A research team, led by Farren Isaacs and George Church of Harvard University Medical School, was able to make precise changes to the cell’s protein-making process in 32 strains of E. coli. They replaced one three-letter sequence of nucleotides with another throughout the entire organism, without harming the bacterium.

Although genetic engineers can change one gene in a genome, this is the first time that as many as 314 sites were altered at once, the authors wrote. The method may allow for making larger- scale changes to DNA, which would be helpful if scientists wanted to make many alterations, they wrote in an article published today in the journal Science.

“Our methods treat the chromosome as both an editable and evolvable template, permitting the exploration of vast genetic landscapes,” the authors wrote.

The technology, known as multiplex automated genetic engineering, or MAGE, was created by Church, Isaacs, and others in Church’s group. It can induce gene alterations in a population of bacteria almost simultaneously, creating billions of cellular mutations in a matter of days.

Church helped to start the government-funded Human Genome Project, which decoded the entire human genetic blueprint in 2000. The public project competed with a private effort by J. Craig Venter, who runs the J. Craig Venter Institute, based in Rockville, Maryland. The teams shared credit for the milestone.

Venter in 2007 replaced the genetic structure of one bacterium with the DNA of a second, transforming one species into another. The emerging field of synthetic biology allows scientists to create organisms that don’t exist in nature. These novel designer microbes may allow for new biofuels and foods, scientists say.

Unlike Venter’s discovery, the Harvard team modified DNA directly in live cells, tricking them into thinking it’s their own.

This could be changing, however. The pharmaceutical industry has persuaded several governments to stiffen regulations against fake drugs and to conduct more aggressive raids (see chart). Companies are also devising novel technologies to outfox the criminals. Even the Catholic church is joining the cause, issuing a stern statement in August that it is in “the best interest of all concerned that smuggling of counterfeit drugs be fought against”.

The pope’s concern is justified. Counterfeit drugs can kill. Many are shoddily made, containing the wrong dose of the active ingredient. Taking them instead of the real thing can turn a treatable disease into a fatal one. It can also foster drug resistance among germs. This has been a big problem for a long time in developing countries. Studies of anti-infective treatments in Africa and South-East Asia have found that perhaps 15-30% are fakes. The UN estimates that roughly half of the anti-malarial drugs sold in Africa—worth some $438m a year—are counterfeits.

Roger Bate of the American Enterprise Institute, a think-tank in Washington, DC, cautions that any such estimates should be treated with care. The countries with the most fakes may not be cracking down, so official figures will look rosy; in contrast, countries with a smaller counterfeit trade that are vigilant may end up with more seizures. The World Health Organisation agrees, and has recently taken its estimates off its website. Even so, Mr Bate says his field work has convinced him that counterfeits kill at least 100,000 people a year, mostly in the poor world.

Now it appears that fakes are taking off in the rich world too. Yes, Viagra still tops the list of knock-offs seen by Pfizer, says John Clark, the American drug firm’s global head of security; but fake versions of at least 20 of its products (including Lipitor, a blockbuster cholesterol drug) have been detected in the legitimate supply chains of at least 44 countries. Mr Clark’s intelligence comes from Pfizer’s global network of informants, consumer tip-offs and in-store inspections. He sees worrying trends.

Counterfeiters used to operate chiefly in developing countries, says Mr Clark, but now his firm sees fakes coming from such rich and well-regulated places as Canada and Britain. And the crooks are growing more technologically sophisticated: some can even counterfeit the holograms on packets that are meant to reassure customers that pills are genuine.

A consumer study funded by Pfizer recently found that nearly a fifth of Europeans polled in 14 countries had obtained medicines through illicit channels. That, the firm reckons, makes for a grey market in the EU of over €10 billion ($12.8 billion). Terry Hisey of Deloitte, a consultancy, thinks the global market for fakes could be worth between $75 billion and $200 billion a year. Those staggering sums, he argues, help explain the emergence of a flurry of new technologies and companies hoping to help the drugs industry “secure its global supply chain”.

In July Oracle, an American software giant, unveiled Pedigree, a programme that helps drugs firms “track and trace” pills all the way from the factory to your fingers. IBM has a rival offering, as well as one using radio-frequency identification (RfID) chips, which are embedded in packaging to detect tampering and allow precise tracking. 3M, a materials company, and Abbott Laboratories, an American medical firm, are also rolling out an RfID-based product. A division of Johnson & Johnson, a drugs giant, has developed web-based software to help customs officials quickly verify whether drugs are fake or real.

Poor countries find it hard to take advantage of such technologies. Sophisticated radio tags and database software are not much use in places where street hawkers peddle fakes with impunity. Still, even in such difficult circumstances, a combination of political will and business ingenuity can make a difference.

