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?”
Stem Cell Therapy for COVID-19 Is Gaining Steam in China, But Some Skeptical Scientists Urge Caution
Over the past two months, China's frantic search for an effective COVID-19 treatment has seen doctors trying everything from influenza drugs to traditional herbal remedies and even acupuncture, in a bid to help patients suffering from coronavirus-induced pneumonia.
"This treatment is particularly aimed at older patients who are seriously ill. These kinds of patients are in the danger zone."
Since mid February, one approach that has gained increasing traction is stem cell therapies, treatments that have often been viewed as a potential panacea by desperate patients suffering from degenerative incurable conditions ranging from Parkinson's to ALS. In many of these diseases, reality has yet to match the hype.
In COVID-19, there are hopes it might, though some experts are warning not to count on it. At Beijing's YouAn Hospital, doctors have been treating patients at various stages of the illness with intravenous infusions of so-called mesenchymal stem cells taken from umbilical cord tissue, as part of an ongoing clinical trial since January 21. The outcomes of the initial seven patients – published last month – appeared promising and the trial has since been expanded to 31 patients according to Dr. Kunlin Jin, a researcher at University of North Texas Health Science Center who is collaborating with the doctors in Beijing.
"Sixteen of these patients had mild symptoms, eight are severe, and seven are critically severe," Jin told leapsmag. "But all patients have shown improvements in lung function following the treatment, based on CT scans -- most of them in the first three days and seven have now been completely discharged from hospital. This treatment is particularly aimed at older patients who are seriously ill. These kinds of patients are in the danger zone; it's essential that they receive treatment, but right now we have nothing for most of them. No drugs or anything."
The apparent success of the very small Beijing trial has since led to a nationwide initiative to fast-track stem cell therapies for COVID-19. Across China, there are currently 36 clinical trials intending to use mesenchymal stem cells to treat COVID-19 patients that are either in the planning or recruiting phases. The Chinese Medical Association has now issued guidelines to standardize stem cell treatment for COVID-19, while Zhang Xinmin, an official in China's Ministry of Science and Technology, revealed in a press conference last week that a stem cell-based drug has been approved for clinical trials.
The thinking behind why stem cells could be a fast-acting and effective treatment is due to the nature of COVID-19. The thousands of fatalities worldwide are not from the virus directly, but from a dysfunctional immune response to the infection. Patients die because their respiratory systems become overwhelmed by a storm of inflammatory molecules called cytokines, causing lung damage and failure. However, studies in mice have long shown that stem cells have anti-inflammatory properties with the ability to switch off such cytokine storms, reducing such virus-induced lung injuries.
"There has been an enormous amount of hype about these cells, and there is scant scientific evidence that they have any therapeutic effect in any situation. "
"The therapy can inhibit the overactivation of the immune system and promote repair by improving the pulmonary microenvironment and improve lung function," explained Wei Hou, one of the doctors conducting the trial at YouAn Hospital.
However not everyone is convinced, citing the small number of patients treated to date, and potential risks from such therapy. "We just don't know enough to believe that stem cells might be helpful with COVID-19," said Paul Knoepfler, professor of cell biology at UC Davis. "The new stem cell studies are too small and lack controls, making it impossible to come to any solid conclusions. The chance of benefit is low based on the little we know so far and there are going to be risks that are hard to pin down. For instance, what if a stem cell infusion impairs some kind of needed immune response?"
Other scientists are even more skeptical. "I am concerned about all treatments that use mesenchymal stem cells," warned Jeanne Loring, the Director of the Center for Regenerative Medicine at Scripps Research in La Jolla, Calif. "There has been an enormous amount of hype about these cells, and there is scant scientific evidence that they have any therapeutic effect in any situation. Typically, these treatments are offered to people who have diseases without cures. I'm certain that there will be evidence-based treatments for COVID19, but I understand that they are not yet available, people are desperate, and they will try anything. I hope the sick are not taken advantage of because of their desperation."
Despite such concerns, the steadily rising death toll from COVID-19 means other nations are preparing to proceed with their own clinical trials of mesenchymal stem cells. Jin said he has been contacted by researchers and clinicians around the world seeking information on how to conduct their own trials, with the University of Cambridge's Stem Cell Institute in the U.K. reportedly looking to initiate a trial.
The scale of the global emergency has seen governments repeatedly calling on the corporate world to invest in the search for a cure, and the Australian company Mesoblast – a global leader in cell-based therapies for a range of diseases – are expecting to receive the green light to initiate clinical trials of their own stem cell based product against COVID-19.
