Location Withheld — A researcher has reportedly secured funding for a program he describes as the most significant therapeutic advance in decades: reducing Multiple Sclerosis to Single Sclerosis. The proposal contains no drug, no device, and no patient, and cleared external review with minimal revision. It has since attracted renewed federal interest, which is the reason this edition is being reprinted.
CLASSIFICATION: THE NOMENCLATURE BREAKTHROUGH EDITION — PLURAL-OF-LOCATION REDUCTION ANALYSIS
DISTRIBUTION: Grant Officers, Peer Reviewers Who Recommended Acceptance, One Neurologist No Longer Being Contacted, Patients Diagnosed Prior to This Sentence, Anyone Who Has Read the Disease Name Closely
PREPARED BY: The Externality Research Division, in consultation with the Office of Terminological Reduction
DATE: Previously published. Reprinted by request.
The scientist presented his framework at a regional conference last month.
“Right now patients have multiple. The goal is one.”
He advanced to the next slide.
“After that, we go lower.”
The Framework
The proposal outlines three phases.
Phase I: Multiple Sclerosis → Single Sclerosis
Phase II: Single Sclerosis → Zero Sclerosis
Phase III: Maintenance
Asked what mechanism would accomplish Phase I, the scientist said the mechanism was the point of the research and that if he already had it he would not need the grant.
Asked what Phase III maintains, he said the zero.
Asked whether the phases were sequential, he confirmed that they were, and added that this was what made the plan conservative. A more aggressive investigator, he noted, would have attempted zero directly. He was proceeding one integer at a time, out of an abundance of caution.
The Budget
The award funds a five-year program. The largest line item is Nomenclature Reduction, Phase I. The second largest is Personnel. A third line, smaller, is labeled Modeling Software.
A single line reads Contingency, in the event that it is one. The grant officer who approved the budget reportedly did not know which contingency this referred to and did not ask, on the grounds that a contingency line is standard and that the study was, in any case, projected to run under budget, because it had nothing to purchase.
No funds were allocated to patient recruitment. When this was raised, the scientist explained that the patients already existed, in the sense relevant to the study, which was that their diagnoses did.
Peer Review
The proposal reportedly cleared external review with minimal revision.
Reviewer 1 wrote that reducing the number of scleroses is obviously desirable and recommended acceptance.
Reviewer 2 requested clarification on statistical power and did not otherwise comment.
Reviewer 3 asked whether the applicant understood that the word multiple in the disease name refers to the presence of lesions at multiple sites within the central nervous system, and that it is a plural of location rather than a plural of disease, and that no patient has ever had more than one.
The scientist responded that he thanked Reviewer 3 for confirming the presence of multiples.
The grant was funded.
Clinical Consultation
A neurologist reportedly agreed to meet with the research team.
She explained that the naming convention dates to Charcot in 1868, describes scar tissue distributed across the brain and spinal cord, and has nothing to do with quantity of illness.
The scientist asked how many sites, on average.
She said it varies.
He asked for a number.
She said it varies, and that this was not the useful question.
He reportedly wrote down VARIES — INVESTIGATE and thanked her for her time.
She has not been contacted again.
The Linguist
Following the neurologist’s departure, the team retained a linguist, on the theory that the problem might be one of language rather than medicine. This was the closest the program came to a correct diagnosis.
The linguist explained that some plurals count things and some plurals do not. A plural of location, she said, marks that one thing appears in several places; it does not multiply the thing. She offered an illustration: a person with freckles across the face has freckles at multiple sites but is not suffering from multiple faces.
The scientist asked whether the goal, then, should be to reduce the sites.
The linguist said the goal was to understand the sentence.
The scientist wrote down REDUCE THE SITES, thanked her, and noted that the consultation had been productive, as it had generated a Phase I subgoal. The linguist asked to review the minutes. The minutes were described to her over the phone. She asked that her name be removed. It was moved to the acknowledgments.
Patient Input
The research team reportedly conducted a survey of 240 patients.
Respondents were asked whether they would prefer to have fewer scleroses than they currently have.
Ninety-seven percent said yes.
The team has cited this figure in four subsequent publications as evidence of unmet clinical need.
The remaining three percent were recorded as undecided. Two of them had written, in the margin, that they did not understand the question. This was coded as undecided. One had written that she had one, that she had always had one, and that the question appeared to assume otherwise. This was coded as undecided as well.
One respondent has since written to the team asking what the survey was for.
She reportedly has not received a response.
Statistical Power
Reviewer 2’s request for clarification on statistical power was addressed in a subsequent memo. The team engaged a statistician to compute the number of subjects required to detect a reduction from Multiple to Single.
The statistician asked how the outcome would be measured. The team explained that the outcome was the word. The statistician asked whether the word varied between subjects. The team said it did not; the word was the same for everyone.
The statistician noted that an outcome that is identical across all subjects and does not change has a variance of zero, and that a study measuring it requires either no subjects or infinitely many, depending on which of two errors one preferred to make. He recommended no subjects, as the cheaper of the two.
The team recorded that the study was adequately powered at a sample size of zero and forwarded this to Reviewer 2, who did not otherwise comment.
Competing Approaches
The announcement has drawn attention to at least two rival programs.
A laboratory in the Midwest is pursuing Fractional Sclerosis, on the theory that if the count can be lowered below one, the disease becomes structurally unable to persist.
A second group has proposed Divided Sclerosis, distributing the patient’s holdings across several willing volunteers so that no individual exceeds a manageable share.
The scientist has publicly criticized both.
“You can’t split it. You have to bring it down.”
Asked to elaborate on the difference, he said one was serious science.
The Fractional group has since published a preprint arguing that one-half of a sclerosis is, by definition, less of a disease than a whole one, and that the field has been insufficiently ambitious about the space between the integers. The Divided group declined to comment, citing an ongoing effort to locate a volunteer.