Bottom-up battle

A Ghanaian start-up firm, mPedigree, has come up with a clever way to use mobile phones in this fight. Participating drugs companies emboss a special code onto packages, which customers find by scratching off a coating. By sending a free text with that code, they can find out instantly if the package is genuine or a fake.

Bright Simons, the firm’s boss, argues that technologies like his can be a useful bottom-up complement to top-down enforcement. Having successfully completed initial trials, he says, mPedigree is ready to expand its service in the region. The government of Nigeria, where fakery is rife, recently declared its intention to adopt such a text-based validation system.

Thomas Kubic of the Pharmaceutical Security Institute, an industry-funded outfit, gives warning that this war will be hard to win. After more than 30 years as an investigator, he is sure that crooks will eventually find a way around any defence.

Even so, he thinks novel approaches such as mobile-based validation may “harden the target”, just as a burglar alarm makes your home somewhat trickier to rob. If the cost and complexity of faking drugs goes up, crooks may choose to fake Gucci handbags instead. This would still be theft, not to mention a crime against fashion. But it will not kill anyone.

Doctors would assess her tumor cells, looking for gene patterns that would determine which drugs would best attack her particular cancer. She would not waste precious time with ineffective drugs or trial-and-error treatment. The Duke program — considered a breakthrough at the time — was the first fruit of the new genomics, a way of letting a cancer cell’s own genes reveal the cancer’s weaknesses.

But the research at Duke turned out to be wrong. Its gene-based tests proved worthless, and the research behind them was discredited. Ms. Jacobs died a few months after treatment, and her husband and other patients’ relatives are suing Duke.

The episode is a stark illustration of serious problems in a field in which the medical community has placed great hope: using patterns from large groups of genes or other molecules to improve the detection and treatment of cancer. Companies have been formed and products have been introduced that claim to use genetics in this way, but assertions have turned out to be unfounded. While researchers agree there is great promise in this science, it has yet to yield many reliable methods for diagnosing cancer or identifying the best treatment.

Instead, as patients and their doctors try to make critical decisions about serious illnesses, they may be getting worthless information that is based on bad science. The scientific world is concerned enough that two prominent groups, the National Cancer Institute and the Institute of Medicine, have begun examining the Duke case; they hope to find new ways to evaluate claims based on emerging and complex analyses of patterns of genes and other molecules.

So far, the Food and Drug Administration “has generally not enforced” its regulation of tests created by individual labs because, until recently, such tests were relatively simple and relied heavily on the expertise of a particular doctor, said Erica Jefferson, a spokeswoman for the agency. But now, with labs offering more complex tests on a large scale, the F.D.A. is taking a new look at enforcement.

Dr. Scott Ramsey, director of cancer outcomes research at the Fred Hutchison Cancer Center in Seattle, says there is already “a mini-gold rush” of companies trying to market tests based on the new techniques, at a time when good science has not caught up with the financial push. “That’s the scariest part of all,” Dr. Ramsey said.

Doctors say the heart of the problem is the intricacy of the analyses in this emerging field and the difficulty in finding errors. Even well-respected scientists often “oversee a machine they do not understand and cannot supervise directly” because each segment of the research requires different areas of expertise, said Dr. Lajos Pusztai, a breast cancer researcher at M. D. Anderson Cancer Center at the University of Texas. As a senior scientist, he added, “It’s true for me, too.”

The Duke case came right after two other claims that gave medical researchers pause. Like the Duke case, they used complex analyses to detect patterns of genes or cell proteins. But these were tests that were supposed to find ovarian cancer in patients’ blood. One, OvaSure, was developed by a Yale scientist, Dr. Gil G. Mor, licensed by the university and sold to patients before it was found to be useless.

The other, OvaCheck, was developed by a company, Correlogic, with contributions from scientists from the National Cancer Institute and the Food and Drug Administration. Major commercial labs licensed it and were about to start using it before two statisticians from M. D. Anderson discovered and publicized its faults.

The Duke saga began when a prestigious journal, Nature Medicine, published a paper on Nov. 6, 2006, by Dr. Anil Potti, a cancer researcher at Duke University Medical Center; Joseph R. Nevins, a senior scientist there; and their colleagues. They wrote about genomic tests they developed that looked at the molecular traits of a cancerous tumor and figured out which chemotherapy would work best.

Other groups of cancer researchers had been trying to do the same thing.

“Our group was despondent to get beaten out,” said Dr. John Minna, a lung cancer researcher at the University of Texas Southwestern Medical Center. But Dr. Minna rallied; at the very least, he thought, he would make use of this incredible discovery to select drugs for lung cancer patients.

