Our Fight With Cancer

In these exclusive interviews, we speak to Dr. Christopher Wild (Director of the International Agency for Research on Cancer, IARC – an intergovernmental agency forming part of the World Health Organisation of the United Nations), Prof. Nic Jones (Director of the Manchester Cancer Research Centre and former Chief Scientist of Cancer Research UK), Dr. Patrick Soon-Shiong (Physician, surgeon, scientist and philanthropist) and Olivia Newton-John (Singer, songwriter, actress and entrepreneur).  We discuss the very nature of cancer itself; how it affects us, and our society.  We look at the causes of cancer, it’s impact around the world, and- most importantly, how we can fight it.

Humanity has been astonishingly successful. We have used intelligence to combat our physical weakness; becoming the dominant species on the planet. Our arrogance dictates that we see ourselves as free of predators, but the truth is that we- ourselves- are that predator. Cancer is a disease that emerges from deep within us- from the very DNA that forms the basis of life itself. This disease claims over 8 million lives each year, taking 22,000 of us, each and every day.

Dr. Siddhartha Mukherjee in his 2011 book ‘The Emperor of All Maladies‘ writes that, “Cancer, we now know, is a disease caused by the uncontrolled growth of a single cell. This growth is unleashed by mutations- changes in DNA that specifically affect genes that incite unlimited cell growth. In a normal cell, powerful genetic circuits regulate cell division and cell death. In a cancer cell, these circuits have been broken, unleashing a cell that cannot stop growing. that this seemingly simply mechanism- cell growth without barriers- can lie at the heart of this grotesque and multifaceted illness is a testament to the unfathomable power of cell growth.  Cell division allows us as organisms to grow, to adapt, to recover, to repair- to live. And distorted and unleashed, it allows cancer cells to grow, to flourish, to adapt, to recover, and to repair- to live at the cost of our living. Cancer cells grow faster, adapt better. They are more perfect versions of ourselves…

To confront cancer…” he continues, “is to encounter a parallel species, one perhaps more adapted to survival than we are. This image- of cancer as our desperate, malevolent, contemporary doppelganger- is so haunting because it is at least partly true… If we, as a species, are the ultimate product of Darwinian selection, then so, too, is this incredible disease that lurks inside us….

Conservatively, cancer costs the world (in premature deaths and disability) close to $1 trillion every year; or around 1.4% of global GDP. In very real terms it is like the world loses an economy the size of Australia each and every year. The social costs are even higher- there are few people on the planet who, by the time they reach adulthood, will not have been affected by cancer in some way. It is for those reasons that the fight against cancer has been described as “one of the most significant scientific challenges faced by our species…

So what is the true scale of cancer in our society, and how will we beat it?

In these exclusive interviews, we speak to Dr. Christopher Wild (Director of the International Agency for Research on Cancer, IARC – an intergovernmental agency forming part of the World Health Organisation of the United Nations), Prof. Nic Jones (Director of the Manchester Cancer Research Centre and former Chief Scientist of Cancer Research UK), Dr. Patrick Soon-Shiong (Physician, surgeon, scientist and philanthropist) and Olivia Newton-John (singer, songwriter, actress and entrepreneur).  We discuss the very nature of cancer itself; how it affects us, and our society.  We look at the causes of cancer, it’s impact around the world, and- most importantly, how we can fight it.

[bios]Dr. Christopher Wild obtained his PhD in 1984 from the University of Manchester, UK, and was awarded an IARC postdoctoral fellowship (held at IARC) and subsequently a UK Royal Society European Exchange Fellowship (at the Netherlands Cancer Institute, Amsterdam). In 1987, he rejoined IARC as a staff scientist and later became Chief of the Unit of Environmental Carcinogenesis. In 1996, he was appointed to the Chair of Molecular Epidemiology at the University of Leeds; he headed the Centre for Epidemiology and Biostatistics and became Director of the Leeds Institute of Genetics, Health and Therapeutics in December 2005. Dr Wild was elected Director of IARC from 1 January 2009.

The main research interest of Dr Wild is to understand the interplay between environmental and genetic risk factors in the causation of human cancer. He proposed the concept of the “exposome” to match the genome in order to better address this research topic. He has particularly sought to apply biomarkers in population-based studies to this end in relation to liver and oesophageal cancers. He supervises directly the Gambia Hepatitis Intervention Study.

Professor Nic Jones is Director of the Manchester Cancer Research Centre, a unique partnership between Cancer Research UK, The Christie NHS Foundation Trust  and The University of Manchester. He is also Director of the Cancer Research UK Manchester Centre, and leads a research team at the Cancer Research UK Manchester Institute (link is external).

Professor Jones’ team are investigating networks of molecules in cells that can help drive cancer development and growth. The group are focussing on one particular network that reacts to many different signals – like growth factors – and controls key processes in cells, such as when to divide and when to self-destruct. It is hoped that understanding more about the role of this network, and how it can go wrong in cancer, will help us find new ways to treat and prevent the disease.

In January 2016, Professor Jones stepped down from the position of Cancer Research UK Chief Scientist after five years in the role. During this time, he helped shape the life-saving research we fund and how it is translated it into new treatments for patients.

Dr. Patrick Soon-Shiong a physician, surgeon and scientist, has pioneered novel therapies for both diabetes and cancer, published over 100 scientific papers, and has over 170 issued patents worldwide on groundbreaking advancements spanning myriad fields of technology and medicine.

Dr. Soon-Shiong serves as Chairman of the Chan Soon-Shiong Family Foundation and Chairman and CEO of the Chan Soon-Shiong Institute of Molecular Medicine, a non-profit medical research organization and Chairman and CEO of NantKwest, a Nasdaq listed immunotherapy company focusing on Natural Killer cells. He currently co-chairs the CEO Council for Health and Innovation at the Bipartisan Policy Center and is a member of the Global Advisory Board of Bank of America. He is an Adjunct Professor of Surgery at UCLA, and a visiting Professor at the Imperial College of London and Dartmouth College. The Friends of the National Library of Medicine has honored him with their Distinguished Medical Science Award, he was the Ellis Island Medal of Honor Award Recipient, and the recipient of the Gilda’s Club New York City Award for the Advancement of Cancer Medicine.

In 2016 he launched Cancer Moonshot 2020 a coalition of biotech, pharma, academia, community oncologists, payers and government agencies committed to accelerating next generation sequencing, proteomics, big data analytics and immunotherapy drug development for all cancer types.

