in 2018, it will be Brett Saunders who will settle into the CEO's chair. 

Mega deals are certainly becoming the norm these days, with for example, the imminent merger of Dow Chemical and legendary DuPont for $130B, but such deals have been evident even in the beer business, vis-a-vis the $108B acquisition of SAB Miller by Anheuser-Busch InBev; even though such deals do irk legislators in terms of potentially being "anti-competitive", it is the tax inversion play that is currently creating a firestorm of controversy, particularly in the embattled pharmaceutical industry.

It's one thing for a Burger King to acquire a Canadian staple like Tim Horton's ($12B US) in order to lower its corporate tax rate, but that's coffee and burgers. It's not quite as serious or life-threatening as disease and drugs, where being seen to be ruthlessly stacking up profits at the expense of the sick and the old leaves a distinctly more bitter taste on the tongue. Bringing in sales in the tens of billions of dollars is one thing (and one which has not inandof itself caused much ruckus), but artificially domiciling an American entity on foreign shores for the sole purpose of tax avoidance is seen as insatiable corporate greed. 

In the case of the Pfizer-Allergan deal, the advantage for New York-based Pfizer is that essentially they become acquired by Dublin-based Allergan, domiciling them in highly desired Ireland, with tax breaks (from their current 25% down to as low as 17%) that will save them many millions per year. Allergan themselves are more of a New Jersey company, operationally, than Irish, but that's all in the game as they say in the trade. Regulators are watching these deals extremely closely and their actions have scared off some from proceeding, e.g. the $55B AbbVie-Shire deal that went south after a move by US Treasury Sevretary Jack Lew to deincentivise tax inversion deals. 

The timing is hardly ideal, what with the current furore involving individuals in the hot seat over pharmaceutical price-gouging, such as J. Michael Pearson of Valeant (themselves a previous tax inversion player) and the globally maligned Martin Shkreli of Turing Pharmaceuticals, among others. The scrutiny such types are receiving from both Congress and the bandwagon-jumping Democratic Presidential candidates (Hilary Clinton and Bernie Sanders) is having an impact on the industry in general, essentially rebranding the pharmaceutical industry as an avarice-laden tax-avoiding moneygrabber. 

So what's the reality? Well, working in the venture capital business, clearly I do not have a problem with corporations making profits (huge or otherwise) from expensive investments in hardcore R&D! That those profits come from sophisticated, safe and effective drugs for treating human disease is another no-brainer. As to the desire to avoid paying taxes to the country those drugs were discovered in, well, that is another thing entirely. But, and it's a big but, if the actions taken by giant corporations to avoid or lower their taxes are legal, then who can blame them?! If we could do it, would we?!

Such corporations employ a whole slew of people to help boost the bottom line, and just as they would not ignore advice from their own legal counsel on a strategic business matter, why would they be expected to not take advantage and profit from tax loopholes suggested to them, when the law actually permits it? The solution is very clear - if governments are not happy with tax inversion deals then they need to get off their backsides and do something about it via new legislation - in the meantime, Barack Obama going as far as to call the activity "unpatriotic" is hardly helpful. 

But it's funny how we hear that term way more in relation to big, bad pharma, than we do for the much more Obama-sanctioned and socially acceptable Facebook, Google or Apple; at one point it was reported that Google was paying a tiny five percent corporate tax rate, due to tax avoidance manoeuvres. But it's no secret (even if it was) that such companies (Facebook and Google in particular) are reputedly in bed with US intelligence-gathering systems, so then I guess it's okay if they pay minimal domestic taxes and have more offshore-stored cash than anyone in history. In the case of Apple, it was recently estimated that of their $200B cash stash, wait for it, as much as $190B is very comfortably stashed, offshore. The numbers say it all. 

Anyway, I think it's also an oversimplification to think of the Pfizer-Allegran deal as strictly a tax inversion play, per se, even if it comes hot on the heels of a failed attempt by Read to acquire AstraZeneca last year, in another (UK) inversion move. There is unquestionable synergy between the two companies' offerings, with Pfizer adding in Allergan brand names such as Botox, Restasis and Namenda onto their considerable roster, which includes Viagra, Lyrica and Lipitor, among many others. Additionally, Pfizer has been rumbling about splitting into two business units for a while now, and this merger would strengthen the argument for an established products unit separated out from their innovative business unit - a decision on that by Read is expected by Q4 2016.