First, though, he asked two statisticians at M. D. Anderson, Keith Baggerly and Kevin Coombes, to check the work. Several other doctors approached them with the same request.

Dr. Baggerly and Dr. Coombes found errors almost immediately. Some seemed careless — moving a row or a column over by one in a giant spreadsheet — while others seemed inexplicable. The Duke team shrugged them off as “clerical errors.”

And the Duke researchers continued to publish papers on their genomic signatures in prestigious journals. Meanwhile, they started three trials using the work to decide which drugs to give patients.

Dr. Baggerly and Dr. Coombes tried to sound an alarm. They got the attention of the National Cancer Institute, whose own investigators wanted to use the Duke system in a clinical trial but were dissuaded by the criticisms. Finally, they published their analysis in The Annals of Applied Statistics, a journal that medical scientists rarely read.

The situation finally grabbed the cancer world’s attention last July, not because of the efforts of Dr. Baggerly and Dr. Coombes, but because a trade publication, The Cancer Letter, reported that the lead researcher, Dr. Potti, had falsified parts of his résumé. He claimed, among other things, that he had been a Rhodes scholar.

“It took that to make people sit up and take notice,” said Dr. Steven Goodman, professor of oncology, pediatrics, epidemiology and biostatistics at Johns Hopkins University.

In the end, four gene signature papers were retracted. Duke shut down three trials using the results. Dr. Potti resigned from Duke. He declined to be interviewed for this article. His collaborator and mentor, Dr. Nevins, no longer directs one of Duke’s genomics centers.

The cancer world is reeling.

The Duke researchers had even set up a company — now disbanded — and planned to sell their test to determine cancer treatments. Duke cancer patients and their families, including Mrs. Jacobs’s husband, Walter Jacobs, say they feel angry and betrayed. And medical researchers see the story as a call to action. With such huge data sets and complicated analyses, researchers can no longer trust their hunches that a result does — or does not — make sense.

“Our intuition is pretty darn poor,” Dr. Baggerly said.

This article has been revised to reflect the following correction:

Correction: July 7, 2011

An earlier version of this post misstated Dr. Steven Goodman’s affiliation at Johns Hopkins University. He is a professor of oncology, pediatrics, epidemiology and biostatistics, not the director of oncology biostatistics.

MASSDEVICE ON CALL — Medtronic Inc. (NYSE:MDT) faces new heat over the Infuse bone growth product, this time for allegations that the therapy caused excess bone growth in the spinal canal of 70 percent of patients in an independent clinical trial.

In what has become a familiar cry against the Infuse product, doctors on the company’s payroll were accused of concealing vital information from published studies.

A 2004 paper written about a clinical trial conducted by MDT’s paid consultants maintained that no harm was done to patients and that any excess bone growth, known as ectopic bone, didn’t cause any ill effects.

Just a few months ago, a clinical trial found that nearly three quarters of patients had unwanted bone growth in their spinal canals, and the trial was cut off after only 34 of hundreds of enrolled patients had received the implant, the Milwaukee Journal Sentinel reported.

The allegations continue to stack the deck against the Infuse implant, which has been widely used to fuse spinal vertebrae during surgeries since 2002.

A study published last month accused the Fridley, Minn.-based company of concealing that the bio-engineered bone growth protein can increase the risk of infertility in men. Last week two U.S. Senators demanded that the medical device giant turn over documents relating to internal correspondence with paid consultants and researchers who worked on product trials, expanding the investigation into whether physicians on the company’s payroll concealed the infertility risk.

A critical review of Infuse’s complications will be published in the Spine Journal this week.

Readers may recall that Venter’s paper touched off a big debate about the potential benefits and dangers of ‘creating’ life in the lab. President Obama asked his Bioethics Commission to hold several hearings on the topic and issue a report with recommendations on how the new field of synthetic biology (syn-bio) should be monitored. At the end of last year, the Commission recommended moderate oversight.

But Baker’s piece is largely about the new problems scientists face in synthesizing more complicated genomes before viable commercial products can be developed. The promise of inexpensive vaccines and alternative fuels is probably a long way off yet.

“Most of us are still working on a small scale because there are interesting questions there and because that’s what we have the technology to build,” says James Collins, a biomedical engineer at Boston University in Massachusetts. “We frankly don’t understand biology well enough to start designing genomes de novo.”

