New Jersey resident Richard Mancuso considers the late William Halford a medical pioneer.
Carolyn Goatley, a 55-year-old software engineer who lives in Louisville, Kentucky, said Halford, a Springfield resident and faculty member at Springfield's Southern Illinois University School of Medicine, "did a wonderful thing" and "changed my life."
Mancuso, 54, a part-time truck driver and author, had similar words of thanks for his improved health, saying Halford "completely changed everything."
But Dr. Anna Wald, a herpes vaccines researcher and infectious-diseases physician at the University of Washington in Seattle, said Halford carried out "bad science" and "very disturbing" and unethical experimentation on patients with genital herpes. He secretly injected patients with his unproven vaccine in Springfield hotel rooms and on the West Indian island nation of Saint Kitts and Nevis.
Until Kaiser Health News revealed Halford's unsupervised and unsanctioned research on humans a few months after his death in June 2017, SIU officials had praised Halford as a groundbreaking genius in search of a cure for herpes.
But SIU spokesperson Rikeesha Phelon has nothing positive to say about him now.
"Halford intentionally participated in activities that violated SIU policies and procedures and that violated federal regulations," she said in a statement. "This was in no way known at the time or in any way condoned by SIU School of Medicine. Dr. Halford went to great lengths to conceal his misconduct from the university."
Five years after Halford's death at 48 from a rare nasal cancer, the Louisiana native's legacy remains up for debate. But there have been new developments in the saga, which made national headlines and attracted attention from Congress.
Officials from the company Halford co-founded, Rational Vaccines Inc., first headquartered in Springfield and now based in suburban Boston, said they have been encouraged by the response from the scientific community to Rational's efforts to regain respect.
They said the controversies enveloping the company in its early days resulted from Halford acting as chief science officer and disregarding protocols to advance his research and help herpes sufferers as much as possible before cancer killed him.
Using discoveries Halford made in federally funded, supervised animal research during his 10 years at SIU – work that RV has expanded upon since his death – Rational officials said they have built out their staff, working with the necessary regulatory agencies and making sure all the rules are followed.
They plan to begin early-stage human trials of vaccines later this year in Great Britain and the United Arab Emirates to treat and prevent herpes.
They said they hope to work with the Food and Drug Administration and launch clinical trials in the United States a few years after that, first on a therapeutic vaccine and then a preventive vaccine.
"We're not letting the research die, because it's important research," said Agustin Fernandez Santana, the former Hollywood director and producer who partnered with Halford in forming Rational Vaccines in 2015 and now is the company's chief executive officer.
"There's a lot of people suffering," Santana said. "We've always had the patients behind us, and that's given us a lot of wind in our sails because there is a need for this, whether it's ours or someone else's. Whoever can solve this problem is a hero."
SIU, as the co-owner of a patent based on Halford's discoveries, may be eligible to receive some royalties if Rational's vaccines are successfully brought to market, Phelon said, but no royalties have been received to date.
A civil lawsuit filed in 2018 against Rational by three herpes patients who received injections of Halford's therapeutic vaccine and say they developed complications afterward remains pending in U.S. District Court in Springfield.
The quest for a cure
Herpes is a sexually transmitted disease that infects one in seven to one in eight people in the United States and the rest of the world in the 14-49 age group and can lead to social isolation, depression and suicide.
Genital herpes is mostly undiagnosed and dormant but can cause painful outbreaks of blisters on the genitals and other parts of the body, and other medical complications. Antiviral treatments can ease symptoms, but there is no known cure.
Halford was branded a "rogue" scientist in new coverage nationwide after Kaiser Health News first broke the news a few months after his death: The small-scale overseas clinical trial that Halford spearheaded on behalf of Rational, testing the vaccine he created to treat herpes, Theravax, lacked an "institutional review board" from SIU or an outside organization to oversee patient safety and quality.
Santana, who isn't a scientist, said he wasn't aware of this important detail at the time. SIU officials said they weren't aware, either, but weren't responsible because the trial was conducted by Rational.
Rational reported in a news release in October 2016 that its clinical trial of Theravax earlier that year in St. Kitts resulted in "stunning reductions in herpes symptoms" among the 17 U.S. and British patients who received a series of three shots over a three-month period. However, those results never have been published in any peer-reviewed scientific journals.
