Tracing through anecdote and science the development of a hotly contended area of research, this account expounds the dawn of genetic engineering in the United States in 1974, through the early stages of its uptake in South Africa, to the current situation, in which approximately 80 percent of maize in South Africa is genetically modified for drought resistance. The guide through this history is Jennifer Thomson, whose own story of how she came to choose genetic modification (GM) as a career and her path-breaking involvement in the development of GM research. She describes the spread of this technology into other parts of Africa and her venture into unknown territory to develop crops resistant to drought, insects, and viruses, a journey in which she came up against the multinational Monsanto. The book describes a remarkable personal and scientific evolution and looks to a future in which staple crops may be grown in difficult conditions by smallholder farmers and help Africans achieve food security.
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About the Author
Jennifer Thomson is emeritus professor in department of molecular and cell biology at the University of Cape Town and is one of the world's leading scientists in the field of genetic modification. She is the author of Genes for Africa: Genetically Modified Crops in the Developing World and Seeds for the Future: The Impact of Genetically Modified Crops on the Environment.
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Food for Africa
The Life and Work of a Scientist in GM Crops
By Jennifer Thomson, Leonie Hofmeyr-Juritz
Juta and Company LtdCopyright © 2013 UCT Press
All rights reserved.
The SAGENE years
After my post-doc at Harvard Medical School ended in 1977, I took up a lectureship back in South Africa, in the Genetics Department at the University of the Witwatersrand (Wits) in Johannesburg. I applied to the Council for Scientific and Industrial Research (CSIR), which was, in those days, the government agency dispensing research grants, for funds to continue my work on genetically modified bacteria. When the Head of the Genetics Department, Nancy van Schaik, read my application, she wrote to the CSIR, pointing out that this was a field of research which had caused a great deal of discussion worldwide and that they might want to consider some guidelines for South Africa. She didn't know whether the people reading my application would be up to date with what was going on elsewhere. The National Institutes of Health (NIH) of the US had published their guidelines in 1976 for research involving recombinant DNA molecules and, on receiving Nancy's letter, the CSIR realised they had better set up some sort of a body to ensure that these guidelines were implemented in South Africa. They accordingly established the South African Committee for Genetic Experimentation (SAGENE). To help them in their task they invited Herb Boyer to visit.
In 1976, together with the venture capitalist, Bob Swanson, Herb had co-founded Genentech, the first biotechnology company based on GMOs, and served as vice-president of the company until his retirement in 1991. Herb, working at the University of California, San Francisco, had been one of the first scientists to discover that genes from bacteria could be combined with genes from higher organisms, eukaryotes, to create recombinant (or genetically modified) organisms. In 1977, he and his collaborators synthesised the gene coding for the human growth hormone inhibitor, somatostatin. He transferred it into the bacterium, Escherichia coli (E. coli), and developed the product in a fermenter. This was followed by the production of synthetic human insulin. Prior to that, diabetics worldwide had been treated with insulin extracted from the pancreas of animals such as pigs or cattle. Not only was this expensive, but some sufferers experienced allergic reactions to the foreign hormone. Herb's team solved these problems in one fell swoop, but helped to create a whole new problem, in the form of the soon-to-be-maligned field of genetically modified organisms (GMOs).
An extremely positive outcome of Herb's visit was the role of SAGENE in the certification of laboratories for the use of GMOs. Before a scientist could apply to the CSIR for research funding in this field, SAGENE had to approve the laboratories in question as being compliant with the US NIH guidelines. As many universities in the country were keen to foster this type of research, they were forced to upgrade and equip laboratories to a given standard. The scientists in question also had to give evidence of having been trained in the correct safety standards. This led to the running of a number of training courses, resulting in a network of scientists working on a variety of projects using GMOs. This certainly stimulated the growth of modern biotechnology in South Africa.
A visit to Basel
In 1978, a year after I had joined Wits University, I attended a life- changing three-week course on genetic engineering in the Basel laboratory of Werner Arber, who was shortly to receive the Nobel Prize for his pioneering work in this field. Werner Arber had discovered restriction enzymes which are able to cut DNA at specific sequences. This allowed other scientists to splice any piece of DNA together as long as the specific sequences at their ends matched — hence the term 'genetic engineering'.
The course was held under the auspices of the European Molecular Biology Organisation. Usually, South Africans were excluded from attending, because of our government's apartheid policy. But somehow, someone pulled strings, and against all odds I was accepted to attend the course. What an experience! Genetic engineering was only about five years old and we were learning techniques from the very people who had developed them, and using the earliest bacteriophage vectors. Among these pioneers were professors Ken and Noreen Murray. Ken's group developed the vaccine against hepatitis B, the first vaccine to be made using genetic engineering. He was also one of the founders of the UK-based biotechnology company, Biogen, and was knighted in 1993. Noreen held a personal Chair in Molecular Genetics at the University of Edinburgh and was made a Commander of the Order of the British Empire in the 2002 New Year Honours list. Sir Ken and Lady Noreen founded the Darwin Trust of Edinburgh, a charity which supports young biologists in their doctoral studies.
