July 21 | 2022
The U.S. must fund more biotech innovation – or other countries will catch up faster than you think
Dr. de Rivero Vaccari is an Associate Professor of Neurosurgery at the University of Miami Miller School of Medicine and a Public Voices Fellow of The OpEd Project. His research focuses on understanding the molecular mechanisms of inflammation in the central nervous system after injury and disease with the goal of identifying therapeutic targets that can be used for the development of anti-inflammatory therapies.
In the coming years, U.S. market share in biotech will decline unless the federal government makes investments to improve the quality and quantity of U.S. research, writes the author.
Photo by Eric Prouzet on Unsplash
The U.S. has approximately 58 percent of the market share in the biotech sector, followed by China with 11 percent. However, this market share is the result of several years of previous research and development (R&D) – it is a present picture of what happened in the past. In the future, this market share will decline unless the federal government makes investments to improve the quality and quantity of U.S. research in biotech.
The effectiveness of current R&D can be evaluated in a variety of ways such as monies invested and the number of patents filed. According to the UNESCO Institute for Statistics, the U.S. spends approximately 2.7 percent of GDP on R&D ($476,459.0M), whereas China spends 2 percent ($346,266.3M). However, investment levels do not necessarily translate into goods that end up contributing to innovation.
Patents are a better indication of innovation. The biotech industry relies on patents to protect their investments, making patenting a key tool in the process of translating scientific discoveries that can ultimately benefit patients. In 2020, China filed 1,497,159 patents, a 6.9 percent increase in growth rate. In contrast, the U.S. filed 597,172, a 3.9 percent decline. When it comes to patents filed, China has approximately 45 percent of the world share compared to 18 percent for the U.S.
So how did we get here? The nature of science in academia allows scientists to specialize by dedicating several years to advance discovery research and develop new inventions that can then be licensed by biotech companies. This makes academic science critical to innovation in the U.S. and abroad.
Academic scientists rely on government and foundation grants to pay for R&D, which includes salaries for faculty, investigators and trainees, as well as monies for infrastructure, support personnel and research supplies. Of particular interest to academic scientists to cover these costs is government support such as Research Project Grants, also known as R01 grants, the oldest grant mechanism from the National Institutes of Health. Unfortunately, this funding mechanism is extremely competitive, as applications have a success rate of only about 20 percent. To maximize the chances of getting funded, investigators tend to limit the innovation of their applications, since a project that seems overambitious is discouraged by grant reviewers.
Considering the difficulty in obtaining funding, the limited number of opportunities for scientists to become independent investigators capable of leading their own scientific projects, and the salaries available to pay for scientists with a doctoral degree, it is not surprising that the U.S. is progressively losing its workforce for innovation.
This approach affects the future success of the R&D enterprise in the U.S. Pursuing less innovative work tends to produce scientific results that are more obvious than groundbreaking, and when a discovery is obvious, it cannot be patented, resulting in fewer inventions that go on to benefit patients. Even though there are governmental funding options available for scientists in academia focused on more groundbreaking and translational projects, those options are less coveted by academic scientists who are trying to obtain tenure and long-term funding to cover salaries and other associated laboratory expenses. Therefore, since only a small percent of projects gets funded, the likelihood of scientists interested in pursuing academic science or even research in general keeps declining over time.
Efforts to raise the number of individuals who pursue a scientific education are paying off. However, the number of job openings for those trainees to carry out independent scientific research once they graduate has proved harder to increase. These limitations are not just in the number of faculty openings to pursue academic science, which are in part related to grant funding, but also the low salary available to pay those scientists after they obtain their doctoral degree, which ranges from $53,000 to $65,000, depending on years of experience.
Thus, considering the difficulty in obtaining funding, the limited number of opportunities for scientists to become independent investigators capable of leading their own scientific projects, and the salaries available to pay for scientists with a doctoral degree, it is not surprising that the U.S. is progressively losing its workforce for innovation, which results in fewer patents filed.
