Tamas Bartfai

Last updated
Tamas Bartfai
Born8 July 1948
Budapest
NationalityUS Swedish
EducationStockholm University
Yale University
Hebrew University
Alma materRockefeller University
OccupationNeuroscientist

Tamas Bartfai (born 5 July 1948), is a Hungarian neuroscientist with interests in neurotransmission, neuropeptides, prostaglandins, fever, and drug discovery. As of 2015, he is a professor in The Scripps Research Institute, and an adjunct professor at Stockholm University, the University of Oxford, and the University of Pennsylvania. [1] As an author, he is widely held in libraries worldwide. [2]

Contents

Biography

Bartfai was born in Budapest, Hungary in 1948. He was a student of mathematics, physics, and chemistry before translating his skills into biochemistry, pharmacology and neuroscience. He earned his Ph.D. at Stockholm University, and studied post-doctorally at Yale University with future 2000 Nobel Laureate Paul Greengard, the Hebrew University with Shimon Gatt, and The Rockefeller University with 1972 Nobel Laureate Gerald M. Edelman among other professorships and visiting professorships. [3] Bartfai has trained over 40 Ph.D. students and over 200 post-doctoral fellows and master's students. Many of his students are in leading positions in the pharmaceutical industry and 16 of them are full professors at universities.[ citation needed ]

He taught as a professor at Stockholm University, the Karolinska Institute, Yale University, Rockefeller University, University of California at Los Angeles, and Stanford University.

He succeeded to the Berzelius chair the Nobel Laureate Bengt I. Samuelsson at the Karolinska Institute, and Floyd E. Bloom at Scripps. Between these appointments he was Senior VP for Central Nervous System Research at Hoffmann-La Roche in Basel, Switzerland.

He is a member of the Academia Europaea, an elected fellow of the American Association for the Advancement of Science (AAAS), a member of Royal Swedish Academy of Sciences, and a member of the Hungarian Academy of Sciences.

In 2013, his accomplishments were celebrated with a rare symposium his honour at the Swedish Royal Academy of Sciences (Kungliga Vetenskapsakademien) entitled "Frontiers in Neurochemistry". [4]

In 1966, he was awarded the Eötvös Medal and, in 1985, he was also then awarded the Svedberg Prize for biochemistry in 1985, Swedish Society for Biochemistry, Biophysics and Molecular Biology and the Swedish National Committee for Molecular Biosciences (Svenska nationalkommittén för molekylära biovetenskaper). In 1992, he was then awarded the Hilda & Alfred Eriksson Prize by The Royal Swedish Academy of Sciences and also the Ellison Medical Foundation Senior Scholar Award in 2002.

Humanitarian efforts

From 1974 to 2002, he was an active member of various non-governmental organisations and effective apolitical entities: the International Committee of the Red Cross; chemical, biological warfare entities; formulation of [global] problems, threats and treaties entities; ethical committees for vaccine programmes; bacterial vaccine development and distribution efforts; and landmine issues and the technologies to eradicate the seemingly insurmountable complex international problems. [3] He generally shuns publicity about his efforts[ citation needed ] for immediate patient treatment in the aftermaths of, for example, the Chernobyl disaster and the Fukushima Daiichi nuclear disaster. Bartfai is an expert on the detection, destruction and decontamination of chemical and biological weapons, and the immediate treatment of radiation exposure. He advises governments, the United Nations, and a number of non-governmental organisations. He has also driven development of a landmine detection system called "Hundnos" by the Swedish company Bofors, or "Bofors schnauzer". [5] It works by sucking air, without sand, into a chamber with crystals coated with antibodies to trinitrotoluene (TNT). This so-called artificial bloodhound is both more efficient and cheaper than training dogs. [6] [7] [8] [9]

With Per Askelöf and Stefan B. Svenson, Bartfai created the first acellular pertussis (whooping cough) vaccine that is part of the current triple vaccine. [10] Briefly, they cloned the pertussis toxin, mapped the antigenic epitopes using antibodies from individuals, who had the disease and or were vaccinated with the old whole-cell vaccine, and attached these antigenic peptides onto the diphtheria toxin as a carrier and adjuvant in one. This model is now used to produce other safe acellular vaccines. They also showed that 'toxoidation' of whole bacteria with formaldehyde — the method all manufacturers used to produce the highly neurotoxic pertussis vaccine — did not work on Bordetella pertussis because there are no free amino groups on the toxin of over 200 amino acids. This is both surprising and unlikely, but obviously can happen. Statistically, there should be at least ten lysines, but, there are none.

