Interview with David Bowtell

This article was originally published in issue 3 of the MMIM newsletter.

Professor David Bowtell is the Director for Research at the Peter MacCallum Cancer Centre. Although Prof Bowtell studied veterinary science, he has never worked as a vet. Instead, he found himself in biomedical research, initially working as a cell biologist. Here he talks about his work and how the MMIM database can help.

The Peter MacCallum Cancer Centre, or ‘Peter Mac’, as it is affectionately called, is unique in Australia, with an all-inclusive approach to cancer treatment. It is a specialist cancer hospital, where research, support and care are fully integrated. As well as boasting one of the largest cancer research facilities, Peter Mac runs clinical trials and offers state-of-the-art services and care, including medical imaging. Peter Mac is the only centre of its kind in Australia, with very few similar institutions existing outside of the United States.

Prof Bowtell likens his position as Director to the ‘captain of a footy team’ – he has a leadership role but also needs to kick a few goals himself. As well as working in his own lab, he coordinates other aspects of the Centre, including writing grants for the research division as well as the genomics program specifically.

In addition to his role as Director, Prof Bowtell runs a large medical genomics laboratory, which has a focus on ovarian and gastric cancers as well as carcinoma of unknown primary (CUP). CUPs are cancers that do not have a known point of origin, but their sources can be detected by taking biospecimens and testing samples. One test that is extremely useful for CUPs is microarray testing, and it is this data that is present on the MMIM database.

Prof Bowtell became involved in MMIM through his lab. He feels that MMIM is important for cancer research as it allows scientists to gather clinical information, which can then be related to known genetic information. This facilitates the development of predictive models for oncology as well as for other areas.

His lab started working with spotted microarrays in 1999. They now use microarrays (specifically Affymetrix microarrays) to classify different cancers into patterns of gene expression. For example, the primary source of CUPs can be determined by using microarray technology to compare it to cancers with known primary locations.

Tumours from patients with the same type of cancer, but different outcomes, can also be compared to analyse for risk of reoccurrence of tumour formation after remission. This can help doctors plan long-term treatment, as an increased risk would indicate more aggressive treatment.

When asked about his thoughts on a ‘cure for cancer’, Prof Bowtell said that at Peter Mac, researchers are studying the molecular basis for different types of cancer. They are looking at the individual molecular pathways involved and treating each one separately. It seems that there are multiple cures for cancer, rather than the single one that we were previously searching for.

Molecular genetic information can help at all stages of cancer development: diagnosis; staging (determining how advanced the cancer is); planning treatment; implementing treatment; assessing family risks; and managing these family risks.

Peter Mac is involved in cutting-edge research into chemoprevention, which can be likened to vaccination – chemotherapy can be used to prevent cancer ever forming in high-risk patients. And while early detection of cancer is important, genetic information can indicate how aggressively to treat a tumour that has been found promptly. This type of individualised treatment may be the way of the future, and comprehensive organisation and sharing of the information, in a format such as MMIM, is a vital tool for this type of research.

The moon is actually brie, Skeldon reports

Ken Skeldon, of the University of Glasgow, has been touring with his lecture about moon hoax theories. He spoke at UTS for Science Week. He picked a few of the popular “facts” used to promote the idea that NASA’s moon landings have been faked and debunked them. It was very entertaining. I really can’t capture how much fun he made it; the presentation included Stairway to Heaven by Led Zeppelin being played backwards and some trippy optical illusions, but here’s the gist of the argument anyway. I didn’t need this lecture to be convinced that people who think the moon landing was hoaxed are fruits, but it was good to have the science of it as well as the politics. (Not that I’m finding NASA all that impressive these days; but its current failures shouldn’t negate its past successes.)

The flag is waving; it shouldn’t because there’s no atmosphere.
Because there’s no atmosphere, the flag had to have a rigid pole to hold it open. There is no footage showing the flag waving on its own; however there is footage of it moving while the astronauts were struggling to get the flag into place. Once they let go, it took a little longer to stop moving than it would on earth, because there were less forces acting against it.

