Orexin—a brain peptide that maintains wakefulness

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Emmanuel Mignot

Stanford University School of Medicine

Masashi Yanagisawa

University of Tsukuba

For identification of orexin, a brain peptide that maintains wakefulness, and the discovery that orexin deficiency causes uncontrolled sleep in narcolepsy—revealing a key insight into the nature of sleep

The 2026 Albert Lasker Basic Medical Research Award honors two physician scientists for the identification of orexin, a brain peptide that maintains wakefulness, and for discovering that orexin deficiency causes uncontrolled sleep in narcolepsy. Through an astounding experimental intersection, Emmanuel Mignot (Stanford University School of Medicine) and Masashi Yanagisawa (University of Tsukuba) revealed a key insight into the nature of sleep. Yanagisawa began with an intriguing cellular protein of unknown function. Through an ambitious biochemical approach, he unearthed peptides that animate it and demonstrated that the resulting signaling system keeps animals awake. Mignot started, in contrast, with clear physiology—the disease narcolepsy. Individuals with this neurological disorder succumb to bouts of sleepiness, and the most common form prompts sudden loss of muscle tone and even collapse. In a heroic feat of genetic sleuthing, Mignot tracked the source of inherited narcolepsy in dogs. His venture led to the same protein that Yanagisawa was studying. Their work has cracked open a molecular dissection of sleep regulation, reinforced the immune system’s involvement in human narcolepsy, and pointed toward new treatments for this illness and other sleep disturbances. In the United States, narcolepsy affects at least 1 in 2000 people. Experts believe that many cases are never diagnosed.

Rousing revelations

In the late 1990s, Gregor Sutcliffe (Scripps Research Institute, La Jolla) was looking for genes that operate in specific parts of the brain. In 1998, postdoctoral fellow Luis de Lecea showed that one of them—from a region called the hypothalamus—encodes a precursor of two peptides that resemble each other. A synthetic version of one of the peptides, which he named hypocretins, elicited an excitatory response in neurons grown in the lab. These observations suggested that the hypocretins are secreted neurotransmitters, made by a particular group of hypothalamic neurons.

The physiological role of the hypocretins would crystallize in the lab of Yanagisawa, then at the University of Texas Southwestern Medical Center. Simultaneously and independently, a different topic had captured him. A family of cell-surface proteins called G protein-coupled receptors (GPCRs) translate a vast array of environmental cues into appropriate responses by sparking intracellular signaling pathways. GPCRs had already proven themselves useful as targets for drugs that, collectively, treat myriad disorders.

Genomic studies had revealed many potential human GPCRs with unknown jobs. To explore the undeciphered biology that these so-called “orphan” receptors enable and expose new therapeutic possibilities, Yanagisawa sought molecules that stimulate them.

Toward that end, he undertook a search for peptides in the brain that would selectively goad particular GPCRs. He and postdoctoral fellow Takeshi Sakurai ground up rat brain and subjected the material to chromatography that sorted its components based on their chemical and physical properties. They applied the resulting portions individually to cultured human cells, each of which was engineered to produce a distinct orphan GPCR. Then they monitored for the calcium spikes that reflect receptor signaling.

Luck shined upon them, and the 5^th or 6^th receptor that they tested perked up. By sequentially harvesting the desired fractions and performing additional rounds of the procedure with different separation criteria, they purified two peptides that specifically provoke the receptor. Further analysis led them to genes that encode a precursor protein, containing both peptides, and a second GPCR, closely related to the first, that also responds to the peptides.

Additional experiments indicated that the peptides inhabit a portion of the brain’s hypothalamus that classical lesioning studies had implicated in feeding. To probe this connection, Yanagisawa injected the peptides into the brains of live rats. This treatment stoked food intake; furthermore, fasting boosted activity of the precursor gene. Yanagisawa named the neuropeptides orexins after the Greek word orexis, which means appetite. The orexins turned out to be identical to Sutcliffe’s hypocretins, reported the previous month. Yanagisawa had now unveiled both elements of the signaling system—the receptors as well as their triggers.