"We're talking to at least three major governments," said Silviu Itescu, CEO and Managing Director of Mesoblast. "We are working with groups in Australia, the U.S. and the U.K., and I expect there'll be trials starting imminently in all those jurisdictions."
Itescu is bullish that the therapy has a good chance of proving effective, as it recently successfully completed Phase III trials for severe steroid-refractory acute graft versus host disease (GVHD) – a condition which leads to a very similar disease profile to COVID-19.
"The exact same cytokine profile is occurring in the lungs of COVID-19 infected patients as in GVHD which is destructive to the local lung environment," he said. "If our cells are able to target that in GVHD, they ought to be able to switch off the cytokine response in COVID lung disease as well."
"What we should be focusing on now is not the possible boost to the stem cell field, but rather doing rigorous science to test whether stem cells can help COVID-19 patients."
Jin is hopeful that if the imminent trials yield successful results, the U.S. FDA could fast-track mesenchymal stem cells as an approved emergency therapy for COVID-19. However, Knoepfler cautions that there is a need for far more concrete and widespread proof of the benefit before regulatory bodies start ushering through the green light.
"What we should be focusing on now is not the possible boost to the stem cell field, but rather doing rigorous science to test whether stem cells can help COVID-19 patients," he said. "During a pandemic, it's reasonable to do some testing of unproven interventions like stem cells in small studies, but results from them should be discussed in a sober, conservative manner until there is more evidence."
BREAKING: The First U.S. Test to Detect If a Person Has Potential Immunity to COVID-19 Was Just Developed
While testing for COVID-19 ramps up around the country, there's another kind of testing that will prove equally important to combating the pandemic: one that can detect whether someone has already been infected.
"The idea is that this assay can be established anywhere in the world following these steps."
Why is this important? As former FDA commissioner Scott Gottlieb wrote in today's Wall Street Journal: "If a sizable portion of a local community has some protection, authorities can be more confident in relying less on invasive measures. Once deployed, serological tests are cheap, straightforward, and easy to scale."
Now, a microbiology lab at the Icahn School of Medicine at Mount Sinai, led by Dr. Florian Krammer, has just announced the development of this serological test. Leapsmag spoke with Daniel Stadlbauer, a post-doctoral fellow in the lab who helped lead the work.
Is yours the first serological test available?
They did something similar in South Korea. In the U.S., it's the first of these tests.
How close are we to rolling this test out to the public?
Last week, we started this process and we finished the protocol today. Mount Sinai is trying to roll this out in the next few days in the clinic to see which patients have been infected with coronavirus recently or have been infected at all.
The protocol we uploaded today can be used as a template for other research labs or hospitals to follow the steps we provided and they should then be able to set up the antibody test. The idea is that this assay can be established anywhere in the world following these steps.
Are there any bottlenecks to getting this rolled out – supply chain or regulation obstacles?
There are no regulations that say you can't do it. Research labs and hospitals for sure can do it. I'm not aware of supply chain issues because you need basic lab equipment and materials, but I don't think those are in short supply right now.
How does the test work?
People coming to the hospital who are suspected to have infection with coronavirus, their blood gets taken routinely. This blood can be used for our test, too. The test will tell you if this person has antibodies against coronavirus. You can also test the blood of people who are not currently sick to see if this person was infected, say, a month ago. If there are antibodies in the blood, you can say this person is probably immune to getting it again.
It will be essential workers who need to be tested first, like nurses, firefighters, and doctors. It will be great to know that they would not put themselves or others at risk by going back to work because they cannot spread the disease.
"People probably cannot get reinfected once they mount a good immune response and have good antibody levels."
How soon after infection does the test detect if you have antibodies?
Usually after 7 days of infection.
How long do the antibodies last to confer immunity?
Those studies need to be done – right now it's unclear. People probably cannot get reinfected once they mount a good immune response and have good antibody levels. How long those level last still needs to be investigated. But they won't get reinfected in the next, I would say, six months.
How accurate is the test?
Very accurate. The advantage – which is bad for us but good for the test – is that humans have no baseline immunity to this coronavirus. It means that when you have not been infected, you have pretty much no antibodies, which is why it can spread so easily. But once you have antibodies in your blood, we can detect them and it's a clear difference between antibodies or no antibodies.
Where should hospitals and labs go for more information on how to build their own tests from your work?
They should check out our lab website to find the detailed protocol to download.
If I am a person who just wants to take this test to find out if I've already been infected, what should I do?
It will be done soon in the clinical setting. I don't know yet how widely it will be available. The more research labs and hospitals that set up this testing, the more people who can be tested in the future.
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.