This episode of Project Mātauranga profiles Hemi Cumming and his colleagues from Victoria University. They want to synthesise pateamine – a natural compound found in sea sponges. It has the potential to be a powerful anti-cancer drug, but its complex chemical make-up presents significant challenges. To become a commercially successful drug, the pateamine mimic must be able to be mass produced while retaining the original compound’s key functions.
Transcript
Dr Ocean Mercier
Māori have always been scientists, and we continue to be scientists. Our science has allowed us to live, work and thrive in the world for hundreds of years. My name is Dr Ocean Mercier, and I’m a lecturer in pūtaiao Māori at the Victoria University of Wellington. My job takes me all over the world to talk about Māori science and how traditional knowledge is being married with western science here in Aotearoa in order to find innovative solutions to universal global issues.
In this programme, we are going to show you how these worlds of science are intersecting and how the paths to our future are being formed.
Dr Ocean Mercier
Since the birth of modern medicine, scientists have searched to find a cure for cancer. Understanding the genetic abnormalities that lead to cancer, and how we can control or stop them, is at the forefront of today’s medical research. Ko te mate pukupuku te tino kaipatu i ngā uri o Aotearoa, ā, ko te iwi Māori te iwi e tino patua ana. (Cancer is a major cause of death among New Zealanders. Māori people are most affected.)
Searching for a solution, though, is Victoria University biochemistry PhD student Hemi Cumming. Like his tūpuna who practised the art of rongoā Māori, Hemi’s looking to nature to find answers to some of modern medicine’s most complex problems.
Kei te whakamahi a Hemi i tētahi matū pūhui e kitea noatia ana i roto i te kōpūpūtai – te āhua nei, kei te aukati tēnei matū i te tipuranga mai o ngā pūtau mate pukupuku. (Hemi is working with a unique chemical compound that’s only found in a rare native marine sponge – a chemical that seems able to inhibit the growth of cancerous cells.)
Ki te kimi a Hemi rātou ko ōna hoa mahi i tētahi huarahi whakatārua i te matū nei, tera pea, ka tūpono ki tētahi tikanga whai hua hei tiaki tūroro mate pukupuku, tētahi rongoā rānei. (If Hemi and his team can find a way to replicate the chemical, their research could lead them to the discovery of an effective treatment, or even cure, for cancer.)
Hemi Cumming
Ko te mea e tino ratarata ana ki a au i roto i aku nei mahi, arā ko ngā nunui o ngā hua i waenganui i a tātou i tēnei ao. Arā ko ngā hua o Tane Mahuta, ko ngā hua o Tangaroa. Mai rā anō tātou te iwi Maōri e tūhono ana ki ngā āhuatanga o tēnei ao, arā he hononga whakapapa. Arā mai i tēnā ka mōhio tonu tātou. Arā, i ngā painga a tēnei ao mo tātou, a te tinana, a te wairua hoki. Ko tāku nei mahi, ana, ki te mau ana i ētahi o ēnei o ngā titirohanga o tātou te iwi Māori, ana, engari ki te mau ana i ngā taonga, i ētahi o ngā mōhiotanga a iwi-kē, arā, i roto i te putaiao. (The thing I like most in the work I am doing is the abundance of resources we have around us. The abundance from Tāne Mahuta. The abundance from Tangaroa. Māori have always had a connection with our environment. It’s a genealogical connection. From that, we know the goodness our environment provides for us – physically and spiritually also. My job is to take some of our Māori perspectives and incorporate them with knowledge of other people in the area of science.)
Dr Ocean Mercier
I te haerenga o te roopu rangahau nei ki te ruku moana i waho o Moho Kāherehere, ka maea ake rātou me tētahi tauira nō te kōpūpūtai, he hanga nō Aotearoa anake. (When a research team went on a diving expedition off the remote coast of Fiordland, one of the samples they collected was an undiscovered marine sponge that’s only ever been found in Aotearoa.)
Nā wai rā, ka kitea e Ahorangi Northcote, kei roto i te kōpūpūtai te matū pateamine. (Associate Professor Northcote found that the sponge contained an unusual natural chemical – pateamine.)