There aren’t any stars in any of the pictures, but there are no clouds on the moon to block them.
Because the moon is reflective, it has an incredibly bright surface. The cameras had to majorly underexpose in order to show the astronauts in the pictures at all; if the exposure had been normal, the surface and the astronauts would have been “washed out”.

There are non-parallel shadows in the pictures, suggesting multiple light sources.
It’s an optical illusion that a single light source only gives parallel shadows; shadows meet at the light source.

The astronauts and lunar module appear to be lit in the shade.
On a clear night, the moon appears crisp because sunlight from behind it reflects in all directions, regardless of what angle it hits the moon at. This is what makes the moon such a bright light source. The astronauts and lunar module had light from the sun behind them to illuminate them.

Dust anomalies: there were no plumes of dust from the moon rover, and no crater was formed when the lunar module landed.
The moon rover didn’t leave plumes of dust as cars do on earth, because of the reduced gravity. The lunar module didn’t form a crater upon landing because it didn’t crash down; it drifted down gently.

The astronauts wouldn’t have been able to survive the radiation they would be exposed to in the Van Allen Belt.
The Van Allen Belt consists of three types of radiation: alpha particles (protons), beta particles (electrons) and gamma radiation (light radiation, which is actually harmful). They only passed through the alpha radiation, which is much easier to block: it is blocked with polyurethane, as opposed to gamma radiation, which can only be blocked with lead.

Some photos with different foregrounds have identical backgrounds.
Without anything in between, relative distance is harder to judge; the photos were taken from different angles and/or distances.

Some of the pictures show “props” that are clearly man-made.
The brain can make anything seem like anything else, given the suggestion.

And some proof that the moon landings did happen…
* All the live video footage was transmitted by a network of satellite dishes during the Apollo missions, including some in Australia (The Dish).
* Over 382 kg of moon rock was brought back.
* Gravity measured from original footage checks at 116/earth’s gravity, as expected.
* Over 130 separate lunar energy studies rely on reflectors left behind by astronauts.

Some reading material…
http://www.moontruth.com
http://www.redzero.demon.co.uk/moonhoax
http://www.clavius.org
http://www.badastronomy.com
http://www.nasa.gov
http://www.iangoddard.net/moon01.html
http://www.google.com/maps

Roo burger, anyone?

I just got home from an interesting panel put on by the ASC. Here’s my write-up…

First up was Mike Archer, palaeontologist and Dean of UNSW’s Faculty of Science.

According to Professor Archer, we need 1.5 million square kilometres of land to be set aside for conservation if we want to ensure the healthy evolution of species. Since it’s hardly practical to kick people off that much land to create national parks, instead we need to convince them that it’s worth their while.

There have been interviews with farmers about the drought; in the background are dead cows… and bouncy kangaroos. Being native, they’re adapted to this habitat. Most farmers see kangaroos as competition for their cattle, so they have no interest in preserving them or their habitat (which houses many other species). Bribing these graziers won’t help the situation, it’s not reliable as it’s too easy to cheat that kind of system. There needs to be something inherent about that habitat itself that makes farmers want to look after it.

There are 200 million years of evolutionary distance between humans and kangaroos, which means that we don’t have many diseases in common. The only disease we can catch from kangaroos is toxoplasmosis, which we’re more likely to catch from cats, and which kills marsupials.

Basically, it’s all about sustainable use; just one way of practically conserving the environment.

The next speaker was John Kelly, spokesman for the Kangaroo Industry Association and an exporter of kangaroo meat.

According to Kelly, kangaroo has been the red meat of choice for 40 000 years; there’s just been a 100-year hiccup in its popularity. There are many advantages to eating roo meat. It’s low in “bad” fats and contains some “good” fats, has a wild, gamey taste, and good environmental credentials.

