Thursday, September 17, 2015

The Best Motivation Ever is One That Gets Someone to Believe In Themselves. What do You Say to a Dying Person? Part 2

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When I got a message from him a few months ago, after a while of him not having responded to my last one... I was so gladdened. 

This guy was terminal. I thought, like many friends I'd made through this blog, he was another one who'd passed... His story was another level of devastating though. His partner, who'd messaged me while he was circling the drain, was also a cancer patient. And he'd died while Aden, who's given me permission to share his name now, was unconscious. Aden had to wake up to that... after a life of abandonment and neglect at the hands of foster carers and this disease too... That was horrible... And when I heard that, at first, as I talked about in this post, I did't know what to say...

But I was doubly glad to get that message. Because in it - he told me that he had a shot at survival! His doctors were convinced by him to take some drastic measures. He wanted to live, and to share his story and help others, despite all his pain, SO BAD that he was willing to go through anything! And I kept him going, sharing funny jokes, amazing videos, being there for him, just talking - anything to keep him smiling.

But a few days ago, after us asking eachother how the other was (the capacity for people to care for others' pain, despite what they're going through themselves, always strikes me),  he messaged me again... this time saying,

"I dont even know if im okay anymore, I dont even know if i really care."
"Whats the point all this?" Why keep trying?

Again I didn't know what to say for a bit. What do you say to a dying man (he still, despite his attempts, would likely still die) when he's got nothing much left to live for?

For a while I agnoized over this... but eventually I decided to do what I'd heard Dr Teo, world leading brain surgeon, founder of the Cure Brain Cancer Foundation and PASSIONATE, REAL Doctor does... I've heard that when he sees patients, with what other doctors have pronounced "inoperable brain cancer" the first thing he says to the patient is "If I operate on you... there's an 80% chance you'll die, right there, on the operating table. If this works though... you'll have another half year of life. Before I operate... I want you to tell me: WHAT ARE YOU GONNA DO WITH THOSE 6 MONTHS?"





When I heard from someone that he'd said that to them... The raw power of that... the sheer will I saw it conferring onto others, struck me. 

Without knowing it... I'd done something similar to others in the past. People going through depression, those who were looking for meaning in life... I'd told them to view their time on this world as a means to something, something most (though not all, I always let them help themselves) found, after talking to me, to be one that ended up leaving others happy. For my own purpose is to try and make this world as good a place as possible... 

What better way of making yourself happy is there, I figure, than making someone else smile. Unlike money, power, fame, or women (or men)... that feeling of making a difference... that could never be taken away from you, or made to seem hollow or meaningless in the long run.

And then I'd told them that they COULD do all those things. That the only thing that limits them is themselves. That, even if they PHYSICALLY, or mentally couldn't do a few of those things right now... they could still do incredible things. And those incredible things, no matter how "tiny" they seemed... were still making incredible ripples to some. And that THAT'S what mattered in the end...

But again... what do you say to a dying person? After a while...
I told him this; " It's horrible what you've been through. And I wish I could do something to take it away, but I know I can't. 

But one thing you do have power over is how much you can take out of your days. And that can still be lots. 
It's not easy to see, especially when there seems no point to all this, especially all you've been through, especially if you're restricted by so many things... But there are some things in this world that are awesome and are beautiful and they are worth living for. The most beautiful of those I find is that of friendship. And that connection people can have to others... it can be awe inspiring. 
Your friends, they're still there for you, right? Even if they're not always able to be there, I'm here - from across the world and happy to talk whenever I can about anything. And I WANT To. As do those friends who may just not know what to say right now." As you reading this know, I didn't for a few days too...
  
"But even if they're not - I found at some points. When going through the most depressing, painful points... that going back to the things that REALLY mattered, the things that are beautiful in their simplicity, made it worthwhile. 
Watching things in nature got me to realise that again. I guess as a fisherman... the interactions everyday things have to eachother got me going. I know you love learning too... About how things work. That fascinates you. And you can still do that! No matter what.
But the thing that really matters is what you're doing right now... your work to make others see what its like. And to make others smile... And THAT my friend is something you can STILL DO!"

And a few days later... I realise now looking back... he wrote this post. Go read it. Go tell him how awesome he is, and wish him luck and well in his recovery from that surgery. Despite all he's going through... he's STILL doing this.  

His words back, I'll always hold dear and treasured. His resolve and determination, will always inspire me. Indeed... it's often thoughts of him, and others I've felt pass... who keep me working on my cure for cancer and to help as many people in this world as I can. 

And he assured me my words were good too... He told me, as part of his message back that "that was inspirational.. that was incredible.... I think i might do something like that.... And yes, if its no problem for you to do that.. if its no trouble, if you would like to.. I wouldnt mind if you linked my blog inside yours"

That's half of what this post is about. These words I've said though could help so many others reading on... Because he also told me that for "so long" he'd been trying to fight off his depression and anxiety. And that "[I'm] Just so bitter now, and i dont want to be...."

He found this courage from what I told him. This is something I wanna tell all of you... 

Life can take so much away from us sometimes. It can make us feel weak, and powerless and incapable of doing anything. And when it does so for so long, when it causes, or when we're already at a point where it feels like our mind is against us... it can seem impossible to get out of. 

But one thing will always be true. No matter how dire situations get... no matter how bad things seem... there will ALWAYS be something still worth going for. And there will ALWAYS be things YOU CAN STILL DO. You can always make an impact in someone's life. You can always take steps to being a better, stronger person. Whether you're stuck behind a desk, at the bottom of the ladder in your firm, not there yet, whether you're trapped in a world that tells you you can't do what you wanna, and have no means of getting past those burdens, or whether you're stuck caring for 3 kids 

And I hope this amazing man, who is lying in a bed somewhere right now, going through the toughest times in life, makes you see that. 

You will ALWAYS have a Second Way of Looking at Things.


Aden's blog - 1 more time: 

Tuesday, September 8, 2015

How I'm Planning to Cure Cancer. My Big Idea.

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Okay, so I've been harping on to my friends/family and other connections I have about this big idea I have to "cure cancer". I've been able to explain it to many close friends, and whenever I get time, I explain the idea and process to doctors, researchers, CEOs, med student, as well as laymen friends, but I guess I realised it'd be good to get it down on paper, in a place that many people can access and understand and possibly give feedback or further ideas on. 


