Was Ray Howell Responsible for His Crimes?

Annals of ScienceWas Ray Howell Responsible for His Crimes?A small-town doctor’s abuse of power shocked his community and family. Then he was diagnosed with a rare neurological condition, leaving his culpability in doubt.By Adeline GossJune 11, 2026Illustration by Vanessa Saba; Source materials courtesy TKSave this storySave this storySave this storySave this storyIn 1983, Ray Howell opened a family-medicine clinic among the tidy lawns of Roachdale, Indiana. Roachdale was a humble town, best known, perhaps, for hosting an annual cockroach race, and Howell had a humble mission: to make a dent in Indiana’s rural-doctor shortage. “Getting rich is at the very bottom of my list of reasons for wanting to become a physician,” he had written in a medical-school essay. Howell had envisaged Tri-County Family Medical Clinic as an informal place. He hugged and prayed with his patients and sometimes provided free care when they couldn’t pay. On his days off, Howell taught Sunday school, went on medical missions to Haiti, and was the team doctor for some of his children’s sports teams.Evangelical, physician, family man: this is how Howell appeared to most of the Roachdale community on October 18, 2011, when he was arrested on charges of recklessly distributing controlled substances, often in exchange for sex. Howell eventually pleaded guilty to several charges, including one involving the death of a young man, and a Drug Enforcement Agency investigation linked his illicit activities to three other deaths. He was sentenced to four years in prison, one of several American physicians convicted of similar crimes involving sexual exploitation during an explosion in opioid-related deaths nationally. What makes Howell different from these other physicians is that Howell’s brain isn’t normal. It is so abnormal that it’s stored under neon lights in a refrigerated room at the University of California, San Francisco, and neurologists who have studied it are uncertain about who was responsible for these crimes: Ray Howell, or his disease. I know, because I’m one of them.Howell died in 2018, at age sixty-four, and I learned about him when I was a neurology resident at U.C.S.F. I reached out to Howell’s wife, Melynda, who invited me to Indiana. A few weeks later, she greeted me at the front door of her suburban home, where she lives with her daughter Caryn, her son-in-law, and four of her twenty-five grandchildren. Melynda is youthful, warm, and self-deprecating, with a gray bob, a soft voice, and a tendency to giggle. She met Ray when he was a high-school senior and she was a sophomore, and she still talks about him breathlessly, like a girl with a crush. “I loved his intellect,” she said, “because he was so much smarter than I was.”Ray had been born to older parents in Shoals, Indiana, in a house without indoor plumbing. In high school, he wore a pocket protector, and “he didn’t mind telling you that he knew things,” Melynda told me. Ray studied at the University of Evansville, and Melynda typed his essays for him, joking that the A’s were partly hers. When Ray was accepted to medical school, in 1976, it was mentioned in the Shoals newspaper. They married when Ray was twenty-one and Melynda was nineteen.Being married to Ray meant accommodating rigid habits. Every night, he consumed a baby aspirin; Vitamin D, E, and B-complex supplements; three almonds; honey; apple-cider vinegar; a cup of bran; one orange; one apple; one banana; two prunes; and a cup of yogurt. For exercise, he ran eight miles around a nearby lake. In extreme weather, rather than miss a day (which made him irritable), he ran inside the house—around the first floor, down the stairs, around the basement, up the stairs, then up to the top floor. He applied a similar intensity to his faith. He bought Bible-study notecards and studied until he had much of the book memorized. In the eighties, he became involved in medical missions after an initial trip to a hospital in a mountainous region of Haiti. He ultimately went on sixteen more mission trips. (Melynda helped him pack his supplements into special containers.)There is a seventeen-year age spread between Ray and Melynda’s children: their first child, Kris, was born on Ray’s first day of medical school, then Mendy, Samantha, Caryn, Emilye, and Katye. As their family grew, Ray picked up shifts at urgent cares and local hospitals, but he still found time to help with homework and tuck the kids into bed. Even now, Melynda often refers to Ray as “Dad,” or “Daddy,” including when she spoke to me. That was Daddy. Always moving, always spreading the Lord’s word.When I take a neurological history from my patients, I ask them to tell me about the first moment that something felt off. Most people, or their family members, can remember a change like that, and it can be a clue to the diagnosis: for Alzheimer’s, it can be repetitive questioning; for A.L.S., painless weakness. None of the Howells could pinpoint a moment. “It’s so hard to say, because my whole life he was just a quirky individual,” Caryn recalled. “I remember introducing him to my friends and being, like, ‘He’s kinda weird.’ ”In Ray’s forties, his obsessions became more irritating, but he remained on-theme: diet, exercise, religion. He filled up gallon-size milk jugs in the bathtub, drove them to work, and drank gallons of water each day. He photocopied pages on diet and exercise from health magazines and stored these in the car in grocery bags. Ray’s oldest child, Kris, continued to go to his dad for primary care as an adult, as did his wife and children. “He’d tell you exactly the same thing, every single visit,” Kris told me. “He passed out the same handouts every time.”Ray’s daughter Samantha, recalled that Ray stopped wearing deodorant, believing it caused cancer. “The stench!” Samantha remembered. “I couldn’t breathe sometimes!” He got into a Qigong routine that included rhythmic patting of his body. “Oh, the body slapping,” Samantha said. “He would wake up early in the morning and go into the bathroom and just start slapping, slapping, slapping, all over his skin, legs, arm, belly, wherever all he could slap. It was so loud! Christmas morning at my Grandma Hardwick’s house, we were all sleeping and he woke us up at 5:30 a.m.”Ray’s visits to Haiti had exposed him to vodou and sparked an interest in spiritual warfare—the idea that humans, knowingly or unknowingly, are participants in a battle between Christ and the Devil—and he began helping church members cast out evil spirits, anointing them with oil. Saturday mornings in the Howell home had long been a time for prayer together, but Ray started going down to the basement instead, to read the Bible alone. He annotated his personal copy in tiny script. Between the pages, he tucked small notecards with handwritten prayer lists, a hundred names on a single card. The way Melynda sees it, he was retreating “into the Bible, into God’s will.”By the early two-thousands, the model of the U.S. rural family doctor was becoming increasingly difficult to sustain, amid industry consolidation and administrative and technological requirements. Ray told Melynda that fewer patients were coming to Tri-County Medical, and many weren’t paying their bills. He ratcheted up his moonlighting—working at urgent cares across central Indiana on his days off—but the long hours left him exhausted and scatterbrained. One day, the local pharmacy called Kris, concerned about an antibiotic prescription Ray had given one of his children: “It was this crazy huge dosage,” he recalled. “Not even close to the amount that a child should be given.” Another time, Ray forgot to put the car in park and left his teen-age daughter, Katye, inside, asleep. She woke up as the car started rolling downhill, and had to climb into the driver’s seat.Around 2007, Ray came to Melynda with a plan to save the clinic: he would specialize in pain management. Melynda opposed the idea, “Just the way it could go. The reputation that you would get.” The prescription-opioid epidemic was in full force in Indiana. But Ray had made up his mind, and Melynda couldn’t talk him down.Ray did his due diligence, hiring an addiction counsellor, administering urine drug tests, and completing a course in pain management. Despite these safeguards, the reality of administering a pain clinic during the opioid epidemic made its way to Tri-County Medical. Katye, who aspired to become a doctor like her father and worked at the clinic during high school, remembers Ray’s pager going off at all hours with desperate patients asking for early refills. In December, 2008, Ray hired a nurse with an expired nursing license who was later arrested and charged with stealing his blank prescription pads and prescribing opioids in his name, including to her boyfriend and brother. Then, in February, 2009, several pharmacists in Danville, Crawfordsville, and Connersville, a town two hours east, reported Ray to the D.E.A., noting that Ray’s own scripts contained large quantities of controlled substances and that his patients often attempted to get prescriptions filled early. A regional D.E.A. agent at the time went to Roachdale to investigate the case, and began collaborating with the Putnam County prosecutor, Tim Bookwalter. In the Tri-County Medical parking lot, there were cars that were registered in counties over a hundred miles away.This led to a broader investigation. In April and May of 2009, the D.E.A. sent an undercover Indiana State Police officer into Ray’s clinic. According to the D.E.A. agent, she requested diet medications because she was tired and needed a “kick.” Without