A year ago, scientists from Imperial College in London published a paper in Cancer Research in which they reported their discovery of a strong association between the risk of breast cancer and a molecular change in a particular white blood cell gene called ATM. Looking for a chemical effect called methylation which switches genes on and off, they analysed blood samples from almost 1400 women — almost half of whom developed breast cancer between 3 and 11 years later. The researchers showed that women with the highest methylation levels in the ATM gene were twice as likely to develop cancer as those with the lowest levels.
Earlier this year, Emanuel Petricoin presented a paper at the Miami Breast Cancer Conference in which he reviewed the development of new blood tests for both the early detection and treatment of breast cancer. One of the approaches that he highlighted was a test based on unique glycoproteins that can be identified by quantitative mass spectrometry of breast tumours. The basic premise is that proteins associated with the tumour find their way into the blood stream, thus serving as a biomarker.
Perhaps one of the most promising techniques has been developed by Henri Tiedge at the State University of New York Downstate in Brooklyn. He studied regulatory ribonucleic acids (RNAs) — specifically brain cytoplasmic RNAs — that are important mediators of gene expression in nerve cells. Realising the importance of his work, Tiedge secured a US patent (7,510,832), and subsequently published his groundbreaking findings in Carcinogenesis. The RNA was expressed at high levels in invasive breast carcinomas but was not detectable in normal breast tissue or benign tumours such as fibroadenomas. Tiedge has recently been awarded a $50,000 grant to assist in commercialization of his blood test.
Although breast cancer tests based on biomarkers in the blood stream will soon be available in the clinic, they will not replace diagnostic imaging devices such as our dual-modality Aceso system. To treat a patient with breast cancer successfully, the doctor needs to know exactly where the lesion is located.]]>
The occasion yesterday was the mid-year graduation ceremony at the University of Cape Town for the faculties of engineering, health sciences and science. For the students, over fifty of whom received their doctoral degrees, this was an auspicious occasion. Their commencement was undoubtedly a day of affirmation, when all their hard work was rewarded, with five of the graduates having an affiliation with CapeRay.
Daniel Auger, who worked for CapeRay as a research engineer in 2011, earned his PhD in biomedical engineering for his work on mapping the myocardial mechanics of the right ventricle using 3D magnetic resonance imaging. Adijat ‘Wumi’ Inyang, supervised by CEO Kit Vaughan, earned her PhD for the development of a novel meniscal prosthesis for the knee based on composite materials, while Miné Zantow, mentored by CapeRay director Tania Douglas, was awarded an MSc for her thesis on the use of image analysis to determine the size and behaviour of droplets in microfluidic systems.
The guest speaker was Derek Hanekom, our country’s Minister of Science and Technology, who, in offering encouragement to the graduates, invoked the words of Mahatma Gandhi, “Live as if you were to die tomorrow. Learn as if you were to live forever.”]]>
Just published in the American Journal of Roentgenology is a paper by a group of Japanese researchers from Nagoya who studied the ability of neuroradiologists to diagnose acute cerebral infarction when viewing brain CT images. They compared a 21-inch high-resolution LCD monitor with the original iPad and concluded, “Our results show a small difference between medical-grade LCD monitors and iPad, and this is acceptable compared with past reports.” The newest iPad, with four times the resolution (2,048 x 1,536 pixels) and its Retina display, will surely mount a serious challenge to the traditional LCD monitor.
The Mayo Clinic, established in Rochester, Minnesota in 1889, is among the world’s most prestigious medical centres. They have always been at the cutting edge of medical technology — the heart-lung machine was developed there in the early 1950s — and in 2013 they have adopted Apple’s mobile devices on a grand scale. There are more than 15,000 iOS devices (iPhones and iPads) connected to the clinic’s network and in daily use by their staff who run custom in-house applications (or “apps”). One such app called Synthesis enables physicians to have instant access to patient records, including CT scans and laboratory results.
As we reported last year, at CapeRay we designed our user interface for the Soteria around an iPad. The radiographer can use gesture-based interaction — pinch to zoom, two finger panning to move the image around, and one finger sliding for contrast control — to review the captured images (see one of Soteria’s first mammograms at left). However, as emphasized by Nephosity, who recently secured FDA approval for their MobileCT Viewer, the iPad may not (yet) be used to diagnose breast cancer.
