Russell J. Howard

Russell J. Howard is an Australian-born executive, entrepreneur and scientist. He was a pioneer in the fields of molecular parasitology, especially malaria,[2][3][4][5][6] and in leading the commercialisation of one of the most important methods used widely today in molecular biology today called “DNA shuffling" or "Molecular breeding",[7] a form of "Directed evolution".

Russell J. Howard
Born
Australia
NationalityAustralian
Known forMalaria Research, Biotechnology Industry
AwardsAdvance Global Australian Award, Overall winner and Biotechnology Award, 2013[1]
Scientific career
FieldsBiotechnology
InstitutionsNIH, DNAX Schering Plough, Maxygen, GSK, Affymax, NovoNutrients, Garvan Institute of Medical Research, Immutep, NeuClone,

His contributions to malaria research over an 18-year period began in Australia at the Walter and Eliza Hall Institute of Medical Research, then continued as a tenured Principal Investigator at the National Institutes of Health (NIH) in Bethesda, MD, USA, and continued at the biotechnology companies DNAX (now Schering-Plough Biopharma) and Affymax in California. Thirteen years of his group's malaria research on antigenic variation in malaria[2][3][4][5][6][8][9][10][11][12][13][14][15][16][17][18] culminated in the first molecular cloning of the malarial antigen PfEMP1,[19] a parasite protein that this human malaria parasite expresses on the surface of malaria-infected red cells[4][5][20] This antigen represents critical biological functions for the parasite including immune evasion and adherence to microvascular endothelial cells.[21] During this time Howard served on the World Health Organization's Special Program for Research and Training in Tropical Diseases and the USAID program for research and vaccine development in malaria.

While Howard was President and Scientific Director at Affymax Research Institute, Willem 'Pim' Stemmer[22] conceived and developed DNA shuffling Technology.[7] This revolutionary technology for improving the expressed phenotype of genes, pathways, plasmids, viruses and genomes gave birth to the creation and spinout of Maxygen Inc.[23] where Howard was CEO for 12 years (1997-2009).

He took the company public in 1999[24] and led its growth with 10's of corporate partnerships and technology application programs that led ultimately to the development and commercialisation worldwide of 10's of Life Science products in diverse fields. Maxygen exploited DNA Shuffling technology across the entire Life Sciences spectrum, creating new companies dedicated to Agricultural Products (Verdia[25]) and Industrial Chemical opportunities (Codexis[26]) as well as a Protein Pharmaceuticals Business (Perseid[27]).

In 2008, Howard left Maxygen to found Oakbio Inc. in 2009. He remains Chairman of Oakbio Inc. (doing business as NovoNutrients Inc.), in Sunnyvale, California, USA. NovoNutrients uses proprietary microbes for CO2 capture from industrial processes. Industrial CO2 emissions are used as sole carbon source and H
2 gas as sole energy source to manufacture bacterial biomass, or single cell protein, a source of high quality protein for aquaculture and in future, for human foods .

Upon taking up residence in 2012 in Sydney, Australia, Howard became Executive Chairman of NeuClone Pty. Ltd., a clinical stage biotechnology company dedicated to development of biosimilars of monoclonal antibody drugs.

In 2013 Howard joined Prima Biomed Pty. Ltd., based in Sydney, Berlin and Paris, later renamed Immutep Pty. Ltd., as Non-Executive Director. In 2017 he took the role of Non-Executive Chairman and continues today in this role. Immutep develops novel immuno-oncology and autoimmune drugs based on its LAG3 patent estate.

He was Commercial Strategy Advisor at the Garvan Institute of Medical Research's Kinghorn Centre for Clinical Genomics in Sydney, 2015–2018.[28][29]

Howard has published over 145 scientific publications in refereed journals and is an inventor on nine issued patents.

Education

Howard graduated from Box Hill High School in Melbourne, Australia and later majored in Chemistry and Biochemistry at the University of Melbourne, culminating in a PhD in 1975 where he studied the carbohydrate and central metabolism of Caulerpa simpliciuscula, a marine green alga.[30]

Employment

He spent his first postdoctoral studies from 1976 to 1979 at the Immunoparasitology Laboratory at the Walter & Eliza Hall Institute in Melbourne, with frequent visits and collaborative work on sialic acids at the Biochemisches Institut at Christian Albrechts Universitat in Kiel, Germany. He started working as a Research Associate in the Malaria Section of the National Institutes of Health in Bethesda, Maryland before earning his tenure in the same institution in 1987. From 1988 to 1992, he worked at the Laboratory of Infectious Diseases of the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto, California, USA, with dual roles, studying cytokine genes for Schering Plough, the parent organisation of DNAX Research Institute, and leading his Infectious Diseases laboratory there on malaria work funded by DNAX and USAID.[31]