So what is it? Is it REALLY a cure? When could it help me or a family member? 

I want to stress that this is just an idea right now. Though many researchers I've talked to are intrigued and say it's very possible that it could be a solution, it's still just in my head for now. There is evidence and proof of concepts for many integral parts of it though. The key is figuring out the gaps and finishing it off. Which I will do soon.

But before I go onto the cure, he's some background on the idea, and the way this disrupts the entire way we're thinking about finding a cure. 


Why The Cure Hasn't Been Found Yet.


The internet is FILLED with conspiracy theories trying to explain this. How can it be that despite BILLIONS of dollars and DECADES of modern research, WE STILL HAVEN'T FOUND IT? 

IT'S THE EVIL PHARMACEUTICAL COMPANIES AND THE GOVERNMENTS! THEY DON'T WANNA FIND A CURE, BECAUSE IT MAKES SOOOO MUCH MOENY!

Well... Yeah... I mean there could be an unknown treaty, or some gang of evil people we don't, and will never know about buried deep beneath every big, small and starting up pharmaceutical/biotech company and government body in the world that stops them from disclosing it... But though there is merit in the idea that pharmaceuticals won't invest in a drug that won't make money (the thing is they have to, it costs billions of dollars to develop 1 drug, takes 10-12 years to do, for an overall 6% chance that it passes trials. Recovering the money alone would require them to charge obscene amounts for drugs. They have to profit on top of that to exist) and though they are bastardly organisations that bribe doctors and misrepresent, or even commit fraud to get drugs approved for sale, this logic fails under the tiniest of scrutiny because if there WAS one single drug out there that could cure it all, or one single target that all cancers are susceptible too, a company would have made tens of BILLIONS of dollars off it by now



A Ted Talk explaining the volatile nature of drug investment; the base reasons behind it that I explained briefly above, and a pretty simple, radical, but very possible solution that can get MORE investment in clinical trials that get drugs to market!

Why Cancers Are So Hard To Treat. How we're doing it Now.


The thing is... there ISN'T a single pathway that you can attack to cure cancer. There isn't some miracle drug or herb that can absolve, or kill off all cancer cells either... Hell, we shouldn't even be talking about curing cancer - because in truth... cancer is not 1 single disease.


We shouldn't even be calling it "cancer." 
We should be calling them "cancers." 

Cancer occurs when a normal cell in our body gets its DNA, the "code" that's behind every function and thing in our body, damaged, which causes it to mutate in such a way that it starts multiplying, uncontrollably, or that it becomes immortal, and doesn't kill itself, as it should, when damaged, or something like that. When multiple mutations occur simulatenously, or when it's combined with other processes that make it evade, or even adapt, almost evoultionarily, to reject the way the body's immune system, which usually polices for, and kills thousands of potential cancers every day, works, it can become bad enough to threaten our very lives. This is a great resource that outlines these methods - be warned though - it is designed to be understood by medical students, so it can be confusing. YouTube gives a lot of this information pretty well though! Ask me anything you want about cancer, I'll try and answer it (if I don't know, I'll learn!)  

There are billions of "base pairs" in a person's DNA, so many pathways a cell could mutate down if damaged (many of which we don't know), so finding the cure for even ONE particular cancer's SUBTYPE is hard. When you consider that every type of cancer has multiple general pathways by which these mutations generally occur, and that EVERY PERSON'S cancer is different (even 2 people with the same, most specific class of cancer will have slightly different mutations), that every person's response to therapy is different and that EVEN IN EVERY PATIENT, THERE'S NOT 1 SINGLE MUTATION PROFILE - pancreatic cancer patients on average have 26 - meaning that every patient has, effectively, MULTIPLE CANCERS at once - which may or may not respond to the same treatments... it seems nearly impossible to find a miracle, silver bullet for even ONE subcategory of cancer. 

But that's not to say there isn't hope. And that there isn't progress. Childhood cancer survival rates for blood cancers (accounting for 40% of all childhood cancers) has improved from less than 10% surviving beyond 10 years in the 1970s, to over 80% today. Survival rates in adult cancers have similarly followed suit, though not all cancers have as high a survival rate as that today. I know mine didn't. But the overall trends are showing improvement due to the fruits of research. And that is good!

Overall survival of cancer for children IS on the up! Data from England from 1990 to now. 
An essay I wrote on how to translate the fruits of basic research into cures faster! I'm writing a book on this topic of improving the pharmaceutical industry soon too. That essay is a "prelude" to it.

More recently though, as we've learned more about cancers, their genetic/tumour profiles and learnt more about how different cancers with different mutated regions of DNA work and respond to treatment, we've been able to start rolling out more personalised treatments. Personalised in the sense that we can now examine a person's cancer cells, look at what mutations have occurred in it, and, through knowledge gained from either our increased knowledge of the molecular pathways of cancer or clinical trials, prescribe treatments that suit the individual patient

This boost in and of itself is remarkable. And as other areas of cancer and of our genome, and body in general become elucidated, we're gonna get overall better outcomes for cancer patients around the globe. Which is bloody awesome! 

The Regulome Explorer - a genome map that highlights to researchers the connections between different mutation regions (often, mutations down one pathway can affect the expression of other proteins in different, but interrelating pathways) and clinical outcomes too. This kind of specificity is becoming a reality! But, as I learned from talking to leading researchers in the Garvan Institute, Sydney, educating doctors, and patients when talking about whole genomes, on how to interpret these things is another issue altogether. 

Immunotherapy is also an emerging, promising field that promises to improve treatments. It essentially describes any effort to engage a patients' own immune system to fight their cancer. This is done by using various mechanisms to allow a patients' immune system to recognise cancers as invaders (eg: dendritic cell cancer vaccines), using specifically designed, cancer targeting immune system components (eg: monoclonal antibodies and adoptive T cell therapies, which are interesting as they take patients' own white cells and redesign them to be cancer killers) or by decrease cancer cells' own immune-evasion mechanisms, to allow patients' immune systems actually stop, recognise and kill cancer cells (eg: checkpoint inhibitors, polsacchraides; aka magic mushrooms). 