Consolidation of big ticket players and the often-incurred tax benefits is a trend that is causing a lot of controversy in the pharmaceutical business, but it's unlikely to go out of fashion in the near term - I imagine that companies such as Merck (now relegated to #2 in the world) and troubled GSK may well be watching closely and wondering if they could similarly benefit - but if the US Treasury gets its way and enacts new laws in the interim, such megamerger deals may be scuttled. For those that are considering it, the government is watching closely and time may well be running out, so time is indeed very much of the essence!

Bio and Strasbourg felt like the perfect FIT last week!

I have been a little quiet over the last week or two, not least due to the fact that I was out of the country, in Europe, attending the 2015 edition of the BioFIT event which was held in Strasbourg this year. It's a really nice time of year to be in Europe, especially in Strasbourg, home to the biggest and most renowned Christmas market in France. Unfortunately, recent events in France (and elsewhere) caused security issues to be top-of-mind, in total contrast to the meaning and message of Christmas, but that has become more-or-less normal in today's changed world. 

You know, after attending the huge American BIO meeting in Philadelphia this summer, there was something charmingly relaxed about this smaller European version, even if entering the partnering hall felt something like a "deja vu" with the similar set-up! This year's gathering in Strasbourg hosted some 1,100 delegates and 900 companies from 30 countries, and included 70 speakers (of which I was one!) and 8 hosted events, all wrapped up inside a compact two day event. 

As you can see above, there were some pretty heavy duty sponsors and partners supporting this event, which underlines the fact that European life science business development and partnering is alive and well, and makes the trip worthwhile for us in that we can get to sit down with representatives of the European offices of various big pharma we normally meet at BIO in the USA (not forgetting BIO-Europe in Munich!). 

That there was a hunger for partnering at this meeting, even following so soon on the heels of the bigger meeting in Munich merely a month prior, was emphasised by the fact that there were several thousand meeting requests sent by the time the event kicked off. Speaking personally, it was tough to find time to attend (m)any of the plenary sessions due to the back-to-back meetings scheduled in my agenda - but that's a luxurious problem to have!  Apparently, there were over 2,500 one-to-one meetings at the event, which is pretty healthy for a couple of days. 

The various panel sessions were very cleverly housed inisde the partnering area itself, separated from but open to passers-by, which encouraged them to stop and have a listen, and maybe wander in to take a seat and partake of the lively conversation taking place. Our own panel on the funding challenge was most stimulating indeed, and even though we had plenty left to say, the 90 minutes flew by and we had to call it a day so that people could jump on the bus to the Bio party. 

Undoubtedly, either due to the fact that it was in Europe, or further that we were in Strasbourg itself, the pace felt less frenetic and frenzied than other bigger conferences, so it was both relaxing and productive at the same time. Breaks in the middle of the day were set up to maximise mingling and networking, which they did, and with enough time to not have to cut each conversation short so that one could meet others or grab some fresh herring and sauerkraut before they were gone! 

A pretty non-stop 48 hours of partnering it was too, in life science's very own version of speed-dating, with a whole slew of bright, orange-curtained meeting booths along the side, and people rushing out of one to go racing off to another, tablet or phone in hand, and bags slung over their shoulders. We need more baggage for this type of speed-dating, it seems, but life science is serious business and overall the event did nicely facilitate new introductions and no doubt the elaboration of previously established personal and business relationships. 

My only one gripe about the meeting scheduling system would be the apparently random fire that some people approach it with; the idea being to send out as many invites as possible to anyone who seems even vaguely relevant, and see what sticks. Before the event, I declined various invites reluctantly, feeling a little bad for doing so. Closer to the meeting, with my schedule filling up, I was quicker to decline and felt less reluctance to do so. And after racing to a few meetings to be asked "Did I invite you or was it the other way round?" or "I can't remember why I invited you, now!" - well, what can I say? 

I don't really understand why people would invite professional entities to come meet them in a booth with no clear intent, or not even making sure they remember inviting them! Trust me, it is the easiest way to ensure that they won't be accepted by those entities, again, and worse, they have a mark against them. Perhaps in some offices it is enough to show you have a full agenda to justify the trip's expense, but I would rather have a half-full 1-2-1 meeting agenda involving key potential partners plus free time to attend various sessions, than lose time in totally non-productive meetings. 

