With this issue we introduce a simpler but, we hope, no less useful format for the Digest. Instead of individual digests of news articles, links to the source articles, and a meta-digest with commentary, we instead present the meta-digest/commentary and links to the original source articles. Let us know what you think.

Digest readers know that a brain-computer interface (BCI) has already entered human clinical trials and that BCIs will soon be ready for prime time. When they are, writes Clive Thompson in Slate, “they’ll introduce some fascinating moral and legal shifts. The ongoing battle over the life and death of the supposedly brain-dead Terri Schiavo would play out quite differently if Schiavo herself could signal her desires, or even if we knew just a bit more about her mental state.” We may be forgiven for intruding on the thoughts of patients unable to express them, but what about intruding on your thoughts, and even on your character? When you consider that yesterday’s relatively large-grained PET and fMRI scanners have helped pinpoint regions in the brain responsible for:

• Decision-making;
• Memory storage and retrieval;
• Emotions, including fear and affection; and
• Character traits, including extroversion, empathy, and persistence,

then we are in for some eye-openers about people as scanning goes molecular. We are also in for some ethical and social challenges as “neuroentrepreneurs” and “neuromarketers” learn how to exploit our greater neural transparency. While it is comforting that “neuroethicists” are alert to the issue, people enamored of – and governments and politicians beholden to – an unfettered free market are not likely to pay much heed.

In addition to the digital representation of the psyche (the “psychome,” perhaps?) the future of medicine in the next ten to 20 years will unquestionably revolve around the digital representation of the individual patient’s physiology derived from the genome and molecular-level scans, and processed using the tools of systems biology and computational physiology. As a member of the international Physiome Project, the University of Auckland in New Zealand has already produced a digital skeletal system, digital heart, and digital lungs, with the nervous, endocrine, immune, sensory, skin, kidney-urinary, and reproductive systems to follow. (The brain may take a bit longer.) The Physiome Project will lead ultimately to safe and effective pharmacogenomic medicine while eliminating the cost and delay of clinical trials, by allowing digital drugs to be tested quickly on the digital patient to be sure they work prior to using the real drug on the real patient.

While we wait for the Physiome Project’s software approach to mature, there are improved “wetware” approaches emerging today. They include a new lab chip that can test in minutes whether cells respond to antibiotics and other stimuli (pathogens, toxins, radiation, chemotherapy, etc.), eliminating the need to culture bacteria to assess their sensitivity to antibiotics. It is claimed to be simple to use, inexpensive, low power (a watch battery will do), portable, provide real-time results, and be applicable to “an enormous number of problems.” Another available approach is a recently FDA-approved DNA chip that can determine how quickly a patient will likely metabolize many commonly prescribed medications and therefore help the doctor determine the appropriate dosage for that patient. It does all this simply by analyzing two enzymes.

While those chips are designed for specific purposes, gene chips often have a more general exploratory application and generate mountains of data. Several tools now available to help researchers analyze massive genetic datasets will help accelerate the development and adoption of genetic diagnosis and therapies. So will a new method of genetic engineering that involves shining a laser on a cell bathed in a solution of the genetic material to be introduced into the cell, and presto! – the cell wall opens, gulps in some of the genetic material, and closes again. No harm is done to the cell, which grows and multiplies normally, except that it is now genetically different.

The result of such advances in medical science and technology is astonishing progress toward cures for disease. Consider just a few of the advances reported in the last couple of months:

• The discovery of a genetic “master switch”in the liver that triggers type 2 diabetes. The discoverers went on to test simple, inexpensive, and safe anti-inflammatory salicylate drugs to counter the inflammation caused by the gene and thus halt the disruption of insulin production caused by the inflammation. The drugs have worked in mice, and human trials are under way.
• The prevention of lupusin mice by changing a single receptor gene. This won’t cure existing sufferers, but it could prevent the disease from taking hold to begin with.
• A technology that finds and eliminates cancer stem cells– the cells most difficult to eradicate using standard radiation and chemotherapies. It is entering the commercialization phase, though it may take five years.
• A genetically re-engineered HIV virusthat attacked metastasized melanoma cells in the lungs of living mice. HIV viruses could be re-engineered to target other cancers and diseases, as well.
• The gastrointestinal stromal tumor drug SU-11248 could receive expedited approval from the US Food and Drug Administration for patients who do not respond to the drug Gleevec. The drug is one of a new class that targets molecular defects, and it may also be effective against renal cell carcinoma.
• “Progenitor” heart cells, similar to stem cells, could also lead to regeneration therapy for damaged heart tissue. A few hundred progenitor cells cultivated in vitrocan be turned into more than a million muscle cells.
• Human embryonic stem cells have been engineered to become motor neurons. This could have profound implications for the treatment of ALS and spinal cord injuries. The key to this breakthrough apparently lay in the timing of the engineering intervention, which appears to be different for different animals and may explain why experimental successes in mice have not worked in humans.

Advancing just as fast as digital psychology/biology and lab/gene chips is the field of nanomedicine. There are now more than 60 nanotechnology-based drugs and drug delivery systems plus more than 90 nano-based medical devices or diagnostic tests under development. They include Qdots (“Quantum dots”) that can track molecules around the insides of cells and are being developed to spot cancer at its earliest stage. Even better, “photo-thermal nano-shells” of gold infused into mice sought out cancers and then, when heated by near-infrared light, killed the tumors without damaging healthy tissue. Then there are self-assembling, man-made nanofibers that have helped repair spinal cord injuries and bone in mice. Not least, there is the possibility of microscopic implantable sensors made of carbon nanotubes to monitor blood sugar, cholesterol, hormone levels, and whatever else is of interest.

