U.S.-Brazilian research team to tackle deadly intestinal diseases with genetically enhanced goats’ milk

Scientists in Brazil and at UC Davis are teaming up to develop a herd of genetically modified dairy goats, whose milk is expected to protect against the types of diarrheal diseases that each year claim the lives of more than 2 million children around the world.

The team plans to have a milk-producing herd of these goats established in Brazil within two years and hopes to begin human trials with the genetically enhanced goats' milk within three to five years. The milk will carry increased levels of the human enzyme lysozyme. Known to impart important immunological benefits, lysozyme is found at very high levels in human breast milk but at very low levels in goats' milk.

The new project, funded with a $3.1 million grant from Brazil's Ministry of Science and Technology, is under the leadership of Aldo Lima, professor and director of the Clinical Research Unit and Institute of Biomedicine at the Federal University of Ceara, in Forteleza, Brazil.

"This collaborative study and effort is timely and geographically important," said Lima, who studies the causes, mechanisms, and short-term impact of persistent diarrheal illnesses and enteric infections in Northeast Brazil.

"The interaction between under-nutrition and diarrhea has been a long-lasting concern in developing countries," Lima said. "We have a great opportunity to do something extraordinary to improve people's lives by developing bio-products for treatment and prevention of infant diarrhea, one of the main causes of child mortality in regions like the Brazilian semi-arid region."

"This is an exciting partnership that promises to increase our understanding of how lysozyme destroys the harmful bacteria that cause intestinal infections and diarrhea, and encourages the growth of beneficial bacteria," said UC Davis animal science professor James Murray.

"We fully expect that the lysozyme-rich milk that these goats produce will provide remarkable improvements in the health of the children in those parts of Brazil that struggle with diarrheal diseases," said UC Davis animal scientist Elizabeth Maga. During the past 10 years, she and Murray have developed a herd of genetically modified dairy goats at UC Davis and studied how the beneficial properties of human milk might be introduced into the milk of dairy goats.

Their research has shown that dairy goats can be genetically engineered to carry the human gene that causes them to produce elevated levels of lysozyme in their milk. Furthermore, they have shown that pigs that were fed the lysozyme-rich milk were better able to fend off bacterial infections than were those animals that were fed goats' milk that did not contain the human enzyme.

The lysozyme enzyme is a protein found in the tears, saliva and milk of all mammals.

"We all consume lysozyme in our saliva every time we swallow," Murray said. "By increasing lysozyme levels in goats' milk, we are simply providing more of a healthful protein that poses no toxic or allergenic problems."

Providing the bridge between the scientists in Brazil and the United States are two former UC Davis animal science graduates and postdoctoral fellows, Marcelo Bertolini and Luciana Bertolini, who are married, both now faculty members at the University of Forteleza.

Other members of the research team include Renato Moreira of the University of Fortaleza and Manoel Odorico of the Federal University of Ceara, Fortaleza, and Vicente Jose de Freitas of the State University of Ceara. Freitas is head of a certified lab, where transgenic goats were recently generated with a different protein for medical applications.

During the first two years of the project, Murray and Maga will work with the Bertolinis and Freitas to transport semen or embryos from transgenic goats at UC Davis to the State University of Ceara, and establish the new breeding and milking herd there for the study. All of the genetically modified animals will be in a closed herd, without contact with other domestic animals. Additionally, these animals are not intended to be given or sold to producers or released into the population at the current time. In Brazil and at UC Davis, the researchers will also clone goats from genetically engineered cells that carry the human lactoferrin gene. Lactoferrin is another important human milk protein with antimicrobial properties.

Laboratory studies in both countries will focus on characterizing the effects of the lysozyme-rich milk on different strains of bacteria, as well as similar studies with lactoferrin. Feeding trials will also be carried out in animal models to ensure the safety and efficacy of consuming goat milk containing these important compounds, singularly and in combination.

The long-term goal for the project, which would require renewed funding after three years, is to determine whether the lysozyme-rich goats' milk offers a safe and efficient method for preventing and treating diarrheal diseases in people. After extensive studies in the lab and using animal models, the goats' milk carrying enhanced levels of lysozyme would be provided to children from some of the Brazilian communities that are plagued by diarrheal diseases.

"Brazil is a very forward thinking nation that is looking to biotechnology to solve some of its most pressing human health problems," Murray said. "We are honored to be working with our colleagues in Brazil on this project."

"Scientists worldwide must demonstrate that the 'gene revolution' may offer important tools for solving the problems of the very poor, much as the 'green revolution' did during the 1960s," said Luiz Antonio Barreto de Castro, state secretary for research and development for Brazil's Ministry of Science and Technology. He noted that the Brazilian-U.S. initiative to express lysozyme in the milk of goats is one of a series of projects funded by the Brazilian Biotechnology Network, also known as RENORBIO, established in 2006 in Northeast Brazil to apply the best science in the world to solve the social problems of Brazil's semi-arid region.

Brazil's vast semi-arid region occupies approximately 1 million square kilometers (386,000 square miles) in all nine states of Northeast Brazil and extends to a significant part of Minas Gerais, a state in the southeast part of the country. Seventy-eight percent of Brazil's poorest counties are located in this region, where child mortality due to neonatal diarrhea is twice the national average. In many of those counties, one out of 10 children dies before the age of 5, which is comparable to child mortality rates in some African countries.

"We are hopeful that the results of this lysozyme-rich goats' milk project and findings from other RENORBIO research projects will extend beyond Brazil's semi-arid region to also benefit sub-Saharan Africa," Barreto de Castro said. "Brazil is the best partner in the world to develop tropical agriculture and transfer this technology to Africa."

Media contact(s):

• James Murray, UC Davis Animal Science, (530) 752-3179, jdmurray@ucdavis.edu
• Elizabeth Maga, UC Davis Animal Science, (530) 752-5930, eamaga@ucdavis.edu
• Marcelo Bertolini, University of Fortaleza, Brazil, mbertolini@ymail.com
• Pat Bailey, UC Davis News Service, (530) 752-9843, pjbailey@ucdavis.edu