Lesson learned on that one - decline, decline, decline! After a hard day of partnering and panelling on December 1st, we did get a nice bus ride through old Strasbourg to the Bio party, where a selection of fine Alsatian wines and gourmet munchies were available in various rooms on two floors of a grand old mansion, and it was the perfect way to decompress after the travelling and its accompanying jetlag! A quiet walk by the side of the river back in the direction of the hotel was simply the perfect ending to a great day. 

Congratulations to the entire team @BIOFIT_EVENT for a most enjoyable and very productive time and stay in Strasbourg, and particular thanks to Ramona Pirv-Chicireanu and Claire Lesnik who helped arrange everything prior to my trip and made me feel most welcome and looked after during the event itself. After such royal treament, who knows, maybe I will see everyone again next year?! ;)

To be (decaffeinated) or not to be - that is (no longer) the question - because both work!

After decades of back and forth about the pleasures and perils of our favourite morning imbibation, it finally transpires that science is confirming once and for all that knocking back a few mugs of Joe is rather good for us! That dark, tasty liquid many of us kickstart our day with is not just laced with caffeine, which itself has antioxidant properties, but there are a slew of other beneficial compounds in there as well. 

After a recent spate of news items about the benefits of coffee, for those who drink a few cups of coffee each day comes data from a much more significant study (published yesterday online) suggesting that not only does coffee reduce our risk of Alzheimer's disease, stroke, liver disease, and Type 2 diabetes, but positively impacts our longevity in general. This is not surprising to me, having worked in a biotech company focused on age-dependent diseases - if you impact the aging process itself, then you can slow down the onset of age-dependent diseases - and if those diseases limit one's lifespan, then delaying their onset will lengthen one's life!

Where the matter remains less clear is the quantity of caffeine that is good for us, not least because there are so many variables in both the type of coffee and the brewing process used that comparing your cup of coffee to mine might not be possible. Additionally, and perhaps surprisingly, the authors in this most recent study saw the same benefits between regular and decaffeinated coffee; while this does not mean that caffeine is not beneficial, it clarifies that the major benefit is probably derived from other compounds. 

This could go some of the way to explaining diverging opinions on the benefits of caffeine itself, if measurements were made of just caffeine levels in a beverage, regardless of what other components were involved. The various components in coffee presumably contribute together to the observed benefits, and if caffeine is unusually high then it is possible that things get out of balance, and possible detrimental effects occur. But for those who cannot give up their cup of Joe and who switched to decaffeinated coffee for health reasons, well, it could be that they have unwittingly found their very own fountain of youth!  

The authors involved in this large, ongoing study involving three cohorts and hundreds of thousands of individuals (and substantial follow-up analysis over some 30 years) offer some suggested mechanisms for the observed beneficial effects of coffee. They state that the chlorogenic acid, lignans, quinides, trigonelline and magnesium in coffee contribute to reduce both systemic inflammation and insulin resistance, and this would quite clearly be beneficial for both diabetes and cardiovascular disease. To that end, they detected an association between coffee consumption and reduced risk of total or cause-specific mortality in the population, and that association held for both regular as well as decaffeinated coffee. 

This is in more or less total agreement with an earlier study (hundreds of thousands of people) reported in the New England Journal of Medicine which also proved the association between coffee consumption and longevity. It is clear in the figure below that even one or two cups a day can reduce risk of death by roughly 5%, so even at the lowest "dose" the effect is observed, while those who were between 4-5 cups a day saw the most benefit. In this study, individuals who went beyond the high dose apparently began to see a reversal of the benefits. 

The more recent study seemed to concur that at least there was no added benefit beyond the 5 cups a day mark, if not that it actually began to reverse the benefits observed up to that level of consumption. So it seems that those of us who hit coffee hard first thing and continue through the early morning (I am one of those types!) all the way up to 5-6 cups are probably not doing a whole lot of harm - let's put it that way - and may well be doing a bucket (or mug) load of actual good! 

It is worth pointing out that such studies are observational in nature and while indeed proving an association of coffee drinking with beneficial outcomes, they do not prove a cause-and-effect link between coffee and lack of a disease or increased longevity. But perhaps the most reassuring aspect for us coffee addicts is that the work certainly seems to have put to bed some of the negative press about coffee/caffeine; even if getting to sleep in that bed remains difficult if you overdo it! 

