A Look Back at Science’s 2022 Breakthroughs
Posted on by Lawrence Tabak, D.D.S., Ph.D.
Happy New Year! I hope everyone finished 2022 with plenty to celebrate, whether it was completing a degree or certification, earning a promotion, attaining a physical fitness goal, or publishing a hard-fought scientific discovery.
If the latter, you are in good company. Last year produced some dazzling discoveries, and the news and editorial staff at the journal Science kept a watchful eye on the most high-impact advances of 2022. In December, the journal released its list of the top 10 advances across the sciences, from astronomy to zoology. In case you missed it, Science selected NASA’s James Webb Space Telescope (JWST) as the 2022 Breakthrough of the Year [1].
This unique space telescope took 20 years to complete, but it has turned out to be time well spent. Positioned 1.5-million-kilometers from Earth, the JWST and its unprecedented high-resolution images of space have unveiled the universe anew for astronomers and wowed millions across the globe checking in online. The telescope’s image stream, beyond its sheer beauty, will advance study of the early Universe, allowing astronomers to discover distant galaxies, explore the early formation of stars, and investigate the possibility of life on other planets.
While the biomedical sciences didn’t take home the top prize, they were well represented among Science’s runner-up breakthroughs. Some of these biomedical top contenders also have benefited, directly or indirectly, from NIH efforts and support. Let’s take a look:
RSV vaccines nearing the finish line: It’s been one of those challenging research marathons. But scientists last year started down the homestretch with the first safe-and-effective vaccine for respiratory syncytial virus (RSV), a leading cause of severe respiratory illness in the very young and the old.
In August, the company Pfizer presented evidence that its experimental RSV vaccine candidate offered protection for those age 60 and up. Later, they showed that the same vaccine, when administered to pregnant women, helped to protect their infants against RSV for six months after birth. Meanwhile, in October, the company GSK announced encouraging results from its late-stage phase III trial of an RSV vaccine in older adults.
As Science noted, the latest clinical progress also shows the power of basic science. For example, researchers have been working with chemically inactivated versions of the virus to develop the vaccine. But these versions have a key viral surface protein that changes its shape after fusing with a cell to start an infection. In this configuration, the protein elicits only weak levels of needed protective antibodies.
Back in 2013, Barney Graham, then with NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and colleagues, solved the problem [2]. Graham’s NIH team discovered a way to lock the protein into its original prefusion state, which the immune system can better detect. This triggers higher levels of potent antibodies, and the discovery kept the science—and the marathon—moving forward.
These latest clinical advances come as RSV and other respiratory viruses, including SARS-CoV-2, the cause of COVID-19, are sending an alarming number of young children to the hospital. The hope is that researchers will cross the finish line this year or next, and we’ll have the first approved RSV vaccine.
Virus fingered as cause of multiple sclerosis: Researchers have long thought that multiple sclerosis, or MS, has a viral cause. Pointing to the right virus with the required high degree of certainty has been the challenge, slowing progress on the treatment front for those in need. As published in Science last January, Alberto Ascherio, Harvard T.H. Chan School of Public Health, Boston, and colleagues produced the strongest evidence yet that MS is caused by the Epstein-Barr virus (EBV), a herpesvirus also known for causing infectious mononucleosis [3].
The link between EBV and MS had long been suspected. But it was difficult to confirm because EBV infections are so widespread, and MS is so disproportionately rare. In the recent study, the NIH-supported researchers collected blood samples every other year from more than 10 million young adults in the U.S. military, including nearly 1,000 who were diagnosed with MS during their service. The evidence showed that the risk of an MS diagnosis increased 32-fold after EBV infection, but it held steady following infection with any other virus. Levels in blood serum of a biomarker for MS neurodegeneration also went up only after an EBV infection, suggesting that the viral illness is a leading cause for MS.
