25

             

Final Fling

Frederic de Hoffmann, the new chancellor, seemed capable and earnest. A Harvard physicist who had helped develop the hydrogen bomb, de Hoffmann said his primary emphasis would be to maintain a climate that allowed creativity free rein.¹ Yet he told comptroller Del Glanz that no matter how high the quality of the science, they needed to raise money and balance the budget first. Reserved and unassuming, the forty-eight-year-old was soon working so many hours that his life at home and his life at the Institute seemed to have merged. Before long, they didn’t have to worry if they could make the next payroll.

Thanks to de Hoffmann, Salk carried almost no administrative duties and was free to concentrate on his research. Although many resident fellows thought his time as a laboratory scientist was behind him, Salk himself felt that he had more contributions to make. Conducting research on both multiple sclerosis and cancer, he lacked the single-minded focus that had led to the polio vaccine. To some this seemed foolhardy; few scientists investigated two such disparate diseases. At the same time, he was writing another philosophical book and traveling to Paris and New York, where Gilot had her studios.

With regard to cancer, Salk and his senior research associate, Sam Rose, were trying to decipher those parts of the immune system that suppressed tumor growth. “Jonas was enthusiastic about harnessing the immune system to reject tumor cells,” explained Walter Eckhart, then a postdoctoral fellow in Dulbecco’s lab. Salk and Rose drew blood from animals, concentrated the immune cells, and reinfused them to try to arrest cancers. “Actually, it wasn’t a bad idea,” Eckhart said, “but they didn’t start with mice or rats; they started with cows. We all thought that was crazy.”² All, that is, except Armand Hammer. Enthused over the prospect of a cure for cancer stemming from Salk’s work, the oil tycoon had agreed to fund the Armand Hammer Cancer Research Center, which included Dulbecco, Cohn, Holley, and fifteen other Institute investigators in an integrated approach to cancer. Salk served as cancer council chairman, although he rarely discussed cancer research with Dulbecco, Cohn, or Holley—an omission which would turn out to have serious consequences.

In 1972, Rose took another position, and Salk’s son Peter joined his lab. Peter had just finished medical residency training and settled in La Jolla with his wife. Although he had not obtained a PhD or any formal training in immunology or cancer biology, Peter replaced Rose, a senior scientist. “As far as I could tell,” a research assistant observed, “Peter was the cancer program.”³ A picture in Human Behavior shows Salk in a white coat, standing in his lab. “Still primarily a biologist and a physician,” the caption reads, “Salk confers with a researcher in the Armand Hammer Laboratory where the search for a cure for cancer is underway.” Another portrays him working side by side with his son. “Peter Salk joins his father in research projects that mix precision and daring,” it reports.⁴ Salk, however, had no NIH grants, no publications in cancer journals; his tumor immunology program languished.

His work on multiple sclerosis was progressing better, due in large part to the addition of two young investigators, Fred Westall and Vanda Lennon. Westall, a straight-talking, scrappy young man, had a PhD in chemistry from the University of California, San Diego, and significant experience in protein synthesis. “Most find complex answers to simple questions,” an Institute president said of Westall, “Fred discovers simple answers to complex questions.”⁵ When Westall sought advice from other researchers about which lab to join, they warned him not to work with Salk. “It will ruin your career,” he was told. Nevertheless, Westall found the idea of human application appealing. “I don’t think there are too many chemists in the world who have the opportunity to work on a therapy.” Harry Weaver, still directing research for the National Multiple Sclerosis Society, arranged for Australian immunologist Vanda Lennon to join them. He considered Lennon and Westall the two young hopes of the MS society, and he wanted them together.

Salk continued to study experimental allergic encephalitis (EAE) in animals since its neurologic damage resembled MS. EAE could be induced by inoculations of myelin basic protein (MBP) derived from the brain or spinal cord. His laboratory, as well as others, had shown that after induction of EAE with small doses of MBP, they could protect the animals from developing full-blown disease by giving high doses of MBP. These high doses induced desensitization in the same way that a series of shots of ragweed pollen extract could desensitize a person suffering from an allergy to ragweed and help prevent attacks of hay fever or asthma.

