Knowledge of an individual’s genetic makeup can help scientists figure out how to treat a disease—part of an emerging field known as personalized medicine.

MIT Technology Review, March 27, 2009 — A number of scientists bared their genetic souls recently as part of the Personal Genome Project, a study at Harvard University Medical School. They were among the first of the eventually 100,000 volunteers who will agree to place their genetic profiles on the Internet.

Genetic profiling can provide information on what diseases may befall us. And knowledge of an individual’s genetic makeup may also help scientists figure out how to treat diseases—part of an emerging field known as personalized medicine.

As many doctors freely admit, says Julie Johnson, director of the Center of Phamacogenomics at the University of Florida (UF), prescribing medicine is “more of an art than a science.” Approved drugs work—but not 100 percent of the time, and not for 100 percent of the population. Some people have no response to certain drugs, and others experience severe side effects.

What determines whether a particular treatment is effective or leads to severe side effects is our genes, scientists believe. Personalized medicine holds the promise of tailored medical treatments based on genetic information, rather than a one-size-fits-all approach.

The UF center participated in studies on warfarin, a blood thinner prescribed for millions of Americans to prevent heart attack or clotting after a heart attack. Too little of the drug causes a risk of clotting, and too much can cause excessive bleeding. “There’s a very narrow window, and there’s a great deal of variability among patients,” says Johnson. “A lot of work in the past decade has uncovered several genes that help explain a great deal of that variability.” In 2007, the FDA cleared a genetic test for sensitivity to warfarin to help doctors prescribe the correct dosage, although the tests are not yet widely implemented.

The UF center is also focusing research on drugs prescribed for hypertension, in an attempt to find the genes that “will predict how much a person’s blood pressure will go down if they’re administered certain medicines,” says Johnson.

Speeding the Process

Part of what has contributed to the increasing interest in personalized medicine is the speed and cost of sequencing genomes. The first human genome took many years and millions of dollars to sequence. The price has already dropped into the thousands instead of millions of dollars, and it’s expected to continue to fall. The journal Science listed “faster, cheaper genome sequencing” as one of the top scientific advances in 2008.

These advances have increased the speed of research in the field. John Reed, the president and CEO of Burnham Institute for Medical Research, a center with campuses in San Diego, CA, and Orlando, FL, says that the Florida campus has engaged in major initiatives related to personalized medicine. While Burnham’s research has traditionally focused on cancer and on neurodegenerative and inflammatory diseases, the scientific team is expanding into obesity, diabetes, and metabolism research.

“We all have friends who can eat french fries every day and never gain weight, while the rest of us will have a hard time getting the belt to fit,” says Reed. “There are genetic differences in how we metabolize food—individual metabolic rates, hormone signaling—that’s all just being worked out.” Burnham is partnering with the clinical research institute at Florida Hospital, particularly the diabetes center, to engage in research on the metabolic systems of the patients there.

A related field of research involves investigating which chemicals can affect the actions of proteins, encoded by specific genes. This is a natural path to drug discovery, but it can also aid in genomic research. “A chemical probe can be used in basic research to help identify the role of a protein or a pathway, aiding in understanding the biology of a particular gene,” says Patrick Griffin, chair of Molecular Therapeutics at Scripps Florida, a campus of Scripps Research Institute headquartered in California.

The National Institutes of Health (NIH) funds four molecule-screening centers in the United States to rapidly test a library of chemicals against specific proteins. Scripps Florida operates one of the four centers.

Burnham operates a second of those NIH molecule-screening centers at both its California and Florida research centers. Currently, its screening output can tackle half a million chemicals in one day, but the new system being developed in Orlando will be able to handle as many as 2.2 million chemicals a day.

The fields of genome research and rapid drug discovery are coming together to enhance each other, says Reed. “We’ll be able to, with far more accuracy, define for whom a drug is really going to work, and to avoid a lot of trial and error that we experience when we’re confronted with a health issue.” He and other researchers in the field see a time not too far in the future when understanding individual genomes will lead to better, more effective medical treatments for everyone.

