The Next Normal: Supporting Biomedical Discovery, Clinical Practice, and Self-Care

As we start year three of the COVID-19 pandemic, it’s time for NLM to take stock of the parts of our past that will support the next normal and what we might need to change as we continue to fulfill our mission to acquire, collect, preserve, and disseminate biomedical literature to the world.

Today, I invite you to join me in considering the assumptions and presumptions we made about how scientists, clinicians, and patients are using critical NLM resources and how we might need to update those assumptions to meet future needs. I will give you a hint… it’s not all bad—in fact, I find it quite exciting!

Let’s highlight some of our assumptions about how people are using our services, at least from my perspective. We anticipated the need for access to medical literature across the Network of the National Library of Medicine and created DOCLINE, an interlibrary loan request routing system that quickly and efficiently links participating libraries’ journal holdings. We also anticipated that we were preparing the literature and our genomic databases for humans to read and peruse. Now we’re finding that more than half of the accesses to NLM resources are generated and driven by computers through application programming interfaces. Even our MedlinePlus resource for patients now connects tailored electronic responses through MedlinePlus Connect to computer-generated queries originating in electronic health records.

Perhaps, and most importantly, we realize that while sometimes the information we present is actually read by a living person, other times the information we provide—for example, about clinical trials (ClinicalTrials.gov) or genotype and phenotype data (dbGaP)—is actually processed by computers! Increasingly, we provide direct access to the raw, machine-readable versions of our resources so those versions can be entered into specialized analysis programs, which allow natural-language processing programs to find studies with similar findings or machine-learning models to determine the similarities between two gene sequences. For example, NLM makes it possible for advocacy groups to download study information from all ClinicalTrials.gov records so anyone can use their own programs to point out trials that may be of interest to their constituents or to compare summaries of research results for related studies.

Machine learning and artificial intelligence have progressed to the point that they perform reasonably well in connecting similar articles—to this end, our LitCovid open-resource literature hub has served as an electronic companion to the human curation of coronavirus literature. NLM’s LitCovid is more efficient and has a sophisticated search function to create pathways that are more relevant and are more likely to curate articles that fulfill the needs of our users. Most importantly, innovations such as LitCovid help our users manage the vast and ever-growing collection of biomedical literature, now numbering more than 34 million citations in NLM’s PubMed, the most heavily used biomedical literature citation database.

Partnerships are a critical asset to bring biomedical knowledge into the hands (and eyes) of those who need it. Over the last decade, NLM moved toward a new model for managing citation data in PubMed. We released the PubMed Data Management system that allows publishers to quickly update or correct nearly all elements of their citations and that accelerates the delivery of correct and complete citation data to PubMed users.

As part of the MEDLINE 2022 Initiative, NLM transitioned to automated Medical Subject Headings (MeSH) indexing of MEDLINE citations in PubMed. Automated MeSH indexing significantly decreases the time for indexed citations to appear in PubMed without sacrificing the quality MEDLINE is known to provide. Our human indexers can focus their expertise on curation efforts to validate assigned MeSH terms, thereby continuously improving the automated indexing algorithm and enhancing discoverability of gene and chemical information in the future.

We’re already preparing for the next normal—what do you think it will be like?

I envision making our vast resources increasingly available to those who need them and forging stronger partnerships that improve users’ ability to acquire and understand knowledge. Imagine a service, designed and run by patients, that could pull and synthesize the latest information about a disease, recommendations for managing a clinical issue, or help a young investigator better pinpoint areas ripe for new interrogation! The next normal will make the best use of human judgment and creativity by selecting and organizing relevant data to create a story that forms the foundation of new inquiry or the basis of new clinical care. Come along and help us co-create the next normal!

A New Frontier: The Impact of a 1959 Board Meeting

Guest blog by Ken Koyle, MA, Deputy Chief of the History of Medicine Division (HMD) at the NIH National Library of Medicine. This post celebrates the important work performed by our archival professionals and the archival collections held by the library, from which the source material was drawn, as NLM celebrates International Archives Week #IAW2022.

In November 1959, when construction of NLM’s current building at NIH was still underway and digital computing was in its infancy, the NLM Board of Regents convened on the third floor of the Old Red Brick building for a demonstration of the indexing process. When Board Chairman Michael E. DeBakey, MD, asked if computer technology could be used in indexing, NLM Director Col. Frank B. Rogers, MD, was ready with an answer. Dr. Rogers, clearly interested in the emerging technology of automated data processing (ADP), described an article by Robert S. Ledley, DDS, in that month’s issue of Science and noted that Dr. Ledley was already contracted with NLM to report on using computers in indexing.

