• Already-emerged technologies and techniques underlie the U.S. National Cancer Institute’s confidence that it will be essentially out of a job by 2015. And that’s without considering the rapidly emerging technologies we discuss in Health Futures Digest.
• Viruses may be losing their evolutionary edge in being able to mutate faster than vaccines can keep up. Old vaccines can now be genetically re-engineered to tackle new viruses, and “naked DNA” vaccines that cause an immune response without causing the disease are under development for several major diseases.
• A much-needed new class of antibiotics created using the latest technologies of molecular medicine, and a long-overlooked potential nemesis for at least some antibiotics, are under development.
• An inhalable insulin dispenser could soon receive regulatory approval, and inhalants for a multitude of other diseases and conditions, including pain management, are in the works. They will likely have a significant impact in lowering the cost of administering IVs to patients, besides being potentially more effective, faster-acting, and easier on the patient.
• A non-toxic, protein-based drug for deadly and aggressive hepatocellular cancer has shown such promise in early tests that it has been put on the fast track for FDA review and possible approval.
• A game that helps diabetic children monitor their blood glucose levels properly might be useful in combination with a newly FDA-approved intelligent insulin pump and glucose monitor system, which takes the math — or guesswork — of determining insulin dosage out of the patient’s unreliable hands.
• A prototype “intelligent pill” monitors vital signs inside the body and releases its drug payload according to need.
• Organ and limb transplants are well established, face transplants are coming, and the world’s first tongue transplant has just been done.

The End of Cancer All Over Again

In the 1990s, when the war on cancer seemed lost, a New York Times science writer was criticized for over-enthusiastically reporting a cancer drug that had worked in mice. It is now known that cancer is not so simple; instead, that it is produced by an astronomical combinatorial explosion of interactions among 30,000 genes and 100,000 proteins. The difficulty of finding specific combinations that cause disease is a cause of skepticism about finding genetics-based treatments and cures for multifactorial genetic illnesses such as heart disease and cancer.

But astronomical numbers are not what they used to be, given such technologies as biochips (of which we have just met the next generation and such new approaches as the HapMap project to map “haplotypes,” groups of genes that behave predictably. The future of genetic engineering will likely involve the haplotype and in silico cellular biology.

The magnitude of the problem has not stopped the director of the National Cancer Institute from anticipating “the elimination of suffering and death due to cancer” by 2015. It is not that the Institute has grown any less cautious and conservative; such optimism reasonably follows post-HGP (Human Genome Project) understanding of the genome, and the acceleration of technologies — in particular, the “biochip,” “microarray,” or “gene chip” — bringing advances in drug discovery and development, cancer classification, and early detection. The microarray helped bring the leukemia drug Gleevec, and is facilitating the creation of a “global cancer map” to classify all cancers based on their particular pattern of abnormal genetic activity.

All this is leading to a new way of classifying and diagnosing cancers: “breast cancer” is too imprecise; what is needed is a diagnosis that identifies an individual tumor’s specific genetic activity. It will not only revolutionize diagnosis, but treatment also: a drug that works in only a small percentage of patients is worthy of approval if we know precisely what genetic activity it prevents, and if we know whether a patient’s cancer has that particular activity. It is the gateway to customized medicine.

Microarrays are also helping discover “biomarkers” — early warning signals. Researchers recently found a pattern of proteins which they then used to diagnose early-stage ovarian cancer with 100 percent accuracy in a small test group of women. Early detection may be our best bet for actually curing cancer rather than simply managing it as a chronic disease, which has already become the case for many prostate, breast, colon, and lung cancer patients.

A hundred or so smart drugs are currently in the U.S. Food and Drug Administration (FDA) pipeline to join the handful of successful smart drugs like Rituxan, Herceptin, and Avastin, which have validated the approach of profiling cancers in molecular detail to find their vulnerabilities. Three — Iressa, Velcade, and Bexxar — have received FDA approval in just the last four months, and physicians are beginning to have difficulty keeping up.