Industrial activities

Bartfai has made the transition from academia to industry and back again. He is an inventor on multiple patents in the pharmaceutical and paper industries.

Bartfai has been involved as a consultant at almost all large pharmaceutical companies, including Astra, Roche, Novartis and Pfizer, and co-launched several biotech companies. As an executive or consultant he has consulted on, directed or co-directed the development of at least eight approved drugs. Five of these were "first-in-class" drugs: as a consultant to Astra, the first selective serotonin reuptake inhibitor for depression (zimelidine, and later alaproclate), the first proton-pump inhibitor (omeprazol/Losec-Prilosec – the most successful drug of all time)[ clarification needed ] for 'heartburn', as a consultant to Roche, the catechol-O-methyltransferase inhibitor (Tasmar-tolcapone) used in Parkinson's disease, the first benzodiazepine–antagonist (flunitrazepam) for treatment of benzodiazepine overdoses, and as a consultant to Novartis the sphingosine 1-phosphate agonist gilenya-fingolimod as the first oral multiple sclerosis drug. He has also worked on four current drug candidates that as of 2015, are in phase 2 and 3 clinical trials.[ needs update ] One of the most promising ones is the amyloid Αβ antibody that the Banner Alzheimer's Institute, [11] Roche and the U.S. government are testing in Colombia for prevention of Alzheimer's disease. [12]

Bartfai participated in developing the enzymatic, non-chlorine paper bleaching for BillerudKorsnäs and Tetra Pak. He has also consulted for Saab, Siemens, and Nestlé.

Further research and some other major achievements

Bartfai has published over 400 peer-reviewed papers. [13]

Bartfai has made a large impact on studying fever and its neuroscientific origins. For example, Bruno Conti and Bartfai used a grant from Larry Ellison of Oracle Corporation to create the "coolmouse". It broke the dogma that all mammals have a 36.7 °C core body temperature and only for short periods of fever or hypothermia in surgery can this be changed. They generated a transgenic mouse where the temperature set-point is manipulated during the entire life of the animal to 36.1 °C. This small but life-long hypothermia shows that the dogma is wrong and that these are healthy, fertile, normal-weight animals, who live about 25 percent longer than wild-type littermates. It was one of the last dogmas of physiology. [14]

The discovery of muscarinic acetylcholine receptors in the brain (simultaneously with Sir Arnold Burgen and Solomon H. Snyder, 1973) earned Bartfai the Svedberg prize in 1985. Most Alzheimer's disease symptom-modifying drugs are still aimed at increasing muscarinic acetylcholine receptor stimulation in the cerebral cortex and hippocampus. Originally this receptor was not thought to be present in the brain, only in the periphery. Since Sir Henry Dale's time it was thought that muscarinic receptors were only present in the gut and since Otto Loewi that they are also in the heart, but the brain was not thought of as a site of expression. However, the cerebral cortex, the hippocampus, and the striatum are rich in the muscarinic acetylcholine receptors. They are receptors comprising seven transmembrane elements and come in five subtypes. [15] Bartfai's group identified these receptors in search of the molecular mechanisms of memory. They were looking for the scopolamine-binding protein to understand how scopolamine, then a favourite of neuropsychologists, produces a reversible loss of memory.

Research on the coexistence of classical transmitters and neuropeptides, [16] and frequency-dependent chemical coding led to Bartfai receiving the 1992 Eriksson prize shared with Håkan Persson, who discovered brain derived neurotrophic factor. Bartfai showed with Tomas Hökfelt, Marianne Schultzberg, and Jan M. Lundberg firstly that acetylcholine and vasoactive intestinal peptide can coexist in nerve terminals and act synergistically when released. Secondly, they showed that the neurotransmitters' release occurred at different nerve activity levels. For example, a neuron containing norepinephrine and neuropeptide Y will release first norepinephrine at 0.5–3 Hz and then neuropeptide Y at 3–20 Hz stimulation. Both neurotransmitters cause vasoconstriction, but the effects of norepinephrine are now widely prolonged by neuropeptide Y. Their work showed that the chemical palette of neurons were expanded qualitatively and frequency dependently. [17]

Cytokines, such as interleukin-1 can be synthesized and released by neurons. Bartfai's group showed interleukin-1, then called the endogenous pyrogen, is released from the adrenal medulla and brain and demonstrated that the endogenous pyrogen can control body temperature by acting at receptors and hyperpolarizing hypothalamic gabaergic interneurons that control thermogenesis in brown adipose tissue, and thus core body temperature and the fever response., [18] [19]

Bartfai has published two books with Graham Lees, Ph.D., on drug discovery and development: "Drug Discovery: from bedside to Wall Street" [20] and "The Future of Drug Discovery: who decides which diseases to treat?", [21] which are both also published in Japanese and Mandarin. He is a contributor of many books with colleagues in Stockholm and the USA on neuropeptides and on the coexistence of neurotransmitters.

