In the present instance, going back to the liver-pill circular, I had the symptoms, beyond all mistake, the chief among them being “a general disinclination to work of any kind.”
What I suffer in that way no tongue can tell. From my earliest infancy I have been a martyr to it. As a boy, the disease hardly ever left me for a day. They did not know, then, that it was my liver. Medical science was in a far less advanced state than now, and they used to put it down to laziness.
“Why, you skulking little devil, you,” they would say, “get up and do something for your living, can’t you?” — not knowing, of course, that I was ill.
And they didn’t give me pills; they gave me clumps on the side of the head. And, strange as it may appear, those clumps on the head often cured me — for the time being. I have known one clump on the head have more effect upon my liver, and make me feel more anxious to go straight away then and there, and do what was wanted to be done, without further loss of time, than a whole box of pills does now.
You know, it often is so — those simple, old-fashioned remedies are sometimes more efficacious than all the dispensary stuff.
Jerome K. Jerome, Three Men in a Boat (to say nothing of the dog), 1889.
September 27, 2014
August 24, 2014
It is a most extraordinary thing, but I never read a patent medicine advertisement without being impelled to the conclusion that I am suffering from the particular disease therein dealt with in its most virulent form. The diagnosis seems in every case to correspond exactly with all the sensations that I have ever felt.
I remember going to the British Museum one day to read up the treatment for some slight ailment of which I had a touch — hay fever, I fancy it was. I got down the book, and read all I came to read; and then, in an unthinking moment, I idly turned the leaves, and began to indolently study diseases, generally. I forget which was the first distemper I plunged into — some fearful, devastating scourge, I know — and, before I had glanced half down the list of “premonitory symptoms,” it was borne in upon me that I had fairly got it.
I sat for awhile, frozen with horror; and then, in the listlessness of despair, I again turned over the pages. I came to typhoid fever — read the symptoms — discovered that I had typhoid fever, must have had it for months without knowing it — wondered what else I had got; turned up St. Vitus’s Dance — found, as I expected, that I had that too, — began to get interested in my case, and determined to sift it to the bottom, and so started alphabetically — read up ague, and learnt that I was sickening for it, and that the acute stage would commence in about another fortnight. Bright’s disease, I was relieved to find, I had only in a modified form, and, so far as that was concerned, I might live for years. Cholera I had, with severe complications; and diphtheria I seemed to have been born with. I plodded conscientiously through the twenty-six letters, and the only malady I could conclude I had not got was housemaid’s knee.
I felt rather hurt about this at first; it seemed somehow to be a sort of slight. Why hadn’t I got housemaid’s knee? Why this invidious reservation? After a while, however, less grasping feelings prevailed. I reflected that I had every other known malady in the pharmacology, and I grew less selfish, and determined to do without housemaid’s knee. Gout, in its most malignant stage, it would appear, had seized me without my being aware of it; and zymosis I had evidently been suffering with from boyhood. There were no more diseases after zymosis, so I concluded there was nothing else the matter with me.
I sat and pondered. I thought what an interesting case I must be from a medical point of view, what an acquisition I should be to a class! Students would have no need to “walk the hospitals,” if they had me. I was a hospital in myself. All they need do would be to walk round me, and, after that, take their diploma.
Then I wondered how long I had to live. I tried to examine myself. I felt my pulse. I could not at first feel any pulse at all. Then, all of a sudden, it seemed to start off. I pulled out my watch and timed it. I made it a hundred and forty-seven to the minute. I tried to feel my heart. I could not feel my heart. It had stopped beating. I have since been induced to come to the opinion that it must have been there all the time, and must have been beating, but I cannot account for it. I patted myself all over my front, from what I call my waist up to my head, and I went a bit round each side, and a little way up the back. But I could not feel or hear anything. I tried to look at my tongue. I stuck it out as far as ever it would go, and I shut one eye, and tried to examine it with the other. I could only see the tip, and the only thing that I could gain from that was to feel more certain than before that I had scarlet fever.
I had walked into that reading-room a happy, healthy man. I crawled out a decrepit wreck.
Jerome K. Jerome, Three Men in a Boat (to say nothing of the dog), 1889.
July 19, 2014
Scott Greenfield on an interesting attempt by the US government to get private delivery firms to act as an unpaid arm of law enforcement:
In the future, everyone will be a cop for 15 minutes.