A decent summary of the function of the immune cells I'll be talking about most in my solution latet on, that are used most in immunotherapies. CTL = cytotoxic, or toxic to cells, T lymphocyte (lymphocyte = white cell). The B cell pathway, which I'll talk about later, produces antibodies which can go ahead and kill cells without having to go through complex procedures which recruit other cells to come in and help kill them or require cooperation from cells - cancers don't usually cooperate. 
Dendritic cells are professional antigen presenting cells (which are required to activate T helper cells as seen in the diagram above). As seen below, they can activate the immune system against cancers by marking it a foreign substance which T cells can then respond to. Other immunotherapies and their basic ideas are also featured in this great infographic. TCR = T cell reeptor, which allows T cells to go around and examine, or police for bad cells, which their TCRs can regonise. And MHC, seen in both pictures, is, how presenting cells (in MHCIIs case at least) show T cells something bad is about. 





These immunotherapies, if combined with conventional therapy and surgeries, or even on their own, could increase cancer survival rates hugely into the future! Some go so far as to say it's the future of cancer treatment... But hell, my own bone marrow transplant is a crude - hit 'n' miss version of immunotherapy. And it's been around for decades! They gave me someone else's blood stem cells (a common misconecption by many is that they actually need to take your bone marrow. In truth, the procedure on the donor end is similar to a plasma blood donation in over 90% of cases), which make all the blood cells in your body, including your white cells which comprise your immune sysetem. Hence, after the transplant is complete, I've got someone else's immune system in me, and though we're matched, tiny differences between my immune system and my donors are bound to be present, and his immune system will detect and kill those cancer cells, where mine couldn't. 

Adoptive T cell therapy, with a  twist - it's using the HIV virus to manipulate T cells from the patients'  own body to become targeted to cancers. These T cells are then cultured and popped back into the patient's body. But though it's cool this is happening, can this method be used viably on every patient? That's the conundrum my solution seeks to solve.


Though there's this trend I talked about above of more personalised therapies coming out, they aren't personalised in the sense that it actually gives a patient their own, unique treatment that's targeted to their own, unique cancer cells (which, as we know now, can vary, and hence react different to treatment, immencely). The same goes for many immunotherapies. Though the method in the video above is using the patient's own immune system, it still is DISEASE SPECIFIC. It isn't using a widely appliable methodology, one that can potentially work for multiple cancers because it FOCUSES ON ONLY 1 TARGET. 

There have been other cool ideas that try and combine the personalised approach with immunotherapies. This is one of them. When I saw this announced, I was almost over the moon that someone had been thinking like me (my solution and how I got to it is right in the next section)! Essentially - these guys look at individual patient's cancer cells and the mutations they have at them through cytogenetics/flow cytometry methods, and then use computer analysis to determine which cancer-specific proteins will appear on the surface, or be excreted by cancer cells and cancer cells alone, because you don't want to attack healthy, needed cells, due to cancer's DNA being scrambled (the damage done to the DNA leads to these "tumour specific antigens" - TSAs or "tumour associated antigens" - TAAs being present on cancers). From there, white cells are drawn from the patient's blood, hypersensitized and then exposed to those "Tumour Specific Antigens" (those cancer-specific proteins they found before). T cells will now find these cancers specifically, and go on to induce death in them.  

Awesome! Genius! But very cost intensive - both time and money wise - as it takes weeks to 6 months to analyse patients' samples and then determine tumour specific proteins, and thousands, even tens of thousands, to perform those tests in highly specified labs.  Time is something not every cancer patient has. And money, well, unforunately, the way our world works, if this method can't make money, or show extraordinary results, that can be worth it (because even if governments decide to take the short straw and fund it when a company won't, they still have to justify its expense. Right now, though it has shown promise in SOME patients, it still may not hit later trials, or the market, for its viability. Unless it cures 100% of people, then I'll be happy I was wrong) it may never reach second or third phase trials. 

My Solution: 

A broader way, a method, rather than a single target, to get patients' own immune systems killing off cancer cells is what I'd been trying to come up with for ages. And unlike others, it has to cheap, and viable for patients too. And for a while now, I've had an amazing idea in my head that I've been developing, reading up on, and, it seems almost too good to be true, it may just work! Here it is: 


Okay, so how did I come up with it? I wanted to find a one-size-fits-all solution for cancer. I'd seen and talked to too many other cancer patients who'd suffered, and who'd died to this disease to just sit around and do nothing. But I understood the challenges that came with this, and I understood the nature of our current way of finding treatment options; the ultimate aim - to get approved for use against one disease, was not going to foster that easily. 

I knew about immunotherapies, and how they worked, and was very excited about them. Particularly about the potential to find, and hence provide targets to attack, tumour specific antigens which could then be used as "cancer vaccines" - (I can hear the collective clenching of butcheeks of the anti-vaccers reading on here...) vaccines that aren't the typical preventative ones we get for the flu or other diseases, but ones that introduce a foreign particle into the body to induce an immune response against camcers. 

I saw the work by this research team, who was using information on cancer genome databases to predict how likely a patient would respond to immunotherapies, and contacted them, suggesting, "Why not use those databases to find tumour specific antigens?" To my glee, they were already doing that. 
I then asked, "Well could you then identify common trends between cancers, once you'd found some, check that the immune response you generate against them won't hurt healthy cells, and design tumour vaccines that could be used for multiple subdivisions of cancers in a way that doesn't require individual patients to be tested, and have specific vaccines designed specifically for them?", essentially asking him if they could scale the operations up and look for common links, and correlate the information they had with clinical knowledge of what healthy cells may express. To that, he said that it was theoretically possible, and his team had published 1 article on 1 disease to that tune, but that it hadn't been done til then. Hopefully I ignited a spark in his mind, and hopefully he's gone out and done a bit more of digging because he seemed excited by the idea...

But I remember agreeing with the words of a Leukaemia Foundation researcher I was speaking to on the night I gave this speech, nearly 2 years ago now. "Though I'm working on, and bringing immunotherapy to Austraila, I wish there was a way we could make it apply more widely." 

I also knew that a lot of them failed because they failed to induct donors' immune cells against their own cancers in the first place, or they were too disease specific. Which is why I thought, "Well, why don't we use a patient's OWN cancer cells, harvest them maybe, and find out what their tumour specific antigens are." I thought of how you could possibly do that, and the idea of using inactivated, or killed off cancer cells came to mind after a while. What better way to create a vaccine against something was there than to use the dead version of itself? And it was actually one of my treatments I was getting for GVHD (graft versus host disease),  the major side effect of my bone marrow transplant, that gave me inspiration for what to do next. 