Salk and his team worked to elucidate the structure and biologic activity of the MBP protein by analyzing samples from the nervous tissue of pigs, cows, and rats, as well as human brains. They investigated the relationship between the source of MBP, dose and schedule of administration, and control of EAE in lab animals. Westall liked working with Salk. Although he was a celebrity, there was no trace of arrogance in his attitude. He didn’t spend much time in his laboratory, but enough to set the tone. Every experiment was prewritten; everyone received a copy in advance. “You knew what was going to happen, when it was going to happen, and how it was going to happen,” Westall recalled. He considered Salk thorough to the point of punctiliousness. “We looked at how you inject it, where you inject it, the amount you inject, how often you inject. Do you treat for ten days, twenty days? Do you use MBP from humans or guinea pigs or cows? We covered everything.”⁶ In one experiment, they used one hundred guinea pigs a week.

Westall respected Salk’s intellectual honesty; he never overinterpreted data. “We’d do these experiments in every combination and permutation, and whatever the result, that was the result.”⁷ Yet Salk rarely published those results; he only reported data he considered unique or clinically relevant. All Westall could recall were two abstracts in Neurology and three book chapters. Peter Salk concurred: “Much of the EAE work never saw the light of day.”⁸ As a result, Institute scientists had no idea what Salk had done. “We probably could have written a hundred publications,” Westfall speculated, given what they found: MBP extracted from the brains of rabbits, cows, pigs, and humans had similar structures.⁹ The suppressive effect of MBP depended on the dose and length of therapy. And it appeared safe; monkeys treated for ninety days showed no signs of toxicity. When he heard these findings, Weaver thought time had come to test MBP in humans.

Conducting research on both cancer and multiple sclerosis required a large laboratory and substantial funds; nevertheless, Salk didn’t like to think about money; he never had. In the past, if he overspent, O’Connor had covered it. His grant requests to the NFIP had been pro forma. Now he was treated like any other investigator. Salk tried to convince NF leadership that his research related to their new mission, prevention of birth defects. They did not accept his argument. In 1971 his NF support had been reduced to $50,000 every six months.¹⁰ Once again, Salk faced a financial crisis. He could not squeeze more money from the cancer center; Hammer scrutinized its distribution. And despite Weaver’s best efforts, the MS Society had limited research funds. By now, most fellows applied to the National Institutes of Health or National Science Foundation for funding. Salk had submitted an NIH grant that had been rejected. He could not adhere to the NIH’s strict guidelines, and at fifty-seven, he could not compete with the brilliant young molecular biologists around the country.

What Salk needed was another Basil O’Connor. He looked over the list of trustees and decided to approach William Bernbach, a legendary figure in American advertising. Salk sent Bernbach a long letter that described his work on multiple sclerosis and cancer, with human trials as the next logical step, and explained that accomplishing this required the generosity of one who displayed true concern for mankind. “Basil O’Connor was such a man,” he wrote, “and I have not yet had the good fortune to find another.”¹¹ He requested a million dollars each year beginning as soon as possible. Bernbach declined the request.

So he tried another tack. He wrote to trustee Sol Linowitz, who had made millions when he helped found Xerox, and reminded him of Slater’s suggestion that he endow a chair in human creativity to symbolize the Institute’s interest in the humanities. Salk said he would be pleased to occupy the position. “The attitude prevails that I am costing the Institute money,” he admitted. An endowed chair would “allow me to function as I would like to be able to do without feeling pressured.”¹² At the same time, Salk contacted Edgar Bronfman, CEO of the Seagram Company, saying how much he appreciated the Bronfman Foundation’s intention to establish an endowed chair with him as the first recipient. No such offer had been made. Neither Linowitz nor Bronfman chose to become his benefactor. Salk had estimated a $600,000 budget for 1972. He was becoming desperate. He requested that the NF send his entire $100,000 up front, rather than in biyearly allotments, citing “cash flow needs.”¹³

Then he met Morris Diefenbach. Vice president of the CertainTeed Products Corporation, a building materials supplier in Pennsylvania, Diefenbach had developed multiple sclerosis and hoped that Salk’s research might lead to a curative therapy. In 1973, he offered to set up the CertainTeed Jonas Salk Foundation to raise funds for MS research. Salk could not refuse. “Jonas had this habit of big swings of money, no money, money, no money,” Westall recollected. “If somebody walked in off the street and handed him a check, he’d take it.”¹⁴ Now, however, there had been a procedural change: Salk could no longer accept money outright; he had to go through the Institute’s new gatekeeper, Frederic de Hoffmann.