Kaiser also reported an even more surprising aspect of Halford's research. Before Rational was formed and in the years leading up the clinical trial in St. Kitts, Halford, who had a Ph.D. but wasn't a physician, injected herpes patients with his vaccine in Springfield hotel rooms in a self-styled, unauthorized preliminary trial.
Santana said he wasn't aware of the extent of this unsupervised activity when he first met Halford. SIU officials said they weren't aware, either, but investigated the allegations because the testing apparently involved SIU labs and property.
SIU was informed in September 2022 by the U.S. Department of Human Services' Office for Human Research Protections that it wouldn't face any sanctions related to the injections in hotel rooms or the Saint Kitts clinical trial, and that Rational apparently wouldn't be investigated, according to documents Illinois Times obtained from SIU under the Freedom of Information Act.
The sanctions could have included the loss of SIU's research funding from the federal government. SIU School of Medicine receives an average of $4.5 million per year in federal research funding, Phelon said.
"No sanctions have been imposed," she said. "Still, SIU School of Medicine did establish a number of interventions to strengthen the responsible conduct of research and emphasize each individual's obligation to integrity and compliance with ethical research activities."
Documents obtained by the newspaper also indicate the FDA initiated a criminal investigation into Halford's research involving humans, and SIU supplied more than 2,000 documents in response to a federal subpoena. But no charges have resulted, and Phelon said SIU hasn't received any communication from the FDA since 2018.
FDA spokesperson Jeremy Kahn referred an IT reporter to the U.S. attorney's office for the Central District of Illinois for any comment on future prosecution. Katherine Boyle, a spokesperson for U.S. Attorney Gregory Harris, said in an email response to the newspaper, "We can neither confirm nor deny the existence of an investigation."
Former SIU researcher Edward Gershburg, who collaborated with Halford on herpes research at SIU on mice and guinea pigs and now is Rational's chief technology officer, said he can't judge Halford on his sometimes controversial efforts to ease suffering from herpes, one of the world's most common sexually transmitted infections.
"It's hard to say what I would do if I were in his shoes," Gershburg said.
Halford, who didn't have herpes, injected himself more than two dozen times, and injected three of his family members, to help prove the vaccine's safety in patients with genital herpes, most commonly caused by herpes simplex virus 2, or HSV-2. He said he didn't develop complications even though chemotherapy for his cancer, which was diagnosed in February 2011, already had suppressed his immune system, and his family members didn't develop complications, either.
"Given the five-year survival rate for such patients, it was unlikely I would survive long enough to advance a (herpes) vaccine to clinical trials by the traditional route," Halford wrote in a research paper on the St. Kitts trial that was rejected for publication.
"My cancer responded to chemotherapy and radiation by August 2011, but by then I had come to appreciate that time was of the essence – carpe diem!" Halford wrote.
After that point, Halford apparently began the injections on himself, his family and on herpes patients, according to documents, his writings on his blog and his words recorded in a YouTube video for a future documentary on his life. His widow, Melanie Halford, who no longer lives in the Springfield area, declined to be interviewed.
A new approach
The work of Halford and Rational is novel because it focuses on development of a herpes based on a live, but weakened – or attenuated – form of herpes virus.
When he was working to create a mutant herpes virus that attenuated and test it in animal models, Halford complained to reporters that it was difficult to convince the scientific community to even consider a live, attenuated vaccine because of concerns that the vaccine could unintentionally lead to herpes infections in patients without the disease.
He noted that live, weakened virus strains have been used for years in childhood vaccines to protect against measles, mumps, rubella and polio. But since the 1970s, genetic-engineering techniques that allowed viruses to be created with pieces of protein from a virus instead of a live virus made scientists skittish about attenuated-virus vaccines, he said.
However, Dr. Anna Wald, the researcher from University of Washington, said the diseases addressed by attenuated live-virus vaccines are different from herpes. Someone who contracts measles, for example, develops lifelong protection against reinfection by measles, while herpes sufferers deal with successive outbreaks and don't develop natural immunity, she said.
