When Beneforté ‘super broccoli’ was launched onto selected UK supermarket shelves in October 2011, it represented a special achievement for UK bioscience — a consumer-focused, nutritionally enhanced product that had been in development for more than two decades by two BBSRC-supported world-class research institutes and a specialist technology transfer company, part-owned by BBSRC. Beneforté broccoli is two to three times higher in a compound called glucoraphanin from which sulforaphane is derived upon ingestion. Studies in animal model systems have shown that sulforaphane can lead to lower rates of heart disease, act against some forms of cancer and boost the body’s levels of antioxidant enzymes, which can protect DNA from damage and is thought to be a useful component of healthy ageing.1–5
Beneforté broccoli, developed by conventional breeding techniques, is born from research on the fundamental biology of plants and the link between human nutrition and health at the John Innes Centre (JIC) and the Institute of Food Research (IFR), respectively. Both institutes receive strategic funding from BBSRC — £28m in 2010 for JIC and £13m for IFR, which provides for long-term research programmes and supporting infrastructure. This allows the institutes to pursue mission-led, far reaching research programmes that translate their science into new products, services or advice.
Translating work from laboratory bench to supermarket shelf also requires specialist commercial and legal expertise
But the journey from wild broccoli variety to supermarket product has taken decades and is not just about science. Translating work from laboratory bench to supermarket shelf also requires specialist commercial and legal expertise, which was achieved in collaboration with Plant Bioscience Limited (PBL), a company formed in 1994 to develop innovative research into patented and licensable technologies. PBL is jointly and equally owned by JIC, BBSRC and the Sainsbury Laboratory and is located on the Norwich Research Park with JIC and IFR, forming a unique nucleus of cutting-edge science in the UK. BBSRC has representation of the board of the company. “The broccoli is selling well at M&S,” says PBL Managing Director Jan Chojecki. “If this is sustained, there will certainly be a flow back to British science.”
The Italian Connection
The story begins in the Mediterranean in the early 1980s when Professor Richard Mithen, currently at IFR, was on a field trip to collect rare plants as part of his PhD at the University of East Anglia. “We collected wild brassicas in southern Italy and Sicily, and that material was sent into various seed banks in Italy, Sweden and Spain,” says Mithen. “I was able to go on this expedition because of Professor Harold Woolhouse, the then Director of the John Innes Institute, who provided me with a small grant to cover some of my travel costs.”
I knew that a certain wild brassica could be the source of novel alleles that may boost the level of glucoraphanin
His PhD involved analysing chemicals in the wild brassicas, called glucosinolates, which were thought to protect the plants from pathogen and insect attack. Mithen, in collaboration with Professor Roger Fenwick and his team at IFR, was the first person to analyse these plants for glucosinolates, which at this time were considered to be toxins. Later, their role as a phytonutrient became apparent. Research at IFR and elsewhere in the UK and US suggested that a particular compound, sulforaphane, derived from the glucosinolate, glucoraphanin, had certain anticancer and health-promoting properties. After a stint in Africa working on the germplasm conservation of wild cowpeas, Mithen returned to JIC to look at brassicas afresh.
“I knew that a certain wild brassica could be the source of novel alleles that may boost the level of glucoraphanin, although, at that time, we did not understand the genetics underlying the accumulation of these compounds,” says Mithen. “So we started a programme to explore the genetics of glucosinolates as well as to develop broccoli breeding lines with high levels of these compounds.” Some of the work was funded through a 1996 BBSRC Case studentship award to Kathy Faulkner at JIC.
Beyond the Lab
But a great deal more investment would be needed to bring a product downstream from plant breeding all the way to a finished product on supermarket shelves. To attract and justify such investment, PBL secured the intellectual property (IP) and applied for relevant patents in the mid-90s. “Developing a product with a health-related consumer benefit, based on a nutrient that the consumer has never heard of — a novel approach at the time — is still unprecedented in a fresh vegetable,” says Chojecki.
In 2000, PBL teamed up with Seminis, one of the major vegetable seed companies, which at the time accounted for almost half of the global broccoli seed market. Chojecki explains that PBL’s reasoning for partnering with Seminis was to achieve broad public benefit. “It was necessary to work with a major company that could deliver high quality varieties, and that had the long-term commitment and market presence to work with the supply chain to communicate the benefits of such an innovative concept all the way to the consumer.”
