Patient H.M. (40 page)

The relationship was already over, though. Annese just didn't know it yet.

In July 2011, William Bradley, the chairman of Annese's department at UCSD, received an email from Bruce Rosen, a colleague of Corkin's who ran the Martinos Bioimaging Center at Massachusetts General Hospital. The email was cc'd to Corkin and her colleagues at MIT/MGH but not to Annese.

“I wanted to establish a friendly contact with you to solicit your help in resolving a potentially challenging issue between Jacopo Annese and the team of investigators here at the MGH and MIT, led by Sue Corkin, who have been involved in studying H.M. for nearly five decades,” Rosen began. He complained not only that Annese had been denying them access to “critical data that we need for our further analysis,” but that “several press articles have come out about this brain, which fail to mention who the brain was donated to, and who was involved in this research. This certainly further inflamed the situation, even beyond the scientific issues….Folks here are pretty frustrated, to say the least, and have even talked about legal action to get the brain back.” He asked Bradley to tell Annese that “just running off with the brain is not really the right thing to do.” Then he made a not-so-subtle threat: “I'm worried,” he wrote, “that we may have some more fundamental psychopathology to deal with, but I hope that I'm wrong, and that he is just a misguided young scientist without appropriate mentoring to understand just how damaging to his scientific career this sort of behavior will be.”

Bradley responded: “I suspect that what we have here is a failure to communicate rather than Jacopo running off with the goods. I haven't seen any evidence of that since he has been here at UCSD. But I should let him respond. I suspect this will all work out.”

Rosen wrote back to Bradley, reiterating that Corkin and her group had “been trying for over a year to get him to return data, and the brain” and that they “were quite explicit about what they were expecting.” He also reminded Bradley that “the group here was pushing for legal action, since the brain was donated to MGH legally, but I convinced them that you would help prod him to do the right thing. I think all sides would be greatly embarrassed if such a famous historical figure as H.M. became the object of a legal squabble.”

In March 2013, a summit meeting was held in New York City to negotiate the conflict that had arisen over the control of Henry's brain. The meeting was held in a boardroom on the eighth floor of the headquarters of the Simons Foundation, on Fifth Avenue, and was chaired by Gerald Fischbach, director of life sciences at the Simons Foundation. The foundation may have been chosen to preside over the conflict in part because it was a neutral entity, one of the few major private or public scientific foundations that had not at one time or another funded research on Henry. Annese and Corkin were present, as was the president of the Dana Foundation, a $240 million agency that had funded some of the postmortem work with H.M.'s brain. A number of other researchers and administrators from UCSD and MIT and MGH were there, too, though the focus was clearly on resolving the discord between Annese and Corkin. Things had not improved since Rosen's email a year prior. In fact, communication had broken down entirely. Annese and his colleagues at the Brain Observatory had proceeded with their work, completing a 3-D digital model of Henry's brain based on the block-face imagery and performing the first postmortem measurement of the lesion. Annese had also written and submitted a paper based on that work to a journal called
Nature Communications
. Whether or not the withholding of the requested block-face imagery and the tissue samples was warranted—settling the ownership of that data was one of the issues on the agenda of the meeting—Annese's act of writing and submitting that paper without consulting with Corkin and her colleagues was at the very least a violation of academic etiquette. The paper was sent to four peer reviewers. Three of the reviewers were very positive. The fourth reviewer was Suzanne Corkin. The meeting in New York City was called soon after she received it.

A week before the meeting, MIT had sent administration officials at UCSD a formal demand that they turn over all 2,401 slices of Henry's brain to a representative of MIT, who would shepherd it to a brain bank called the MIND Institute at the University of California, Davis. The MIND Institute was run by David Amaral, a former colleague of Corkin's. Amaral was present at the meeting in New York, as was Matthew Frosch, the neuropathologist who had, along with Annese, performed Henry's brain extraction, and Jean Augustinack, the MGH researcher who was working on her own paper based on postmortem neuroanatomical analysis of Henry's brain.