Virginia Commonwealth University School of Medicine researchers have discovered that adult animals with hearing loss actually re-route the sense of touch into the hearing parts of the brain.

In the study, published online in the Early Edition of the Proceedings of the National Academy of Sciences the week of March 23, the team reported a phenomenon known as cross-modal plasticity in the auditory system of adult animals. Cross-modal plasticity refers to the replacement of a damaged sensory system by one of the remaining ones. In this case, the sense of hearing is replaced with touch.

About 15 percent of American adults suffer from some form of hearing impairment, which can significantly impact quality of life, especially in the elderly.

“One often learns, anecdotally, that ‘grandpa’ simply turned off his hearing aid because it was confusing and no longer helped. Our study indicates that hearing deficits in adult animals result in a conversion of their brain’s sound processing centers to respond to another sensory modality, making the interpretation of residual hearing even more difficult,” said principal investigator Alex Meredith, Ph.D., a professor in the VCU Department of Anatomy and Neurobiology.

“Whether this becomes a positive feedback cycle of increasing hearing difficulty is currently under investigation, but these findings raise the possibility that even mild hearing loss in adult humans can have serious and perhaps progressive consequences,” Meredith said.

The findings provide researchers and clinicians with insight into how the adult brain retains the ability to re-wire itself on a large scale, as well as the factors that may complicate treatment of hearing loss with hearing aids or cochlear implants.

The study was supported by a grant from the National Institutes of Health.

Meredith worked with postdoctoral fellows Brian L. Allman and Leslie P. Keniston, both in the Department of Anatomy and Neurobiology.

Journal reference:

1. Brian L. Allman, Leslie P. Keniston, and M. Alex Meredith. Adult deafness induces somatosensory conversion of ferret auditory cortex. Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0809483106

Adapted from materials provided by Virginia Commonwealth University.

MSNBC.com, March 26, 2009 — Here’s the best-case scenario for the government’s plans to spend $19 billion on computerized medical records: seamless communication among doctors and patients, and far fewer mistakes.

And the worst-case: $19 billion goes down the drain.

The medical industry is hoping for the first outcome, even while some fear the second, as the Health and Human Services Department tries to get hundreds of thousands of doctors to quit using paper files and join the digital age.

The money for the massive undertaking is in the economic stimulus bill that President Barack Obama signed into law last month.

“We need to get this right,” said Dr. David Kibbe, a senior adviser at the American Academy of Family Physicians. “Adoption of information technology for its own sake really is not the end game.”

The end game, Kibbe and others say, is for doctors’ offices and hospitals to be able to easily share patient information, something the vast majority can’t do today. That would cut down on mistaken and unnecessary procedures and give doctors faster access to more accurate information about patients’ medical histories and drug regimens.

Text reminders to take meds
The goals get even more ambitious. A forum on Capitol Hill Monday focused on making medical information not just digital but wireless. Patients could be reminded via mobile devices to take their medications, and send back details like weight and blood sugar level.

Medical costs for chronic conditions like diabetes are driven up dramatically because patients don’t adhere to their medical regimens; wireless technology could help.

“The promise of these applications is that we can improve the health and productivity of people with chronic disease,” Gregory Seiler, a vice president at BeWell Mobile Technology, Inc., said at the forum sponsored by the New America Foundation and the wireless industry trade group CTIA.

The government’s history of undertaking major technological upgrades isn’t entirely encouraging.

The FBI spent four years and $170 million trying to modernize its paper-based case system, only to kill the project in 2005. Before that, the Federal Aviation Administration wasted more than $1 billion trying to overhaul the air traffic control system.

For advocates of the health technology transformation, the biggest fear is that the money could pay just for making paper records electronic, without giving doctors and hospitals much greater ability to connect.

“It’s not going to improve the decisions that either providers of care or patients make unless we get that information to move from the existing stovepipes,” said Zoe Baird, president of the Markle Foundation, which works to improve health care and national security.

