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Research Matters

By Terry Magnuson, October 6, 2021

Although international collaborations present significant research opportunities, challenges face U.S.-based institutions working across national borders. Enhancing international collaboration requires recognition of differences in culture, legitimate national security needs, and critical needs in education and training. To address these matters, in 2011 the National Academies held the Examining Core Elements of International Research Collaboration workshop. They concluded that the globalization of science, engineering, and medical research is proceeding rapidly.

In 2019, the Federation of American Societies for Experimental Biology (FASEB), which represents 30 U.S. scientific societies, reaffirmed the importance that international collaborations have on discovery and innovation. Such collaborations play critical roles in biological research, ranging from deciphering the human genome to stemming the spread of infectious diseases, such as Ebola, Zika, and now COVID-19. FASEB emphasized the delicate balance between fostering an environment of open scientific collaboration while protecting U.S. investments and discoveries. Policies that confirm appropriate utilization of critical resources and discoveries are needed to ensure continued engagement of international scholars in U.S. research endeavors.

Most recently, the American Academy of Arts and Sciences undertook an initiative called the Challenges for International Scientific Partnerships (CISP) to assess the importance and the complexities of international scientific collaborations. In their report “America and the International Future of Science,”  the Academy highlighted the importance of worldwide science by quoting President Harry Truman: “When more of the peoples of the world have learned the ways of thought of the scientist, we shall have better reason to expect lasting peace and a fuller life for all.”

The CISP initiative outlined several recommendations to address the challenges of international scientific collaboration:

  • Any restrictions on international collaborations involving federally supported research should be well-justified and carefully/narrowly defined. Large-scale scientific endeavors are an important component of our nation’s overall science and technology enterprise. The United States must be prepared to contribute support for operations outside the United States. Scientific talent arises across the globe at an increasing rate as many countries invest in building a more robust science and technology enterprise.
  • Many of the most pressing scientific questions are not defined by national boundaries and require global collaboration for advancement. Both fundamental questions and those related to broad societal problems frequently involve people with different capabilities, perspectives, and access to resources. Forming teams with the best skills to address a research challenge increasingly draws on international collaborators.
  • To maintain leadership in fundamental research, it is essential that the United States continues to have an academic education and research system that is open, strong, and attractive and welcoming to international students. In 1960, federal funding represented 45% of all global R&D, while today it accounts for less than 10%. Our country should examine investing in R&D and approving policies that facilitate, support, and foster its scientists in collaborating internationally.
  • The United States must engage with the broader scientific community if America is to be among the world leaders across all scientific fields. Scientific partnerships are an important element of foreign policy and international relationships and necessitates cooperation.
  • The United States must look not only to those nations that are presently strong, but also to those that are emerging, as scientific partners. Without support and commitment to collaboration from the U.S. government, U.S. scientists may be excluded from some of the world’s leading scientific projects and associated technological advances, especially as multinational funders promote increasingly large international projects.
  • Most importantly, the United States must be engaged in the development of global ethical frameworks for research. As discoveries and technological capacities increase, ethical questions are becoming more complex.

The scientific community certainly understands the benefits of international scientific collaboration. However, risks of such collaboration to U.S. national security are now at the forefront of debate. Those risks must be acknowledged along with the benefits from scientific collaboration with countries that are potential adversaries.

Permalink: The U.S. and International Science

By Terry Magnuson, September 1, 2021

A recent Science Focus article discussed theories of why giraffes have long necks. The most obvious suggested that their length, which can reach up to 6 feet, evolved because it gives the animal access to the topmost leaves of trees, eliminating competition for food. Another theory is that the long neck is used as a weapon, wielded in fights between males. Male giraffes indulge in bouts of “neck fighting” to gain access to females, swinging their necks at each other and using their thick, heavy heads to break vertebrae. The males that reproduce most successfully do have the longest necks.

If sexual selection is the cause, males should have noticeably longer necks than females — but the difference is too small to be explained by sexual selection alone. Another theory is that the long neck helps the animal spot predators, or maybe the large surface area assists in regulating body temperature. It might also have evolved in response to giraffes’ legs getting longer, ensuring that they could continue to drink at waterholes.

