In the elite world of medical research, Dr. Harold Varmus is at the top of the heap. He runs the government’s biggest health research engine, the National Institutes of Health, and won the 1989 Nobel Prize for his groundbreaking work on cancer genes.

Yet Varmus, 59, has proposed such a radical, power-to-the-people idea involving Internet publishing that the rest of the medical establishment is at his throat – partly out of self-interest, but partly out of genuine concern that Varmus’ plan would add dramatically to the chaos of medical information and misinformation already on the Net.

Aided and abetted by computer whizzes at the National Library of Medicine, Varmus wants to do the unthinkable: Put the full text, not just abstracts, of research papers on the Net in an expedited way, and – here’s the grabber – in some cases without the peer review that journals like the New England Journal of Medicine and the Journal of the American Medical Association have long used as a way to weed out solid studies from schlock.

This is cage-rattling stuff – not just because it might mean scooping journals on medical news, but because some scientists might choose to bypass the traditional journals altogether in favor of speedier publishing – with less rigorous review – on the Net, all under the NIH imprimatur.

Speaking by phone from New York City last week, Varmus, who will leave NIH at the end of the year to head Memorial Sloan-Kettering Cancer Center, said he is and always has been a believer in peer review. This is the process by which, before accepting an article for publication, medical editors send it to outside experts who pore over the data looking for errors in methodology, science or interpretation.

And initially, all of the research that Varmus envisions for the new site, to be called PubMed Central, just posted last Thursday and scheduled to be operational in January, will indeed be forwarded from journals that have vetted the work.

This research – in biology, medicine, agriculture, and plant sciences – could be posted after publication in a major journal, which nobody objects to. Or before it appears in print, which critics say could make mainstream medical journals obsolete.

“This would be a surefire method of killing ourselves,” says Dr. Marcia Angell, interim editor-in-chief at the New England Journal of Medicine. If the Journal took the time and care to review articles, then handed them right to PubMed Central, by the time the Journal published the work “it would be just an archive. . .we would be committing suicide.” As it is now, the Journal posts its new research on its own Web site the night before the print publication becomes available.

And then there’s the even more controversial, back-door route to getting research in the public domain fast that Varmus has developed with David Lipman, director of the national center for biotechnology information at the National Library of Medicine.

The idea, still a work-in-progress, is to have a “screening” process in which papers that might never be submitted to a mainstream journal would be posted on the Net if they were forwarded by a “certifying group.” This non-peer-reviewed material would be clearly labelled as such.

A still-to-be-created committee would figure out who would qualify as a certifying group, but initially, this would be any organization with at least three members who are principal investigators on research grants from agencies such as the NIH, the National Science Foundation, the Department of Energy, etc.

The point is to “develop a way to disseminate research results in a way that allows anyone access any time, any place,” says Varmus, who dislikes the “gatekeeper” role that major journals now play.

The goal, he says, is fast, “barrier-free” access to medical research. No passwords, no need to “register” on a Web site to read a research study, no fees to Web surfers. In fact, in PubMed Central, the costs of publishing could be picked up by the authors of papers – whose funding often comes from taxpayers anyway – instead of those who want to read the work online.

Some people love this idea. Among them is Barbara Lackritz, a St. Louis, Mo. cancer patient and patient advocate who says that to keep up with the latest research, she needs more than the abstracts most Web sites offer. “The more information we can get out there for people to read and understand, the better off we are all going to be,” she says.

Dr. Helga E. Rippen, a physician-engineer who runs a health information think tank at Mitretek Systems in McLean, Va., agrees. “I’m into as much information as somebody wants,” she says, though she adds there’s also a need to teach consumers how to evaluate and interpret complex, raw medical data.

But Dr. Sidney Wolfe , director of Public Citizen’s Health Research Group, a health research-based advocacy organization in Washington, D.C., is leery about rushing unreviewed research into the public domain. “Needless to say, the sooner people get information, especially information with public health impact, the better. But it’s only better if it’s accurate.”

Biased, incomplete or incorrect medical information can do serious damage, he notes. Though physicists have posted preliminary research results on the Net, there’s considerably more risk when medical researchers do so, he adds.

And Angell, of the New England Journal, is appalled. “I believe in the marketplace of ideas,” she says. “But you can’t just throw up everything – advertising, old wives’ tales, research studies – on the Net and hope people can figure out what’s valid and what isn’t.”

