It’s not often that a research article barrels down the straight toward its one millionth view. Thousands of biomedical papers are published every day. Despite often ardent pleas by their authors to “Look at me! Look at me!,” most of those articles won’t get much notice. Attracting attention has never been a problem for this paper though. In 2005, John Ioannidis, now at Stanford, published a paper that’s still getting about as much as attention as when it was first published. It’s one of the best summaries of the dangers of looking at a study in isolation – and other pitfalls from bias, too. But why so much interest? Well, the article argues that most published research findings are false. As you would expect, others have argued that Ioannidis’ published findings themselves are false. You may not usually find debates about statistical methods all that gripping. But stick with this one if you’ve ever been frustrated by how often today’s exciting scientific news turns into tomorrow’s de-bunking story. Ioannidis’ paper is based on statistical modeling. His calculations led him to estimate that more than 50% of published biomedical research findings with a p value of < 0.05 are likely to be false positives. We’ll come back to that, but first meet two pairs of numbers’ experts who have challenged this. Round 1 in 2007: enter Steven Goodman and Sander Greenland, then at Johns Hopkins Department of Biostatistics and UCLA respectively. They challenged particular aspects of the original analysis. And they argued we can’t yet make a reliable global estimation of false positives in biomedical research. Ioannidis wrote a rebuttal in the comments section of the original article at PLOS Medicine. Round 2 in 2013: next up are Leah Jager from the Department of Mathematics at the US Naval Academy and Jeffrey Leek from biostatistics at Johns Hopkins. They used a completely different method to look at the same question. Their conclusion: only 14% (give or take 1%) of p values in medical research are likely to be false positives, not most. Ioannidis responded. And so did other statistics heavyweights. So how much is wrong? Most, 14% or do we just not know?
A technology once used to scan silicon wafers for defects now moves through the human body scanning organs down to the level of a single cell. According to Dr. Melissa Knothe Tate, biomedical engineer and professor at University of New South Wales, this Google Maps-like technology promises to be a medical coup. Using the technology developed by German high-tech manufacturer Zeiss, Tate currently leads a project that explores osteoporosis and osteoarthritis. Just as Google Maps is able to zero in on a location and then zoom in and show the finer details, Tate is able to focus on a whole joint (the knee, say, or the hip) and then rapidly and dramatically increase the level of detail right down to the cellular level. The technology allows Tate and her colleagues to collect and analyze, with additional help from Google algorithms, terabytes of data and to accomplish in a matter of weeks what once might have taken up to 25 years. Tate's research group also uses the most advanced microscopic and MRI technologies to investigate how movement and weight bearing affects the passage of molecules within joints. Combined, these techniques help them explore the relationship between blood, bone, lymphatics, and muscle. “For the first time we have the ability to go from the whole body down to how the cells are getting their nutrition and how this is all connected,” Tate said in a press release. “This could open the door to as yet unknown new therapies and preventions.” The first researcher to use the semiconductor system in humans, Tate presented several papers on her research at the Orthopedic Research Society meeting in Las Vegas. In her research she has focused on the human hip and osteoarthritis. Specifically, in osteoarthritic guinea pigs, Tate has demonstrated a connection between molecular transport through blood, muscle, and bone, and how this is impacted by disease. Just like humans, guinea pigs develop osteoarthritis as they age. Increasingly, scientists believe this condition to result from a breakdown in cellular communication. For this reason, understanding the molecular signaling and traffic between tissues could unlock a range of treatments, including physical therapies and preventative exercise routines. “Advanced research instrumentation provides a technological platform to answer the hardest, unanswered questions in science,” Tate said. She believes this will open up “avenues for fundamental discoveries, the implications of which may be currently unfathomable, yet which will ultimately pave the way to engineer better human health and quality of life as we age.” Longer, better years of living ahead!
At Experimental Biology 2015 the Public Affairs Advisory Committee for the American Society for Biochemistry and Molecular Biology held a panel discussion titled Who Should Fund Biomedical Research? The three-member panel, which included Harvard’s Venkatesh Narayanamurti, Ph.D., offered up insights on alternatives, from private investment to crowd-funding. One common mantra was the need to get the public engaged and understand why biomedical research is so important. Moderator Benjamin Corb, director of public affairs for ASBMB suggested a change in language, for example changing the term ‘basic research’ (research that advances fundamental knowledge about the world) to ‘discovery’ or ‘foundation’ research. He noted that some Americans have said they did not support ‘basic’ research because they believed we should be doing ‘advanced’ research. Panelist Jai Ranganathan Ph.D., suggested using a model that he said NPR does well – consistently putting out interesting, quality content to cultivate an engaged audience. Ranganathan talked about crowd-funding, an idea that he helps promote through SciFund Challenge, a nonprofit that helps train scientists on how to connect to the public and create a more science engaged world. He doesn’t suggest throwing an idea on Kickstarter and expecting random people to give money – the audience has to care and in order to care they have to make a connection, so long term public outreach is essential. Ranganathan pointed out that an added benefit of crowdfunded science is that there are no strings attached. A recent paper on the nonprofit’s website was titled “Moving Beyond a Social-Networks-Only Picture of Science Crowdfunding,” and it talked about how researchers can’t expect to raise substantial or consistent funds if they only reach out to their personal networks. It promoted journalists and non-governmental organizations (NGOs) as important resources. The organization hosted its own panel discussion “Using Social Media Without Blowing Up Your Scientific Career.” Claire Pomeroy, M.D., of the Albert and Mary Lasker Foundation said there has been a 20 percent loss of the NIH-funded research budget and a growing complacency among the public that scientific breakthroughs will continue despite cuts in funding. Pomeroy cited results from a Pew research study that shows 61 percent of U.S. adults say government investment is essential for scientific progress, while 34 percent said private investment will be enough even without help from the government. Not so, said Pomeroy, while private foundations play a key role in funding, they are not able to fill the gap alone. She thinks researchers need to come together to urge increased funding from all sources, be it industry, government, academia, or philanthropy – “grow the whole pie” for funding instead of dividing it. The panelists agreed that research is a societal good, and that scientists need to do a better job at conveying both what has been accomplished and what still needs to be done. At the wrap-up each panelist was asked to describe the current state of biomedical funding in one word. The answers were telling: “poor,” “inadequate,” and “a tragedy.”
