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THE BUSINESS OF BIOTECH
While Egypt has long produced some of the region’s top scientists, knowledge has not always led to profits. A series of biotechnology initiatives with global implications could change that.
BY RASHAD MAHMOOD
Biotechnology and Egypt are not exactly words that are commonly associated. However, several new initiatives are strengthening Egyptian research capacity, and adoption of biotechnology in several sectors is on the rise.
Broadly speaking, biotechnology refers to the use and manipulation of living things, with applications in medicine, agriculture, pharmaceuticals and industrial production. The most spectacular uses of biotechnology involve transplanting genes from one organism to another. In 1997, for example, scientists placed genes from jellyfish into mice, allowing them to glow in the dark under fluorescent light and even pass the trait on to the next generation.
Developments in biotechnology are mostly dependent on links between academic research institutions and the private sector. Genentech, one of the world’s largest biotechnology firms, established the pattern when Herbert Boyer, a professor at the University of California, San Francisco, co-founded the company to commercialize some of his discoveries. Genentech was the first to produce artificial insulin and has gone on to produce and develop some of the most important drugs of the last 30 years.
Red Sea research
One crucial area of biotechnology research is the identification of new microorganisms and finding potential applications for the various substances they produce. Finding potentially useful compounds in the environment is nothing new. Perhaps the classic case is Alexander Fleming’s 1928 discovery that a type of mold could kill bacteria, leading to the development of penicillin and other antibiotics. However, with modern technology and knowledge of DNA, scientists are much more sophisticated in their search for new compounds and drugs.
At the American University in Cairo (AUC) Hamza El Dorry is leading a team of scientists that are searching for novel compounds and microorganisms in the Red Sea. His research is still in its early stages but could have significant scientific and business applications.
El Dorry is working on the Red Sea microbiome project, seeking out new microorganisms and compounds that have the potential to develop into marketable products. In describing the project, El Dorry compares the Red Sea to the human body. “In fact, there are 10 times as many bacterial cells living in different environments in the human body as there are human cells,” he says. Because many of these bacteria cannot be grown in the laboratory, they are difficult to study, and scientists are only now discovering the details of how these organisms interact with human systems. Likewise, oceans are habitats for diverse microorganisms capable of surviving under diverse environments. Such microorganisms are difficult to study because of the challenge of simulating their natural habitats in the laboratory. However, with recent genomic technologies, the details of such microorganisms are coming to light.
Such technologies include genome sequencing, which used to be a long, laborious task. The human genome project, which sequenced the entire human genome, took 10 years. With the equipment available at AUC, “we can sequence an entire human genome in days,” according to Rania Siam, associate professor of biology and director of the biotechnology graduate program. The technology is known as “high throughput genomic sequencing,” and it allows the processing of many fragments of DNA simultaneously, whereas older methods had to tackle one sequence at a time. “Seventy percent of the data that we are gathering are from novel organisms that have never been studied before,” says Siam. “The sea is the last unexplored frontier on earth.”
King Abdullah University for Science & Technology (KAUST) in Saudi Arabia is a partner on the project and has provided $5 million over four years. The actual sample collection is being done in partnership with KAUST and Woods Hole Oceanographic Institution, the world’s largest independent marine research organization.
El Dorry and Siam are focusing their efforts on parts of the Red Sea known as brine pools. These are depressions 2,300 meters below the surface, with high concentrations of salt and heavy metals, and heated by tectonic activity. During their latest expedition to the Red Sea, brine pool temperatures as high as 68 degrees Celsius were measured, and some had salt concentrations over 10 times higher than normal seawater. Metals include sulfides of zinc, copper, iron and other elements of high economic value. El Dorry notes that several reports have documented the economic potential of mining the metals from brine pools.
The advantage of studying microorganisms that live in such a harsh and toxic environment is that “if they can survive there, they can survive anywhere,” according to El Dorry. Many of the organisms survive by consuming organic matter such as cellulose. It is usually too big for the bacteria to ingest, so they have to break it up using a cellulase, an enzyme that can fracture cell walls into smaller pieces.
Enzymes have many industrial applications because they can speed up chemical reactions or cause changes that otherwise would not occur. Cellulase applications include the extraction of juice from fruits, pulping of paper and production of biodiesel. However, most enzymes are designed to work under the same conditions of temperature, salinity and pH that exist where the organism that originally produced them lives. El Dorry says that cellulases currently used in industry are not very tolerant of salinity, “so you often need to remove the salt before you process something.” However, if they can isolate the genes responsible for producing cellulase in the brine pools, they will have the genetic code for a durable form of the enzyme that potentially could be lucrative.
In addition to cellulases, the team of scientists working on the project has placed provisional patents on other enzymes they have discovered in the brine pools for potential industrial applications, including restriction enzymes that have several biotechnological applications and are used to cut strands of DNA. Additionally, they have identified hydrogenases that can be used for hydrogen production as an alternative renewable form of biofuel and bioenergy. “These provisional patents give us a year and a half to prove our discoveries so that we can file for a full patent,” says El Dorry.