Sustainable kangaroo harvesting can prevent then from becoming over-populated and therefore over-grazing an area. For the past 30 years, kangaroo harvesting has been carefuly monitored and no negative effects on ecology have been observed. The RSPCA and the Australia Veterinary Association agree that an animal killed instantly in its own habitat is under much less stress than an animal that’s penned, starved, and then taken to place that smells of death to die. Roo harvesting also provides jobs and revenue to remote rural communities.

Next up was Ron Hacker, Chair of the Department of Agriculture.

He said that kangaroo populations have increase significantly since while settlement, especially in sheep farming areas, because of increased water supplies and removal of dingos.

Commercial harvesting doesn’t always help sustainable farming: it ceases to be commercially viable before reaching population levels that are found in drought conditions. This makes it a renewable resource that should be managed to suit everyone.

Then there were questions

What cuts sell the best?
The same as for beef, it is used for steaks and manufacturing, works well for salamis (but needs fat added). The tails are used in Korea, where it’s believed that one can acquire qualities from eating certain foods. The tail is believed to give the kangaroo its stamina.

What about conservation of the species?
There are seven main species of macropod. Of theses, the Western grey, the Eastern grey, the red and the wallaroo are abundant. It’s all about supply and demand: people don’t have the tradition to eat roo, but there’s also limited supply because of limited quotas of what can be harvested.

What’s to guarantee that kangaroo hunting won’t go the way that fishing and whaling has?
There is much less known about marine ecology compared to kangaroo ecology. We know a lot about them: their numbers are estimated annually, so the sustainable level of hunting them can be determined much more easily.

Many of the opponents of kangaroo harvesting (eg VIVA and PETA) have an agenda about all animals and don’t want any animals to be eaten or kept as pets. They’re moving towards being terrorist groups. They feed the idea that all wildlife is endangered, so we shouldn’t interact with it.

* * *

I’m not sure what I think of all this. I won’t eat roo meat regardless, as it’s not kosher. But I’d like to have a position. I suppose that I support them in theory, at least, but I’d like to know how likely hunters are to shoot a rare macropod species by mistake, and who’s really done this research. Because if it’s someone with a vested interest, it’s definitely fishy. And some of the things they said contradicted other statements: they said that they would be over-supplying if they harvested enough to bring populations down to drought levels, but also that the quotas limit their supply. So, the jury’s still out.

Spotlight on diabetes

This article was originally published in issue 2 of the MMIM newsletter.

Associate Professor Colman is a consultant endocrinologist and is the head of the Royal Melbourne Hospital’s Diabetes and Endocrinology Clinics and Services. After completing his medical degree, he undertook research training in Melbourne and then Boston, before returning to Melbourne to work. He now researches early diagnosis of Type 1 diabetes and still treats patients as a consultant. In this role he tests how diabetes treatment is progressing, and looks for problems or complications.

Although this work focuses on young children, adults can also develop type 1 diabetes. When asked why he chose to work with Type 1 diabetes, Colman cited the greater knowledge of the genetics of Type 1 as one factor. With Type 2, we know there must be genetic causes but we don’t really have a clear idea of what they might be. With Type 1, however, the genetics are much clearer.

Colman is researching the possibility of detecting type 1 diabetes before symptoms are seen. Type 1 diabetes has a strong genetic background, putting relatives of sufferers at increased risk. However environmental factors affect whether it will actually develop. Some researchers have suggested the possibility of a particular viral infection acting as a determining factor.

In order to study this, Colman’s research group is running several different projects with people who don’t (yet) have Type 1 diabetes, looking for antibodies to pancreatic cells.They are studying risk factors that may cause it to develop.

Colman and his colleagues decided to work with MMIM because it allows a spectrum of many different people to be put together, giving the big picture. For the first time, relatives of type 1 sufferers; children with a parent with type 1; and randomly selected school children can be compared directly. They wanted to compare data on a large scale, and as Colman states, ‘MMIM has given us this opportunity’. Hopefully, putting it all together will help determine risk factors and thereby prevent diabetes.

