Rapamycin-related Side Effects in Kidney Transplant

Here’s yet another study of the side effects of Rapamycin (Sirolimus) in kidney transplant patients. 46% of the patients discontinued Rapamycin, with proteinuria, edema, and oral ulcers listed as the most difficult to manage, and more likely to cause discontinuation.

For more than a decade I’ve been reading similar studies with similar conclusions and it’s getting old, so here’s my suggestion for oral ulcers caused by Rapamycin: 30-60 seconds of antiseptic mouthwash twice a day. When I started taking Rapa I had ulcers by the dozens – ulcers on top of ulcers – but within three weeks of starting the mouthwash the ulcers disappeared, and haven’t returned in 13 years.

Scientifically anecdotal evidence isn’t worth a hill of beans but in this case it could be a dirt cheap solution for a painful and potentially costly problem. Immunosuppressive options are extremely limited so give mouthwash a try before you scratch Rapa off the list.

 

Advertisements

Rethinking Immortality

I’m not rethinking the desirability of immortality. That’s best left to those far from death and lacking perspective. I still think the pursuit of human immortality is a worthy cause (see here). But the more I think about it, the more I think it simply isn’t possible to radically extend lifespans for humans as we know them.

The insurmountable hurdle in the quest for immortality is going to boil down to an evolutionary box canyon where, because of all the good-enough-for-reproductive-work “choices” made before, you just can’t get there from here. Evolution rewards expediency and economy, making do with what’s at hand and finding multiple, often opposing, uses for everything biological. Because of this, attempted improvements in the workings of the body at some point lead to a problem elsewhere. Pharmaceutical development is always an attempt to improve the benefits and reduce the costs, but the tradeoffs can never completely be eliminated. When man finds a new use for a wheel it could be a table top. When evolution finds a new use for a wheel it’s likely to be the table legs, chairs, half the fireplace, the front door, and part of the driveway too.

A counter argument can be made that there are some creatures on earth that live extraordinarily long lives, and by discovering their secrets we’ll be able to emulate them. While that research no doubt will lead to some improvements in longevity, those other species aren’t us. Different evolutionary histories lead to different box canyons (e.g. trees aren’t that smart and tortoises have to bear the indignity of petting zoos). We’ve been social animals for far longer than the last decade, and as a result our immune systems may be the most complex in the world. This has allowed us to survive domesticating animals and sending kids to daycare to trade secretions, but targeting all manner of pathogens over a lifetime inevitably results in false positives. Systemic inflammation and an early demise is one of the likely results. Being warm-blooded, with a far higher metabolic rate than a bristlecone pine or tortoise, is another example of a beneficial trait that imposes a significant set of hurdles to immortality. Biology is a package deal composed of millions of interrelated pieces. Because of this evolutionary baggage, picking and choosing the traits we’d like and putting them together doesn’t mean they will work the way we intend.

Reduce/reuse/recycle engineering isn’t the only issue. Once reproduction stops, anything that sends you to an early grave after that can accumulate in the genes virtually unmolested. To a large extent, aging is the result of that genetic neglect. In theory, that category of defect should be fixable with little downside. The bad news is that there are likely millions of such defects that would need to be identified and changed. The even worse news is, once altered, many of them will turn out not to have been deleterious junk after all – which leads back to the Rube Goldberg engineering problem.

This doesn’t mean that immortal biological beings couldn’t be created someday. Unfortunately it would require a complete re-engineering from the ground up, and the final result would be something quite different from the original. It’s the same problem as with the Transhumanists’ idea of uploading our minds: Human mind and body are an inseparable, integrated whole. In fact, if you look at human behavior objectively, the body is clearly in charge of the mind. Much of what we do revolves around simply maintaining homeostasis, with emotions created to motivate us to action, and most of the rest is a direct or indirect attempt to enhance reproductive success (e.g. buying a Ferrari). What would be left if that were removed or radically altered? I’m not sure, but it definitely wouldn’t be recognizably human. Even if the technical problems of uploading a brain could be solved, once separated from the bodily milieu it would cease to be you, and that’s hardly immortality.

Though immortality may be beyond our reach, it doesn’t mean increased longevity is a lost cause. While our evolutionary heritage may have screwed us on a grand scale, increasing healthy lifespans by a significant percentage is a near certainty. If markets are allowed to operate, it could happen well within those filthy daycare tots’ lifetimes. But I’m afraid that will have to do, you lucky little bastards. Wetware life will always be too short.

Killing Mortality: A Call To Arms

Bob and I are such kindred spirits I couldn’t resist using this again.

Something big is happening. If you are young and talented, looking for a way to change the world, consider this idea: Curing aging and mortality. We’ve finally reached the inflection point and the next phase where the biggest advances in the field will be made.

Everything medicine does to extend lifespan today amounts to treating the symptoms while leaving the underlying causes unaddressed. But that’s starting to change. The pieces are falling into place and there is nothing other than ourselves [1] that can stop it. There’s still a great deal that needs to be done in proteomics, genomics, microbiomics, epigenetics, etc, so the big breakthroughs will almost certainly be too late for me, but the singularity obsessed trans-humanists are right about at least one thing: Aging and mortality as we know them are doomed. It will happen in stages rather than one dramatic discovery, but it will happen.

One of the greatest impediments to progress today is the amount of information is so vast it’s impossible for anyone to understand and integrate enough of it to discover what it all means. Originally I had envisioned a medical connectome of sorts – an enhanced search and visualization tool – as a means of discovering the connections hidden in the huge body of medical knowledge and highlighting new directions for research. But with the progress in AI and deep learning there is no longer a need for that sloppy, sluggish, human interpretive middleman, allowing progress to dramatically accelerate. In many areas it’s already underway and gaining speed.