In 1994, he was named President and Scientific Director of Affymax, Inc. where he managed teams working on small molecule drug lead discovery using combinatorial chemistry and high throughput target screening. His independent malaria work continued at Affymax with support from USAID and Affymax, leading to cloning of the PfEMP1 gene while at Affymax.[19] After Affymax was purchased by GlaxoWellcome, Howard led technology transfer and interchange in combinatorial chemistry, drug discovery and optimisation between Affymax and GlaxoWellcome worldwide. During this time, Molecular breeding or DNA shuffling Technology was conceived[7] and the nascent company Maxygen Inc. incubated for later spun out from Affymax-GlaxoWellcome.[23]

From 1997 to 2009, Howard worked as Maxygen's CEO, focusing on human, including, protein pharmaceutical drugs and vaccine discovery, as core business. Non-core businesses were successively incubated, nurtured and spun-out (Codexis[26]) or sold (Verdia[25]). In 2008, he left Maxygen with $200MM in cash, no debt, on-going clinical stage drug development programs and multiple partnerships and licenses with other parties.

Following his departure, Howard started Oakbio, Inc., doing business as NovoNutrients Inc, a privately held Clean Technology company in Sunnyvale, California, USA. NovoNutrients captures CO2 from industrial waste gas streams and uses microbial chemosynthetic systems to capture and convert this carbon resource to protein-rich microbial biomass and valuable chemicals, sequestering a Green House Gas from accumulation in the atmosphere.

In 2012 Howard moved residency from Silicon Valley, California, where he had worked for 25 years, to Sydney, Australia.

From Sydney, Howard acts as Executive Chairman of NeuClone, Non-Executive Chairman of Immutep and Chairman of NovoNutrients.

Financing leadership

With Howard as CEO, Maxygen, Inc. completed its initial public offering of $110MM in 1999, just two years after its spinout from Affymax-GlaxoWellcome.[24] In March 2000, Maxygen raised another $150MM in a Secondary Public Offering. More recently, Howard and colleagues at NeuClone, Pty. Ltd. raised >$10 MM (AUS) from private investors in Sydney to support development of a portfolio of 10 biosimilar monoclonal antibodies.

Recognition & research

Howard has been awarded three Doctor of Science (honoris causa) degrees, one from the University of Technology, Sydney, Australia in 2004, one from the University of Queensland, Brisbane, Australia in 2008 and the third from the University of Melbourne, Melbourne, Australia in 2014. He was awarded the inaugural Grimwade Medal for Biochemistry, Department of Biochemistry & Molecular Biology, University of Melbourne, in 2016. Howard's >145 publications tackle topics ranging from the metabolism of the algae Caulerpa simpliciuscula, to the molecular pathogenesis of human cerebral malaria and the role of parasite antigenic variation and infected cell adherence in disease virulence. His papers reflect successful use of the tools of biochemistry, protein chemistry and structure-function, molecular biology, cell biology, large animal studies, and field studies with humans.

Patents

Howard is an inventor on nine patents. At the NIH he patented discovery, characterisation and cloning of a novel gene encoding a soluble malarial antigen, called PfHRP2[32] that the most lethal human malaria releases into the blood. This discovery led to a rapid, sensitive, inexpensive and reliable diagnostic test for malaria infection that the NIH licensed commercially.[33] This test has been used worldwide for over 15 years.[34] In 1990 and 1995, he and his colleagues at Affymax applied for the patents of antigenic determinants obtained using a pathogenic agent or a derivative that presents a restricted set of antigens, and recombinant DNA clone from Plasmodium falciparum. While working at Maxygen Inc., he and his colleagues developed three patents for the following technologies: antigen library immunisation using polynucleotides encoding flavivirus and alphavirus; multivalent antigenic polypeptides; and optimisation of immunomodulatory properties of genetic vaccines