Few U.S. doctors use electronic records
The U.S. lags behind many other countries in adoption of electronic health records. A report in the New England Journal of Medicine, based on surveys from 2007 and 2008, found that 4 percent of physicians had extensive, fully functional electronic records systems, while 13 percent had more basic systems.

Typically, many systems aren’t connected to other physicians or hospitals. Dozens of vendors compete to sell proprietary systems that often cannot communicate with each other. Installation costs are prohibitively expensive for some doctors, particularly those in small practices.

Lawmakers and the Obama administration hope the stimulus legislation can begin to solve such problems. The bill envisions new standards to drive development of systems that are better able to communicate, and requires doctors and hospitals to show they’re going to be able to put those systems to “meaningful use.”

Computerizing records will “save money, improve the quality of care for patients and make our health care system more efficient,” HHS spokesman Nick Papas said.

‘Devils are in the details’
But important details are missing from the legislation. Plus, a health secretary is not yet on the job, and just Friday the administration named a national coordinator for health information technology — Dr. David Blumenthal, a former Harvard Medical School professor who advised Obama during the presidential campaign and once worked for Sen. Ted Kennedy, D-Mass., chair of the Senate’s health committee.

The stimulus bill directs $17 billion in incentives through Medicare and Medicaid to nudge doctors and hospitals toward electronic record-keeping beginning in 2011. In 2015, financial penalties will start for doctors and hospitals if they haven’t done so.

What systems will be deemed acceptable? How will doctors and hospitals be able to show they will put such systems to meaningful use? Those questions remain largely unanswered.

Preliminary technological standards are due at the end of this year. That doesn’t give doctors, hospitals or technology companies much time to get up and running by 2011.

The bill also contains $2 billion for items such as health technology grants, training initiatives and state programs. The uncertainty surrounding this money has touched off heavy lobbying from interest groups hoping for a piece.

“The devils are in the details and we don’t know the details,” said Janet Marchibroda, head of the nonprofit advocacy group eHealth Initiative.

Still, many health care professionals foresee a more connected health care system ahead.

“It will take time to get there,” said Tom Romeo, IBM’s vice president for government health care. “But everything’s in place to really make a huge jump forward now like it never has been before.”

NEW YORK — March 26, 2009 — The US Food and Drug Administration (FDA) has approved tigecycline (Tygacil) for the treatment of adult patients with community-acquired bacterial pneumonia (CABP) caused by susceptible strains of indicated pathogens. The approval was based on results of 2 randomised, double-blind, active-controlled, multinational studies which evaluated tigecycline for the treatment of CABP in adults. The 2 studies were conducted at 116 sites in 28 countries and evaluated the efficacy and safety of tigecycline compared with levofloxacin in 859 patients who were hospitalised with CABP. Results showed that clinical cure rates of patients hospitalised with CABP were comparable for both tigecycline and levofloxacin. Clinical cure rates in clinically evaluable patients were 90.6% for tigecycline and 87.2% for levofloxacin in 1 study and 88.9% for tigecycline and 85.3% for levofloxacin in the other study. The most common treatment-emergent adverse events in patients treated with tigecycline were nausea (26%) and vomiting (18%). Adverse events may occur after the drug has been discontinued. SOURCE: Wyeth Pharmaceuticals

American Association for Cancer Research, 03/26/09 — Omega-3 fatty acids appear protective against advanced prostate cancer, and this effect may be modified by a genetic variant in the COX-2 gene, according to a report in Clinical Cancer Research, a journal of the American Association for Cancer Research.

“Previous research has shown protection against prostate cancer, but this is one of the first studies to show protection against advanced prostate cancer and interaction with COX-2,” said John S. Witte, Ph.D., professor of epidemiology and biostatistics at the University of California San Francisco.

For the current study, researchers performed a case-control analysis of 466 men diagnosed with aggressive prostate cancer and 478 healthy men. Diet was assessed by a food frequency questionnaire and researchers genotyped nine COX-2 single nucleotide polymorphisms.

