Peter Singer is driven by a postcard in his mind. On a trip to a remote village in Pondicherry, India, three years ago, Singer - head of U of T's Joint Centre for Bioethics and one of the leading bioethicists on a massive initiative to improve health in the developing world - made a surprising discovery. There, among the mud-floored, thatched-roofed huts, was an information kiosk hooked up to the Internet.

Fishermen were using that computer to get U.S. Navy weather satellite information to avoid stormy weather. Farmers were checking grain prices on the local market to assess the value of their crops and young people were searching for employment opportunities 100 km away. There was even a college student working on her zoology homework.

"I think many people have a postcard in their minds of what they're trying to work towards. My postcard is a group of kids crowded into this hut with a computer in the background, beaming away and smiling and engaged. It's a prime example of science and technology having a real effect on the lives of people who need it most."

Today, Singer is using that grass-roots initiative as inspiration for his goals in global health. "Imagine if we could make that kind of impact in life sciences, harnessing our knowledge and resources against the world's most dire health problems."

Those problems, stemming largely from widespread disease and malnutrition, have led to a sobering new statistic: life expectancy is 80 years and rising in the developed world, 40 years and falling in the developing world. Insists Singer: "It's the mother of all ethical challenges."

Key players in the world of big science agree. Last year, researchers from around the globe were awarded over $430 million to get creative in addressing the biggest health issues in the developing world. The initiative is called the Grand Challenges in Global Health, funded by the Bill and Melinda Gates Foundation, the Wellcome Trust and the Canadian Institutes of Health Research and managed by global health experts at these organizations and the Foundation for the National Institutes of Health.

Scientists are working on 43 forward-thinking solutions, from reprogramming disease-spreading mosquitoes so they won't bite humans to encasing vaccines in heat-resistant bacteria to eliminate the need for refrigeration. The common thread: pushing that life expectancy up.

Whether they are successful will depend a lot on innovative science, to be sure. But it will also require buy-in from the people for whom these solutions are developed. That's where Peter Singer and a growing network of the world's top bioethics brains come in.

Singer, Jim Lavery, Abdallah Daar, Ross Upshur and Jerome Singh, have received a CDN $12 million Grand Challenges grant - arguably the largest ever single bioethics grant in the world - to help the leaders of all 43 projects address the ethical, social and cultural issues that they will undoubtedly come up against.

The team has two big mandates during the grant's five-year lifetime: first, to provide an advisory service to the project leaders as they grapple with these issues, and then to publish what they've learned so that future researchers will have good guidelines to follow.

"This is incredibly high-risk science," says Lavery, a professor in the Department of Public Health Sciences and a research scientist at the Centres for Inner City Health Research and Global Health Research at St. Michael's Hospital, who is also co-principal investigator along with Singer on the Grand Challenges grant.

"There is amazing potential. But the ethical, social and cultural issues are new and complicated and unknown. And if you don't address them properly and carefully, the whole thing could just shut down."

An example of that high-risk science is a genetically modified mosquito trial, which took Lavery to Mexico and Trinidad recently to help investigators select a site.

Dengue virus, a flu-like disease transmitted through mosquito bites, is a huge killer in the world's tropical zones. This particular Grand Challenges project involves genetically engineering mosquitoes so that they can't transmit the virus - either by programming them to die as soon as they get it, or by sterilizing them so the population eventually dies out.

To pick the best trial site, Lavery is looking at several factors. "We want to know if we'll be able to have fruitful relationships with the community, if they have a good regulatory structure in place, what the political and economic environments are like, how the health authorities feel about it, and so on. Our goal is to deal with these problems in an up-front and constructive way, and engage communities in ways that maximize the likelihood that these new technologies will ultimately be adopted."

How will they tackle that lofty goal? The answer is deceptively simple: networking.

Evolving out of a strategic alliance between U of T and 15 health care organizations in Toronto, the Joint Centre for Bioethics (JCB) has fostered a wide reaching network of experts from around the world.