apparent medical justification, Ray prescribed her a Schedule IV weight-loss stimulant called Adipex, explained to her that it was comparable to amphetamine, and said it would treat her depression, although she hadn’t said she was depressed. The D.E.A. found that Ray’s annual prescriptions for controlled substances had nearly tripled between 2006 and 2009. The doses and frequencies were unusually high: one patient was prescribed fifty thirty-milligram oxycodone tablets per day, at least twenty times higher than the maximum daily dose recommended by the Centers for Disease Control, and a dose that would be high even for a patient with severe pain from metastatic cancer. In 2007, another patient filled seven prescriptions for ten to seventy tablets of hydrocodone in less than a month. Between 2006 and 2010, four of Ray’s patients died by overdose, including a thirty-three-year-old man named Rex Showalter.Finally, in April, 2010, the D.E.A. raided Tri-County Medical and found a litany of incomplete records for the inflow and outflow of controlled substances. Ray eventually paid a sixty-five-thousand-dollar civil penalty for the record-keeping violations. In the background, Bookwalter, the county prosecutor, was also building a criminal case.By the fall of 2010, Ray, unaware of Bookwalter’s mounting case, seemed weary and preoccupied with his clinical demands and financial trouble. Then, over her school’s winter break, Katye decided to work at the clinic again. One day, a clinic nurse pulled her aside and told her that Ray was sleeping with a patient.Melynda doesn’t remember how she found out about this allegation—“I’ve blocked out so many of those kinds of memories”—but she acknowledges that Ray had been unfaithful to her for decades. His first affairs had been soon after they married, Melynda remembers; he had expressed remorse, and she forgave him. Then, in the nineties, he had an affair with one of his patients. “Ray was a very kind person, and he was very good at listening, and I think they took that as being flirtatious or being interested in them,” Melynda remembered. “But nevertheless, it was wrong, you know, totally wrong.”Now, with another allegation of Ray sleeping with a patient, Melynda again stood by him. She remembers the tension taking a toll on him: “You could just see him crumble.”In February, 2011, Ray came to Melynda with an article from one of his health journals. It was about frontotemporal dementia, a disease in which proteins build up and damage cells in the frontal and temporal lobes of the brain, causing socially inappropriate behavior, including, in some cases, sexual behavior. Ray said to Melynda, “I think this is what I have.” Melynda assumed this was just an excuse.Ray continued to work. That spring, some Tri-County Medical staff told Melynda that Ray seemed to be hearing voices. At home, he became chatty and volatile; once, he couldn’t figure out how to open the door to a closet and ripped it off its hinges. In May, Ray had what Melynda called a “breakdown.” He was talking continuously, “like the two-year-old that just would not leave your side,” Melynda remembered. She and Kris took Ray to a behavioral-health center, where she says he was evaluated and placed in an intensive outpatient program for one week. He received cognitive testing that revealed memory impairment and “severe general emotional distress.” He was prescribed antidepressants, and a neuropsychologist raised the possibility of either F.T.D. or early Alzheimer’s disease, recommending further evaluation by a neurologist. Ray wrote on a paper copy of his neuropsychology report, circling and underlining. He put three asterisks next to the line: “Current results indicate that treatment of his depression and stress should be the primary focus of initial intervention.” At the top of the report, Ray wrote a note to his primary-care doctor: “Mark, thanks so much, look this over—if you think I’d be better off seeing a neurologist or a psychiatrist, let me or Melynda know.”Katye and Melynda worried about Ray’s capacity to practice medicine, so, from May to July, 2011, they decided that Katye would once again join Ray at the office, this time “to protect him and protect other people,” Katye told me. She started going into exam rooms with Ray. “I think, looking back on that summer, we definitely shouldn’t have let him practice,” she said. “But we didn’t know. The doctor didn’t tell us to not let him practice, and we trusted the doctors.”Finally, that August, Ray’s office staff contacted one of his doctors, who reported him to the Indiana State Medical Association. He was required to see a geriatric psychiatrist, who noted that Ray’s parents had died of dementia, one of Ray’s brothers had Alzheimer’s, one paternal uncle had been committed to an “insane asylum,” and several male