Black-and-white photo of Dr. Rogers leaning on a stack of books with bookshelves in background.
Dr. Frank Rogers at NLM, 1962.

Dr. Rogers was instrumental in NLM’s first explorations of automated processes and had a clear vision of the potential of electronic computing, including how it could improve efficiency at NLM, but his optimism was tempered by prescient realism. Dr. Rogers recognized—and conveyed to the Board—that the potential benefits of ADP would require a commensurate investment of staff time and labor. “We should not forget that ‘automatically’ means ‘because we told it to do so beforehand,’ and this in itself may turn out to be quite a trick.” Dr. Rogers made it clear that the computer age would bring a change in work, but not necessarily a reduction in work. “Remarkable as the capacity of the computer may be for sustaining a long sequence of operations, it is nevertheless ultimately only the end-phase of that still longer sequence which must include as a first phase the human labor of input.”

Acknowledging the upfront labor investment in ADP was only part of Dr. Rogers’ insight. He also explained that the human work was not only substantial and necessary, but also incredibly complex: “The instructions [for a computer] are a thousand times more detailed, for the simplest task, than those required to be given to the . . . clerk.” Unleashing computers’ potential would require staff to think in new ways, conceive new methods of organizing data, and embark on a new journey of continuous learning and professional development.

Black-and-white photo of members of the NLM Board of Regents posing for a photo. Four members sit behind a table stacked with papers. 13 members stand in the background. Dr. Rogers is featured on the far right.
Dr. Frank Rogers (far right) with the NLM Board of Regents meeting in the “Old Red Brick,” 1957.

Along with the challenges of training staff to work with ADP equipment came the interminable problem of cost. Much as today’s public institutions are grappling with the costs of cloud computing, digitization, and increasing storage requirements, Dr. Rogers had to balance the potential benefits with the considerable costs of computer equipment. The type of computer necessary to realize Dr. Rogers’ vision would cost about $1.5 million in 1960—98% of NLM’s total budget of $1,566,000.

Undeterred, Dr. Rogers found an answer to the funding problem by collaborating with another agency that would benefit from the increased processing speed of scientific literature that the envisioned system could provide: the National Heart Institute. They provided the initial funding, NLM did the legwork, and in 1963, the new MEDLARS computer went into service. Dr. Rogers had realized his vision of bringing automated indexing to NLM. As Surgeon General Luther Terry said at the Board meeting in April 1961, “If any institution ever stood on the borderland of a new frontier it is the National Library of Medicine.”

Computer operators working with the Honeywell 800 mainframe computer, originally acquired by NLM in the 1960s.

Dr. Rogers was very clear about the issues of cost, labor, and expectations in his 1960 presentation to the Board, including his overarching concern about balancing NLM’s core mission with these potential new directions:

[The] purpose of the Library is not to operate a particular machine system, however great an acrobatic achievement that might be in itself. It is not to publish and distribute a particular index in a particular way, however ingenious and successful that operation may be deemed to be. It is not even just to be a good library, however great and distinguished that library may be. It is rather, by virtue of being a library, to use every available bibliothecal means to promote awareness of and access to the subject content of recorded medical knowledge, to the end that the science of medicine will advance and prosper.

More than 60 years later, NLM still holds fast to that purpose. As stated in our statutory mission and reiterated in our current strategic plan, we are here “to assist the advancement of medical and related sciences and to aid in the dissemination and exchange of scientific and other information important to the progress of medicine and to the public health.” Our continued pioneering work in data science is just one way we accomplish that mission.

Mr. Koyle joined HMD in the NLM Division of Library Operations in 2012. Before joining NLM, Ken served as a medical evacuation helicopter pilot and a historian in the U.S. Army. He is the co-editor with Jeffrey Reznick of Images of America: U.S. National Library of Medicine, a collaborative work with HMD staff.

Midnight in the Library

Right now, I am reading The Midnight Library by Matt Haig. It’s a fanciful story of a woman in limbo between life and death who finds herself in a magical library, and each book represents one of the lives she could have lived had she made even one tiny different decision. She then finds herself in many of these lives, experiencing what could have been.

This book got me thinking about how NLM helps people experience lives that could be. I see this on two levels:

The first is the scientific pathway: What if . . . ? What if we knew more about the interactions between evolutionary forces and molecular constraints (like the work of Aravind Iyer, PhD), or fully appreciated the potential of proteins for genome engineering (like the discoveries made by Eugene Koonin, PhD), or could envision how and why proteins fold or switch their folds (as explored by Lauren Porter, PhD), or had the power to enable machines to understand human thought (like the research from Dina Demner-Fushman, MD, PhD). In addition to the discoveries by our NLM intramural researchers, our vast literature and data repositories hold answers that could change lives: why some genetic structures lead to human characteristics, or why a certain biochemical compound helps prevent infection. We help scientists discover these pathways and connections by providing them with the tools to uncover what could be.

