12 May 2009

What we need to accelerate biomedical research and fight aging

A few hundred years ago I could not have been born. I was massive - 4.9 kg - and the birth eventually turned caesarean and took many long hours. I owe my life to medical science. One day, 11 years later, I was out biking and realized for the first time that the annihilation following my death would be infinite. Now, 25 years after my complicated birth, I think a lot about whether medical science, rejuvenation research of the SENS variety in particular, will save me a second time.

Sciences from genetics to pharmacology to artificial intelligence have run into the quagmire of complexity. How can we model and manipulate complex systems when the numbers of variables are enormous and the combinatorial possibilities seem endless? How can we search and find genuine cures for cancer and HIV when the little buggers are the playground of evolution itself? How can we interfere with the aging process when the ways in which aging is expressed in the body could fill an encyclopaedia?

The solution will probably involve a concerted move to vast, quasi-open repositories of research data that can be crawled by statistical algorithms (Anderson 2008, Halevy et al 2009). But good research data is expensive and progress is slow. High-throughput research centres are rare. If you agree with me that drastic methods are called for, here is my suggestion:

What we need to accelerate biomedical research and fight aging

1. Safe and inexpensive brain surgery

To do better biomedical research we need better control over the chemistry of our own brains. Specifically, we need safe and inexpensive application of deep brain stimulation (DBS) implants to the reward circuit of anyone who wants it. This sounds daunting but fortunately it's happening already. DBS to the reward circuit turns out to be an extremely effective treatment for various psychiatric conditions: in February of 2009 Medtronic received FDA approval to use the procedure to treat obsessive compulsive disorder, and clinical trials for depression, potentially a much larger patient group, are well under way (read the press release here). More generally, DBS is becoming standard treatment in late-stage Parkinson's disease, dystonia and tremor. The most popular implant - Medtronic's Activa system - has been applied to more than 40.000 patients since 1997, and DBS is currently being explored as a treatment option for everything from epilepsy and chronic pain to anorexia and obesity. The risk of serious complications such as hemorrhage is currently at 1-3% and the cost of the procedure is at €30.000 (not counting the cost of regular follow-ups). By comparison, plastic surgery generally cost ca $3.000-6.000. Give it a few years.


2. Widespread use of enhanced motivation through deep brain stimulation

Electrodes in the reward circuit can generate highly rewarding brain stimulation (RBS) in rats and humans alike (Wise 1996 , Heath 1972). In human patients, this is carefully avoided - DBS implants in the reward circuit are used merely to normalize brain activity (Schlaepfer et al, 2008). In rats however, RBS has been used as a powerful operant reinforcer to motivate animals to perform various behaviours, such as run on treadmills, lift weights and learn new skills (Burgess et al 1991, Garner et al 1991, Hermez-Vasquez et al 2005). There is every reason to assume that the same kind of training could be utilized by human beings with DBS implants in their reward circuits.

If brain surgery could be made as safe and inexpensive as plastic or dental surgery, I believe millions would opt for an implant that gave them the artificial incentive necessary to enjoy challenging behaviours for several hours every day: RBS for every stroke on a rowing machine; RBS for every correct answer on a maths-tutorial; RBS for learning a new language or skill; RBS for drug-free urine samples; RBS for anything you normally wouldn't know how to get done. Given the enormous health-benefits of regular physical exercise, it is quite possible that RBS-driven exercise would pay for itself on a societal level and eventually be recommended by doctors. How would you spend two daily hours of artificial motivation?


3. RBS-driven research centres and biomedical outsourcing

Obviously, a project as ethically charged as this one would require legislation and policy to prevent abuse. Hospitals and private clinics would carefully regulate which behaviours were allowed artificial reinforcement: physical exercise, sure, as long as there's a time limit; academic learning, maybe, as long as there's no way to cheat. I believe a third form of behaviour - RBS-driven research - would also be permitted. That is, it would be possible to set up research centres, similar to blood banks, where volunteers with DBS implants could come to participate in basic biological or medical research, using pedagogical instruction (e.g. JoVe, bioscreencast), with RBS being delivered at key points in the protocols to drive enthusiasm for mundane and repetitive tasks: RBS for getting the PCR going; RBS for having pipetted all the antibodies onto microarrays; RBS for getting the samples from the freezer; RBS for each classified blot; RBS for each autoclaved tray of equipment. You get the idea.

Such research centres, involving hundreds of thousands of volunteers world-wide, working a few hours every week, would allow something we could call biomedical outsourcing - industry, hospitals and academic institutions could request large quantities of data without having to organize and finance the necessary research. 100 volunteers working four hours per week could save an institution more than a quarter million euro every year and would free scientists up to pursue more challenging tasks. With a sufficient number of volunteers, research would accelerate dramatically, particularly in fields such as biology where much of the practical work is monotonous and requires little or no understanding of the broader purpose of the techniques involved.
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