William Talley Summerlin and his false claims of transplantation without rejection.

Overview

 Summerlin (b.1938) was a dermatologist based at the world-renowned Sloan-Kettering Institute in New York who claimed to have found a way of transplanting skin, corneas and other tissues between unrelated members of a species or even across species without the need for any anti-rejection drugs. He claimed that he could avoid the normal rejection process by incubating or culturing the tissue for some weeks prior to making the transplant. His downfall was precipitated by his being caught enhancing, with a felt tip pen, patches of purportedly black skin transplanted onto white mice. The phrase painting the mice became a euphemism for the faking of research results. He published pictures of rabbit eyes and showed live specimens to colleagues and visitors in which he claimed that one perfectly normal looking eye had received a transplant of an incubated human cornea from a cadaver and the other eye which showed obvious signs of tissue rejection had received a transplant of a fresh, non-incubated human cornea. In fact the perfect eye had not received any treatment and no rabbits ever received these double eye transplants at the Sloan-Kettering partly because they had been considered unethical. A detailed report by an investigating committee at Sloan-Kettering concluded that his transplant data was largely fabricated or falsified. After his dismissal from Sloan-Kettering, he returned to work as a dermatologist.

I have made extensive use of the research into this case described by Joseph Hixson in his 1976 book about the affair entitled The Patchwork mouse which also contains a reprint of the Sloan-Kettering Report of the Summerlin peer review committee.

Career timeline

 Summerlin was born in South Carolina and received his medical degree from the Emory School of Medicine in Atlanta, Georgia. According to Joseph Hixson, Summerlin was accused of cheating in an exam at Emory but was exonerated for lack of evidence. After positions in Texas and the University of Stanford he went to work with the world-renowned immunologist Robert Good, first at the University of Minnesota and then at the Sloan-Kettering Institute in New York.

At Sloan-Kettering, Robert Good appointed him to a senior clinical position as head of the hospital cutaneous disease service and to the equivalent of a full university professorship within the research institute; very senior roles for a 35-year-old.

After his employment was terminated by Sloan-Kettering he returned to clinical practice and an internet search in early 2015 suggests that Summerlin was still a practising dermatologist in Arkansas.

Cultured skin samples remain viable and can be re-grafted to the donor

At Stanford, Summerlin worked with Dr Marvin Karasek and they demonstrated that donated skin could remain viable for several weeks if left in a commercial solution used for culturing human tissue. This incubated or cultured skin could be re-grafted onto the original donor just like fresh skin despite major visible changes suggesting deterioration during storage. Transplanting skin within the same individual (autografting) was already an established procedure but they had shown that removed skin could remain viable and transplantable for a substantial period of time after removal.

In a 1973 paper on which Robert Good was a co-author, it was reported that corneas cultured in the same way as skin samples also remained clear and viable when cultured although no transplantation results were reported. Thus corneal tissue could also be stored for extended periods in culture which was a practically useful observation but not a major “game changer”.

Cultured skin and corneas evade the normal rejection process?

Transplanted skin and organs from unrelated individuals (allograft) is normally rejected but not between identical twins and members of highly inbred strains of laboratory mice. Sir Peter Medawar and Sir Frank Macfarlane Burnet shared the Nobel Prize in 1960 for demonstrating that the body becomes tolerant to things it recognises as self very early in life. They showed that mice become immunologically tolerant to foreign tissue if exposed to it soon after birth. These mice would later accept transplants from this foreign strain without rejection.

Summerlin’s demonstration of the viability of cultured skin samples even though they underwent considerable visible changes seems to have triggered the hypothesis that they might also lose their immunogenicity during storage and thus evade rejection. This would have been a discovery of major practical importance for the whole field of organ transplantation i.e. the possibility of skin and organ transplants between unrelated individuals and perhaps even between species with no need for anti-rejection drugs.

Whilst still at Stanford, Summerlin began some experiments with human volunteers to test whether cultured skin samples could be transplanted onto another person without being rejected. He used different sexes for this grafting because one can distinguish between male and female cells and thus distinguish between graft survival, as opposed to healing caused by growth of the recipient’s own new cells.

Onto each subject he made three small grafts:

  • One using the recipient’s own skin which survived as expected
  • One using fresh skin from an unrelated donor which was rejected after two weeks
  • One using cultured skin from an unrelated donor which he claimed survived.