After Fischbach called the meeting to order, Annese began by telling the group that he hoped they could quickly draft a retroactively applicable materials transfer agreement to settle the dispute. A materials transfer agreement, or MTA, is a legal contract that typically accompanies any important biological specimen when it is moved from one institution to another. It sets guidelines as to whether the transfer is permanent or temporary, and defines ownership. An MTA had not been drafted when Corkin gave Henry's brain to Annese: Instead she just passed him the cooler containing the brain at the JetBlue gate four years before, with no paperwork whatsoever. Annese now told the group that he didn't really care where Henry's brain ultimately resided, though he wanted to make sure that whatever happened his laboratory would receive fair credit and recognition for all the time and money and labor it had invested and that the conflict they were in the midst of wouldn't somehow damage his reputation.

“I never felt like I owned the brain,” Annese said. It appeared, at that moment, that the question of where Henry's brain would ultimately be housed—whether it would remain with Jacopo Annese at UCSD or be moved at MIT's request to David Amaral at UC Davis—might be settled quickly.

“And how would you like to set this up,” Gerald Fischbach, the meeting chairman, asked, “if it doesn't really matter where the tissue resides? Do you want to decide that now? Or decide it by committee?”

Corkin interjected.

“It's not a decision by committee,” she said. “Because it's a decision by the people who own the tissue. And that's MGH and MIT. And our decision is that we would like it to go to David's lab.”

“In what sense do you own the tissue?” the chair asked.

“We have a brain donation form,” Corkin said.

She then passed around a copy of the form, the one signed by Tom Mooney on December 19, 1992, a month after he became Henry's conservator.

The meeting lasted two and a half hours and became increasingly contentious. One of the items on the agenda was a discussion of the
Nature Communications
paper, which some at the table did not want to be published. Annese made what he hoped would be taken as a conciliatory gesture, telling Corkin that the journal's editor had agreed to add her name as a co-author.

Corkin said that adding “names to that paper wouldn't make it publishable. It needs to be rewritten. As a serious scientific document.”

“It's not a serious scientific document?” Annese asked.

“It's not sophisticated scientific writing,” Corkin said.

“That's not what the other three reviewers said.”

Jean Augustinack, the researcher who planned to collaborate with Corkin on her own anatomical paper based on the MRI imagery of Henry's brain, jumped in: “Maybe the point is that [Annese's paper] is not the
definitive
anatomical paper.”

“Of
course
it's not,” Corkin said. “Of course it's not.”

The chairman intervened.

“Somebody just read it and reviewed it,” he told Corkin, “and they already determined it was publishable.” Then, referring to Annese's and Agustinack's similarly themed papers, he continued: “We've got the knotty subject of two publications here. And I'm uncomfortable criticizing a publication that I have not been a part of. If Jacopo feels that, in his scientific judgement, it merits publication, and the reviewers have accepted it, well…It may not turn out to be
the
definitive paper. And that may be left to you, Sue, and your colleagues, or to you, Jacopo.”

“It's just melodrama,” Corkin said, referring to Annese's paper.

“The reviewers found it very sound,” Annese said.

“You call him
Henry,
” Corkin said. “I mean, it's so chatty! ‘During the operation, Henry…' ”

“Please, Sue, send me your comments,” Annese said. “One of the reviewers said the data was stellar.”

The bickering continued, and the meeting ended a half hour later. In a follow-up memo that was sent to all the participants, Dana Foundation adviser Guy McKhann summarized what he saw as the major decisions made. He wrote that Corkin and her colleague Matthew Frosch would both be added as co-authors on Annese's paper and that they would provide their comments and edits to Annese by April 15, after which Annese would resubmit to the journal. McKhann also wrote that while the “ultimate location” of Henry's brain would someday be the MIND Institute at UC Davis, it would be up to Annese and Amaral to determine what tissue would be transferred and when.