– Apologies to Andy Warhol
And if you don’t fulfill your duty, the government will indict you. United Parcel Service decided it was a better business move to pay off the government, at a price tag of $40 million. Federal Express refused. The government has now indicted FedEx for its refusal to capitulate.
The indictment relates to internet “pharmacies,” that ship drugs to people who may have no prescription and without having been treated by a physician. Not all internet pharmacies are evil, and not all prescriptions filled are wrongful, but the government nonetheless demands that delivery companies be not only its eyes and ears, but its arms and legs, in this battle of its war against crime. If only corporate America would faithfully serve its master, it would make law enforcement’s job so much easier.
The indictment is the typical slinging together of vague back-end anecdotes which, when the salient details are studiously omitted, create the disturbing appearance of complicity, if not exactly wrong-doing. After all, shouldn’t a delivery company know that it’s being used by criminals? Because it’s their responsibility to spy on packages, or see into the hearts of recipients, or know each back office deal of their customers?
Ironically, it’s not that FedEx wants to deliver contraband, but that the government refused to cooperate.
H/T to Amy Alkon for the link.
May 14, 2014
Amity Shlaes talks about a movement to allow more freedom of choice, but in an unusual and tightly regulated sector:
For decades now the Food and Drug Administration has maintained an onerous and slow approval process that delays the debut of new drugs for fatal diseases, sometimes for years longer than the life span of the patients desperate to try them. Attorneys and scholars at the Goldwater Institute of Arizona have crafted legislation for the states that would allow terminally ill patients to try experimental drugs for cancer or degenerative neurological diseases earlier. These “Right to Try” bills are so scripted that they overcome the usual objection to delivery of such experimental drugs: safety. Under “Right to Try,” only drugs that have passed the crucial Phase 1 of FDA testing could be prescribed, thereby reducing the possibility of Thalidomide repeat. Second, only patients determined to have terminal cases would be eligible to purchase the drugs, making it harder to maintain that the drug will jeopardize their lives.
Representatives in Colorado, Louisiana, and Missouri approved the “Right to Try” measure unanimously. Citizens of Arizona will vote on the effort to circumvent the FDA process this fall.
Why the popularity? The phrase “Right to Try” appeals especially in a nation that senses all too well the reductions in freedom that come as the Affordable Care Act is implemented. The recent success of The Dallas Buyers’ Club, a film about a man who procured experimental drugs for AIDS patients, also fuels the “Right to Try” impulse. Some of the popularity comes from our culture of choice. In Colorado, where citizens have choice about abortion, and now the choice to use marijuana, they may also get what seems an elemental choice, that to try to save their own lives.
But of course “Right to Try” also sails because of the frustration of tragedy. Years ago a man named Frank Burroughs founded the Abigail Alliance after conventional options failed to cure his 21-year-old daughter’s cancer. Abigail’s oncologist tried to get Abigail newer drugs, Erbitux or Iressa from AstraZeneca, the company with which Pfizer hopes to merge. But the drugs were not available in time to save the girl. The Abigail Alliance is attempting on the federal level what Goldwater is trying for states: The federal bill’s name is the Compassionate Care Act. “Those waiting for FDA decisions, mainly dying patients and those who care for them, view the agency as a barrier,” co-founder Steve Walker explained simply. And who can disagree? Many of the supporters of “Right to Try” or the Abigail Alliance are businesspeople or scientists who are motivated to honor ones they have lost to illness; others are racing to save sick family who are still living. Yet others labor for patients in particular or science in general.
May 7, 2014
In Forbes, Matthew Herper looks at how Novartis is transforming itself in an attempt to conquer cancer:
“I’ve been an oncologist for 20 years,” says Grupp, “and I have never, ever seen anything like this.” Emily has become the poster child for a radical new treatment that Novartis, the third-biggest drug company on the Forbes Global 2000, is making one of the top priorities in its $9.9 billion research and development budget.
“I’ve told the team that resources are not an issue. Speed is the issue,” says Novartis Chief Executive Joseph Jimenez, 54. “I want to hear what it takes to run this phase III trial and to get this to market. You’re talking about patients who are about to die. The pain of having to turn patients away is such that we are going as fast as we can and not letting resources get in the way.”