The following year, Yanagisawa and postdoctoral fellow Richard Chemelli engineered mice to lack the orexin genes, expecting that the manipulation would knock out an appetite instigator. To their chagrin, food consumption and body weight remained largely steady.

Maybe, reasoned Yanagisawa, grams of chow and weight perturbations didn’t tell the whole story of the animals’ eating behavior. Mice are nocturnal, so he decided to watch them at night, when they ingest most of their food. He and his trainees deployed an infrared camera, which allowed them to record in the dark. They played back the videos at double speed to save time, trading off this tedious task and trying not to doze off.

One day, Chemelli noticed something strange. A mouse that was grooming and scampering about suddenly fell on its side. It lay immobile for a minute or so—and then got up and resumed its activities. This phenomenon occurred in all of the mice that lacked orexin and never in those that carried even one normal copy of the gene.

Prominent among the possible explanations was epilepsy, so the researchers hooked up the mice to gadgets that would establish whether seizures were plaguing the rodents. During collapse, their muscles went slack and their brain waves reflected rapid eye movement (REM) sleep, the phase in which dreams occur. Typically, mice—and people—pass through a sizable period of non-REM sleep before entering REM sleep. The abrupt shift, without the intervening non-REM stage, mimics what happens in humans with narcolepsy.

Yanagisawa described these observations in August 1999 on the heels of a publication from a distant arena.

Sniffing out a narcolepsy gene

Two weeks earlier, Mignot had reported that an inherited form of canine narcolepsy arises from a mutation in the second orexin receptor gene that Yanagisawa had uncovered, orexin receptor-2. This success marked the culmination of a 10-year genetic mapping crusade.

In 1979, Stanford sleep-research pioneer the late William Dement had determined that two copies of a defective gene cause narcolepsy in Dobermans and Labradors; its identity was unknown. A decade later, Mignot decided to track down the culprit, a formidable task, given that the dog genome had not been sequenced or even coarsely mapped, and limited tools were available for the quest. But he didn’t want to pass up a shining opportunity to discern the basis of narcolepsy.

Although all of the affected dogs in each breed descended from a single ancestor, stretches of their DNA had diverged over generations, as chromosomes swapped chunks during sexual reproduction. The sick animals, though, shared the marred gene; moreover, the closer any DNA sequence lay to it, the greater the odds that it, too, would appear in individuals with disease. By exploiting this biological fact, Mignot homed in on his quarry.

After years of painstaking labor, he was eyeing a span of DNA that carried only two genes. Comparison with the same tract from healthy chromosomes revealed that the sequence of one of them was garbled in narcoleptic dogs; it encoded orexin receptor-2. Furthermore, Dobermans and Labradors held different genetic errors, each of which resulted in loss of a large—and distinct—chunk of protein.

At a stroke, Yanagisawa’s and Mignot’s discoveries—published within a single month—divulged the basis of one of the most mysterious neurological disorders. Narcolepsy in two mammalian species stems from insufficient orexin signaling (Figure 1).

Amazing experimental convergence
A project that aimed to assign function to a putative signaling-pathway receptor landed on the same molecular system as did a search that assumed nothing about cellular function, but pinpointed an abnormal piece of DNA with a known effect on an animal. Yanagisawa showed that lack of orexin causes narcolepsy in mice (top left); Mignot mapped the dog narcolepsy gene to the orexin receptor-2 (top right). The orexin pathway governs sleep and wakefulness (bottom).

The receptor structure was rendered using the Protein Imager web interface Tomasello G, Armenia I, and Molla G. Bioinformatics. 2020; 36, 2909–2911.
Illustration: Heather B. McDonald

Viral defense gone awry

Mignot knew that a single mutation in orexin or its receptor would not explain narcolepsy in humans. In contrast to the situation in dogs, the human affliction is rarely familial.