Further evidence came last year from a discovery published in the journal Nature by William Robinson, Stanford University School of Medicine, Stanford, CA, and colleagues. The NIH-supported team found a close resemblance between an EBV protein and one made in the healthy brain and spinal cord [4]. The findings suggest an EBV infection may produce antibodies that mistakenly attack the protective sheath surrounding our nerve cells. Indeed, the study showed that up to one in four people with MS had antibodies that bind both proteins.
This groundbreaking research suggests that an EBV vaccine and/or antiviral drugs that thwart this infection might ultimately prevent or perhaps even cure MS. Of note, NIAID launched last May an early-stage clinical trial for an experimental EBV vaccine at the NIH Clinical Center, Bethesda, MD.
AI Gets Creative: Science’s 2021 Breakthrough of the Year was AI-powered predictions of protein structure. In 2022, AI returned to take another well-deserved bow. This time, Science singled out AI’s now rapidly accelerating entry into once uniquely human attributes, such as artistic expression and scientific discovery.
On the scientific discovery side, Science singled out AI’s continued progress in getting creative with the design of novel proteins for vaccines and myriad other uses. One technique, called “hallucination,” generates new proteins from scratch. Researchers input random amino acid sequences into the computer, and it randomly and continuously mutates them into sequences that other AI tools are confident will fold into stable proteins. This greatly simplifies the process of protein design and frees researchers to focus their efforts on creating a protein with a desired function.
AI research now engages scientists around world, including hundreds of NIH grantees. Taking a broader view of AI, NIH recently launched the Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) Program. It will help to create greater diversity within the field, which is a must. A lack of diversity could perpetuate harmful biases in how AI is used, how algorithms are developed and trained, and how findings are interpreted to avoid health disparities and inequities for underrepresented communities.
And there you have it, some of the 2022 breakthroughs from Science‘s news and editorial staff. Of course, the highlighted biomedical breakthroughs don’t capture the full picture of research progress. There were many other milestone papers published in 2022 that researchers worldwide will build upon in the months and years ahead to make further progress in their disciplines and, for some, draw the attention of Science’s news and editorial staff. Here’s to another productive year in biomedical research, which the blog will continue to feature and share with you as it unfolds in 2023.
References:
[1] 2022 Breakthrough of the Year. Science. Dec 15, 2022.
[2] Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. McLellan JS, Chen M, Leung S, Kwong PD, Graham BS, et al. Science. 2013 May 31;340(6136):1113-1117.
[3] Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, Elledge SJ, Niebuhr DW, Scher AI, Munger KL, Ascherio A. Science. 2022 Jan 21;375(6578):296-301.
[4] Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Lanz TV, Brewer RC, Steinman L, Robinson WH, et al. Nature. 2022 Mar;603(7900):321-327.
Links:
Respiratory Syncytial Virus (RSV) (National Institute of Allergy and Infectious Diseases/NIH)
Multiple Sclerosis (National Institute of Neurological Disorders and Stroke/NIH)
Barney Graham (Morehouse School of Medicine, Atlanta)
Alberto Ascherio (Harvard T.H. Chan School of Public Health, Boston)
Robinson Lab (Stanford Medicine, Stanford, CA)
James Webb Space Telescope (Goddard Space Flight Center/NASA, Greenbelt, MD)
The dramatic disease MS, even more terrible when it arises at a young age, draws attention to the complex clinical pictures with different nuances, especially with subtle onset.
As a medical student first and then as an ophthalmologist, I always hoped that the real cause would be found and consequently the effective therapy on this.
Many hypotheses and assumptions have been formulated, now something concrete seems to be emerging with what has been demonstrated by these recent researches, which call into question the EB Virus.
It is also natural to wonder what the determining factor in the development of this sort of self-aggressive response to the sheath of nerve fibers after is contracting this viral infection.
The speech becomes even more complex, since we also find the different distribution of the frequency of MS disease in relation to the different geographical latitude and increases rising from the Equator to the North [1].