References: Kahn, Jennifer (2003). “The End of Cancer (As we Know it).” Wired, Issue 11.08, August; Bailey, Ronald (2003). “Bioengineering Made Simple: Is Human Genetic Engineering Realistic?” Reasononline, July 9; Mishra, Raja (2003). “Advances begin to tame cancer.” Boston Globe, July 6; Tansey, Bernadette (2003). “Cancer sleuthing: Bay Area companies among those profiling the disease.” San Francisco Chronicle, July 6.

Can Vaccines Keep Up?

The discovery of HIV “superinfection” with multiple strains, resulting in mutant strains, adds urgency to the search for an end to AIDS before possibly virulent and intractable mutations proliferate. Genetic tests on a superinfected woman established that two viruses had mixed and produced a hybrid that took over from the original virus.

But work on a vaccine for West Nile virus shows how fast we can now respond to new threats. The West Nile vaccine was created by genetically re-engineering a safe and effective 70-year-old vaccine for yellow fever, a flavivirus like West Nile, substituting West Nile genes for yellow fever genes. It proved safe and effective in primate trials and could be ready for human clinical trials by the end of the summer.

Alternative approaches include a “naked DNA” vaccine which uses proteins from the pathogen to induce an immune response without actually causing the disease (unlike traditional vaccines.) The approach is also being applied to vaccines for HIV, anthrax, Ebola and several other diseases in addition to West Nile, but no naked DNA vaccine has yet been approved for use in humans, and some test results suggest they may not work in everybody.

References: Associated Press (2003). “Superinfections Spawn Mutant HIV.” Wired News, July 15; Philipkoski, Kristen (2003). “West Nile: Beware the Bug’s Bite.” Wired News, July 16.

New Approaches to Antibiotics

Most antibiotics block bacteria’s ability to synthesize proteins or cell membranes. A new approach blocks the inter-bacterial communication that enables them to work in unison to defeat regular antibiotics that would kill them if they were isolated. The approach uses molecules synthesized from one of the communication chemicals in Pseudomonas aeruginosa, a bacterium that chronically infects nearly 70 percent of cystic-fibrosis patients, and is “definitely generalizable to other bacteria,” according to one expert.

The molecules have been shown to block the inter-bacterial communication, but are not yet in themselves very potent and will probably need to be used together with conventional antibiotics to eliminate an infection.

A promising and closer alternative approach is to use bacteriophages — viruses that eat bacteria. Bacteriophage therapy could be available this year; in fact, it has been around for a long time in the East (and as a result, diabetic amputations are practically unknown in the Republic of Georgia) but was not pursued in the West particularly following the discovery of antibiotics. Now, a British company has already begun phase 2 (UK) clinical trials of a phage cream to kill staph infection in the nasal passages and on surgical instruments.

There are some limits on what phages can do, but no apparent downsides.

References: Zacks, Rebecca (2003). “Busting Up Bacterial Gangs.” Innovation, July/August; Philipkoski, Kristen (2003). “West Recruits Bacteria Assassins.” Wired News, June 30.

Inhalable Drugs

The first inhalable insulin is about to land on an FDA desk seeking approval. Of three contenders, two are powders and one is a liquid. All are aerosolized for delivery deep into the lungs. Delivering an exact amount of insulin to the bloodstream is critical, and there is some debate about whether the powder or liquid form is most effective and convenient for the patient, an issue that may be left to the market to decide.

Other products being developed or considered for inhalation include drugs for growth hormone deficiency and anaphylaxis, vaccines, antibiotics, cancer drugs, contraceptives, treatments for neurological disorders and hepatitis C, and THC for pain management. An inhalable morphine is in phase II trials and fentanyl in phase I trials, both for pain management for cancer, AIDS, and post-surgical patients.

The benefits of pain management inhalants accrue not just to patients but also to the healthcare system, since they would significantly reduce the cost — in staff time and materials — of administering IVs. To prevent abuse and misuse, one opioid analgesics inhaler can identify its user and has keys to prevent overdosing. “So,” as Wired‘s Kari Dean puts it, “one day patients might get the keys to their morphine.” Dean’s article is a comprehensive review of the state of inhalables, including a table showing who’s doing what and when.