Whatever the reason for the long neck, it creates a physiological engineering problem as described in a recent Science Advances article, which was summarized in a Science commentary. Researchers from China, Norway, and Denmark compared gene variants of a male giraffe with those of other mammals, including the giraffe’s closest relative: the short-necked, zebra-sized okapi. These animals diverged about 11.5 million years ago. The data identified 490 genes with unique adaptations in the giraffe. Many of the DNA variants were in genes linked to cardiovascular features, bone growth, and the sensory system.

A giraffe’s heart must pump blood at a pressure that is approximately 2.5 times higher than humans. DNA sequencing of the giraffe genome found seven unique DNA variants in the gene Fgrl1 (Fibroblast Growth Factor Receptor Like 1).

The researchers used CRISPR gene editing techniques to insert the giraffe variants into the Fgrl1 gene of mice. Not surprisingly, the mice did not grow long necks, and they did not show any obvious change in their cardiovascular system. However, when the researchers gave the modified mice a drug to induce high blood pressure, they stayed healthy, and their blood pressure rose only slightly. The unmodified control mice developed hypertension and associated kidney and heart damage.

The Fgfrl1 giraffe variant does something to the cardiovascular system that counteracts the effects of hypertension in mice, but the mechanisms are not known. There is not yet any evidence that Fgrl1 is one of the genes that causes hypertension in humans, but studying how the giraffe variants do protect mice from hypertension could lead to important new cardiovascular pathways for therapeutic investigations.

The study also highlights other DNA variants unique to the giraffe. Previous research has shown that giraffes have the best vision of all hoofed mammals, which — with their height — allows them to scan the horizon more effectively than other animals. The study also shows that the giraffe lost at least 53 olfactory genes compared with the okapi. So it traded its sense of smell, which is not as important given how far off the ground their head is, for improved eyesight — a definite benefit for their height. The team also found variants in genes that regulate sleep patterns. These findings could explain why giraffes only sleep 40 minutes per day and about three to five minutes at a time.

I use giraffes to illustrate the importance of genomic variants in health. We now know that DNA differences in the gene have profound physiological differences across all mammals. How is this example tied to UNC Research’s priorities? One of our seven research priorities is “Precision Health and Society,” which is focused on tailoring health care practice, delivery, and therapeutics to unique individual circumstances, using factors from genetics to social and environmental influences.

Francis Collins, director of the National Institutes of Health, has declared precision health a priority initiative for the agency as well.

“Precision medicine is really an effort to capture all of the specifics about an individual’s health from their environmental exposures, health behaviors, various aspects of their physiology, their metabolism, as well as genetic information through a variety of genomic loci,” Collins recently shared.

Just as giraffes’ necks allow them to reach great heights, the expertise of UNC researchers allows them to do the same across fields. I look forward to sharing more regarding Carolina’s unique contributions to precision health and society later this year.

Permalink: Giraffes, Genomics, and Physiology

By Terry Magnuson, August 2, 2021

Amanda Phingbodhipakkiya was a budding neuroscientist when she shifted away from bench science to focus on enhancing how scientists communicate with the public. After receiving a master’s in fine arts from the Pratt Institute, she launched her career as a science-focused muralist known for expressing complex ideas through art. One example of her work is Beyond Curie, a portrait series of 42 women who have made significant contributions in STEM fields.

The National Academies expands on Phingobodhipakkiya’s work of bridging the arts and humanities with hard sciences through a study that unpacks how the integration of work by artists and humanists with scientists promotes innovative thinking, new spaces, and ideas.

And it is universities that create conditions for discovery by sustaining robust, multi-stranded, creatively adaptable research and scholarly and artistic missions.

UNC-Chapel Hill’s strategic plan, Carolina Next: Innovations for Public Good, emphasizes the importance of promoting and integrating the scholarly work of artists and scientists. Biologist Bob Goldstein is one of many of our faculty doing just that. His research uses the nematode C. elegans to understand how cells develop into organisms. But it was his interest in the arts that inspired him to launch Art & Science: Merging Printmaking and Biology — a two-part honors course he teaches alongside art professor Beth Grabowski. Goldstein has also taken integrating arts and science to heart through his own artistic work, Gig Posters for Scientists, which are hand screen printed posters for distinguished scientists visiting Carolina. He learned the art form from Grabowski, who literally wrote the book on printmaking.