To dig deeper, he measured quantities of orexin in the cerebrospinal fluid of 17 people. It was undetectable in seven of the nine narcoleptic patients, yet it showed up in all eight controls. Examination of postmortem brain tissue backed up these data. The hypothalamus of people with narcolepsy displayed a global loss of the peptides and their messenger RNA: Either the cells that normally fabricate orexin had vanished or they had lost their capacity to manufacture the peptide. In contrast, neighboring, intermingled neurons that make a different neurotransmitter remained intact. This specificity indicated that selective catastrophe had struck the orexin system. At the same time, Jerome Siegel (University of California, Los Angeles) reported similar findings: Postmortem brains of people with narcolepsy lacked 85-95% of their orexin-producing neurons while nearby neurons persisted.

Mignot also studied the genes for orexin and its receptors in people with narcolepsy. As expected, 73 out of 74 of them carried normal sequences. The one individual with a mutation—in the orexin gene—had early-onset and severe disease, and the peptide got hung up in the intracellular secretory pathway. The absence of orexins in most human cases, along with the rare person who harbored the genetic glitch and suffered from unusually harsh symptoms, strongly implies that orexin deficiency underlies the illness.

These results revitalized an idea that narcolepsy arises from a misguided immune response. In the early 1980s, the late Yutaka Honda (University of Tokyo) linked the human leukocyte antigen (HLA) region of the genome to susceptibility. This zone encodes proteins that help protect the body from harmful microbes. Notably, certain versions of certain HLA genes predispose people to autoimmune disorders; in 1992, Mignot had pinned down the troublesome HLA signature for narcolepsy through a study of African Americans, whose genetic diversity in this area allowed him to disentangle the relevant contributor.

The 2009 H1N1 influenza pandemic fortified the autoimmune connection and provided mechanistic clues. Infection—or immunization with an especially potent vaccine against the virus—increased the risk for narcolepsy. Furthermore, a retrospective study by Mignot and colleagues in China uncovered a seasonal pattern of onset, consistent with the notion that winter upper-airway pathogens escalate vulnerability. Together, these observations suggested that a microbial trigger incites an immune attack—perhaps directly on orexin-producing neurons—in some people whose HLA profile tilts them toward the disease (Figure 2). In 2023, Mignot identified additional genetic risk factors for narcolepsy. All of them highlight the immune system.

Collateral damage
In Mignot’s proposed model for narcolepsy in humans, immune cells that fend off viral infections subsequently destroy orexin-producing neurons in the brain’s hypothalamus. This wayward autoimmune attack, which can occur in people with a specific HLA profile, causes narcolepsy.
Illustration: Heather B. McDonald

Actualizing the dream

The orexin discoveries have already delivered new medicines. Drugs that block orexin receptors offer insomnia treatments that avoid many problems of traditional sleep aids. Because they inhibit wakefulness rather than force sedation, they induce more natural sleep; furthermore, they have a low propensity for dependency or tolerance. Several are now on the market. Conversely, chemicals that spur orexin receptor-2 promise to revolutionize narcolepsy therapy, and they might also benefit people with other conditions that are associated with excessive sleepiness. The first agent in this class, Takeda’s oveporexton (marketed as Orzeyful™), received FDA approval just last month, in August 2026.

Mignot and Yanagisawa have brought the sleep field from the classical world of anatomy into the modern realm. Until their breakthrough, scientists investigated sleep by crude means—obliterating certain areas of the brain, for instance, and documenting the effects. Such blunt methodology did not afford detailed illumination of the phenomenon. The orexin system defines the first molecular handle for how the body regulates sleep and wakefulness, and it thus has provided an entryway for elucidating this central process.

by Evelyn Strauss

Selected Publications – Emmanuel Mignot

Matsuki, K, Grumet, FC, Lin, X, Gelb, M, Guilleminault, C, Dement, WC, Mignot E. (1992). DQ (rather than DR) gene marks susceptibility to narcolepsy, The Lancet. 339, 1052.

Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong P, Nishino S, Mignot E. (1999). The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 98, 365-376.

Peyron C ….. 21 authors ….. Mignot E. (2000). A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat. Med. 6, 991–997.

Stephansen JB ….. 28 authors ….. Mignot E. (2018). Neural network analysis of sleep stages enables efficient diagnosis of narcolepsy. Nat. Commun. 9:5229. doi: 10.1038/s41467-018-07229-3.