Diefenbach’s first meeting with de Hoffmann regarding the CertainTeed Jonas Salk Foundation did not go well. “There is no question,” Diefenbach told Salk, “but what his principal concern is that your name would be associated with our foundation. … Although I would not want to repeat them, he made certain statements concerning you and your research work as related to previous financial arrangements which I’m sure you would find most disturbing.”¹⁵ Their conversation had become heated; de Hoffmann argued over every point. Nonetheless, he had a problem to solve—Salk was draining money from his coffers—and Diefenbach posed a possible solution.

At the July 12, 1973, executive committee meeting, de Hoffmann presented Diefenbach’s proposal to form a foundation that would raise $500,000 annually for Salk’s lab.¹⁶ Robert Holley, representing the resident fellows, objected. He warned that the granter should not be misled into believing clinical trials would soon commence, as had been the case with Armand Hammer. Holley insisted Salk’s research undergo a thorough review first, as should all the Institute laboratory programs on a regular basis. With those concerns voiced, the executive committee agreed to Diefenbach’s proposal in concept only. What Salk did not foresee in pursuing the CertainTeed offer was that it would open Pandora’s box, releasing the fellows’ pent-up feelings about him as a scientist and his unbridled freedom.

“Salk’s enormous staff and space generated irritation,” resident fellow Edwin Lennox divulged.¹⁷ Having dispelled the notion of the Institute as a haven exempt from financial concerns, de Hoffmann and Glanz encouraged fellows to apply for federal grants. “I’m not qualified to judge Salk academically,” Glanz said. “I’m just an old bookkeeper. But here the fellows are getting government funding, doing their bit to help the Institute, and Jonas is not.”¹⁸ Others were less politic. Lennox considered Salk’s scientific knowledge somewhat shallow: “Frankly, I think he got in over his head.”¹⁹ An undercurrent of antagonism flowed through the Institute. “The scientists who were there, the Nobelists, the pre-Nobelists, really didn’t like Jonas,” observed a young researcher who had recently come to La Jolla. Salk did not stand in their ranks; “they more or less laughed behind his back.”²⁰ Lennox thought Salk was oblivious to their opinion of him. Psychiatrist Arnold Mandell disagreed. He knew how painful their rejection had become. “Jonas was a common man lost among the geniuses in his own institute.”²¹ Even so, Salk did not suspect that the resident fellows he had attracted to La Jolla had formed a cabal.

The intrigue centered on the internal review of his laboratory as recommended at the executive committee meeting. On July 22, de Hoffmann received a memo summarizing what the reviewers, comprising the selfsame resident fellows, called “grave misgivings.” With regard to Salk’s multiple sclerosis research, they noted several excellent laboratories were studying the relationship between EAE and MS; Salk likely would not contribute new insights. Furthermore, the proposed experimentation on MS patients could not be justified. “We think that accepting major support for an expanded activity in this field is ill-advised,” they warned, “and could well lead to further damage to the reputation of the Institute.” Although the informal evaluation was supposed to encompass only the research Salk proposed to carry out with CertainTeed funds, the group critiqued his cancer program as well. “Nothing in his brief presentation suggested that he had anything original to propose,” they reported.²² They recommended review by an external scientific panel. The memo was signed by Mel Cohn, Edwin Lennox, Robert Holley, Leslie Orgel, and Roger Guillemin.

After that the resident fellows sent a letter to the chairman of the board, John McCloy, that emphasized the imperative for external review of the Institute’s scientific programs. Under de Hoffmann’s leadership, the financial crisis that had plagued them had almost dissipated, due in large part to their efforts, they wrote. Of the Institute’s $6.1 million budget, $4.1 million had come from federal grants they had obtained. “These successes,” they argued, “can only continue if our claim to do outstanding scientific work seems credible to the scientific community. It would be tragic to jeopardize our major source of long-term funding through the pursuit of programs of the type the CertainTeed Jonas Salk Foundation wishes to support and intends to bring to public notice in the Institute’s name.” Lest McCloy minimize their concerns, they advised, “We would gravely regret having to send this letter to the members of the Board of Trustees for it expresses our rather harsh judgments about Dr. Salk’s proposed program.”²³

Salk, in the meantime, had signed a letter of agreement with CertainTeed. “You have transformed my life,” he wrote the corporation’s board chairman. “I did not know how very heavily the problem of funding for our research weighed upon me until you began to lift the burden. … It has kindled new enthusiasm, imagination, and courage.”²⁴ Salk never suspected what would soon ensue.