We were taught plant transformation by Marc van Montagu who, together with Jeff Schell and Mary-Dell Chilton, developed the first plant vectors based on bacterial plasmids and worked out how to introduce foreign genes into plants. They discovered the gene transfer mechanism between the soil bacterium, Agrobacterium tumefaciens, and plants, which resulted in the development of methods to convert Agrobacterium into an efficient delivery system for genetic engineering and thus create transgenic plants. Marc was granted the title of baron by King Baudouin of Belgium in 1990. In 1982, he and Jeff founded the biotechnology company, Plant Genetic Systems Inc., in Belgium. It is now part of Bayer CropScience. Jeff was also made a baron, and they both visited South Africa on a number of occasions to help in the development of plant biotechnology. Mary-Dell is a Distinguished Science Fellow at Syngenta Biotechnology, Inc. and in 2002 Syngenta created the Mary-Dell Chilton Center, a conference centre at their facility in Research Triangle Park, North Carolina.
We learned how to do Southern blots from their inventor, Ed Southern. These blots are used for DNA analysis and were routinely used for genetic fingerprinting and paternity testing prior to the development of microsatellite markers for this purpose. Ed also used the concept of Southern blots in the development of modern microarray slides. He founded the company Oxford Gene Technology based on this process and was made a knight bachelor in the June 2003 birthday honours. He is the founder and chair of the Scottish charity, The Kirkhouse Trust, which focuses on agricultural crop improvement research for the developing world, and specifically on legumes.
When Werner Arber's Nobel Prize was announced I wrote to congratulate him. His young daughter, Silvia, wrote a charming reply:
When I come to the laboratory of my father, I usually see some plates lying on the tables. These plates contain colonies of bacteria. These colonies remind me of a city with many inhabitants. In each bacterium there is a king. He is very long, but skinny. The king has many servants. These are thick and short, almost like balls. My father calls the king DNA, and the servants, enzymes. The king is like a book, in which everything is noted on the work to be done by the servants. For us human beings these instructions of the king are a mystery. My father has discovered a servant who serves as a pair of scissors. If a foreign king invades a bacterium, this servant can cut him in small fragments, but he does not do any harm to his own king. Clever people use the servant with the scissors to find out the secrets of the kings. To do so, they collect many servants with scissors and put them onto a king, so that the king is cut into pieces. With the resulting little pieces it is much easier to investigate the secrets. For this reason my father received the Nobel Prize for the discovery of the servant with the scissors.
One evening, walking the wet streets of Basel to dinner, Marc van Montagu asked me about my future plans. I told him that I wanted to work in the field of plant genetic engineering but didn't know how to go about it. He invited me to spend time in his lab in Ghent.
The Ledeganck Street lab, Ghent
I spent an eye-opening month with Marc's students in the Ledeganck Street lab, as we called it. Cramped would be too generous a name for the conditions they worked in. Corridors had been turned into labs, cupboards had become electron microscope units, and at times people resorted to working in shifts in order to get access to equipment. How different from Wits, where space was abundant but skilled people were in severely short supply. What I learned in that month, and from many more shorter visits to Marc's lab, set me up for my future career in plant genetic engineering, but it would take 10 more years before I finally landed in the right environment, at the University of Cape Town, to put these plans into action.
Marc was born in 1933 in Ghent in a period of great economic recession. He was raised in a working-class neighbourhood. The cotton factories where most of the men, and even young boys, worked at the time were dark, noisy and filled with clouds of dust floating around the spinning machines. As Marc wrote of these factories in his article 'It is a long way to GM agriculture': 'They were so frightening and convincingly repulsive that I felt I never wanted to be obliged to work there' (Van Montagu, 2011). Perhaps it was this that spurred him on to do well in school, helped by a school teacher uncle who insisted he go to the best primary school within walking distance. He started his PhD in the heady days of the birth of the new science called molecular genetics, but his first job was as the deputy director of an institute for training technicians and technical engineers for the nuclear industry. He soon saw the light, however, and joined the physiological chemistry laboratory of the University of Ghent. At the end of the sixties he was joined in the Ledeganck Street lab by his friend, Jeff Schell, and together with Mary-Dell Chilton, working at Washington University, St Louis, Missouri, they founded the field of plant genetic engineering.
To get there, however, they had to find a workable plant gene vector to transfer genes into plant cells. The race was fierce between Ghent and St. Louis, with both labs using the new technique of Southern blots to demonstrate that foreign genes were integrated in the plant genome. The battle to publish first was won by Mary-Dell (we will meet her again in Chapter 7) and the only record of the Ledeganck Street lab data is a talk given at a Cold Spring Harbor Symposium in 1978 (Van Montagu, 2011).