“Disruptive innovation” is a term introduced by Clayton Christensen 15 years ago in his book The Innovator’s Dilemma, describing how a product gains a foothold at the bottom of the market, moves relentlessly upward, and then finally surpasses well-entrenched competitors. Within just three years the iconic iPad would appear to be on that upward trajectory.]]>
Wits Enterprise, the commercialisation arm of the University of the Witwatersrand in Johannesburg, celebrated the achievements of its inventors and innovators earlier this week. For their inaugural event they invited CapeRay’s CEO, Kit Vaughan, to speak on the topic “Successes and Pitfalls in Commercialising University Intellectual Property.” Vaughan chose as his subtitle “Ten Lessons I Have Learned,” describing his own experience over the past three decades.
Lesson number 1 — never underestimate the value of a good patent — has its origins at Clemson University in South Carolina where Joon Park was Professor of Bioengineering. In the late 1970s orthopaedic implants were tending to loosen and Park identified the problem as the interface between the implant and the bone cement. His solution was a simple one — to pre-coat the implant with bone cement — and the university secured US Patent 4,491,987 on 8 January 1985. Clemson licensed the technology to Zimmer and in 1987 the royalty income was $750,000, half of which was paid to Park. Not bad for an idea that was pooh-poohed by his fellow academics!
Lesson number 2 — it is possible to patent and to publish your ideas — concerns the collaboration of two biochemists, Edward Sturrock from Cape Town and Ravi Acharya from Bath in England. Their research focused on the crystal structure of an angiotensin-converting enzyme (see image at left) that plays a key role in the treatment of high blood pressure. They filed their provisional patent in the UK on 12 September 2002 and it was granted in multiple countries, including US Patent 7,704,319 that issued on 27 April 2010. Sturrock and Acharya also submitted their crystal structure to Nature who published their article on 19 January 2003. Importantly, the paper had been submitted on 21 October 2002, after the priority date for their patent.
Vaughan’s other lessons included: (3) don’t try to run a company while holding down a full-time academic job; (4) it helps to have a supportive technology-transfer office; (5) take advantage of grants and government’s fund-matching programmes; (6) create a shareholders’ agreement that is simple and investor-friendly; (7) venture capital funding can be as tough as the Dragons’ Den; (8) the university can serve as the ideal feeder for your employees; (9) get your first product to market as soon as possible; and (10) for the really “Big Idea,” seek international investors.
Universities, as the beneficiaries of government funding, have an obligation to ensure their intellectual property is transferred to the public domain.]]>
In 1961 Mary-Claire King was just fifteen when she watched her best friend die of a kidney tumour. She recalls, “Her death was devastating. It seemed so unfair. It wasn’t a conscious decision, but I said to myself, something needs to be done. It’s the little pebbles that make a path.” King’s youthful determination led to a spectacular breakthrough thirty years later when she was a distinguished professor of genetics at the University of California at Berkeley.
In a seminal paper, published in Science in 1990, King and her colleagues provided evidence for the existence of the first gene for hereditary breast cancer. They showed that chromosome 17 was the locale of a gene — later named BRCA, short for BReast CAncer — for inherited susceptibility in families with early-onset disease. King’s research transformed the field, enabling the gene to be cloned and the development of a simple diagnostic test.
Earlier this week the actress Angelina Jolie wrote an op-ed piece in The New York Times, revealing that she had undergone a double mastectomy earlier this year despite the absence of breast cancer. Her mother had died of ovarian cancer at age 56 and Jolie, having been diagnosed with the faulty BRCA1 gene, decided on prophylactic surgery. Her doctors estimated she had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer. “Once I knew that this was my reality,” she said, “I decided to be proactive and to minimize the risk as much as I could.”
Jolie described in considerable detail the surgical procedures, including the subsequent reconstruction of her breasts with implants, commenting that her choice did not in any way diminish her femininity. She stated that her chances of developing breast cancer had fallen to less than 5 percent, and concluded: “Life comes with many challenges. The ones that should not scare us are the ones we can take on and take control of.”