Dr. Soon-Shiong performed the world’s first encapsulated human islet transplant, the first engineered islet cell transplant and the first pig to man islet cell transplant in diabetic patients. He invented and developed Abraxane, the nation’s first FDA approved protein nanoparticle albumin-bound delivery technology for the treatment of cancer. Abraxane was approved by the FDA for metastatic breast cancer in 2005, lung cancer in 2012, and pancreatic cancer in 2013. The drug is approved in the U.S. and E.U. for metastatic breast cancer, lung cancer and advanced pancreatic cancer, making it the only drug of its kind to be approved in first line therapies across this broad spectrum of tumors in both the US and EU.

From 1997 to 2010 Dr. Soon-Shiong has served as founder, Chairman and CEO of two global pharmaceutical companies, American Pharmaceutical Partners and Abraxis BioScience. Both were acquired for multi-billion dollars in 2008 and 2010. In 2011 he founded NantWorks, an ecosystem of companies to create a transformative global health information and next generation pharmaceutical development network.  In 2015 he initiated the public offering of NantKwest, setting a record when trading opened on Nasdaq as the largest biotech IPO by market cap in history. In 2016, he received the Franklin Bower Award for Business Leadership from The Franklin Institute.

Olivia Newton-John’s appeal seems to be timeless. With a career spanning more than five decades she is still a vibrant, creative individual adored by fans around the globe. Born in Cambridge, England in 1948, the youngest child of Professor Brin Newton-John and Irene, daughter of Nobel Prize winning physicist, Max Born, Olivia moved to Melbourne, Australia with her family when she was five. Her first big break was winning a talent contest on the popular TV show, “Sing, Sing, Sing,” which earned Olivia a trip to London. By the age of fifteen she had formed an all-girl group called Sol Four and, in 1963, Olivia was appearing on local daytime TV shows and weekly pop music programs in Australia. When she eventually took her prize-winning trip to London, she teamed up with her friend from Melbourne, Pat Carroll (now Farrar), to create a double act, “Pat & Olivia,” and the duo toured army bases and clubs throughout the UK and Europe. Olivia cut her first single for Decca Records in 1966, a version of Jackie DeShannon’s “Till You Say You’ll Be Mine,” and in 1971, she recorded a cover of Bob Dylan’s “If Not For You,” co-produced by Bruce Welch and fellow Aussie and friend, John Farrar, whom she continues to collaborate with today.

Olivia’s U.S. album debut, “Let Me Be There,” produced her first top ten single of the same name, with Olivia being honored by the Academy Of Country Music as Most Promising Female Vocalist and a Grammy Award as Best Country Vocalist. This proved to be only the beginning of a very exciting career. With more than 100 million albums sold, Olivia’s successes include four Grammy Awards, numerous Country Music, American Music and Peoples Choice Awards, ten #1 hits including “Physical,” which topped the charts for ten consecutive weeks, and over 15 top 10 singles. In September 2008, Billboard Magazine listed “Physical” at #6 on their Top 100 Songs Of All Time list and in 2010 listed it as “The Sexiest Song of All Time”.

In 1978, her co-starring role with John Travolta in “Grease” catapulted Olivia into super-stardom. This film’s best-selling soundtrack featured the duets “You’re The One That I Want” and “Summer Nights,” with Travolta, as well as her mega-hit, “Hopelessly Devoted To You.” To date “Grease” remains the most successful movie musical in history. Her other feature film credits include “Funny Things Happen Down Under,” “Toomorrow,” “Xanadu,” “Two Of A Kind,” “It’s My Party,” “Sordid Lives,” “Score: A Hockey Musical,” and “A Few Best Men.

Throughout her career, the much-loved star, who danced with Gene Kelly in “Xanadu,” hosted the popular internationally syndicated “Wild Life” television show, was bestowed an O.B.E. (Order Of The British Empire) by Queen Elizabeth in 1979, has held many humanitarian causes close to her heart, particularly since the birth of her daughter Chloe in 1986. Olivia was named the first Goodwill Ambassador to the United Nations Environment Programme and in 1991, served as the national spokesperson for the Children’s Health Environmental Coalition (CHEC), which was founded after the tragic death of Chloe’s best friend from a rare childhood cancer. Her devotion and shared commitment to CHEC’s (now Healthy Child, Healthy World) mission and goals enabled the organization to receive worldwide attention and support.

Her charmed life has not been without its share of upset. In the 90’s, Olivia successfully overcame her own battle with breast cancer, which inspired her self-penned and produced album, “Gaia,” her most personal album reflecting upon her experiences with cancer. She used these experiences to gain greater self-awareness and became a positive inspiration to millions of people battling cancer. As a breast cancer “thriver”, Olivia has become increasingly well known and respected for talking openly about her battle with breast cancer and for promoting public awareness of the importance of early detection. Her personal triumph over cancer led her to announce her partnership with Austin Health and the creation of the Olivia Newton-John Cancer and Wellness Centre (ONJCWC) on the Austin Campus in her hometown of Melbourne, Australia. In April 2008, Olivia led a team of fellow cancer survivors, celebrities and Olympians on a trek along the Great Wall of China and raised more than $2 million to find a new way to treat cancer and build the ONJCWC. After continuing the fundraising efforts and helping to raise nearly $200 million, the ONJCWC, opened in June 2012, and provides a comprehensive range of services and facilities for cancer treatment, education, training and research including a wellness center for the mind, body and spirit . In 2014, Olivia was thrilled when the Olivia Newton-John Cancer Research Institute opened on the grounds of the ONJCWC. The strategic co-location of research laboratories and research-training within a clinical environment enables clinicians and researchers to work together to integrate clinical medicine with basic and translational cancer research for the ultimate benefit of cancer patients.

Continuing her efforts to create breast health and cancer awareness, Olivia launched the Liv Aid ®, a breast self-examination aid that assists women to exercise breast self-exams correctly (www.Liv.com). Olivia credits her own breast self-exam as the first step to her eventual diagnosis of breast cancer. Now, 22 years later (and cancer free) she has become a passionate advocate in creating awareness for early detection and, encouraging women to take a more active role in their breast health.