This corner of the board is what I'm talking about.

Extracorporeal photopheresis is the name of that traetment. More detail on it is here (a blog post I did on it). And while I was reading up on it, weighing up whether I should do it or not (though it was non toxic, I find this ironic, because it potentially caused my blindness in my left, and near-miss with blindness in my right eye, it was intrusive), as I always do for any of my treatments, I inevitably came across how they thought it worked. Though they weren't sure yet, the proposed mechanism of action for it was essentially that by taking out the white cells of the body, siphoning them away (which required the insertion of a permanent central line into my jugular vein. You can see how that'd be intrusive) from the blood, and irradiating them under UV light, activated T cells, the ones that were currently attacking me from inside and causing my GVHD (graft versus host disease, the side effect of having someone else's blood stem cells - which produces THEIR white cells, aka immune system, in my body), would "apoptose", or self destruct. As they apoptosed, their membranes, or outside, would "bleb" away, or break apart and wrap around the insides of the cells, allowing for them to be taken up by antigen-presenting cells, mainly dendritic cells, that prime the immune system to recognise from those blebs (which would contain protein particles specific to those T cells attacking me - you coudl almost call them T-cell specific antigens) by gobbling up the T cells that were attacking me from within, and presenting their marker proteins for killing by other T cells in lymph nodes, When memory T cells are also recruited, this kills off T cells attacking me indefinitely.

"This same process could be used for cancer!" I thought. So I rushed away and did my research and found that not too many people were actually thinking down this line. See, prior to this, the idea of using your own, dead cancer cells as vaccines had been tried. Others had gotten as excited as I was by the idea, but they had always failed to do significantly better because it had failed to induce a strong enough immune response, if one at all. But this method, which broke those cells down and allowed antigen presentation of tumour markers to T cells, could! And so I went on to learn more about apoptosis, how it worked, the latest we knew about it (because we don't know everything yet), antigen presentation and the methodology of cancer vaccines before one day I stumbled onto this article. 

People were already doing, essentially my idea! Havesting a mouse's own own tumour cells, killing them off, outside the body, with radiation (which I also was thinking of using, as its cheap, easy and most importantly, it induces apoptosis in cells) and then injecting those apoptosing, blebbing away products back into the body to see if an immune response was generated. And it was. That article focused on the idea that it needed to be BLEBS, not the rest of the dying cell material that inevitably comes with them, that needed to be injected in, and is urging that the results from this warrant further investigation of this in actual leukaemia patients - my very own disease. One phase 1 clinical trial had actually used leukaemic blast cells to do that and 2/4 patients with AML - the most aggressive leukaemia, had responded!!  Only last year too had those papers been published. They probably weren't as I'd thought up my ideas, I realised.  Hell - while writing this, I found that one company was already looking to try these in large scale studies for melanoma and had even produced a video explaining the process! Check it out!


Great, right? My work was done! My idea was coming true!!

But not yet... 

Though it is exciting my idea is already out there, being investigated and being done, the fact is, it's still not helping all patients. Meaning it wasn't the cure, as I thought it could be. There were various things blocking the way. I've made a pact to send the researchers, who may not be aware of the work of others in the field, information about other techniques others were using, or more insights into immunology and dendritic cell vaccines that they hadn't looked at, that they may want to add into methods in the future to increase efficacy. Things such as those I wrote up in this corner of that board. 

One of a few extra things they could do to increase the efficacy of this method. And below - more of this, and the fact that this methodology will work best with other standard, and other newer cancer therapies. Sorry about the bad quality pics. Click for close ups. I'll get a better one when I'm home.




There are many reasons why this method could be failing. I plan on sending these to those researchers soon. Perhaps the cancer cells harvested weren't being apoptosed properly in the first place? Radiation is the methodology used in both of these studies, as well as others that have looked into this idea, but there are other agents around that could induce apoptosis more effectively in cells ex vivo (out of the body). Maybe apoptotic blebs and dendritic cell/antigen presenting cell complexes (antigen-MHCII  complex formed at least) weren't reaching lymph nodes? Ensuring dendritic cell loading of vaccines happened in areas of inflammation or areas where immune system signalling molecules, chemokines, of the right type were being released was vital.  Maybe the wrong version of CD4+, or T helper cells, the ones that respond to antigen presentation, were being produced. TH17 cells have been shown to be several times more immunogenic than TH2 cells and there are different signalling molecules that induce their activation. Maybe these need to be given to patients simultaneously?  

But I also knew one thing. Perhaps this methodology alone was doomed to fail in some people, because of the fact that cancers have many methods of escaping the immune system. Some patients may have cancers with these mutations or adaptations in them. Meaning that with this alone... they'd be doomed. 

How cancer cells evade the immune system. 4 major ways they do. 4 ways for this method to fail.

But. 

I've recently come up with a solution to the next part of the problem. One to help even those patients whose cancers could evade the immune system! Because so far we've been talking solely about inducing a T cell response against cancer. What about the B cells? The other major leukocyte? Why not get them involved? 

I can't believe, looking back, that it took me so long of thinking of this idea. But then again... many great solutions, great businesses, and great cures have come from simple, elegant solutions, from a new way of looking at a problem. The fourth and final corner of my whiteboard goes into what that idea is.


Essentially - it's a way to get patients to get their own, autologous, tumour-specific antibodies to be produced to attack cancers! I'd call it "autologous tumour specific antibody production". Or an "autologous /b cell vaccine". Antibodies, unlike T cells, don't require co-stimulation that can be blocked by cancers, through methods such as those in the video above. They don't have limits on where they can go (at least not as much) due to poor tumour microenvironments adapted to shooing away regular immune cells (antibodies are just glorified proteins in comparison to cells). They can be produced by the body in almost endless amounts, and though B cells do often require T cell costimulation, or T cell independent costimulation to start producing antibodies, these can be stimulated in other ways simultaneously to  allow B cells to produce those vital antibodies. 

How this works? Well to explain it better - when we harvest cells for use for use to induce apoptosis in them and bare the cancer's secret treasure - the Tumor Specific Antigens or Tumour Associated Antigens - that mark them as different, we keep a portion (I say half on the whiteboard, but the real proportion will vary) to use as testers to determine what T cells bind to them. 