Summerlin made his findings public at scientific and semi-scientific meetings and in April 1973 he formally published these supposed findings, a paper which is still in the scientific record.

On March 30th 1973 at a meeting in Arizona for science writers, Summerlin presented a paper entitled Organ Transplantation without Immunosuppression in which he claimed that skin which had been maintained in culture solution for 4-6 weeks “becomes universally transplantable without rejection” with similar claims for corneas and adrenal glands. He claimed that human corneas could be successfully transplanted to rabbits.  His remarkable claims were widely reported in the local and national press including the New York Times . He published a scientific paper in March 1973 entitled “Organ-cultured cornea: an in vitro study” which mentions as a “personal communication” his claim that “cultured skin” could be transplanted to unrelated individuals but reports no transplantation studies. At the end of this paper it states that:

“Further investigations are underway to evaluate the practical application of this simple organ-culture technique using allogenic and xenogenic” (i.e. between different species) “transplantation”.

In a spate of presentations that followed shortly after the Arizona meeting he claimed that his technique had been applied to other organs. He claimed that cultured adrenal gland transplanted between unrelated mice had survived for 6 months and that cultured human corneas from cadavers had survived in rabbits’ eyes for over 6 months whereas fresh transplants had all been rejected within six weeks. An extended piece by Lee Edson in the New York Times entitled “A secret weapon called immunology” was published just a few weeks before his suspension from Sloan Kettering. It illustrates the attention that was being paid to Summerlin’s work and its apparent long-term potential. The piece is a historical review of some of the landmark discoveries in the “new science” of immunology and Summerlin’s boss, Robert Good is mentioned and quoted several times in the piece. At the end of the article Edson discusses Summerlin’s findings that skin, cornea and other tissues can be kept viable and available for transplantation for weeks or even months after harvesting if they are properly cultured. He also reports the remarkable finding that not only does this seemingly hibernating tissue come to life when transplanted back to the original donor but also when it is transplanted into an antigenically dissimilar host the expected process of tissue rejection does not occur. According to Edson, Summerlin had successfully grafted human, pig, guinea pig and rat skin onto mice. The tissue survives on the new host but retains its own “personality” e.g. black skin transplanted onto a white mouse remains black and female skin transplanted onto a male animal retains its inactivated extra X chromosome (Barr body). Edson speculates that it may be possible to store skin and organs for months prior to transplantation and that the culturing process might be the ultimate solution to the rejection process. Summerlin’s claimed findings seemed to offer the realistic prospect of organ banks with supplies of stored tissues and organs available off the shelf for routine transplantation with no need for long-term anti-rejection therapy after surgery.

Research groups from around the world tried unsuccessfully to repeat Summerlin’s transplantation experiments. Other scientists began requesting precise details of his culturing technique and some even visited New York to try to learn the secrets of Summerlin’s technique. Sir Peter Medawar, the Nobel prize-winning immunologist, was one of those visitors who were shown rabbits that had supposedly received transplants of human cornea; freshly harvested tissue in one eye and tissue “cultured for several weeks” in the other. It later transpired that in fact only one eye had received a transplant and the other eye was unscarred and perfectly clear because it had not had any surgery. The idea of using alternate eyes for fresh and cultured corneal transplants had been rejected on both humanitarian grounds and because initiating the process of rejection with a fresh graft would sensitize the rabbit and make it much more prone to reject any other transplant. Medawar later suggested that he and some colleagues had serious reservations about the veracity of Summerlin’s claims and other members of Good’s team had not been able to repeat the successful transplant of cultured skin.

The “painting the mice” incident and consequent enquiry

On March 28th 1974, Summerlin was scheduled to have a meeting with his boss Dr Good to discuss some of the groups’ skin transplantation results. Good had some concerns about Summerlin’s transplantation data because another staff member had been unable to confirm Summerlin’s findings and Good had drafted a paper to report these negative results. Summerlin took to this meeting two white mice that had supposedly received transplants of black skin and en route to Good’s office he enhanced the fading dark skin patches with a felt tip pen. Good apparently did not look closely at the mice and did not notice the deception but when the mice were returned to the animal house a suspicious technician rubbed the blackened area with alcohol and removed the black ink. This disturbing finding was immediately reported to Dr Good and his deputy Dr Lloyd Old.