For his part, though, Dr. George Lundberg, former editor of the Journal of the American Medical Association, is gloating.

Now editor of Medscape, an online health information service with access to 25,000 research articles, and its spinoff, Medscape General Medicine, an electronic medical journal, Lundberg says it is possible to put peer-reviewed medical information on the Net without the long delays in standard medical publishing. (At the New England Journal, for instance, it takes seven months from the time a paper is submitted to the time it is published.)

In fact, in a way, he’s beaten Varmus to the punch. Medscape, he says, does peer review its articles, but fast – in three to five days, not the 28 that print journals take.

So far, only a handful of existing journals have agreed to supply material to PubMed Central, including the National Academy of Sciences, the Journal of the American Society of Cell Biology, the Canadian Medical Association Journal, and a British entrepreneur who publishes biomedical journals.

But that should change as scientists realize the potential for getting work out quickly, says Jo McEntyre, a fellow at the National Library of Medicine. “Scientists love it,” she says, “because they are the ones who do the research.”

Because of the sheer volume of medical research, many scientists can’t get their work published in high-profile journals, she says. This may be especially true for “negative” studies that find that a cherished hypothesis doesn’t hold up.

Angell, the New England Journal editor, disputes this, noting that when a truly important hypothesis yields negative findings, those results are likely to be published.

The real problem, Angell contends, is that everybody assumes that “we live in a sea of good research,” much of which never sees the light of day. In reality, she says, there’s not a lot of good clinical research out there.

The New England Journal, accepts only 10 percent of the articles submitted. “And we’re not weeping as we reject what we reject,” she says. “We sometimes weep [ about] what we have to accept.”

But Varmus is undeterred. “It will take time,” he says of the new venture. But “in the first year, we’ll show what we can do.”

To read about the government’s new health Web site, go to (http://www.PubMedCentral.nih.gov) or to www.nih.gov/welcome/director/pubmedcentral/pubmedcentral.htm. To read a critique of the proposed site, read a June 10, 1999 editorial in the New England Journal of Medicine at www.nejm.org.

Evaluating health data on the Net

When the government’s new health research Web site, to be called PubMedCentral, goes online in January, it will join thousands of medical sites already available to Web surfers.

Roughly 45 million American households now have online access and half of all US adults use the Net to search for health information, says Dr. Helga E. Rippen, a physician-engineer who tracks such things for Mitretek Systems, a think tank in McLean, Va. Health-related Web sites are constantly being created and abandoned. An estimated 10,000 to 25,000 are up now.

But the quality of information on these sites varies widely, from peer-reviewed articles posted by medical journals such as The New England Journal of Medicine to thinly-disguised advertisements for pharmaceuticals to utterly unsubstantiated claims by quacks or shysters.

A growing numbeer of health information specialists, including the Internet Healthcare Coalition (www.ihc.net), are concerned about the glut of misinformation on the Net. Here are some tips that may help:

• Look to see who wrote the information, checking the “about us” section of the site. If there’s no author listed, or no credentials for the author, be suspicious.
• Check attribution of the information. Research that has been published in a mainstream journal has been reviewed by experts; so has most information from big government agencies such as the National Institutes of Health or the Food and Drug Administration. Information from drug companies may be reliable, but remember, these companies are selling products.
• Try to determine whether the authors have a potential financial or ethical conflict of interest. Ideally, authors are upfront about this, but many aren’t. A more subtle bias can occur with information put out by patients’ groups, which may be so wedded to one point of view that they exclude others.
• Beware of anecdotal information. Emotional testimonials can be convincing – but also misleading or irrelevant to you.
• When you read a study, check the methodology. Was there a control group? How many people were in the study? How long were they followed? Was the study “double-blind”? (This means neither doctors nor patients knew until the study was over who was taking the real drug and who, the placebo.)
• Just as you’d get a second opinion from a doctor, don’t rely on one Web site. Read many sites and cross-check what you find.
• If a treatment seems too good to be true, it probably is.

For decades, hepatitis C, a potentially fatal liver virus harbored by 3 million Americans, was a virtual black box.

Scientists knew there was some kind of nasty virus afoot in the land – and in the nation’s blood supply. In fact, they knew that one in five people who got a blood transfusion came down with infections caused by it. But they couldn’t find the virus itself. In fact, they didn’t even have a name for the disease it caused, dubbing it simply non-A, non-B hepatitis.