Reference: Dean, Kari L. (2003). “Breathing New Life Into Medicine.” Wired News, July 16.

Another Cancer On the Run

A fast-tracked protein-based drug called arginine deiminase (ADI) could be approved in Europe next year and in the United States soon after to treat hepatocellular cancer, a very aggressive cancer that kills extremely quickly. Of 19 patients given only months to live and treated with ADI for three months, two are in complete remission, tumors have shrunk by more than half in seven, and have stopped growing in seven more.

ADI attaches to and degrades arginine, an amino acid in the blood, which hepatocellular cancer (and advanced stage melanoma and kidney cancer) need to grow. It does not cause hair loss or vomiting.

Reference: Ward, Karla (2003). “Lexington firm’s cancer drug makes strides: Liver treatment near approval in Europe.” Herald-Leader, July 30.

The Game of Diabetes

A prototype wireless game helps diabetic children monitor their blood-glucose levels properly and receive the correct doses of insulin. The child checks his or her glucose level with a meter that beams the data to a palmtop PDA, into which s/he also enters her insulin dosages. The PDA transmits the level and dosage data wirelessly to a central server. The game proper starts after the day’s third test, when the child begins to guess his or her next glucose level based on the trends indicated by the PDA.

Early tests indicate that children who play the game check their glucose levels more often than those who so not. The trick may be in getting a generation of children brought up on Quake, Doom, and other incredibly powerful and riveting commercial computer games to remember to play their diabetes game.

Still, such a game might be useful in conjunction with Medtronic’s newly FDA-approved “intelligent” insulin pump and glucose monitor system, where the blood sugar reading is transmitted directly to an intelligent insulin pump incorporating a computer that calculates the proper dosage. “The new pump system is so smart it recommends the proper insulin dosage to the patient, after considering a number of variables, such as the amount of insulin previously delivered and still active in the body. The system simplifies this critical information process, so patients no longer feel as though they need to be mathematicians in order to keep their blood sugar levels in control,” says a company press release.

The pump is practically an artificial pancreas. It automatically receives a blood glucose value via wireless and returns accurate glucose results in five seconds. The system uses “the thinnest lancet on the market” and “one of the smallest test strip blood volumes (0.3 microliters).” The system’s data can also be downloaded to a computer for long-term storage and longitudinal data analysis.

References: Unknown (2003). “Making Diabetes a Game.” Technology Review, Prototype section, July/August; Medtronic (2003). “First Wireless Insulin Pump System Designed To Simplify And Improve Diabetes Management Receives FDA Clearance.” Press release, July 7.

Smart Pills Get Smarter

There are smart pills that can figure out for themselves where to go to fix a problem; now here’s one that knows how much drug to release.

Besides its one milliliter payload of drugs for (say) AIDS, cancer, or diabetes, the penny-sized, stomach-acid-resistant, prototype Intelligent Pill (“iPill”) packs sensors to monitor its swallower’s body temperature and pH balance (and perhaps one day, glucose level) and a microchip to process the sensory data and issue commands to a built-in micropump that administers drug doses according to need or at pre-programmed times.

Its supercapacitors power it for up to four hours, which the developers are working to increase to 24. Its electronics fill a space “less than that of 10 blood cells.” It passes through the body as solid waste in one to three days. It could be on the market in four to five years at a cost of about ten cents per pill.

Reference: Knapp, Louise (2003). “Diagnosis and Medicine in a Pill.” Wired, July 28.

First Tongue Transplant

The recipient of the world’s first tongue transplant has was recovering well four days after the procedure, with no swelling, normal color and blood flow, though there is still a risk of rejection and in any event, the patient will likely not regain the sense of taste, his surgeon predicts.

Reference: Reuters (2003). “Tongue transplant man doing well, Austrian doctor.” (Pakistan) Daily Times, July 28.