At the October 12 executive committee meeting, held in advance of the Institute’s board meeting, Holley presented the internal review of Salk’s laboratory to which they had referred in de Hoffmann’s July 22 memo. He reported that the fellows were greatly concerned about the quality of Salk’s proposed research with projected expenditures five or ten times the amount justified on scientific grounds. They advised the chancellor not to accept new funds for this program until they obtained an outside review, which might suggest program modifications that would be acceptable with “a minimum of embarrassment.” Holley proceeded to recount Salk’s reaction when apprised of this recommendation: no one was going to review his program, and he had the votes on the board of trustees to get his way. “I found it absurd for Dr. Salk to suggest that any scientist’s program is above criticism,” Holley complained. “If the Executive Committee takes the position that Dr. Salk’s program does not have to meet any scientific standard, it will make a mockery of any claim that the Institute is a responsible scientific institution.”²⁵

Holley’s vindictive statements seemed out of character for this quiet, modest man who enjoyed taking long walks on the beach to look at tide pools. His warning that the Institute’s survival was threatened by the man who had built it surprised some trustees. Likely, he was angered that the allocation of Hammer’s annual million-dollar donation included $162,000 to him and Cohen, whereas Salk received $400,000. Perhaps inflamed by his co-conspirators, he thought the time had come for someone to rein in Jonas Salk.

Two weeks later, at the October 24 board meeting, Salk had a chance for rebuttal. Instead of justifying his proposal or contradicting Holley’s offensive comments, he suggested the board view CertainTeed’s offer not as a danger but as an opportunity. He reminded them of the academic freedom intended in the founding of the Institute; nevertheless, he did not object to an external assessment of all the laboratory programs.²⁶ Although he maintained his composure, Lorraine Friedman knew it distressed Salk to be rebuffed by his colleagues. Had he not founded the Institute, he told her, he wouldn’t have been invited to become a member.²⁷ Mandell worried about his friend. He was having trouble sleeping, losing weight—symptoms of depression.²⁸

The executive committee requested an outside review panel from the Rockefeller Institute, led by Maclyn McCarty. This meant Salk would have to convince the esteemed geneticist who had discovered that DNA carries genetic information that his own research was worthwhile.

The January 30, 1974, annual fellows meeting was quite a contrast to the first Guillemin had attended years earlier, a meeting which radiated collegiality. Guillemin had already begun to regret the part he had played in the showdown he knew was coming. He later wrote a contrite letter to Salk, expressing his regrets at having been pulled into the collusion against him. When they reached the agenda item “Disposition of Review Committee Reports,” in accordance with their newly adopted procedures, the external review was presented to the resident and nonresident fellows.²⁹ For each program, the conclusion read, “Favorable report, no action required.” Then they came to Salk’s. He turned to face the jury and hear their verdict: tolerance for his unorthodox approaches or condemnation.

No surprise to anyone, except perhaps Salk, the expert panel panned the cancer program. They said his extensive experiments had merely replicated those performed for years by tumor immunologists. Furthermore, Salk’s future plans held limited promise. Peter Salk, who had carried out most of the work, had no training in immunobiology. They recommended he seek a postdoctoral fellowship in a prominent laboratory and that Salk recruit a senior scientist trained in tumor immunity. Salk said nothing.

To the resident fellows’ astonishment, the panel rated the multiple sclerosis program highly. Neuroscientists nationwide held Salk in high regard. The reviewers found his laboratory group had accomplished a great deal in their approach to EAE, most notably in defining the relationship of structure to biologic activity. Regarding his proposal for human application, working in collaboration with Eli Lilly, the external reviewers considered the steps outlined “well-conceived, with adequate precautions to minimize possible risks.”³⁰ After the meeting, no one congratulated Salk on his MS program, and he did not gloat over its favorable appraisal. Several fellows urged him to terminate the cancer program and concentrate on EAE. He did not defend his cancer work and simply said that he would take their recommendations “under advisement.”³¹