Associate Professor Peter Northcote
Well, believe it or not, this is actually a sample of the sponge that pateamine came from. This is Mycale hentscheli, and in 1989/1990, we went out and found this sponge in Fiordland, and from these samples, we isolated this new compound, which we call pateamine, which has potential anti-cancer activity, and it’s this compound that Hemi is actually trying to make simplified analogues of, which may have more activity in cancer than the original substance. We look at sponges in particular for anti-cancer compounds because sponges don’t move, they are stuck to the rock and they don’t have many physical defences, so we believe that they use chemistry to defend themselves from predation and other animals encroaching over top of them. We hope that, by looking in these sorts of organisms, we’re more likely to find compounds that might be useful in treating cancer.
Dr Ocean Mercier
The children of Tangaroa have been found to contain many healing properties. Compounds from sponges are being used to fight the AIDS virus. Corals and molluscs are used for orthopaedic implants. Pain relievers from sea snail venom and infection-fighting agents from shark skin are also being studied.
Mō ngā tūroro mate pukupuku, ko te pateamine pea te oranga, nā te mea, i te āhua nei, he patu pūtau mate pukupuku tāna mahi. (For cancer sufferers, pateamine offers real hope, and the natural chemical appears to inhibit the growth of cancerous cells.)
Engari, he uaua te kimi, ka mutu, kei ngā wāhi hohonu o te moana e noho ana, nā reira, tino kore nei e taea te tiki atu i a ia hei rongoā mō mate pukupuku. (But the fact that it’s only found in tiny amounts deep underwater makes using it to fight cancer impossible.) Nā reira e ngana ana a Hemi rāua ko tana kaiarataki, a Ahorangi Paul Teesdale-Spittle, ki te tāruarua i te pateamine, kia huhua ai te puta, kia noho ai hoki hei rongoā. (Hemi and his supervisor Associate Professor Paul Teesdale-Spittle are trying to create a simplified synthetic version of pateamine that can be mass produced and potentially used in medicine.)
Associate Professor Paul Teesdale-Spittle
Pateamine was isolated about 20 years ago, so it’s been worked on for a long time, and about 5 years ago now, we identified that it binds to a very unusual protein target, something that no kind of clinical drug binds to, for example. In fact, no small molecule, drug-like molecule, has been found to bind to it. So, that’s what got us excited again in pateamine, and Hemi’s project has been to synthesise an analogue or a mimic of pateamine that will retain its functional properties and may allow us to target particular proteins within the cell.
Dr Ocean Mercier
A tumour begins to develop when a cell experiences a mutation that makes the cell more likely to divide than is normal. The altered cell and its descendants grow and divide too often. These cell's descendants divide excessively and look abnormal. As time passes, one of these cells experiences another mutation. This cell and its descendants are very abnormal in both growth and appearance. If the tumour that has formed from these cells is still contained within its tissue of origin, it is called in situ cancer. The escaped cells may establish new tumours at other locations in the body. Pateamine inhibits these mutations and a mimic that acts in the same way has the potential to be a significant step forward in treating cancer.
Associate Professor Paul Teesdale-Spittle
And so pateamine is extremely toxic to dividing cells, and that makes it a very interesting compound from the perspective of treating cancer.
Hemi Cumming
There aren’t many people who have not felt the effects of cancer, and that includes people in my family. So, my grandfather passed away a few years ago from cancer, so I’m fully aware of how it can just completely suck the life out of you until you pass away. This idea that, you know, that I can contribute or explore cancer treatments is definitely a key driver.
Dr Ocean Mercier
Ko te nuinga o nga mate kino pērā i te mate pukupuku, e ahu kē mai ana i te tipu tūperepere mai o ngā pūtau rerekē i roto i ō tātou tinana. (Many harmful medical conditions like cancer are caused by the abnormally rapid growth of cells within our bodies.)
Tērā pea mā te pateamine te tipu o ēnei pūtau rerekē nei e akutō, pērā i te haumanu iraruke, engari, nā te mea, he uaua te kimi, kei roto hoki i te wai hohonu e noho ana, kāore e taea te pateamine te mahi, mēnā kei tōna āhua tūturu ia. (The natural chemical pateamine could slow down this abnormal cell growth as effectively as current medical techniques like radiotherapy, but because it’s only found in tiny amounts and in deep water, using pateamine in its natural state is impossible.)
Hemi Cumming
We represent chemicals as models because obviously we can’t see them. The black balls in this model represent carbon, the white balls represent hydrogen, and these are connected with a chemical bond. Now, pateamine, the chemical that we’re concerned with, is much more complex than this. So, when we’re drawing our chemicals on paper, we use a certain shorthand where we represent carbons with bends and bonds with lines, and we represent all other atoms using their letter. Now, this may not look like much to a non-chemist, but using this shows us a blueprint of the chemical of pateamine. We can use this to take information to design other chemicals that have that same function.