Olivia continues to give back to the community generously and has been acknowledged many times by charitable and environmental organizations for her ongoing efforts, among them: the American Red Cross, the Environmental Media Association, the Women’s Guild of Cedar’s Sinai Medical Center, and the Rainforest Alliance and Concept Cure. In 1992 she created National Tree Day, which is responsible for planting more than 10 million trees in Australia. Most recently she co-founded One Tree, One Child, an international school initiative with the goal of having every child under the age of ten plant at least one tree.

In the new millennium, her international recognition has continued to grow. She was invited by the Vatican on behalf of Pope John Paul II to perform at the “Jubilee Celebration for the Sick and Healthcare Workers” and, she was thrilled to perform at the Opening Ceremony of the Sydney 2000 Olympics to an estimated global viewing audience of four billion people. Adding to this Olympic experience is what Olivia feels is one of her most memorable moments – the honor of carrying the Olympic Torch during the Olympic Torch Relay.

In 1983, as an entrepreneur with a desire to bring “everything Australian” to the world, she opened her first store, Koala Blue, with her friend and former singing partner, Pat Farrar.  Her passion for Australia was proven once again when Olivia and Pat launched their distinctly Australian wines under the iconic homegrown Koala Blue brand, to proudly bring the “taste of Australia” to the rest of the world in 2002. That year Olivia was also inducted into the prestigious Australian Music Hall Of Fame at the 16th Annual Aria Awards. Then, in 2006 she received the Lifetime Achievement Award, presented by friend John Travolta at the G’Day L.A. Gala.

In February 2005, along with her business partners Gregg Cave, Warwick Evans and Ruth Kalnin, Olivia opened the Gaia Retreat & Spa in Byron Bay, New South Wales, Australia, as an ideal place to renew, refresh and restore. The retreat has received numerous awards since it has opened including: the Conde Nast Traveller 2008 Readers’ Spa Award Winner for the “Favourite Overseas Hotel Spa: Australasia & South Pacific.” In 2014, Gaia also became a member of Virtuoso, the travel industry’s leading luxury network spanning over 26 countries and 9,000 travel advisors. 2014 also saw the launch of Gaia’s elite and acclaimed skin care line, “Retreatment.

In 2008, Olivia married “Amazon John” Easterling and, together they are spreading the word about the importance of preserving the Rainforest and, the health values found in the botanicals of the Amazon. They currently serve as spokespersons for the renowned wellness company TriVita and are working closely with the ACEER Organization (Amazon Center for Environmental Education and Research) to help the indigenous people of the Amazon gain ownership and title to their land. In September 2009, they also joined forces with Prince Charles’ The Prince’s Rainforest Project to further stress the global importance of preserving the Rainforest.

Also in 2010, Olivia was honored with the prestigious Medal of the Order of Australia from Governor General Quentin Bryce. In addition to starring in films and on television and writing books and music, Olivia continues to spend time in the recording studio.

Olivia released her second book, LivWise: Easy Recipes For A Healthy, Happy Life (Murdoch Books) in Australia in 2011. (Her first book, A Pig Tale, an environmentally-themed story written for children, was released in 1993.) In LivWise, Olivia explains her belief in the importance of eating a healthy diet in order to maintain wellness and balance and, Olivia’s proceeds from the sale of the book benefit the ONJCWC. I

In April 2014, Olivia began her residency at the Flamingo Las Vegas with “Summer Nights,” a musical journey through her career in movies and music. To coincide with the show, she released “Hotel Sessions” an EP collection of songs recorded in hotel rooms in Melbourne over a ten-year period with her nephew Brett Goldsmith. The CD is dedicated to her late sister Rona Newton-John, who was always supportive of Olivia and Brett working together. Due to the popularity of the Las Vegas show, Olivia’s residency has been extended through December 2016 and, a 2-CD set, “Summer Nights – Live in Las Vegas” was released.[/bios]

Q: How has cancer played a part in your life? 

[Olivia Newton-John] I had some unfortunate experiences of cancer before my own diagnosis.

My dearest friends, Nancy and Jim Tudor lost their daughter to Wilms’ tumour at a young age; she was best friends with my own daughter who was just a little girl at the time- it was devastating for all of us.

I also remember being young, and having a girl-friend who had cancer.  She took me to lunch and said, “I have the big C.”  Even 35 years ago, it was something people didn’t talk about openly, it was very feared.

Cancer is something I’d always grown up being fearful of, and the same week I received my own cancer diagnosis, my father died of liver cancer.   Since then, I lost my sister 3 years ago to brain cancer.

Like so many, I’ve lost many of my closest friends and family to cancer.

Q: How did you feel when you were first diagnosed?

[Olivia Newton-John] When I was first diagnosed with cancer, I started laughing with disbelief… My father had just died of cancer that week, I was supposed to go on tour, and I now I was facing this diagnosis too.   At the beginning, I was stunned and tried to make light of the situation to cope, but the tears came later.

As soon as I started going through testing and staging, the dread set in.  That was the time I had to make a decision to be positive; I had a child to take care of and couldn’t afford to not be positive.

Q: What is cancer?

[Dr. Christopher Wild] Cancer at its most basic level, is a disease where normal cells of the body start to grow in an unregulated fashion.

Once they grow beyond a certain point, these cells start to invade adjacent and it’s that invasiveness which causes the eventual spread of cancer throughout the body, to other organs, leading to the breakdown of the function of those organs and… eventually…to the death of the patient.

[Prof. Nic Jones] At the simplest level, cancer is a disease that involves normal cells being changed in terms of their behaviour. Cancer causes cells to become unregulated, they divide when they’re not supposed to divide and- as a result of this- they grow in an uncontrolled way, forming tumours. These tumours can cause problems locally where they arise, invading surrounding tissue- and they can also spread to other parts of the body. In terms of people dying from cancer, it’s usually due to the metastasis- the spread that occurs. Once that happens, it’s extremely difficult to treat successfully.

Over the past few years, we have also learned that cancer is a very complex genetic disease. This uncontrolled behaviour of cancer cells versus normal cells is due to changes in certain genes present within the cell. These genes control how cells respond to signals, how they divide, and more. By mutating and changing these regulatory genes, we see the abnormal behaviours we associate with cancer cells.

We now know an awful lot about cancer and what causes it. This has given us the foundation on which we build the promise of more successful future treatments.

Q: Do we really understand the causes of cancer?

[Dr. Christopher Wild] We can think of understanding the causes of cancer at two levels: what changes cause a normal cell to become cancerous and what are the risk factors which lead to those changes.