A successful trial would prove a milestone in the fight against the demon that has plagued living things since dinosaurs roamed the Earth. Coupled with the exploding capabilities of DNA-sequencing machines that can unlock the genetic code, recent drugs have delivered stunning results in lung cancer, melanoma and other deadly tumors, sometimes making them disappear entirely – albeit temporarily. Just last year the Food & Drug Administration approved nine targeted cancer drugs. It’s big business, too. According to data provider IMS Health, spending on oncology drugs was $91 billion last year, triple what it was in 2003.
But the developments at Penn point, tantalizingly, to something more, something that would rank among the great milestones in the history of mankind: a true cure. Of 25 children and 5 adults with Emily’s disease, ALL, 27 had a complete remission, in which cancer becomes undetectable. “It’s a stunning breakthrough,” says Sally Church, of drug development advisor Icarus Consultants. Says Crystal Mackall, who is developing similar treatments at the National Cancer Institute: “It really is a revolution. This is going to open the door for all sorts of cell-based and gene therapy for all kinds of disease because it’s going to demonstrate that it’s economically viable.”
H/T to Megan McArdle for the link.
November 29, 2013
Nick Gillespie on the mindnumbingly awful exercise of FDA regulatory power in shutting down personal DNA testing company 23andMe:
Personal genetic tests are safe, innovative, and the future of medicine. So why is the most transparent administration ever shutting down a cheap and popular service? Because it can.
In its infinite wisdom, the Food and Drug Administration (FDA) has forbidden the personal genetic testing service 23andMe from soliciting new customers, claiming the company hasn’t proven the validity of its product.
The real reason? Because when it comes to learning about your own goddamn genes, the FDA doesn’t think you can handle the truth. That means the FDA is now officially worse than Oedipus’s parents, Dr. Zaius, and the god of Genesis combined, telling us that there are things that us mere mortals just shouldn’t be allowed to know.
23andMe allows you to get rudimentary information about your genetic makeup, including where your ancestors came from and DNA markers for over 240 different hereditary diseases and conditions (not all of them bad, by the way). Think of it as the H&M version of the haute couture genetic mark-up that Angelina Jolie had done prior to having the proactive mastectomy that she revealed this year.
Peter Huber of the Manhattan Institute, a conservative think tank, has an important new book out called The Cure in the Code: How 20th Century Law is Undermining 21st Century Medicine. Huber writes that whatever sense current drug-approval procedures once might have had, their day is done. Not only does the incredible amount of time and money — 12 years and $350 million at a minimum — slow down innovation, it’s based on the clearly wrong idea that all humans are the same and will respond the same way to the same drugs.
Given what we already know about small but hugely important variations in individual body chemistry, the FDA’s whole mental map needs to be redrawn. “The search for one-dimensional, very simple correlations — one drug, one clinical effect in all patients — is horrendously obsolete,” Huber told me in a recent interview. And the FDA’s latest action needs to be understood in that context — it’s just one more way in which a government which now not only says we must buy insurance but plans whose contours are dictated by bureaucrats who arbitrarily decide what is best for all of us.
November 24, 2013
In the New York Times, Mary Lou Jepson talks about the near-total loss and recovery of her life:
In my early 30s, for a few months, I altered my body chemistry and hormones so that I was closer to a man in his early 20s. I was blown away by how dramatically my thoughts changed. I was angry almost all the time, thought about sex constantly, and assumed I was the smartest person in the entire world. Over the years I had met guys rather like this.
I was not experimenting with hormone levels out of idle curiosity or in some kind of quirky science experiment. I was on hormone treatments because I’d had a tumor removed along with part of my pituitary gland, which makes key hormones the body needs to function.
In my experience it can be difficult to find a doctor to help a patient do this. I believe it is only partly because of the shortage of endocrinologists, doctors who specialize in the hormonal systems. Some doctors seemed not to believe that every hormone mattered. How many other patients like me have failed to find their ideal balance of medications?
There is evidence that careful tuning of these hormones can lead to dramatic personal and professional outcomes. Doctors and patients should consider replacement of every known hormone that is missing. New neurochemicals are identified by researchers every few years and should be studied as possible additions to the mix.
And access to these medications should not be hindered. As it stands today, some of the hormones I need daily to stay alive and to thrive can be, and frequently have been, blocked at the whim or neglect of a doctor’s office, insurance company or pharmacy. And still, 18 years after my surgery and despite great advances in endocrinal science, I need to fight to get them.
