Health

DNA scans for everybody who did a failed drug trial

The pharma industry is littered with cases of drugs that showed good promise, but proved to be too dangerous when they got into human trials. Dangerous side effects will cancel development for most drugs. In some cases, such as Vioxx and Fen-Phen the dangerous effects were discovered later, and the drugs pulled from the market.

Some people got better on the drugs, others had bad side effects. Sometimes those bad side effects will be the result of various environmental factors, or perhaps rarely they will be bad luck. However, I suspect that some good portion of the time, they will be due to genetic factors in the test subject.

DNA sequencing is getting cheaper every day. Even today the whole genome can be done for $5,000 wholesale and many expect it to be hundreds before long. Collections of 600,000 to 1,000,000 SNPs can be read for a few hundred dollars.

It strikes me that the drug companies will want to make efforts immediately to get DNA samples, if they don’t have them, from all the people who participated in the trials of failed drugs, particularly those who had the bad side effects. And to get those samples sequenced. Because in some cases, they may well find a connection between the bad reaction and genetic patterns. They might find cases where all the side effects had one gene and all the regular reactions had another.

If they do find this, then suddenly they will have a billion dollar drug on their hands again, with much of the work already done, presuming the FDA and other regulatory agencies accept this approach. With the gene identified, making a test for it would be very cheap, and suddenly a useful drug might be available to those who have no problems with it. This might leave the people with the reacting DNA out in the lurch of course, and nobody is likely to try to find a drug for them in the immediate future.

If people get large DNA scans, those scans should remain in the possession of the patient or their doctor. There are already laws forbidding insurance companies in some jurisdictions from using DNA data to adjust insurance, but there will be powerful forces trying to reverse this.

DNA results will also explain differing efficacies of the drugs. It’s already been learned that many people need different doses of the same drug, and also that some drugs work on men but not on women, for example.

I expect this will be standard practice for future drug trials, but my point today is that since many of these people are still alive, we can reach into the past and learn the truth about long-past drug trials as well, and perhaps get a brief flood of new useful substances as long as the patient is DNA typed in advance.

Squicky memory erasure story with propofol

I have written a few times before about versed, the memory drug and the ethical and metaphysical questions that surround it. I was pointed today to a story from Time about propofol, which like the Men in Black neuralizer pen, can erase the last few minutes of your memory from before you are injected with it. This is different from Versed, which stops you from recording memories after you take it.

Both raise interesting questions about unethical use. Propofol knocks you out, so it’s perhaps of only limited use in interrogation, but I wonder whether more specific drugs might exist in secret (or come along with time) to just zap the memory. (I would have to learn more about how it acts to consider if that’s possible.)

Both bring up thoughts of the difference between our firmware and our RAM. Our real-time thoughts and very short term memories seem to exist in a very ephemeral form, perhaps even as electrical signals. Similar to RAM — turn off the computer and the RAM is erased, but the hard disk is fine. People who flatline or go through serious trauma often wake up with no memory of the accident itself, because they lost this RAM. They were “rebooted” from more permanent encodings of their mind and personality — wirings of neurons or glia etc. How often does this reboot occur? We typically don’t recall the act of falling asleep, or even events or words from just before falling asleep, though the amnesia isn’t nearly so long as that of people who flatline.

These drugs most trigger something similar to this reboot. While under Versed, I had conversations. I have no recollection of after the drug was injected, however. It is as if there was a version of me which became a “fork.” What he did and said was destined to vanish, my brain rebooting to the state before the drug. Had this other me been aware of it, I might have thought that this instance of me was doomed to a sort of death. How would you feel if you knew that what you did today would be erased, and tomorrow your body — not the you of the moment — would wake up with the same memories and personality as you woke up with earlier today? Of course many SF writers have considered this as well as some philosophers. It’s just interesting to see drugs making the question more real than it has been before.

Medical stories making it feel like the 21st century

High posting volume today. I just find it remarkable that in the last 2 weeks I’ve seen several incredible breakthrough level stories on health and life extension.

Today sees this story on understanding how caloric restriction works which will appear in Nature. We’ve been wondering about this for a while, obviously I’m not the sort of person who would have an easy time following caloric restriction. Some people have wondered if Resveratrol might mimic the actions of CR, but this shows we’re coming to a much deeper understanding of it.

Yesterday I learned that we have misunderstood death and in particular how to revive the recently dead. New research suggests that when the blood stops flowing, the cells go into a hibernation that might last for hours. They don’t die after 4 minutes of ischemia the way people have commonly thought. In fact, this theory suggests, the thing that kills patients we attempt to revive is the sudden inflow of oxygen we provide for revival. It seems to trigger a sort of “bug” in the [[w:mitochondria], triggering apoptosis. As we learn to restore oxygen in a way that doesn’t do this, especially at cool temperatures, it may be possible to revive the “dead” an hour later, which has all sorts of marvelous potential for both emergency care and cryonics.