A drawback with nano-scale things is that they are below microscopic, and can only be viewed via electron microscopes and other expensive proxy devices. The best optical microscope can image objects no smaller than 200 nanometers, but a prototype computer-assisted optical microscope has succeeded in imaging features as small as 40 nanometers and might be able to go below 10 nanometers. If successfully developed, such a microscope could be used in many processes requiring nanoscale precision.

The accelerating advances in medicine evidenced above (and below, and indeed throughout all issues of the Digest) highlight the increasing importance of evidence-based medicine. There will soon be so many diagnostic and treatment options to choose from, at least until definitive cures are found (perhaps at the individual genetic level), that conscientious doctors and informed patients will want to review them all. The only way for that to happen is through a publicly-accessible distributed database of the results of all treatments, including experimental treatments and tests, at the patient level, linked to decision-support tools that help the doctor and the patient arrive at the most appropriate tests and therapies for that particular patient.

Other recent advances include:

Plastic Blood Vessels: The plastic tubing used as prosthetic vascular grafts in some 200,000 US hemodialysis patients, especially if smaller than 6 mm in diameter, soon clogs up as blood platelets stick to the inside surfaces. A new polyurethane coated with a chemical additive releases nitric oxide (NO) that stops platelets sticking together. The nitric oxide has the added benefits of stimulating growth in the cells lining blood vessels and retarding the growth of smooth muscle that might constrict an artificial vessel. Successful animal experiments have been reported, the very first of which was led by the Detroit Medical Center’s chief of vascular surgery. If long-lasting NO-eluting plastic blood vessels eventually make their way safely into humans, it would have a significant impact on cardiovascular surgery in general – not just for hemodialysis access – and they may compete with other novel approaches to revascularization, such as tissue engineering of the heart and blood vessels.

Bioartificial Kidney: The bioartificial kidney we first reported in August 2003 is now beginning 72-hour clinical (efficacy) trials, having earlier successfully completed a 24-hour safety trial in ten patients. It may not be too soon for those who make a living from the dialysis business to begin thinking about their futures.

Skin Printer: “Skin printers” under development use “ink” prepared from cells from a patient’s body, cultivated to produce more of them in a nutrient-rich liquid. After measurements of the patient’s wound are fed into a computer, the printer prints (in cellular ink) an image of the wound area onto a biodegradable plastic tissue, which serves as a temporary scaffold for the cells until the graft holds naturally. The method will reduce scarring and eliminate immune responses. Clinical trials are anticipated soon, and a product could be available to hospitals in five years. There is no reason why such a printer, given enough print heads, could not print whole organs with many layers of different cell types, but that more ambitious goal will take longer.

iPACS: An example of how healthcare technologies can come rapidly down in cost as a result of acceleration in computing generally, is a California doctor’s adoption of the Apple iPod and free (open source) award-winning software called OsiriX for viewing radiology images. Megadollar radiology imaging monitors and PACS software will either have to come down to reasonable prices or risk being viewed as unaffordable luxuries – nice, but not necessary – because things will only get better. Consider that Hewlett-Packard recently unveiled a circuit element measuring just 2-3 nanometers, which contrasts with the 90 nanometer size of the smallest circuit elements in today’s chips, and that a consortium of industry heavyweights called the Holographic Versatile Disc (HVD) Alliance has been formed to agree on standards for a disk that could store a terabyte of data. The disks will also transfer data at over one gigabit per second, or 40 times faster than a DVD. These types of technological advances are what led to the iPOD in the first place, and they are not stopping there: a prototype cell phone contains a projector that can project an image onto a wall or desktop. Goodbye, expensive dedicated radiology viewing room.

Finally, and a propos of nothing, some notes on artificial intelligence:

Though lacking in detail, a reported achievement in creating software that functions as a mind is sufficiently intriguing and potentially boggling to be worth a mention here. Perspex, as it is called, is a way of writing any computer program as a geometrical structure like an artificial neuron, rather than as a series of instructions. Such programs would be self-healing. “Not only does the invention of the Perspex make it theoretically possible for us to develop robots with minds that learn and develop, it also provides us with clues to answer the philosophical conundrum of how minds relate to bodies in living beings,” says a University of Reading press release.

You don’t hear much scoffing at the notion of artificial intelligence these days. Perhaps it’s because of such advances as Perspex and chips just on the market whose “adaptive artificial intelligence” can add intelligence and personality, speech input (recognition), and speech output (talking), to a product for less than a dollar US. Consumers will soon see “user interface features that were never before affordable.” For instance, a robot puppy “may get hungry or sleepy, have specific food preferences, or tend to be excitable or grumpy.” The chip can also endow individual product units with unique “birth characteristics” which, along with the unit’s unique experiences over time, result in no two units being exactly alike. The chips could also enable a light switch or a thermostat to learn a user’s preferences for patterns of use and settings and meet those desires automatically – no setup required. It’s a pity the chips were not around in the bygone days of the hard-to-program VCR (remember those?)