WATSON/FORSTER story

One has identified a novel prostate cancer-stopping compound he’s about to trial on himself, while the other is looking at genes to see why he and his family get a rare and undiscoverable version of the disease:

PROSTATE SCIENTISTS: A life and death double act

Jim Watson (left) and Richard Forster (right) are a double act.

This pair of late middle-aged men – one tall, the other compact, both fit-looking – could be about to present a comedy show, so polished and warm is their demeanour.

But there’s nothing funny about what they’re about to tell us.

In fact, it’s a matter of life and death. Theirs – and quite possibly that of millions of men around the world.

Drs Jim and Richard are eminent New Zealand scientists, and they both have advanced prostate cancer.

This devilish disease has escaped the confines of their prostate glands and will, almost certainly, lead to their premature deaths.

Except, neither man accepts he is about to die.

Professor Jim Watson is a renowned immunologist whose work is recognised globally, while Dr Richard Forster has an international reputation in his field of biotechnology and bio-fuels (see below for a rundown on their careers).

Both diagnosed with advanced prostate cancer around the same time, they have formed a unique partnership to apply their knowledge to develop a treatment for those who learn their diagnosis too late for conventional therapy.

These are men in a twilight zone whose cancer has spread, who get temporary relief (maybe five years) from hormone therapy, but who face the prospect of becoming “hormone refractory”, an end stage of the disease that is currently incurable.

The prospect of early death is not the only thing driving Drs Watson and Forster. There is altruism – “we both have prostate cancer and we want to save lives” – but also something more powerful: anger. Anger at the limitations of the prostate cancer testing system and at the lack of better treatment options.

When Jim Watson opened their “double act” presentation to the annual conference of the Prostate Cancer Foundation of NZ last weekend, he described how he came to be in this predicament.

Five years ago, he felt sick, in a non-specific way, so he went to his GP for tests. Nothing was found. Several months later he was tested again and pronounced healthy.

Still feeling sick, he changed his GP, who was the first to offer Dr Watson a prostate-specific antigen blood test, which found his PSA level had reached 987 (when, for his age, it should have been about 5 or 6, or less).

His cancer had metastasized to five sites in his bones, and his Gleason grade was an alarming 9 out of 10.

He was soon told he had four months to live – and he “felt angry”, angry about a health system that does not encourage GPs to offer PSA tests and digital examinations. Unluckily for him, the first GP he visited didn’t “believe” in prostate screening.

After years of hormone therapy to suppress the cancer and watching his PSA drop to 0.8, he is now at the stage where cancer cells have found a way around the treatment, as they invariably do once the tumour has spread. He is hormone refractory.

But he refuses to give in: “I’ve been a scientist for 45 years and I want to find a way through that for males.”

With Dr Forster, he is applying his knowledge of cancer biology and immunology to develop ways to help the body’s immune system fight cancer.

Richard Forster’s story is similar, but different in an important way.

Prostate screening had little chance of discovering his cancer early, because he and the men in his family may share a genetic trait that means PSA tests show nothing untoward and the low PSA reading does not match changes in the prostate texture using the GP’s finger.

The problem was – much like many prostate patients whose fathers knew or said little about the exact nature of the disease before it killed them – he knew nothing about that until it was too late.

“I had this pain, I go to my GP, my PSA is in the background range (less than 4). It can’t be prostate cancer. I’m given antibiotics for a supposed infection. Meantime, the cancer has escaped.”

When it’s finally diagnosed, he is found to have an aggressive version (Gleason grade 9), and his PSA has started to double every nine days: “I was given about four years to live.”

He has since learned his father, whose cancer spread to his pelvis in his 70s , had a PSA of 3000 when he died.

Dr Forster, too, is now on a course of hormone therapy, “where at the end there is nothing”.

So he and Dr Watson have formed a company, Caldera Health Ltd, Auckland, to fill that “nothing” with viable treatment.

As he told his audience, they find it wryly amusing that “you have to get cancer to start a company to treat cancer”.

They’re taking a three-pronged approach to their work. They want:

•    Very early detection. Diagnosis needs to be better and earlier, with screening in the early 40s: “GPs must encourage men to have tests.”

•    Improved longevity through changes to life-style and diet.

•    “Modernised” treatment options for those whose cancer becomes resistant to hormone therapy.

Dr Watson says they’ve been looking at the molecules that come out of tumour cells and are investigating a range of biomakers that have never been explored before.