Recruiting star faculty members such as Abdallah Daar from Sultan Qaboos University in Oman and attracting up-and-coming thinkers such as Jerome Singh to the Master of Health Science in Bioethics (MHSc) program, the JCB has created a capacity that makes it a standout in the international bioethics community.

That successful recipe of idea swapping and team building is also the driving force behind its approach to the Grand Challenges initiative. "We really work as a team - an increasingly global team," says Singer, who recently forged partnerships with two people from India and Ghana, both graduates of the JCB's MHSc program. "And we think of ourselves as serving a global community and helping create strong voices in the South."

The concept of 'Voices of the South' is a key element of the group's master plan. They have set out to connect with bioethicists in the developing world and with other stakeholders who might influence outcomes - from government officials to non-governmental organizations (NGOs) to chief executives of biosciences companies.

"Imagine a network of tens or even hundreds of people working collaboratively on the issues surrounding a new technology and its adoption, giving input and feedback," says Singer. "That's the sort of engagement that we need. It oughtn't to be Northern voices dominating the conversation here - it should be Southern voices guiding the adoption. So fostering that network is a big part of our job."

Abdallah Daar's cellphone is never far from reach. Preparing to combine a meeting with a quick lunch, he cradles his phone with one shoulder, finishing up another business call while ordering a sandwich.

Multi-tasking is somewhat of a specialty for Daar, a professor in both Public Health Sciences and Surgery, director of the Program in Applied Ethics and Biotechnology and co-director (with Singer) of the JCB's Canadian Program on Genomics and Global Health.

The latter, Daar's brainchild and the reason he came to U of T, has caused a sea change at the JCB in recent years, shifting its central focus from issues such as end-of-life care to the broader health issues facing millions of the world's poor.

In 1998, while a visiting professor at U of T's Faculty of Law, Daar was immersed in writing a WHO-commissioned report on biotechnology, genomics and global health. "I became convinced of the need to apply the fruits of the research in biotech and genomics very quickly to help the millions of people dying in the developing world," recalls Daar. "The ideas in that report became the basis for creating the Canadian Program on Genomics and Global Health at the JCB."

The program, launched in 2000, is the largest of its kind and has attracted an unprecedented $22 million in the last year alone - $10 million from Genome Canada and $12 million for the Grand Challenges project.

Singer and Daar were involved in the Grand Challenges long before the money came in the door, helping the Gates Foundation and the National Institutes of Health identify the most pressing global health issues and then articulate the 14 overarching challenges under which the individual projects fall (see sidebar).

Daar's counsel is sought after elsewhere in the world as well, and his advisory work serves double duty for the Grand Challenges project. This April, for example, he'll head to Egypt for the annual meeting of the African Union's biotechnology panel, on which he serves. There he'll have access to some of Africa's leading thinkers on biotechnology R&D - a ready-made focus group for ferreting out the many ethical, social and cultural issues the Grand Challenges will raise.

This kind of networking, says Daar, is what makes the JCB approach so unique. "Our expertise is absolutely based on being linked to the developing world. We don't do armchair ethics - we're out there in the real world, doing empirical work. And part of that means listening. We don't tell the world what needs to be done; we let the world tell us what we need to do."

It's 4:30 on a March afternoon and Jerome Singh is in a hurry. In half an hour he's due at his first French lesson."Right now my French is very basic, mostly gleaned from watching the French Open tennis tournament!" confesses Singh, a core member of the JCB team and one of a growing number of collaborators living in the developing world.

Singh is based in his hometown of Durban, a large, multicultural city on South Africa's east coast. There he heads up the ethics and health law program at the Centre for the AIDS Programme of Research in South Africa, and teaches a bioethics course at the University of KwaZulu-Natal's law school.

A graduate of the JCB's Master of Health Science in Bioethics Program and currently an adjunct professor at U of T's Department of Public Health Sciences, Singh is leading the Grand Challenges bioethics advisory service in partnership with Jim Lavery. With an impressive five degrees under his belt, including a bachelor's and a master's degree in law as well as a PhD, Singh hardly needs to pad his resumé with more courses. But his latest trip to the classroom has a very strategic purpose.