Last week we were told of an absolutely astounding new drug which treats all sorts of genetic disorders. A pill curing all those things sounds like a miracle. It works by altering the ribosome so that it ignores certain errors in the DNA which normally make it abort, causing complete absence of an important protein. If the errors are minor, the slightly misconstructed protein is still able to do its job. As an analogy, this is like having parity memory and disabling the parity check in a computer. It turns out parity errors are quite rare, so most of the time this works fine. When a parity check fails the whole computer often aborts, which is the right move in the global scale — you don’t want to risk corrupting data or not knowing of problems — but in a human being, aborting the entire person due to a parity check is a bit extreme from the individualistic point of view.

These weren’t even all the big medical stories of the past week. There have been cancer treatments and more, along with a supercomputer approaching the power of a mouse brain.

Patient's room phone with basic presence

Those who know about my phone startup Voxable will know I have far more ambitious goals regarding presence and telephony, but during my recent hospital stay, I thought of a simple subset idea that could make hospital phone systems much better for the patient, namely a way to easily specifiy whether it’s a good time to call the patient or not. Something as simple as a toggle switch on the phone, or with standard phones, a couple of magic extensions they can dial to set whether it’s good or not.

When you’re in the hospital, your sleep schedule is highly unusual. You sleep during the day frequently, you typically sleep much more than usual, and you’re also being woken up regularly by medical staff at any time of the day for visits, medications, blood pressure etc.

At Stanford Hospital, outsiders could not dial patient phones after 10pm, even if you might be up. On the other hand even when the calls can come through, people are worried if it’s a good time. So a simple switch on the phone would cause the call to be redirected to voice mail or just a recording saying it’s not a good time. Throw it to take a nap or do something else where you want peace and quiet. If you throw it at night, it stays in sleep mode until 8 or 9 hours. Then it beeps and reverts to available mode. If you throw it in the day, it will revert in a shorter amount of time (because you might forget) however a fancier interface would let you specify the time on an IVR menu. Nurses would make you available when they wake you in the morning, or you could put up a note saying you don’t want this. (Since it seems to be the law you can’t get the same nurse two days in a row.)

In particular, when doctors and nurses come in to do something with you, they would throw the switch, and un-throw it when they leave, so you don’t get a call while in the middle of an examination. The nurse’s RFID badge, which they are all getting, could also trigger this.

Now people who call would know they got you at a good time, when you’re ready to chat. Next step — design a good way for the phone to be readily reachable by people in pain, such as hanging from the ceiling on a retractable cord, or retractable into the rail on the side of the bed. Very annoying when in pain to begin the slow process of getting to the phone, just to have them give up when you get to it.

Versed for couple's counselling

I’ve been away because I had to have my gall bladder removed, thanks to a gallstone the size of a small moon. Unfortunately they had to do it “old school” rather than laproscopically, which means the recovery is so much more fun.

The immersion into the hospitalization system (first time in the US) will generate some blog posts, but today let me add thoughts on one element that surprised me. Almost exactly a year ago, I wrote speculating on the use of Versed for torture. I still wonder about that, and now I have a direct experience. Though I was not told about it, the anesthesiologist included one of the amnesia-inducing drugs into the pre-op “calm you down” sedation coctail. I remember him doing that injection, and getting a bit flushed from that, but it’s blank after that. No memory of any discussion after, of being wheeled to the operating room and receiving the actual injection to make me unconscious for the procedure. Those events never laid down.

(When I asked the surgeon about not being told I would receive this drug, she at least had a sense of humour and said, “How do you know you weren’t told?” Indeed, I don’t know that. And to pile on the irony, I brought the movie “Momento” to the hospital, and watched it during my recovery.)

It is disturbing to have a memory deliberately erased. We’ve all lost memories, found periods in which we can’t recollect anything about particular event or stretch, but this is different.

Still, it got me wondering about bizarre uses to which this might be put. I already speculated on torture and sinister uses. And we know about the use for date-rape which is highly disturbing. I wondered about its application to deep dark secrets.

The scenario is this. You have a couple. One or both of them volunteer for an amnesia inducing drug. Then, you pour out your heart, with all the deep dark secrets you’ve been hiding, kinky fantasies you’ve been begging for, and wait for the reaction. If your own memory is not going to store, you make notes on the reactions. When you’re done, you know what secrets you can tell, and which would be relationship-destroying or particularly hurtful. Of course, the tested party needs to cooperate, and not say, “Oh, I had better pretend to not be bothered by that so that this horrible thing does not become lost to me” and and better not be a good actor. Or couples who are in the “both want to break up but are not admitting it for the sake of the other one” state could discover it and talk it out — though one could also make a computer program to solve that problem.