To this geographical condition, perhaps the role of temperature could be linked, which could induce
damage by damaging the microcirculation of nerve fibers: at low temperatures microinfarcts would arise triggered by the precipitate of cryoglobulins.
This type of autoantibody can occur after EBV infection in some individuals [2]
Could we think that some components derived from the necrosis of some tissue structures induce the production of Auto Antibodies that cross react with healthy nervous tissue?
References:
[1] Disanto G, Pakpoor J, Morahan JM, Hall C, Meier UC, Giovannoni G, Ramagopalan SV. Epstein-Barr virus, latitude and multiple sclerosis. Mult Scler. 2013 Mar;19(3):362-5. doi: 10.1177/1352458512451942. Epub 2012 Jul 5. PMID: 22767435.
[2] Berentsen S. New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia. Front Immunol. 2020 Apr 7;11:590.
What happens if said micro-organisms are exposed to carcinogens of various sorts? Do we need to revisit SMON and perhaps even earlier, bis(2-chloroethyl) sulfide to have a clearer picture of the landscape?
I thank the Director, Dr Tabak
for what is stated in this article and for the space that is granted to me.
MS : Which is the real Trigger?
We read that Multiple Sclerosis could be linked to a previous EBV infection (very frequent in the population) but, fortunately, most people infected with this virus do not develop MS.
We wonder what spark triggers the fire: as for a territory, there can be the spread of flames after a spark only if there is a series of environmental conditions beyond the fuel (drought, wind, care of the territory, etc.); so also in our body the extent of the onset of diseases is conditioned according to nutritional status, stress, comorbidity, environmental conditions, etc. ..
EBV + MS . Several authors hypothesize the mechanisms of action of self-aggressive cross-reaction that can be produced in various modes and conditions [1,2]]
Cryoglobulins.
With regard to the role of exposure to low temperatures, this type of antibodies could damage both cellular and tissue structures as a result of microvascular damage from occlusive cryoprecipitates [3]: this would be the next Trigger, to which the production of Cross reacting antibodies would also be linked on healthy biological components.
We could argue that cryoglobulins are also present in other conditions but MS does not arise, it is however possible that with EBV there is a trigger in the context of a further state of cross reaction.
Finally, for the cold temperature it is not essential to go to the northern latitudes, we must also consider exposures in areas with strong environmental refrigeration as well as the habit of taking iced foods and drinks. This contact with cold food suddenly lowers the temperature not only of the oral cavity but by conduction the blood flow of nearby anatomical structures, being able to perhaps induce the precipitation of cryoglobulins even in the brain circulation.
References:
[1] Lanz TV, Brewer RC, Ho PP, et al. Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Nature. 2022;603(7900):321-327. doi:10.1038/s41586-022-04432-7
[2] Robinson WH, Steinman L. Epstein-Barr virus and multiple sclerosis. Science. 2022 Jan 21;375(6578):264-265. doi: 10.1126/science.abm7930. Epub 2022 Jan 13. PMID: 35025606.
[3] Berentsen S. New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia. Front Immunol. 2020 Apr 7;11:590. doi: 10.3389/fimmu.2020.00590. PMID: 32318071; PMCID: PMC7154122
Multiple Sclerosis (MS) and Spinal Cord Injury (SCI) are terrible pathological events that both have in common the sad characteristic of often afflicting people at a young age, with an inexorable destiny over time. Despite having a different agent that causes them (biological autoimmune for MS, traumatic for SCI) both have as a detrimental result motor paralysis and sensory deficit, with the related neurovegetative dysfunctions of the visceral systems.
If for MS more and more effective therapies are envisaged and adopted, for the conditions of patients with SCI it is hoped that soon solutions can be found to regenerate wounded neurological structures[1], to restore motor and sensory functions, with the normalization of the visceral systems, on which the well-being of the individual depends.
References:
[1] Nature 611, 438 (2022)
doi.org/10.1038/d41586-022-03605-8