Perhaps instead of encouraging scientists to propose less innovative projects in order to increase their chances of getting grants, the U.S. government should give serious consideration to funding investigators for their potential for success -- or the success they have already achieved in contributing to the advancement of science. Such a funding approach should be tiered depending on career stage or years of experience, considering that 42 years old is the median age at which the first R01 is obtained. This suggests that after finishing their training, scientists spend 10 years before they establish themselves as independent academic investigators capable of having the appropriate funds to train the next generation of scientists who will help the U.S. maintain or even expand its market share in the biotech industry for years to come. Patenting should be given more weight as part of the academic endeavor for promotion purposes, or governmental investment in research funding should be increased to support more than just 20 percent of projects.
Remaining at the forefront of biotech innovation will give us the opportunity to not just generate more jobs, but it will also allow us to attract the brightest scientists from all over the world. This talented workforce will go on to train future U.S. scientists and will improve our standard of living by giving us the opportunity to produce the next generation of therapies intended to improve human health.
This problem cannot rely on just one solution, but what is certain is that unless there are more creative changes in funding approaches for scientists in academia, eventually we may be saying “remember when the U.S. was at the forefront of biotech innovation?”
Dr. de Rivero Vaccari is an Associate Professor of Neurosurgery at the University of Miami Miller School of Medicine and a Public Voices Fellow of The OpEd Project. His research focuses on understanding the molecular mechanisms of inflammation in the central nervous system after injury and disease with the goal of identifying therapeutic targets that can be used for the development of anti-inflammatory therapies.
March 14 | 2023
Too much of this ingredient leads to autoimmune diseases, new research shows. Here's how to cut back.
Scientists are looking at how salt affects our cells, and they're finding more reasons to avoid htoo much of it.
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For more than a century, doctors have warned that too much salt in your diet can lead to high blood pressure, heart disease and stroke - and many of the reasons for these effects are well known. But recently scientists have been looking deeper, into the cellular level, and they are finding additional reasons to minimize sodium intake; it is bad for immune cells, creating patterns of gene expression and activity seen in a variety of autoimmune diseases such as multiple sclerosis, lupus, rheumatoid arthritis, and type-1 diabetes.
Salt is a major part of the ocean from which life evolved on this planet. We carry that legacy in our blood, which tastes salty. It is an important element for conducting electrical signals along nerves and balancing water and metabolites transported throughout our bodies. We need to consume about 500 milligrams of salt each day to maintain these functions, more with exercise and heavy sweating as that is a major way the body loses salt. The problem is that most Americans eating a modern western diet consume about 3400 milligrams, 1.5 teaspoons per day.
Evidence has been accumulating over the last few years that elevated levels of sodium can be harmful to at least some types of immune cells. The first signal came in monocytes, which are immune cells that travel to various tissues in the body, where some of them turn into macrophages, a subset of white blood cells that can directly kill microorganisms and make chemical signals that bring other types of immune cells into play.
Two years ago, Dominik N. Müller from the Max-Delbrueck-Center in Berlin, Germany and Markus Kleinewietfeld, an immunologist at Hasselt University in Belgium, ran a study where they fed people pizza and then measured their immune cell function. “We saw that in any monocytes, metabolic function was down, even after a single salty meal,” Kleinewietfeld says. It seemed to be the cellular equivalent of the sluggish feeling we get after eating too much. The cells were able to recover but more research is needed to answer questions about what dose of sodium causes impairment, how long the damage lasts, and whether there is a cumulative effect of salt toxicity.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations.
The latest series of experiments focused on a type of T cell called T regulatory cells, or Tregs. Most T cells release inflammatory mediators to fight pathogens and, once that job is done, Tregs come along to calm down their hyperactive brethren. Failure to do so can result in continued inflammation and possibly autoimmune diseases.
In the lab, Kleinewietfeld and his large team of international collaborators saw that high levels of sodium had a huge effect on Tregs, upregulating 1250 genes and downregulating an additional 1380 genes so that they looked similar to patterns of gene expression seen in autoimmune diseases.
Digging deeper, they found that sodium affected mitochondria, the tiny organelles inside of cells that produce much of its energy. The sodium was interfering with how the mitochondria use oxygen, which resulted in increased levels of an unstable form of oxygen that can damage cell function. The researchers injected those damaged Tregs into mice and found that they impaired the animals' immune function, allowing the inflammation to continue rather than shutting it down.