To be tricky, my companion in the pre-op room could have decided to tell me things there without my being aware I had received the drug — it is quite common now in sedation coctails — in which case I would not have thought to fake my reactions. Technically, though I trust her, I can not be sure via my own memory that she did not.

These drugs are currently Schedule IV, so they don’t see such non-medical use, but one can imagine other bizarre uses. For example, confidential job interviews. Consider applying for a job to work on a confidential project at a company. They might give you an NDA, or they might give you Versed and tell you the whole deal, knowing you won’t be talking about it. Or truly “embargoed” releases to the media, or trials of secret products before a focus group. And these aren’t as scary as the suggestions of use in torture or policework I already made. Certainly when it comes to any official use, we need a law requiring that any administration of such drugs be paired with complete videotaping of the entire episode and secure storage and authentication of the videotape — if we allow such use at all. (Unfortunately we are probably going to see use whether we permit it or not.)

There could be medical uses. For example, say you have the cliche’d incurable, non-communicable fatal disease and some number of months to live. You could be told, and given the choice about when you should be told in a way you’ll remember it. It’s like creating test versions of yourself to try new and dangerous ideas and report back if the real you should absorb them.

Now I should note that there are barriers to the ideas I worry about above. The drugs are not 100%. You can’t be sure they will block the long term storage of memory. And they also sedate you, put you in a calmer, non-natural mental state so they might not really be too useful in job interviews and other circumstances. (Even for torture, they might make you more able to tolerate the non-damaging torture they would want to do to you, just as they help you tolerate surgical squicks.)

But the drugs are going to get better, if they haven’t already in secret labs. There are documents of experimentation with amnesiac drugs in intelligence contexts back to Viet Nam. Who knows what the black labs have discovered? We are going to have to get used to a world where memory is more fungible, and we call can be temporarily the character from Momento.

DNA/Medical testing services that promise what they won't tell you.

Today many services offer MRI scans for a fee. DNA testing services are getting better and better — soon they will be able to predict how likely it is you will get all sorts of diseases. Many worry that this will alter the landscape of insurance, either because insurance companies will demand testing, or demand you tell them what you learn from testing.

Many criticise the MRI scan services because they quite often show up something that’s harmless but which inspires a medical demand to check it out just to make sure. That check-out may be expensive or even be invasive surgery.

So people are suggesting, “don’t get tested because you don’t want to know.” However there is stuff you do want to know, and stuff that may be useful in the future.

I propose escrowed testing services that promise not to tell you, or anybody, certain things that they find. For example, they would classify genetic tendencies for diseases for which there is no preventative course, like Parkinsons or Alzheimer’s. Many would say they have no desire to know they might get Parkinson’s as they get older, since there is nothing they can do but worry.

The service might escrow the data themselves with the big added plus that they would regularly re-evalutate the decision about whether you might want to know something. Thus, if a preventative treatment comes along that is recommended for people with your genes, then they would recognize this and tell you the thing you formerly didn’t want to know. They would also track what new things can be tested, and tell you when a re-test might make sense as technology improves.

The information could also be escrowed with a trusted friend or relative. You might have a buddy or spouse who could get the full story, and then decide what you need to know. A tough role of course, perhaps too tough for a spouse, who would worry about your pending Parkinson’s almost as much as you. You can’t easily use relatives, because they share lots of your DNA, at least for DNA scans.

Of course, your doctor is an obvious person for this, but this goes against their current principles and training.

Of course there is a legal minefield here. One would need a means to provide pretty good immunities for the escrowers, while at the same time not allowing them to be totally careless. The honest belief that information was in the don’t-tell profile should be enough to provide immunity.

There is another risk here, of course, which is that strangers, even doctors, can’t be fully trusted with the final decisions on your health. You will be taking a risk that the 3rd parties won’t work quite as hard at solving problems or even paying attention to them as you would. In fact, you’re doing this because you would worry too much.

There’s another benefit to this. Many people, if told to expect something, will invent it. This is very common with things like drug side-effects. In order to avoid this, when I take a new drug, I don’t read the long PDR list of side-effects. Instead, I have Kathryn read them. Then I can wait until I truly sense something and ask if it’s a side effect, rather than expecting it. The same principle applies here, though that suggests you need somebody very close as your health escrow. Of course again your doctor would be the right choice here, so that when you went there to say “I’m feeling numbness in my fingers” she could say, “Ah, well now it’s time to tell you about this thing we found in your gene scan.” Possibly a system that lets the doctor search, but not read, the gene scan, could help.