Goldstein and Grabowski share a common interest in what it means to think like both an artist and scientist. Of the 14 slots in their course, seven are filled by students who meet biology prerequisites and seven by students who meet art prerequisites. This creates an interesting mix of students who may not have encountered one another otherwise. The recent Endeavors story “Through a Different Lens,” describes how the course strengthens education by allowing students to step outside their major to do something new.

Jacqueline Lawton, a talented faculty member from the Department of Dramatic Art, explores how theater can convey health and environmental issues to the public. In 2016, she wrote and developed “ARDEO,” a one-act play about the lives of health practitioners and victims of burns. She worked in collaboration with School of Medicine professors Bruce Cairns and Amy Weil to explore how patients and doctors communicate with each other and how theatre artists can be of service to patients, doctors, and the public at large.

She followed that play with “Freedom Hill,” which focused on environmental justice in coastal communities. For its development, she worked in collaboration with David Salvesen, Mai Nguyen, and Amy Cooke, all three of whom are members of environmental programs at UNC. The play tells the story of the founding of Princeville, North Carolina, and how its people continually face the rising tides of the Tar River. Although not a coastal city, and despite being fortified by a levee, the Tar River floods during major hurricanes, causing continual devastation to the community.

An exciting new Carolina program that illustrates even broader scholarly interconnections is the Southern Futures Initiative — a campus-wide initiative connecting the arts, history, public health, and entrepreneurship — which is supported by UNC’s world-class archives and library expertise. Southern Futures aims to cultivate vibrant scholarship about the American South by engaging literary scholars, historians, geographers, anthropologists, religious studies scholars, and others that have sustained long-term inquiry in North Carolina, across the United States, and abroad.

Given that today’s challenges and opportunities are both technical and social, addressing them calls for the full range of human knowledge and creativity. I am excited the strategic plan can be a successful path toward this type of critical integration.

Permalink: Creating Discoveries through Artistic Endeavors

By Terry Magnuson, July 1, 2021

President Biden’s FY2022 discretionary budget request to Congress includes $6.5 billion for creating an Advanced Research Projects Agency for Health (ARPA-H) within the National Institutes of Health (NIH). Authorization for ARPA-H is also included in the Cures 2.0 bipartisan draft legislation that was released on June 22. The goal of the agency will be to “drive transformational innovation in health research and speed application and implementation of health breakthroughs.”

NIH Director Francis Collins, together with White House Office of Science and Technology Policy (OSTP) Director Eric Lander, OSTP’s Tara Schwetz, and NIH’s Larry Tabak published a commentary in Science outlining how ARPA-H would focus on time-limited projects with goals, benchmarks, and accountability to develop a flexible and nimble strategy for preventing, treating, and curing a range of diseases. The article was followed up with a webinar conducted on June 25, where Collins and Lander answered questions.

ARPA-H is a new model for NIH, which usually supports peer-reviewed fundamental research in university, non-profit, and government labs. Scientists funded by NIH have discovered molecular and cellular mechanisms underlying health and disease, which have led to new clinical treatments. The commentary cites two articles (1,2) showing that fundamental discoveries supported by NIH have been critical for new therapeutics approved by the US Food and Drug Administration. To be sure, the model by which NIH supports fundamental research will not change. But the authors argue that high risk/high yield innovative ideas do not always fit existing NIH support mechanisms — most proposals are directed at solving practical problems.

President Biden stated that ARPA-H should be modeled after the Defense Advanced Research Projects Agency (DARPA) that embraces a nimble, flexible research strategy that accepts failure. The DARPA approach has driven breakthrough advances for the Department of Defense for more than 60 years. Building on DARPA’s success, Collins et al. argue that an initial mission could be, “To make pivotal investments in breakthrough technologies and broadly applicable platforms, capabilities, resources, and solutions that have the potential to transform important areas of medicine and health for the benefit of all patients and that cannot readily be accomplished through traditional research or commercial activity.”  The commentary stresses that those projects supported by ARPA-H would develop solutions that foster breakthroughs to serve patients at levels ranging from the molecular to the societal and to drive those solutions to the point of adoption.