As a result, Wald said it shouldn't be assumed that an attenuated live-virus vaccine to rev up the body's immune response and treat or protect against herpes will be more effective than any other type of herpes vaccine under development.
Santana, in response to Wald's argument, noted that the vaccine to prevent chickenpox is a live-virus vaccine and has been effective for decades. Chickenpox is a disease caused by a virus in the same family as the viruses that cause herpes.
However, Wald said that unlike herpes, chickenpox behaves like other rash-causing diseases of childhood. And she said a vaccine to prevent shingles – a painful condition caused by a recurrence of the virus that causes chickenpox – has been much more effective than a live attenuated vaccine when the vaccine is created with a harmless subunit of protein from the virus.
Halford used layman's terms to address Wald's argument in an August 2016 posting on his blog. He said many people who suffer with recurrent herpes "do so simply because their immune system was duped by this most stealthy of viruses into believing that herpes is just another part of the body to be tolerated, rather than attacked."
An effective herpes vaccine, he said, "reawakens the immune system out of this stupor and gets the body's immune system back in the game."
Large pharmaceutical companies have been unsuccessful thus far in creating an effective herpes vaccine, and they have focused on methods that don't employ attenuated live viruses. Rational may be one of the few companies in the world working on a live-virus model for effectively treating and curing HSV-2, which causes most genital herpes, and HSV-1, which causes most oral herpes, which take the form of cold sores, and a growing number of cases of genital herpes.
"Acting on his own"
Halford met many of the herpes patients he injected in Springfield hotel rooms in online forums for herpes patients, while others heard about his earlier research and emailed him in search of help, Goatley said. She connected with Halford through an online forum and later traveled to Springfield to serve as one of his research subjects.
Lisa Buchanan, director of the division of compliance oversight in the Office for Human Research Protection, summarized Halford's activities in a Sept. 7 letter for SIU School of Medicine dean and provost Dr. Jerry Kruse. Buchanan said that information from SIU indicated Halford "apparently tested his unapproved HSV-2 vaccine on at least 15 people," in addition to himself, between 2011 and 2014.
The letter said several doses of the vaccine were found in the researcher's freezer at SIU.
Phelon said Halford's lab at SIU remains "contained," and all biological materials are "in storage." Documents produced by SIU in response to the Freedom of Information request indicated that SIU paused its internal investigation of Halford's activities, upon orders from the FDA, to allow the FDA investigation to proceed.
FDA officials have not given SIU the go-ahead to resume its internal investigation, Phelon said.
U.S. Sen. Chuck Grassley, a Republican from Iowa, sent a letter in January 2018 to then-SIU System President Randy Dunn that said Halford "may have violated almost every requirement" in federal law regarding the use of humans in research for vaccines administered at the Crowne Plaza Springfield and in a Holiday Inn Express.
Dunn responded later that same month that SIU's institutional review board investigated the matter, was fully cooperating with federal authorities and "takes this matter very seriously and continues to take steps to address it."
A lawyer representing SIU told Buchanan in a letter obtained by IT that the federal Human Research Protection office didn't have regulatory authority over SIU for Halford's experiments from 2011 through 2014 and that Halford was "acting on his own, in a clandestine manner, and outside the scope of his SIU employment."
"While we do not necessarily agree with SIU's conclusions on this issue," Buchanan wrote, "we do acknowledge that it is far from clear that it could be demonstrated, under the appropriate legal standards related to (the office's) authority, that SIU was responsible for the actions of this researcher while he was conducting the described experiments during that time period."
At Buchanan's request, SIU put in place a "Corrective and Preventive Action Plan," though an attorney for SIU said in an October 2018 letter to Buchanan that "because Dr. Halford intentionally hid his actions from the university, it is difficult, if not impossible, to prevent such a situation from happening again."
The corrective plan includes making research in ethics a "routine standing agenda item" to be addressed by the dean at internal meetings with leaders, students and employees of the medical school, starting a confidential hotline for reporting suspected ethical breaches, and expanding mandatory education and training on ethical conduct involving research with human subjects.
The research continues
Rational gained national attention before Halford's death because of a pledge by Silicon Valley billionaire Peter Thiel's investment firm, Thiel Capital, to invest in Rational. Thiel was a co-founder of PayPal and was an early investor in Facebook.
