Bubble Boy, Berlin Patient and Butterfly Patient


March 2020

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Three examples of stem cell therapies have made history: the cure of X-SCID-affected Jack Crick, the cure of the Berlin patient who, with the help of stem cells, escaped both HIV and leukemia and the rescue of the butterfly child Hassan, who was close to death before genetically modified stem cell therapy saved his life and gave him a future. Their cases, however, have remained highly regarded individual cases to this day. All patient stories are interesting against the background that they embody the future potential and the associated hope in stem cell therapy - but still represent the exceptional situation.

Patient Jack Crick

2004 Born in May
2004 X-SCID is diagnosed in September. The search for a suitable bone marrow donor unsuccessful. Gene therapy using the patient's own blood stem cells is successful, even without chemotherapy.
2011 Patient has had no symptoms since.

Attending Physician
Bobby Gaspar, Great Osmond Street Hospital, London


SCID stands for severe combined immunodeficiency;


A weakening of the immune system due to the absence or lack of lymphocyte function; mutations in genetic information (DNA) cause the disruption of T cell development. The patients' immune systems cannot cope with the pathogens in our normal environment and the affected children must therefore live in a sterile environment.



Collection of hematopoietic stem cells (CD34-positive); inserting the corrected gene into the test tube using a retroviral vector (taken from the mouse leukemia virus); stem cells are returned to the patient.

Advantages: Use of own cells instead of foreign cells; low risk of rejection or incompatibility; no suitable donor necessary.

The introduction of a new gene can lead to changes in cell properties or to degeneration (cancer). Cases are known where patients developed leukemia. The trigger seems to be the retroviral vector. Research is being carried out on the use of newer HIV-derived lentiviral vectors, for example, which have a much better safety profile.

Search terms: Bubble Boy, David Vetter, Jameson Golliday

Patient Timothy Ray Brown

1966 Born in Seattle, USA
1995 Diagnosis: HIV positive
until 2006 Treatment using highly active antiretroviral therapy (HAART): 600 mg Efavirenz,
200 mg Emtricitabine and 300 mg Tenofovir
2006 Diagnosis of acute myeloid leukemia (AML); chemotherapy treatment
2007 Treatment by allogeneic stem cell transplantation from a donor with a mutation in the CCR5 cell surface receptor. The mutation prevents the HI virus from penetrating the cells.
since 2007 HI virus no longer detectable using common procedures
2008 Leukemia identified again; second stem cell transplantation (same donor)
since 2008HI virus undetectable using common procedures; leukemia treatment successful; neurological disorders diagnosed

09/2020 Died of another attack of leukemia


HLA-type: B57


Attending Physician

Dr. Gero Hütter, Benjamin-Franklin-Klinikum Charité Berlin (bis 2009)

Bone marrow donor

HLA type: B57
Mutation: delta 32 on receptor CCR5


Transplantation of allogeneic stem cell transplantation of a donor with a mutation in the cell surface receptor CCR5. The mutation prevents the HI virus from entering the cells.


It is not clear whether this individual case is reproducible. The procedure is very expensive. In 2012, Steven Yukl (University of California, San Francisco) investigated nine billion patient blood cells using polymerase chain reaction (PCR). After several attempts he identifies fragments of the virus genome in the blood plasma. Douglas Richman (University of California, San Diego) also conducts blood tests and finds no residues. He considers contamination in the Yukl test possible; in addition, PCR is highly sensitive and error-prone.


Search terms: The Berlin Patient, Mississippi Baby, London Patient


Patient Hassan

Born in 2008 started treatment at the age of 7
2015: After fleeing from Syria to Germany, he suffered infections and chronic skin lesions as a result of the inherited disorder epidermolysis bullosa.
2015-2016: Skin graft involving 80 percent of the patient’s skin. Since then, the patient has been largely free of symptoms.


Attending Physician
Tobias Rothoeft, Kinderklinik Bochum 
Tobias Hirsch, Universitätsklinikum Bergmannsheil (plastic surgeon)
Michele De Luca, Center for Regenerative Medicine at the University of Modena (stem cell researcher)

Epidermolysis bullosa

Epidermolysis bullosa is an inherited disorder. Children with this condition are sometimes called butterfly children, because their skin is as fragile as a butterfly’s wings. This is because the upper layer of the skin (epidermis) is not properly attached to the layer underneath (dermis). People with this disease have a defective LAMB3 gene. This gene encodes the laminin-332 protein.


Skin cells from Hassan were sent to Italian experts in Modena for culturing. The scientists used retroviral vec­tors to insert a healthy LAMB3 gene into the skin cells. Retroviral vectors are viruses which have been specially modified to carry genes into cells. The genetically modified stem cells in the piece of skin were then cultured in a clean room laboratory to produce large pieces of skin suitable for grafting. Over a series of three operations in Germany, scientists then grafted the cultured tissue. In total, they replaced 80 percent of Hassan’s skin.

The new skin contains roughly the same amount of the laminin-332 anchor protein as normal, healthy skin.


There are around 35,000 children with epidermolysis bullosa in Europe. The severity of the disease varies great­ly. Until now, no treatment aimed at eliminating the underlying cause of the condition has been available. All gene therapies carry a risk that the new gene could be inserted into the wrong place in the genome, however. This can disrupt cell regulatory processes and cause cancer.
The treatment Hassan underwent was risky and laborious. It was justified by the extent of his suffering and the fact that there was no prospect of his suffering being relieved by any other treatment.

Search terms: Patient Hassan, butterfly child




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