How to beat your islamic wife. tutorial video

Seriously, I love how these threads sometimes take on a life of their own. This one went from guidelines to wife-beating to animal testing.

escap wrote: Yep. I also love how there's someone else on this forum at 2:20 in the morning. I guess I'm not the only one with insomnia. (need a "sleepy" icon)

Indeed, sir. [yawn]

Well, I'm a proverbial night owl and this getting up in the morning for work is killing me. (Never. Been. A. Morning. Person. Ever.)

laura, supposedly one needs less sleep as you get older but that must kick in after 50 or 60 'cause during Christmas vacation I slept 9hrs EVERY DAY. ( I did go out drinking every night, though...) You?

MichaelKeys wrote: this getting up in the morning for work is killing me.

Go to bed!!!

What's so terrible about testing analgesics on consenting humans who volunteer to undergo a small burn, or be part of a study on pain relief following a tooth extraction or other minor surgery? Since humans are the beneficiaries of drug research, perhaps they should be a little more willing to assume some of the risks involved.

laura wrote: What's so terrible about testing analgesics on consenting humans who volunteer to undergo a small burn, or be part of a study on pain relief following a tooth extraction or other minor surgery? Since humans are the beneficiaries of drug research, perhaps they should be a little more willing to assume some of the risks involved.

You cannot start by taking millions of random chemicals off the shelves and giving them intracranially or intrathecally one-by-one to volunteers at random dosages in the hope of finding something useful against pain or any other indication. That would be completely unethical, illegal, and inefficient; you'd run out of human population before you found a drug. In our society, euthanasia of a purpose-bred animal is acceptable when something goes wrong but putting down a volunteer or prisoner is not. There is not enough money in the world to pay the medical bills of the test subjects or compensate their families.

Of course humans assume some of the risks. In order to do the test you describe, and it is certainly done (in 4 phases) as part of the process, you need a decade or more of animal and other kinds of research first before it would be meaningful, let alone practical or ethical. First of all, you have to have an idea about what mechanism you're going to target, and that will generally require working up from lower organisms to a few pretty serious experiments in mammals where euthanasia beforehand or afterwards is a must, or where a mouse lacking the target has to be genetically engineered specifically for the purpose. No role for humans here. Then comes finding a hit: you potentially have to sift through a real catalog (called a deck) of millions of real compounds, potentially supplemented by billions of synthesizable virtual compounds, to get down to a list of a few dozen scaffolds to take forward. Robots, high throughput assays, and virtual screening help; human volunteers would not. Then comes lead optimization: typically 2-3 years of back and forth between chemists and pharmacologists, adjusting the lead structures to increase affinity for the target, increase specificity, decrease toxicity, increase bioavailability. Typically 1000 variations will be tried on the lead, and assays may be on proteins, cells, organs. Some animals will be needed in this phase and it would be unethical, inefficient, and prohibitively expensive to use humans. If you're very lucky (and most projects will have failed by this point) then you're down to a small handful of pre-clinical candidates. The government will not give approval for trying these in people before they've shown some safety and efficacy in animals, nor would a sane doctor be prepared to administer them. If it kills a rat in small dosages, it's highly likely to kill a human. If it has no bioavailability in a rat, it probably has no bioavailability in a human. If it has no efficacy in a rat, it probably has no efficacy in a human. It can fail teratogenicity in days in mice because of the short lifecycle, and if so, no point in trying it out and monitoring in humans for years. Typically you have to go back to lead optimization a couple of times and maybe change strategy along the way, try a prodrug, etc. If one or two of the clinical candidates makes it all the way through, typically at the $20-$30 million mark and 5-10 years in, if you've been really lucky, you've reached halfway. The next half (in terms of time and cost and risk) is humans, starting with Phase 1, which involves risking healthy young male human volunteers, to establish maximum dosage and safety. Then come phases 2,3 (pre-market) when many candidates fail, and 4 (post-market) to establish dose and efficacy and continue monitoring safety. This long, expensive, risky process is what it takes to create new medicines to save lives, cure diseases, reduce suffering.

By the way: most drugs that work in humans also work in animals, and veterinarians can prescribe a superset of what a doctor can, so pets are also ultimately beneficiaries.

laura wrote: ... although I gotta say I prefer most cats to most humans.

Please! How can you say that? Don't you know that cats are...ha! Gotcha!

laura wrote: One problem, to my mind, is Western medicine's overreliance on the biochemical model, which results in a narrow framing of medical progress in terms of finding new drugs. We have zillions of drugs, and how many of them actually cure disease as opposed to masking symptoms and throwing the body further out of balance? And how many are actually harming people? Western medicine has its obvious benefits and breakthroughs, but it tends to ignore nutrition, wellness, the mind-body connection, etc. Thankfully systems such as Chinese medicine and Ayurveda are becoming more well-known, but alternatives to the system still tend to be discredited as loony and/or dangerous (at least the AMA gave up trying to destroy chiropractic). I don't want a return to the Middle Ages, and I'm smart enough not to fall for genuine quackery. But I hope to see an integrated, less mechanistic health care framework developed that depends less on Big Pharma ...

Well biochemical models have brought us vaccines, antibacterials, antivirals, chemotherapy for cancer, etc. etc. etc. All the previous big killers of the past are so tamed in the West to the point that only now do trickier degenerative conditions manifest themselves more often, in concert with the 20-30 year increase in lifespan and decrease in infant mortality Western medicine has brought us in a century or so. And there's a great deal to be said for masking symptoms when no cure is available; in the good old days people just suffered and died horribly and in pain. When it comes to actual evidence and epidemiology, there's just no contest; life without access to the discoveries of modern medical science is on average shorter and nastier. Have fun with your Chinese medicine and Ayurveda -- in fact, all sorts of extra-strength placebos, ancient and modern, have certain levels of efficacy. You could even follow your antiscientific muse to its logical conclusion and put down the computer and join a hunter-gatherer tribe if you wanted, but spare a thought for friends and loved ones battling HIV or cancer, where the new drugs can't come fast enough, and no amount of chakra realignment will buy them another 10-20 years of life of reasonable quality. I've lost friends to AIDS and certain random cancers who would still probably be alive if they'd become sick just a year or two later; haven't you? And I know people living relatively normal lives with other kinds of horrific incurable diseases whose progress and symptoms are substantially kept at bay by medicines; don't you?

And like them or not, no one else but Big Pharmas (who survive by purchasing lots of good ideas from little pharma and biotech and bringing to market those few that make it through the million-to-one chances) have the equipment or long-term capital or know-how required to tackle the remaining hard problems. Even if they're not particularly interested in diseases that only affect the poor and those that still only have access to the traditional medicine you're espousing, they're the best we've got and the only ones with a proven track record.

And yes: anyone who eschews evidence in favor of magic is sorely misinformed or pretty far from rational, and dangerous in my opinion if they promote that kind of thinking in others.