News: Gates Takes On Malaria

30 October 2005

San Francisco--Bill Gates is going after bugs in a big way--but not the computer kind. Today, the billionaire co-founder of Microsoft and his wife, Melinda, announced that their philanthropic foundation is giving $258.3 million to researchers to help fight the parasites that cause malaria. It is the single biggest donation from a charitable organization to fight malaria ever given.

"Deaths from malaria have doubled over the last 20 years," Gates said during a teleconference call. "It's a tragedy that the world has done so little to stop this disease that kills 2,000 African children every day," Gates said.

Forty percent, or $107.6 million, of the new funding will go to support clinical trials of a prototype vaccine aimed at protecting children against severe malaria, which is under development at GlaxoSmithKline's GSK Biologicals unit, in Rixensart, Belgium. The Bill & Melinda Gates Foundation has earmarked another $100 million for efforts to speed development of drug treatments for patients already suffering from malaria. And $50.7 million will go to develop insecticides and other techniques for controlling mosquitoes.

In the teleconference call with Gates, Glaxo's chief executive, Jean-Pierre Garnier, said he has no illusions that the company will make money by developing a malaria vaccine. "I do it because it's the right thing to do and because it's an exciting adventure for our scientists," Garnier says.

Even so, the malaria research could have some positive upside for Glaxo's commercial products, particularly for future versions of "pandemic" vaccines--drugs that could be used to protect people against new and virulent influenzas, such as the avian flu. Here's why: Key to the success of a malaria vaccine is a so-called "adjuvant," a formulation that primes the immune system to respond to a vaccine. Glaxo researchers are hopeful that the work they are doing on malaria adjuvants will pay off as they develop vaccines for future pandemic illnesses.

Taking on a challenge as scientifically and emotionally appealing as creating a malaria vaccine is also a great recruiting tool, Garnier says. "I have top-notch scientists coming to work for Glaxo who won't work for other big pharma companies," Garnier asserts, because they want to work on problems like malaria. Glaxo's competitors include companies such as Pfizer and Schering-Plough.

Having someone else foot the bill doesn't hurt, either. In recent years, large pharma companies have sharply curtailed many research programs that once explored pharmaceuticals for treating diseases that largely afflict impoverished people. For instance, only 13 out of 1,223 new medicines marketed by major drug companies between 1975 and 1997 could be used for tropical diseases, according to Doctors Without Borders.

Malaria research has been particularly squeezed. Although work on a malaria vaccine had gone on for years at SmithKline Beecham (which became GlaxoSmithKline following a merger in 2000), corporate managers considered scuttling the program as recently as 1999 to cut costs. The program survived largely because its leading researcher pledged to find outside grants to supplement his budget--a move then unheard of in the pharmaceutical industry.

In 1999, the Gates Foundation awarded its first grant supporting malaria research. Prior to the grants announced today, the Gates Foundation had, since 1999, already put more than $250 million toward malaria research efforts. That makes them big spenders. According to a study slated to be released on Monday by a nonprofit group, the Malaria Research and Development Alliance, total research and development spending on malaria totaled $323 million in 2004. More than half of that money was given by just two groups-- the U.S. National Institute of Allergies and Infectious Diseases and the Bill & Melinda Gates Foundation.

Even so, trying to create a vaccine against a parasite is a daunting task. Vaccines aim to provide the body with lasting immunity against a disease and so are seen as the most cost-effective way to safeguard against illness. Yet science has yet to produce a commercial vaccine against any parasite, living organisms that can adapt and change with startling agility.

Last year, a team of researchers in Mozambique and at GlaxoSmithKline published the results of a clinical study of a prototype malaria vaccine, involving 2,000 children. They found the vaccine (administered with its specially designed adjuvant) cut the risk of malaria by 30% for children overall and reduced the risk of the most fatal versions of malaria by 58%.

Ripley Ballou, Glaxo Vice President of Clinical R&D Early Development, says that the new money will support the development of more widespread clinical trials, which will take place over the next two to three years. Glaxo expects to try the vaccine formulation in approximately 17,000 young children in at least six countries throughout Africa.

If the trials go smoothly, a malaria vaccine could be ready for widespread use by 2011, says Melinda Moree, director of the PATH Malaria Vaccine Initiative, a nonprofit created in 1999 by the Gates Foundation to accelerate such research and development efforts.

Other multinational companies are also getting involved in fighting malaria. For instance, Exxon Mobil, which has 5,000 employees in 20 countries throughout Africa, kicked off its own antimalaria programs in 2001. Steven C. Phillips, who directs the program, says that although he supports research programs aimed at developing a vaccine, companies must also use existing medical therapies and countermeasures to save lives. "The global community shouldn't underestimate the complexity of developing a vaccine," Phillips says.

Garnier predicted that other pharmaceutical companies will follow Glaxo's lead in doing work on widespread diseases that afflict impoverished people. "Companies will come to this because you have people like Bill Gates around the table," Garner said. "Bill has reinvented philanthropy and made it a can-do enterprise."

http://www.forbes.com/sciencesandmedicine/2005/10/30/malaria-gates-philanthropy-cz_ec_1030malaria.html

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Forbes: Chutzpah Science

Even the Gates Foundation would run out of money if all it did was buy vaccines. So now it's going about inventing them, too.

Stefan Kappe is a bug-killer. Every week in a tiny, humid room (nicknamed The Swamp) at the nonprofit Seattle Biomedical Research Institute, Kappe and his colleagues slit open between 2,000 and 3,000 mosquitoes to collect the microscopic parasites that cause malaria. By knocking out a gene essential to the parasite's development, Kappe hopes to create a vaccine against malaria. It's an audacious goal--no one has ever made a commercial vaccine that protects against any parasite, much less malaria, which threatens 40% of the world's population. Half a billion get the disease every year and more than a million die of it.