There is a chance we could skip the whole apoptosis inducing, tumour cell harvest process altogether and skip to this B cell part if there were a way we could create and mature naive T cells, which haven't been taken out if they're autoreactive (I say naive ones, because they'd be more likely they'd adhere to tumour cells, though thinking about it, it could produce false positives, or 'B cell vaccines' that produce self reactive antibodies which is unsafe - a procedure would be needed to eliminate these in that case. I get ahead of myself, this part of the idea is under formulation as you can see haha), and activate them. But preferentially, the other method will be used, as it produces tumour specific T cells which is vital for the next part. 

The tumour specific T cells that are determined from the responses to tumour cells themselves can also be cloned (T cells can be cloned right now, and the major thing which stops them from being cloned, the lack of stimulation by target cells, isn't an issue in this environment, where we're using the target cells - cancer cells) to isolate clones anyway and reinjected back into a patient, to create a larger adoptive T cell response. Perhaps a reason why the first step fails in many patients is that a large enough response isn't generated. And this may be enough to kill cancers on their own.

What needs to be done then is we run the patients' entire (or a large portion of their entire) T cell/white cell population, after having had the patients' cancer cells being apoptosed, introduced into the body with Dendritic cell adjuvants and allowed time to create ample amounts of tumour-specific T cells, against isolated tumour cells, and see which ones adhere. An apheresis machine, or a "donation" of patient T cells and sending it to a lab capable of doin his, will be required. That bit, seeing if/which T cells adhere, can potentially be monitored robotically, independent of people (as is done in the video below, in what is an amazingly cool project), or it can be done in a more scientific manner which I'm sure I, or one of you, will think up soon (as I'm writing this, I'm realising that we could simply monitor for release of Il5, IL9 or other cytokines they release - depending on what kind of THelper cell attaches, as they release different ones, once they've attached to a target cell. OMG I'VE FOUND IT, a much easier way to do this!), but once it is, the T cell will then have its T cell receptor examined, which will elucidate the antigen that the cancer has as its tumour associated antigen!



Once we know what that tomour specific antigen, or that protein complex that marks them, we can simply inject it into the blood, in an environment where T cells are simultaneously active (which it will be if tumour-specific THelper cells are floating around) or in other circumstances, where other co-stimulators of B cells are present, and get B cells that'll produce antibodies specific to a cancer acting against cancer. From there - you could essentially have a T and B cell, autologous antibody production unit that is specific to one person's cancer!

Holy shit. I may have done it. I may have fucking done it. 

Why this will Work. Why this could Fail. 
The pros and cons and the assumptions I've made.


Pros:

  • This works on A LOT of levels, simulatenously. 
  • This method can be combined with other therapies right now. 
  • It is one that can be applied to a whole bunch of cancers, and initiate immune responses to them. 
  • It is one that can work in poor areas too, if the methodology can be reduced to something easy, and replicable, which I believe it can. 
  • Even if it can't, the costs of this will be minimal in contrast to the cost it takes to treat people with the top of the line, latest cancer drugs right now. 
  • And the fact that part 2 of this will require a machine, which can be commercialised, means it can still make money, and hence, it won't be lost in the latrines of the pharmaceuticals and the patents they've made. 
  • If this doesn't work to cure cancer, the very technique, at least the "second half" involving the removal and immunostimulation of patients' tumour cells, could be used to find targets for cancer drugs in a new manner. 

I can potentially patent this idea. But I don't really care if someone else gets it. If it's someone who doesn't want to do anything with it - I've got all these documents of work stored up in Peddal - an electronic public dating list for files which can prove I got to these conclusions before anyone else did. 

The reason this has kept me up at nights... thinking... are the friends I've lost to this disease. The people I know still suffering because of it. The heartbreak I've seen others go through, and the pain I've gone through myself. 

That's what I want to end. 

For Good. And I hope this can actually do this. But. As my wise old dad says - if you have an idea, put it out there and don't be ashamed, afraid, or scaerd if it gets shot down, because in the end, that will allow you to stand back up next time with a better, more bulletproof idea. So let's do that!

The cons/The Assumptions:

  • It will require specialised labs/equipment to do some of these procedures. Apheresis machines aren't cheap. To run or purchase. (You only need apheresis for part 2 - the B cells - though.) 
  • I'm assuming that analysing T cell receptors as they attach to cancer cells will lead to antigens being found. T cell receptors are slightly different to antigens (proteins/antigens don't necessarily act as ligands to them) so it may take a few shots to find the right antigen. I've read up on it briefly. I'll be looking into it in more detail later.   
  • I'm assuming a lot about the potential for antigens, once they're found, to be converted into antibodies inside the patient. I may be going too many steps ahead, and realise later that it's an easy process that a dumb ol' medical student could've reseaerched. Don't worry, I'll be looking into it. But how a protein or peptide (the patient's own antigen), if found, can be replicated and reinjected back into the patient at levels to initiate a B cell response is, right now, beyond me. Don't worry, I'm looking into it though. 
  • I'm assuming all cancers will have external Tumour Specific Antigens or Tumour Associated Antigens (the difference, TAAs usually refer to antigens secreted by the cancer) that can be targeted by antigens if the entire process works. Of course, combination with other therapies to make tumour microenvironments, for instance, more permeable to the immune system which'll be key to this treatment, will be advocated for; probably required to be honest. 
  • The latter brings about another idea. This assumes a patient's immune system is still intact. That isn't always the case, especially with blood cancer patients. However, with current treatment, in many instances, patients can be brought to a stage where their immune systems are competent. If not, perhaps extracorporeal (outside the body) applications will need to be looked into in more detail too. 
  • There are a lot of steps in this process, where each part could fail. Maybe I need a direct route/plan. 


But if this works... goddamnit... it could be amazing. And I really hope it does.

Sunday, September 6, 2015

Dad. The Jokester. The Savior. The Forgotten One.

Last post:                                     My Story:                                         Next One
Dad. My Forgotten Carer. For best results, and to watch all the videos - read this on the website.
I've talked a lot over the last few weeks and months, and years as well, about how much I'm thankful for my family; my carers. But though I've talked a lot about what my amazing mother has done; her sleeping by my bedside, being there for me, every day of my life, even before diagnosis (no matter how badly I treat her) and though I've dedicated an article to my amazing brother, who also despite all the jokes, the trolls and sometimes abuse I hurl at him, is always the first at my side when I'm screaming out at night in pain; I haven't really talked about my Dad as much. 