There was one confounder in the analysis and that was the combination of coffee and smoking, which is very popular with many. Not only did the study reiterate the negative effects of smoking, but it was apparent that coffee in no way made up for all of the detrimental effects of smoking, in terms of disease and lifespan, so if you do consume smoke with your caffeine, then you are back at high risk again. There's just nothing positive about smoking, and nothing is going to change that conclusion anytime soon. 

So, the bottom line in 2015 seems to be that not only is regular, moderate coffee consumption not bad for you, it might in actual fact be very good for you, and coffee now firmly establishes itself on the menu of a healthy, balanced, daily diet. It's no longer a bad habit to worry over and try to refrain from, rather it is something that for a change one can smile about. Imagine, we may finally have found something that tastes wonderful and makes us feel great, and yet it is (now) not considered to be something that is bad for us?!

What is the world coming to?! We can now indulge in a formerly "naughty" habit, and potentially live disease-free for longer, and even live longer as a result?! On that note, I was kind of busy this morning and only managed 3 cups of the office Joe, so after dinner tonight I am going to celebrate this news with a small cup of my new killer Kilimanjaro Kenyan blend - that should push my meter into the 4-6 cups range today, ensuring my longevity until at least tomorrow! :)

Sometimes it pays to put the CAR-T before the horse!

                

The term "personalised medicine" is becoming ever more prevalent these days, and it is partciularly relevant in cancer therapy, where increasinly we begin to talk about individual cancers in, well, a very individual way. It's no longer just the fact that a cancer we have heretofore referred to primarily in generic terms (say, breast cancer) is becoming better understood in terms of sub-types of that cancer; but additionally, science is racing ahead in terms of using an individual's own cells as part and parcel of therapy and even a potential cure. 

Cancer immunotherapy is in an explosive growth phase today, one which is trying desperately to keep up with the prevalence and growth of cancer itself. One such avenue of intense investigation is the approach known as "CAR-T" therapy whereby a patient's own immune cells (T-cells) are engineered ex vivo in a laboratory and then reintroduced to the patient with potent new cancer-targeting warhead receptors. One company that is making big news in this regard currently is French biotech, Cellectis, which is starting to edge (race?) ahead of competitors such as Novartis, Kite Pharma and Juno Therapeutics. 

Why? Well, although all of these companies are in clinical development on various CAR-T immunotherapies, the latter three are focused on autologous adoptive cell therapy (ACT), whereby the patient themselves function as the donor. Cellectis on the other hand are utilising the allogeneic or donor approach, whereby the engineered T-cells come from a matched donor rather than the patient. Their UCART system made the news everywhere this week with some spectacular results achieved at the Great Ormond Streert Hospital (GOSH) in London, England. 

The story revolves around a barely 1-year-old baby girl, Layla, who has been in treatment for a very aggressive form of acute lymphoblastic leukemia (ALL) since she was 14 weeks old - after both chemotherapy and a subsequent bone marrow transplant, her cancer had returned - and her parents were told to prepare for the worst as doctors were out of options. In such drastic situations, doctors are becoming more willing to try essentially anything, and so it was that little Layla became the first human on the planet to be treated with the novel experimental treatment of Cellectis. 

The T-cells that were introduced into her system were edited using the TALEN gene-editing tool, which has been in the news alongside analogous techniques using zinc finger nucleases or Crispr/Cas9 as the future of gene-editing therapy in disease. To cut a long story short, these altered T-cells were silenced in terms of attacking Layla's healthy tissue as well as being resistant to a chemotherapeutic, but exhbited potent targeting and cancer-killing properties. The hopes surrounding this last ditch effort to save the little girl's life were massive, and they were massively rewarded with the outcome that just two months later, Layla is now cancer-free and home with her parents! 

"Her leukemia was so aggressive that such a response is almost a miracle. As this was the first time that the treatment had been used, we didn't know if or when it would work, so we were over the moon when it did." said Professor Paul Veys, Director of Bone Marrow Transplant at GOSH who led the team treating Layla.