Researchers divided omega-3 fatty acid intake into four groups based on quartiles of intake. Men who consumed the highest amount of long chain omega-3 fatty acids had a 63 percent reduced risk of aggressive prostate cancer compared to men with the lowest amount of long chain omega-3 fatty acids.

The researchers then assessed the effect of omega-3 fatty acid among men with the variant rs4647310 in COX-2, a known inflammatory gene. Men with low long chain omega-3 fatty acid intake and this variant had a more than five-fold increased risk of advanced prostate cancer. But men with high intake of omega-3 fatty acids had a substantially reduced risk, even if they carried the COX-2 variant.

“The COX-2 increased risk of disease was essentially reversed by increasing omega-3 fatty acid intake by a half a gram per day,” said Witte. “If you want to think of the overall inverse association in terms of fish, where omega-3 fatty acids are commonly derived, the strongest effect was seen from eating dark fish such as salmon one or more times per week.”

Adapted from materials provided by American Association for Cancer Research.

COLUMBIA, Md. and MUNDELEIN, Ill., March 26, 2009 /PRNewswire via COMTEX/ —-ACell, Inc. and Medline Industries, Inc. jointly announced today that Medline has signed an exclusive marketing and distribution agreement for ACell’s MatriStem(TM) Wound Care Matrix. Under the agreement, ACell will manufacture and Medline will market and distribute the products.

ACell’s MatriStem regenerative medicine technology is a naturally occurring bioscaffold derived from porcine tissue. When MatriStem is placed onto a wound, it is resorbed and replaced with new native tissue where scar tissue would normally be expected. MatriStem devices, currently available in sheet and powder form, can be used in a broad range of medical applications such as wound care, general surgery, gastrointestinal surgery, urology and plastic and reconstructive surgery.

MatriStem Wound Care Matrix facilitates the healing process and is used on partial and full-thickness wounds such as diabetic, venous, arterial and pressure ulcers, and first and second-degree burns. The infected foot ulcer is the most common reason for hospitalization among patients with diabetes, resulting in over 200,000 days of inpatient care. Diabetes related amputations cost the health care system approximately $3 billion a year. Wound care devices, home health care and hospital costs associated with wound care, cost the U.S. healthcare system over $7 billion in 2007.

“As a well-established advanced wound care company, Medline will be an excellent partner for marketing and distributing our MatriStem Wound Care Matrix,” stated Jim DeFrancesco, President and CEO of ACell, Inc. “We look forward to utilizing our unique regenerative medicine technologies in future collaborative efforts with Medline for creating additional advanced wound care products.”

Jonathan Primer, President of Medline’s Wound Care Division, commented, “We are pleased to announce our exclusive agreement with ACell to market and distribute its proprietary MatriStem Wound Care Matrix. The MatriStem preclinical studies are innovative in the field of bioscaffolds and we look forward to partnering with ACell to continue the advancement of wound care research.”

About ACell

ACell, headquartered in Columbia, MD, offers a range of medical devices based on its patented and proprietary extracellular matrix technologies. MatriStem devices have received FDA clearances for applications in wound care, soft tissue repair, and general surgery. The devices are manufactured in ACell’s cGMP facility based in Lafayette, IN. For more information on ACell, visit our website, www.acell.com.

About Medline

Medline, headquartered in Mundelein, IL, manufactures and distributes more than 100,000 products to hospitals, extended care facilities, surgery centers, home care dealers and agencies and other markets. Total revenue for Medline in 2007 exceeded $2.86 billion. Meeting national and international quality standards, Medline is FDA QSR compliant and ISO 13485 certified. Medline serves on major industry quality committees to develop guidelines and standards for medical product use, including the FDA Midwest Steering Committee, AAMI Sterilization and Packaging Committee, and various ASTM committees. For more information on Medline, visit our website, www.medline.com.

SOURCE ACell, Inc.

21st Century Medicine

Laser healing: Researchers at Massachusetts General Hospital are developing a method to heal surgical incisions with laser light. Surgeons Ying Wang and Min Yao position a metal frame that directs a green surgical laser over the incision. The frame keeps the instrument steady and at a measured distance from the skin. They shine the light onto the cut to activate the dye, leaving it on for three minutes.
Credit: Porter Gifford

Lasers and a century-old dye could supplant needles and thread.