I guess it's hard sometimes for men to express one anothers' appreciation for eachother. I'm fine with it... I love the fat bugger, and though I love hearing his dismissive, embarrassed reaction when I sneak in a little "I love you" over the phone, or as he hands me something, I really do mean it. 

One of my favourite Youtubers showing how awkward it can be at times for many Dads to hear those three little words.

So why haven't I thanked him yet? As he rightly deserves? Well... I guess it's harder to describe his role and make it seem really meaningful. Mum - well, she was a MACHINE, the brain, the torso of this movement. Always keeping us going. Keeping us protected in advance, booking appointments, looking after me most of the time; all the while somehow working and keeping the house in order too. Nirav, my brother, the limbs. Since he could drive, in the middle of his last year in high school, he was given the keys and made to dart around Sydney, moving bags of clothes, delivering boxes of food, taking me to appointments, and, more recently, events where I could have fun (when the parents were unable or unwilling); all at the expense of HIS own desires. 

But where would dad stand? What would he be in this, the body section of my life? 

Well... I've got to say. He's been the heart. 

It's not that he doesn't do the practical stuff. Oh no - he's there when we need him most, taking his fair share, often more, of the shifts when I was in hospital, or when I needed to get to an appointment (and couldn't get myself there). He's there for me when I need him too... catching me, both literally, and figuratively, whenever I fell. I still remember the words he said to me one night, when he cradled me, like a baby in bed again, and I asked, I pleaseded softly, "What's the meaning of this all? Why do we live? Why do we do this?" He didn't know it at the time... But I was in severe, clinical depression, struggling to come to terms with the loss of a friend. And it was those words that got me out of it. 

But I'd say the most important, most impactful role in this journey was his relentless quest to keep me smiling. 

And by god he did that part of his job well.


Always making light of any situation. Dad constructs a shrine, with offerings to boot, for himself as he wins Sunday morning tennis (for once). 


When you feel like you're at complete bottom in life... Humour can be a great way to distract you from your troubles. Or even make them feel trivial. And there were MANY instances where he managed to do that.

I remember almost straight after diagnosis, the day after I think, when I was allowed home for the last time before chemo. One of the things you gotta do before you start any (well most) chemos, as a young man at least, is store sperm for the future. Many chemos can leave you temporarily, or even permanently infertile.  

So there I was, still shocked, still in denial, still afraid of what was to come the day after these  scary doctors told me I had a tiny chance of staying alive; a 17 year old, shy, somewhat repressed kid sitting in the middle of this waiting room with 3 or 4 other dudes, holding a small little cup in my hand with my Dad next to me. 

I still remember the weird, slightly disgusted look the receptionist gave me as she handed me the cup. I can still feel the judging eyes of the others in the room as I looked down, avoiding eye contact. In my mind, I was picturing them shaking their heads, muttering, softly, about the sin I was about to commit. 

To be honest, I didn't know what to expect myself. Was I just supposed to awkwardly excuse myself and somehow find the inspiration, amidst all that, to, to put it bluntly, blow a load in a cup? 

But then Dad leaned over and whispered this joke in my ear. 

"The Queen was inspecting London General H0spital one day, when suddenly she noticed a man in his room, masturbating furiously..."

I shook my head slightly, amused. The Usual. Dirty. Dad joke was incoming...

"In shock, she turned to the doctor and asked, 'What the hell is this? How dare he do this in front of ME!'

But the doctor replied. 'Oh no Your Highness, this man has a condition where he produces too much sperm. He needs to release himself every few hours or his organs may fail!' 

The queen nodded, still shaken, and walked further down the ward, and noticed another man in his room, this time, getting a blowjob from a nurse.


'And what's this then?' the Queen said furiously. 


'Same disease. Better insurance.' " 

A typically crass, typically DAD joke, in a typically awkward situation. 
But that one joke eased that tension, and amazingly... it made me  smile. 


That was the first time I'd done that since diagnosis. 

And then with a pat on the backside and a whisper in my ear, "Time to spill it" he left me walking, still embarrassed, still self-conscious, but still, trying to smother a smile, into that room. 


And since then he, and I, as I've learned (some may say, been corrupted) from his antics, have done SO much more. 

If you thought that joke was dirty... you should see some of the chain emails he sends me. He always happens to have a perfectly suited joke f0r any moment. But some of the more spontaneous moments we've shared have been the most hilarious. The ones that made me forget the pain, the ones that got us AND the doctors and nurses laughing, the ones that picked me up. At least half the "Humour in Hospital series" features him - check em out if you still want a laugh after all this. 

But of all of the funny moments over the years, this would have to be on of our favourite, and one of my brother (Nirav)'s least favourite. I'd say it just narrowly trumps the time Dad and I cracked up in the lifts (once we were safe), after smuggling a 40 inch TV into the hospital without anyone noticing
One morning after a doctor's appointment, this was not too long after my second bone marrow transplant in 2013, we got a call from Nirav asking us for Red Rooster, his favourite fast food joint. So we decided to get him some. 


Moral of the story... be careful what you wish for. 





Trollin the bro - What Cancer Patients Do In Their Spare Time #4
So we went out for a hospital appointment and got a text from my bro to get him some Red Rooster.Moral of the story... Be careful what you wish for...We actually picked out red ones for this purpose ahahahaha
Posted by Nikhil Autar on Monday, 9 September 2013
So we went out for a hospital appointment and got a text from my bro to get him some Red Rooster.Moral of the story... Be careful what you wish for...We actually picked out red ones for this purpose ahahahaha
Posted by Nikhil Autar on Monday, 9 September 2013

Poor Nirav was sick at the time, and so keen to get some good food into him, I almost feel bad for doing this looking back. But then I watch it one more time, and see his typical, "I-want-to-be-mad-but-I-can't-believe-they-did-this", smothered smile, and laugh again.


Unfortunately Nirav ends up on the butt end of a lot of our practical jokes...




Trollin the bro - What Cancer Patients Do In Their Spare Time #2
Hey guys - we have a new hammock!!Had...
Posted by Nikhil Autar on Wednesday, 15 May 2013
That was actually an accident. But still, no regrets. For best results - keep your mouse clicking at halfway through that video and replay his face as he gasps over and over again.
Disclaimer... no children were harmed in the making of this production. 