Many technologies must fall into place before researchers will be able to routinely work with even tens of genes at a time. Putting together huge DNA molecules is time-consuming and expensive, and designing biological components to perform a particular task is a challenge for parts of genes, let alone whole genomes. Transplanting DNA molecules into cells is not easy, nor is getting the DNA to ‘boot up’ once it is in place. And because the genomes will be far from perfect, researchers will need ways to tweak and test many variants.

Baker quotes Venter, who thinks that adapting genomes to work in different cell types will prove to be the biggest challenge to scientists. The creation of the first synthetic cell was illustrative, she writes, as Venter’s team “had to remove certain enzymes from recipient cells to keep them from cutting up the foreign DNA. And moving to other species is going to be even more difficult.”

The company plans to use the stem cells for its own research and to sell them to other laboratories that are working on ways to use stem cells to treat diseases, repaire injured organs or replace damaged tissue.

Shares of International Stem Cell rose 5 cents, or nearly 5 percent, Thursday to $1.11.

The launch of the U.S. bank came after the company received regulatory approval for its methods of collecting the donor eggs, which are known as oocytes.

The company’s scientists in 2007 developed a way to produce pluripotent stem cells from unfertilized eggs that then have the potential to become nearly any of the more than 200 types of adult cells found in the human body.

These human parthenogenetic stem cells, or hpSC’s, avoid the political and moral controversies tied to stem cells grown from human embryos. They also appear to overcome a major technical obstacle facing other types of stem cells.

Patients receiving therapies derived from embryonic stem cells must take immunosuppressive drugs like the ones given to patients who undergo donated organ transplants in order to prevent their bodies from rejecting the foreign cells.

Another category of stem cells created from adult skin cells have offered hope for avoiding rejection issues when using the cells in the donors. However, recent research by scientists at the University of California San Diego in mice raised new questions about whether those induced pluripotent cells might actually be rejected.

International Stem Cell researchers say the simpler genetic fingerprint found in their oocyte-derived stem cells should make them compatible with the immune systems of millions of potential recipients.

“There is growing recognition that online communities not only provide a place for members to support each other, but also contain knowledge that can be mined for public health research, surveillance, and other health-related activities,” said Mandl, director of the Intelligent Health Laboratory at CHIP and co-principal investigator of the project along with Weitzman.

Members of TuDiabetes.org were invited to participate in a “data donation drive” and share data about their hemoglobin A1c (or A1c) status, a health metric used to measure diabetes control over a prolonged period of time.

Through an application called TuAnalyze, based on CHIP’s Indivo personally controlled health record, TuDiabetes members were able to share their health data anonymously or publicly. All of the submitted data was aggregated and displayed on state- or country-level maps in near real-time.

“We were hoping to gauge the community’s willingness to share their personal data for public health surveillance,” said Mandl, an associate professor at Harvard Medical School, “and give them a tool that allowed them to securely share their data, all the while supporting socially-based encouragement and a sense of community activism.”

Within three months, 17 percent of total active TuDiabetes members and 21 percent of active users in the United States had signed on to TuAnalyze. Among all TuAnalyze users, 81.4 percent chose to share their A1c data in aggregate, while 34.1 percent also chose to display their personal A1c data on their TuDiabetes profile. The average unadjusted A1c reported by TuAnalyze users in the United States was comparable to that reported in the most recent National Health and Nutrition Examination Survey (NHANES) by the Centers for Disease Control and Prevention (CDC).

Early adopters (i.e., those who signed on to TuAnalyze within the first two weeks of launch) reported lower average A1c values than those signing onto the application later, as did members who shared their A1c data openly on their TuDiabetes profiles versus those who only shared their data in aggregate, and members who shared multiple A1c values versus those who only shared one.

“TuAnalyze has allowed the members of TuDiabetes that have used it to share their diabetes data and connect as a community around it,” said Manny Hernandez, founder of TuDiabetes and president of the Diabetes Hands Foundation, the nonprofit that runs the site. “This application has given us an initial glimpse of the kinds of things we can learn as a community, and caused us to focus our time and resources on matters that are pressing and relevant to our members.”

Mandl commented that, “Our experience with this project tests certain fundamental assumptions about how we can conduct science across populations, including people’s willingness to share data for public health research for their community, as opposed to for themselves, and what we need to do to encourage that. In this instance, we have demonstrated a tool that respects member confidentiality preferences while securely allowing aggregation of data to benefit the community at large.”

“While they produce high-quality data, large, structured population-based reporting systems are not nimble, and provide no opportunity for interaction or feedback,” added Weitzman, an assistant professor at Harvard Medical School. “Science is changing and there is emerging an expectation and desire among participants for a continued research relationship and an opportunity to learn more about their own disease, for which online networks provide a platform.”