Since the CertainTeed Jonas Salk Foundation had been created to support Salk’s MS research, and that research had received a positive review, the board of trustees had to allow the collaboration to go forward. On February 8, 1974, Morris Diefenbach announced the establishment of the CertainTeed Jonas Salk Foundation. Its brochure displayed pictures of Salk and noted the Foundation’s mission was to encourage the great scientist to “apply his talents in the pursuit of his present interests.”³² It went on to say the CertainTeed Products Corporation believed American industry should provide leadership in supporting programs directed toward improving quality of life. It planned to use corporate management and personnel to raise $2 million over thirty-six months. To kick off the fundraising campaign, Françoise Gilot contributed fifty signed lithographs as gifts for those who contributed $1,000 or more.

Unfortunately, the CertainTeed Jonas Salk Foundation did not live up to its expectations. Diefenbach blamed the Institute board; with the eight-month delay, they had lost the opportunity to solicit funds before the 1973 tax year ended. Salk had assumed the money was forthcoming and entered January of 1974 with a $165,000 deficit. In April, de Hoffmann told the trustees that the CertainTeed Jonas Salk Foundation agreed to pay $205,000 for direct expenses, but two months later Diefenbach sent a note to the Bank of America placing a hold on further disbursements to the Salk Institute.³³ Diefenbach’s health and authority within the company were deteriorating; shortly thereafter he resigned from the Foundation. Instead of reacting with shock or anger, Salk wrote to the president of the corporation saying he appreciated its generosity; Diefenbach had worked with “great dedication.”³⁴ In the end, donations from the CertainTeed Jonas Salk Foundation amounted to $60,000.³⁵

Meanwhile, Armand Hammer had become impatient. He expected a return from his investments and, disillusioned that Salk had not cured cancer, lost interest in his work. Having spent the anticipated funds, Salk had overdrawn his account. At the January 1976 board meeting, de Hoffmann reported all labs as solvent except Salk’s. His research costs totaled more than $300,000; his funding sources remained uncertain.³⁶ The National Foundation had notified him that Salk’s special grant was being discontinued on June 30. What an embarrassment to the man who had founded the Institute. Westall thought the NF leadership was “brutal” to Salk. “They treated him like crap.”³⁷

Salk wrote to Sam Ajl, the Foundation’s vice president for research, practically begging to continue his grant without requiring him to go through their standard review process. Ajl told Salk to complete the usual application. “Let me assure you,” Ajl added, “I have your best interests at heart.”³⁸ Salk complied. A few months later, the NF’s Research Advisory Committee recommended approval of a two-year terminal grant in a reduced amount through June 30, 1978. With diminishing funds and no one to rescue him, Salk had to reduce his staff and relinquish laboratory space. “The institute kept nibbling away at him,” Westall said, “taking more and more of his lab. Finally they took half of it away.”³⁹

Despite this financial strain, Salk’s multiple sclerosis work flourished. With an eye toward human studies, his group was searching for the best source of MBP. Salk did have some doubts about whether EAE was a valid model for multiple sclerosis, the cause of which was still unknown. When he seemed to be procrastinating, Weaver became impatient. He told Salk it was time for human studies or support from NMSS would cease. In response, perhaps justifying his action to himself, Salk wrote to Weaver, “Since the knowledge still lacking to justify a clinical study can be obtained only by doing it, I believe that the time has come to do it.”⁴⁰

This would not be the first clinical trial of MBP. Los Angeles neurosurgeon Barry Campbell had carried out a limited study in sixty-four patients using myelin basic protein from human brains, taken at autopsy, which he called BP. Half received a BP shot each week for thirty months; half a placebo for a year, followed by BP for eighteen months. After 4,253 injections of BP, he reported no deleterious effects. Campbell compared neurologic symptoms between the two groups and thought the experimental group showed some improvement.⁴¹ Belgian researchers also conducted a trial using human and bovine BP. They treated thirty-five patients for up to eleven months and found that BP did not reduce the number of relapses.⁴² Both trials had their shortcomings: In the former, response had been assessed by patients’ self-reports, not neurologic exams. In the latter, the number of subjects was too small to be conclusive. And both had the obvious disadvantage of requiring human brains as the source for BP.

