WHAT’S IN A TREE?

KUCHING, Malaysia.(WNL)- Bintangor belongs to the family Guttifarae, which includes the mangosteen. There are over 50 species of Bintangor (C.lanigerum), found mostly in western Sarawak; of this number, two are now known to have medicinal value. To the local population the Bintangor is known mostly as a timber tree of good quality, with an attractively grained wood.

Bintangor grow in the lowland and hill forests; some even thrive on poor, sandy soil. The different types of Bintangor are identified by the structure and veneration of their leaves. The larger kinds of Bintangor can attain a girth of up to 10 feet.

At the beginning of the current project, the research team ask the Forest Department to supply 50 kg of Bintangor resin. The good news is that the healing sap can be obtained without killing the tree; the bad news, as far as Forest Officer Hj. Osman Ismawi was concerned, is that each tree yields less than gram of resin per tapping. Bintangor don’t grow densely; lots of arduous footwork went into collecting the necessary quota of latex.

Besides locating and preserving the valuable tree, Hj. Osman’s team is also collecting seedlings for systematic plantation. Some of the these are planted in groves, others scattered in clearing inside virgin forests. " The Bintangor is a handsome tree!’ the veteran forester says with pride. " Calophyllum, means ‘beautiful leaf’," see how glossy, how delicately veined? It is beautiful!"

KUCHING, Malaysia (WNL)- "AIDS Cure From Sarawak Rainforest!" the headlines trumpeted when the 100-foot Bintangor tree made is debut as a potential natural remedy in the late 1980s: if only thing were that simple!

The Bintangor story starts in 1986. Scientist from the Harvard University Arboretum and The University Of Illinois, Chicago, teamed up with the Forest Department of Sarawak, a Malaysia state on the island of Borneo.

The aim of the study was to interview traditional healers and comb the rainforest for new substances, possibly with tumour-arresting properties; the project was funded by the National Cancer Institute (NCI) in the USA.

After several years of jungle bashing, two varieties of Bintangor (Calophyllum lanigerum) were identified as "Posibble HIV-inhibiting" compounds: Calanolide A could be extracted from the leaves and twigs, and Costatolide (also known as Calanolide B) from the latex (sap) of the tree.

This was good news in more ways than one: The world urgently needs new and hopefully better drugs to combat the AIDS pandemics and the Bintangor flourishes even in longed-over forest. Calanolide B is present in the latex which can be sustainably harvested by tapping, without destroying the tree, and Calanolide A, because it is rare, can be recreated synthetically.

In 1993, Calanolide A was approved by the NCI for pre-clinical trails. But there was still a long way to go.

"we know what Calanolide does in the test tube: it inhibits the proliferation of HIV," explains Dr. Tuah J. Jenta, a Malaysia Scientist with a degree in physical chemistry which is actively engaged on the Bintangor project. Educated in the UK, Dr Jenta lectured the University of Sarawak (UNIMAS) for a couple of years, just at the time when the Bintangor wave crested. "The pre-clinical trials were encouraging enough to justify the commencement of clinical trials," he notes.

After the pre-clinical trial MediChem, an 11-year-old biotech firm based in Lemon Illinois, was invited to join in strategies alliance with the state Government of Sarawak based Sarawak MediChem Pharmaceuticals, Inc. was special formed for the purpose of developing and clinically testing Calanolide A, an anti-HIV-inhibiting compound derived from the Bintangor tree.

Calanolide A inhibits HIV by attaching itself to an enzyme that the virus needs to reproduce, disabling the reproduction process. The clinical trials consisted of testing Calanolide A’s safety, according to FDA standards, in normal, healthy volunteers. The tests went well in establishing that the drug is well-tolerated and had no serious side effect, according to Thomas Flavin, a MediChem advisor and architect in the deal.

"They (the Sarawak side) benefit by learning the process and making contacts over here, " Michael T. Flavin, president and founder of MediChem, told a business magazine in May 1998.

"The alliance calls for an information and technology exchange.

Sarawak scientist, whose salaries and living expenses are covered by their government, are in Lemont working to develop the potential AIDS drugs.

We benefit because these scientist are highly trained and contribute right away to the project."

The state government of Sarawak provided a required license for MediChem, which will allow the company to develop Calanolide A commercially. The Sarawak Government also helps with financing the project. Should Sarawak MediChem Pharmaceutical’s drug prove marketable, Sarawak and MediChem will split the revenues equally.

Dr. Jenta represents the Sarawak Government’s interest in MediChem. His official designation is "Treasurer," but he takes an informed interest in the research and Developments. Though stationed in Illinois, his work demands frequent trips to Sarawak.

In the USA, the slow process of testing Calanolide A grinds on. Phase IA studies, which have been completed, are designed to define safety limits.

Phase IB has started with the selection of volunteers for actual testing. HIV positive persons are alerted through hospitals, even in the internet. Volunteers are very carefully informed of the potential risks and benefits of the programme designed to control the proliferation of HIV. The company is testing a synthetic form of the compound they found in the Bintangor tree on 32 HIV-positives patients.

The testing lasts six months and is being performed at six research centers across the United States. The test results will shed light on blood concentration and other physiological effects of two daily doses of the drug.

Phase II will assess the therapeutic potential of Calanolide A, and establish how the drug combines with others. Optimum does have to be determined, side effect monitored. "HIV treatment is not a one time dose, like popping a pill for a headache," Dr. Jenta explains, "It’s a long-term exercise. Frankly, there’ insufficient clinical data to say that if you take this drug for 15 years you will be cured; no HIV drug has been around for more then 10 years. HIV mutates all the time, it becomes resistant to standard drugs. There is a need for more, better HIV drugs. The Calanolide programme has a lot of potential."

According to Thomas Flavin, Phase II testing will probably begin in July 1999 and the volunteers will be monitored for six months. If all does well, Calanolide A could be ready for commercial by September 2000. Is there such thing as an HIV preventative? All the drugs now being used aim at preventing the developing of full-blown AIDS in a HIV patient, but none can stop a person from contracting HIV.

Will Calanolide be expensive? The pricing mechanism is dictated by the pharmaceutical companies, and they are frequently criticized for greed. Glaxo, for example, has reduced the cost of its HIV drugs, so other companies may follow suit. The problem is that a new drug may consume millions before it reaches the market, if it ever does. Ten substances may be tested before one is found to be successful; the end user of the one miracle cure pay for the nine duds.

Bintangor researcher has cost millions already, and to date there are no guaranteed results or profit. As Calanolide passes the various tests, Sarawak MediChem exploring the idea of licensing its commercial production to a pharmaceutical giant with a huge manufacturing capacity and marketing network. "The new drug is arousing interest international gatherings like the 12^th World Conference on AIDS in Geneva recently," says Dr. Jenta.

"Interested parties can approach us. If there’s potential for commercial partnership, the mechanism mechanisms for facilitating this are in place."

One main objective of the Calanolide A programme is to demonstrate the usefulness of natural products, even if they need to be synthesized for volume. Supplies of Calanolide A from natural resources are insufficient for commercial application. The fact that the drug molecule is reason enough to preserve the forest from which sprang. Both synthetic and natural substances are included in the tests.

Inspired by the Bintangor story, an Australian firm from Melbourne, AMRAD Natural/Pharmaceutical Products, has recently started to look for new medicine in the Sarawak’s jungle. All field exploration has to be done under the auspices of the Sarawak Biodiversity Centre, a governmental body which supervises the commercial exploitation of the state’s natural resources.