Weitzman noted, “If we are serious about understanding and ameliorating disease, we need to find a way to engage entire populations in health research cost-efficiently, to understand the experience and patterns of illness and the ways in which patient populations are undertaking and responding to treatments.”

Going forward the CHIP team is collecting more complex data on quality of care and adverse events within the population using TuAnalyze and exploring how to engage the community in a more permanent and longitudinal way.

TuAnalyze was developed with support from the U.S. Centers for Disease Control and Prevention.

Drugs such as Prozac that alter a patient’s mental state already have an impact on moral behaviour, but scientists predict that future medical advances may allow much more sophisticated manipulations.

The field is in its infancy, but “it’s very far from being science fiction”, said Dr Guy Kahane, deputy director of the Oxford Centre for Neuroethics and a Wellcome Trust biomedical ethics award winner.

“Science has ignored the question of moral improvement so far, but it is now becoming a big debate,” he said. “There is already a growing body of research you can describe in these terms. Studies show that certain drugs affect the ways people respond to moral dilemmas by increasing their sense of empathy, group affiliation and by reducing aggression.”

Researchers have become very interested in developing biomedical technologies capable of intervening in the biological processes that affect moral behaviour and moral thinking, according to Dr Tom Douglas, a Wellcome Trust research fellow at Oxford University’s Uehiro Centre. “It is a very hot area of scientific study right now.”

He is co-author of Enhancing Human Capacities, published on Monday, which includes a chapter on moral enhancement.

Drugs that affect our moral thinking and behaviour already exist, but we tend not to think of them in that way. [Prozac] lowers aggression and bitterness against environment and so could be said to make people more agreeable. Or Oxytocin, the so-called love hormone … increases feelings of social bonding and empathy while reducing anxiety,” he said.

“Scientists will develop more of these drugs and create new ways of taking drugs we already know about. We can already, for example, take prescribed doses of Oxytocin as a nasal spray,” he said.

But would pharmacologically-induced altruism, for example, amount to genuine moral behaviour? Guy Kahane, deputy director of the Oxford Centre for Neuroethics and a Wellcome Trust biomedical ethics award winner, said: “We can change people’s emotional responses but quite whether that improves their moral behaviour is not something science can answer.”

He also admitted that it was unlikely people would “rush to take a pill that would make them morally better.

“Becoming more trusting, nicer, less aggressive and less violent can make you more vulnerable to exploitation,” he said. “On the other hand, it could improve your relationships or help your career.”

Kahane does not advocate putting morality drugs in the water supply, but he suggests that if administered widely they might help humanity to tackle global issues.

“Relating to the plight of people on other side of the world or of future generations is not in our nature,” he said. “This new body of drugs could make possible feelings of global affiliation and of abstract empathy for future generations.”

Ruud ter Meulen, chair in ethics in medicine and director of the centre for ethics in medicine at the University of Bristol, warned that while some drugs can improve moral behaviour, other drugs – and sometimes the same ones – can have the opposite effect.

“While Oxytocin makes you more likely to trust and co-operate with others in your social group, it reduces empathy for those outside the group,” Meulen said.

The use of deep brain stimulation, used to help those with Parkinson’s disease, has had unintended consequences, leading to cases where patients begin stealing from shops and even becoming sexually aggressive, he added.

“Basic moral behaviour is to be helpful to others, feel responsible to others, have a sense of solidarity and sense of justice,” he said. “I’m not sure that drugs can ever achieve this. But there’s no question that they can make us more likeable, more social, less aggressive, more open attitude to other people,” he said.

Meulen also suggested that moral-enhancement drugs might be used in the criminal justice system. “These drugs will be more effective in prevention and cure than prison,” he said.

Much of what happens to you in the hospital in the name of diagnosing and healing is invasive. Depending on what ails you, a doctor may need to ream out an artery to get more blood to your heart, or flood your body with a poison to kill cancerous cells, or saw through the bones of your leg to replace a crumbling hip or a worn-out knee. If a stranger came at you with a scalpel or syringe in a back alley, you would consider it assault and battery. But in a hospital most of us willingly schedule an appointment and pay big money to be precision-poked and carved because we trust our doctor’s skill and knowledge and assume the alternatives—illness, incapacity or early death—are surely worse.

But how many patients truly understand the alternatives or the risks and benefits of the test or treatment they are undergoing? One of the guiding principles of modern health care is that, except in an emergency, doctors must get the patient’s permission before the start of any invasive medical procedure. That “informed consent” is supposed to be based on an earlier conversation during which physicians make sure patients understand what the procedure will and will not do, along with its benefits and risks relative to other options.