By 1988, they had found the virus and given it a name. By 1990, they had a detection test with which to screen blood donors. A year later, they had a treatment. By 1998, the number of new infections was cut by 80 percent and the risk of catching hepatitis C from donated blood was down to 1 in 100,000.

Today, treatments have progressed to the point where some people have not just experienced temporary remissions but may be cured.

Yet hepatitis C is still a huge threat. It has become the leading reason for liver transplantation. Granted, there’s now a two-drug regimen to treat it, but it makes many people feel worse than having the disease. The regimen, called Rebetron, has also generated fury among patients because of the controversial way the manufacturer, Schering-Plough, markets it.

Worse, many of the 3 million Americans who are infected with hepatitis C don’t even know it yet, because infection can smolder for years without causing symptoms. Eventually, more than 80 percent of people who come down with the virus end up with chronic infections. Of these, 20 percent go on to get cirrhosis, the destruction and scarring of liver tissue; of those, 20 percent develop liver cancer after 10 years and another 20 percent, end-stage liver disease.

Because so many people are infected and because of the long course of the disease itself, the death toll, now 10,000 a year, is likely to triple in coming years.

The first step toward combatting that, health officials say, is testing, especially for anyone who had a blood transfusion or organ transplant before 1992, when a new detection test made the blood supply safe. People who’ve used intravenous drugs are also at risk. Like the AIDS virus, hepatitis C is spread through blood contact, and, to a lesser extent than AIDS, through sex.

But luckily, testing just got easier. In the last few weeks, a $70 home test kit made by the Home Access Health Corp. began reaching stores. You prick your finger at home, put a few drops of blood on a piece of filter paper and mail it to the lab. You get the results, confidentially, in 10 days. You can also be tested at a doctor’s office or hospital, though the test is not part of a routine physical and may not be covered by insurance.

If the test comes back positive, you need more blood tests – for levels of enzymes that show whether you have liver damage. If you need it, your doctor will recommend a liver biopsy to see how much inflammation and cirrhosis (scarring) you have.

If the scarring is mild, some people postpone treatment on the grounds that the disease progresses slowly, and treatment with Rebetron, the “bundled” or pre-packaged combination of two drugs – interferon and ribavirin – can be long and miserable. Interferon causes intense flu-like symptoms such as fever, chills and joint aches; ribavirin can cause severe anemia.

Indeed, after discussion of the pros and cons, says Dr. Fredric Gordon, medical director of liver transplantation at Lahey Clinic Medical Center in Burlington, 25 percent of his patients decide not to be treated. For some, it’s “just too early” in the disease. Others “want to wait for better drugs.”

Many patients, however, do grit their teeth and go for it; among them, a 47-year old Malden man, who asked that his name not be used. He felt fine before treatment, he says, but now feels like he’s got the flu whenever he gives himself an injection of interferon. So far, he’s been taking Rebetron for four months now and has eight to go. But his liver tests already show improvement, and he’s determined to stick it out.

That makes sense, because while interferon alone yields a sustained response 10 percent of the time, interferon plus ribavirin can quadruple that. (A sustained response is defined as undetectable levels of virus six months after the end of treatment.)

“I tell patients that if by six months after treatment they’re free of the virus, there’s a 90 percent chance they’re cured,” says Dr. Sanjiv Chopra, director of clinical hepatology at Beth Israel Deaconess Medical Center.

But Rebetron, or more precisely, its manufacturer, Schering-Plough, nonetheless draws ire from many patients.

In June, 1998, the US Food and Drug Administration approved Rebetron as a bundled product. That means it’s sold – for $1,440 a month – as a package containing Schering’s interferon, called Intron A, plus ribavirin, an antiviral drug discovered by ICN Pharmaceuticals and now made by Schering.

The catch is that ribavirin is only FDA-approved as part of the Rebetron package. “Ribavirin by itself doesn’t work. The only thing that works is the combination. What’s not known is whether combinations [ of ribavirin] with other interferons work as well as with Schering’s,” says Dr. Bruce Bacon, a liver specialist at Saint Louis University in Missouri.

That irks patients who want to combine ribavirin with interferon made by other companies, notably Amgen and Roche Laboratories, in the hope, so far unproved, that the other interferons might be less toxic or more effective.

“It’s outrageous,” says Brian Klein, a founding member of HAAC, the Hepatitis C Action and Advocacy Coalition, based in San Francisco and New York. Not only does bundling prevent other researchers from testing their interferons with ribavirin, “the bundling hides the outrageously inflated cost of the little pills because you can’t buy them separately.”