That finding dovetailed nicely with a 2019 paper in Nature from Navdeep Chandel's lab at Northwestern University, which showed in mice that inhibiting the mitochondrial use of oxygen reduced the ability of Tregs to regulate other T cells. “Mitochondria were controlling directly the immunosuppressive program, they were this master regulator tuning the right amount of genes to give you proper immunosuppression,” Chandel said. “And if you lose that function, then you get autoimmunity.”
Kleinewietfeld's team studied the Treg cells of humans and found that sodium can similarly decrease mitochondrial use of oxygen and immunosuppressive activity. “I would have never predicted that myself,” Chandel says, but now researchers can look at the mitochondria of patients with autoimmune disease and see if their gene expression also changes under high salt conditions. He sees the link between the patterns of gene expression in Tregs generated by high salt exposure and those patterns seen in autoimmune diseases, but he is cautious about claiming a causal effect.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations. He says a high salt diet could also have an indirect effect on immune function through the way it affects the gut microbiome and the molecules made by microbes when they break down food. But the research results are too preliminary to say that for sure, much less parse out the role of salt compared with other possible factors. “It is still an exciting journey to try to understand this field,” he says.
Additionally, it is difficult to say precisely how this research in animals and human cell cultures will translate into a whole human body. Individual differences in genetics can affect how the body absorbs, transports, and gets rid of sodium, such that some people are more sensitive to salt than are others.
So how should people apply these research findings to daily life?
Salt is obvious when we sprinkle it on at the table or eat tasty things like potato chips, but we may be unaware of sodium hidden in packaged foods. That's because salt is an easy and cheap way to boost the flavor of foods. And if we do read the labeled salt content on a package, we focus on the number for a single serving, but then eat more than that.
Last September, the U.S. Food and Drug Administration (FDA) began a process to update labels on the content of food, including what is meant by the word “healthy” and how food manufacturers can use the term. Many in the food industry are resisting those proposed changes.
Chandel cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker.
Until labels are updated, it would be prudent to try to reduce sodium intake by cutting down on packaged foods while making your own food at home, where you know just how much salt has been added. The Mayo Clinic offers guidance on how to become more aware of the sodium in your diet and eat less of it.
Chandel thinks many people will struggle with minimizing salt in their diets. It’s similar to the challenge of eating less sugar, in that the body craves both, and it is difficult to fight that. He cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker. “Dietary antioxidants have failed in just about every clinical trial, yet the public continues to take them,” Chandel says. But he is optimistic that research will lead us to a better understanding of how Tregs function, and uncover new targets for treating autoimmune diseases.
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Bob Roehr is a biomedical journalist based in Washington, DC. Over the last twenty-five years he has written extensively for The BMJ, Scientific American, PNAS, Proto, and myriad other publications. He is primarily interested in HIV, infectious disease, immunology, and how growing knowledge of the microbiome is changing our understanding of health and disease. He is working on a book about the ways the body can at least partially control HIV and how that has influenced (or not) the search for a treatment and cure.
In this week's Friday Five, new research that could help prevent Alzheimer's. Plus, why you should care about smart senior towns, how to reverse being drunk, money can make you happier if you're this type of person, and personalized anxiety medicine.
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The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. Christopher Martens, director of the Delaware Center for Cogntiive Aging Research and professor of kinesiology and applied physiology at the University of Delaware, and Dr. Ilona Matysiak, visiting scholar at Iowa State University and associate professor of sociology at Maria Grzegorzewska University.
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- Could this supplement help prevent Alzheimer's?
- Why you should care about smart senior towns
- Here's how to reverse being drunk
- Money can make you happy - if you're this type of person
- Personalized anxiety medicine
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Matt Fuchs is the host of the Making Sense of Science podcast and served previously as the editor-in-chief of Leaps.org. He writes as a contributor to the Washington Post, and his articles have also appeared in the New York Times, WIRED, Nautilus Magazine, Fortune Magazine and TIME Magazine. Follow him @fuchswriter.