The U.S. must fund more biotech innovation – or other countries will catch up faster than you think
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?”
Podcast: Should Scientific Controversies Be Silenced?
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
The recent Joe Rogan/Spotify backlash over the misinformation presented in his recent episode on the Covid-19 vaccines raises some difficult and important bioethical questions for society: How can people know which experts to trust? What should big tech gatekeepers do about false claims promoted on their platforms? How should the scientific establishment respond to heterodox viewpoints from experts who disagree with the consensus? When is silencing of dissent merited, and when is it problematic? Journalist Kira Peikoff asks infectious disease physician and pandemic scholar Dr. Amesh Adalja to weigh in.
Dr. Amesh Adalja, Senior Scholar, Johns Hopkins Center for Health Security and an infectious disease physician
Listen to the Episode
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Scientists Are Studying How to Help Dogs Have Longer Lives, in a Bid to Further Our Own
The sad eyes. The wagging tail. The frustrated whine. The excited bark. Dogs know how to get their owners to fork over the food more often.
The extra calories dogs get from feeding patterns now used by many Americans may not be good for them from a health and longevity viewpoint. In research from a large study called the Dog Aging Project, canines fed once a day had better scores on cognition tests and lower odds of developing diseases of organs throughout the body: intestinal tract, mouth and teeth, bones and joints, kidneys and bladder, and liver and pancreas.
Fewer than 1 in 10 dog owners fed their furry friends once daily, while nearly three fourths provided two daily meals.
“Most veterinarians have been led to believe that feeding dogs twice a day is optimal, but this is a relatively new idea that has developed over the past few decades with little supportive evidence from a health standpoint,” said Matt Kaeberlein, PhD, Co-Director of the Dog Aging Project, a professor of pathology and Director of the Healthy Aging and Longevity Research Institute at the University of Washington. Kaeberlein studies basic mechanisms of aging to find ways of extending the healthspan, the number of years of life lived free of disease. It’s not enough to extend the lifespan unless declines in biological function and risks of age-related diseases are also studied, he believes, hence the healthspan.
The Dog Aging Project is studying tens of thousands of dogs living with their owners in the real world, not a biology laboratory. The feeding study is the first of several reports now coming from the project based on owners’ annual reports of demographics, physical activity, environment, dog behavior, diet, medications and supplements, and health status. It has been posted on bioRxiv as it goes through peer review.
“All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans. It just happens much faster in dogs.”
“The Dog Aging Project is one of the most exciting in the longevity space,” said David A. Sinclair, professor in the Department of Genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. “Not only is it important to help our companions live longer and healthier, but because they are like people and share the same environment and many of the lifestyles as their owners, they are the perfect model for human longevity interventions.”
The epigenetic clock — and specifically changes in gene expression resulting from methylation of cytosine and guanine in the DNA — provides the critical connection between aging in dogs and people. “All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans,” Kaeberlein said. “It just happens much faster in dogs.” These methylation changes, called the “methylomes,” have been associated with rates of aging in dogs, humans, and also mice.
In a 2020 study young dogs matched with young adults and aged dogs matched with older adults showed the greatest similarities in methylomes. In the Cell Systems report, Tina Wang of the University of California, San Diego, and colleagues wrote that the methylome “can be used to quantitatively translate the age-related physiology experienced by one organism (i.e., a model species like dog) to the age at which physiology in a second organism is most similar (i.e., a second model or humans).” This allows rates of aging in one species to be mapped onto aging in another species, providing “a compelling tool in the quest to understand aging and identify interventions for maximizing healthy lifespan.”
In the Dog Aging Project study, 8% of 24,238 owners fed their dogs once daily, the same as the percentage of owners serving three daily meals. Twice-daily feedings were most common (73%), and just over 1 in 10 owners (11%) “free fed” their dogs by just filling up the bowl whenever it was empty — most likely Rover’s favorite option.
“The notion of breakfast, lunch, and dinner for people in the United States is not based on large studies that compared three meals a day to two meals a day, or to four, “ said Kate E. Creevy, chief veterinary officer with the Dog Aging Project and associate professor at Texas A&M University. “It’s more about what we are accustomed to. Similarly, there are not large population studies comparing outcomes of dogs fed once, twice, or three times a day.”
“We do not recommend that people change their dogs’ diets based on this report,” Creevy emphasized. “It’s important to understand the difference between research that finds associations versus research that finds cause and effect.”
To establish cause and effect, the Dog Aging Project will follow their cohort over many years. Then, Creevy said, “We will be able to determine whether the associations we have found with feeding frequency are causes, or effects, or neither.”
While not yet actionable, the feeding findings fit with biology across a variety of animals, Kaeberlein said, including indicators that better health translates into longer healthspans. He said that caloric restriction and perhaps time-restricted eating or intermittent fasting — all ways that some human diets are structured — can have a positive impact on the biology of aging by allowing the gastrointestinal tract to have time each day to rest and repair itself, just as sleep benefits the brain through rest.
Timing of meals is also related to the concept of ketogenesis, Kaeberlein explained. Without access to glucose, animals switch over to a ketogenic state in which back-up systems produce energy through metabolic pathways that generate ketones. Mice go into this state very quickly, after a few hours or an overnight fast, while people shift to ketogenesis more slowly, from a few hours to up to 36 hours for people on typical Western diets, Kaeberlein said.
Dogs are different. They take at least two days to shift to ketogenesis, suggesting they have evolved to need fewer meals that are spaced out rather than the multiple daily meals plus snacks that people prefer.
As this relates to longevity, Kaeberlein said that a couple of studies show that mice who are fed a ketogenic diet have longer lifespans (years of life regardless of health). “For us, the next step is to analyze the composition of the dogs’ diets or the relationship of multiple daily feedings with obesity,” he said. “Maybe not being obese is related to better health.”
To learn more, the Dog Aging Project needs dogs — lots of dogs! Kaeberlein wants at least 100,000 dogs, including small dogs, large dogs, dogs of all ages. Puppies are needed for the researchers to follow across their lifespan. The project has an excellent website where owners can volunteer to participate.
Nutritional strategies are often not built around sound scientific principles, Kaeberlein said. In human nutrition, people have tried all kinds of diets over the years, including some that were completely wrong. Kaeberlein and his colleagues in the Dog Aging Project want to change that, at least for people’s canine companions, and hopefully, as a result, give dogs added years of healthy life and provide clues for human nutrition.
After that, maybe they can do something about those sad eyes and the frustrated whine.