cousins did prison time. The psychiatrist’s impression was that Ray, too, likely had some familial dementia, possibly Alzheimer’s disease. I reviewed the psychiatrist’s report. “Even though he scored in the mild to moderate range on screening tests, his neuropsychological test results and family history are quite ominous,” he wrote. “He has manifested impaired judgment, poor professional boundaries, odd behavior and personality changes for several years. Rather than confronting the problems and seeking medical evaluation, his wife and office staff have essentially covered for him . . . Dr. Howell should not continue to practice medicine in any manner.”At the psychiatrist’s recommendation, Ray closed Tri-County Medical. Soon after, Ray’s medical license was suspended by the state of Indiana. Life was dramatically better for the Howells after the clinic was closed. “There was this feeling of relief,” Melynda recalled. “This is what’s wrong with Daddy.” Melynda took away Ray’s car keys. When she left for work, she would set him up with lists of activities—“busy work,” she called it. The whole thing was sad, she said, but it was manageable. Then, just two weeks after the office closed, Melynda came home, and Ray wasn’t there. She got in the car and drove around the nearby lake, afraid that Ray had drowned himself. Finally, she got a call. Ray had been arrested at their home earlier that day.On October 18, 2011, Ray was booked into the Putnam County Jail on fifteen felony counts. Three involved furnishing false or fraudulent records for controlled substances. The other twelve were of “recklessly, knowingly, or intentionally” distributing or dispensing controlled substances—at times, to manipulate his patients into having sex.Three women interviewed in an affidavit described having penetrative or oral sex with Ray. He was prescribing each of them narcotics, benzodiazepines, stimulants, or some combination of the three. Several other women described Ray making sexual advances: hugs, back rubs, kisses on the lips, or suggestions that they masturbate to relieve their anxiety. When I spoke with Bookwalter, the prosecutor, he remembered the women’s stories as disturbingly repetitive. “We found this pattern,” he told me. “As they got on the drugs, he would up the prescriptions. They would become very dependent on him. They called themselves ‘almost zombies’ after a while. And in most cases, he would become sexually aggressive. He would kiss, he would give rubs on their bottoms, bodies, he would get erections.” Sometimes, God would come up, Bookwalter told me, adding that Ray once told a patient that God wanted him to impregnate her.One of the women was pregnant while under Ray’s care. During her visits, he gave her hugs and backrubs, touched her backside, and eventually attempted to kiss her, while escalating her prescriptions for oxycodone, oxycontin, and morphine. Later, the woman’s daughter was born with opiate dependence and had to stay in the hospital for several months after birth. Another patient, who later testified, stood out for the degree of entanglement with Ray. At first, she told the court, Ray was just managing her migraines and hypertension. Then he gave her escalating doses of oxycodone and oxycontin, and “started giving me hugs.” Ray began calling her on the phone, and would say that “a way to relieve stress was through masturbation. He talked about that and he said that he would be able to do it in his office,” she said. “We ended up in a hotel room. Or sometimes we would meet and he would prescribe me drugs at Subway.” The doses got higher, and he also started her on morphine. “He said at one point we were spiritually married,” she said. The relationship lasted almost a year.Linda Showalter, whose thirty-three-year-old son Rex had died in February, 2010, had been worried that Ray was giving Rex too much medication. “He was sitting around falling asleep all the time,” Linda told me. She encouraged her son to go to rehab, which he did. Weeks later, however, he went back to Howell, who prescribed him methadone, oxycodone, and Xanax. Rex died from aspiration and multiple-drug ingestion four days later, according to an affidavit. “He didn’t overdose,” Showalter testified. “He took the prescriptions that this guy prescribed for him.”“In thirty years, I’ve never seen anything like it,” Bookwalter, the prosecutor, said about the extent of Ray’s crimes. “Nothing before or after. Hope I never do again, too.”One morning, Melynda brought me to the basement to go through a box she had found that contained Ray’s personal archives: a scrapbook with news stories about his time in Haiti; his medical-school essays. Improbably, and unbeknownst to Melynda, the box contained a clue into Ray’s mental state at the time of his crimes: a microcassette recorder, with a cassette inside. Melynda didn’t know how to operate the recorder, so I helped her turn it on.Ray’s voice filled the room, quick and precise, with a Hoosier twang. Melynda sighed, hearing him again. “It’s such a strong voice,” she said. “I haven’t heard that strong Ray voice for a long time.”