MIT Technology Review, March 27, 2009, by Lauren Gravitz — Despite medicine’s inestimable progress over the past century, surgery can still leave scars that look more appropriate to Frankenstein’s monster than to the beneficiary of a precise, modern operation. But in the Wellman Center for Photomedicine at Massachusetts General Hospital, Irene Kochevar and Robert Redmond have developed a method that has the potential to replace the surgeon’s needle and thread. Using surgical lasers and a light-activated dye, the researchers are prompting tissue to heal itself.

Laser-bonded healing is not a new idea. For years, scientists have been trying to find ways to use the heat generated by lasers to weld skin back together. But they’ve had a difficult time finding the right balance. Too little heat and a wound won’t heal; too much and the tissue dies. Eight years ago, one of Kochevar and Redmond’s colleagues was examining pathology slides of cells killed by this kind of thermal healing when it occurred to him that it might be possible to use just the light of a laser, rather than its heat.

While the idea of skin weaving itself back together may sound more like superhero lore than surgical skill, the science is startlingly simple. The team took advantage of the fact that a number of dyes are activated in the presence of light. In the case of Rose Bengal–a stain used in just about every ophthalmologist’s office to detect corneal lesions–the researchers believe that light helps transfer electrons between the dye molecule and collagen, the major structural component of tissue. This produces highly reactive free radicals that cause the molecular chains of collagen to chemically bond to each other, or “cross-link.” Paint two sides of a wound with Rose Bengal, illuminate it with intense light, and the sides will knit themselves back together. “We call this nano suturing,” Kochevar says, “because what you’re doing is linking together the little collagen fibers. It’s way beyond anything that a thread of any kind can do.”

The benefits of such nano suturing are manifold. In just about every case, it appears to result in faster procedures, less scarring, and possibly fewer infections, since it seals openings completely and leaves no gap through which bacteria can penetrate. This makes it particularly well suited for closing not only superficial skin incisions but also those made in eye and nerve operations. In eye surgeries, such as corneal replacement, stitches that can cause irritation and infection must sometimes be left in place for months, which can aggravate complications. In nerve surgeries, damage from scar tissue can decrease the conduction of neural impulses. “If you put a needle through skin, it’s not a big deal,” says Redmond. “But if you put it through a nerve it’s a big deal, because you’re destroying part of the nerve.”

Light Work
The operations take place in a surgical suite of tile and stainless steel. Min Yao, a surgeon on Kochevar and Redmond’s team, has carted a medical laser up from the lab downstairs. The instrument is already used for eye, ear, nose, and throat procedures, and its green light has just the right wavelength for maximum absorption by the pink Rose Bengal stain. The better the light is absorbed, the more it activates the dye and the more complete the collagen cross-linking. The box that generates the laser light is barely larger than a stereo receiver; a thin fiber-optic cable snakes out of its side, and it gives off an appletini-green glow.

For this particular test surgery, on the skin of an anesthetized rabbit, surgeon Ying Wang measures and marks a patch of skin to be removed, an elliptical, leaf-shaped patch 1.5 centimeters wide by 3.5 centimeters long. After removing the tissue, Wang begins closing the wound. Surgical cuts typically require two layers of suturing: buried, or subcutaneous, stitches to bring deep tissue together, and superficial ones to close up the skin itself. Wang moves her needle and thread through the subcutaneous layer, working her way deftly from one end of the incision to the other. Then she moves on to the epidermal layer.

Wang closes up the right half of the cut with three stitches, black thread standing out against the rabbit’s pink skin. Then she takes a vial of Rose Bengal and drips the neon-pink dye onto either side of the unclosed portion of the wound. She threads the laser’s fiber-optic cable into a metal stand, which maintains a set distance between laser and tissue while holding the light steady; a lens focuses the beam into a sharp, straight line that can be aligned with the incision. Wang positions the stand on the rabbit’s flank, dons a pair of orange safety glasses, sets a timer, and steps down on the pedal that activates the laser. A green glow washes over the room.