We certainly understand a lot more about the underlying mechanisms of how cancer develops- – the molecular changes in cells as they grow in an unregulated fashion- and how they become invasive. The last few years have seen unprecedented advances in these areas of fundamental knowledge.

At the same time, over the last four or five decades, we have learned a tremendous amount about the factors in the environment, lifestyle and genetics which can provoke some of those molecular changes. Smoking is predominant in its contribution to total cancer burden worldwide, but other major risk factors are often underestimated, such as include chronic infections. For example, about 1 in 6 cancers worldwide (and 1 in 3 in Sub Saharan Africa) are linked to infections of one type or another. There are other important risk factors including radiation, sunlight, alcohol, environmental contaminants and now- increasingly- obesity and a lack of exercise. You also have occupational exposures to chemical processes which can represent an increased cancer risk.

Q: What are the most significant cancers?

[Dr. Christopher Wild] The answer to that question really depends on where you live. In the high income countries we see a predominance of lung cancer and other cancers associated with tobacco such as oesophagus, throat, bladder and so on. We also see a huge number of breast, prostate and colorectal cancers. For some of these, prostate and colon cancer being prime examples, we really still don’t understand the major causes although different aspects of lifestyle are suspected to be important..

In the developing world, we see really high incidences of cancers of the liver, stomach and cervix for example. Despite the limitations on treatments in these regions for these cancers there are some hopeful messages in that there are effective vaccines against Hepatitis B as a cause of liver cancer and human papillomavirus as a cause of cervical and some other cancers. There are also excellent approaches for the early detection and treatment of cervical and breast cancers, for example.

Q: What is the social and economic burden of cancer in the world?

[Dr. Christopher Wild] It’s a very difficult calculation to make. The raw numbers state that currently around 12.5 million people are diagnosed with cancer, and around 7.5 million will die from the disease. The bad news is that in 20 years time, those numbers are going to be a lot higher- we predict that in two decades time over 21 million people will be diagnosed with cancer and over 13 million will die – each and every year. These increases are based only on the effects of an aging population and there being more people in the world The economic burden of treating and caring for such numbers of people is a huge one, felt especially keenly in countries where resources are limited.

So just in numbers, you can see the huge burden of this disease worldwide. On top of that you have the social and emotional impact of the disease which is even more difficult to measure but felt heavily at a personal level across society. In many developing countries cancers occur in relatively young people, parents of young children, and the hardship that places on the family is devastating.

Q: Why do you want to fight cancer?

[Dr. Patrick Soon-Shiong] I’ve always been frustrated, from a scientific perspective, that we’re going down the wrong-paths in our war against cancer.  The evidence I was seeing personally through patients I’ve been involved with treating showed me that there was a huge opportunity in winning this war.

We have patients alive 9 years out now who have metastatic pancreatic cancer.  We have patients alive 10 years out with non-hodgkins lymphoma.  We have patients alive 9 years out with metastatic Ewing’s sarcoma.  We have patients alive 10 years out with metastatic colon cancer.

The fact that we’re seeing these patients alive tells us that we need to widely adopt and validate the work we’re doing.

The science of genome sequencing has taught us that every human cancer is unique to itself, and that means we have to work together as a planet to fight this war.

Q: Why has cancer been so hard to fight? 

[Dr. Patrick Soon-Shiong] Cancer has been hard to fight not just because it’s complex, but because we’ve made some wrong-assumptions about it from the start, meaning that many of our avenues of research and treatment haven’t worked.

We now have the chance to re-evaluate the assumptions we’ve made about cancer, and with the benefit of new information about the complexity and heterogeneity we now know we’ve been pursuing the wrong path.

Q: Why is now the right time for us to fight cancer?

[Dr. Patrick Soon-Shiong] For the first time in history, we have a convergence that’s allowing us to direct our fight against cancer.  Technology has converged with insights from Biology which, in turn has allowed us to create drugs that can activate the immune system.

Technology now allows us to analyse the human genome with a high-throughput, something which we simply could not do before.  We’ve been able to get down to the ‘transcriptor,’ and work with DNA at the protein level.

When you get down to the protein, you can get down to the peptide and eventually down to the level of 10^-18 moles of molecules, showing us how molecules interact with the surface of tissue.  At this level, drugs have real interaction.

Convergence has allowed us to cross the boundaries of scale and technology has generated huge amounts of data.  The convergence of supercomputing and machine-learning is allowing us to generate new insights and has in fact taught us that we can’t kill cancer without activating the immune system.

The whole understanding of the human immune system from the killer-cell to the dendritic cell, T-Cell and so on has converged to be available at one point in time, now.

The knowledge that we’ve been going down the wrong path, the convergence of our understanding of cancer, and our own immune system and the access to technology to do something with this knowledge is the basis of the Cancer Moonshot.

Q: Why has cancer and the fight against it become so culturally significant versus other diseases?

[Dr. Christopher Wild] First, the sheer numbers and the visible presence of the disease…. everybody knows somebody affected by cancer. At the same time it can seem to strike randomly without an obvious reason.

I say to the staff in our Agency that while we’re predominantly doing research… and so on one level we’re professionals studying cancer , at the same time none of us have been untouched by this disease in our own lives.

Second, when you don’t understand something- and when it seems to strike randomly- there’s a fear associated with that. cancer has been seen previously as a death sentence because treatments were so often ineffective.

Those factors,- the scale and lack of understanding- give cancer that aura. However, knowledge and openness have evolved and changed a lot in the developed countries over the last two to three decades. In contrast, in the developing world , a lot of those original fears and lack of understanding persist and still need to be addressed.

Q: Do you see differences in the types of cancer and attitudes towards the diseases in the developed vs. developing world?

[Dr. Christopher Wild] The types of cancers are quite different, as I mentioned earlier, but also the occurrence of cancer is increasing most rapidly in the developing world. In addition, in these same countries cancer often affects younger people, those who are at the heart of their family- providing income.

Since cancer is mainly a disease of ageing- you found (sadly) that people in the past died of other things first, particularly infectious diseases. As the life expectancy in the developing world is increasing so unfortunately the incidence of cancer is increasing as well. Those developing countries are only just now becoming more aware of this double-burden they will increasingly carry of both infectious and chronic diseases.

In the very few surveys we do have in developing countries- it’s clear that there is also a lot less understanding about cancer in the average person in the street. It’s still most often seen as a hopeless situation- a death sentence. This is something which is now different in the more developed high income countries.

