In course three, we briefly touched on the idea of business in biology. In particular, we talked about how economics and smart business decisions influence ecology and conservation decisions. We also talked in course one about how non-science factors influence the process of science. And money and business decisions are another example of a non-science factor that influences the scientific process. Money drives which diseases get researched and which treatments or devices get brought to market. The massive costs associated with clinical trials also influence how much you'll eventually pay at the pharmacy when you pick up your medicine. And why in the generic forms are so much cheaper? So how does biological research work? What does grant money have to do with it? And what does the business of biological research look like? And how do money flows drive research directions? So let's start with the description of how biological research works. Biological research generally falls into two categories. We have basic research and translational or preclinical research. Basic research is designed to answer fundamental questions about how life works. Basic research can occur in cell lines which are cells grown in additional laboratory or with model organisms. We touched on model organisms like zebrafish and frogs in the last module. And we'll talk about them in more depth later in this course. Someone doing basic science research may be trying to understand how a certain population of cells responds when treated with a chemical or other substance. For example, when I was in graduate school, I was looking at how gene expression, which is when genes are turned on or off, was different between male and female neural stem cells. Much ecology, and evolution research like what we talked about in course three also falls under basic science research as well. Basic biomedical research and some educational studies where the final application is in the classroom rather than the clinic leads to translation or preclinical research and eventually on to clinical research. Translational research takes insights from basic research and applied them to larger and more complex models and preparation for moving to clinical research. We'll talk more about how clinical research works later in this module. For example, basic research may have revealed that a certain cellular process is important for promoting uncontrolled cell division and eventually cancer. Translational research would test a compound that inhibits this process first in cells and later in animal models to determine possible dosing. If the compound is promising, it may even make it to the clinical research stage and be tested in humans, the clinical phase. All of this testing is very, very expensive and involves large teams of scientists. Biomedical research occurs in either university, industry, or government laboratories. In universities, the work is typically performed either by students or postdoctoral fellows, also called postdocs. Postdocs are individuals who have earned a doctoral degree but are seeking additional training or trying to learn a certain skill set prior to getting a permanent position in academia, industry or a governmental lab. Some research is performed by permanent research like research associates or professional research assistants. They do research either as part of someone else's project or their own if they have independent funding. In the academy, researchers may or may not teach as well, depending on their funding sources. And industry or governmental positions, the majority of researchers are in stable permanent positions that typically pay better than academic positions. And less research is performed by trainees. In private industry settings, research is typically funded through product sales. In academic or nonprofit organizations, scientists write for private or federal grants. Private grants come from foundations, either started by wealthy individuals like the Bill and Melinda Gates Foundation, or focus on specific conditions or diseases, and typically funded through donations like the American Cancer Society. Federal grants come from taxpayer dollars. In terms of biomedical research in the United States, the National Institutes of Health, or the NIH is a major funder. There's also quite a bit of research that happens in governmental labs at the NIH. Here's a picture of the research complex in Bethesda, MD. Basic research and research dollars for other sciences, including educational research, at least in the United States, comes from the National Science Foundation, or NSF. Additional governmental entities in the US, such as the Department of Defense, the Department of Education, or the Department of Agriculture will also fund various research projects. And each agency has a variety of grants available through various programs. So, for example, NIH is made up of 27 some institutes or centers. And each institute funds research in a very specific area. So, for example, the National Cancer Institute or NCI focuses on research on cancer while the National Institute of Mental Health, focuses on research on mental health. The NSF is eclectic and includes various directorates which are different centers or departments. NSF funds research in many science domains, including educational research as well as specific programs for improving undergraduate education, understanding human learning in general, holding workshops and developing and sending educational technologies just to name a few examples. Within each agency there are a variety of grants available depending on the stage of a scientist's career in the development of a project. So for example, NIH has training grants that are specifically designed to support either a graduate student