Unfortunately, what typically happens in hospitals and clinics across the U.S. is far from ideal: On the way into surgery or some test or treatment, a nurse or technician slips the patient a clipboard of legalese to sign. In most cases, that piece of paper is either a vague permission slip acknowledging that the patient has been “informed” about the procedure, or it reads like a legal waiver—a laundry list of every single side effect and rare complication that could possibly go wrong. These badly written, hastily signed forms are meaningless or worse, health literacy experts say. Research consistently confirms that the flawed permission slips do not improve the patient’s understanding or safety. Nor do they protect hospitals or doctors from misguided malpractice suits.

In hopes of filling the gap, a growing number of medical centers are now turning to technology—specifically, interactive computer programs that are designed to get beyond the one-size-fits-no-one consent form. These software solutions vary widely in approach and targeted audience. Some are aimed at doctors, others at patients. Some are meant to be reviewed with a health care provider during an office visit; others can be watched with family members at home. Health researchers still debate each approach’s effectiveness. Rigorous outside testing of them has barely begun. But everyone lauds the goals these new approaches share. First, the programs aim to help make the discussion of the relative pros and cons of every invasive procedure—from angioplasty to tonsillectomy—more meaningful for the patient. Second, they aim to get doctors talking about benefits and risks much earlier in the diagnostic and treatment process so that patients can make truly informed choices about their own health care.

Strong evidence that traditional consent forms fail to inform patients or improve their care has been growing for more than a decade, says Harlan M. Krumholz of Yale University, who studies the ways the system goes wrong. One of the most telling nationwide investigations, he says, was a review published in 2000 of 540 forms collected from 157 randomly selected U.S. hospitals by a public health team led by Melissa M. Bottrell, then at New York University and now with the U.S. Department of Veterans Affairs. Its analysis revealed a haphazard mess: Some forms were short and vague; others were long and confusing. Many contained legalistic language that muddied the decision-making character of the consent process. Only about one in four of the forms went beyond a basic description of the procedure to include common risks, benefits and alternatives.

In nearly 60 percent of the documents studied, protecting “against liability” was the rationale given for using the permission slips, according to the hospitals submitting the forms. Too often, Krumholz says, the informed consent process has deteriorated into “largely a risk management tool for hospitals—a way to try to avoid malpractice suits—instead of a way to promote good decisions. And that seems to me a real shame.”
Often the forms do not achieve even that self-defensive aim, says attorney Jeffrey F. Driver, who advises Stanford University Medical Center on medical malpractice cases. For one thing, research suggests the legalistic tone of such forms irks patients and makes them suspicious of their doctor and the hospital, and that suspicion may increase the likelihood of a later suit. Plus there is good evidence that the long list of potential medical complications does nothing to help people distracted by illness or anxiety understand that even a medical procedure performed perfectly may still produce undesirable results, Driver says. His research showed that patients often sue because they mistakenly assume that a known complication of their procedure is the result of medical error. Lengthy forms only fueled such cases. “We realized what we needed was much better patient education up front,” Driver says, “to make sure the patient’s expectations of what could happen were similar to the doctor’s.”

Communication is essential no matter what the approach. Dean Schillinger, an internist and health literacy specialist at the University of California, San Francisco, and his colleagues recently published a review of 44 small studies of different programs aimed at improving the informed consent process. The key to enhancing patient understanding of risks and trade-offs, they found, was to have a high-quality discussion—whether prompted by a computer program or in response to a simply written printed explanation of pros, cons and alternatives. Anything that got patients to reiterate what they have learned in their own words significantly improved the consent process.

Two new options
One of the first decisions hospitals face when purchasing a technology-based system is whether they want to focus more on the physician’s side of the informed consent process or the patient’s side. In 2006 the Stanford Medical Center chose a patient-oriented product from a Chicago-based company, Emmi Solutions.

Patients log on to one of Emmi’s online computer modules from the doctor’s office or at home. All the programs are interactive and self-paced, typically taking about 30 minutes to complete, although they can be paused or reviewed. Nearly 200 frequently performed procedures—from colonoscopy to hip replacement—are covered. Doctors can enable the viewer to type a question to them or someone else on their staff and send it for a response in an online chat.

One of the audiovisual program’s advantages over strictly paper-based forms is that it automatically checks for comprehension and flags certain items for deeper discussion. For example, the program keeps track of all questions raised by patients as well as every time they request more information. That list alerts the doctor to address the remaining concerns or confusion during the next appointment. Then, before the procedure, patients still sign a very brief written consent, signifying they have watched the interactive program and have had a discussion with their doctor. “Informed consent is the process, not the form,” Driver says. “The piece of paper should just be a tickle to their memory about what’s been discussed.”