My own laboratory
Back in Johannesburg, all was not well with me and the Genetics Department at Wits. I was a bacterial geneticist and needed to supervise postgraduate students in that discipline. But most of the students interested in pursuing this line of research were registered in the Microbiology Department and I had no access to them. Feeling uncertain, I left in mid-1982 for a sabbatical year at the Massachusetts Institute of Technology (MIT).
This was a heady time for industrial biotechnology. New companies were starting up all around me, many involving people I was working with at MIT. For instance, Charlie Cooney, in whose lab I was working, was one of the founders of Genzyme, which began life close to the MIT lab in Cambridge and is now a multimillion dollar company (2010 revenues were in the order of US$ 4 billion) with some 10 000 employees working in countries throughout the world. They now concentrate on medical applications, but in the early days their focus — as the name implies — was on genetically engineered enzymes. Indeed, my work in Charlie's lab involved cloning the enzyme heparinase, produced by the bacterium Flavobacterium heparinum. Heparin is an anticoagulant used in medical procedures such as heart surgery and excessive use can cause unwanted bleeding. It was thought that heparinase, which degrades heparin, could prevent such side effects. In fact, the enzyme, whose gene was finally cloned in 1996, is now used primarily for the preparation of breakdown products of heparin for research purposes.
I got caught up in this excitement and, uneasy about my future at Wits, started a job hunt for a position with one of the start-up biotechnology companies in America. News of my enquiries reached South Africa and, before I could make any plans, I was summoned to meet Dr RR Arndt, the Deputy President of the CSIR, in Washington DC, where he was on business. He asked me whether I would like to start a Laboratory for Molecular and Cell Biology (LMCB) at Wits.
The LMCB premises started small, on the top floor of the Gatehouse Building at Wits University, in which my former home, the Genetics Department, was located. After four years it numbered some 30 people, including a group at the Onderstepoort Veterinary Research Institute in Pretoria, who were involved in animal nutrition. One of our research interests became the use of naturally occurring and genetically modified bacteria in the gut of ruminants such as cows and sheep, to improve animal nutrition.
With the memories of the start-up companies in America fresh in my mind, I decided to test the waters in South Africa for a similar venture. Together with a business friend I drew up an investment proposal for 'South Africa's first biotechnology company based on genetic engineering — AFROGEN'. The scientific advisory board was to include colleagues at Wits and Onderstepoort, and Dr Dave Woods. The projects would be largely Africa-specific and would include diagnostics for plant and animal diseases, as well as animal vaccines. The research was to be carried out mainly in the LMCB, but some would also be done in the laboratories of members of the advisory board. The estimated costs for the first three years of operation, 1985 to 1987, were R3 403 000, equivalent in today's terms to R32.8 million (about US$ 3.8 million). Start-up funding included money for market research to estimate returns on investments.
The Industrial Development Corporation and an organisation called the South African Inventions Development Corporation showed some initial interest, but after numerous meetings with business leaders, I came to realise that, in South Africa at that time, venture capital meant investment in a concept for which there were already orders in place, such as a fork-lift on the back of a truck. The suggestion was then made that the concept be modified and renamed AFROGEN Technology Transfers, which would act as an intermediary between existing research laboratories and the marketplace, closing the technology transfer gap between researchers and the marketplace. This was clearly not my field of expertise, so the idea of AFROGEN quietly died. Little did I know that in 2003 I would become the first chair of the board of a similar organisation concentrating on agricultural biotechnology, the African Agricultural Technology Foundation.
Restructuring the CSIR
During this period I reported regularly to Dr Arndt, as well as to James Bull, chief director of the National Chemistry Research Laboratory, and Brian Clark, Head of the National Institute for Materials Science. At this time, the government, which had previously paid for almost all the CSIR's expenses, decided that the organisation should become more self-sufficient, a change which Brian viewed with great enthusiasm. He played a major role in the subsequent reorganisation of the CSIR and eventually became their next president. This led to the departure of many scientists, including James and me. James became head of the Department of Chemistry and was appointed Head of the Department of Microbiology at the University of Cape Town (UCT). I wrote up this transition in 1993 with Johan Lutjeharms (previously in the National Research Institute of Oceanology at the CSIR and, by that year, Head of the Ocean Climatology Research Group in the Department of Oceanography at UCT) in an article entitled 'Commercializing the CSIR and the death of science' (Lutjeharms and Thomson,1993). I had wanted to call it 'Commercializing the CSIR and the prostitution of science', but we felt that might be a bit too provocative.
Excerpted from Food for Africa by Jennifer Thomson, Leonie Hofmeyr-Juritz. Copyright © 2013 UCT Press. Excerpted by permission of Juta and Company Ltd.
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Table of Contents
List of acronyms ix
Chapter 1 The SAGENE years 19
Chapter 2 From SAGENE to the GMO Act 31
Chapter 3 Into Africa 49
Chapter 4 To Davos and further into Africa 63
Chapter 5 A South African National Biotechnology Strategy 87
Chapter 6 African National Biotechnology Strategies 97
Chapter 7 The maize streak virus story 107
Chapter 8 David vs Goliath 121
Chapter 9 Food for Africa 133