A miracle seems like the appropriate word when considering that the technology had only ever been tested on rodents in a laboratory, never on a human. But the team at GOSH, working in collaboration with colleagues at UCL and the specialists at Cellectis, got things bang-on and hit the nail square on the head, with no apparent undesired reactions. Experts working on patient-derived T-cell therapies have criticised the allogeneic approach of Cellectis due to graft-vs-host concerns, i.e. the rejection of foreign donor cells by the host, but Cellectis appear to have put such concerns to bed - and not in the bed of their patient!

Cellectis themselves are clearly very excited about this early result, not least because they claim that their approach is both faster and cheaper than single patient-specific gene therapies. Cost is not something we like to worry about when it comes to cancer, but with drug costs already an extremely political issue of late, and various biologics costing hundreds of thousands per course, any alternative that lowers prices will get the attention of payers/reimbursers in the healthcare system. In their press release of last week, Cellectis COO Mathieu Simon stated -

“We expect to accelerate our clinical development of TALEN gene-edited allogeneic CAR-T therapies to further confirm this encouraging clinical proof of concept”.

Naturally, while Cellectis shares did jump in price upon this news, caution is being expressed by the experts involved, not least because it is a one-off success to date. Science requires multiple repeats of key findings before writing them into the annals of modern medicine, but I will bet that if little Layla now moves on to a cancer-free life that most of us and especially her will delight in even this "n" of one. 

“We have only used this treatment on one very strong little girl, and we have to be cautious about claiming that this will be a suitable treatment option for all children. But, this is a landmark in the use of new gene engineering technology and the effects for this child have been staggering.” said Professor Waseem Qasim of the UCL Institute of Child Health and a consultant immunologist at GOSH.

We are keeping a very close eye on such developments at AmorChem, because we have two related programs in our portfolio - one which utilises a modification of the TALEN tool used in Layla's treatment, and the other which is a high-profile  allogeneic immunotherapy approach also utilising donor T-cells to attack patient cancer cells - and so the success obtained in the GOSH treatment is very encouraging indeed!  

In 2015 - even "bringing home the bacon" is now a bad thing?

You know, as explosive a life as it has become in terms of mind-blowing new technology, instant global communication, and wild scientific/medical advances, I cannot help but feel that it used to be so much easier living in ignorant bliss. As in, living in ignorant bliss, rather than the non-stop and currently in vogue fussing over dying. People used to be able to live without all of the pulpit-hammering non-stop proselytising about how we are killing ourselves by living thereby facing imminent condemnation and death.

No, I am not talking about the Catholic church, though it sure sounds like it, but am instead referring to the never-ending barrage of information and lists shoved at us documenting how most of the things we enjoy are bad for us and will one day kill us. We mustn't smoke, we shouldn't go out in the sun, we best not drink, we cannot eat anything that tastes even remotely amazing, and even with all that, if we don't get off our backsides and run them up that hill, well, we are still going to die! 

I mean, how did people make it past even 50 in the good old bad old days, given how uninformed and under-educated they all were? Well, the answer is of course that people generally didn't live as long (and that may be not be such a bad thing for society), but I am not sure it was just the bad habits that caused that because it is largely modern medicine (and not the elimination of our bad habits) that today allows people to survive the cardiac disease and certain cancers with which bad habits are linked. 

As if life hasn't become unbearable enough, with us being informed that we should become greens-eating fat-free sugar-averse salt-detesting sun-intolerant slim, albino robots - we now hear the ultimate salt-in-the-wound claim that one of the most beloved foods on the planet, bacon, is a sure-fire killer that must be avoided at all costs! Are you kidding me?! On top of all the other nasty things we must cut out of our life, ruthlessly, bacon has now been added and may even be top of the list along with cigarettes?!

What?! Beam me up Scotty, or take me now, Jesus, depending on your preference! Yep, in a recent new report by the World Health Organisation (WHO), the agency announced that bacon, sausages, hot dogs and maybe even burgers, were as carcinogenic as cigarettes, which on the surface sounded like some grandstanding headline pulled from "Vegetarian Weekly" or some other hysterical rag. The shocking thing is - they are serious. 

It seems that processed meats in general, and bacon and sausage in particular, are laced with potent potential carcinogens that can be aligned with the likes of toxins such as asbestos or even arsenic, when it comes to ties to certain classes of cancer. Holy smokes! No, make that unholy smokes! Red meat in general appears to be quite evil, but if one simply must indulge in its sinful pleasures, then it's best to partake of fresh red meat; this has considerably less salt, fat and chemicals in it, and so is less toxic to us humans. The guys of "Mountain Men" are probably a lot healthier than us, then, living in part off fresh, unprocessed red meat. 