Some patients resort, perfectly legally, to asking “compounding” pharmacies, notably Fisher’s Specialized Pharmacy Services in Pittsburgh, to convert bulk ribavirin powder into capsules for them, which they then take with other companies’ versions of interferon. Betty Stein, a pharmacist-owner at Fisher’s, says the pharmacy fills orders every day for hepatitis C patients and charges only $225 for a month’s supply.

Other patients, including a 25-year old Roxbury woman, have gotten ribavirin through patient-organized buyer’s clubs. “It’s a good thing I did, because Shering-Plough monopolized the drug,” says the woman, who used ribavirin with “consensus” interferon, a rival product to Schering’s that combines several components of interferon and which, she hopes, may have a “better track record.”

But Schering is “not going to unbundle” Rebetron, says company spokesman Bob Consalvo. Cost is not an issue because insurers usually pay, he says. And if patients are poor and have no insurance, the company provides the drugs free, he adds.

Recently, some patients have been adding other drugs to the regimen, notably a flu medicine called amantadine. According to research presented at a recent conference, Italian scientists found that by six months after treatment, 43 percent of patients on this triple-drug therapy had a sustained response versus 5 percent with two drugs.

Dr. Thomas Najarian, a Belmont internist, says he’s encouraged by such findings. So is one of his patients, William Bochicchio, 43, a contractor from W. Ossipee, N.H., who used the triple therapy for nine months. It was “pretty rough,” but he’s been virus-free for two years and says, “I’m cured.”

And there could be even better treatments in the near future, including “pegylated” interferon – interferon hooked to a chemical called polyethylene glycol. This compound would be injected just once a week. Now in clinical trials, pegylated interferon alone may be as effective as Rebetron, says Dr. Ray Chung, medical director of liver transplantation at Massachusetts General Hospital in Boston.

Also in the pipeline are protease and helicase inhibitors, which could combat replication of the virus directly. Anti-fibrotic drugs to reduce scar tissue in the liver may also help.

Some patients also take an herbal remedy called milk thistle, sold as a dietary supplement. This may improve scores on liver tests, but there’s no evidence it eradicates the virus.

The bottom line is that if you think you’re at risk, get tested. And if you test positive, at least take common-sense steps, like not exacerbating liver damage by drinking alcohol. And of course, talk with a doctor about what treatment, if any, to have.

“This is a pretty stubborn, insidious disease,” says Bochicchio, the New Hampshire contractor. “The virus eats away at your liver, slowly but surely.”

Living with hepatitis C

He’s only 31, still on the verge of a blossoming career as a DNA researcher at Harvard Medical School. But this biochemist, who for professional reasons asked that his name not be used, has been plagued his entire life with hepatitis C.

He was “an Rh baby,” he says, meaning that because of a blood abnormality, he was vulnerable as a fetus to a potentially fatal anemia caused by antibodies in his mother’s blood. Indeed, his mother had lost a previous baby this way.

So he was given transfusions while he was still in the womb – in the 1960s, before tests became available to monitor the blood supply. He often felt, growing up, that he was “getting older faster than I should have been,” but he still played softball, went skiing, hiking and studied. “I had no idea I was sick,” he says.

By the time he was diagnosed with hepatitis C – at 27 – his liver was severely scarred. By 28, he had liver failure. At 29, he had a liver transplant. (Hepatitis C is so prevalent, in fact, it is now the leading cause for liver transplantation.)

To prevent the virus, which still lingered in his body, from attacking the new liver, he underwent therapy with interferon and ribavirin for a year. That treatment, which causes intense flu-like symptoms, was “worse than the disease.. . .You get really depressed and hopeless,” he says.

But “it is something you can get through and I think treatment is worth it, even though it’s horrible,” he says. He urges anyone who may be at risk to get tested and treated.

After all, he’s now virus-free for the first time in his life. And that, he says, is “pretty cool.“

The experiments creating the biggest buzz among spinal cord researchers are those involving fetal cell, stem cell or embryonic stem cell transplants. So far, most of the research is in animals, though some studies are beginning in people.

In all three methods, the idea is essentially the same: To implant in the damaged spinal cord immature cells that can be nudged to grow into many, perhaps all, of the thousands of different types of nerve cells in the body. The immature cells can also be genetically engineered to produce large quantities of the chemical messengers believed to stimulate new nerve growth.

