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?”
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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.
Trying to get a handle on CRISPR news in 2019 can be daunting if you haven't been avidly reading up on it for the last five years.
CRISPR as a diagnostic tool would be a major game changer for medicine and agriculture.
On top of trying to grasp how the science works, and keeping track of its ever expanding applications, you may also have seen coverage of an ongoing legal battle about who owns the intellectual property behind the gene-editing technology CRISPR-Cas9. And then there's the infamous controversy surrounding a scientist who claimed to have used the tool to edit the genomes of two babies in China last year.
But gene editing is not the only application of CRISPR-based biotechnologies. In the future, it may also be used as a tool to diagnose infectious diseases, which could be a major game changer for medicine and agriculture.
How It Works
CRISPR is an acronym for a naturally occurring DNA sequence that normally protects microbes from viruses. It's been compared to a Swiss army knife that can recognize an invader's DNA and precisely destroy it. Repurposed for humans, CRISPR can be paired with a protein called Cas9 that can detect a person's own DNA sequence (usually a problematic one), cut it out, and replace it with a different sequence. Used this way, CRISPR-Cas9 has become a valuable gene-editing tool that is currently being tested to treat numerous genetic diseases, from cancer to blood disorders to blindness.
CRISPR can also be paired with other proteins, like Cas13, which target RNA, the single-stranded twin of DNA that viruses rely on to infect their hosts and cause disease. In a future clinical setting, CRISPR-Cas13 might be used to diagnose whether you have the flu by cutting a target RNA sequence from the virus. That spliced sequence could stick to a paper test strip, causing a band to show up, like on a pregnancy test strip. If the influenza virus and its RNA are not present, no band would show up.
To understand how close to reality this diagnostic scenario is right now, leapsmag chatted with CRISPR pioneer Dr. Feng Zhang, a molecular biologist at the Broad Institute of MIT and Harvard.
What do you think might be the first point of contact that a regular person or patient would have with a CRISPR diagnostic tool?
FZ: I think in the long run it will be great to see this for, say, at-home disease testing, for influenza and other sorts of important public health [concerns]. To be able to get a readout at home, people can potentially quarantine themselves rather than traveling to a hospital and then carrying the risk of spreading that disease to other people as they get to the clinic.
"You could conceivably get a readout during the same office visit, and then the doctor will be able to prescribe the right treatment right away."
Is this just something that people will use at home, or do you also foresee clinical labs at hospitals applying CRISPR-Cas13 to samples that come through?
FZ: I think we'll see applications in both settings, and I think there are advantages to both. One of the nice things about SHERLOCK [a playful acronym for CRISPR-Cas13's longer name, Specific High-sensitivity Enzymatic Reporter unLOCKing] is that it's rapid; you can get a readout fairly quickly. So, right now, what people do in hospitals is they will collect your sample and then they'll send it out to a clinical testing lab, so you wouldn't get a result back until many hours if not several days later. With SHERLOCK, you could conceivably get a readout during the same office visit, and then the doctor will be able to prescribe the right treatment right away.
I just want to clarify that when you say a doctor would take a sample, that's referring to urine, blood, or saliva, correct?
FZ: Right. Yeah, exactly.
Thinking more long term, are there any Holy Grail applications that you hope CRISPR reaches as a diagnostic tool?
FZ: I think in the developed world we'll hopefully see this being used for influenza testing, and many other viral and pathogen-based diseases—both at home and also in the hospital—but I think the even more exciting direction is that this could be used and deployed in parts of the developing world where there isn't a fancy laboratory with elaborate instrumentation. SHERLOCK is relatively inexpensive to develop, and you can turn it into a paper strip test.
Can you quantify what you mean by relatively inexpensive? What range of prices are we talking about here?
FZ: So without accounting for economies of scale, we estimate that it can cost less than a dollar per test. With economy of scale that cost can go even lower.
Is there value in developing what is actually quite an innovative tool in a way that visually doesn't seem innovative because it's reminiscent of a pregnancy test? And I don't mean that as an insult.
FZ: [Laughs] Ultimately, we want the technology to be as accessible as possible, and pregnancy test strips have such a convenient and easy-to-use form. I think modeling after something that people are already familiar with and just changing what's under the hood makes a lot of sense.
Feng Zhang
(Photo credit: Justin Knight, McGovern Institute)
It's probably one of the most accessible at-home diagnostic tools at this point that people are familiar with.
FZ: Yeah, so if people know how to use that, then using something that's very similar to it should make the option very easy.
You've been quite vocal in calling for some pauses in CRISPR-Cas9 research to make sure it doesn't outpace the ethics of establishing pregnancies with that version of the tool. Do you have any concerns about using CRISPR-Cas13 as a diagnostic tool?
I think overall, the reception for CRISPR-based diagnostics has been overwhelmingly positive. People are very excited about the prospect of using this—for human health and also in agriculture [for] detection of plant infections and plant pathogens, so that farmers will be able to react quickly to infection in the field. If we're looking at contamination of foods by certain bacteria, [food safety] would also be a really exciting application.
Do you feel like the controversies surrounding using CRISPR as a gene-editing tool have overshadowed its potential as a diagnostics tool?
FZ: I don't think so. I think the potential for using CRISPR-Cas9 or CRISPR-Cas12 for gene therapy, and treating disease, has captured people's imaginations, but at the same time, every time I talk with someone about the ability to use CRISPR-Cas13 as a diagnostic tool, people are equally excited. Especially when people see the very simple paper strip that we developed for detecting diseases.
Are CRISPR as a gene-editing tool and CRISPR as a diagnostics tool on different timelines, as far as when the general public might encounter them in their real lives?
FZ: I think they are all moving forward quite quickly. CRISPR as a gene-editing tool is already being deployed in human health and agriculture. We've already seen the approval for the development of growing genome-edited mushrooms, soybeans, and other crop species. So I think people will encounter those in their daily lives in that manner.
Then, of course, for disease treatment, that's progressing rapidly as well. For patients who are affected by sickle cell disease, and also by a degenerative eye disease, clinical trials are already starting in those two areas. Diagnostic tests are also developing quickly, and I think in the coming couple of years, we'll begin to see some of these reaching into the public realm.
"There are probably 7,000 genetic diseases identified today, and most of them don't have any way of being treated."
As far its limits, will it be hard to use CRISPR as a diagnostic tool in situations where we don't necessarily understand the biological underpinnings of a disease?
FZ: CRISPR-Cas13, as a diagnostic tool, at least in the current way that it's implemented, is a detection tool—it's not a discovery tool. So if we don't know what we're looking for, then it's going to be hard to develop Cas13 to detect it. But even in the case of a new infectious disease, if DNA sequencing or RNA sequencing information is available for that new virus, then we can very rapidly program a Cas13-based system to detect it, based on that sequence.
What's something you think the public misunderstands about CRISPR, either in general, or specifically as a diagnostic tool, that you wish were better understood?
FZ: That's a good question. CRISPR-Cas9 and CRISPR-Cas12 as gene editing tools, and also CRISPR-Cas13 as a diagnostic tool, are able to do some things, but there are still a lot of capabilities that need to be further developed. So I think the potential for the technology will unfold over the next decade or so, but it will take some time for the full impact of the technology to really get realized in real life.
What do you think that full impact is?
FZ: There are probably 7,000 genetic diseases identified today, and most of them don't have any way of being treated. It will take some time for CRISPR-Cas9 and Cas12 to be really developed for addressing a larger number of those diseases. And then for CRISPR-based diagnostics, I think you'll see the technology being applied in a couple of initial cases, and it will take some time to develop that more broadly for many other applications.