Q: Are there any differences in cancer between ethnicities?

[Dr. Christopher Wild] What we see very clearly are differences in the rates and types of cancer geographically. If you go to Sub Saharan Africa and South East Asia you see a lot of cancers of the liver , stomach , oesophagus and cervix – often associated with chronic infections.

In the Western countries- , North America and Europe you see a lot of cancers of the lung, colorectal and breast with a mix of these two patterns in countries in a process of economic and social transition.

Those are very striking patterns but seem to be associated mainly with differences in risk factors. In general the differences between ethnic groups within a population are much smaller and where there are differences, for example in prostate cancer rates between different ethnic groups in the USA, it’s unclear how much this is due to shared environments or shared genes. However there are some individuals at a particularly high risk because they have inherited a specific form of a gene that predisposes to cancer.

The overwhelming message , however, is that it’s lifestyle and environment that drives the risk rather than the ethnic make-up of the population.

Q: Is cancer a modern-world disease?

[Dr. Christopher Wild] Cancer has probably always been there…

Nevertheless, there are some important developments in the modern world which mean that cancer is a greater burden than ever before. Firstly, life expectancy is increasing and cancer is predominantly a disease of old age- Secondly, many risk factors were introduced in the modern world! Smoking, obesity, lack of exercise, occupational exposures… these are all things we’ve introduced with a more western lifestyle.

In contrast, not all risk factors are new, in Sub Saharan Africa and parts of Asia many cancers are linked to an infection- and those infections are not new.

Therefore there have always been cancers but due to ageing, changing lifestyles, changing environments and population growth – we are seeing more people suffering the disease.

Q What are the biggest challenges and opportunities in cancer detection?

[Dr. Christopher Wild] One of the major challenges we have is that cancer is often detected so late and one of the biggest opportunities therefore is to move this detection forward….
Because of the way cancer develops, through the multiplication of cells- the cancer has reached a large percentage of its final size before it’s detected – meaning that you don’t see it until it’s well-advanced… unless you really make an effort to look for it. In the developing world, most cancers are detected at a very late stage- often when they have spread to other organs in the body, making it very difficult to treat.

The fact that this disease takes such a long time to develop also gives us opportunities through screening and other approaches to catch it sooner. Technologies in molecular testing and imaging have certainly played an important role in the earlier detection of cancer…

The other important factor is an awareness of the disease- with people understanding some of the signs of early stage cancer. This awareness extends to the medical services and health professionals who must be alert and responsive to the disease and it’s early symptoms.

[Prof. Nic Jones] If we are ever going to make an impact in reducing deaths from cancer, we have to do more to diagnose cancer at an earlier stage.

We can split diagnosis into two parts. Firstly is how we affect the behaviour of people. We need people to recognise the symptoms of cancer and do something about it. They shouldn’t be scared to go to their GP, but should get checked out. We need to be educating people as to what the signs of cancer are, and give them confidence to get checked. In most cases, everything is fine- in some cases, it’s an early sign of cancer. People must understand that the sooner we detect cancer, the better the chances of recovery and cure are. Equally we must educate GPs in terms of recognising the signs and transferring patients on to specialists at an earlier stage. This is tough- it’s very difficult to change people’s behavioural patterns- but we are making inroads. Tobacco control has been hugely successful in changing people’s behaviour towards tobacco…

The second area is how we identify- for example- blood borne markers as signs of early cancers. That’s a big area of research we need to invest in more. We tend to invest more in therapeutics than diagnosis, and I feel that balance has to change somewhat. Globally, we need to invest more into early diagnosis- creating accurate, sensitive blood borne tests.

Q: What does it mean to ‘win the war’ against cancer? 

[Dr. Patrick Soon-Shiong] Just look at HIV/AIDS, we’ve not ‘won the war’ on HIV yet we have.  People are living with HIV/AIDS and are not dying of HIV.  People could soon live with chronic Hepatitis, but not die of hepatitis.

The opportunity to have cancer, but not die of cancer is real.

If you want to call this a cure, maybe you can- but the opportunity to have cancer but not die of the disease is a huge opportunity which will impact millions, and millions of lives.

The most important thing when fighting cancer is to make sure that we give patients a good quality of life through their treatment, and allow them to live as long, and as fully as we can.

Q: How do you enable collaboration in the war against cancer?

[Dr. Patrick Soon-Shiong] Collaboration comes with great difficulty, but it’s happening.

There’s a common vision that stakeholders have, and when we can provide the infrastructure and knowledge base- people see that they’re better together than apart.

There will always be leaders and followers in any collaborative ecosystem, and what’s exciting for us is that we now have our leaders, and the followers will follow.

Involving the patient is important, just look at HIV.  A large element of progress was because the patients fought for it, and the same will happen with cancer.  Let me give you a practical example… You could ask your oncologist today if they use Taxol and Nystatin and they will no doubt say yes.  These drugs are the ‘asprins of oncology.’  We know however, that these drugs have fairly severe side-effects.  We also know that inside the cancer tissue there are protein biomarkers that can tell us whether a patient is resistant to Taxol, Nystatin or other drugs.  How do we give Taxol or Nystatin today? We guess.  We have no idea which patient has the protein marker that’s resistant or sensitive.  We give the drug, we wait and see.  It’s trial and error.

With GPS (Genomic Proteomic Spectrometry) cancer, we can literally measure at a quantitative level, the presence or absence of biomarkers that reveal the sensitivity or resistance to Taxol or Nystatin.  We could know that fact before treatment.

Oncologists need to learn to be like infectious disease specialists.  You wouldn’t give an antibiotic without testing whether the patient is sensitive to it… yet with something as lethal and toxic as a chemical poison, we just give it blindly and rely on trial and error.

Q: What are the biggest challenges and opportunities in the field of cancer treatment?

[Dr. Christopher Wild] The biggest challenge is the heterogeneity of the disease. We’re speaking about ‘cancer’ but you can develop cancer in virtually any organ of the body, and each of those cancers may have quite distinct underlying molecular changes. This means that each cancer will respond differently to treatment, and is the reason why some patients respond well to a specific treatment while others don’t.

In the past there was very little understanding of why this heterogeneity in response existed. What’s exciting now is that as more is understood about the underlying molecular changes, it’s becoming possible- for the first time- to speak about the particular characteristics of this cancer and this patient, leading to the possibility of so-called “stratified medicine” or “personalized medicine”.