The cigarette reference definitely hits home when one considers that typically (but of course not exclusively) a majority of smokers who develop lung cancer have smoked for many decades and usually tens of times per day. The WHO implies that someone who eats even close to one sausage per day, increases their chances of getting colon cancer by as much as 20%! In almost hilarious fashion, by means of an alternative, the WHO states to "Eat beans, not meat." Now that's a tempting choice after a hard week's work when it's time for Sunday brunch - "Yeah you know what, I think I will forgo the 'All-American', just bring me the kidney bean cretons and the plain yogurt omelette, thanks!" 

There's been strong reaction from all sides to this life-changing earth-shattering news. Maybe it's a plot by aliens who know the soldiers of the world will never be capable of fighting for and saving the world, without a bellyful of juicy, tasty bacon?! Epidemiologist Tim Key of the University of Oxford did have some words of wisdom for us, published in the UK's Daily Mail newspaper. 

“We’ve known for some time about the probable link between red and processed meat and bowel cancer. You could try having fish for your dinner rather than sausages, or choosing to have a bean salad for lunch over a BLT.”

How lovely. More beans. And I am pretty sure they don't mean Heinz Baked Beans, or Canadian Maple'n'Pork Beans, in a lovely salty, sugary, tomato and pork sauce! Naturally, the meat industry hasn't exactly taken kindly to the WHO report, and are fighting back with the type of vigorous accusations that are once again also reminiscent of the cigarette industry. 

“They tortured the data to ensure a specific outcome; people in countries where the Mediterranean diet is followed, like Spain, Italy and France, have some of the longest lifespans in the world and excellent health.” 

I thought it was us who were to be tortured by not being allowed to eat bacon, but Betsy Booren (VP of Scientific Affairs at the North American Meat Institute) thinks it is the data that were tortured! She did remind one and all however that the nations mentioned above use high amounts of processed meat as part and parcel of the Mediterranean diet, and that is associated with longevity. Ah, but they are allowed to drink red wine by the bucketload, so then as long as we drink red wine, we will all be fine?!

Like everything else in life, the message is of course about moderation. Do a little of a lot of things, and you will probably live, yet will still die. Do none of those things, and you will perhaps live longer, but miserably, yet still die. So why kill ourselves trying to live longer? It's all good. Just like it's all bad. Sugar is bad. Salt is bad. Sun is bad. Smoke is bad. Fat is bad. Alcohol is bad. Red meat is bad. Calories are bad. Even oxygen is bad! But we absolutely must breathe oxygen - even if the reactive oxygen species it produces via normal metabolism is bad  - so we got zero choice on that one. 

I tend to think that if even oxygen is bad (while still being good) for us, then what the hell, suck it in and get on with life. If oxygen leads to ROS production, which is at the heart of the aging process, contributing to both inflammation and disease, and yet we cannot live without it - what are we gonna do? Stop breathing? Go on a quest for another gas that may sustain life? Start swallowing vast quantities of antioxidants which we know don't work clinically? 

We are oxygenated, ROS-producing machines, and it's our several decades of inhaling oxygen and fighting the ROS that produces, which plays a large part in our living, aging and dying. With and without disease. So if getting your hands on a bacon and brown sauce sandwich after running up that hill for thirty minutes gives you a life-affirming and life-sustaining rush of dopamine and endorphins? I say go for it - but maybe just choose multigrain unprocessed bread for the sandwich, and no butter- we can't have it all, and some things are worth dropping if it means a weekly dose of beautiful back bacon! :) 

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! :)

A cleaner crisp(e)r way of editing the code!

We hear so much about CRISPR (discussed in a previous blog) and gene editing these days that it feels like the technique has been around for a decade (or more), and not something relatively unheard of before 2012.  Yet it's still an advance very much in its infancy, and one not without a healthy (no pun intended!) burden of controversy weighing it down. 

The heaviness surrounding the use of the CRISPR-Cas9 system lies in its potential not only to edit and correct disease-causing mutations or defective genes such that we revert to a normal genotype and phenotype, but also due to the fact that the technique may very well be open to "abuse" (or perhaps misuse) by those wishing to alter some part of their non-diseased phenotype. We want our baby to have blonde hair and blue eyes, for example. 