Dad would also keep me busy, and exercising a lot of the time. And part of his job as chief entertainment officer (CEO he calls himself) was to get me out and doing normal stuff. For a long time in my recovery phase, he and I would go watch a movie every Monday night, when the tickets were cheap. He was the one who'd urge me, drag me to start exercising after a chemo of Bone Marrow Tranpslant; starting from me on wobbly feet, only managing to walk laps in the pool, to full blown runs and games of tennis every afternoon. That's nothing when you think about the hours of training he put in with me to prepare me for that amazing 200km ride we did to raise funds for cancer research


But the thing I looked forward to most was when he took us out on the boat to fish. 





What Cancer Patients Do In Their Spare Time #1
Deep sea fishing on a chartered boat!The fish is a morwong (aka sweetlip, deep sea bream) - this was after pulling up other fish and 500g sinkers in 50 - 100m of water all day haha. It's tiring stuff but fun nonetheless!
Posted by Nikhil Autar on Wednesday, 23 January 2013
This was me about a few weeks after the second toughest chemo I'd gotten, a mere month after I had seizures and consequent hallucinations that left me in Intensive Care for 2 weeks, a few weeks before I started work-up for my second transplant. Some would say it's a bit rash to be out on a boat, in the middle of the ocean, then. But hell. Dad's training, juicing (well, he did the whole juice thing for a week before deciding it was too much) and motivation got me to a stage where I was ready for it! 

But of course, not all these moments were flashy. He's not well known for sharing, both on the plate and on the boat.




What cancer patients do in their spare time #6
Sand shark that I caught today =] About 1.2m took 20 mins to pull up.
Posted by Nikhil Autar on Saturday, 25 January 2014
The fish was on MY LINE, and I was pulling it up, but dad thought my hook was "snagged"; stuck on the bottom or on the reef. In his very words, he said "Oh, it is a fish!" before deciding to reel it up for himself, taking all the glory, despite me doing all the hard work in hooking, and getting it off the bottom. To this day, we still argue about whose fish it was. 


C'MON THOUGH - IT WAS ON MY LINE!!!
(I'm sure he has a response to this coming...)

But this was one of those more memorable, one of my most favourite moments. I was cramping, a lot one Sunday morning, and just stuck in the shroud of fear, frustration and gloom that pain brings. Then I hear Bon Jovi playing in the computer room, three sets of walls away, my Dad's voice booming horribly off key over the top. After a while, and a few more '80s classics, (with a few Indian classics throwin in between of course), he barges into my room, ushers me and my sleepy brother into the next one and together he and mum serenade us with karaokes and dances of the latest and greatest Indian Pop. After a few minutes of me complaining about being dragged out of bed, that "my poor muscles were too cramp-prone to sing and dance along", I found myself belting out classics and dancing too. After a while, the playlist turned to one of Dad's favourite songs - Mumford and Son's "Little Lion Man,". As his favourite bit, the long banjo solo, came on, I had the genius idea of drawing a Guitar on his Belly. The rest is history folks.  










What cancer patients do in their spare time #5: popstar dad
What cancer patients do in their spare time #5Drew a guitar on Dad's belly... was not disappointed.#superstar #guitarhero #partylikearockstar
Posted by Nikhil Autar on Saturday, 21 December 2013

He's not perfect. He's had his share of gaffs and failed jokes inbetween. And he is NOTORIOUSLY lazy. "If you want something done, don't nag me, tell me once and it'll be done in 3 - 6 months" is his favourite mantra, to mum's constant irritation. But he, almost single handedly, has been the reason I've been able to smile, and thence been able to help others through this blog over the past few years. 


And I can't thank him enough for it.
I'm surprised I'd forgotten to officially, on here, 'til now. 

But over the last few years, the last 6 months in particular, we've started getting frustrated with eachother. I'm now 2 and a half years post second transplant. This graph that one of my transplant doctors showed me... one that showed that where I was at now was where the people surviving was essentially the same... that I was essentially cancer free FOREVER -  took me out from under my feet...




   
But though my chances of relapse are near zero now... I'm still suffering. The nature of the bone marrow transplant procedure, one that's designed to get another person's immune blood cells, and hence, immune system (as white cells are included in that, and as blood stem cells are found in the bone marrow) being produced inside me to kill off any cancerous bone marrow, means that it can, in 30-70% of cases, have long term effects. Though we're matched perfectly in terms of tissue, there are slight differences between my donor and my immune system still, so his white cells are attacking parts of my body; namely my skin, my muscles/nerves (the probably cause of the cramping) and my liver in a process called Chronic Graft versus Host Disease (cGVHD). 

The chronic nature of that disease, as well as the unexpected, yet all too real, surprise diseases that seem to come my way (a second seizing episode, my left eye being blinded, nearly followed by my right and another, completely different cancer appearing in my rib to name the most serious of those) has made it very frustrating for me, but also for everyone at home. 

I'm supposed to be getting better after all this. Getting back to real life and getting back to being me, right? But for the last few years, I've been unable to get back into study, unable to be independent for months on end (causing me, and my family grief); just unable to get into a constant rhythm as disease after disease and setback after setback came up. 

And somewhere in that time, we began to fight. Over HOW I was approaching my diseases and my life. And one key theme that keeps coming up - Why I won't believe in, and take any alternative medications or try any alternative things to treat, or at least ease my symptoms. It's not that I don't, I understand that many of our medicines came from traditional medicines, that these medicines and techniques may have an effect that hasn't been studied, or can't be studied using modern science, and often say that "I"m happy to try it. Just make sure it's safe and unobtrusive." But he tries to convince me, urges me to "believe in the medicines", and that they work. 


Wheat grass juice. One of the alternative medicines I tried while I was relapsing that failed to live up to its "miracle cure" status...


But I mean, I can't do that. I don't feel I need to. The mindset I used to overcome my whole disease in the first place relied on logic. I'd take a step back, take away all the doubts and fears with questions and analyse the options I had and take the one that seemed most promising. When I was diagnosed, that option was "Go forward, thinking and focusing on the present, what I could control, rather than the past." When I relapsed, and was told I had a tiny chance of survival, that I should consider palliative care, that option was "Look for anything and everything that could help in the literature. Analyse HOW they worked, so I could apply it to my case, and present it to my doctors convincingly, so they did do a second transplant", something only possible with a years' medical knowledge under my belt, something that's probably the reason I'm still here. 