Evans R, Kimura H, Alexander R, Davies CH, Faessel H, Hartman DS, Ishikawa T, Ratti E, Shimizu K, Suzuki M, Tanaka S, Yukitake H, Dauvilliers Y, Mignot E. (2022). Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients. Proc. Natl. Acad. Sci. USA. 119, 1-10. doi: 10.1073/pnas.2207531119.

Ollila HM ….. 88 authors ….. Mignot EJ. (2023). Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy. Nat. Commun. 14:2709. doi: 10.1038/s41467-023-36120-z.

Selected Publications – Masashi Yanagisawa

Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JRS, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, and Yanagisawa, M. (1998). Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 92, 573-585.

Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, and Yanagisawa M. (1999). Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell. 98, 437-451.

Willie JT, Chemelli RM, Sinton CM, Tokita S, Williams SC, Kisanuki YY, Marcus JN, Lee C, Elmquist JK, Kohlmeier KA, Leonard CS, Richardson JA, Hammer RE, and Yanagisawa M. (2003). Distinct narcolepsy syndromes in orexin receptor-2 and orexin null mice: molecular genetic dissection of non-REM and REM sleep regulatory processes. Neuron. 38, 715-730.

Mieda M, Willie JT, Hara J, Sinton CM, Sakurai T, and Yanagisawa M. (2004). Orexin peptides prevent cataplexy and improve wakefulness in orexin neuron-ablated mice: Implications for the therapy of narcolepsy-cataplexy. Proc. Natl. Acad. Sci. USA. 101, 4649-4654.

Nagahara T, Saitoh T, Kutsumura N, Irukayama-Tomobe Y, Ogawa Y, Kuroda D, Gouda H, Kumagai H, Fujii H, Yanagisawa M, and Nagase H. (2015). Design and synthesis of non-peptide, selective orexin receptor 2 agonists. J. Med. Chem. 58, 7931–7937.

Irukayama-Tomobe Y, Ogawa Y, Tominaga H, Ishikawa Y, Hosokawa N, Ambai S, Kawabe Y, Uchida S, Nakajima R, Saitoh T, Kanda T, Vogt K, Sakurai T, Nagase H, and Yanagisawa M. (2017). A non-peptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models. Proc. Natl. Acad. Sci. USA. 114, 5731-5736.

Funato H ….. 34 authors ….. Takahashi JS, and Yanagisawa M. (2016). Forward genetic analysis of sleep in randomly mutagenized mice. Nature. 539. 378-383.

Award Presentation: Jeffrey Friedman

Marcel Proust’s classic novel Swann’s Way begins with a meditation on the porous boundary between wakefulness and sleep. The narrator describes a midnight world where thoughts bleed into hallucinations, and the mind struggles to move cleanly between consciousness and sleep. For most of us, that blurring is occasional. For patients with a disease known as narcolepsy, it is ever-present: they fall asleep hundreds of times a day, begin dreaming almost as soon as they doze off, sometimes even while still awake, and can collapse, fully immobile, when they feel a sudden rush of emotion. It is a disorder that can make an ordinary day—driving, holding a job, even laughing at a joke—dangerous.

The cause of this often-devastating disorder was unknown until the discoveries of this year’s Lasker Award winners for Basic Medical Research: Emmanuel Mignot and Masashi Yanagisawa. Working independently, they found that orexin, a brain peptide, keeps us awake, and that its loss causes the uncontrolled sleep of narcolepsy—a finding that has reshaped our understanding of what controls when we sleep, when we wake, and when we dream.

Narcolepsy affects roughly one in two thousand people and was coined by Jean-Baptiste-Édouard Gélineau in 1880 from the Greek words for “stupor” and “attack.” Its full features stayed a mystery until the 1950s when scientists described the ordered phases of sleep, culminating in REM sleep, the vivid dreaming stage marked by rapid eye movements, and a brain that is fully active despite an immobile body.