The second is how NLM helps people see their what if using the amazing richness of the resources that we make available through our collections. Our resources—which encompass clinical insights, medical information, care guidelines, and self-management—help clinicians determine how to care for people with complex diseases or diagnose an illness in a timely manner. Our repository of clinical information available through PubMed ensures that those in need can access well-reasoned, recognized guiding principles for their care, and our MedlinePlus web resource provides patients and their families and friends with reliable, up-to-date health information to support and encourage healthy behavioral changes.

As in The Midnight Library, books alone do not inspire discovery, guide clinical care, or inform self-management. In Haig’s novel, a fictional librarian who knows the collection shows the main character how to select books by carefully listening to her goals and needs. It is the main character’s engagement with the books that helps her explore the lives she could have lived. At NLM, we too have librarians—located in Bethesda, Maryland, and around the country through NLM’s Network of the National Library of Medicine—who organize the library’s collections and guide patrons toward the best choice of resources. Our resources must be findable, accessible, interoperable, reusable, and actionable! And then, the person—scientist, clinician, patient—must actively engage with the material.

As we approach the future of data-powered health, guided by the NLM Strategic Plan (2017-2027), we will fulfill our mission to collect biomedical literature, organize it, preserve it, and make it accessible to the world. As the knowledge of health and biomedicine continues to grow faster than we can process, we will turn our attention to applying emerging tools, including machine learning and artificial intelligence, to make it easier to find our materials and more efficient to examine them. Through our Extramural Programs, we will continue to stimulate new ways of presenting information to scientists, clinicians, patients, and the public so they can explore possible lives to be lived and test out their promise of better health for society. What lives can we help you explore?

MLA ’22: NLM as an Engine for Innovation and Discovery

Guest post by Amanda J. Wilson, Chief of the NLM Office of Engagement and Training (OET), and Dianne Babski, Associate Director for Library Operations.

NLM is excited to participate in the annual Medical Library Association (MLA) conference MLA ’22: Reconnect, Renew, Reflect, held virtually from April 27 to May 2 and on-site in New Orleans from May 3 to 6.

Information on how NLM products, services, and programs support innovation and discovery is available at NLM @ MLA’22. We encourage to you visit the NLM Technical Showcases on May 5 for a PubMed update with Amanda Sawyer, an introduction to NIH Data Management and Sharing Policy from Dr. Lisa Federer, and a PubMed Central update and information about NIH preprints with Katie Funk. The NLM Update on May 6 with Dianne Babski, Amanda Wilson, and Network of the National Library of Medicine (NNLM) Project Director Martha Meacham will include the latest activities and be followed by an interactive Q&A.

If you missed the April 28 session, check out the NNLM Day @ MLA: National Update page to hear about NNLM members’ work and accomplishments over the past year and to learn how the regions took advantage of their new configuration, partnerships, upcoming activities, and available opportunities. For example, the NNLM Center for Data Services hosted a session to help professionals implement the NIH Data Management and Sharing Policy, with concurrent sessions from the NNLM Training Office and NNLM Public Health Coordination Office. NNLM Day will reconvene in November 2022, so be sure to let us know your topics of interest.

MLA, which comprises more than 400 institutions and 3,000 professionals, is one of NLM’s key stakeholder groups that inform our products, initiatives, and services. MLA’s annual meeting offers NLM the opportunity to introduce new products and initiatives, get feedback on our services, and explore ways to better support the medical library community. As an NIH institute and a national library, NLM continually adapts to changes in the research ecosystem, including data standards, scientific developments, technological advancements, and the evolving norms of how we operate together.

As a catalyst for innovation and discovery, NLM is committed to equipping health science information professionals and the public at large with tools, platforms, and the ability to conduct today’s data-intensive research and community outreach. Please visit NLM @ MLA’22 to learn how you can become part of this partnership as we develop health information solutions and joint programs to support the future of health information.

Ms. Wilson coordinates engagement, training, and outreach staff from across NLM to elevate NLM’s presence across the United States and internationally. OET is also home to the Environmental Health Information Partnership for NLM and coordinates the Network of the National Library of Medicine.

Ms. Babski is responsible for the management of one of NLM’s largest divisions, with more than 450 staff, who provide health information services to a global audience of health care professionals, researchers, administrators, students, historians, patients, and the public.

Meet the NLM Investigators: L. Aravind Iyer, PhD, Uncovers the Language of Our DNA

NLM is home to a robust research enterprise. Before the COVID-19 pandemic, I introduced you to two researchers from our Intramural Research Program (IRP), Dr. Lauren Porter and Dr. Xiaofang Jiang.