Dr Ocean Mercier
The potentially life-saving chemical pateamine can’t be applied as a medical treatment in its natural state, engari, tērā pea koia te tauira e puta ai i te tangata he momo matū pērā i a ia hei patu i te mate i roto i ō tātou pūtau (but perhaps it could be used to build a mimic that actually works to fight cancerous cells). The task of building a mimic of pateamine that actually works started with Hemi and his colleagues unpicking the compound’s complex chemical structure, but the hard work will be designing and building a simplified version from readily available chemical building blocks.
Kei roto a Hemi Cumming, tauira tohu kairangi o te Whare Wananga o Wikitōria, i te roopu rangahau (Hemi Cumming, biochemistry PhD student of Victoria University, is part of the research group) that’s studying the chemical properties of a rare native sponge. Kei roto i te kōpūpūtai te matū pateamine (Within this sponge is the chemical pateamine) that’s able to target and inhibit the growth of cancerous cells. Unfortunately, it’s impossible to use in its natural state as a medical treatment, because it’s only found in tiny amounts in deep water, but if Hemi and his colleagues can build a chemical mimic of pateamine, their research could lead to better treatments or even a cure for cancer and other genetic diseases.
Associate Professor Paul Teesdale-Spittle
Right, we’re going to need what? Something to build a body from, aren’t we?
Hemi Cumming
Well, how big is that?
Associate Professor Paul Teesdale-Spittle
Yeah. How many of those have we got? Have we got enough parts?
So, synthesising a molecule like pateamine is actually relatively complex and difficult to explain the processes we go through without using an analogy. So, today we’re using analogy around designing a bird and building it from LEGO blocks. So, the LEGO blocks, for us, are representing an array of different molecules that we could choose from to assemble our bird, and we have to decide which parts to build it from, how to assemble it – from the atoms, from what bonds to make, and we would go to our chemical stores and from there, we can select simple molecules, so that give us pre-assembled bits of structure. So, we’ve got some here and some here. In fact, all of these represent the different types of structure that we could get in the store. So, you get thousands and thousands and thousands of compounds that may have value in building up the molecule we’re trying to build. We have to choose which ones will make useful contributions to the synthesis of the molecule. So which ones can we get from our chemical stores to connect together through the chemistry that Hemi does when he’s building pateamine?
Dr Ocean Mercier
Ko te mahi a Hemi, he hanga tauira rūnā o te pateamine, ki ngā matū e taea ai e ia te kohi ake i te whare matū o te whare wānanga me ngā umanga hoko matū. (Hemiʼs task is to build a simplified version of pateamine using only the readily available ingredients from the university’s chemical store and industrial suppliers.) Kia maha ngā tauira, kia mau tonu hoki i ngā tauira te ahei ki te aukati i te mahi hanga pūmua a nga pūtau mate pukupuku. (This mimic must be able to be mass produced and must also retain the chemical’s key function of inhibiting protein production in cancerous cells.) E angitū ai, me āta whakaraupapa, me āta hanga a Hemi i ngā matū tika ki ō rātou wāhi tika. (To be successful, Hemi must gradually combine the chemical building blocks in just the right way.)
Hemi Cumming
So, we have two of our basic building blocks that we just got from our chemical stores. Essentially, we have A and B that we want to put together, and we can do that in our reaction flask where we are trying to create an environment that facilitates these two building blocks coming together. In this reaction, we have put in dry ice to cool the reaction down, which helps prevent other byproducts. Now, what we are trying to do is create C. Now, essentially you can think of C as being a larger building block that is more complex than A and B. We can repeat this process where we are gradually building a much larger and complex building block where we hope to put these larger building blocks together to hopefully get to our pateamine mimic.
Dr Ocean Mercier
Kua oti i a Hemi rāua ko ōna hoa mahi he tauira rūnā o te pateamine te hanga, me te whakapono, ka mahi ngā tauira nei i ngā mahi a te pateamine. (Hemi and his colleagues have designed a simplified version of pateamine that they believe will mimic its key behaviours.) Hēoi, kua tangohia, kua nekehia, kua tāruaruatia rānei ētahi o ngā matū o te pateamine tūturu, kia ngāwari ake te hanga tauira. (In this new blueprint, a number of pateamineʼs components have been removed, moved or duplicated to make it easier to synthesise.)