There are some areas of particular promise here. If you look at breast cancer or melanoma- drugs are being tailored to a sub-type of the cancer based on a particular genetic change.
It is important though to maintain an international perspective – as these very sophisticated treatments are only available in rich countries. In the low income countries, many patients still have no access to standard cancer treatment and too many do not even have access to basic pain relief let alone palliative care. This is truly unacceptable. We have to ensure that people have access to treatments, and equity of access. That’s something which is desperately lacking globally.

On top of this, if we consider that the burden of cancer may nearly double over the next two decades; we cannot hope to solve that problem by incremental improvements in treatment alone. This is really the biggest challenge to cancer treatment; that is just can’t solve the impending problem. Therefore we absolutely must scale up in unprecedented fashion a commitment to prevention and early detection. To me, this is where there is an almighty imbalance in our efforts globally- as a society- in our current approach to tackle cancer.
One of the lessons is that it’s very difficult to change individual behaviours. Look at the example of the fight to get people to stop smoking…. I remember when I started research I assumed that if you gave people information, they would act on that and avoid harmful exposures. However, you come to realise that the biggest impacts have been policy decisions around banning advertising and increasing taxes. If you increase the cost of a packet of cigarettes you reduce consumption. When we’re thinking about newer problems such as with obesity and physical inactivity… we have to realise it’s not just an individual choice, but a problem with the structure of our societies and cities.

The predominant investment over the last 30-40 years has been to fight the disease… by curing patients. But from now on there has to be a far greater emphasis on prevention, with innovative and integrated initiatives across different sectors of society and government.

[Prof. Nic Jones] The more we learn and understand cancer, the more we realise how complex it is. We knew that cancer was not a ‘single‘ type of disease, but the level of complexity we now see in cancer is mind-boggling. The types of genetic changes that can give rise to cancer are varied, and differ enormously from one patient to the next. Right now we use a one-size-fits-all treatment regime- and that’s not going to be suitable in the future. We increasingly have to tailor treatment for the individuals themselves based on the genetic characteristics of their tumour. This personalised medicine approach is exciting, beginning to happen, and gives us a lot of optimism for the future.

We also face a big issue of cancer not being a static disease. The genetic changes one sees within a cancer continue as the disease evolves- it’s dynamic. We are treating a disease which is constantly changing its genetics, and we have to respond to those changes in the treatment regime we apply- otherwise resistance to chemotherapy and even targeted therapy- can develop rapidly and efficiently. Our aim is to stay one step ahead of the cancer.

There is a similar situation in radiotherapy, which is used to treat around 50% of all cancer patients. The current approach is somewhat of a one-size-fits-all regime, but we now know that patients, and tumours themselves, have different sensitivities to radiation treatment- depending on those genetic changes. We need to understand how a particular tumour or patient will respond to a particular dose of radiotherapy- this will allow every patient to get the optimal dose of radiation for treatment. Personalisation doesn’t therefore just apply to drugs.
There has been some discussion about the relationship between stem-cells and cancer. Much of this actually centres around the origin of cancer. There is a body of work that suggests that stem-cells are more likely to be the cell of origin of particular cancers- giving rise to the changes that cause mutations and behaviours that cancer cells have. That could well be…. and some evidence suggests that stem-cells or stem-like cells are inherently more resistant to some types of treatment. It’s a very interesting area, and one that has a lot of validity.

Q: What has been the impact of computing on the fight against cancer?

[Prof. Nic Jones] The great thing about being in science and research is that it’s very open. We publish our results quickly, and that information is then available for the whole research world to digest, explore, repeat and so on. It’s a very important aspect of science. The internet has helped this enormously, we now have incredible access to data and studies- we can communicate better as individuals and organisations- and can collaborate more effectively, and build consortiums.

If you look at the genetics of cancer, a lot of information is coming out of huge international consortiums working together on a common goal. The data coming out of this kind of work is put on the internet live, you almost have instant-access to the data from these big sequencing endeavours.

Computer science is hugely important in cancer research. We have a mind-boggling amount of data, and it takes very complex bioinformatics and computer modelling to really make sense of it.

Q: How do institutions choose ‘which‘ cancers to prioritise?

[Prof. Nic Jones] This is a question which we have been looking at in some detail.
We certainly look at the clinical need… there are certain cancers such as lung, pancreatic, oesophageal and brain where- relative to some other cancers such as breast, leukaemia and lymphoma- the research spend has been low, even though the clinical need is huge. If one looks at survival in these cancers I’ve mentioned, it’s extremely poor compared to breast cancer where 80% of women survive 5 years or more. In lung and pancreatic cancers, you’re in the single numbers. One good way of doing it is to look at the clinical need and the level of research spend. You quickly then find many devastating cancers which clearly do need more investment. This is not just an opportunity, but a real need to invest for the future.

Q: Are there any key ethical debates emerging from the fight against cancer?

[Prof. Nic Jones] There has been some debate about the fact that many treatments extend life, but often only for a short time, and with a quality of life which is not necessarily good. And these treatments cost a lot of money. There is an ethical dilemma that arises in this sense in terms of the fact that we have a fixed pot of money for healthcare in the country, and it must be spent effectively.

Thankfully, I don’t have to answer these questions- but organisations like NICE make recommendations after taking into account the clinical benefit of treatments, and the cost to the healthcare system. These are tremendously difficult decisions, as no matter what is decided- there will be people who feel it’s the wrong decision. These issues cannot be addressed by clinicians or researchers, it has to be done by a committee with the range of expertise to simultaneously consider all aspects.

Q: What is the role of policy makers, academics and business in the fight against cancer?

[Dr. Christopher Wild] One really exciting development was the United Nations high-level meeting (of heads of state and government) discussing non-communicable diseases. This took place in New York in September last year. It’s only the second time that the UN, at the level of the General Assembly, has discussed a health issue. The last time was for HIV/AIDS. A political declaration on the control of non-communicable diseases, including cancer came from that meeting.

The encouraging thing about this is that policy makers and now seeing cancer and other chronic diseases such as diabetes and cardiovascular disease- as health problems worldwide, not just in the richer countries.

This context provides an excellent political momentum for many players to work together towards cancer control.