Three minutes later, the timer beeps and Wang releases the pedal. She removes her safety glasses, moves the laser stand away, and inspects her handiwork. A small line is visible–a remnant of the Rose Bengal stain and of the black marker used to trace the location of the incision prior to surgery. But when she tugs on the wound, using a pair of forceps in each hand to pull the skin apart, the skin holds taut, and there’s little visible evidence of the cut itself.

A Bright Future
“It’s a very interesting technology, which would be useful to anyone who does any kind of skin surgery–plastic surgeons, dermatologists,” says Robert Stern, a professor of dermatology at Harvard Medical School and chief of dermatology at Beth Israel Deaconess Medical Center in Boston. He notes that the technology must still prove itself, and he isn’t yet convinced that the benefits will offset the costs of photochemical dyes and laser equipment, which are far pricier than a needle and thread. But, he says, the potential to minimize scarring and perhaps speed healing “could be nice for patients and improve outcomes [too].”

So far, use of the technique in humans has been limited to skin surgeries: in a clinical trial, 31 patients with skin cancers and suspicious moles had their three-to-five-centimeter excisions closed with sutures on one side and photochemical tissue bonding on the other. The dermatological procedure will be submitted to the U.S. Food and Drug Administration for approval, which the researchers are awaiting before beginning additional human trials. Animal experiments have already shown the technique to be useful in nerve, eye, and blood vessel surgeries, among others–so useful, in fact, that Kochevar and Redmond have surgeons ready and waiting to start human trials the moment the hospital approves them.

“Talk to just about any physician about this, and they have an idea for how it could be used,” Kochevar says. The technology is limited by tissue depth: it works only where light will penetrate, so it could never replace subcutaneous sutures or be effective on dark or opaque tissue like liver and bone. The scientists have licensed the technology to a brand-new startup, still in stealth mode, which plans to commercialize the technology once it receives FDA approval. The company has just begun seeking its first round of funding.

Proceedings of the National Academy of Sciences — Patients who have lost part of their visual awareness following a stroke can show an improved ability to see when they are listening to music they like, according to a new study published March 23 in the journal Proceedings of the National Academy of Sciences.

Every year, an estimated 150,000 people in the UK have a stroke. Up to 60% of stroke patients have impaired visual awareness of the outside world as a result, where they have trouble interacting with certain objects in the visual world.

This impaired visual awareness, known as ‘visual neglect’, is due to the damage that a stroke causes in brain areas that are critical for the integration of vision, attention and action. Visual neglect causes the patient to lose awareness of objects in the opposite side of space compared to the site of their brain injury.

If the stroke occurs in the right hemisphere of the brain, these patients tend to lose awareness of visual information in the left side of space. This occurs even though the area of the brain associated with sight is not damaged.

The researchers behind the study, from Imperial College London, the University of Birmingham and other institutions, suggest that listening to their favourite music may help stroke patients with impaired visual awareness to regain their ability to see.

The new study looked at three patients who had lost awareness of half of their field of vision as a result of a stroke. The patients completed tasks under three conditions: while listening to their preferred music, while listening to music they did not like and in silence. All three patients could identify coloured shapes and red lights in their depleted side of vision much more accurately while they were listening to their preferred music, compared with listening to music they did not like or silence.

For example, in one task, patients were asked to press a button when they could see a red light appear. One patient could point out the light in 65% of cases while he was listening to music he liked, but could only recognise the light in 15% of cases when there was no music or music he did not like being played.

The researchers believe that the improvement in visual awareness seen in these patients could be as a result of patients experiencing positive emotions when listening to music that they like. The team suggest that when a patient experiences positive emotions this may result in more efficient signalling in the brain. This may then improve the patient’s awareness by giving the brain more resources to process stimuli.

