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! :)