Although an exciting concept for NIH, Collins acknowledges a lot of work and community input are needed to organize this new approach. DARPA can serve as a model, but biological systems are much more complex than the engineered systems on which DARPA focuses. ARPA-H will need to pioneer new approaches.

It is important to note that ARPA-H is to be funded with new appropriations that will not cut into increasing base budgets for NIH’s 27 institutes and centers. And any new medical treatments that come out of ARPA-H will still need to go through the long road of clinical testing and regulatory approvals. Although there is widespread enthusiasm supporting opportunities to improve the way NIH operates, the authors acknowledge that a focus only on short-term results would undermine approaches that have made possible advances to technologies for detecting, treating, and curing diseases.

Permalink: NIH on a Path to Add a DARPA-Like Model

By Terry Magnuson, June 1, 2021

In April, Nature reported on the rules and regulations that U.S. universities and researchers must adhere to when reporting foreign financing and collaborations. While new, these rules do not represent a significant change from the past. U.S. funding agencies have required grantees to report funding from foreign sources for some time. What has changed is that since 2018, penalties — and, in some cases, criminal charges —  have been more frequently imposed on scientists who failed to report foreign activities. Most cases involved funding from the Chinese government, and the arrest or censure of many scientists of Chinese descent. Rightfully so, concerns were expressed by the scientific community that these actions amounted to racial profiling.

In 2019, the National Science and Technology Council (NSTC) launched an effort to clarify and strengthen national policies on research security by issuing a unified set of guidelines for universities to create teams devoted to all aspects of research security, including cybersecurity and export controls. These teams also provide training for faculty members in these areas and those who are considering participating in foreign talent programs that recruit and fund researchers for their expertise. Funding agencies were instructed to establish ways to vet foreign visitors. Along with the NSTC guidelines and memorandum, the National Defense Authorization Act (NDAA) included some broad research security requirements, such as federal agencies must have disclosure rules, and that the Office of Science and Technology Policy (OSTP) must ensure the rules are consistent across agencies.

The NSTC report was issued just days before President Biden was sworn in. On May 28, geneticist Eric Lander was confirmed by the Senate as the next director of OSTP, so follow-through on NSTC guidelines may be getting traction soon. In February, several university groups, including the Association of Public and Land-grant Universities (APLU) and the Association of American Universities, sent a letter to the Biden administration asking for a public comment period to air their views on the report, which is typical before major agency announcements. As of April 5, a response has not been received. It is still unclear how the new administration will approach the concerns of universities and scientists.

Nonetheless, the National Institutes of Health (NIH) has moved ahead and is now asking for copies of contracts or agreements with foreign institutions when applying for or submitting updates on existing grants. The implementation of these changes has been delayed until January 25, 2022. The agency is also requiring scientists to certify by electronic signature that the information submitted in applications about foreign funding is accurate.

Few would argue the importance of preventing foreign espionage and intellectual theft on university campuses. However, universities are speaking out against overly burdensome regulations. In addition, immigration of thousands of students and scholars — which has been critically important to science and innovation — has come under threat in this country. There is no question that immigration of highly skilled scientists increases the economic, intellectual, moral, and public health of this country.

As AAU President Barbara R. Snyder recently stated: “We are pleased that President Biden has proposed a path for the best and brightest from around the world to stay and continue to contribute to our nation after finishing their graduate studies in the United States.” She adds that Congress must act now on implementing long-term immigration reform that will keep home-grown talent while attracting the world’s best and brightest scholars.

I ended last month’s Research Matters with the AAU’s recommendations for strengthening American higher education through opportunity, accountability, equity and inclusion, and safety. With the President’s proposed investment in research and ongoing congressional hearings supporting a stronger research budget, coupled with the acknowledgement of the importance of international science, the research community is ready for a research ramp-up.

Permalink: Foreign Influence, Immigration, and Funding