The Hawaii Papaya Genome Project - Technology Transfer in Real-Time
May 16, 2005

Papaya is a principal fruit crop of tropical and subtropical regions worldwide. Papaya fruit is a major export commodity in Hawai'i, and can also be produced in Florida, the Rio Grande Valley of Texas, and in southern California. Papaya trees are grown for fruit and papain, a commercially valuable proteolytic enzyme. Papaya fruit is rich in vitamin A and C and helps in preventing blindness due to lack of vitamin A in the diet of children of developing countries. Papain, obtained from papaya latex, is the most widely utilized member of a large family of cysteine proteases. Papain is used to develop selective inhibitors of animal cystein proteases that exhibit abnormal activity in a variety of diseases including: muscular dystrophy, osteoporosis, pulmonary emphysema, and tumor growth. Papain also has direct medical applications for wound debridement, removal of necrotic tissues, external treatment of hard tissues, removal of warts and scar tissue, amelioration of acne, depilation, skin cleansing, and is included in toothpaste. It is used for treatment of Parkinsonism and for tetanus vaccines and immunoglobulin samples for intravenous injection.

Hawaii’s Papaya Industry

Papaya is one of the most important commercial agricultural crops in the State of Hawaii and was threatened by extinction by the papaya ring spot virus (PRSV). Although the PRSV was reported in the State of Hawaii in the 1940’s, it was discovered in Puna on the island of Hawaii in 1992 where 95% of Hawaii’s papaya was grown. In 1995 the PRSV was widespread in Puna and the total state papaya production fell from a peak production of 58.2 million lbs in 1993 to 35.6 million lbs in 1998, a decrease of 39%. In Puna the production decrease was even greater at 52% and threatened the end of commercial papaya cultivation in Hawaii. The transgenic Rainbow papaya developed by Dr. Dennis Gonsalves, then at Cornell University and currently the Director of the US Department of Agriculture Pacific Basin Agriculture Research Center (PBARC) in Hilo was ready for field trials in 1991. After seven years of field-testing and compliance with the US regulatory requirements the transgenic Rainbow papaya was released for consumption in 1998.

There is no doubt that the transgenic papaya saved the papaya industry in the State of Hawaii and now constitutes about 40% of all papayas grown in Hawaii. The destructive effects of the PRSV for the non-transgenic papaya still exist. However, growers continue planting the non-transgenic papaya, which commands a premium price in foreign markets like Japan. Japan does not currently allow the importation of the transgenic papaya. Many of the papaya growers are now able to grow traditional varieties of papaya because the transgenic Rainbow helps control the amount of virus in the growing areas and acts as a barrier to the PRSV when planted adjacent to the non-transgenic plants. Moreover, the transgenic papayas grow in areas where the PRSV had caused previous devastation. The island of Oahu now grows substantially more acres of papaya then it did before the transgenic Rainbow papaya was released. Rainbow has also been used as a genetic source to produce new varieties that are especially suited for growing on Oahu.

Currently, the transgenic papaya can be marketed in Canada and the mainland USA, but not in Japan, a major market for the Hawaiian non-transgenic papaya. The Japanese papaya market can be expanded significantly if the transgenic Rainbow papaya were introduced. Efforts to get the transgenic papaya deregulated in Japan began in 1998 and were taken up by the Hawaii papaya industry, USDA, and the State of Hawaii with the aid of local scientists that had developed the transgenic papaya. Although progress has been made in obtaining technical information to get the transgenic papaya deregulated in Japan, some key areas in understanding the genetic composition of the transgenic papaya are still required.

The Papaya Genome Project
In early 2004, Dr. Ray Ming a researcher at the Hawaii Agriculture Research Center (HARC) published a paper in the prestigious journal Nature relating the papaya to fundamental discoveries of incipient sex chromosome evolution development in all species. This landmark research received the interest of the entire scientific world. Inspired by this publication by a local researcher, the University of Hawaii Center for Genomics, Proteomics and Bioinformatics Research Initiative (CGPBRI) led by Dr. Maqs Alam, the Maui High Performance Computing Center (MHPCC), the USDA/ PBARC and HARC, created the Hawaii Papaya Genome Project in the spring of 2004.

Papaya is attractive as a model system for genetic and genomic research for many reasons, including:

• First transgenic organism to be sequenced
• A system to explore tropical tree genomes
• A small genome of 372 Mbp (million base pairs), about 10% smaller than the rice genome of 420 Mbp, which has been completely sequenced; but 10% of the human genome approximately 3,000 Mbp
• Diploid inheritance, with nine chromosomes in its gametes;
• A short juvenile phase (3 to 8 months) and generation time (9 to 15 months);
• Continuous flowering throughout the year;
• An efficient breeding system, each fruit producing about 1000 seeds, and a single tree producing hundreds of fruit in its lifetime;
• A well-established clonal propagation system that allows testing of individual plants in multiple environments;
• Numerous types of flowers ranging from complete female, to hermaphrodite, to complete male with gradual variations in between.

Summary:
The first use of the transgenic papaya genome sequence data will be to assist in the deregulation of the transgenic papaya in foreign countries such as Japan. In January 2005 as a proposal for deregulation of the transgenic Rainbow papaya was being prepared by the Hawaii Papaya Industry Association a question was raised by the Japanese regulators concerning the genetic modification of the papaya genome to make it resistant to the PRSV. The USDA estimated that it would take 8-10 months with available resources to answer the question and asked the Hawaii Papaya Genome Project team for assistance. Although the papaya genome is not completed, the question relating to a segment of the papaya genome in question was resolved in three weeks and the proposal was submitted without delay. This was a situation where basic science was of immediate practical use, an example of technology transfer in real time. The Hawaii Papaya Genome Project and it’s importance to the Hawaii papaya industry will be the topic of a scientific conference planned in Hawaii for the Spring of 2006.

Due to the success of the transgenic Rainbow papaya in the field and marketplace over the past seven years, it has been described as the perfect model for successful biotechnology in Hawaii where local researchers (University of Hawaii, US DOA, HARC.) and small farmers collaborated to find a solution which avoided financial disaster for an important local industry.