Bornavirus In 1989, Lipkin was the first to identify a
microbe using purely molecular tools. During his time as chair at UC Irvine, Lipkin published several papers throughout the decade dissecting and interpreting
bornavirus. Once it was apparent the viral infections could selectively alter behavior and steady state brain levels of
neurotransmitter mRNAs, the next step was to look for infectious agents which could be used as probes to map anatomic and functional domains in the
central nervous system (CNS). By the mid-1990s, it was asserted that "Borna disease is a neurotropic negative-strand RNA virus that infects a wide range of vertebrate hosts," causing "an immune-mediated syndrome resulting in disturbances in movement and behavior." This led to several groups across the globe working to determine if there was a link between Borna disease virus (BDV) or a related agent and human neuropsychiatric disease. The group was formally called Microbiology and Immunology of Neuropsychiatric Disorders (MIND) and the multicenter, multi-national group focused on using standardized methods for
clinical diagnosis and blinded laboratory assessment of BDV infection. After nearly two decades of inquiry, the first blinded case-controlled study of the link between BDV and psychiatric illness was completed by the researchers at Columbia University's Center for Infection and Immunity in a joint effort that concluded there is no association between the two. Lipkin noted that "it was concern over the potential role of BDV in mental illness and the inability to identify it using classical techniques that led us to develop molecular methods for pathogen discovery. Ultimately these new techniques enabled us to refute a role for BDV in human disease. But the fact remains that we gained strategies for the discovery of hundreds of other pathogens that have important implications for medicine, agriculture, and environmental health."
West Nile Virus In 1999,
West Nile virus was reported in two patients in
Flushing Hospital Medical Center in Queens, New York. Lipkin led the team identifying West Nile virus in brain tissue of
encephalitis victims in New York State. During the five years after the first reported case, Lipkin worked on a study with the
National Institutes of Health (NIH) and the
Wadsworth Center at the
New York State Department of Health to determine how a vaccine could be developed. While they had some success with the immunization of mice with particles resembling the structural protein prME of West Nile Virus, as of 2018, there is still no human vaccine for West Nile Virus.
SARS-CoV Chinese scientists first discovered the
severe acute respiratory syndrome (SARS)
coronavirus in February 2003, but due to initial misinterpretation of the data, the information of the correct agent associated with SARS was suppressed and the outbreak investigation had a delayed start. Advanced hospital facilities were at the greatest risk as they were most susceptible to virus transmission, so it was the "classical gumshoe epidemiology" of "contact tracing and isolation" that brought swift action against the
epidemic. Lipkin was requested to assist with the investigation by Chen Zhou, vice president of the
Chinese Academy of Sciences and Xu Guanhua, minister of the
Ministry of Science and Technology in China to "assess the state of the epidemic, identify the gaps in science, and develop a strategy for containing the virus and reducing morbidity and mortality." This brought the development of
real-time polymerase chain reaction technology, which essentially allowed for the detection of infection at earlier time points as the process, in this instance, targets the N gene sequence and amplify the analysis in a closed system. This markedly reduces the risk of
contamination during processing. Test kits were developed with this PCR-based assay analysis and 10,000 were hand-delivered to Beijing during the height of the outbreak by Lipkin, whereupon he trained local clinical microbiologists on the proper usage. He became ill upon his return to the U.S. and was quarantined. Lipkin was asked to join the
Defense Science Board Task Force on SARS Quarantine Guidance during the height of the SARS outbreak between 2003 and 2004, to advise the
U.S. Department of Defense on steps to domestically manage the epidemic. As part of the EcoHealth Alliance, Lipkin's center worked in conjunction with an
NIH/
NIAID grant assessing bats as the reservoir for the SARS virus. 47 publications resulted from this grant, which also included assessment on
Nipah,
Hendra,
Ebola, and
Marburg viruses. This proved to be significant research on the overall study of viral reservoirs as it was determined that bats carry coronaviruses and either directly infect humans with an exchange of bodily fluid (such as a bite) or indirectly by infecting an intermediate host, such as swine. Lipkin addressed a health forum in Guangzhou in January 2004 where China Daily reported him as saying: "SARS virus is probably rooted and spread by rats." In 2016, the Chinese government awarded him the International Science and Technology Cooperation Award, the nation's top science honor for foreign scientists, and in January 2020, it awarded him a medal marking the People's Republic of China's 70th Anniversary, both awards for his work during the
2002–2004 SARS outbreak and in strengthening China's public health system.