The General Method
Colleagues have begun to describe the underlying approach as portable. If a plural in a disease name can be reduced, the reasoning goes, then any disease named with a plural is a candidate.
Proposals now circulating include reducing Multiple Myeloma toward Single Myeloma, bringing Multiple Organ Failure down to a more manageable count of organs, and addressing Multiple Personality by encouraging consolidation. A working note suggests that Chronic conditions might be reclassified as Acute, on the grounds that Acute sounds shorter.
One investigator proposed the most efficient version of the method, which is to leave the illness untouched and change only the name, achieving the reduction on paper while sparing the patient any procedure. He was reportedly surprised to be told this was already the plan.
The Naming Committee
A professional body reportedly convened a working group to consider whether the disease should be renamed to avoid further confusion.
The group met four times.
It concluded that renaming a condition after 158 years would introduce significant risk of confusion.
A member asked what the current risk was.
The minutes record no answer.
The minutes do record that the working group recommended no action, that the recommendation was adopted unanimously, and that the meeting during which the confusion was discussed was itself later described by two attendees as confusing. This was not entered as evidence.
Ethics Review
The institutional review board reportedly approved the study on the grounds that the protocol involved no intervention, no patient contact, and no procedure of any kind.
Asked what the study consisted of, the scientist said modeling.
Asked what was being modeled, he said the reduction.
The board reportedly noted this in the file and approved it unanimously.
One member abstained. Her written statement reads, in its entirety: I would like it recorded that I asked.
The Model
The modeling described to the board reportedly consists of a spreadsheet. The first cell contains the current count. Subsequent cells contain lower numbers. The final cell contains zero, formatted in bold.
A member of the team who requested anonymity confirmed that the model is complete, that it runs, and that it arrives at zero every time. Asked how, he explained that this was the finding.
A mathematician consulted informally noted that the cell after zero contains a negative number, and asked what a patient with negative scleroses would be understood to have. The scientist reportedly wrote down NEGATIVE — INVESTIGATE, and observed that if the patient could be brought below zero, the surplus might be transferred to the two rival programs still looking for a volunteer.
Renewed Federal Interest
The program has recently come to the attention of a federal office, which is the occasion for this reprint. The office is reportedly evaluating whether the count-reduction method could be applied across the nomenclature of disease as a portfolio, on the reasoning that many conditions are named with a number and that lowering all of them at once would represent a considerable aggregate reduction.
A briefing document prepared for the office reportedly lists the projected savings in scleroses, myelomas, and organs, and describes the initiative as budget-neutral, since no clinical activity is contemplated at any stage.
Asked whether the office had consulted a physician, a spokesperson said the initiative was terminological and therefore fell outside the scope of medicine. Asked whether it fell inside the scope of anything, the spokesperson said it fell inside the scope of the office.
Media Coverage
The program has been described in press coverage as:
- “A bold new direction”
- “Elegantly simple”
- “Long overdue”
- “The kind of first-principles thinking the field has been missing”
Three outlets have reported that the scientist is working to cure multiple sclerosis.
None have reported what he is actually doing.
The scientist has not requested corrections.
Bottom Line
- What Happened: A researcher secured a five-year grant to reduce Multiple Sclerosis to Single Sclerosis, then to Zero, on the belief that the multiple in the name is a quantity of disease rather than what it is — a plural of location, describing scarring at several sites in one nervous system belonging to one patient who has one condition.
- Why It Matters: Every institution positioned to catch the error — peer review, the neurologist, the ethics board, the statistician, the naming committee — encountered it, and each returned the applicant a reason the program could proceed, because a lower number is easier to approve than a sentence is to read.
- The Complication: There is no mechanism. The grant funds the search for the mechanism, the model reaches zero by arithmetic rather than by treatment, and the study is adequately powered at a sample size of zero because its outcome is a word that is the same for everyone.
- What Happens Next: A federal office is evaluating whether to apply the method to every disease named with a number, the count on the spreadsheet continues downward past zero, and the woman who asked whether any of this would help her is still waiting for the part that involves her.
Closing Statement
At a public forum last week, a woman diagnosed in 2011 reportedly stood and asked whether any of this would help her.
The scientist said the research was still at an early stage.
She asked whether, at any stage, it would help her.
The scientist said that was a good question.
She said it wasn’t, and sat down.
The moderator moved to the next question.
Corrections
A previous edition described the scientist’s program as a treatment. It is a naming argument with a budget.
THE EXTERNALITY reported that no neurologist had endorsed the work. One has. He is the scientist’s brother-in-law and has asked us to note that he was not listening closely at the time.
A previous edition placed Charcot’s description of the disease in 1858. It was 1868. The count, we note, was off by ten, which we have since brought down to zero.
Editorial Footnotes
- Multiple sclerosis is a real disease. The multiple in its name is a plural of location: it denotes lesions — areas of scarring, or sclerosis — at several sites within a single patient’s central nervous system. It has never denoted a quantity of separate illnesses, and no patient has ever had more than one multiple sclerosis. The term dates to Jean-Martin Charcot, who described the condition in the 1860s.
- The scientist, the grant, the framework, the three reviewers, the neurologist, the linguist, the statistician, the survey, the two rival programs, the naming committee, the review board, the federal office, and every quotation herein are fictional. The disease, the meaning of its name, and the fact that it refers to location rather than count are not.
- Reducing a number in a name reduces the number in the name. The Externality takes no position on whether this should be confused with medicine, and observes only that at least five separate institutions in this account declined to take that position either.
- The Externality regrets that it was unable to reach the woman diagnosed in 2011 for comment. It notes that she appears, so far, to be the only party to the program who understood the question.