Ko te whāinga a Hemi, kia whakapai ake i ngā tauira pateamine, kia puta ai a ia he tauira ngaio ake. (With this slightly altered version of pateamine as his goal, Hemi has gradually combined the basic building blocks to make more complex structures.) Kua oti kē i a rātou ko ōna hoa mahi, ngā tauira matū tūāpapa e toru te hanga, ā, ko te tumanako, kia whakahonohonotia ēnei kia puta ai he tauira tino ngaio pū o te pateamine. (He and his colleagues now have three major building blocks that they hope will fit together to make a fully functioning pateamine mimic.)
Hemi Cumming
I believe that it will definitely retain the function that pateamine has in its cell, and I guess the question is how well does it do that. But that’s the beauty of the way that we’ve designed it that we can actually redesign it so that we can add or remove features of these compounds.
Associate Professor Peter Northcote
Synthesis is more than just a science. You have to be very skilled in the lab. You have to have a skilled set of hands. You have to have the creativity to see new ways of making these compounds, and you also need to have persistence because you may get nine-tenths of the way to your synthesis only to find an unachievable target, and you then have to go back and try a different way to get to the same place, and this can be frustrating and so it requires a very skilled and special person that can continue on in these conditions.
Associate Professor Paul Teesdale-Spittle
Our LEGO bird here clearly is not going to have the properties of a real bird. Although we’ve mimicked some features, it’s actually not going to be functional. I should think if we try and get it to fly, it won’t. But when we design molecules, we actually are able to design molecules that have the functions of the more complex natural products that we’re basing our design on, and that’s essential for us. We have only succeeded if we retain the function of the molecule in our simplified mimic in a way that we clearly have not done with this particular bird.
Hemi Cumming
So, this is where the cycle ends in Victoria University’s million-dollar NMR facility where we can take our building block C that we’ve just synthesised and put it into our NMR machine. This is essentially a huge magnet that allows us to analyse the chemical and structural make-up of our compounds that confirms what we have made. And hopefully very soon, this NMR machine will tell us whether we’ve made our pateamine mimic.
Dr Ocean Mercier
Hemi and his colleagues are at a key stage of their project. They’re about to find out if their pateamine mimic will fit together and function the same as the natural chemical on which it’s based. Success could potentially lead to a medical breakthrough that could help cancer sufferers all over the world.
New Zealand is one of many countries trying to position itself as a world leader in research and development. Achieving this will depend on scientists like Hemi Cumming and how well we utilise our natural resources. But the chemical complexities of the natural world make any attempt at duplication extremely difficult.
Associate Professor Paul Teesdale-Spittle
The natural world is full of molecular complexity. Everything you see has, if we can see it, it’s built from molecules, and within nature, there are molecules that are designed to interact with proteins, nucleic acids, the components of cells, so it’s an excellent place to go and find biologically active molecules. That is why nature makes molecules – it is to be biologically active – and the complexity and the array of structures that have been developed over aeons of evolution is more than we would naturally stumble upon within a synthetic laboratory.
Associate Professor Peter Northcote
If you look into the natural source, not only will the compound be active, hopefully, against the target, but it also has to be able to pass through a body of a living thing and so the compounds that are produced in nature that have actively passed some of the very tests that you’re going to require. So, nature has been around for over a billion years and has gradually come up with clever ways of doing things. New Zealand does have a unique environment, and therefore the marine organisms living around the coast of New Zealand are different, and this particular example is endemic – it occurs nowhere else but New Zealand to the best of our knowledge. And so, yes, by analysing these organisms and finding these compounds, not only do we learn new things about how biology works, how our bodies work, but there’s always the potential that these compounds could be used pharmaceutically, and if they can, the economic return to New Zealand would be significant.
Dr Ocean Mercier
Kei te whakatata a Hemi ki te paerangi e oti ai i a ia he tauira ngaio pū o te matū pateamine, engari, he wero nui te hanga tauira pērā. (Hemi is on the cusp of putting together a mimic of the chemical pateamine but faces a complex challenge rebuilding its structure).
Hemi Cumming
Trying to make this final connection has proven very difficult, but it’s just another challenge, which is quite typical in this type of research, and you just have to be persistent and be quite determined because, you know, of the ultimate outcome and benefits that it potentially could have.