But Santana, Rational's CEO, said some news media incorrectly reported that Thiel, who has been critical of the FDA's slow, bureaucratic process for evaluating drugs and other treatments, financed the clinical trial in St. Kitts. That wasn't the case, Santana said, though Thiel, which provided funding afterward, has contributed $5 million of the total $42 million raised from Rational's investors to date.
After Rational's news release about the 2016 clinical trial in St. Kitts, the government of the country said it wasn't aware of the trial beforehand and that Rational didn't go through the proper channels to ensure patient safety. The government said it was launching an investigation, but no results of the investigation have emerged, and the office of Saint Kitts Prime Minister Terrance Drew didn't respond to a request for comment.
Rational CEO Santana said neither HHS nor the FDA has investigated Rational, and the company, with about 25 full-time employees and consultants, has made many strides forward.
The company has estimated that a therapeutic herpes vaccine could generate more than $5 billion in revenues per year, and a preventive vaccine could yield more than $10 billion in revenues annually while improving the daily lives of millions of people.
The company in 2021 conducted a five-year follow-up study of side effects among the Saint Kitts patients that hasn't been published yet, but in general, shows "remarkable safety" and "no side effects," Santana said.
However, testimony in depositions that are part of the lawsuit filed by three former patients who received Halford's therapeutic vaccine – two of them in the St. Kitts trial and one in the Holiday Inn Express in Springfield – indicated their health complications haven't abated.
One found his herpes symptoms got worse and he developed "neuropathic symptoms," another saw her herpes outbreaks worsen and developed "shooting pains and fatigue," while the third developed leg pain, ringing in the ears, stabbing pain in the head and right ear, and "cognitive difficulty," according to paid testimony on behalf of the patients from Dr. Jonathan Zenilman of Johns Hopkins University.
Santana declined to comment on the patients' allegations, which the company is disputing in court, other than to say that the two patients injected in St. Kitts failed to complete the three-shot regimen.
Controversies surrounding Halford's conduct have made it difficult at times to raise money for the company's research, Santana said. But he said scientists at governmental agencies in the United States and overseas have been encouraging.
Through the FDA, Rational already has conducted three non-interventional clinical studies in the United States on herpes in preparation for future human studies, Santana said. And the company has repeated some of the animal studies Halford performed to prove to the research community that the positive impact on herpes symptoms were valid, Santana said.
Goatley, one of Halford's hotel patients, said she is glad to see Halford's research being carried on. She said she never felt misled by Halford about the potential risks and benefits of his vaccine to treat what she called a "stigmatized disease."
When she received three different injections in 2013, she "wanted to know whether it would help me. I just wanted to try it. I didn't consider it a cure."
Afterward, she experienced a dwindling of her severe, herpes-related pain, known as herpetic neuralgia, a virtual elimination of herpes outbreaks, and she was able to stop taking antivirals. The neuralgia actually disappeared for two years before coming back, though it's not as severe as before the injections.
What Goatley views as the vaccine's overall benefits persist to this day, she said.
"I'm not suffering anywhere near what I was before," she said.
Mancuso, one of the St. Kitts patients, was experiencing 25 to 30 herpes outbreaks per year before the injections. A few months after the injections, the outbreaks stopped, and he went without any outbreaks for 15 months, he said.
He now experiences three to four outbreaks per year, he said.
Mancuso started an online petition – pennyforyourthoughtscampaign.net – asking Congress to "fast track" the FDA approval process for a herpes vaccine, and he has self-published a book, Asking for a Friend, about his experience with Halford's herpes vaccine.
Mancuso said Halford's unconventional methods may have delayed the benefits of his discoveries reaching patients on a national or global scale, but he appreciated Halford's willingness to help patients like him.
Mancuso said he remains frustrated about the delays that scientists say are necessary to prove herpes vaccines are safe and effective.
"It's crazy to me that these guys have something that works and people cannot get it," he said. "This is something that can change the medical field forever. I'm just very lucky to be a part of it."
Dean Olsen is a senior staff writer at Illinois Times. He can be reached at dolsen@illinoistimes.com, 217-679-7810 or twitter.com/DeanOlsenIT.