Related Research Articles

<span class="mw-page-title-main">Neurotransmitter</span> Chemical substance that enables neurotransmission

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.

<span class="mw-page-title-main">Acetylcholine</span> Organic chemical and neurotransmitter

Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic.

<span class="mw-page-title-main">Acetylcholine receptor</span> Integral membrane protein

An acetylcholine receptor or a cholinergic receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.

<span class="mw-page-title-main">Cholinergic</span> Agent which mimics choline

Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin. Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells.

<span class="mw-page-title-main">Excitatory synapse</span> Sort of synapse

An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travels, each neuron often making numerous connections with other cells of neurons. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell.

<span class="mw-page-title-main">Chlorphenamine</span> Antihistamine used to treat allergies

Chlorphenamine, also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis. It is taken orally. The medication takes effect within two hours and lasts for about 4–6 hours. It is a first-generation antihistamine and works by blocking the H1 receptor.

<span class="mw-page-title-main">Muscarinic acetylcholine receptor</span> Acetylcholine receptors named for their selective binding of muscarine

Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers. They are mainly found in the parasympathetic nervous system, but also have a role in the sympathetic nervous system in the control of sweat glands.

<span class="mw-page-title-main">Neuropeptide</span> Peptides released by neurons as intercellular messengers

Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart.

<span class="mw-page-title-main">End-plate potential</span> Voltages associated with muscle fibre

End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters are exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.

Neuropharmacology is the study of how drugs affect function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain. Molecular neuropharmacology involves the study of neurons and their neurochemical interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central and peripheral nervous systems. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, psychological disorders, addiction, and many others.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfigurating synaptic connectivity.

<span class="mw-page-title-main">Galanin</span>

Galanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors.

<span class="mw-page-title-main">Muscarinic antagonist</span> Drug that binds to but does not activate muscarinic cholinergic receptors

A muscarinic receptor antagonist (MRA), also called an antimuscarinic, is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the nervous system, and muscarinic receptor antagonists work to prevent this transmission from occurring. Notably, muscarinic antagonists reduce the activation of the parasympathetic nervous system. The normal function of the parasympathetic system is often summarised as "rest-and-digest", and includes slowing of the heart, an increased rate of digestion, narrowing of the airways, promotion of urination, and sexual arousal. Muscarinic antagonists counter this parasympathetic "rest-and-digest" response, and also work elsewhere in both the central and peripheral nervous systems.

A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The nAChR is named for its affinity for nicotine.

An H3 receptor antagonist is a type of antihistaminic drug used to block the action of histamine at H3 receptors.

<span class="mw-page-title-main">Xanomeline</span> Chemical compound

Xanomeline is a small molecule muscarinic acetylcholine receptor agonist that was first synthesized in a collaboration between Eli Lilly and Novo Nordisk as an investigational therapeutic being studied for the treatment of central nervous system disorders.

<span class="mw-page-title-main">Vedaclidine</span> Chemical compound

Vedaclidine (INN, codenamed LY-297,802, NNC 11-1053) is an experimental analgesic drug which acts as a mixed agonist–antagonist at muscarinic acetylcholine receptors, being a potent and selective agonist for the M1 and M4 subtypes, yet an antagonist at the M2, M3 and M5 subtypes. It is orally active and an effective analgesic over 3× the potency of morphine, with side effects such as salivation and tremor only occurring at many times the effective analgesic dose. Human trials showed little potential for development of dependence or abuse, and research is continuing into possible clinical application in the treatment of neuropathic pain and cancer pain relief.

<span class="mw-page-title-main">Oxaprotiline</span> Chemical compound

Oxaprotiline, also known as hydroxymaprotiline, is a norepinephrine reuptake inhibitor belonging to the tetracyclic antidepressant (TeCA) family and is related to maprotiline. Though investigated as an antidepressant, it was never marketed.

Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord. For example, most opioids cause sedation when given at a sufficiently high dose, but peripherally selective opioids can act on the rest of the body without entering the brain and are less likely to cause sedation. These peripherally selective opioids can be used as antidiarrheals, for instance loperamide (Imodium).

References

  1. ↑ The Scripps Research Institute page for Bartfai
  2. ↑ "Bartfai, Tamas". worldcat.org. Retrieved August 29, 2016.
  3. 1 2 Curriculum Vitae Tamas Bartfai as of 2007
  4. ↑ "Frontiers in Neurochemistry", a one day symposium [ dead link ]
  5. ↑ Brink SA (1996). "Bofors Schnauzer – a Biosensor For Detection of Explosives". Proceedings of the EUREL International Conference on the Detection of Abandoned Land Mines, Edinburgh, UK. 431: 33–6.
  6. ↑ in the Service of Peace and Electronic nose mimics hundnos [ dead link ] for related news
  7. ↑ A Cheap Landmine Detector that Acts like a Tumbleweed for alternative technologies
  8. ↑ Biosensors Based on Piezoelectric Crystal Detectors: Theory and Application for a similar patent application on the technology
  9. ↑ Antibody coated crystal chemical sensor [ dead link ] for similar systems of antibody coated crystals
  10. ↑ Askelöf P, Rodmalm K, Wrangsell G, Larsson U, Svenson SB, Cowell JL, Undén A, Bartfai T (February 1990). "Protective immunogenicity of two synthetic peptides selected from the amino acid sequence of Bordetella pertussis toxin subunit S1". Proc Natl Acad Sci U S A. 87 (4): 1347–51. Bibcode:1990PNAS...87.1347A. doi: 10.1073/pnas.87.4.1347 . PMC   53472 . PMID   2304902.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ↑ Banner Research Institute home page
  12. ↑ "NIA statement on crenezumab trial results: Anti-amyloid drug did not demonstrate a statistically significant clinical benefit in people with inherited form of Alzheimer's disease". National Institute on Aging. 2022-06-16. Retrieved 2023-11-28.
  13. ↑ Tamas Bartfai – List of publications 1972–2009
  14. ↑ Conti B, Sanchez-Alavez M, Winsky-Sommerer R, Morale MC, Lucero J, Brownell S, Fabre V, Huitron-Resendiz S, Henriksen S, Zorrilla EP, de Lecea L, Bartfai T. (Nov 3, 2006). "Transgenic mice with a reduced core body temperature have an increased life span". Science. 314 (5800): 825–8. Bibcode:2006Sci...314..825C. doi:10.1126/science.1132191. PMID   17082459. S2CID   693990.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ↑ Bartfai T, Anner J, Schultzberg M, Montelius J (July 1974). "Partial purification and characterization of a muscarinic acetylcholine receptor from rat cerebral cortex". Biochem Biophys Res Commun. 59 (2): 725–33. doi:10.1016/s0006-291x(74)80040-9. PMID   4853542.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ↑ Bartfai, T., Iverfeldt, K., Brodin, E., Ögren, S. (1986). "Functional consequences of coexistence of classical and peptide neurotransmitters". Prog. In Brain Res.(Edited by Tomas Hökfelt, Kjell Fuxe and Bengt Pernow. 68: 321–30. doi:10.1016/s0079-6123(08)60247-2. PMID   2882558.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ↑ Bartfai T, Iverfeldt K, Fisone G, Serfözö P (1988). "Regulation of the release of coexisting neurotransmitters. Review". Annu Rev Pharmacol Toxicol. 28: 285–310. doi:10.1146/annurev.pa.28.040188.001441. PMID   2898236.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ↑ Schultzberg M, Andersson C, Undén A, Troye-Blomberg M, Svenson SB, Bartfai T (1989). "Interleukin-1 in adrenal chromaffin cells". Neuroscience. 30 (3): 805–10. doi:10.1016/0306-4522(89)90171-1. PMID   2788829. S2CID   27793131.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ↑ Bartfai T, Schultzberg M (May 1993). "Cytokines in neuronal cell types. Review". Neurochem Int. 22 (5): 435–44. doi:10.1016/0197-0186(93)90038-7. PMID   8485449. S2CID   25742367.
  20. ↑ Bartfai T, Lees GV (2006). Drug Discovery: from Bedside to Wall Street. Elsevier/Academic Press, Amsterdam, London, San Diego, etc.
  21. ↑ Bartfai T, Lees GV (2013). The Future of Drug Discovery: who decides which diseases to treat?. Elsevier/Academic Press, Amsterdam, London, San Diego, etc.
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