When confronted by with the painting accusation, Summerlin admitted the offence in the presence of Drs Good and Old. Summerlin was immediately suspended, senior management informed of what had happened and a group of six senior scientists appointed to a peer review committee to inquire into all of Summerlin’s research activities. The findings of this group were reported to the president of the Sloan-Kettering Center and they largely repudiate the transplant findings claimed by Summerlin.

Some of the key points in this report are summarised below.

  • The essentials of the “painting” incident were accepted by all parties.
  • The committee could find no substantiated evidence of successful allografts of skin in mice. One mouse surviving from Summerlin’s days at Minnesota in which skin from an albino strain had been successfully transplanted to an agouti coloured mouse was found to be a hybrid and so survival of the graft was not unexpected. The committee was incredulous that Summerlin had not tested the animal to exclude this possibility. At Minnesota he used his own animals rather than those supplied and authenticated by animal house staff.
  • Summerlin could not produce any mice where a successful allograft of cultured skin could be seen and tested. There were no records of the substantial numbers of successful allografts claimed by Summerlin in grant applications, presentations, publications and manuscripts. The committee considered it inconceivable that a scientist making such a momentous discovery would not keep some specimens to support his findings. Summerlin claimed that all mice had been sacrificed to confirm that host and donor were not tissue type compatible (like the surviving hybrid mouse from Minnesota).
  • Other groups around the world had failed to repeat Summerlin’s successful allografting of cultured mouse skin. A few transfers of skin across mouse strains by others in Summerlin’s lab were initially claimed but when analysed, no trace of surviving donor skin could be found (i.e. healing rather than successful grafting). Judging success of skin transplants solely by appearance is inadequate because white or pale hair growth (on a black mouse) may occur in the region of a graft simply because of surgical trauma, the effects of graft rejection and healing. Black mouse skin when cultured loses pigment-producing cells and if transplanted to another identical black mouse can appear much lighter and be mistaken for a successful graft of white skin.
  • No grafts of corneas from another rabbit or from human cadavers had become permanently established in the eyes of recipient rabbits. Despite this Summerlin had made public claims that “cultured” human corneas were surviving and healthy in host rabbits 6 months after transplantation whereas fresh corneas were rejected within 2 weeks.
  • The ophthalmic surgeons responsible for the corneal grafting at both Minnesota and Sloan-Kettering confirmed that no rabbits had ever received transplants into both eyes and no transplants of cultured corneal tissue had taken place in New York until September/October 1973. Yet Summerlin displayed rabbits with one eye showing signs of rejection and the other normal looking eye which Summerlin said had received a graft of a cultured human cornea. One of these occasions where such rabbits were displayed was at a meeting of the Board of Scientific Consultants for the Sloan-Kettering Center on October 4th Summerlin claimed that the rabbit’s clear eye had received a graft of cultured human corneal tissue months previously. Nobel Prize winner Sir Peter Medawar was present at this meeting and was convinced that the good eye of the rabbits had not been subjected to any surgery. Summerlin also provided photographs that were published in World Medical News with captions indicating that one opaque eye had received a graft of fresh human cornea whereas the apparently normal eye had received a graft of cultured human cornea.
  • No one else at either Minnesota or New York had achieved long-term grafts of human corneal onto rabbit eyes even if they had undergone a period of culturing. The committee found that:

“The only possible conclusion is that Dr Summerlin was responsible for initiating and perpetuating a profound and serious misrepresentation about the results of transplanting cultured human corneas to rabbits”.

  • They were unable to make definite conclusions about the human skin allografts conducted in Minnesota but did question whether normal healing rather than graft survival had been observed.
  • Culturing made no difference to the survival of parathyroid or adrenal gland transplants.

It was recommended that Summerlin’s employment at the Sloan Kettering should be terminated. A paid medical leave of absence prior to this termination was offered so that Summerlin could undergo psychiatric care for an emotional illness. In a later interview with the New York Times (Jane Brody, 1974) the president of Sloan-Kettering attributes Summerlin’s fraudulent activities to a mental illness. The investigating committee found that Summerlin was guilty over a considerable period of time of:

Irresponsible conduct that is incompatible with the discharge of his responsibilities to the scientific community”.