In late June Kappe was one of 43 principal scientists to win a chunk of the multiyear Grand Challenge awards, funded largely by the Bill and Melinda Gates Foundation. The Gates Foundation has set aside $450 million for the project, while the Wellcome Trust and the Canadian Institutes of Health Research are chipping in another $31.6 million. The goals for all the projects are breathtakingly grand: Give a child a vaccine without using a needle. Make vaccines that don't need to be refrigerated. Make plants that grow in dry climates more nutritious. Genetically modify mosquitoes so they can't spread diseases such as malaria and dengue virus. "These [projects] probably wouldn't get funded by the National Institutes of Health," says Richard Klausner, director of global health at the Gates Foundation and formerly director of the National Cancer Institute. "They're too risky, too ambitious. And that's exactly what we wanted."

Bill Gates' $28.8 billion foundation is more than double the size of the runner-up, the $11 billion Lilly Endowment, and the projects it has taken on are supersize. On the top of the agenda: battling the diseases that plague developing nations. The Gates Foundation has already pledged $1.5 billion to bring routine vaccines to the poorest children around the world. Now Gates wants to push scientists to create a more powerful arsenal.

To put together its list of 14 "challenges," a panel of scientists sifted through recommendations from 1,000 researchers--from biochemists to mathematicians--around the world. Grant winners will have to invent technology on a deadline. Miss a milestone and the money stops. That hardheaded approach makes the applications more like business plans than traditional research programs, Klausner says.

Such research also represents a healthy half-step between pure academic research and for-profit development. "It's good to try things that stretch the university a bit toward providing products in situations where the commercial world won't," says Nobel Laureate David Baltimore, who also serves as president of the California Institute of Technology and has won a $13.9 million Gates grant. The grantees pledge to make their technologies available at no or little charge to developing nations, though they retain marketing rights in developed markets.

When Florence Wambugu, founder of A Harvest Biotech Foundation International in Kenya, heard about the Gates grants, she immediately thought about three packages of sorghum seeds sitting in cold storage in Des Moines, Iowa. A cousin of corn, sorghum is a staple for half a billion people worldwide, even though it lacks much nutritional value. Five years ago Pioneer Hi-Bred International (a subsidiary of DuPont) figured out how to slide a critical gene from corn into sorghum to make a variant with more lysine--an essential amino acid. The researchers published their work, then filed the details (along with 200 seeds) in cold storage. The sorghum market simply wasn't big enough for Pioneer, says Paul Anderson, research director of DuPont crop genetics.

But Wambugu, who remembered the project from past discussions with Anderson, wanted those seeds. She called Anderson and asked if Pioneer would help her foundation develop better sorghum for African farmers. Wambugu and Anderson worked on their joint proposal for 20 months, ultimately winning $16.9 million from the Gates Foundation. Pioneer agreed to further nutritional enhancements to the sorghum strain, to train African scientists, and to donate the know-how (and seeds) from its earlier work. Wambugu has created a network of allies in Africa that will develop new crops as well as coax governments to okay the use of bioengineered seeds.

Delivering a drug via inhalation--that challenge inspired Harvard professor David Edwards to found a company in 1997. The novel delivery mechanism has commercial potential in treating diabetes, since prosperous countries are full of diabetics. Eli Lilly & Co. and Alkermes (which now owns the technology) are trying out inhaled insulin on 1,000 patients.

How about the same method to deliver vaccines, sparing the costs of refrigeration and needles?There's scant commercial potential here, but there's a need. In 2003 Edwards started the nonprofit Medicine in Need to develop the technology, which is very tricky. You have to dry the vaccine without killing the cells in it, and you have to make the particles small enough to be inhaled but not so small that they are exhaled. Edwards and his collaborators are getting a $7.6 million Gates grant.

Caltech's grant was for finding a way to equip the body to fight a disease that it may not be prepared to tackle, such as AIDS. Most vaccines and therapies try to bulk up the body's existing defenses, say, by boosting the immune system. Baltimore wants to rewrite the body's disease-fighting instruction manual. He aims to take hematopoietic stem cells--the bone marrow cells that form blood cells in the body--and reprogram them by adding genes that direct the cells to produce unnatural antibodies. So far he and his colleagues have primarily demonstrated that they could help mice beat tumors this way. "This approach is such a leap beyond where we are today," says Baltimore.

Malaria is a classic example of a disease that pharmaceutical companies are reluctant to tackle. The parasites that cause malaria go through four major developmental stages, some in humans and some in mosquitoes. Most experimental malaria vaccines target the mature parasite as it is wreaking havoc in a patient's blood. Kappe's $13.5 million grant, by contrast, aims to stop the equivalent of teenage parasites while they're developing in the human liver.

In his insect swamp, Kappe develops a culture of red blood cells with malaria parasites that lack a key gene for development. The mosquitoes feed on the blood, absorbing the parasites. After the parasites have matured further, Kappe harvests them to build a mouse vaccine. Although the parasites can't develop further (and so can't cause malaria in the mice), they do excite the immune system. Kappe is using his grant to begin human trials.

His colleague in Africa, Patrick Duffy, won a $19 million award to pin down which forms of malaria are most deadly to children, and Dominic Kwiatkowski at Oxford University got a $16.4 million grant to explore which variations in the human genome protect some people from ever contracting malaria.

"These grants are different from standard research programs, which are about learning, not about producing things," says Baltimore. "The Gateses have made a commitment to seeing that something gets done."

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