Perhaps unsurprisingly, news of Jolie’s decision generated considerable debate. Myriad Genetics, the company that developed the diagnostic test and is now facing a legal challenge to its monopoly in the US Supreme Court, saw its stock rise after the announcement. A recent paper in the Journal of the American Medical Association has shown that prophylactic mastectomy does indeed reduce the risk significantly. It’s intriguing to think how one woman’s discovery almost a quarter of a century ago led to another woman’s decision to take control of her own destiny.]]>
Yesterday the Cancer Council in Australia announced that the country was gaining the upper hand in the war against cancer, with 60,000 lives saved over a two-decade period. They attributed their success to three factors: prevention, screening and treatment. One of the issues identified was obesity — a major risk factor for bowel and breast cancer — and the Council suggested that weight reduction programmes had contributed to the improved statistics. This begs the question: can exercise lower breast cancer risk?
In a study published last year in the Journal of Clinical Oncology, researchers from Seattle showed that women who exercised and dieted to lose a moderate amount of weight also experienced a reduction in their oestrogen levels and other hormones associated with increased breast cancer risk. They studied 439 overweight and post-menopausal women aged 50 to 75 who were sedentary, and divided them into four groups: (1) a diet group who cut out sugary beverages and desserts while increasing fruit, vegetables and fibre; (2) an exercise group who did five 45-minute aerobics classes per week; (3) a group who both dieted and engaged in brisk walking; and (4) a control group who made no change to their diet or exercise habits.
At the completion of the 12-month study, groups 1 and 3 saw the greatest benefit, having dropped an average 10% of their starting weight, and also experienced a statistically significant reduction in their oestrogen levels and other hormones. Anne McTiernan and her co-authors estimated that a 5% weight loss may reduce a woman’s breast cancer risk by 22%. Interestingly, women in group 2 who exercised but failed to lose weight did not lower their hormone levels.
Another study, just published in Cancer Epidemiology, Biomarkers & Prevention, by researchers from the University of Minnesota reported that women who exercised five times a week for 16 weeks demonstrated changes in their oestrogen metabolism. “Ours is the first study to show that aerobic exercise influences the way our bodies break down oestrogens to produce more of the ‘good’ metabolites that lower breast cancer risk,” said lead author, Mindy Kurzer.
Can the findings from these two studies be reconciled? Perhaps they can. Although exercise may not lower oestrogen levels per se, it does appear to change the break down of oestrogen and modify the metabolites that, in turn, reduce the risk of breast cancer. This is good news for women who are willing to make the effort and exercise.]]>
Sixty years ago, three Soviet scientists published a paper, in Russian, entitled “Study of electronic emission during the stripping of a layer of high polymer from glass in a vacuum.” They demonstrated that a process called triboluminescence — where relative motion between two contacting surfaces produces visible light — converts mechanical energy into electromagnetic radiation, including X-rays. As often happens in the history of science, this phenomenon lay dormant for over fifty years until 2008 when a group of physicists from the University of California at Los Angeles (UCLA) published an article in Nature entitled “Correlation between nanosecond X-ray flashes and stick-slip friction in peeling tape.”
Like all good entrepreneurs, the researchers filed a provisional patent before publication and assigned the intellectual property to their employer. Three years ago one of the inventors, Carlos Camara, formed a company called Tribogenics to commercialise the metal-polymer technology which they licensed from UCLA. Their small powerful X-ray sources are scalable and can be configured as single point emitters or clustered into flat-panel arrays of X-ray pixels that can be individually addressed. Since the fragile glass tube and high voltages have been eliminated, these X-ray sources are apparently safe to use in any environment.
So how does the technology work? According to the authors, “As the tape peels off, the sticky acrylic adhesive becomes positively charged and the polyethylene roll becomes negatively charged, so that electric fields build up to values that trigger discharges. At a reduced pressure, the discharges accelerate electrons to energies that generate Bremsstrahlung X-rays when they strike the positive side of the tape.” While there are experts like Ken Suslick at the University of Illinois who are skeptical that so much of the mechanical energy can be transformed into X-rays, Camara and his team at Tribogenics are pushing ahead regardless.