Weaver believed that no one would be better at determining the true potential of MBP for treating MS than Salk. He knew how to conduct a clinical trial, how to work with the pharmaceutical industry and the FDA, how to negotiate the bureaucracy. Although his polio vaccine trials were twenty years in the past, Westall agreed that Salk still had this expertise. “It’s like riding a bicycle,” he said. “Once you do it, you don’t forget.”⁴³ Weaver trusted Salk to make sure the trial was conducted properly and expeditiously. After he made the decision to proceed, Salk seemed energized. Since medicine was not practiced at the Institute, Salk sought collaborators at the University of California, San Diego. He also contacted Eldon Shuey, head of biochemical research at Lilly Research Laboratories. They had developed a method to prepare myelin basic protein from pigs and cows that yielded consistent product, and Shuey thought they could scale up the production. When Salk and a representative from Eli Lilly met with staff at the FDA’s Bureau of Biologics, Salk wisely presented this not as a therapeutic trial of MBP but as an exploratory study to clarify whether EAE was a valid model for MS and to establish safety at the dosage level selected. The FDA seemed amenable, and Salk awaited approval to open the trial. Many hopeful patients had signed up to participate. Then, on September, 12, 1977, just as things were falling into place, Harry Weaver died of lung cancer. He had not lived to see the start of the trial he had promoted.

The Study of Myelin Basic Protein as a Possible Therapeutic Agent in Multiple Sclerosis opened in January of 1978 with UCSD professors John Romine and W. C. Wiederholt as collaborators.⁴⁴ Eli Lilly agreed to prepare the myelin basic protein. As opposed to poliomyelitis investigators, who had tried to block his every move, or colleagues at the Salk Institute, who had expressed “grave misgivings” about his work, multiple sclerosis researchers were refreshingly supportive. Weaver had fostered those positive relationships early on when he introduced Salk to leaders in the field. Several top neuroscientists offered to analyze immune responses in the trial patients. Campbell sent flow sheets from his earlier BP trial for Salk’s use. Others in the field lent moral support. “Let me wish you the best of health, productivity and happiness for the New Year,” wrote Bornstein, one of the first to study EAE.⁴⁵ When Elizabeth Roboz Einstein learned the FDA had approved his trial, she wrote: “This brought back some cherished memories when some ten years ago you came to my laboratory and later to the house and we discussed the basic protein. … At this stage of the game, when you embark on treatment with the basic protein, my sincere wish is that you succeed.”⁴⁶

Salk’s collaborators may have changed for the better; but the press had not. “Polio Hero Salk May Be Near Multiple Sclerosis Remedy,” announced the Milwaukee Journal.⁴⁷ “Jonas Salk Stalks Another Killer,” reported the Philadelphia Enquirer, displaying a photograph of Salk in his white coat and ascot standing in front of the Institute, gazing out to the ocean. “If the experiment proves successful,” it read, “Salk … will once again become a national hero.”⁴⁸ A UPI story on Salk’s trial, featured in newspapers throughout the country, resulted in a flood of patient letters.

“I heard on the news about the grant you all received for MS research,” wrote J. Neufeld. “Don’t want you to think I got excited but—Whoooeee! If I can help you in any way … just holler.”⁴⁹ H. Ousley of San Francisco wrote: “I am a mess and would like to volunteer my services as a guinea pig.”⁵⁰ Some told their own tragic story. A. Mastro of Dunmore, Pennsylvania, had been diagnosed with MS when her son was a year old. “To see life pass me by,” she wrote, “to watch my family grow and to be not able to share active experiences with them is truly discouraging to me.”⁵¹ A novelist from Carmichael, California, told Salk: “I write in the mornings in a slow, narrowing band of energy. I write as if every page I write will be my last.”⁵² S. Meyers, a psychiatric social worker and mother of three, confided, “My secret most fervent wish is to be able to dance with my husband at our son’s Bar Mitzvah.”⁵³

Others sent sorrowful notes about loved ones. “As a desperate mother,” wrote L. Foster of Calumet City, Illinois, “I am pleading for help for our daughter … 26, married nearly three years. She and her husband are deaf.”⁵⁴ One mother wrote for her son, a former football star and president of his school, who could no longer write. Others just wanted to encourage Salk. “Whether the experiment succeeds or fails,” wrote a woman plagued by fatigue, “it boosts one’s morale to know someone cares enough to try.”⁵⁵ V. Bachmann thanked him for his concern, saying, “Up until now, we who are afflicted had nothing to hope for except hope.”⁵⁶

Within a few weeks, Salk received more than a thousand letters. Some were handwritten, some typed when the fingers had become too weak to write, some on pink stationery, some decorated with flowers. They arrived from all over the United States—Titusville, New Jersey; Newburyport, Massachusetts; Mansfield, Ohio. And all were heartfelt. In his earlier years, Salk had written a response to every note. Now he resorted to a standardized letter. Perhaps he was wiser or more tired, or just too sad. Maybe he lacked the conviction that a successful outcome was in sight.