Disputes between organizations on whether prescriptions, test results or proper forms were transmitted or not. Communication breakdowns. A Kafka-esque nightmare of constantly needing another approval. It can take weeks to be notified of a rejection.
H/T to Tim O’Reilly for the link:
— Tim O'Reilly (@timoreilly) November 24, 2013
August 8, 2013
ThinkProgress reports that CNN’s Dr. Sanjay Gupta has changed his position on the medical use of marijuana:
CNN’s Chief Medical Correspondent Dr. Sanjay Gupta reversed his position on marijuana’s health benefits and apologized for his previous stand against it in an article Thursday for CNN. In 2009, Gupta penned an op-ed advocating against marijuana, where he advised as a doctor that “marijuana isn’t really very good for you.” At the time, he was in the running for an appointment to Surgeon General.
Since then, additional research and his work on a documentary have convinced him otherwise.
“I apologize because I didn’t look hard enough, until now,” he said. “I didn’t look far enough. I didn’t review papers from smaller labs in other countries doing some remarkable research, and I was too dismissive of the loud chorus of legitimate patients whose symptoms improved on cannabis.”
“We have been terribly and systematically misled for nearly 70 years in the United States, and I apologize for my own role in that.”
June 21, 2013
In The Economist, some new ideas about silver:
Silver has long been known as more than bling. In the fifth century BC Hippocrates noted its ability to preserve food and water. In the late 19th century silver-nitrate eye drops were administered to newborns to prevent conjunctivitis (though this remedy has since been replaced with an antibiotic). Today silver is routinely found in wound dressings and catheters to treat or prevent infections. Yet, despite its widespread use, the source of silver’s antibacterial properties has remained shrouded in mystery.
Now Jose Morones-Ramirez, from Boston University, and colleagues think they may have cracked it. As they report in Science Translational Medicine, silver fights bacteria in a number of ways.
First, silver ions (as atoms stripped of some of their electrons are known) help, through a process known as the Fenton reaction, to convert hydrogen peroxide into molecules called hydroxyl radicals. Radicals are unstable and readily react with cellular components, damaging them. Indeed, an excess is thought to contribute to ageing-related illnesses in humans. However, the researchers found, concentrations of silver ions low enough to leave human cells unscathed nonetheless appear to wreak havoc on bacterial ones.
Using a dye that glows in the presence of hydroxyl radical, Dr Morones-Ramirez treated the bacterium Escherichia coli with silver nitrate (a source of silver ions). The E. coli glowed, and then promptly bit the dust. But when the bacteria were first bathed in a chemical which mops up the hydroxyl radicals, they survived. This points to silver’s effect on the production of hydroxide radicals as the explanation.
June 19, 2013
History Today linked to an article in their archives from 1975 from Pamela Vandyke Price discussing the ancient provenance of Vermouth:
When the great vermouth establishments refer to their product as ‘the oldest form of wine in the world’, they are not exaggerating. If we could travel in time, we might find many of the wines praised in antiquity to be harsh, sour and coarse to our palates, but the ‘aromatized wine’ that we know as vermouth would then have existed and, even if we drank it for medicinal or preventive reasons rather than for enjoyment, we could recognise it and relate it to the vermouths of today.
Vermouth can be, and often is, made wherever wine is made. The ancient Egyptians used both wine and beer, plus juniper, frankincense, celery, lotus leaves and honey, in the treatment of certain ailments; and it is by a method of infusion, maceration, distillation, or two or all three of these processes that, essentially, vermouth is made today. In Book IV of the Odyssey, Helen throws a drug given to her by an Egyptian lady into the bowl in which the wine is to be mixed and diluted before dinner; this ‘had the power of robbing grief and anger of their sting and banishing all painful memories’ — an efficacious aperitif, assuring good digestion. At the end of the third millennium B.C. what is perhaps the first written doctor’s prescription is recorded in cuneiform script on a tablet from the Sumerian city of Nippur — a physician notes that certain powders should be infused with a type of wine.
[. . .]
Other families in the drink business were quick to see the possibilities for vermouth, setting up in Turin, Marseilles and Sete (again in proximity to mountain herbs and a quantity of wine), and in Chambray. Many of them are still family concerns, even though they are great empires of the drink business. Martini & Rossi, who were founded about 1840, replaced a much older concern making vermouths and liqueurs at Pessione, near Turin (the head of that firm was the grandfather of Giovanni Angelli, founder of Fiat); the superb museum now established alongside the Pessione installations is a necessary detour for anyone interested in the history of wine from the earliest times.