In a striking new development set to make the CRISPR technique an even more disruptive technology, one of the pioneers in the field just published a paper in Cell, yesterday, outlining the discovery of a new nuclease, Cpf1. Feng Zhang of the Broad Institute in Cambridge (MA) felt that as exciting and useful as the CRISPR-Cas9 system is, there was still benefit in seeking to refine it, and refine it he just did.

As technically brilliant as CRISPR editing is, there are a few drawbacks which clearly niggled at Zhang, who returned to the world of bacteria and went hunting for alternates to Cas9.  Having discovered Cpf1 in bacteria, his team isolated Cpf1 from some sixteen different bacterial strains and found two that could cut human DNA.Zhang then went about more fully characterising its properties in comparison to Cas9. 

One reason why Cas9 is not a perfect choice lies in the fact that it needs two guide RNAs to facilitate appropriate cutting of DNA; Cpf1 needs just one. Additionally, Cas9 is a considerably larger protein than Cpf1; coupled to the need for just one guide RNA, this makes Cpf1 easier to package and deliver to cells. Furthermore, and by no means least, Zhang discovered that both the sites of cleavage and their nature were distinct between the two nucleeases; this difference potentially makes the cutting and insertion of DNA by Cpf1 a much more accurate and efficient process - an explosive finding. 

Cas9 cuts both strands of DNA at the same position, leaving the DNA with blunt ends, the repair of which is hard to control and prone to errors. Cpf1 on the other hand leaves sticky end overhangs, which should make it much easier to control the appropriate insertion of the appropriate piece of exogenous DNA into a gene. As explained bu Zhang - "The sticky ends carry information that can direct the insertion of the DNA. It makes the insertion much more controllable" - which can only be a good thing. 

There's an unexpected bonus in all of this, which centres on the ongoing and brutal legal dispute over who-discovered-what in the CRISPR-Cas9 story. The two contenders in this dispute are the Broad Institute of MIT-Harvard (including Zhang et al.) and UC Berkeley, whose Jennifer Doudna is a major player along with her collaborator Emmanuelle Charpentier. In what may be true irony, even though Zhang and the Broad hold 10 patents on the technology, it is Doudna in particular who is often singled out by the media as the discoverer of CRISPR-Cas9. So one of the two sides is clearly winning the patent war and the other is winning most of the credit for the discovery. 

It may all come down to that staple of laboratory life - the lab notebook - given that the Regents of the University of California have asked the USPTO to approve "patent interference" to determine who was the inventor in those 10 patents belonging to Zhang and the Broad. It's going to get messy, almost certainly, and even the commercial end of this story is already messy, with both Zhang and Doudna originally listed as co-founders of Editas Medicine, a Cambridge-based biotech company set up to develop medicines based on the CRISPR system. Doudna has since exited, but not before selling her patent rights to another biotech, the UK's CRISPR Therapeutics, the founder of which is none other than, wait for it, a certain Emmanuelle Charpentier! 

There's gold in them hills, with Editas having raised additional funds totalling $120M in August, and a new player on the scene, Intellia, having raised some $70M in recent weeks. No shocker that Intellia is connected to Berkeley, by the way. But there's a lot more than mere millions at stake here, not least because scientists often care way more about credit, than their line of creidt! Some talking heads are already earmarking Doudna and Charpentier for the Nobel Prize, and you can bet that this rankles Zhang and MIT. 

It's fascinating stuff of course, and full of the passionate competitiveness and resulting drama that is at the heart of groundbreaking scientific discovery. With the recent patent interference request by the Regents of UC, it looks like it may well be a case whose outcome will come with its very own theme tune - "The Winner Takes It All" - because the USPTO is likely to come out squarely on one side or the other. This may just turn out to the scientific equivalent of the OJ Simpson trial and verdict, and you can expect some heavy duty (but non-violent!) fall-out if a severe injustice appears to have been done. 

Well, it's a simply gorgeous late September Saturday afternoon here in Montreal, and so I am off to get a few kilograms of baby back ribs onto the barbecue, smoking, as my trademarked "Belfast Cowboy Fiery Maple Hickory Smoke" sauce bubbles gently on the side. I've got some seriously hungry ranchers coming in later, so I better get to it. That's it for this one, so, until next time! :)