Ideally, the cells would be transplanted into a patient within a week or two of injury, but the ultimate goal is to use them months or even years later to stimulate nerve growth.

In embryonic stem cell transplantation, cells are taken from embryos at the 8- to 12 cell-stage, says Dr. John W. McDonald, director of the spinal cord injury program at Washington University in St. Louis. These cells, isolated for the first time only a year ago, then differentiate into every type of cell in the body, including spinal nerve cells.

In fetal cell transplants, tissue is taken from the spinal cords of aborted fetuses. Researchers at the University of Florida are already trying this method in a few patients to see if it yields new nerve growth.

At Cedars-Sinai Medical Center in Los Angeles, researchers are gearing up for a study in which they would take nerve stem cells from the brains of patients with spinal cord injuries, grow them in large numbers in the lab, and re-inject them to trigger new nerve growth. Once thought non-existent in adults and still tough to identify in the lab, neural stem cells – presumably left over from fetal development – have been shown to exist in the brain in the lining of spaces called ventricles, in the hippocampus, a memory center, and in the spinal cord.

If the basic cell transplant strategy works in humans – and researchers should know in two to five years – it could eclipse everything else now in testing.

Already, researchers have been able to insert into neural stem cells “marker” genes that show where the cells migrate after being injected into animals and what kinds of nerve cells they become, says Dr. Evan Snyder, a neuroscientist at Children’s Hospital in Boston.

In fact, preliminary research shows that if human neural stem cells are injected into mice three or four days after a spinal cord injury, the cells move to exactly where they’re needed and start replacing the cells that were damaged, Snyder notes.

At a neuroscience meeting next month, McDonald’s team will present data showing that embryonic stem cells can restore function by replacing cells lost after spinal cord injury in rats, even if they’re transplanted as long as nine days later.

Ten years ago scientists scoffed at the thought that a paralyzed person could walk again; today they’re counting on it.

Four years after being paralyzed from the neck down in a riding accident, Christopher Reeve is preparing to walk again, a feat long assumed to be impossible for any quadriplegic, even Superman.

As scientists work to develop drugs to minimize acute spinal cord damage and hunt for new ways to spur regeneration even long afterwards, Reeve is trying to “meet the scientists halfway. . .”

Speaking openly, often eloquently, by phone from his Bedford, New York home, despite his reliance on a respirator to breathe, Reeve believes that, ultimately, “recovery will go to the fittest.”

So every day, he has an electrical device attached to his muscles to stimulate contractions. “I have no loss of tone whatsoever,” he says, adding that his calf muscles “are the exact same size as when I was injured.”

To prevent osteoporosis, which can be caused by a lack of weight-bearing exercise, he is strapped to a “tilt table” and raised to a vertical position to force his weight onto his feet.

He also “walks” on a treadmill — his weight suspended in a harness, his feet propelled by the moving belt. The theory is that spinal nerves can be retrained to make the legs move in a coordinated way, even though the messages that control voluntary leg movements can’t get from the brain down to the legs across the damaged area of the spinal cord.

Ten years ago, if anyone as badly injured as Reeve even dreamed of walking again, scientists would have scoffed. Reeve’s injury is not only high on his spinal cord, it’s “complete,” which means the nerve fibers are cut all the way across, not just partway, as in some cases.

Indeed, the dogma has long been that, while nerves in the arms and legs regenerate, those in the central nervous system do not — a grim fact of life for 10,000 Americans a year whose spinal cords are injured as a result of car crashes, sports accidents and violence, and for the quarter million more living with their injuries, most of whom with fewer resources than Reeve.

But thanks to an explosion of new research — some to be presented next month at a major neuroscience conference in Miami — that pessimism is cracking.

“It will be a long, arduous path, but I no longer think it’s impossible for people with severe, even high, spinal cord injuries, to walk again,” says Dr. Evan Snyder a neuroscientist at Children’s Hospital in Boston and one of the leaders in spinal cord regeneration research.

“There is tremendous new hope. The neat thing is that the central nervous system does have the capacity to regenerate — we just need to harness it. And we’re also getting better at using advances in electronics and surgery to maximize a person’s independence,” says Dr. John W. McDonald, director of the spinal cord injury program at Washington University in St. Louis.

Electronic devices can help paralyzed patients gain control over their bladders; a drug called NT-3 seems to help the bowel work on command; and early data suggest another drug called inosine helps healthy nerves grow toward the damaged area.