It’s an interesting thought that at some stage in the future, an experiment performed with an off-the-shelf roll of Scotch Tape mounted on ball bearings in a vacuum chamber could lead to a miniature X-ray source that will aid in the diagnosis of breast cancer.]]>
In the late 1950s researchers at ICI Pharmaceuticals in the UK were actively looking for a class of anti-oestrogen compounds, hoping to developing a morning-after contraceptive pill. Arthur Walpole and his team synthesised tamoxifen, a drug that has subsequently become the endocrine treatment most widely used in breast cancer, both in adjuvant therapy and for advanced disease. Earlier this week a paper appeared in the Journal of Clinical Oncology showing that if women who are being treated with tamoxifen see a decrease in their breast density, they have a 50% lower risk of dying from breast cancer.
The research team was led by Per Hall at the Karolinska Institutet in Sweden who followed almost a thousand patients over a 15-year period. “To the best of our knowledge, this is the first time mammographic density change has been used as a prognostic marker of response to tamoxifen,” wrote Hall and colleagues. Measuring the change in breast density could therefore be a simple and effective method for assessing whether a drug is working or not.
These findings by the groups in Connecticut and Stockholm, which are supported by a recent paper in Clinical Imaging by Vincenzo and Concetta Giuliano, suggest the need for a screening tool that incorporates both full-field digital mammography and automated breast ultrasound in a single instrument. At CapeRay we are currently building such a device — our dual-modality Aceso model — that will be clinically tested later this year.]]>
There are distinct parallels with the reality television programme Dragons’ Den that features entrepreneurs who pitch their business ideas to a panel of VCs in order to secure investment finance. The contestants are often product designers who try to convince wealthy businessmen and women — the eponymous “dragons” — to invest money in exchange for a percentage of the company’s shares. The dragons ask probing questions and, more often than not, the entrepreneur walks away empty-handed. The format is clearly successful as there are now two-dozen versions of the programme around the world.
At the Dublin meeting there were 43 companies pitching their investment opportunity to 32 VC and private equity firms. Each of us had just ten minutes to make our case, to explore the answers to questions such as: What is the problem we are solving? What are the benefits of our solution? How large is the market opportunity? The format differed from Dragons’ Den in that the VC firms initiated their due diligence after our presentations in one-on-one meetings rather than during the plenary session. Much less stressful!
This was an international event with start-up companies like Calon Cardio from Wales, FBC Device from Denmark and Aerogen from Ireland. The VC firms also covered a wide geographic area, with Abingworth from the UK, Gilde from the Netherlands and Lighthouse from the USA. CapeRay was one of three diagnostic imaging companies represented, while there were two other companies with novel breast cancer products. Chronix from California has developed a real-time diagnostic blood test that is used by the oncologist during treatment, and MitaMed from Ireland utilises an energy-based technology called electroporation to treat solid tumours.
Was this a successful event for CapeRay? Simply stated, “Yes”. We have initiated discussions with potential investors and partners and, most importantly, we learned a great deal about the VC landscape.]]>
Securing regulatory approval from the FDA is the sine qua non for any medical device company that seeks to market and sell its products in the USA. There are two approaches by which this approval can be achieved: pre-market approval (PMA), a sometimes lengthy process requiring extensive clinical trials; and the so-called 510(k) approach, where a company’s new product needs to demonstrate equivalence to a predicate device.
In justifying the increase in the CDHR’s budget, the agency has set some performance benchmarks for itself, with the aim of reviewing and deciding on 80% of PMA applications within 180 days of filing and 93% of 510(k) submissions within 90 days. This is good news for companies like CapeRay that need to release their products into the market within a reasonable time period.
“These are tight budget times, and the FDA budget request reflects this reality,” said the FDA Commissioner, Margaret Hamburg. “Our budget increases are targeted at strategic areas that will benefit patients and consumers and overall strengthen our economy. Through the good work of the FDA, Americans will receive life-saving medicines and devices approved as fast as or faster than anywhere in the world, confident in the medical products they rely on daily.”
The FDA’s history is an interesting one, dating back to the late 19th century, in the period after the Civil War. A landmark piece of legislation that launched the agency was the Pure Food and Drug Act of 1906, prohibiting interstate commerce in misbranded and adulterated food and drugs. For over a century the FDA has sought to balance the need to protect the American consumer, on the one hand, with the desire of those same consumers to have access to the latest and most innovative medical technologies.]]>