William Dement, at Stanford, helped establish this architecture, and discovered that in narcolepsy, the boundaries between sleep and wakefulness collapse. After a presentation in San Francisco, a veterinarian told him of a dog that collapsed whenever excited—a condition known as cataplexy. Dement went looking for similar dogs and built a colony of narcoleptic dogs at Stanford. When one Doberman passed the condition to her puppies, it became clear that canine narcolepsy could be caused by a mutation in a single gene.

Here Emmanuel Mignot, a French-trained psychiatrist and pharmacologist, entered the scene. Mignot had persuaded the French government to let him fulfill his military service by joining Dement’s group to study a new wakefulness-promoting drug developed by a French company. Instead, he became fascinated by the narcoleptic dogs. In 1989 he committed to something audacious: hunting down the narcolepsy gene using a brand-new technique called positional cloning. To do so in dogs, he would need to personally accomplish what for human genes was the output of a worldwide effort: identifying a single DNA change out of three billion. In this method, one narrows the search through breeding studies, first to a chromosome, then to a region small enough to identify and characterize specific genes. To use an analogy: if you were looking for one particular house from space, you wouldn’t search house by house. You’d localize it to a continent, then a country, then a city, and so on. By 1999, working largely on his own, he had narrowed the search to one of two genes. He had every reason to believe he was alone.

But at UT Southwestern in Dallas, Masashi Yanagisawa was closing in on a different narcolepsy gene—this one in mice. Yanagisawa had already made a major discovery as a graduate student, and as an encore was endeavoring to identify novel signaling molecules in the brain. Using biochemistry, he found a novel neuropeptide, a signaling molecule released by one neuron and acting on another connected to it. In early studies he found that injections of the peptide transiently increased food intake, so he named it orexin, based on the Greek word for “appetite.” But when he made a mouse lacking this gene, there was no change in food intake. So he did something that hadn’t been done before: he bought one of the first commercially available infrared cameras and filmed the mice at night, when they are normally awake. And watched. And watched some more. After 2 weeks of mouse videos, a colleague noticed something unusual: periodically, some of the mice would stop moving, remaining completely immobile for several seconds.

At first they thought the mice were seizing, so they performed electrical recordings of the mouse brain—another first. But the mice weren’t seizing. The recordings revealed they were in REM sleep. The mice had narcolepsy, caused by mutation in the orexin gene.

In a remarkable convergence, at precisely the same time, Mignot found that one of his two candidate genes for canine narcolepsy carried a mutation in the receptor for orexin that Yanigasawa had discovered earlier in mice. Signaling molecules act on receptors to produce their effect, much the way radio waves act on receivers to yield a response in the form of sound. The cause of narcolepsy became clear in an instant: it could result from a mutation either in the signal, or in the receiver.

The work progressed rapidly from here. Yanagisawa showed that administering orexin directly into the brain of narcoleptic mice suppressed cataplexy and promoted wakefulness. Mignot found that a child with narcolepsy had a mutation in orexin itself, but that in nearly all narcolepsy patients, an autoimmune attack kills the orexin-producing cells.

These findings have had a major impact on treatment. Blockers of orexin were developed to promote sleep, leading to a new class of non-sedative drugs for insomnia. And more recently, drugs that activate orexin signaling have been developed to treat narcolepsy, with dramatic improvements in wakefulness and near-complete suppression of cataplexy. The FDA approved this new drug just last month, as a breakthrough treatment.

Mignot and Yanagisawa continue to push the field forward. Mignot seeks to understand what provokes the autoimmune attack on orexin-producing nerve cells. Yanagisawa seeks to understand why a period of sleeplessness leads to a compensatory increase in the need for sleep, a phenomenon known as sleep debt. He has recently found another mutation in a gene he named Sleepy that increases sleep debt.

Together, by elucidating the neural mechanisms controlling sleep, wakefulness, and the onset of our dreams Mignot and Yanigisawa have solved a mystery first contemplated by Hippocrates and Aristotle. Please join me in welcoming this year’s Lasker recipients to the podium.

Emmanuel Mignot

JAMA Viewpoint

Acceptance Remarks: Emmanuel Mignot

What an audience! Thank you for being here today. Never did I dream of being recognized by a group like this. It is beyond anything one dares to imagine. Dr. Goldstein, I owe you an apology. Everyone fears their LDL far more than their orexin levels. So I have used your and Mike Brown’s names, many times, to explain to my friends how incredible this award is.