Annese and Corkin both quickly sent the memo back to McKhann, each having heavily edited it. Regarding the ultimate location of the brain, Annese wrote the following: “Dr. Corkin
requested
that the ultimate location of the tissue will be with Dr. Amaral at UC Davis.” As for Corkin, she struck through the line that said Amaral and Annese would collaborate on the timing and details of the transfer. Instead, she wrote, UCSD would simply “transfer all of H.M.'s brain tissue, including the tissue that has already been mounted,” to an agent of MIT. At that point, “MIT and MGH will write a materials transfer agreement, which will allow UC Davis certain rights to use and distribute the tissue owned by MIT and MGH.”

As far as Corkin was concerned, she and her colleagues owned the brain, period, and Annese had no say in the matter whatsoever.

Despite the ongoing and unsettled question of where Henry's brain would reside, the New York meeting did accomplish at least one thing: Now that Corkin and Frosch had been retroactively added as authors on Annese's
Nature Communications
paper, Corkin and Annese
had
to communicate to complete the revisions process, breaking the long and chilly silence between them. What this new correspondence revealed was that despite what she'd said during the meeting, Corkin's central problem with the paper, the one she pushed back on hardest, didn't have much to do with Annese's chatty writing style. Instead she was concerned with something Annese had discovered in Henry's brain.

Specifically, Annese's analysis of the block-face images and the tissue itself had revealed a previously unreported lesion in Henry's frontal lobe. The lesion was in the left hemisphere and appeared to have been caused by a man-made object. In his draft of the paper, Annese speculated that my grandfather had created the lesion during the operation while he was levering up Henry's frontal lobes to access the medial temporal lobes. This was a significant finding. As one of the paper's anonymous peer reviewers pointed out, “much of the neuropsychological literature on H.M. has made the case that so-called frontal function was intact.” This stood in stark contrast to the new paper, where, the reviewer stressed, “Annese and colleagues unequivocally demonstrate that frontal white matter was affected, likely by the surgical approach. Their future investigations that will examine detailed histology in this region will be of great importance, because if there
is
significant white matter pathology within frontal systems, that may have implications for a retrospective reinterpretation of H.M.'s neuropsychological findings.” In other words, for the previous six decades neuropsychologists such as Corkin had interpreted their experimental results with Henry under the working assumption that his lesions were restricted to the medial temporal lobes. The discovery of this new lesion in a different part of Henry's brain might call some of their conclusions about the functions of the medial temporal lobes into question and require a reexamination of all that old data.

When Corkin sent Annese her revisions of his paper, she deleted all references to the frontal lesion. In a note to Annese, she explained that “the frontal lobe lesion does not appear on either the in situ scans [the MRI scans made while the brain was still in Henry's skull] or the fresh brain photos” and that “any consideration of it would be highly misleading.” She followed up with an email stating that she and her colleagues at MIT and MGH “believe that there is a good chance that the alleged orbitofrontal lesion is a handling lesion,” meaning that it was caused after death, during the extraction and subsequent handling of the brain. She added that “there is no intent by the Martinos [MGH] group and me to hide evidence.”

Annese responded with a series of images from in situ MRI scans that, contrary to Corkin's assertions, appeared to give clear views of the lesion, demonstrating that it could not have resulted from the postautopsy handling of the brain. Annese also sent imagery of some of the slides bearing that portion of Henry's frontal lobes, and these slides seemed to confirm that the lesion resulted from the use of a man-made object, such as a flat brain spatula. The lesion, Annese wrote to Corkin, “was previously unreported (we ascertained it was present even in the 1992–93 MRI scans) and together with other data represents new evidence in the case. I really don't understand the reluctance; this is not image data reconstructed from K-space; this is real, flesh and blood. There's a lesion outside the medial temporal lobes, it is conspicuous and it should be reported. Remember, the goal of this paper and the archive is to catalyze new investigations as well as new debates, like the one we have been having.”