Surgeons can also do “tendon transfers” to restore limited movement to paralyzed muscles by hooking them to still-functioning tendons. Many primary care doctors don’t think to recommend this, McDonald says, but by re-jigging tendons so a patient can grasp things between the thumb and forefinger, a person may be able to feed himself.

Indeed, a half-dozen new therapies to repair damaged spinal cords, including cell transplants, are or soon will be in human trials, says Dr. Wise Young, a neuroscientist at Rutgers University in New Jersey. “The hope is that if we can get 10 to 15 therapies going in parallel, at least one of them will hit.”

None of the new approaches was “dreamt of 10 to 15 years ago,” adds Arlene Chiu, who runs the spinal cord injury program at the National Institute of Neurological Disorders and Stroke. “So on that basis, I’d say things are very promising,” even though, so far, most research is in animals, not people.

Still, the challenges are daunting, almost as if evolution had “decided” that a spinal cord injury was so devastating, it was not worth investing the resources it would take to heal it.

The spinal cord, which runs inside the backbone, is only as thick as a thumb, but it’s through this channel that the brain sends signals through descending nerves onward to muscles and organs and carries messages, such as pain signals, up through ascending, sensory nerves.

Deep in the center of the cord lie the nerve cell bodies called “gray matter;” branching out from these are tendrils called dendrites, which catch incoming electrical signals; also projecting out are filaments called axons through which nerves send outgoing signals.

Some axons are long, running the entire length of the cord. Because they are coated with a white insulating material called myelin, bundles of axons are called “white matter.” Both white and gray matter also contain supporting cells called glia, and oligodendrocytes, which make the myelin.

The organization of the cord means that below an injury, nerves (and the muscles and organs they control) don’t work well or at all, while above it they do. It also means that below certain injuries, a person can feel nothing — neither pain nor pleasure.

If you injure your cord in the neck region, you may not be able to breathe without a respirator because the nerves that control the diaphragm won’t work; if you injure your cord farther down, you may have control over breathing and arm movements, but not over your legs, bladder and bowel. If the cord is not severed all the way across, there may be some function below the injury because some nerves still work.

When the cord is injured, there is instant damage to the immediate area: the bony vertebrae crush axons, rendering them useless. But for days, weeks, even months later, the damage spreads up and down the cord.

Ruptured blood vessels no longer deliver oxygen, causing waves of cell death. Damaged cells pump out glutamate, which triggers a cascade of chemical events that is fatal to nerve cells, including the release of destructive oxygen molecules called free radicals.

The injured cord also pumps out chemical signals such as IN-1 that inhibit regeneration of nerves. Axons that survive the initial injury may also lose their myelin coating, without which they can’t transmit signals. Glial cells clump into scar tissue, making it even harder for nerves on both sides of an injury to hook up. And inflammation, including the influx of immune cells that destroy nerve cells, further fans the flames of destruction.

But in 1990, the picture began to brighten when Dr. Michael Bracken and his team from Yale University showed that a drug called methylprednisolone, injected in huge doses in the first eight hours after injury, prevented some of this damage by blocking free radicals.

“This was the first time anything had been shown to work in spinal cord injury,” says Bracken, a neurologist. To this day, methylprednisolone is the only drug approved to treat either acute or chronic spinal cord injury.

But other ways to treat the cord in the immediate aftermath of injury are in the pipeline, including a drug called an AMPA antagonist that blocks glutamate receptors, likely to be studied in humans soon, and another called interleukin-10 that blocks inflammation, at least in rats.

Cooling the body after injury also slows damage in rats, says Naomi Kleitman, a neuroscientist at the Miami Project to Cure Paralysis.

The implications are compelling. The more doctors can limit the immediate injury, the more they can focus on the really tough part: restoring nerve function in people whose spinal cords were injured months or years earlier.

It’s a tall order, but Christopher Reeve is ready: “I expect full recovery — up to and including walking.” SIDEBAR 1: Getting a lift from new devices, wheelchairs

The holy grail of spinal cord research is to restore some or all nerve function, but even in the most optimistic scenarios, that’s still five years away. In the meantime, however, new devices and better medical care can improve the quality of life for the estimated 230,000 Americans living with spinal cord injuries, and for many others with mobility disorders as well.

