Ruth Arnon

Ruth Arnon was born Ruth Rosenberg in Tel Aviv on June 1, 1933, the youngest of three children.[2] Her parents, Sara and Alexander Rosenberg, were a teacher and an electrical engineer, respectively; the family changed its surname to Erez after 1948.[3] Although her parents encouraged music, she recalled an early attraction to science and nature.[2] Deborah Eilon-Sereni, her biology teacher at the Herzliya Hebrew Gymnasium, was among the people who influenced her interest in science.[2]

Arnon skipped a school grade and completed high school at seventeen.[2] She wanted to join the Nahal but was not accepted by the army at that age, so she enrolled in chemistry at the Hebrew University of Jerusalem.[4] After her first year she joined the academic reserve, continuing her studies before entering regular military service.[2] She studied at the university from 1950 to 1955 and completed her master's degree in 1955.[5]

In 1955–1956, Arnon served as a second lieutenant in the Israeli Navy.[6] As a chemistry officer, her duties included testing materials used by the service.[2] During her military service she began doctoral research on the immunological properties of proteins, initially working with Ephraim Katzir and subsequently with Michael Sela, whose first doctoral student she became.[2] She later described the opportunity to pursue doctoral work at the Weizmann Institute as “the aspiration of my life.”[5]

Her doctoral research examined why some proteins provoke immune responses while others do not, using laboratory-produced proteins with deliberately selected amino-acid sequences.[2] The work contributed to understanding the chemical basis of antigenicity and the immunochemistry of enzymes.[6] She completed her doctorate in 1960; although the research was conducted at Weizmann, the degree was formally awarded by the Hebrew University because Weizmann was not then accredited to grant degrees.[2] From 1960 to 1962 she undertook postdoctoral research at Rockefeller University in New York, where she studied immune responses to enzymes.[5][2]

Arnon returned to Israel in 1963 and established a laboratory at the Weizmann Institute, where she continued her research career.[2] She worked as a researcher and then as a senior researcher from 1966 to 1971, becoming a full professor in 1975.[5][6] Her research developed around synthetic antigens, artificial vaccines, autoimmune disease, immune responses to parasites, and the targeting of drugs to malignant tumors.[2]

Working with Michael Sela, Arnon investigated how synthetic, protein-like substances could stimulate or inhibit immune responses.[5] This research helped establish the use of synthetic polypeptides in immunology and opened approaches to synthetic vaccines and treatments for autoimmune diseases.[5] One finding was that a small synthetic peptide could induce antibodies that reacted with a natural protein.[5]

The research that led to Copaxone began in 1967, when Arnon and Sela sought to understand the immune response involved in multiple sclerosis and to develop an animal model of the disease.[2] Their experiments concerned experimental autoimmune encephalomyelitis, or EAE, in which the immune system attacks myelin.[7] They synthesized short protein-like polymers, hoping that a positively charged synthetic substance would induce the experimental disease.[2] The compounds were designed to mimic myelin basic protein, but did not produce the expected disease.[1]

The researchers then reversed the question: rather than asking whether the substances could induce EAE, they tested whether they could suppress it.[1] Copolymer-1, also called COP-1, suppressed the disease in guinea pigs.[1] Subsequent experiments showed that it could both prevent disease in animals and suppress it after symptoms had appeared.[8] Arnon, Sela, and Dvora Teitelbaum developed the polymer, and Teitelbaum led many of the subsequent studies.[2]

Copolymer-1 is a synthetic, random copolymer made from four amino acids—alanine, glutamic acid, lysine, and tyrosine—and contains polypeptides of different lengths and sequences.[1] The first published results, in 1971, suggested that it might “be of help as a potential suppressive agent for EAE and diseases of a similar nature.”[1] A 1974 patent named Sela, Arnon, and Teitelbaum equally.[8] Results including experiments on monkeys appeared in 1975, followed by publication of an initial clinical trial in 1977.[7]

The transition from animal research to human treatment required clinical collaborators outside the Weizmann group.[1] Neurologist Murray Bornstein of Albert Einstein College of Medicine led a controlled study involving about fifty patients, with results published in the New England Journal of Medicine in 1987.[2] The pilot study suggested that copolymer-1 could benefit patients with relapsing-remitting multiple sclerosis and recommended a larger multicentre trial.[1] Its treated group experienced fewer relapses than the control group.[2][7]

Industrial development introduced additional difficulties: a preparation made in a research laboratory had to be produced at scale with reliable standardization.[1] Teva undertook this work, and manufacturing and standardization requirements contributed to delays in further clinical study.[1] Teva took over development in 1987, and Copaxone received United States approval in 1996, twenty-nine years after the initial research.[7] The drug was used to reduce the frequency of multiple-sclerosis relapses.[4] Clinical trials reported reductions in relapse rates of 25–30 percent among people in the early stages of relapsing-remitting disease.[9]