MERS-CoV Middle East respiratory syndrome (MERS) was first reported in
Saudi Arabia during
June 2012 when a local man was initially diagnosed with acute pneumonia and later died of
kidney failure. The early reports of the disease were similar to
SARS as the symptoms are similar, but it was quickly determined these cases were caused by a new strain called
MERS coronavirus (MERS-CoV). Given Lipkin's expertise with the
SARS outbreak in
China nearly ten years prior, the
Saudi Arabian Ministry of Health granted Lipkin and his lab local access to animal samples related to the initial reported cases. With the rare opportunity, Lipkin's team created a mobile lab able to fit in six pieces of personal luggage and was transported from
New York to
Saudi Arabia via commercial flight to complete the analysis of samples. It seemed unlikely that bats were directly infecting humans, as the direct physical interaction between the two is limited at best. However, it became apparent that
dromedary camels were the intermediary in the transmission between bats and humans, since camel milk and meat are dietary staples in the Saudi Arabian region. The instances of human-to-human transmission appeared to be isolated to case-patients and anyone in close direct contact with them, as opposed to a broad open-air transmission. By 2017, it was determined that bats are most likely the evolutionary original source for
MERS-CoV along with several other coronaviruses, though not all of those types of zoonotic viruses are direct threats to humans like
MERS-CoV and "[c]ollectively, these examples demonstrate that the MERS-related coronaviruses are high associated with bats and are geographically widespread."
Myalgic encephalomyelitis/chronic fatigue syndrome Myalgic encephalomyelitis/chronic fatigue syndrome (
ME/CFS) is a chronic condition characterized by extreme fatigue after exertion that is not relieved by rest and includes other symptoms, such as muscle and joint pain and cognitive dysfunction. In September 2017, the NIH awarded a $9.6 million grant to
Columbia University for the "CfS for ME/CFS" intended for the pursuit of basic research and the development of tools to help both physicians and patients effectively monitor the course of the illness. This collaboration effort led by Lipkin includes other institutions, such as the Bateman Horne Center (Lucinda Bateman),
Harvard University (
Anthony L. Komaroff),
Stanford University (Kegan Moneghetti), Sierra Internal Medicine (
Daniel Peterson),
University of California, Davis (Oliver Fiehn), and
Albert Einstein College of Medicine (John Greally), along with private clinicians in New York City. The team of researchers and clinicians initially collaborated to de-link
xenotropic murine leukemia virus-related virus (XMRV) to
ME/CFS after the NIH requested research into the conflicting reports between
XMRV and ME/CFS. The group "consolidated its vision with support from the Hutchins Family Foundation Chronic Fatigue Initiative and a crowd-funding organization, The Microbe Discovery Project, to explore the role of infection and immunity in disease and identify
biomarkers for diagnosis through functional
genomic,
proteomic, and
metabolomic discovery." The project will collect a large clinical database and sample repository representing oral, fecal, and blood samples from well-characterized
ME/CFS subjects and frequency-matched controls collected nationwide over a period of several years. Additionally, researchers are working with
ME/CFS community and advocacy groups as the project progresses.
Acute flaccid myelitis (AFM) Acute flaccid myelitis (AFM) is a serious condition of the spinal cord with symptoms including rapid onset of arm or leg weakness, decreased reflexes, difficulty moving the eyes, speaking, or swallowing may also occur. Occasionally numbness or pain may be present and complications can include trouble breathing. In August 2019, Lipkin and Dr. Nischay Mishra published a collaborative study with the
CDC in analyzing serological data for serum and
cerebrospinal fluid (CSF) samples of AFM patients. The Lipkin team utilized high-density peptide arrays (also known as Serochips) to identify antibodies to
EV-D68 in those samples. The technology was featured on the Dr. Oz Show in mid-September, illustrating how the enterovirus affects the CSF and the actual Serochip used to do the analysis. In October, the
University of California, San Francisco published a separate collaborative study with the
CDC that confirmed the presence of antibodies to
enterovirus in AFM patient CSF samples using phage display (VirScan). "It's always good to see reproducibility. It gives more confidence in the findings for sure," commented Lipkin in an October 2019 CNN article. "This gives us more support of what we found."
SARS-CoV-2 According to the
Financial Times, Lipkin first learnt of
COVID-19 from contacts in China, where it first emerged, in mid-December. In early January he repeatedly urged his Chinese counterparts to publish the virus's genetic sequencing to aid research, and visited senior Chinese officials, including
Premier Li Keqiang, to discuss the disease. Lipkin described his engagement with the early COVID-19 investigations during an April 2023 interview with the
U.S. House of Representatives Select Committee on the Coronavirus Pandemic. On January 29, 2020, Lipkin flew into
Guangzhou,
China to learn about the outbreak of
SARS-CoV-2. Lipkin met with the epidemiologist and pulmonologist
Zhong Nanshan, the lead advisor to the Chinese government during the outbreak. Lipkin also worked with the
China CDC to access blood samples from across the country for further study into the origin and spread of the virus. Lipkin did not travel to
Wuhan, the epicenter of the outbreak, due to fears that this would prevent him from returning to the United States. On returning to the United States, Lipkin self-quarantined for 14 days. Lipkin later contracted SARS-CoV-2 in New York City, refusing to go to hospital and treating himself with
hydroxychloroquine at home. The conclusion of the genomic analyses was that COVID-19 was not a case of lab leak or human-made infection. In 2023, the paper was alleged by the US Republicans as a coverup based on certain misconducts to eliminate the
lab leak theory. The paper and the controversy became known as the "
Proximal Origin". ==Selected awards and honors==