No matter how great a babysitter you are, or how much knowledge you can impart to successive generations [2], beyond a certain age you become useless in improving your reproductive success. This allows all manner of riffraff to muck up your genome and its expression, and provided these time bombs go off at a sufficiently advanced age there is nothing to stop them. Aging is ultimately the result of this evolutionary indifference to poor design and execution. Everything that happens in the body is the result of sets of instructions being carried out, and we’re now at the point where we can see the instructions, begin to comprehend them, and in some cases rewrite them. It’s time to learn to code in yet another language.

A sampling of reasons for optimism:

Diseases of aging map to a few ‘hotspots’ on the human genome

Researchers produce a catalog of the deleterious and disease-causing genetic variants in healthy people

Brain Architecture: Human Connectome Project

A Virus That Saves Itself By Preventing Bacterial Suicide

Artificial virus silences genes

Current status and perspectives of proteomics in
aging research

International study points to inflammation as a cause of plaque buildup in heart vessels 

Scientists create roadmap to metabolic reprogramming for aging

Scientists See Promise in Deep-Learning Programs

Even a quick survey makes it obvious the breakthroughs in understanding this avalanche of knowledge won’t come from a lone genius working in a lab, but from open collaboration, AI, and massive computing power. Yes, contrary to Hollywood plotlines, Skynet’s cousin will be our savior. So fuck your dreams of being the next Facebook, you could be remembered for killing death [3]. Put down that bong and get started! The clock is ticking…

…It’s hard to say goodbye when all
        the birds are singing in the sky
                They can find a way
                        in the future someday
                                A drug that lets us live forever,
                                          me and you will take it…

______________________________

[1] IP and copyright are crippling impediments to progress and if they invade the field the timeline will slow dramatically. Legislators are another hurdle since they will have no qualms about availing themselves of every possible advance through medical tourism, while denying them to others.

[2] The HBO documentary A Century of Living (1999) is a wonderful example of the insight and perspective that comes with age, as well as the tragedy of its loss.

[3] There’s a lot of money to be made too if you’re burdened by unadulterated greed, acute envy, or student loans.

[4] This is also an excellent description of what a great intuitive trade feels like.

Holiday Rerun – The Assault on Human Variability

This was originally posted in March, barely one month after I started this blog, so hardly anyone saw it. A rebuttal to the redefinition of normal in mental health.

The Assault on Human Variability

Feel free to print it out and flog a school administrator as necessary.

An Important Proof of Concept

I mentioned the idea of creating a virus that would cause immortality in a News and Comment post not too long ago (here). Now there’s some evidence for the potential of the concept in this article: A Virus That Saves Itself By Preventing Bacterial Suicide

Alter your retirement savings estimates accordingly.

Reasoned Decision of The United States Anti-Doping Agency

Here is the condensed version (202 pages) of the Lance Armstrong decision. The full file is evidently over 1000 pages. Among the highlights, more than $1 million paid to Dr. Michele Ferrari. Plus, Six former Armstrong USPS teammates receive bans from USADA

The UCI response will be interesting. Beyond numerous examples of organizational incompetence, the report repeats the prior allegations of collusion and corruption by the UCI in keeping positive tests from coming to light. Deciding what to do is therefore an IQ test of sorts for the UCI, and a score of 100 would greatly exceed my expectations..

 

Pseudo Random News and Comment – ENCODE edition

A major step forward in understanding the human genome and the future of medicine. Screw the economic and market news, this is important. Summary piece first, then more details:

Breakthrough study overturns theory of ‘junk DNA’ in genome

Another Science Hurricane: A Massive Survey of the Genome  Links to some alternate interpretations

ENCODE project: Researchers unlock disease information hidden in genome’s control circuitry

ENCODE project: Millions of DNA switches that power human genome’s operating system discovered

ENCODE project: In massive genome analysis new data suggests ‘gene’ redefinition

ENCODE project: Yale team finds order amidst the chaos within the human genome

ENCODE project: Researchers catalogue functional elements of the genome

Llama Llama Get With Mama: The Magical Semen Ingredient that Makes the Ladies Swoon (Then Ovulate) The other big science news is they’ve probably found the ingredient behind the long-postulated effect. Battle of the sexes is fought on many levels.

Fathers who sleep closer to children have lower testosterone levels So having kids = partial castration. Seems like I read marriage has a similar effect, so together it may result in total castration.

Worst year ever for West Nile in Texas; 40 dead  Plus at least 495 cases of the neuroinvasive form. Where’s that mosquito death ray?

Pirate Bay Founder Arrest Followed By $59m Swedish Aid Package For Cambodia I wonder if Assange checked Ecuador’s fiscal position before requesting asylum?

12 Scary Signs That It’s Time to Leave Your Company  Before they leave you. “Rough patch” + closed door meetings = Run!

Lucky Us: Toilet Paper Priced Like Airline Tickets? Maintaining maximum browser privacy eliminates some of the customized pricing, as does not logging in when you check prices.

Decreased breast cancer risk linked to active lifestyle  Have to get at least one benefit of exercise link in. Yes, it’s a bias I have.

More on lying and cheating:

Study: We lie when we’re short on time or feel justified to do so

Harvard and the politics of large-scale cheating  Ariely reverse engineers the recipe.