While Marty McFly from the movie Back to the Future may be disappointed by how 2015 shaped up, we can’t be so quick to dismiss the sci-fi present within the field of medicine. I remember it quite well: my family and I were watching 60 Minutes on a Sunday night. It was the summer before my senior year of high school, and like most students, I actively avoided thinking about college applications and especially my potential major. However, when the title “Growing Body Parts” appeared on the screen, I couldn’t help but find myself dumbfounded. How could someone actually grow organs from a few cells? After intently staring at the TV for that quick segment, I immediately got to researching. As a high school student, I was easily fascinated. I won awards at international science and engineering fairs because I had a great love for building machines from scratch, but even my hydroelectric turbine and plant microbial fuel cells paled in comparison to the awe manifested in those few short minutes. That same summer night, I decided that I was going to “grow body parts” or more specifically I was going to be a Biomedical Engineer. My hard-wiring for math and science was only the foundation that gave me this great revelation. For at the age of eleven years old, I was diagnosed with cystic fibrosis. Tissue engineering and regenerative medicine are changing how we approach treatments for those with diseases like cystic fibrosis. With a potential to fully heal damaged tissues and organs, regenerative medicine illuminates a new hope to those with conditions that are beyond repair. Much of the therapies present for cystic fibrosis aim to manage the condition through an arsenal of medications, but regenerative medicine has to potential to allow patients to use their own biological machinery to heal themselves within. In fact, the chronic damage accumulated by cystic fibrosis could be reversed. There is much work to be done within the field of pulmonary tissue engineering, but I am swarmed with ineffable joy because this is where my passion and determination find harmony. Sorry, Marty McFly, there are no time traveling cars to report in 2015. Instead, science is heading full speed into a realm that is even more exciting.
Research funding in many countries derives from research bodies and private organizations which distribute money for equipment and salaries. In the United Kingdom, funding bodies such as the Medical Research Council derive their assets from UK tax payers, and distribute this to institutions in a competitive manner. The Wellcome Trust is the UK's largest non-governmental source of funds for biomedical research and provides over £600 million per year in grants to scientists and funds for research centres. In the United States, the most recent data from 2003 suggest that about 94 billion dollars were provided for biomedical research in the United States. The National Institutes of Health and pharmaceutical companies collectively contribute 26.4 billion dollars and 27.0 billion dollars, respectively, which constitute 28% and 29% of the total, respectively. Other significant contributors include biotechnology companies (17.9 billion dollars, 19% of total), medical device companies (9.2 billion dollars, 10% of total), other federal sources, and state and local governments. Foundations and charities, led by the Bill and Melinda Gates Foundation, contributed about 3% of the funding. In Australia, in 2000/01 (the most recent data available), about $1.7B was spent on biomedical research, with just under half ($800M, 47%) sourced from the Commonwealth government (all sources). About $540M came from business investments/funding and a further $220M from private or not-for-profit organisations (totalling 44%). The balance was from state and local governments. Since then there has been a significant in government funding through the National Health and Medical Research Council (NHMRC), whose expenditure on research was nearly A$700 million in 2008–09. The enactment of orphan drug legislation in some countries has increased funding available to develop drugs meant to treat rare conditions, resulting in breakthroughs that previously were uneconomical to pursue.
A new paradigm to biomedical research is being termed translational research, which focuses on iterative feedback loops between the basic and clinical research domains to accelerate knowledge translation from the bedside to the bench, and back again. Medical research may involve doing research into public health, biochemistry, clinical research, microbiology, physiology, oncology, surgery and research into many other non-communicable diseases such as diabetes and cardiovascular diseases. The increased longevity of humans over the past century can be significantly attributed to advances resulting from medical research. Among the major benefits of medical research have been vaccines for measles and polio, insulin treatment for diabetes, classes of antibiotics for treating a host of maladies, medication for high blood pressure, improved treatments for AIDS, statins and other treatments for atherosclerosis, new surgical techniques such as microsurgery, and increasingly successful treatments for cancer. New, beneficial tests and treatments are expected as a result of the Human Genome Project. Many challenges remain, however, including the appearance of antibiotic resistance and the obesity epidemic.
Biomedical research (or experimental medicine) is in general simply known as medical research. It is the basic research, applied research, or translational research conducted to aid and support the development body of knowledge in the field of medicine. An important kind of medical research is clinical research, which is distinguished by the involvement of patients. Other kinds of medical research include pre-clinical research, for example on animals, and basic medical research, for example in genetics. Both clinical and pre-clinical research phases exist in the pharmaceutical industry's drug pipelines, where the clinical phase is denoted by the term clinical trial. However, only part of the whole of clinical or pre-clinical research is oriented towards a specific pharmaceutical purpose. The need for understanding, diagnostics, medical devices and non-pharmaceutical therapies means that medical research is much bigger than just trying to make new drugs.