Mimic caloric restriction as a means to birth control?

I’ll admit that female endocrinology is not something I know a great deal about, but I do know that most of the birth control pills today follow a general strategy of fooling the body into thinking it is pregnant. This stops ovulation and implantation.

It is also the case that certain types of stress, notably caloric restriction and extremely high levels of physical activity can also retard both ovulation and menstruation. In fact, young girls who are serious athletes often do not experience menarche until years later than ordinary girls. (On the other hand, for reasons not fully understood, the average age of menarche has been gettting significantly younger in recent decades.)

The evolutionary reason for the late menarche seems obvious — if times are tough, and food is scarce, it may be best to not have babies right then.

Anyway, there must be some hormonal signals which these levels of stress generate which trigger the reproductive system not to operate. My question is — might it be possible to mimic these signals, without other harmful effects, as a method of birth control and even menstrual supression?

Of course, we’re very interested in other ways to mimic the signals of caloric restriction without the actual restriction, since in all the animals tested so far, caloric restriction results in serious extension of lifespan and youthspan.

Two styles of vitamin and supplement pills

Today there's more evidence we should be taking more and more supplements, but they often come in giant pills that are uncomfortable to take. At the same time, easy to take chewable vitamin pills are also on the market.

So I propose: Divide up all the vitamins and minerals and supplements wanted in a daily regimen. Make a chewable pill that contains all the ones that can go in a chewable pill (ie. don't taste bad, and will maintain proper cohesion.) Then take the ones that can't go in that chewable, and bundle just them in a hopefully smaller, coated pill to swallow.

A vaccine for autoimmune disorders

When our society got rich, we started living much more sterile lives, and a whole bunch of diseases cropped up which are autoimmune disorders. These range from allergies to Chrohn’s Disease, which destroys the bowel. Many of these syndromes did not exist in the pre-sterile world. (Not all autoimmune disorders are this way, of course.)

So some parents have become aware that you need to let your kids play in the muck, and with animals, and get exposed to diseases and parasites so your immune system grows up as you grow up. Otherwise, with nothing to do, it can attack you.

But parents are protective. They are not going to deliberately expose their children to parasites. But there are treatments that have been developed for sufferers of these diseases that give them safe alternatives that their immune system can fight. For example, the spores of parisites that infect other animals, but not humans.

So we need to develop a regime of “vaccines” against autoimmune disorders. A regimen of safe infectious agents that will put the immune system through the paces it expects to go through in the natural world, but which won’t cause damage. And we need to expose children, and possibly even adults, to them through their lives.

Dealing with a pandemic in the post-internet world

There’s a lot of talk about the coming threat of Avian H5N1 flu, how it might kill many millions, far beyond the 1918 flu and others, because of how much people travel in the modern world. Others worry about bioterrorism.

Plans are underway to deal with it, but are they truly thinking about some of the tools the modern world has that it didn’t have in 1918 which might make up for our added risks? We have the internet, and a lot of dot-coms, both living and dead, created all sorts of interesting tools for living in the world without having to leave your house.

In the event of an outbreak, we’ll have limited vaccine available, if there’s much at all. Everybody will want it, and society will have to prioritize who gets what. While some choices are obvious — medical staff and other emergency crews — there may be other ideas worth considering.

Today, a significant fraction of the population can work from home, with phone, computer and internet. The economy need not shut down just because people must avoid congregating. Plans should be made, even at companies that prefer not to allow telecommuting, to be able to switch to it in an emergency.

Schools might have to close but education need not stop. We can easily devote TV channels in each area to basic curriculum for each grade. Individual schools can modify that for students who have internet access or even just a DVD player or VCR. For example, teachers could teach their class to a camera, and computers can quickly burn DVDs for distribution. Students can watch the DVDs, pause them and phone questions to the teacher. (However, ideally most students are able to make use of the live lectures on TV, and can phone their particular teacher, or chat online, to ask questions.) Parents, stuck at home would also help their children more.

Delivery people (USPS, UPS etc.) would be high in line for vaccination to keep goods flowing to people in their homes. You can of course buy almost anything online already. Systems like Webvan, for efficient grocery ordering and delivery could be brought back up, with extra vaccinated delivery drivers making rounds of every street.

Of course not everybody has a computer, but that need not be a problem. With so many people at home, volunteers would come forward who did have broadband. They would take calls from those who do not have computers and do their computer tasks for them, making sure they got in their orders for food and other supplies. Of course all food handlers would need to be vaccinated and use more sterile procedures.  read more »

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