They made it clear that his onerous workload could in no way excuse his behaviour and that his unacceptable pattern of behaviour had started before he had taken up his demanding responsibilities at Sloan-Kettering.

Should Summerlin have been unmasked sooner?

Once Robert Good was formally told about the “painting the mice” incident he acted swiftly and decisively but should he have acted earlier? Summerlin presented his fabricated findings to the Arkansas meeting in March 1973 and his paper “Transplantation of human skin without rejection” was published in April 1973. Summerlin moved from Minnesota to New York in March 1973. Good’s began his move in the autumn of 1972 so the disruption probably affected his level of oversight of his protégée. Summerlin was formally suspended on March 26th 1974 and the investigating group submitted their report on May 17th 1974. One would expect relatively loose supervisory contact between a senior researcher (Summerlin) and his boss (Good). In all of these circumstances this seems like a pretty compressed time-scale. When compared to other cases that I have researched, this fraud was identified and dealt with decisively in almost record time.

The investigating committee exonerated Dr Good of any collusion in the fraudulent activities of Summerlin and accepted that he did not deliberately misrepresent Summerlin’s work. Good merely repeated false claims that he believed to be true. The committee did suggest that Good was partly responsible for the avalanche of publicity surrounding Summerlin’s unsubstantiated claims. They noted that Good may also have been slow to respond when others could not repeat Summerlin’s findings but accepted that the normal trust between collaborators in science would have delayed Good considering that Summerlin was faking his results especially as Good clearly regarded Summerlin as his protégée. At least one visiting fellow initially thought that he had managed to make successful allografts of mouse skin but this was because based on appearance and colour which the committee made clear was not adequate to demonstrate successful allografting. Such hints of possible success would have helped to allay suspicion and delay Good from starting to think the unthinkable about his protégée.

In Jane Brody’s New York Times article she highlights the finding that Robert Good “shares some of the responsibility for the Summerlin case”. She notes that the committee felt that his appointment of Summerlin as a full member of the institute was premature and that Good had been enthusiastic in his claims for Summerlin’s work which was “unsupported by authenticated data”. She also notes their suggestion that Good had responded slowly to intimations of dishonesty made 6 months earlier and that as the senior scientist he failed to oversee the work more closely. Good acknowledged that in some respects he had indirectly contributed to the case and clearly chastened said that the affair had made him “a somewhat wiser and sadder person”.

Sir Peter Medawar had seen rabbits with supposedly successful grafts of human corneal tissue and mice with tufts of white hair said to represent successful allografts of white onto darker skin. Medawar was unconvinced that the tufts of white hair represented successful allografts a point made by the investigating committee. Medawar also correctly thought that the perfect rabbit eyes claimed by Summerlin to have undergone successful “limbus to limbus” graft of human cornea had not actually been operated upon. In a review of Hixey’s book on the affair, Medawar puts this belief thus:

“Through a perfectly transparent eye this rabbit looked at the board with the candid and unwavering gaze of which only a rabbit with an absolutely clear conscience is capable”

He also clearly believed that he should have done more to make his doubts known:

“I simply lacked the moral courage to say at the time that I thought we were victims of a hoax or confidence trick”

He excuses his inaction because he still thought that there was a chance that the underlying claim of successful tissue transplantation without use of immunosuppressive drugs might just be true. If a world-renowned authority and Nobel prize-winner lacked the courage to make an open accusation of fraud then it is no surprise when in other cases those in lesser positions fail to voice their suspicions especially about the actions of a senior colleague.

Endnote

Robert Good was nominated on several occasions for the Nobel Prize and there has been speculation that he might have been awarded the Prize were it not for his association with Summerlin. The first sentence of Good’s Wikipedia entry confirms his reputation:

Robert Good “was an American physician who performed the first successful human bone marrow transplant between persons who were not identical twins and is regarded as a founder of modern immunology.”

An obituary in the New York Times discusses his impressive career achievements and also dubs him “The founder of modern immunology”. In his acceptance speech for his 1990 Nobel Prize for perfecting bone marrow transplantation, Dr E Donnel Thomas acknowledged that Good had carried out the first successful bone marrow transplant some months before his own team.

 

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