or a postdoc during their studies. These often cover full tuition for students In addition to providing a modest salary and health insurance benefits. The bulk of awards are for University faculty, senior researchers like research associates, and other qualified professionals outside of the academy, for example, research in a museum or a nonprofit organization. Okay, so let's say you're a scientist with an idea. What happens next? And how do funding priorities influence the direction that science takes? Okay, so you have an idea. The first step after you have an idea for a research project is to look for grant funds to support the work. Sometimes these ideas need to morph slightly to fit the funding priorities of an agency. Or an idea may sprout after reading through a call for proposals. Since funds are needed to support research, it is very difficult, or in some cases if special equipment or materials is required, impossible to do research without a grant. Professors at universities often have what are called startup funds to help them get started, but must secure grant for continued funding and to continue on their research programs. What funding opportunities are available ends up driving research direction. As any program officer at a federal agency will tell you, program officers, being the people who make the final funding decisions. There are more great ideas out there than there are funds available. So great ideas don't always get funded, at least not right away. One project I work on took four years to finally get funded by the National Science Foundation. It makes sense that agencies would have funding priorities, since there's a limited budget to go around. However, it can create somewhat biased representation of research dollars. Some ideas don't sit in the funding priorities and therefore just sit on the back burner. So even if they're great ideas, if they're not funding priorities, they're not going to get funded. Then the research isn't going to happen, unfortunately. So let's compare this to research on something like breast cancer. Breast cancer unfortunately impacts many people. So people are also more willing to donate or fundraise money to support breast cancer research. For a breast cancer researcher, there are many agencies and foundations that supply grants for research. As a result, we have many decent treatments and new advances are being developed all the time. So let's contrast this with rare diseases. The official definition of a rare disease is one that effects less than 200,000 people per year. Now that's for any single disease. When you take into account the sheer number of individuals in the United States with a rare disease, it actually totals between 25 and 30 million people. Since rare diseases aren't common, there's not a ton of advocacy or research dollars, and consequently very few FDA approved treatments. From a pragmatic standpoint, a million dollar grant that will help fund treatments for millions of people seems better than spending a million dollars to develop treatments that will only impact hundreds of people. However, many of the rare diseases impact children preferentially and are life threatening. So it gets into a moral question too. Should we preferentially fund research for diseases that are life threatening for a few children or diseases that impact many adults? There are several advocacy groups working to support research on rare diseases. And at the federal level, in 2019, NIH announced several new grant awards to form a rare diseases clinical research network. Sometimes rare diseases will receive quite a bit of attention as the result of grassroots efforts. For example, Life According to Sam was a documentary produced by HBO in 2013. The award winning documentary was about Sam, a young man with progeria. Progeria is a very rare genetic disease that effects only a few hundred people worldwide and causes accelerated aging. Sam's family founded the Progeria Research Foundation. Money raised from the foundation was used to fund research that uncovered a gene that causes the disease and also identified a potential therapeutic option. Unfortunately, Sam never benefited from the research done in his name, and died at the age of 17 due to complications from progeria. Another grassroots example is a grant received by the Hannahs Hope Fund by PepsiCo. PepsiCo funded a grant program in the early 2010s. The company's goal with this program was to fund new ideas that would have some kind of measurable positive impact at the community, state, or national level. Those interested in being considered for a grant would submit their idea online. And people could vote on which project that they would like to see funded. Part of the marketing strategy was people could buy Pepsi products and get extra votes by entering a code that was found on the inside of their bottle cap. One of the company's awards was to the Hannah's Hope Foundation. Like the Progeria Research Foundation, Hannah's Hope Fund was started by the parents of a child with a rare genetic disease, in this case, giant axonal neuropathy, or GAN. GAN is a rare disease that causes So degeneration of neurons starting in early childhood. Affected children typically slowly lose muscle control and die in their teens or 20s. As of the recording in this video, there is a gan clinical trial going on that started in 2015, and Hannah seems the person that charity is named for received treatment as part of the trial. According to the foundation's website, all the pre clinical work leading up to the trial was funded through the Hannah's Hope Foundation. So this brings us to our next topic. How does human subjects research work? How to clinical trials work? How does a treatment or device eventually make it to market?