The Cinzano family began in the drink business in the sixteenth century, and in 1757 the brothers Carlo Stefano and Giovanni Giacomo were invested as Master Distillers in Turin; today their business is gigantic, including, among other things, the Florio concern at Marsala, (itself including the former cantinas of Ingham and Woodhouse). Louis Noilly, in business at the beginning of the nineteenth century in Lyons, set up in the vermouth trade with his son-in-law, Claudius Prat and they enjoyed so much success that by 1843 they moved their headquarters to Marseilles. Madame Josephine Prat, who ran the business after the deaths of the two founders, was succeeded by her two children; and her granddaughter, Vicomtesse Vigier, who entered the firm before 1939, directed it until 1970 when she died, over a hundred years old.
It seems a little odd that, with so many modifications of wine-making and changes in the tastes of drinkers, aromatized wine should still be in demand. But, in fact, it is increasingly so. Whenever people order a straight vermouth they are ordering the oldest wine in the world.
June 12, 2013
At Marginal Revolution, Alex Tabarrok links to a new paper by Peter Huber:
[. . .]
The current regime was built during a time of pervasive ignorance when the best we could do was throw a drug and a placebo against a randomized population and then count noses. Randomized controlled trials are critical, of course, but in a world of limited resources they fail when confronted by the curse of dimensionality. Patients are heterogeneous and so are diseases. Each patient is a unique, dynamic system and at the molecular level diseases are heterogeneous even when symptoms are not. In just the last few years we have expanded breast cancer into first four and now ten different types of cancer and the subdivision is likely to continue as knowledge expands. Match heterogeneous patients against heterogeneous diseases and the result is a high dimension system that cannot be well navigated with expensive, randomized controlled trials. As a result, the FDA ends up throwing out many drugs that could do good:
Given what we now know about the biochemical complexity and diversity of the environments in which drugs operate, the unresolved question at the end of many failed clinical trials is whether it was the drug that failed or the FDA-approved script. It’s all too easy for a bad script to make a good drug look awful. The disease, as clinically defined, is, in fact, a cluster of many distinct diseases: a coalition of nine biochemical minorities, each with a slightly different form of the disease, vetoes the drug that would help the tenth. Or a biochemical majority vetoes the drug that would help a minority. Or the good drug or cocktail fails because the disease’s biochemistry changes quickly but at different rates in different patients, and to remain effective, treatments have to be changed in tandem; but the clinical trial is set to continue for some fixed period that doesn’t align with the dynamics of the disease in enough patients
Or side effects in a biochemical minority veto a drug or cocktail that works well for the majority. Some cocktail cures that we need may well be composed of drugs that can’t deliver any useful clinical effects until combined in complex ways. Getting that kind of medicine through today’s FDA would be, for all practical purposes, impossible.
The alternative to the FDA process is large collections of data on patient biomarkers, diseases and symptoms all evaluated on the fly by Bayesian engines that improve over time as more data is gathered. The problem is that the FDA is still locked in an old mindset when it refuses to permit any drugs that are not “safe and effective” despite the fact that these terms can only be defined for a large population by doing violence to heterogeneity. Safe and effective, moreover, makes sense only when physicians are assumed to be following simple, A to B, drug to disease, prescribing rules and not when they are targeting treatments based on deep, contextual knowledge that is continually evolving
March 29, 2013
Demonizing smokers hasn’t forced them to quit … let’s start sending them to psychiatric care instead
When the all the persuasion, “nudging”, shaming, harassment, and legal shenanigans haven’t worked, try taking a leaf out of the old Soviet Union playbook for dealing with dissidents:
Smoking may be a sign of psychiatric illness, experts say. Doctors should routinely consider referring people who smoke to mental health services, in case they need treatment, they add.
The controversial recommendation from the British Lung Foundation, a charity, comes in response to a major report, Smoking and Mental Health, published this week by the Royal College of Physicians and the Royal College of Psychiatrists with the Faculty of Public Health. It says that almost one in three cigarettes smoked in Britain today is smoked by someone with a mental disorder. When people with drug and alcohol problems are included the proportion is even higher.