Between January and December of 1978, eleven patients with MS entered Salk’s first trial. They ranged in age from twenty-one to fifty-six; five were women; all had relapsing or progressive disease. Romine obtained the clinical histories and performed neurologic exams at study entry and biweekly thereafter. They analyzed blood counts, liver function, and urine on a biweekly basis to assess toxicity and sent hundreds of blood and spinal fluid samples to collaborating scientists for immunologic studies. MBP extracted from pigs was injected daily, starting at 75 mg—one hundred times the dose used by clinical researchers in earlier trials. Salk increased the dose up to 300 mg in some patients. They continued MBP until the disease progressed.⁵⁷ Although Romine took responsibility for daily patient care, Salk wanted to meet everyone participating in the trial. “I told him not to see the patients,” Westall recalled, “because what better placebo effect than Jonas Salk saying, ‘You’re going to get well.’ ”⁵⁸

Romine asked patients to keep diaries of their symptoms and function. Patient B. T. reported that MS affected his legs, eyes, hands, bladder, and speech. “My body was changing so rapidly,” he wrote in his diary, “that I didn’t have time to adjust to each new problem as it occurred. … Once on myelin basic protein, some of my symptoms were quickly reversed. … My speech impediments disappeared. The pain in my left eye stopped. … I felt stronger and had more zest for living.”⁵⁹ Another patient, suffering from MS for fifteen years, wrote: “During 1977, my condition worsened. I became dependent on a wheelchair, more despondent. I experienced extreme weakness, lack of bladder control and fatigue.” He spent most days in bed. Then he started MBP. “The level of activity has now increased to the point where I carry on active business affairs, attend frequent evening social and sports events, and put in a normal day from 7:30 am until 11 pm.”⁶⁰ On New Year’s Eve, he attended two parties and left his wheelchair at home. On October 28, 1978, the grateful patients sent Salk a card that read: “Dear Jonas, It is our hope that on your 64th birthday you are feeling as good in body and spirit as we.”⁶¹

That fall, Salk and Romaine conducted an interim analysis for the FDA.⁶² Toxicity had been minimal: six patients had transient local reactions at the injection site; two had low-grade fevers. They had discontinued MBP in two patients because of disease progression. Of the nine patients who had received MBP injections for at least two hundred days, four had improved neurologic exams. All but two, however, still had active MS. Salk and Romine presented their preliminary results at an American Academy of Neurology meeting. They concluded that MBP at this dose could be given daily for six months without significant side effects, but they needed a larger, placebo-controlled trial to determine efficacy.⁶³

In their next trial, Myelin Basic Protein as a Therapeutic Agent in MS, patients were randomized to receive either MBP or placebo.⁶⁴ Within ten months, they enrolled the requisite number of subjects. Before long, however, patients began to complain of itching. Rashes broke out on the chest or back and spread to the arms, legs, and face. Almost every patient was suffering from what Salk knew to be a delayed hypersensitivity reaction to MBP. Eli Lilly could not find any difference between this batch and the MBP produced for the first trail. Salk and Romaine tried changing the dose, the schedule, and the method of injection, giving antihistamines, high-dose steroids, all to no avail. Although they had seen beneficial effects from MBP in some MS patients, the hypersensitivity reaction impeded further study.⁶⁵ Salk had ended up in a blind alley. In mid-October 1981, they would give the last injection of MBP. With Weaver gone and no further funding from NMSS, Salk left the field of multiple sclerosis.

Salk had not been able to halt the relentless progression of MS, to aid those countless patients who sought his help as their lives spiraled downward. A cure for multiple sclerosis would have been his grand finale, but he abruptly exited the stage. Years later, when a pathologist wrote inquiring about his MS work, Salk replied, “I have had my fling.”⁶⁶