“Medications,” Ray was saying, “Elavil twenty-five, one qHS chronic pain, methadone ten to forty, two four times twenty-four hours chronic-pain control, oxycodone thirty-one eighty-one after one, Q less than or equal to four times twenty-four hours PRN breakthrough pain, Xanax four milligrams sixty one two times a day.” The numbers Ray was dictating were not standard doses. “Counselled patient regarding diagnosis, need for follow-up, weight reduction, mind-body exercise, compliance with medication, risks and benefits of controlled substances, including M.V.A., falls, constipation, sedation, and death.” There was a click, then Ray continued. “In summary, it would seem to me, since it was stated by one of the parents that the patient had been quote ‘on the verge’ unquote of doing this for several years, and also, if you look at my office notes, he was actually on less medicine at the time of his death than he had been previously, and actually had been on this same dose of medicine for several years dating back to 2007, I feel that his death could be regarded as an almost inevitable occurrence.” Soon, the tape popped, hummed, then clicked off.Melynda and I sat in silence at the basement table. We stared at the tape, then at each other. “So that had to deal with—” Melynda started. She didn’t have to say Rex Showalter’s name. (Linda Showalter later told me that neither she nor her husband had ever said Rex was on the verge of overdose.)“I don’t know why this is in my possession,” Melynda was saying. “You could tell in the very beginning it was that strong Dr. Howell voice.” But she said she could hear it change into a voice that signalled, “I’m fighting, because I did nothing wrong.”Samantha was watching television one day in early 2012, a few months after her dad’s arrest. Charlie Rose was interviewing a panel of neurologists including Bruce Miller, an expert on F.T.D. at the University of California, San Francisco, and the neurologist who told me about Howell. “I watched this whole episode,” Samantha recalled, “and it was, like, ‘These people are all talking about my dad.’ ” In April, 2012, in the midst of his criminal case, the family petitioned the court to be able to fly Ray to San Francisco to enroll him in dementia research at U.C.S.F’s Memory and Aging Center.F.T.D. is one of the most common causes of early-onset dementia. Abnormal bits of protein clump together inside brain cells in the frontal and temporal lobes, causing those cells to die. The most prevalent form of F.T.D. is the behavioral variant (bvF.T.D.), which disconnects brain networks that integrate sensory and emotional information, weigh reward and punishment, and select the most socially appropriate behavior from available options. Damage to these networks can result in impaired moral behavior, but with preserved moral knowledge. In other words, patients may know when their actions are morally wrong or inappropriate, but they can’t stop themselves from acting wrongly. They often become self-centered, pleasure-seeking, and unconcerned with the consequences of their actions. One study of U.C.S.F’s patients, co-led by Miller, found an association between bvF.T.D. and unlawful behavior: roughly thirty-seven per cent of patients with the disease had engaged in crime, commonly theft, traffic violations, and unwanted sexual advances, compared to roughly eight per cent of patients with Alzheimer’s and three per cent of those with mild cognitive impairment.At U.C.S.F., Ray, now fifty-seven, was found to have abnormal memory, learning, and decision-making, and an MRI of his brain showed volume loss in the parietal lobes, a finding suggestive but not confirmatory of Alzheimer’s disease. When I asked Miller about his team’s assessment of Ray, he remembered disagreement. “Some thought he was a sociopath with no pathology, some thought he had mild Alzheimer’s dementia and was easily manipulated, and a few of us thought he had F.T.D., although we didn’t have strong evidence for it. Even for a center that focusses on F.T.D., it wasn’t really clear.” Still, they wrote down a tentative diagnosis of F.T.D. And, because of Ray’s family history of dementia, they sent DNA samples off for genetic testing.Weeks later, Miller wrote to the court, revealing that Ray’s genetic test came back positive for a hexanucleotide-repeat-expansion mutation in the gene C9orf72, a major cause of both inherited A.L.S. and F.T.D. By age eighty, about two-thirds of people with this type of mutation develop A.L.S. or dementia. Among those with F.T.D, half have