The ability to keep track of a patient’s every click and screen view may also keep malpractice costs down. A would-be litigant dropped her malpractice charge against Stanford when she was shown that her pattern of computer clicks confirmed that she had actually looked at a screen shot describing that complication four times and discussed it with her doctor.

Meanwhile the Veterans Health Administration has chosen a different path, relying on software aimed at doctors. A program called iMedConsent, by Dialog Medical in Atlanta, allows the health team to quickly create consent forms and packets of educational materials tailored to each patient’s needs. Doctors type the name of any of 2,200 medical conditions, treatments or procedures into the program, and a consent form specific to that condition or procedure pops up on the screen. Different parts of the online template detail the procedure’s benefits, risks and alternatives in sixth-grade English or Spanish. The template also prompts doctors to discuss with patients their prognosis if they choose to have no treatment or procedure at all.

If more information is required, physicians can call up and print out educational brochures or illustrations from Dialog Medical’s extensive online library. The patient and doctor can study the information together on the screen, or the patient can take it home to review it at his or her own pace with family members. Because the forms become part of the patient’s electronic medical record, anyone on the health team throughout the VA system can easily check to see what sort of consent discussion occurred and answer any further questions.

U.C.S.F.’s Schillinger applauds any attempt to make the informed consent process “more than just a medical Miranda warning.” But he is concerned that there has not been enough independent research to evaluate the effectiveness of various approaches to providing informed consent. Nevertheless, one thing is clear. True face-to-face interactions turn out to be the best medicine.

Increasingly, however, clinics are preparing to match these embryos — which could survive for decades in suspended animation — with infertile couples who long for a child of their own. It’s a form of third-party procreation that experts predict will only become more common as the number of surplus embryos grows.

Embryo donation has been called the most humane answer to an sticky ethical situation: How to dispose of leftover embryos that are created by infertility treatments and then literally frozen in time?

For the donors, allowing their unused embryos to be thawed and implanted into another woman’s womb means giving their potential offspring a chance at life, when the only other options are to destroy them, donate them to medical research or keep them in deep freeze indefinitely.

For a woman or couple facing infertility, these donor embryos — loaded into straws and immersed in liquid nitrogen three to five days after conception — are often the only hope left at a pregnancy.

But the practice is raising difficult ethical issues, including concerns about the rights of children who would be born to parents with whom they have no genetic ties.

And should such children have the right to know the identity of the people whose DNA created them? Should we even be producing more embryos than can be used at once?

Toronto’s Mount Sinai Hospital — among the largest hospitals in the country — is preparing to begin offering anonymous embryo donation in coming months through its Centre for Fertility and Reproductive Health, Postmedia News has learned.

Vancouver’s Genesis Fertility Centre has also been working on developing an embryo donation program for more than a year. And in Calgary, between 75 and 100 children have already been born through embryo donation at the city’s Regional Fertility Program.

Across the country, embryo donations are being arranged sporadically, here and there, without national guidelines.

Some couples are finding one another on the web, raising concerns that despite a federal act outlawing the purchase of human sperm, eggs and embryos, money may still be changing hands.

“We’ve had people who met on the Internet, which is always dicey,” says Dr. Calvin Greene, medical director of Calgary’s Regional Fertility Program. “Are they selling it, because that’s against the law . . . All you can do is ask them. We don’t send out the RCMP or check their chequebooks.”

Kerry Barnes received a donated embryo in 2009, after six years of infertility treatments that included four rounds of IVF, two surgeries and three miscarriages. Her stomach was once so marked with needle punctures from the hormone shots that she couldn’t find anywhere left to inject herself.

“After the fourth IVF, we said ‘what else can we do?’ ” the Ottawa woman recalls.

A couple with twins born after IVF donated three embryos that had been frozen for almost five years to Kerry and her husband. Only one survived thawing. “We named him Tiger, because he would have been born in the year of the tiger.”

Five weeks after the transfer, Kerry began spotting. By seven weeks, “we knew we had lost him.”

She says more should be done to encourage and help couples donate embryos they no longer want or need.

“I think most people would always be thinking about them in the cold. I know I would.”

Just how many embryos are in deep freeze in the nation’s IVF clinics is a mystery. No one — not the Canadian Fertility and Andrology Society, the professional body of fertility doctors, nor Assisted Human Reproduction Canada — keeps track.

The latter body — a federal agency whose mandate is to protect the “health, safety, dignity and rights of Canadians” who use, or are born of human reproductive technologies — says it has no authority to collect this data.

Only each clinic knows how many are in its freezers at any one time. One large Toronto clinic, for example, has 2,800 embryos.