In addition to enzymes, the team is also searching for new types of antibiotics. Anti-microbial peptides are a broad category of compounds that fight bacteria in a number of different ways. “Because of the continuous emerging bacterial strains that are resistant to antibiotics, scientists are continuously looking for new antibiotics to fight infection”, Siam explains. Therefore, it is important to search for new forms of life that might generate useful anti-microbial peptides. According to Siam, they are currently investigating the properties of several new peptides they have found for pharmaceutical applications.
Technology you can eat
Another important use of biotechnology in Egypt is the development of genetically modified crops. Humans have been tinkering with the genes of agricultural crops for thousands of years through careful selection and breeding. In fact, scientists today are still puzzled how South Americans developed maize thousands of years ago, since the closest wild relative, teosinte, is so different that the connection is nearly unrecognizable. Crossbreeding of plants also has been used to great effect, since hybrids generally outperform their parents.
However, modern biotechnology can go much further than breeding, since it can introduce genes from other species into plants. The earliest genetically modified crops, put on the market in the mid-90s, were insect-resistant tobacco, tomatoes engineered to have a longer shelf life, and soybeans resistant to herbicides. As of 2008, 77 percent of global soybean acreage was genetically modified, according to the 2009 annual report of the International Service for the Acquisition of Agri-Biotech Applications (ISAAA).
In Egypt, there is only one legal, commercially available, genetically modified crop, Bt maize. Bt stands for Bacillus thuringiensis, which is a bacterium found in soil and in the guts of certain caterpillars that produces an insecticidal toxin. By transferring genes from the bacteria to crops, the plants can produce the insecticide themselves, reducing the need for farmers to use pesticides. Bt toxin is species specific, affecting only a few types of insects that prey on crops. “Yields of Bt maize are about 25 percent higher than traditional varieties grown in Egypt and [Bt maize] increases profits by LE 1,350 per feddan [approximately one acre],” says Ahmed Bahieldin, director of the Agricultural Genetic Engineering Research Institute (AGERI), a part of Egypt’s Agricultural Research Center.
Bt maize was first grown commercially in Egypt in 2007 and planted on approximately 700 hectares. Bahieldin expects that by the time data is collected for the 2009-10 growing season, Bt maize will have been cultivated on about 3,000 hectares, a fourfold increase in two years. According to Bahieldin, Egypt produces about 6.1 million tons of maize and imports 4.5 million tons each year, so higher yields could have a significant impact. The next genetically modified crop on the horizon for Egypt is Bt cotton, which he says is in the final stage of the approval process of Egypt’s biosafety commission. The cotton grown would be a combination of Monsanto’s Bt cotton and a traditional Egyptian variety.
Beyond cotton, Bahieldin predicts a form of genetically modified wheat will be the next product to be introduced, probably within three years. This wheat was developed by Hala Eissa, senior scientist at AGERI. The key trait of the wheat she developed is a resistance to drought, allowing it to be grown with little irrigation or even rain-fed in certain parts of Egypt. The key gene involved occurs naturally in barley, so she anticipates that getting approval from the biosafety commission shouldn’t be difficult. “During drought conditions, the new variety has a 20 percent higher yield and can survive even with just one round of irrigation, whereas wheat normally requires several,” Eissa says.
In addition to working to improve yields, scientists are also working to protect against disease. Most wheat grown today is a product of the green revolution, started after World War II by Nobel Prize winner Norman Borlaug. Through intensive breeding, Borlaug developed high-yield varieties of wheat and other crops that have spread around the world. He also discovered a gene that protected wheat from stem rust, which used to cause catastrophic losses of crops. Recently, a new version of stem rust has emerged, called UG-99, named after Uganda where it was discovered in 1999. UG-99 cuts right through Borlaug’s defenses and has spread to Kenya, Ethiopia, Sudan, Yemen and Iran. Bahieldin says Egypt hasn’t been affected yet, but because so many neighboring countries have been “it is just a matter of time.” “Fields hit by UG-99 see yields fall between 40 and 60 percent.” Fortunately, a coalition of scientists, including some affiliated with AGERI, is working in labs in Kenya to develop strains that are resistant.
Overall, Egypt is 24th in the world in terms of genetically modified crop use. The US, Brazil and Argentina account for nearly 100 million of the world’s 134 million hectares of genetically modified crops. While Egypt is working to introduce its second crop, the US grows genetically modified soybeans, maize, cotton, canola, squash, papaya, alfalfa and sugar beets. As of 2009, 46 percent of global hectarage was in developing countries.
However, despite the benefits, cultivating genetically modified crops can be controversial. Because the process entails growing a monoculture, or a large number of nearly identical plants, something that negatively impacts one will affect them all, whereas in traditional agriculture the genetic diversity of the crop usually ensures that at least some survive. Another concern is gene flow from transgenic crops to unmodified plants through pollination. To date there has been little evidence of it. One study conducted in Mexico in 2005 showed 1 percent contamination of wild maize with characteristics from genetically modified maize, while others showed little to no effect.