When we think about how to tackle cancer specifically- there is a very natural co-operation between academics and the drug companies to try and develop new treatments. There are opportunities there to ‘get a return on your investment!’. There is far less money to be made in prevention although the savings for governments are remarkable…

So while there is a natural market and drive to develop treatments using that natural public-private partnership It is down to governments and non-profit organizations to step-in to really make an effort on investing in prevention. There’s less immediate profit in that area, but it will save society a huge amount of money if we can prevent the disease rather than having to treat it.

Q: What is the role of education in the fight against cancer?

[Dr. Christopher Wild] Education to build awareness of cancer and remove the fear of it is very important.

Those educated people are also the people who- in the future- will drive governments to fund more cancer research, and demand emphasis on prevention. Having awareness of the disease can therefore have broader benefits in terms of support for change.

In terms of a professional setting, we need to understand more about the causes of the disease, and then we must invest in understanding how that knowledge can be translated to prevention and put into practice. To give you an example, for many years we had an effective Hepatitis B vaccine- this disease is a major cause of liver cancer – but It took years to get that vaccine to the children who are most in need of it – in the developing world (because of a wide range of financial and health-systems barriers). How do you get a vaccine into rural areas of Africa? How do you establish a cold-chain to maintain the vaccine in good condition? How do you have trained people to deliver the vaccine? How do you educate the population to remove fear of what is being injected into their children? These types of question have to be mainstream for the future of cancer research

For me, research is not just about understanding the causes and demonstrating prevention strategies- we need perform research into how we implement that information. It is through this route that we will see the public health benefits.

Q: What has been the role of philanthropy in the fight against cancer?

[Prof. Nic Jones] In the UK, philanthropy has been absolutely essential. The majority of cancer research is funded through charities. One can discuss and debate whether it should be that way around, whether charitable donations to cancer should be on the back of massive investment by government… but the fact is that without cancer charities and the work they do, progress in fighting cancer would be diminished. The UK public has been incredible in terms of their support for their cancer effort- far greater than most countries I know of. 1 in 3 people get cancer, that’s not just true in the UK, but around the world.

Cancer is the number one fear for the British public, and it’s not surprising. It can hit anybody, rich or poor, regardless of ethnicity. There are no boundaries. As we live longer, the incidence of cancer is going-up- even though our fight is successful and we are treating more cancer. This naturally makes cancer a part of culture, and it’s not surprising that when asked to support our efforts against this disease- people relate to it and want to help.

The fight against cancer is really for the next generation- our children, our grandchildren. We want to make the world a better place for them.

[Dr. Patrick Soon-Shiong] Philanthropy plays a key role in the fight against cancer, as do the public and private sectors.    We need to have the private sector, philanthropy and government to work together if we’re going to have effective outcomes in this fight.

We have to be very careful with philanthropy and government grants however, as there’s a tendency to duplicate- with organisations going down similar paths.  What we need is collaboration and efficiency across stakeholders and borders.

The fight against cancer is global, we have organisations in the United Kingdom, Canada, Israel, India and many other places who are joining the ‘moonshot.’

Q: How will the future cancer treatments differ from those we have today?

[Dr. Patrick Soon-Shiong] The arsenal of treatments we have today can, and should be used, because they are useful.  The arsenal has previously been used blindly.  If we do a GPS test and find the patient has great sensitivity to Taxol for example, it allows us to make intelligent decisions about dosage rather than giving it blindly.

The combination of old and new, and more information, is how the future of cancer treatments will differ.

Q: How close are we to having a world where cancer is a chronic disease?

[Dr. Patrick Soon-Shiong] As I speak to you today, we’re gathered in Chicago, and we’re about to announce working groups on breast cancer, lung cancer, paediatric cancer, melanoma, sarcoma and more.

We’re at war, and we’ve now orchestrated the tools, teams and assets.

All we need to do now is validate our thinking.

Q: What have been the biggest milestones of the past 50 years in our understanding of cancer?

[Dr. Christopher Wild] Without doubt, to my mind, it was the epidemiological demonstration that the majority of human cancers are caused by environmental and lifestyle risk factors. This understanding opened the door to informed prevention. The classic studies were those of migrant populations, geographic variations in incidence and also changes over relatively short time periods. For example, when Japanese populations moved to the USA, within one or two generations they took on the cancer patterns of the USA – that’s clearly not a genetically driven change, it’s a lifestyle and environment change. Rapid changes over time were observed for lung cancer which went from being a very rare disease to being the most common type of cancer. Eventually it was identified that this was due to the habit of smoking cigarettes. Discoveries like this give great hope for our better understanding of this disease and its prevention and it is for this reason I select it as the biggest milestone.

During this period, we have also gained a phenomenal understanding of the underlying structure and changes in cancer cells-. When I studied for my PhD some 30 years ago, we were looking at environmental chemicals and cancer but we didn’t know what part of the DNA those chemicals were damaging in order to provoke cancer. Now we know exactly which genes are damaged, how genes change as the tumour grows, and how chemicals interact with DNA. That’s also been a major step forward and gives hope in two directions. Firstly, it allows us to tailor drugs to specific types of tumour- but we can also learn what caused the changes we see in the tumour. If you are exposed to sunlight or a chemical pollutant- you will see different genetic changes in cells. The risk factor leaves an imprint in the cancer itself. This should provide new clues to causes and prevention.

Q: Is there a role for complimentary medicine in cancer treatment and care?

[Dr. Christopher Wild] We should demand rigorous scientific evaluation of any proposed therapies be they traditional or complimentary treatments.

There is certainly a need to understand that as an individual facing cancer, we each look for different ways to cope- and these methods are not always medical. This has been a very important advance- understanding that the patient needs broad support- psychological and emotional as well as medical. That’s helping people to face, on an individual level- this disease and the impact it has on them and their families.

Q: Do you think we will ever cure cancer?

[Dr. Christopher Wild] If we look back at what’s been achieved in recent years, there have been huge steps forward in the treatment of a number of cancers. This has been in very specific areas such as childhood cancers, breast cancer and testicular cancer- where cure rates and survival are very high. There is hope for more to come in terms of refining treatments
However, if we’re facing twice as many cancers worldwide in 20 years time, it’s hard to imagine curing all these patients. Vision and leadership is needed now to focus efforts on prevention.

[Prof. Nic Jones] If you take the very long term view? I think we will!

Pragmatically, what will happen over the next 20 to 30 years, is that some cancers will be cured- and many will be controlled- in the same way we control diabetes… we don’t cure diabetes, we control it.