As of August 2003, the last published count, a total of 15,615 embryos were in storage at 13 IVF clinics that responded to a survey by Dalhousie University researchers. There are 33 IVF clinics in the country today. And there have been about 60,000 cycles of IVF since 2003.

Experts predict the number of cryopreserved human embryos is now probably triple the 2003 count.

In some cases, couples move away, drop out of treatment or can’t be contacted, effectively abandoning their embryos, some of which have been in cold storage for more than a decade.

The buildup is a byproduct of the IVF process, which requires ovarian stimulation. A woman has to inject herself daily for about 10 days with fertility drugs that simulate her ovaries to produce multiple eggs — 10 to 30 — instead of the usual one. Only the two or three best-looking embryos — fat, round embryos with no evidence of crumbling of any of the cells — are selected for fresh transfer.

The worry is that if doctors keep stimulating women’s ovaries the way they have in the past, “the number of embryos is going to grow,” says Dr. Roger Pierson, a past president of the Canadian Fertility and Andrology Society. “If we stay on the track that we’re on, in five to 10 years, the problem is going to be enormous.”

That will leave more couples who have struggled with infertility facing the anguish of how to “dispose” of their leftover embryos.

Mount Sinai, in Toronto, is compiling a list of patients willing to donate their embryos.

“Their families are complete, the only other option for what to do with the embryos is either store them indefinitely, which is really just delaying a decision, having them destroyed or donating them for use in research studies — and some people aren’t feeling comfortable with any of those options,” says Dr. Ellen Greenblatt, medical director of Mount Sinai’s Centre for Fertility and Reproductive Health.

With embryo donation, “you’re using material that otherwise is sort of wasted to help women and couples form families that they perhaps otherwise could never have,” she says. “And for the couples that have extra embryos in the freezer that really can’t get their heads around not giving that embryo a chance at becoming a child, it’s a very good option for them.”

Under the Toronto program, patients — including couples where both partners are infertile, as well as single women — will be placed on an embryo donation waiting list. Embryos will be offered on a “first-come, first-served basis.” Donors would have to agree to be re-screened for a raft of viruses, such as HIV and hepatitis, before the embryos are thawed and transferred. Donated embryos will only go to women under 50.

Recipients will receive non-identifying information about the donor, such as family history of diseases, but donors will decide whether to reveal their identity when the child reaches 18.

And that’s where things get controversial.

Adult children conceived via donor sperm are already going to court for their right to the records of their biological fathers. Some ethicists argue that it’s wrong to pass on human life anonymously, but infertility clinics say that many donors won’t donate if they can’t do so anonymously.

In Ottawa, Dr. Arthur Leader, a professor of obstetrics, gynecology and medicine at the University of Ottawa and a founding partner of the Ottawa Fertility Centre, once worked with a couple that specified their unused embryos couldn’t go to anyone living within a 100-kilometre radius.

“People put restrictions on where the embryos can go. . . . They don’t want to see children that look similar to their own children,” he says.

Questions have also been raised around who “owns” an embryo, whether it has “rights” under the law. The issue is so controversial that the American Society for Reproductive Medicine has urged clinics in the U.S. not to use the term embryo “adoption.”

The group’s ethics committee argues that while an embryo deserves a higher “moral status” than other human tissue because it holds potential for life, it shouldn’t be viewed as a “person.”

Under Canadian law, the woman who gives birth — and not the biological mother — is the mother of the child. Legally, the baby belongs to whomever delivers it, Greene, of Calgary, says. “Nobody could ever take that baby away from them.”

So far there’s no known shelf life for frozen embryos. Embryos from animals have been cryopreserved for 25 years, thawed and produced offspring.

“The current thought is that they are probably there for millennia,” Pierson says.

That raises the prospect of cross-generational pregnancies. For example, a couple freezes their embryos in 1990. They have a child, but keep paying their annual storage fees to keep their extra embryos in cold storage. Now their daughter is 25 and she and her partner have fertility problems.

“And mom says, ‘Hey, I still have some embryos from the IVF cycle that you were created from. Let’s try those,’ ” Pierson says.

Embryo donation is so new, little is known about the psychological impact on the children born.

“These children would grow up knowing that their biological parents created embryos with the intention of them being born to the genetic parents, but then the parents changed their minds and relinquished them,” says Dr. Christopher Newton, a psychologist at The Fertility Clinic at Ontario’s London Health Sciences Centre.

But the argument has been made that life is better than no life at all.

“These parents took these embryos and raised them and gave children the opportunity to be born and live,” Newton says. “If they hadn’t done that, what would have happened to the embryos?”