Two years ago, the US Food and Drug Administration approved an electronic signalling device that allows some quadriplegics — people whose arms and legs are paralyzed — to regain partial use of one hand. In January, the agency approved another electronic device that restores some control over bladder, bowel and penile function.

And three months ago, Johnson & Johnson began human testing of a fancy, $20,000 wheelchair that can operate on two wheels or four and can climb stairs, go up hills and maneuver over curbs.

To be sure, even with better devices, learning to live with a spinal injury is a task that takes time “and a lot of work,” says Michael Ferriter, 47, a carpenter who was injured in a work accident 20 years ago.

But with every new device and improvement in basic care, the lives of paralyzed people get a bit better, though the amount of care necessary — and the cost, estimated to be $1.4 million over the life of a spinal injury patient — are huge.

That’s because a spinal cord injury can affect every organ and body function below the level of injury: muscles, bones, skin, blood vessels, internal organs and breathing, notes Dr. Daniel Lyons,, medical director of the spinal cord injury program at Health South/New England Rehabilitation Hospital in Woburn.

Without skin sensation, for instance, a person can’t tell when he’s getting sore from sitting too long in one position. This can lead to pressure sores and ulcers, which can lead to infections. The solution here is low tech: having someone monitor the skin, helping the patient change position often, and developing better cushions for wheelchairs.

Blood clots are another challenge. Because a paralyzed person can’t move, blood can pool in the legs and form clots that travel to the lungs. One solution is to take a blood thinner such as Lovenox.

Heart arrhythmias are a problem, too. In a healthy person, signals from the parasympathetic nerves, which tend to slow down heart rate, are coordinated with signals from the sympathetic nerves, which tend to speed it up.

But in many people with spinal injuries, this balance is thrown off. The parasympathetic nerves remain intact because they branch off high on the spinal cord, while the sympathetic nerves, which branch off lower, are damaged. The result is that the heart beats erratically because slow-down messages are not coordinated with speed-up ones. The body can compensate but if it can’t, implantable pacemakers can help.

Breathing, even just coughing, can be another huge problem. The solution is often to use a respirator, which literally pushes air into the lungs, though rehabilitation specialists try to wean people with some remaining nerve function off respirators and teach them to strengthen muscles in the diaphragm and neck to assist with breathing.

Depression is also a threat. Though many patients regain significant quality of life, says Lyons, getting to that point is difficult. “Everyone does it differently,” he says. “Well-educated business executives are often very devastated early on, then do very well as time goes by,” he says.

“Younger people who don’t have a lot of plans for their lives sometimes do well early on, then have more difficulty later as they realize that things will be tough.”

Mobility is an obvious challenge, too. At UCLA and the Miami Project to Cure Paralysis, researchers are trying to retrain damaged spinal cords by suspending a patient over a moving treadmill.

In some patients, the legs move involuntarily, and even do so in a coordinated — left foot, right foot — manner. Researchers theorize that even below the level of injury, there may be a neural “pattern generator” and “memory” in the cord that — without messages from the brain — may make walking possible.

German researchers have demonstrated improvements in mobility by putting such patients on a treadmill, says Reggie Edgerton, a UCLA physiologist pioneering the method. But so far, no one with a “complete” cord injury (one that cuts across the entire cord) has been able to regain the ability to walk.

Of more immediate benefit to many is the Freehand device, made by the NeuroControl Corp., to regain use of a hand.

The Freehand system uses a sensing device taped to the skin on the shoulder. Wires from the sensor run to an external control box and from there to a transmitting coil taped to the chest. Just under that coil is a stimulating device that is implanted surgically under the skin.

Leads from the implanted device run down the arm to electrodes on the fingers and thumb. When the shoulder is moved, signals travel down to the hand. So far, about 150 people worldwide are using the device.

The VOCARE system, distributed by NeuroControl and made in England, is similar. In this case, the implantable part of the system is surgically placed under the skin on the abdomen, with electrodes on nerves to the bladder, bowel and in men, the penis. The transmitter coil is held or taped to the skin over the implant and the unit is controlled externally by the patient if he has sufficient hand control, or by a helper. The device, which allows patients to urinate, defecate or get an erection, is now used by 1,500 people worldwide, most of them in Europe.

Michael Ferriter, the carpenter injured in a work accident, welcomes the new options for treatment of injuries like his. But he also has hard-won advice: “Live healthy — mentally, physically and spiritually until there’s a cure. Don’t wait for it. Live it now. . .You’ve got to do it. That’s what life is about.”