The MMIM project is very exciting for diabetes research, as it allows the possibility of ‘building of resources that would last forever’. The group can ‘already ask questions across the database that we hadn’t been able to do previously’.

When deciding what data to include in MMIM, Colman also included diabetes patient data. This allows a study of the risks of insulin treatment. For example, different types of cancer are suspected to be linked to this type of treatment. Also included is data from the diabetes clinic – there is now ten years’ worth of information about treatment, patient’s cholesterol levels, blood pressure, kidneys and eyes. The possibility for new discoveries are endless and as Colman says, MMIM is ‘pretty unique actually’.

A/Prof Colman is obviously passionate about his work, as he explains how it was originally thought that pancreatic cells don’t regenerate. Now it is believed that they do, which is important for stem cell research. If they do regenerate, it means that the immune system continues to attack the pancreatic cells, so stem cell transplants may not be effective. However it also hints that prevention could also be cure – if the auto-immune reactivity can be halted, then the pancreatic cells can be saved. He also touches on the ‘interesting crossovers’ between Type 1 and Type 2 diabetes.

In summary, though, he agrees that people often think diabetes is a disease where you’ll have to have insulin shots for the rest of your life, but says, ‘it’s not very satisfactory to think that diabetes is something that you just have to deal with’. Hopefully joining the MMIM database will open up more possibilities to change that.

MMIM: an introduction

This article was originally published in issue 1 of the MMIM newsletter.

How often do you worry about your health – the conditions you might develop or inherit? Imagine being able to have your DNA analysed for potential diseases, and dealing with them before they become serious. Or, for those with conditions that are already present, being prescribed medication to match your unique genetic profile.

Many diseases are known or thought to be affected by genetic predispositions. A person is much more likely to develop type 2 diabetes if other family members have the condition. However, diabetes is even more dependent on environmental factors, mainly diet and exercise. People living a Western lifestyle are far more likely to develop diabetes than non-Westernised people, regardless of genetic predisposition. If a person with at risk of developing diabetes is aware of it, he or she can make lifestyle changes to avoid this outcome.

Similarly, several types of cancer are known to have genetic factors. Breast cancer is probably the most famous example. Women with a close relative with breast cancer are more likely to develop it themselves. Certain variations in two genes, BRA1 and BRA2, are associated with breast cancer. DNA testing can be used to identify these variations in individuals.

It is likely that other genes are involved in breast cancer, and that other types of cancer have similar genetic associations. These connections can be made by studying the genetics of past and present cancer patients. Melbourne Health is working to link the relevant genetic data and clinical information for patients with colorectal cancer, diabetes and epilepsy, with more diseases to be added in time.

This project, the Molecular Medicine Informatics Model (MMIM), is a collaborative effort between scientists studying genetic aspects of disease; epidemiologists (researchers of public health); and IT specialists. They are combining their expertise and results to create a virtual database of genetic and clinical data from several different sources (Melbourne Health; Austin Health; the Peter MacCallum Cancer Centre; and the Ludwig Institute for Cancer Research). Scientists can use this database to help them study how certain genes relate to specific diseases.

This is where the benefit to patients, or people who might become future patients, comes in. With the identification of more genetic factors that cause diseases such as cancer, people in higher risk groups, or the general population, can have their genetic make-up tested. If they carry genes that are associated with disease, they can make lifestyle choices to reduce their risks, as well as undertake regular screening so that if they do develop a disease such as cancer, it can be treated at an early stage.

The MMIM database will also help doctors to understand why particular drugs work for some patients and not others. Within one disease, one drug may suit people with one genetic profile, while another works for those with a different profile. This type of information can assist in selecting currently available medication, as well as helping match patients with suitable clinical trials, if the drugs that are obtainable are unsuitable. In this way, treatment is tailored for each individual’s needs.

Prevention is always better than cure, and customised treatment is more accurate than generalised therapy. The MMIM database is forming a network to make this type of medical treatment a reality.