Now I would like you to meet another one of our researchers, L. Aravind Iyer, PhD. A member of the NLM IRP, Dr. Iyer is a Senior Investigator in the Computational Biology Branch of the National Center for Biotechnology Information. His research revolves around uncovering the stories and patterns held within DNA and RNA and is aimed at unraveling the evolutionary forces that shape biochemical functioning and biological form.

Just like any other biological structure, DNA and RNA evolve over time, which can tell a complex story of an organism’s past and illustrate relationships between organisms that aren’t obvious.

See the infographic below to learn more about the exciting research happening in Dr. Iyer’s lab.

Infographic titled: Language of Our DNA and RNA. Listing the featured researcher, L. Aravind Iyer, PhD and his title, Senior Investigator in Computational Biology. 

The first column of the infographic reads: What I'm Working On. The text in the first column lists Dr. Iyer's short term goals to: (1) Decipher evolutionary relationships of organisms (vertical and lateral) and proteins; and (2) Computationally discover biochemical activities of proteins. Next, long term goals are listed as: (1) Create a unified evolutionary theory for biological conflicts; and (2) Understand the contributions of rapid evolution in conflict on other systems.

The second column is titled: How It Works and lists the following text: (1) Reading an evolving story written in DNA/RNA and protein sequences.

(2) Closing gaps in our understanding by applying computational and statistical methods on databases to compare protein sequences and structures.

(3) Determine vertical (ancestral with a picture of an arrow pointing to  descendant) and lateral (one organism with a picture of an arrow pointing to another organism) flow of genetic information.

The third and final column of the infographic is titled: What It Looks Like and has a book in an indecipherable language with a caption that says: Deciphering the language of life written in DNA/RNA and protein sequences.


Now, in his own words, learn more about the man behind the research!

What do you enjoy about working at NLM?
NLM is one of the world’s leading centers (such can be counted on one’s fingers) for deciphering the biochemistry and biology of proteins through computational analysis of sequences and structures. As a national lab, it has an organizational structure and funding framework best suited for the kind of research that I do, which involves an extensive explorative component.

What makes your team unique?
My team embodies a considerable mass of special knowledge regarding protein evolution and function that we accumulated and systematized over a period of several decades. Given that we look at this using various computational methods, my team melds the expertise of people well versed in biology, computer programming, biochemistry, protein structure, and graph-theoretic analysis.

What is your advice for young scientists or people interested in pursuing a career in research?
I think the most interesting discoveries are those that bring together and illuminate disparate areas of inquiry. Hence, spend your early youth acquiring a very diverse knowledge base and technical capacity. Then organize this knowledge into an interconnected network that you can train your intuition on and draw from when confronted with new problems.

When you’re not in the lab, what do you enjoy doing?
Amateur astronomy, reading and writing about history and ancient texts in the original or translations, recreational mathematics, storytelling.

What inspires you?
Lives of past scientists, philosophers, and leaders from around the world. The profound insights found in the works of the ancients.

You’ve read his words, but now you can hear them for yourself. Follow along on the NLM YouTube page for more exciting content from the NLM staff that makes it all possible. If you’d like to learn more about our IRP program, view job opportunities, and explore research highlights, I invite you to explore the newly redesigned NLM IRP webpage.

YouTube: Dr. Aravind Iyer and the Protein Universe

Video transcript

[Iyer] Early in my life, I wanted to be a paleontologist. And that’s what actually led me to molecular biology. At one level, I could say that I wish to understand the whole protein universe. Proteins can be divided into evolutionary units. There’s a part of a protein that’s preserved over evolution because natural selection is maintaining that part for some reason. And one realization, which dawned on us starting around the early nineties—and this was a very profound realization for all of biology—is that there is a relatively small number of these evolutionary units of proteins, which we term domains, which constitutes the entire protein universe of all organisms across the tree of life.

If we can understand the functions of these units, then that goes a long way towards understanding what organisms do. And given there are many gaps in our understanding of what organisms do, one way to get at it is to first, find all these domains. The second aspect of it is predicting functions for them. The first phase of my research, we captured most of the low-hanging fruit, which were the big families conserved across all organisms.

Now we are moving on to the more difficult terrain, but the difficult terrain also holds a lot of promise because many un-understood functions are hiding within that difficult terrain, and it gives these offshoots in the form of biotechnological reagents. There are things like restriction enzymes, the CRISPR systems, and DNA modification systems. All of these have become very popular reagents.

NLM is a world leader in the analysis of protein sequences, protein structures, and inferring evolution from these bits of information. And this has been a very long-standing interest of mine so, this is the place to be.

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