Selected references and publications
  1. "Russell Howard".
  2. Howard, Russell J. (January 1982). "Alterations in the Surface Membrane of Red Blood Cells During Malaria". Immunological Reviews. 61 (1): 67–107. doi:10.1111/j.1600-065x.1982.tb00374.x. PMID 6174414. S2CID 34158070.
  3. Howard, R. J.; Barnwell, J. W.; Kao, V. (1 July 1983). "Antigenic variation of Plasmodium knowlesi malaria: identification of the variant antigen on infected erythrocytes". Proceedings of the National Academy of Sciences. 80 (13): 4129–4133. Bibcode:1983PNAS...80.4129H. doi:10.1073/pnas.80.13.4129. PMC 394214. PMID 6191331.
  4. Leech, J H; Barnwell, J W; Miller, L H; Howard, R J (1 June 1984). "Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes". Journal of Experimental Medicine. 159 (6): 1567–1575. doi:10.1084/jem.159.6.1567. PMC 2187322. PMID 6374009.
  5. Howard, RJ (13 November 1984). "Antigenic variation of bloodstage malaria parasites". Philosophical Transactions of the Royal Society of London. B, Biological Sciences. 307 (1131): 141–158. Bibcode:1984RSPTB.307..141H. doi:10.1098/rstb.1984.0115. PMID 6151679.
  6. Aley, S B; Sherwood, J A; Howard, R J (1 November 1984). "Knob-positive and knob-negative Plasmodium falciparum differ in expression of a strain-specific malarial antigen on the surface of infected erythrocytes". Journal of Experimental Medicine. 160 (5): 1585–1590. doi:10.1084/jem.160.5.1585. PMC 2187501. PMID 6208311.
  7. Stemmer, Willem P.C. (2002). "Molecular Breeding of Genes, Pathways and Genomes by DNA Shuffling". The Scientific World Journal. 2: 130–131. doi:10.1100/tsw.2002.61. PMC 6009264. PMID 29973836.
  8. Leech, J H; Barnwell, J W; Aikawa, M; Miller, L H; Howard, R J (1 April 1984). "Plasmodium falciparum malaria: association of knobs on the surface of infected erythrocytes with a histidine-rich protein and the erythrocyte skeleton". Journal of Cell Biology. 98 (4): 1256–1264. doi:10.1083/jcb.98.4.1256. PMC 2113211. PMID 6371019.
  9. Marsh, K.; Howard, R. J. (10 January 1986). "Antigens induced on erythrocytes by P. falciparum: expression of diverse and conserved determinants". Science. 231 (4734): 150–153. Bibcode:1986Sci...231..150M. doi:10.1126/science.2417315. PMID 2417315.
  10. Howard, R J; Lyon, J A; Uni, S; Saul, A J; Aley, S B; Klotz, F; Panton, L J; Sherwood, J A; Marsh, K; Aikawa, M (1 May 1987). "Transport of an Mr approximately 300,000 Plasmodium falciparum protein (Pf EMP 2) from the intraerythrocytic asexual parasite to the cytoplasmic face of the host cell membrane". The Journal of Cell Biology. 104 (5): 1269–1280. doi:10.1083/jcb.104.5.1269. PMC 2114467. PMID 2437128.
  11. Miller, L. H.; Howard, R. J.; Carter, R.; Good, M. F.; Nussenzweig, V.; Nussenzweig, R. S. (12 December 1986). "Research toward malaria vaccines". Science. 234 (4782): 1349–1356. Bibcode:1986Sci...234.1349M. doi:10.1126/science.2431481. PMID 2431481.
  12. Howard, RJ (1 August 1989). "Malaria: the search for vaccine antigens and new chemotherapeutic strategies". Blood. 74 (2): 533–536. doi:10.1182/blood.V74.2.533.533. PMID 2665847. INIST:7332277.
  13. Howard, RJ; Gilladoga, AD (December 1989). "Molecular studies related to the pathogenesis of cerebral malaria". Blood. 74 (8): 2603–2618. doi:10.1182/blood.V74.8.2603.2603. PMID 2479423. INIST:6773267.
  14. van Schravendijk, MR; Rock, EP; Marsh, K; Ito, Y; Aikawa, M; Neequaye, J; Ofori-Adjei, D; Rodriguez, R; Patarroyo, ME; Howard, RJ (1 July 1991). "Characterization and localization of Plasmodium falciparum surface antigens on infected erythrocytes from west African patients". Blood. 78 (1): 226–236. doi:10.1182/blood.V78.1.226.226. PMID 2070055. INIST:4327267.
  15. Leung, L. L.; Li, W. X.; McGregor, J. L.; Albrecht, G.; Howard, R. J. (5 September 1992). "CD36 peptides enhance or inhibit CD36-thrombospondin binding. A two-step process of ligand-receptor interaction". Journal of Biological Chemistry. 267 (25): 18244–18250. doi:10.1016/S0021-9258(19)37179-0. PMID 1381367.