symptoms by age fifty-eight.Ray’s workup and sentencing happened to occur during a moment of peak optimism in the field of neurolaw. Some proponents of criminal-justice reform hoped that emerging neuroscientific research into human decision-making would revolutionize criminal law, by challenging legal norms that generally presume human actions to be conscious and voluntary. Neurolaw was the subject of a cover story of the Times Magazine in March, 2007. References to the use of neuroscientific evidence in published U.S. criminal-defense opinions roughly quadrupled between 2005 and 2015.Ray’s lawyer seized the moment, and crafted the defense around Ray’s new F.T.D. diagnosis. But Bookwalter, the prosecutor, was skeptical. As he described it, Ray was clearly competent to stand trial. He looked “too good” to have dementia. “Very articulate, very bright guy, very well spoken. Almost kind of irritated.” Plus, Bookwalter argued, the time line didn’t add up. The D.E.A. had found out about Ray’s history of infidelity, and had interviewed a female patient who had described having an affair with Ray while he prescribed escalating doses of pain medications way back in the nineteen-nineties. (Melynda couldn’t remember if this was the same woman she had described Ray having an affair with.) The D.E.A. had also documented Ray’s overprescribing in 2005, years before anyone noticed signs of dementia. Even if Ray had dementia now, he didn’t start with dementia and progress to ethical violations and criminal behavior—he progressed from ethical violations to criminal behavior to dementia. His tendency to abuse his professional power was a character trait, Bookwalter argued, not a disease.Photograph courtesy Melynda HowellIn the American legal system, people can be convicted of a crime provided that they had the mental state, or mens rea, required to commit the crime at the time of the act. What’s counterintuitive for a neurologist like me is that neuroscience has little role in determining mens rea. As Stephen J. Morse, a professor of law and psychiatry at the University of Pennsylvania explains, it’s a legal concept that relies on “folk psychology” to explain behavior: interpreting actions in terms of beliefs, desires, intentions, and so on, not in terms of neurobiological mechanisms, like protein deposition or neurotransmitter levels. Courts infer mens rea from defendants’ actions, statements, and the circumstances surrounding the crime. Modern neuroscience, Morse argues, is not able to definitively determine whether someone acted with mens rea. Functional neuroimaging can capture neural signals associated with simple intentions (like intending to move a finger) and can distinguish between certain stimuli-induced brain activity (like neural patterns in response to monetary rewards, as opposed to erotic images). But these tools cannot decode the spontaneous, specific content of an individual’s intentions or desires. Put in philosophical terms, neuroscience can show crude correlates of certain mental states, but not the “qualia”—the felt sense of knowing, desiring, experiencing. For now, qualia are intrinsically private.Because neurobiological evidence can be seen as especially objective by a jury, even when its application to a specific case is uncertain, judges may be cautious about admitting it. The defense must argue how a neurobiological abnormality, associated at a population level with certain behavior, generated or enabled a specific criminal act by a specific individual. In Ray’s case, C9orf72 mutations can cause bvF.T.D., and bvF.T.D. is associated with criminal behavior, but there is no gene for overprescribing opiates and sleeping with patients.Ray’s lawyer and Melynda encouraged Ray to enter a plea agreement, assuming that Ray would receive a light sentence. After all, he was no longer a threat to society: he had lost his medical license and his practice, and his disease would eventually be fatal. Ray pleaded guilty to five of the fifteen felony counts, including one involving sex with a patient to whom he had prescribed escalating doses of benzodiazepines. But the family’s calculus proved wrong. The judge sentenced Ray to four years in prison and two years of probation. Ray was transported to Plainfield Correctional Facility to serve his term.Even Bookwalter, the prosecutor, acknowledges that prison may have been too harsh for Ray: “He went downhill quick.” Soon after Ray arrived at Plainfield, his quiet dialogue with voices turned into full-blown psychosis. Once, Samantha saw him eating the styrofoam packaging from a sandwich.Ray was eventually moved to a correctional facility that had an in-house infirmary. Sometimes, when his family visited, they would find him standing up on his mattress, naked. He stopped eating and rapidly lost weight. Prison medical records document his behavior with clinical neutrality: “Client believes he is being judged for heinous deeds and stands for hours in judgment . . .” Another document said that he “remains delusional with religious themes of pittance and persecution for all his mundane ill-doings. Will stand straight and rigid in the imaginary delusional ‘lake of fire awaiting angels to rescue me.’ Will voice from time to time visual hallucinations of redeeming angels, beams of light from heaven, or other heavenly creatures/person . . . Sleeps on the floor vs. the bed mat. When bed frame provided . . . voiced intent to practice ‘falling backwards’ . . . to test whether he would be caught by angels. If caught, he was redeemed.’ ” Except for his dialogue with the voices, Ray rarely spoke.Worried about his rapid decline, the family successfully petitioned a judge to release Ray from prison and move him to a nursing facility. Relieved, Melynda called over twenty facilities, but she recalls that it took a year for one to accept him. When he was released from prison, Ray had served two years and lost forty pounds on his already lean frame. His family expected him to die. But Ray got better. His hallucinations became less threatening. He started eating again. “There was no darkness around him anymore,” his daughter Caryn remembers tenderly. “He became chubby. He would eat so much junk food, but nobody cared. We would just give it to him. When I’d go see him, I’d take him whatever he wanted, because we were just so happy to see him smiling and happy. Whenever he would get to come to the house, he would let the girls brush his hair.”For the Howells, the C9orf72 F.T.D. diagnosis absolved Ray not only of his crimes. For some of his children, it also explained his decades of infidelity. Their forgiveness is so absolute that several family members described Ray’s patients as the ones who had taken advantage of him. A genetic diagnosis can do this—it can make outcomes feel inevitable. Melynda remembered that, back in the nineties, when she had confronted Ray about his affair, he couldn’t explain himself, “which told me it wasn’t the Ray that I met when I was fifteen. He had ‘why’s for everything. He knew this was wrong, but he didn’t know why it was going that way. Knowing who he was, knowing that he actually loved me, and he loved the kids, and he loved his life, and he loved the Lord, and he loved studying, and he loved medicine, it just never fit in.”Ray spent four years in the nursing home. He was still quietly hallucinating, but he was also sweet, issuing medical advice to other patients and to staff. In 2018, he died peacefully in bed, with Melynda and their children at his side.Salvatore Spina, a neurologist and neuropathologist at the Memory and Aging Center, which is overseen by Miller, opened the door to a four-degree °C room and we stepped into darkness, engulfed in a loud hum. He flipped on a neon light. The walls were lined with brains. “We have a collection here that goes back more than a decade, several hundreds of them,” Spina said, gesturing at the shelves stacked with plastic containers with little blue handles.Ray had decided to donate his brain to science. After he died, a U.C.S.F. team arranged for his brain to be transported to San Francisco, where it was weighed, photographed, sliced, and stained. Even before patients develop signs of dementia, the C9orf72 mutation produces abnormal proteins called dipeptide repeats, which aggregate inside brain cells. A protein called p62 labels these abnormal proteins for degradation. Later, yet another protein called TDP-43 tends to build up inside brain cells, killing them and causing the brain to shrink.After hearing so much about Ray, I was excited to see how the disease had quietly worked its way through his brain. One of the reasons I became a neurologist was the satisfaction of suspecting a disease, hunting for it, and seeing evidence with my own eyes: a muscle fasciculation, an epileptiform discharge, a lesion on an MRI. Making a neurological diagnosis feels like solving a mystery, and the diseases typically leave a trace.Spina located Ray’s container, carried it to a fume hood, and snapped open the handles. Gingerly, he lifted out bundles of cheesecloth, unwrapped the bundles, and, in his gloved hands, fanned out wet, rubbery slabs of Ray’s brain. “This is the orbitofrontal cortex, important for social functioning, social cognition, and preventing us from making bad decisions. To my eyes, that area looks essentially normal.”He flipped through more brain slabs. “Even the deepest regions of the brain here look over-all normal. The amygdala, the putamen, the globus pallidus, the caudate nucleus, the cerebellum,” he said. “Maybe the thalamus looks a tiny bit smaller in the posterior portion,”—he held up a slab of brain and squinted at it—“but