I can't do the same with homeopathic drugs, which have never shown, in any trial, ever to have an effect, nor with meditation, herbs, tinctures or other things no-one really understands. He insists that I should look to others who have been helped by those methods - friends and family who have benefited, and copy their methods. But they haven't had the same disease at the same severity I had, most examples had no correlation with me whatsoever, and one guy who he'd gotten his "research" off for a fruit called soursop (which has been warned to cause peripheral neuropathy and 'Parkinson's like' symptoms, both things which are present in me, which could make the ALTERNATIVE MEDICINE the cause of my horrible cramps) doesn't even SEE most of his patients - he does them online... so he'd have no clue what issues I had. 

The other major point of contention is how I do TOO MUCH for others in my volunteering, blogging and charity activities... But first off... I feel I don't push myself too hard for others; I've realised and understood that to help others, first you need to be healthy yourself, second; that it's given me inlets to so many opportunities and meet so many amazing people, and finally; he doesn't understand that the purpose I've set myself, to try and do my all to help others, is THE THING THAT KEEPS ME GOING when the world seems bleak, when the pain is real, and when there seems nothing worth living for...

But it's the way that this has all been going... the time that it's taken for me to get back to "normal", the other, outside stressors that hang in the air that's made our discussions turn into arguments, turned our tones much more bitter and turned our friendship and mutual respect into begrudging acceptance that we have to co-exist, at times. We've both said horrible things to eachother. Things I wouldn't say to anyone... ever... I've said to him. He's screamed and shouted back things just as bad... 

Don't get me wrong, when things go wrong, he's still there for me, still there to help. The rib crisis a few weeks ago reminded me of that fact. 

But I'd stopped respecting him, his opinions and his thoughts over the last few weeks or months. Years, at some points, if I'm honest. He accuses me of being "egotistical", a "know it all" just like "my doctors"

And to be honest... I have been. The way I treat my parents when they sit in on consultations with me, giving them irritated looks for asking "stupid" questions which are really just honest questions (I know if I was asked to comment on Dad's planning logistics operations, I'd draw a complete blank)... and they way I sneer, and throw death-stares at them when they bring up things infront of the doctor that made me feel foolish and less "doctorly"; alternative medicines or bad health habits I wanted concealed from them, is just obnoxious. The way I act these days when I dismiss Mum (a qualified, high achieving MBA at a high position in a multinational corporation)'s advice when it comes to starting up my own social enterprise to help charities and businesses alike make money; foolish. 

Our prides, something I don't have, or display much outside the family setting, get in the way, and and we end up butting heads over and over again. 

And in the end, it's only hurting us. Causing me to dismiss possibilities and options that may well relieve my cramping and other symptoms. Stopping us from being the good mates we are.


True. But they may still have effects we haven't been able to find yet... and at the very least... things like meditation, deep breathing and reducing meat consumption are just healthy.


So Dad... I'm sorry for being a jackass. An absolute arse and I'm sorry for not respecting you. Because YOU'VE brought me up to be the man with the values and attitude I have today. It's your belief, your teachings - "that you should leave this world in a better state than you left it in" that drives me. It's your philosophy, "that you should always smile at people. Because you never know whose rough day you just made" that I take with me everywhere; to enrich the lives of those around me, as well as mine. It's your sense of humour that compels me to add "that you could never express those sentiments this beautifully" (as your effective writing skills are nowhere near as good as mine. This bit is an inside joke I may share with you guys one day..)



This video I made about doctors needing to care about their patients more is embodied, essentially on your beliefs. Ones that are strikingly similar to great people like Patch Adams. 

I will try to be more accepting, more respectful, more patient with you and promise to take your advice and apply it at home (instead of just outside the confines of it, as I've been doing), and, as you say, "listen to anything said about you or your ideas without emotion or bias, for there may be wisdom, or an idea in there waiting for you to grab it". I'll listen to any advice you give me and take it to heart, and try to not let bitterness stop me from becoming a better person. Something you've taught me to do, and be. 


But one pearl of wisdom I've heard elsewhere is that often the ones that make us laugh the most are the saddest inside. 



One thing I also want to ask on this Father's day is, Are You Okay? It's not just because R U OK day is coming up this Thursday, but because for all the times you've asked me that question over the years, I've never asked you that back... I've forgotten to...

Maybe no-one has... 


The things you've said to us, the anger you release at times... it doesn't make sense. Once or twice... you seem to have hinted that you're hurting too. Something you don't like to show. 

You've had to watch a person you love go through hell and back. You've had to sit by silently and watch as doctors inserted needle after needle into me, while I lay strapped down in bed in ICU twice (perhaps more times, I can't really remember), watch in horror as my face, in your words, for I can't remember, "distorted, to the point where your right eye was where your mouth should be"; you've had to watch me wither away into this hobbling, pained creature as these cramps and my disease has gotten worse... YOU'VE been through hell and back... And I don't know how you've done it. 

I know you're strong, I know you've also gotten strength from my brother, and his reaction, as well as mine to this whole thing, but to you, and any man reading on who may think this way, it's not weak to admit, or wanna talk about how you're feeling. It's weak to hide it inside; it takes strength to put it out there, at first. But once you do, you're taking the first step to being a happier person. And when you put it that way... it doesn't make sense not to do it, if you are feeling that way. 
You may think you're strong enough, smart enough to do it on your own. But hell, if someone else could help you do it in half the time, you've just saved yourself more time to enjoy life as you want, and deserve to. 

If you do think talking about it may help - please do so. Find a good mate, someone older, someone who you respect, or someone you trust; or else find someone who you never have to see again who is obliged to keep everything you said to them a secret - a psychologist, perhaps to do it with. And if you, or any man is stuck for people to talk to - check out these guys who may be able to help: 

Australia: http://softenthefckup.com.au/
http://www.mensshed.org/home/.aspx
America: http://www.mentalhealthamerica.net/find-support-groups
International: https://www.beyondblue.org.au/resources/for-me/men/depression-in-men

Lifeline: (+61) 131114

Whatever you may or may not be going through - I'll always be here for you dad, as you've always been here for me. And we'll be together forever. Happy Father's day. Enjoy these moments!


Dad and I after chemo #1

Dad and I after finishing the Ride to Conquer Cancer

Dad and I about a week ago tearing up the party as usual!