The ultimate goal has to be curing all cancers, and as much as that vision is a long-way away- it cannot be discarded. Now however, we have three key ways we can make impact:
diagnosing cancer earlier, and preventing cancers occurring in the same place by changing behaviours, environment and so on.

Having better treatments that will keep cancer at bay and will control the disease for significant periods of time

Having treatments that do, where we can, cure cancer.

In many ways, if we prevent a lot of cancer- that’s fantastic… if we control it and not necessarily cure it- that’s great as well- but in some cases, we will cure it too.

Q: What was the role of wellness in your recovery journey? 

[Olivia Newton-John] When I got the diagnosis, one thing I was really afraid of, and didn’t want to do, was chemotherapy.  It was something that frightened me; I’d seen the effects of it on other people and I didn’t want to do it.

My doctor decided to do surgery first to remove the lump, and I ended-up having a mastectomy.  At the time they didn’t think I had to do chemotherapy, and so told me not to worry about it.  After the surgery however, it turned out I had to do a 6 month round of chemo, which turned into 9 months due to how my body’s reaction to it.  I was very resistant to this, and investigated all-sorts of other options, but in the end it was one of my friends who took me to one side and said, ‘why would you not do chemo? You have to do everything you can, you have a daughter to look after!’ so I decided to do the chemo, but do as much as I could outside that to support my body too.

I went on a macrobiotic diet, I had massage and acupuncture after my treatments to cope with the pain and nausea, I was taking herbs and homeopathic treatments too to boost my immune system and well-being.

Protecting and strengthening my mental health was an important part of my journey too.  I was introduced to Deepak Chopra by another woman who had gone through cancer and he introduced me to mindfulness and TM (Transcendental Meditation).  Mindfulness was a huge part of my healing, and he also taught me the importance of doing things like listening to music, and enjoying arts to calm my mind.  Spirituality is a big part of my life.  I chant with my Buddhist friends, I pray with my Christian friends, and I have my own journey too.

I knew that keeping my mind positive had a huge role to play in my recovery.  I have always believed that illness is connected to emotions.  I remember going to see a Sikh friend of mine who is also a doctor, and a deeply spiritual individual.  He connected a lot of alternate therapies and techniques with conventional medicine, and also with mindfulness and other practices and that became important to me.   I also listened to a lot of tapes by Louise Hay in the mornings which helped me start my day positively.

It was my own journey of wellness during my cancer treatment that become a passion, that eventually led to giving my name to a wellness centre at a major cancer hospital in Melbourne, Australia.  To read ‘cancer and wellness’ is a very positive thing, whereas if it’s just a ‘cancer centre’ the connotation could be rather different.

Putting cancer and wellness together gives people hope.

Q: How has the medical profession embraced ‘wellness’ as a wider part of the cancer journey?

[Olivia Newton-John] Initially, there was resistance within the hospital to the wider world of wellness.  The Austin Hospital in Heidelberg, Melbourne is a government run hospital and wellness was a new and creative concept for public health.

As time has passed, the hospital has become more understanding and sympathetic towards wellness, and as they’ve started to see the tangible benefits in patient outcomes, they’ve started to embrace it and really grow those programmes.

The wellness centre connects patients not only with their own journeys, but with other patients, their families and with the doctors themselves.  It helps people stay positive, and lets them do things like art therapy, meditation, yoga, acupuncture, music therapy, group therapy and more.

It’s important to remember though, that philanthropy is absolutely key in these projects which are usually not publicly funded.

Q: What would be your message to others going through their own cancer journey?

[Olivia Newton-John] For people who are going through their own cancer journey, it’s important to realise that treatments have become somewhat kinder, and we’re on the verge of getting treatments such as immunotherapy which allow our own immune systems to fight cancer.

It’s hugely important to keep your mind and body strong.  You have to find something you love to do every day, and instead of talking about cancer with your friends and family have someone else answer those questions and give people those updates so you can concentrate on healing.

I had a girl-friend who called me, and when I told her what was going on she started crying.  That was frightening; it made me scared for myself.   You need to surround yourself with positive people and let someone else answer those questions and concerns about your cancer so you can focus on things you love like taking a walk, exercising, watching a sunset, spending time with your family and all those things.

My dream is that the word cancer is removed from cancer hospitals, and they become wellness centres.  How remarkable would that be?


When we speak of our “fight against cancer” we liken it to a battle against an enemy- in effect, we humanise it.

People conceive of wrathful gods, fickle computers, and selfish genes, attributing human characteristics to a variety of supernatural, technological, and biological agents. This tendency to anthropomorphize nonhuman agents figures prominently in domains ranging from religion to marketing to computer science. Perceiving an agent to be humanlike has important implications for whether the agent is capable of social influence, accountable for its actions, and worthy of moral care and consideration.” (‘Social Cognition Unbound : Insights Into Anthropomorphism and Dehumanization‘ – Waytz, Epley, Cacioppo – 2010)

Where cancer is concerned, the need to perceive it as humanlike is important. This is a disease from within ourselves, a disease that is unique to each individual. In effect, my cancer will be different to yours. The question then begs as to whether the world would mobilise billions of dollars just to fight my cancer- in truth, the answer is no. By perceiving cancer as an agent outside us, we can give it a face (albeit in abstract)- we can turn it into an enemy, and find the will to collectively declare war. A declaration by which we admit that however remote…. there is some prospect of victory.

Cancer is a symptom of being human. “…Illness is the night-side of life” wrote Susan Sontag “...a more onerous citizenship. Everyone who is born holds dual citizenship in the kingdom of the well and in the kingdom of the sick. Although we all prefer to use only the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place.” (Illness as a Metaphor, 1978)

This inevitability of illness, of diseases like cancer is a perverse darkness that draws us together and- in that desperation, brings out something beautiful about our species – our humanity.

Thought Economics

About the Author

Vikas Shah MBE DL is an entrepreneur, investor & philanthropist. He is CEO of Swiscot Group alongside being a venture-investor in a number of businesses internationally. He is a Non-Executive Board Member of the UK Government’s Department for Business, Energy & Industrial Strategy and a Non-Executive Director of the Solicitors Regulation Authority. Vikas was awarded an MBE for Services to Business and the Economy in Her Majesty the Queen’s 2018 New Year’s Honours List and in 2021 became a Deputy Lieutenant of the Greater Manchester Lieutenancy. He is an Honorary Professor of Business at The Alliance Business School, University of Manchester and Visiting Professors at the MIT Sloan Lisbon MBA.