The team also used functional MRI scans to look at the way the brain functioned while the patients performed different tasks. They found that listening to pleasant music as the patients performed the visual tasks activated the brain in areas linked to positive emotional responses to stimuli. When the brain was activated in this way, the activation in emotion brain regions was coupled with the improvement of the patients’ awareness of the visual world.

Dr David Soto, the lead author of the study from the Division of Neurosciences and Mental Health at Imperial College London, said: “Visual neglect can be a very distressing condition for stroke patients. It has a big effect on their day-to-day lives. For example, in extreme cases, patients with visual neglect may eat only the food on the right side of their plate, or shave only half of their face, thus failing to react to certain objects in the environment”.

“We wanted to see if music would improve visual awareness in these patients by influencing the individual’s emotional state. Our results are very promising, although we would like to look at a much larger group of patients with visual neglect and with other neuropsychological impairments. Our findings suggest that we should think more carefully about the individual emotional factors in patients with visual neglect and in other neurological patients following a stroke. Music appears to improve awareness because of its positive emotional effect on the patient, so similar beneficial effects may also be gained by making the patient happy in other ways. This is something we are keen to investigate further,” added Dr Soto.

This research was funded by the British Academy, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council, Medical Research Council and Stroke Association.


Arstechnica.com, March 26, 2009, by Nate Anderson — Skype has become the world’s single largest provider of international calls, surpassing even incumbent telcos like AT&T. Unfortunately for the company, few of these calls generate any revenue, and corporate parent eBay grows impatient.

Skype might not be performing quite as well as parent company eBay would prefer a $2.6 billion acquisition to perform, but that hasn’t dampened worldwide enthusiasm for the VoIP service. Skype is so popular, in fact, that new numbers out from TeleGeography suggest that it has become the “largest provider of cross-border voice communications in the world.” Take that, AT&T!

Actually, AT&T probably doesn’t care, since long distance has lost some of its revenue-generating luster, but the surging popularity of VoIP no doubt keeps future-thinking execs up at nights. Skype’s revenues are more modest than the big telcos, despite its usage numbers; at eBay’s annual meeting earlier this month, the company said that Skype pulled in $550 million in 2008.

Most of Skype’s usage, though, generates no revenue. Its free computer-to-computer calls (certain handsets and mobile devices can now be used as well) have become a hugely popular way of making international calls. TeleGeography estimates that Skype’s international traffic jumped by 41 percent in 2008 and topped 33 billion minutes of use, most of that in free calls. Traditional international calls grew only 12 percent in 2008.

Skype also hopes to work its mojo in the business world, offering a new beta of “Skype for SIP” that allows corporations to route calls from a PBX system over the Internet. As with the consumer version of the software, calls that remain on the Internet and go to other Skype users would be free; calls that connect to the traditional phone network cost pennies a minute.

Growth brings new challenges, of course, and as Skype now handles more international voice conversations than any incumbent telco in the world, governments are beginning to get interested. One of their chief concerns is that mobsters, spies, terrorists, Ponzi schemers, and other assorted bad guys don’t simply get a free pass on eavesdropping by using a VoIP service like Skype. In the US, CALEA rules have tried to bring wiretapping rules into the Internet age.

European authorities also announced last month that they would lead an international effort to “overcome the technical and judicial obstacles to the interception of internet telephony systems.” Skype was singled out for particular attention, though the company told us that “we have capabilities and we have programs in place and [governments are] aware of them.”

Skype’s prominence has also put it in conflict with existing phone companies, especially mobile operators. Skype would love nothing better than to see its software running on every handset in the world; plenty of consumers feel the same way. But wireless operators like to lock down their handsets to prevent exactly this sort of behavior, so Skype has been a key proponent of “wireless net neutrality,” which the FCC declined to act on last year.

And it continues to face internal pressures from eBay, which early last year was publicly talking about its willingness to sell Skype if “synergies” between the two companies failed to materialize.

Still, what company wouldn’t want to have Skype’s problems? Going from startup to the world’s single largest provider of international calls in six years is impressive; more impressive would be to see Skype generate massive revenues even as the cost of voice communications plummets.