The reason is that smoking rates have more than halved over the past 50 years, but the decline has not happened equally in all parts of society.
“Smoking is increasingly becoming the domain of the most disadvantaged: the poor, homeless, imprisoned and those with mental disorder. This is a damning indictment of UK public health policy and clinical service provision,” the report says.
March 14, 2013
In sp!ked, Robin Walsh debunks some of the scare factor from recent reports about antibiotic resistant diseases and the looming pandemic:
The UK’s chief medical officer (CMO), Professor Dame Sally Davies, made a splash in the media this week with her warning that antibiotic resistance is the new climate change. There is a ‘catastrophic threat’ of ‘untreatable’ diseases, she said, which promise to return us to a ‘nineteenth century’ state of affairs. The CMO has form: she warned the House of Commons health select committee about the same problem in similarly stringent terms back in January — a case not so much of apocalypse now, as apocalypse again.
As with all such stories, reading the actual CMO’s report leavens some of the hysterical excesses of the press, which were stoked up by the CMO’s excitable media appearances. Setting out the epidemiology of infectious diseases in the UK, the report highlights that while some drug-resistant infections, such as the well-known Clostridium difficile (C diff) and MRSA, are becoming less widespread, there is an increasing occurence of harder to treat multi-drug resistant bacterial infections, which, although still only in the hundreds of cases per year, are on the rise. The report states that only five antibiotics to fight such infections are currently in phase II or III trials, so the cupboard seems worryingly bare of new, necessary drugs.
So if we’re running short on drugs, how can we make more? A sensible article in the British Medical Journal from 2010 clearly set out the challenges facing the development of new antibiotics. Firstly, there are many regulatory hurdles that make running clinical trials in this area difficult. More importantly, there is a major financial disincentive for drug companies to develop antibiotics. Currently, drugs which are profitable are those for chronic conditions that are prescribed lifelong: painkillers for arthritis, diabetes drugs, and the like. A drug that you take once to cure you is unprofitable; doubly so if it is likely to be husbanded to prevent resistance developing until the patent runs out. A change in government payments to incentivise new antibiotics, like that which already applies to so-called ‘orphan’ drugs for rare diseases, would be an easy and rational step towards producing more drugs that meet our needs.
February 6, 2013
Matt Peckham on the very near future of organ replacement technology:
Say you need a new trachea, a part of the body we’ve already managed to replicate using stem cells and successfully transplant to a human with late-stage tracheal cancer (I’m not making that up or exaggerating). With a 3D printer and a bunch of stem cell-saturated bio-ink, you might be able to just print that trachea on demand thanks to a new technique that lets you pass human embryonic stem cells (hESCs) through a printer nozzle without destroying them.
A team of researchers from Scotland announced Monday that they’d finally managed to get an inkjet-style printer to craft an organic 3D object. Not an actual organ (well, not yet), but these scientists claim they’ve been able to clear a crucial hurdle: getting hESCs, prized for their ability to become cells of any tissue type, to survive the printing process.
The solution involved rejiggering the way the inkjet-style 3D printer worked, specifically the printing valve, which had to be tweaked to ever-so-gently deposit blobs of hESCs in programmable patterns without compromising the viability and functionality of the cells themselves. The researchers figured out how to do this using two types of bio-inks as well as allow for independent control of the amount in each droplet (with considerable control granularity — down to less than five cells per droplet). The results of the experiment were just published in the bio-science print and online journal Biofabrication.
September 28, 2012
Brid-Aine Parnell at The Register, talking about specialized electronic development:
When it comes to electronics, boffins are usually going one way — how to make them smaller, faster and longer lasting, but a few researchers are going against the tide — looking for electronics that can last just a moment and then disappear.
At the University of Illinois, with help from Tufts and Northwestern Universities, scientists have come up with biodegradable electronics that can do their job and then dissolve. Apart from reducing the amount of consumer electronics in landfills, the disappearing gizmos could also work as medical implants, before dissolving in bodily fluids, as environmental monitors or any other device that needs to disappear.
“From the earliest days of the electronics industry, a key design goal has been to build devices that last forever — with completely stable performance,” Illinois professor of engineering and project leader John Rogers said.
“But if you think about the opposite possibility — devices that are engineered to physically disappear in a controlled and programmed manner — then other, completely different kinds of application opportunities open up.”