Working into the new millennium, the high glucosinolate broccoli underwent an intensive breeding programme. In a process that would have gone unseen by the average shopper, traits such as uniform shape and growing at the right time of year, with no yield loss, were selected — a process that took another 10 years. “It’s not trivial. It’s a slow, laborious and you need to be completely competitive with or better than current varieties, plus you need two or three varieties to supply produce in every month of the year and in different growing areas,” says Chojecki.
Brassica Health Benefits
By 2003, while the plant was being fine-tuned right down to the final florets, Mithen was now at IFR building up a portfolio of evidence that the broccoli did indeed have health benefits. There is worldwide interest in understanding why people with a higher proportion of brassicas (others being cabbage, Brussels sprouts) in their diet have lower risks of some diseases, as revealed by epidemiological studies and other analyses.6,7 Mithen and colleagues first showed that the high level of sulforaphane delivered by the new broccoli to the gut was indeed absorbed into the systemic circulation.3 This established that the body takes it up rather than just excreting it.
Collaborating with the Norfolk and Norwich University Hospital, Mithen then showed that men with early signs of prostate cancer who ate the enriched broccoli showed changes in gene expression metabolites consistent with reductions in the risk of cancer developing later.4 A more recent trial (unpublished as of November 2011) measured biomarkers for cardiovascular disease and compared a group eating 400g of super broccoli a week in people with an intermediate risk compared with two control groups.
Bigger, Better Studies
Moving forward, based upon data from the current study, funding has been secured from the Technology Strategy Board (TSB), as part of its Nutrition for Life programme, to complete a larger study with two recruitment centres. One will be in Norwich and one at the University of Reading.8 This study will continue to validate heart health benefits of the high glucoraphanin broccoli variety.
Our ongoing goal is to pin down the mechanisms of action in people with normal diets
“There is a huge worldwide effort on sulforaphane, which has many different types of activity,” says Mithen. “Data from animal and cell models show that it induces antioxidant enzymes and suppresses cell proliferation and chronic inflammation. Our ongoing goal is to pin down the mechanisms of action in people with normal diets as opposed to giving large amounts to mice or rats.”
Chojecki is impressed in the way that Mithen has applied himself to each field necessary to continue to develop the science behind the product — from plant biochemistry to genetics, and then plant breeding through to human health and nutrition. “He is an all too rare example of a scientist who has started in one field but, taking a risk with his scientific career, has moved his research into completely new areas and continued to publish in top journals. And all the while continuing to support the knowledge exchange process.”
He is also looking forward to future publications. “We can be extremely positive. There is a lot of strong science around glucoraphanin in the diet and there is a 2006 EU legal framework to protect consumers,” says Chojecki. “Some headline writers make leaps we don’t endorse; but, to be fair, most of the media content pretty faithfully reflected the press statements that were released by IFR and M&S.”
References
1. N. Juge, R.F. Mithen and M. Traka, “Molecular Basis for Chemoprevention by Sulforaphane: A Comprehensive Review,” Cell Mol. Life Sci. 64(9), 1105–1127 (2007).
2. E.H. Jeffery and M. Araya, “Physiological Effects of Broccoli Consumption,” Phytochemistry Reviews 8(1), 283–298 (2009).
3. A.V. Gasper, et al., “Glutathione S-Transferase M1 Polymorphism and Metabolism of Sulforaphane from Standard and High-Glucosinolate Broccoli (Blood Plasma Levels),” Am. J. Clin. Nutr. 82(6), 1283–1291 (2005).
4. M. Traka, et al., “Broccoli Consumption Interacts with GSTM1 to Perturb Oncogenic Signalling Pathways in the Prostate (Cancer Changes),” PLoS One 3(7):e2568. doi: 10.1371/journal.pone.0002568 (2008).
5. V.A. Kirsh, “Prospective Study of Fruit and Vegetable Intake and Risk of Prostate Cancer,” J. Natl Cancer Inst. 99(15), 1200–1209 (2007).
6. M. Traka and R. Mithen, “Glucosinolates, Isothiocyanates and Human Health,” Phytochemistry Reviews 8(1), 269–282 (2009).
7. N. Tawfiq, et al., “Dietary Glucosinolates as Blocking Agents Against Carcinogenesis: Glucosinolate Breakdown Products Assessed by Induction of Quinone Reductase Activity in Murine Hepa1c1c7 Cells,” Carcinogenesis 16(5), 1191–1194.(1995).
8. New Research Will Help Make Foods Healthier, Safer and More Nutritious: www.innovateuk.org/content/news/new-research-will-help-make-foods-healthier-safer-.ashx.