"French is one of the four main languages spoken in Africa, and I'd like to communicate better with the investigators I'll be liaising with," he says, having recently returned from a trip to French-speaking Mali in northern Africa, where he was consulting on a multi-country Grand Challenges project on malaria. "It will also be a sign of respect when I visit communities in the francophone countries."

Aside from the obvious benefits of his academic credentials, Singh brings an important perspective to the table. Living in a country with "one foot in the developed world and one foot in the developing world," he sees the issues from both sides. "There is a strange dance that goes on in South Africa all the time: there are very advanced scientific institutions here and there's a scientific agenda that gets pushed forward, but there are also really potent concerns from the grass-roots level. Those concerns, and the misunderstanding and demystification of science is a problem here in South Africa. So that's what I experience first hand."

That perspective is invaluable to the Grand Challenges investigators in Africa. "When I was speaking with some of the folks in Mali, they felt comfortable knowing that I am from Africa and can see what their perspective is, because we face similar challenges."

His expertise in AIDS research also puts him ahead of the curve. "Understanding of the ethical, social and cultural issues that arise in research is far more advanced in the field of HIV than in other diseases, because there's been so much campaigning and lobbying. So the Grand Challenges investigators are finding some of my experiences quite helpful, in terms of how we engage with communities and how we address the cultural issues."

Engaging communities is also on Ross Upshur's mind. The fifth principal member of the JCB's Grand Challenges team, Upshur is focused on the group's second mandate: research.

A self-described architect, Upshur will help oversee the research program and write some of the concept papers that will inform it. Making the research broadly applicable means focusing on the overarching themes, he says. And community engagement and cultural acceptability are on the top of that list.

"One issue I'm interested in, for example, is tissue exportation. Many of the projects involved in studying human tissue require fairly complex technology for analysis, which often means transporting specimens from one part of the world to another.

"So we need to be very mindful of what research participants understand about the process of giving up bodily fluids for research in the first place, and then determine the cultural acceptability of taking it elsewhere in the world. Beyond that, what are the implications in terms of patents and benefit sharing with the communities? This all needs to be addressed."

A family physician with a busy practice at Sunnybrook and Women's College Health Sciences Centre and the director of Sunnybrook's Primary Care Research Unit, Upshur brings a clinical perspective to the table. But with a master's degree in philosophy, a background in epidemiology and a long list of international projects focused on environmental health, he thinks far beyond the bench - something the Grand Challenges project leaders welcome.

"Most of these researchers are bench scientists and they recognize very early in the game that the projects they're involved in raise very interesting, difficult and thorny ethical, social and cultural issues."

It's hardly a 40-hour work week, Upshur admits, confessing that his "second shift" begins at 9:00 p.m. after the kids are in bed. But the key is teamwork. "Part of being a productive researcher is having really good functioning teams. And I have great collaborators."

Jim Lavery agrees that collaboration is critical. Asked how his team can possibly tackle the ethical, social and cultural issues of all 43 projects on its own, his response is an emphatic, "We can't."

That is part of the reason why building a critical mass of bioethics experts in the developing world is so important.

"It's sort of like being a talent scout," explains Lavery. "There are a lot of people in the developing world who are much smarter than I am and know those contexts an awful lot better than I do. We want to help them find their voices and then work together to solve some problems and publish some really leading-edge frameworks for doing the kind of upstream science the Grand Challenges initiative represents."

If successful, their work will be an enormous resource to the international health research community. "Billions of dollars are being spent on health research around the world. Clinical trials, which many of the Grand Challenges projects are engaged in, are the fastest growing research segment. So these are huge issues for scientists right now."

Formerly a competitive soccer player and now a coach, Lavery applies a coaching metaphor to the team's capacity building work: "You train them to lose them.

"The best thing that can happen in soccer is that one of my players will go to the national team and I'll lose them. It's sort of the same with this project - we're teaming up with bioethicists around the world so that ultimately they'll have the capacity and the resources to be on the ground, running the show."

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