  16. Handunnetti, SM; van Schravendijk, MR; Hasler, T; Barnwell, JW; Greenwalt, DE; Howard, RJ (15 October 1992). "Involvement of CD36 on erythrocytes as a rosetting receptor for Plasmodium falciparum-infected erythrocytes". Blood. 80 (8): 2097–104. doi:10.1182/blood.V80.8.2097.2097. PMID 1382720.
  17. Howard, Russell J. (June 1992). "Asexual deviants take over". Nature. 357 (6380): 647–648. Bibcode:1992Natur.357..647H. doi:10.1038/357647a0. PMID 1614513. S2CID 4348017.
     • Howard, R.J.; Pasloske, B.L. (October 1993). "Target antigens for asexual malaria vaccine development". Parasitology Today. 9 (10): 369–372. doi:10.1016/0169-4758(93)90085-t. PMID 15463671.
  18. Pasloske, Brittan L.; Howard, Russell J. (February 1994). "Malaria, the red cell, and the endothelium". Annual Review of Medicine. 45 (1): 283–295. doi:10.1146/annurev.med.45.1.283. PMID 8198384.
  19. Baruch, Dror I.; Pasloske, Britten L.; Singh, Hardeep B.; Bi, Xiahui; Ma, Xin C.; Feldman, Michael; Taraschi, Theodore F.; Howard, Russell J. (1995). "Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes". Cell. 82 (1): 77–87. doi:10.1016/0092-8674(95)90054-3. PMID 7541722. S2CID 700863.
  20. Aley, S B; Sherwood, J A; Howard, R J (1 November 1984). "Knob-positive and knob-negative Plasmodium falciparum differ in expression of a strain-specific malarial antigen on the surface of infected erythrocytes". Journal of Experimental Medicine. 160 (5): 1585–1590. doi:10.1084/jem.160.5.1585. PMC 2187501. PMID 6208311.
  21. Baruch, DI; Ma, XC; Singh, HB; Bi, X; Pasloske, BL; Howard, RJ (1 November 1997). "Identification of a region of PfEMP1 that mediates adherence of Plasmodium falciparum infected erythrocytes to CD36: conserved function with variant sequence". Blood. 90 (9): 3766–75. doi:10.1182/blood.V90.9.3766. PMID 9345064.
  22. Willem P.C. Stemmer
  23. Zaffaroni Announces New Start-Up Company – Maxygen, Inc.
  24. Maxygen, Inc. Raises $110 Million In Initial Public Offering of Its Common Stock
  25. DuPont To Acquire Maxygen Subsidiary Verdia
  26. Maxygen Announces Launch of Wholly Owned Chemicals Subsidiary, Codexis, Inc.
  27. Maxygen and Astellas Announce Global Agreement to Develop New Therapies for Autoimmune Diseases and Transplantation.
  28. "Kinghorn Centre for Clinical Genomics Staff". Organisation Website. Garvan Institute. Retrieved 21 February 2014.
  29. Durkin, Patrick. "Russell Howard: scientist, entrepreneur, CEO". Magazine. Australian Financial Review. Retrieved 21 February 2014.
  30. Howard, Russell; Grant, Bruce; Fock, Heinrich (28 June 2008). "Storage and structural products formed during photosynthesis in the siphonous alga Caulerpa simpliciuscula (Chlorophyceae)". Journal of Phycology. 13 (4): 340–345. doi:10.1111/j.1529-8817.1977.tb02938.x. S2CID 84682850.
  31. "Maxygen Lands Grant to Pursue Malaria vaccine". www.bizjournals.com. Retrieved 20 October 2021.
  32. Howard, R J; Uni, S; Aikawa, M; Aley, S B; Leech, J H; Lew, A M; Wellems, T E; Rener, J; Taylor, D W (1 October 1986). "Secretion of a malarial histidine-rich protein (Pf HRP II) from Plasmodium falciparum-infected erythrocytes". The Journal of Cell Biology. 103 (4): 1269–1277. doi:10.1083/jcb.103.4.1269. PMC 2114335. PMID 3533951.
  33. Wellems, T. E.; Howard, R. J. (1 August 1986). "Homologous genes encode two distinct histidine-rich proteins in a cloned isolate of Plasmodium falciparum". Proceedings of the National Academy of Sciences. 83 (16): 6065–6069. Bibcode:1986PNAS...83.6065W. doi:10.1073/pnas.83.16.6065. PMC 386439. PMID 3016741.
  34. Rapid Diagnostic Test Information: Malaria Diagnostic Overview. Archived 10 May 2009 at the Wayback Machine
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