The project occupied Arnon for nearly thirty years before the drug was approved.[2] Its origins lay in an investigation of immune responses rather than an initial effort to invent a medicine.[7] During development, the precise mechanism of action was not fully understood; proposed explanations included competition with a disease-inducing substance for active sites and effects on immune cells and myelin.[7]

Synthetic-vaccine research formed another sustained part of Arnon's work.[5] Her influenza investigations grew from research in the 1970s into whether a small part of an egg-yolk protein could trigger an antibody response.[10] The team identified and synthesized a twenty-amino-acid peptide.[10] Influenza was selected in part because its protein structure was known and it could be studied in laboratory animals.[10] Her work included a fully synthetic influenza vaccine that produced antibodies active against influenza virus under laboratory conditions.[10]

By 2005, experiments had produced promising results in rats whose immune systems had been replaced with human white blood cells, but human trials were still planned rather than completed.[10] The proposed vaccine was intended to cover multiple influenza strains and potentially more than one season.[10] Its strategy focused on protein regions that do not change, combining conserved regions in a synthetic molecule in the hope of inducing immunity against multiple strains.[11]

The influenza research became the basis of BiondVax, founded in 2002, where Arnon headed the scientific advisory board.[2][10] The company later conducted a large clinical trial in Eastern Europe that did not meet expectations.[2] Arnon attributed the outcome to problems in organizing the trial and also said that advances in mRNA vaccines had reduced the need for an expensive universal influenza vaccine.[2]

Arnon's other research included immune responses to the parasite causing bilharzia, anti-cancer approaches, and targeted drug delivery to tumors.[5][2] In a 2023 interview, she said she was still working in a Weizmann laboratory and had begun Alzheimer's-related research with Ruth Maron.[2] Their team studied Tau and APP proteins and identified two peptides that could form the basis of an interaction between them.[2] She reported that peptide treatment in genetically engineered mice prevented cognitive decline when given at three months and restored some lost cognition when administered at six months.[2] The team patented the finding and was investigating its relevance to humans; the reported results concerned animal models, not a human treatment.[2]

Alongside laboratory research, Arnon held successive leadership positions at Weizmann.[6] She headed the Department of Chemical Immunology in 1973–1974 and 1975–1978, directed the MacArthur Center for Parasitology from 1984 to 1994, and served as dean of biology from 1985 to 1988.[6] She was vice president from 1988 to 1993 and vice president for international scientific relations from 1995 to 1997.[6] She held the Paul Ehrlich Chair in Immunology.[4] Her visiting appointments included a professorship at the University of California, Los Angeles, in 1977–1978.[5]

Arnon was elected to the Israel Academy of Sciences and Humanities in 1990, becoming its third woman member and the first woman in its natural sciences division.[2] She chaired the Sciences Division from 1995 to 2001 and served as academy vice president from 2004.[6] In June 2010 she was elected the academy's first woman president.[12] A general assembly of one hundred academy members elected her and vice president-elect Binyamin Ze'ev Kedar, with their terms expected to begin around Rosh Hashana.[12] She held the presidency through 2015.[2]

Her international roles included president of the European Federation of Immunological Societies from 1983 to 1986 and secretary-general of the International Union of Immunological Societies from 1989 to 1993.[6] She was also elected to the European Molecular Biology Organization and served as adviser on science and technology to the president of Israel.[6] In 2015, Arnon and Royal Society president Sir Paul Nurse signed a joint-research agreement that included funding for twelve to fifteen postdoctoral exchange fellows.[13]

Copaxone was Arnon's most significant contribution to multiple-sclerosis treatment, bringing a synthetic-polymer research program into clinical use through collaboration among Weizmann scientists, clinical investigators, and Teva.[1][2] Her broader scientific contribution included demonstrating how deliberately constructed peptides and polypeptides could be used to investigate and influence immune responses.[5] The same research direction connected her early studies of antigenicity with later work on autoimmune disease and synthetic vaccines.[2][6]

Arnon's honors included the Robert Koch Prize in 1979, the Jiménez Díaz Prize, France's Legion of Honour in 1994, and the Hadassah medical prize in 1997.[5] In 1998 she received the Rothschild Prize in Biology and shared the Wolf Prize in Medicine with Michael Sela.[5][2] She received the Israel Prize in medical research in 2001.[5] In 2020 she received a lifetime-achievement award at the OurCrowd Global Investor Summit recognizing her scientific achievements, leadership, and humanity.[2]

Her publication record extended to approximately four hundred scientific articles and book chapters, with another account placing her output at more than four hundred articles, chapters, and books on immunology and biochemistry.[2][4] Beyond those publications, her election as the first woman president of the Israel Academy of Sciences and Humanities marked a further distinction in a career that combined research with leadership of Israeli and international scientific institutions.[2]

Arnon described hearing from people helped by Copaxone as a particular source of satisfaction.[2] She recalled an email from an Irish science editor with multiple sclerosis who said that her condition had worsened on other treatments, costing her both her sight and her job.[2] The correspondent reported that her sight gradually returned after she switched to Copaxone and that she regained her job.[2] Arnon said that receiving the message had added years to her life.[2]