In essence, this work could lead to ways of assisting the immune system to fight cancer in specific ways, something he terms using the body’s innate and adaptive abilities to respond to disease.

He elaborates on how treatment could be modernised, especially in New Zealand, where some of the new drugs used in the US to block prostate cancer are not available. He wants to bring some of the new therapies here to put them into trials.

The best way to handle treatment is to use a variety of therapies so that the tumour cells do not develop resistance.

He believes the biggest weapon available is the immune system and there is a range of molecules now available to stimulate it.

Such immune system enhancement is being used to treat some human cancers – but not prostate cancer: “It’s been shown that the immune system can be activated against bladder cancer, for instance.”

Only one promising immune system treatment – Provenge, from Dendreon Corporation in Seattle – has been developed for approval by the US FDA (which is considering it now) for treatment of advanced prostate cancer, and relatively speaking little money has been spent on prostate cancer.

He believes he may have found an effective immune enhancement compound and is preparing to trial it on himself.

Meantime, Dr Forster is looking at genetic information to see if there are ways of finding prostate cancer early.

He wants to know why, in his own family, there is this deadly tendency for PSA to shut down until it’s too late.

One approach he wants to see adopted is routine assessment of urine immediately after a GP has conducted a digital examination, a testing of molecules dislodged in the process to see if signs of cancer are there: “It starts to build a picture.”

At present, such urine tests are routinely not done in NZ.

His part of the presentation now  moves on to the do’s and don’ts of diet and lifestyle. He is tanned, healthy-looking, lively, speaks rapidly with the enthusiasm of his message. He looks like a farmer, and it turns out he is when he’s not in the science lab.

He talks about the need for regular exposure to the sun – “without being silly” – because of the vitamin D it will bestow on the skin.

It’s well known, he says, that prostate cancer rates climb in populations further away from the Equator.

People should never go without the sun more than 10 days. Pills need high doses to work, whereas even minutes in direct sunlight every day does wonders.

However, his advice comes with a rider: don’t get into the shower straight afterwards and wash the vitamin D away. It takes a while to be absorbed.

“Don’t use soap on your skin where you don’t have to. Soap the bits that need it, of course, but just let water run over the rest.”

He explains about phytochemicals, substances in food and drink that mimic artificial drugs and if chosen carefully aid the process of keeping cancer progression at bay.

These are significantly present in the diets of Asian, Indian and Mediterranean peoples, whose incidence of prostate cancer is low.

He throws a chart up onto the data projector screen and outlines the benefits of various food items, such as tomatoes.

Contrary to popular belief, eating sliced up tomatoes in salads and on toast does no good: they have to be cooked and must be eaten with a little fat or oil to aid uptake (this is especially advisable before a prostatectomy).

Tomato sauce on fish and chips never seemed so right.

He plumps for the brassicas (cabbage, cauliflower, broccoli, brussels sprouts); daily fruit smoothies with strawberries, raspberries; pomegranate juice; salmon oil (or oily fish such as salmon, tuna, anchovies, sardines); Japanese green tea; soy products (soy milk, tofu); other vegetables and fruit; and flavourings like raw garlic, shallots, tumeric, chilli peppers, or mushrooms.

He gets the audience going with one piece of good news – that rich, red pinot noir wine from the cool climate of Central Otago contains resveratol, and should be consumed regularly.

Someone asks if he has shares in Carrick (award winning Otago winemaker), while another suggests the foundation buy a vineyard, or perhaps approach pinot noir makers with a marketing deal.

Dr Forster puts too much red meat and dairy products (especially calcified trim milk) on the “don’t” side of the ledger. Get your calcium from slow-release sources like almonds (10 a day), he says. Sugars and fats should be kept to a minimum, as well.

The presentation ends with extended applause – and Dr Forster handing around another of his dietary weapons, a packet of goji berries, a kind of dried fruit that tastes like apricots.

We’ve just heard from two prostate cancer patients who, unusually, can take a real hand in their own fates.

Who are Dr James Watson and Dr Richard Forster?

Dr James Watson

The University of Auckland Alumni Association says after graduating with a BSc in 1964 and an MSc in 1965, James Watson was awarded a New Zealand Cancer Society scholarship for his PhD research on the synthesis of 5S ribosomal RNA in mammalian cells.

He was a post-doctoral fellow at Syntex Research Centre for Hormone Biology, and then Research Associate at the Salk Institute for Biological Sciences at La Jolla, California.