Like many of you, I have always been fascinated by science. My reason is simple. It works. Nature calls upon us to explore the reality of our universe. What better calling is there? In philosophy, I was a fan of Spinoza. And of Pascal, who separated the geometrical mind from the intuitive, subtle mind. Nothing beats pulling knowledge out of the world around us. We are explorers.

So I have tried to live with wonder and curiosity. And with Camus, the sense that none of it should be taken too seriously. Early on, I chose a human disease: narcolepsy. The reasons were simple. A human tragedy. A clear phenotype. A tractable question. And a hunch that finding its cause could open the door to the nature of sleep itself.

I have let my discoveries guide my steps, more than any technique. That took me from pharmacology to genetics, even to zebrafish, and lately to immunology and deep learning of sleep signals. I even love the HLA complex, which terrifies most scientists! Through it all, understanding the disease stayed my compass. Even today, I wake up chasing the elusive T cell clones that kill orexin cells in narcolepsy.

With AI, we are living a transition as profound as the industrial revolution. That revolution automated production. It also brought wars of escalating scale and stunning atrocity. It was stopped, against all predictions, by the building of the atomic bomb. I am afraid this revolution may also prove massive, and possibly destructive. It will automate knowledge. Perhaps even scientific discovery, the very thing we celebrate today.

For me, though, AI is still just a new tool in the service of our goals. More science. More diseases understood. I have never had so much fun working with my students! But we must stay vigilant, so that our future, and the future of this award, does not become an assembly of AI agents. Let us continue international science together, with the goal of reducing human suffering through medical discovery. This was Albert and Mary Lasker’s intention.

Masashi Yanagisawa

JAMA Viewpoint

Acceptance Remarks: Masashi Yanagisawa

For as long as I can remember, I wanted to be a scientist. When I was finishing high school, my father, who was an engineer-turned-surgeon, told me, “This is the age of biology; if you are interested in biology, go to medical school to do basic research.” It is because of those thoughtful words that I am who I am today.

After my MD degree, I obtained a PhD in pharmacology at Tsukuba, Japan. There I was lucky in my PhD dissertation study to discover endothelin—a potent vasoconstrictor peptide. Then I was again lucky enough to be recruited by Joe Goldstein and Mike Brown to UT Southwestern as an HHMI investigator—without even having done a postdoctoral fellowship.

One of my neighbor scientists on the HHMI floor was the late David Mangelsdorf. Davo Mango used to always bother me by boasting about his exciting research on orphan nuclear receptors—those “lock” molecules in the cell without a known “key” molecule. One day, I snapped back at Davo, saying, “There are only 40 genes in the human genome encoding nuclear receptors; but there are several hundred orphan GPCR genes”—the class of cell-surface receptors I was studying. “Mine is bigger than yours!” That exchange of jokes made me seriously think about “de-orphanizing” orphan GPCRs, which eventually led to our purification of Orexins, new brain peptides, together with Takeshi Sakurai, then a research fellow in the lab.

So, the project was a “fishing expedition” without setting specific goals.

We initially thought orexin regulated appetite—a tremendously important field in medicine—so we were very disappointed when we saw “no phenotype” in orexin-deficient mice generated by Rick Chemelli, a physician-scientist in our lab. Then I found an advertisement by SONY for their brand-new product NightShot —an inexpensive infrared camcorder. So, I asked Rick to start observing the mice during their active nighttime, when they roam around their cage and eat their food. That led to our completely unexpected, serendipitous discovery that orexin-deficient mice suffer from the sleep disorder narcolepsy.

Again, the key was an open-minded scrutiny of very boring mouse videos, without setting a specific hypothesis.

So, our orexin story was “entirely untargeted, open-ended discovery science. This type of science, which is currently under threat, has repeatedly led to enormously important avenues for treating patients”—as phrased by my collaborator, Clif Saper, for his JCI article on this Award. With this invaluable lesson, I would like to conclude. Thank you!