Development of resistance also is a potential problem. For example, if too much Bt corn is planted in one area, most insects that eat it will die; however, those with resistance will survive. If they then mate with another insect that also has resistance, it could lead to the propagation of insecticide-resistant pests. To combat this, farmers are instructed to plant a refuge of non-Bt corn so pests will have some food, reducing the pressure of natural selection toward insecticide resistance. In Egypt, where farm sizes are small, creating a border refuge is not always practical, so Bahieldin advises farmers to plant rows of non-Bt maize interspersed with their Bt maize.
The effect of genetically modified crops on the health of consumers and other organisms is another principal concern. Bt crops have been studied extensively, and a US Department of Agriculture study in 2005 found that although Bt proteins last for a significant length of time in the environment, they are not harmful to non-target species of insects, such as butterflies. A bigger problem is herbicide-resistant plants, which allow for high uses of herbicides to keep weeds in check while leaving the principal crop unharmed. Herbicides can stay in the soil for an extended period of time and potentially contaminate water supplies. Egypt has yet to permit any herbicide-resistant plants to be commercially grown.
The business model of transgenic crops is also a source of concern for some because companies such as Monsanto and DuPont patent the genes of the crops they develop. Traditionally, farmers save seeds from one year to the next for planting; however, this is illegal with patented crops because seeds must be bought each year. There have been numerous lawsuits in the developed world over farmers allegedly saving seeds, violating the patents. Monsanto’s patent for herbicide-resistant soybeans is set to expire in 2014 and will be an important test of how the global market will react to generic biotech crops.
A significant barrier to wider adoption of genetically modified crops is that the European Union, Egypt’s largest market for agricultural exports, is not interested in these new crops. Despite that, Bahieldin thinks the next few years will see significant expansion of biotech crops in Egypt, with most targeted at the domestic market.
Business-minded science
Despite the scientific advances in biotechnology there are few companies actually benefiting from and using biotechnology in Egypt. Rhein-Minapharm, a partnership between Egyptian Minapharm and German Rhein Biotech GmbH, uses biotechnology to produce several important drugs here. They use genetically modified yeast to produce several important drugs, including cancer-fighting interferon, and drugs that prevent and treat the formation of blood clots. However, one company does not make an industry.
“For the biotechnology industry to emerge there needs to be a strong and solid research foundation… There is a symbiotic relationship between research and business,” says Siam. She notes that the recent launch of AUC’s PhD program in biotechnology will help provide graduates as the field expands. Graduates of their existing MA program, launched in 2007, have been in high demand according to Siam.
Developing science and technology skills in Egypt has been an important goal of the government, and it appears that it is starting to pay dividends. In 2007, the government began a big push, announcing a national plan for science and technology, and creating the Science and Technology Development Fund (STDF), according to Aly El-Shafei, executive director of the STDF. Having started operations in March 2008 with an annual budget of LE 200 million, the fund offers a variety of grants. “This is our mandate, to support the complete innovation cycle, the four stages – basic research, applied research, technology development and product development,” says El-Shafei.
In terms of biotechnology, the fund has supported several research projects. El-Shafei says that AGERI has received approximately LE 50 million for 17 projects so far. He says that funding for equipment is capped at 30 percent of STDF grants, and that much of the funding goes toward hiring research staff and salaries, since, “scientists are not paid well in the current structure.”
El-Shafei says that two biotechnology projects that the STDF has funded are particularly promising. The first is a new type of tomato that is resistant to a common virus, which is in the final stages of testing to make sure that it is safe and viable. The second is a new technique for making low-fat cheese using bacteria, developed by Morsi El-Soda, a professor at Alexandria University. He has successfully used the bacteria to make low-fat white cheeses. The STDF performed a market analysis and was told that if the technology could be used for cheddar cheese, it would be a $2.7 billion industry in the US, since low-fat cheddar is notorious for having poor texture and flavor.
The fund is focusing on three areas: renewable energy, vaccine development (especially hepatitis C), and food and agriculture. March 31 was the deadline for proposals related to food and agriculture, of which many were biotechnology related.
A key role of the fund is to help scientists take their research ideas from theory to product. The fund will own the intellectual property rights of anything it supports, and work to protect its rights aggressively internationally, according to El-Shafei. The STDF is also creating a technology venture management company to take the fund’s intellectual property and start developing business models. The hope is that the wealth generated by the company can then be reinvested into funding more research, reducing the need for government funding of the programs.
“Egyptian scientists are known worldwide for their capabilities and their potential,” says El-Shafei. However, Egyptian banks and other investors are not familiar with the risks involved in developing new technology, so the STDF is filling the gap and helping forge links between scientists and businesses. “The business community needs to understand that there is a real change,” he says.
While biotechnology research and utilization in Egypt is still relatively low, there is no question that it will have increasing importance in the coming years. With cutting edge research, and organizations such as the STDF leading the way, biotech pioneers could make the transition from lab research to commercial success, whether their inspiration comes from the Red Sea or a tomato patch.
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