In 1975, he moved to the Department of Microbiology in the College of Medicine at the University of California at Irvine, where he was promoted to full professor in 1979.

In 1981, Professor Watson returned to New Zealand as Professor of Microbiology at the Auckland University School of Medicine, and in 1984 became head of the Department of Molecular Medicine.

In 1994, he established Genesis Research and Development Limited, becoming chief executive in 1998.
He received the university’s Distinguished Alumni Award in 2001.

A biography on the web lists these achievements:

Ex-Managing Director, BioJoule Limited, New Zealand:
• Led development of lignocellulosic processing to produce bioethanol and other high value bioproducts.
• Led development of patent estate, capital raising and sale to Pure Power Global.

Ex-Chief Executive of Genesis Research & Development Limited, New Zealand:
• Founded Genesis in 1994 and listed on New Zealand and Australian Stock Exchanges in 2000 and raised NZ$200 million over this period for technology and product development.
• Led development of an integrated life science gene technology platform and development of patents in both health and plant fields.
• Used the Genesis plant patent estate to partner with International Paper Company, MeadWestvaco and Fletcher Challenge Forests to establish ArborGen LLC

Former research scientist and professor:
• PhD, Auckland University, New Zealand.
• Research career in the United States with Syntex Corporation, Salk Institute.
for Biological Studies, and University of California.
• Professor, University of California, Irvine, 1976-81.
• Professor, founder and Head of the Department of Molecular Medicine, Auckland University, New Zealand, 1983-93.
• Author of more than 200 scientific papers and holder of a dozen patents.

Key professional activities:
• Member of New Zealand government’s Innovation & Advisory Board, 2001-03.
• President of the Royal Society of New Zealand, 2003-06.
• Current chairman of the National Science Panel of the Royal Society.

Dr Richard Forster

Google Dr Richard Forster and references go on for page after page in the scientific areas of biotechnology and research into plants, genetics and biofuels, where he holds patents.

An example on the World Intellectual Property Organization website lists him as co-inventor of something called COMPOSITIONS ISOLATED FROM FORAGE GRASSES AND METHODS FOR THEIR USE.

Less intimidating is his listing on the BusinessWeek website, which says he is co-founder and director of a company called LanzaTech New Zealand Ltd, which develops “platforms for producing fuel ethanol in New Zealand.

The company’s technology is used to allow industrial waste streams to become a resource for bio-ethanol production. LanzaTech New Zealand Ltd. was founded in 2005 and is based in Auckland, New Zealand.”

Further into the website, it says:

Richard Forster PhD serves as Chief Scientist, Plant Division of Genesis Research & Development Corporation Ltd (an organisation founded by Jim watson).

“Dr Forster served as Chief Scientist of AgriGenesis BioSciences Ltd. Dr. Forster served as Head of Forestry at Genesis and, prior to joining Genesis, was involved in science management in DSIR and HortResearch.

“Dr. Forster received his PhD at the University of Dundee and has served on science review committees with the New Zealand Government and with CSIRO.”

He serves as a member of the NZ Royal Society energy panel and was listed as co-author of the panel’s 2006 report 2020: Energy Opportunities .

A website called BioMed Experts lists many of his papers, published here and in the US and Australia, with titles like
Genome characterization of a flexuous rod-shaped mycovirus, Botrytis virus X, reveals high amino acid identity to genes from plant ‘potex-like’ viruses.

Typical is a 1994 listing in the New Zealand Journal of Crop and Horticultural Science abstracts entitled Incidence and distribution of six viruses infecting tamarillo (Cyphomandra betacea) in New Zealand, which he co-authored.

In 1996, NZ Science Monthly reported that a team from HortResearch and the University of Auckland, led by Dr Richard Forster, is to investigate the mechanisms involved in forming dark green islands on plants – are they formed by specific inhibition of virus transport and replication between cells, or is the viral DNA being specifically targeted and degraded?

They will also be trying to understand why these dark green islands arise: are they a generalised resistance response by the host plant or do they result from a viral adaptation to limit damage to the plant?

In 2007, CheckBiotech website had a story about LanzaTech and an overseas company, Khosla Ventures, forming an alliance to focus on the conversion of waste industrial gases into ethanol.

“The company is aggressively pursuing the development of advanced gas to ethanol technologies based on work developed in its laboratories in Auckland, New Zealand.

As part of its two-pronged strategy of technology development and deployment, LanzaTech has sought international patent protection for its ethanol production process and is forming partnerships to commercialize its technologies and processes.”