we also know that it’s a very difficult judgment to do with the naked eye.”Normal was not what I expected. But, I assumed, the truth would become clearer under the microscope. Spina replaced the brain slabs, returned the container to the cold room. In his office, he showed me a copy of Ray’s neuropathology report.At death, Ray’s brain weighed 1,420 grams, a normal weight. Under the microscope, the neuropathologist had seen evidence of C9orf72—there was abnormal p62 staining in Ray’s thalamus and several other brain structures. But Ray’s brain did not stain positive for abnormal TDP-43 aggregates, which are almost always seen in patients who are symptomatic from C9orf72 F.T.D.I left Spina’s office that day feeling anxious. It bothered me that, even years after his criminal behavior and after Ray had died from dementia, his preserved, sliced, and stained brain lacked the feature seen in the great majority of patients who are sick with his disease. This was one of many moments when studying Ray Howell felt like shifting from one foot to the other. Blaming Ray, then blaming his disease.It turns out that Ray Howell is one of only a handful of patients with C9orf72 mutations and profound, progressive, F.T.D-like behavior ending in death, who fail to show abnormal TDP-43 protein inclusions in their brains at autopsy. Bill Seeley, a neurologist and C9orf72 expert at the U.C.S.F. Memory and Aging Center, who evaluated Ray’s brain after he died, explained that in such cases, the mutation may first cause subtle molecular changes in the thalamus that disable what he and his colleagues call the “salience network,” which imbues internal and external stimuli with emotional weight. That damage—so subtle it wasn’t noted on Ray’s MRI—disconnects the patient from their own emotions, and the emotions of others.The building blocks of Ray’s crimes—compulsiveness, transgressiveness, poor boundaries—were there from early adulthood. To believe Ray’s behavior was due to C9orf72 required believing that Ray and C9orf72 were inextricable, that the mutation shaped Ray’s personality long before his dementia set in.This is the conclusion that Miller has come to. Since C9orf72 was discovered, in 2011, scientists have associated the mutation with personality traits that can start in childhood. Miller recalls patients with lifelong obsessiveness and “intense beliefs. Holistic medicine, atheism; it depends on what ideas people grab onto.” One study found that half of mutation carriers had fixed behavioral patterns, with many, according to their caregivers, “always” following rigid daily schedules. Forty-five per cent had a Ray-like pattern of “excessive exercising (mostly jogging)”, and they were “bad-tempered if they could not do this.” Miller says the disease seems to shape psychiatric function over a lifetime, “and then all of a sudden something triggers a deterioration, and at that point we call it F.T.D.”In all of Miller’s years treating people with dementia, Ray is one of the only patients who served significant time in prison. Until Ray’s final year of practice, when he was caring for some of society’s most vulnerable people, his brain still appeared to be functioning well enough that no one was willing to defy him. “This rolled out as tragically as any single case I’ve ever been involved with. Many, many losers,” Miller told me. “Here’s a man who presumably came into the world with really wonderful intentions. He wanted to be a healer. I think he got satisfaction out of healing and helping people. And as the dysfunction in his brain increased, not only was he no longer a healer, but he was in some ways predatory. So I think the tragedy of Dr. Howell is how his disease changed his good intentions into less good intentions. People in power can do horrible things.”While neuroscience can tell us who might be at risk of criminal behavior, it can’t predict which of those people will become criminals, and it can’t identify the mysterious point at which someone with a neurologic disease might lose enough decision-making control to become dangerous. In the Howell family, this problem is personal. One of the cruellest things about C9orf72 is that it has autosomal-dominant transmission: a child of a parent with a C9orf72 hexanucleotide repeat expansion has a fifty-per-cent chance of inheriting it. The Howells know this. They also know that a positive test would cause anxiety and affect their relationships, their children’s lives, their access to certain forms of insurance—and to what end? While there is promising research into using gene-therapy technology to treat C9orf72, there is currently no treatment for the mutation. So the Howells have decided not to find out who has it. Instead, they are watching one another, waiting, praying and, they hope, intervening before anything goes seriously wrong. ?