So when I last saw you, we had these three fragments – green, blue and black – represents these areas of our final target. We had explored previously a way that we can put this together, and so now we’ve successfully made two of these key connections, which essentially gives us all the atoms of our final target. But what is left and proving to be quite challenging is this final connection, which pulls them all together to provide us with our final complete cycle, which is necessary for our final target. The fact that I’m working on something that may prove to be a good treatment for cancer is definitely exciting for me.
Associate Professor Paul Teesdale-Spittle
If we were really lucky and our pateamine analogue takes us down the line of an anti-cancer agent, we might be looking at a market that’s similar to that of Taxol. So, Taxol is an anti-cancer drug that is used for treatment of a range of cancers – breast and ovarian cancer, for example – and the latest data I have for that, which is about 3 or 4 years old, was about US$1.6 billion in sales annually.
Hemi Cumming
What do we do, what we have is a compound that has some quite unique activity in cells. Cancer is definitely a key target for many reasons, but there is the potential that, when we do finally put it into a cell, that we may find other benefits or activities that could be used for other types of treatments.
Associate Professor Paul Teesdale-Spittle
From an international perspective, the more that we can do the research within New Zealand, the more that the benefits from the intellectual property that we develop can be retained within New Zealand. And so it’s our goal to take this molecule as far as we can here, within the New Zealand context, before it’s eventually sold on to a pharmaceutical company to market potentially as a drug. Will we get there? Maybe. It’d be good if we did.
Hemi Cumming
The type of research that we’re involved in is a type of high-risk high reward research where there is a lot to be gained, but there’s obviously that risk that an outcome that we want won’t be achieved. But ultimately, what we will definitely gain is greater knowledge towards these diseases and the knowledge of the way these molecules interact with these processes in the cell. Although there is a lot of risk in terms of no outcome, it’s definitely worth taking.
Dr Ocean Mercier
Kei te haere tonu tēnei mahi rangahau whai take a Hemi Cumming rātou ko ōna hoa, ā, kia oti ia ia te tauira ngaio pū, ka tahuri ki te whakamātautau hohonu i ōna āhuatanga. (The valuable research being undertaken by Hemi Cumming and his colleagues will continue, and extensive testing will be required once Hemi’s mimic has finally been put together.)
Hēoi, kei roto i wā rātou mahi, te tumanako kia pai ake te ao o anamata. Tērā pea kei te wai hohonu a Tangaroa, kei roto rānei i te waokū a Tāne, ngā rongoā mō ngā mate kino o te tangata. (But the work they’re doing offers promise for the future. Perhaps somewhere deep underwater or in the heart of the ngahere lie natural solutions to some of humanity’s most pressing problems).
Ki ngā kaipūtaiao rangatahi pērā i a Hemi Cumming, kei konā te mātauranga Māori hei whakatipu mā rātou, kia puta ai ōna hua ki te ao whānui. (For young scientists like Hemi Cumming, the opportunity’s there to grow our mātauranga Māori and provide real benefits to the world.)
Hemi Cumming
I ahau e tipu ana i roto i te Tairawhiti e tamariki ana kaore ahau i mohio ko tēnei taku ara enagi I konei arak a kite I nga hua ara o te whakatauaki, e ki ana a ko te kai a te rangatira ko te matauranga ara ka kite nga hua me nga paenga te haeremai i era mātauranga. Engari ko tēnei ke tetahi ara kotahi noa moku ara he nui I mua I ahau, no reira he mea tino hirahira tēnei ki ahau. (Growing up on the East Coast as a child, I never knew this would be my path. From this, I have seen the fruits of the proverb: The food of the chiefs is knowledge. I have seen the fruit and advantages of that knowledge. But this is only one avenue for me. This is very special to me.)
Dr Ocean Mercier
Hemi’s project stretches the boundaries of how we use the natural world in the search for innovative solutions to medical problems. If he’s successful in developing a pateamine mimic that’s used in the treatment of cancer, he could join the pantheon of New Zealand scientists, like Rutherford to be recognised internationally. Hēoi, matua kē ake i tērā, koia tētahi o te roopu e kimi rongoā tūturu ana, mā te auahatanga o te pūtaio hōu.
Acknowledgements
Video courtesy of Scottie Productions.
© Scottie Productions, 2013.
