Reflections on Harvard Genomics Spring Summit

Thank you again for attending "Genes, Technology, and Incalculable Ethics: The Family Office of the Future" earlier this spring at Harvard Medical School.

Your insight about how genomics and genetic technologies will fundamentally alter the landscape of our lives is critical to the shaping of its future.

These are tumultuous times, remarkably inviting us to come together to effect powerful change.

Even as genetic technologies offer unprecedented potential to protect our families from disease, so do they place ponderous ethical dilemmas before us.

At our Spring Summit in April, we initiated a process to embrace our responsibilities, especially with regards to our family offices and enterprise, in an intimate venue with its foremost scientists.

The essence of human genomics requires that thought leaders connect in ongoing dialogue about ethical, moral, privacy, societal, legal, and behavioral consequences of its applications. These are not decisions scientists can make alone. Unprecedented challenge requires unique partnership.

Our 2017 Spring Summit was just an introduction to what is to come - we have much to discuss and debate, and there is much we can do.

Expect to hear from us shortly about new developments in genomics and genetics, invitations to personally engage with this fast-paced world, and announcements of the next round of summits being planned for the spring of 2018.

In the interim, please enjoy below brief recap of our day together, as well as recent information we trust will be of interest.

And, as always, please be in touch with any questions or thoughts.

Kindest regards,
Dr. Ronnie Stangler and Dr. Ting Wu


genetics is everywhere

Image © Marinka Masseus - "Under the Same Sun" IPA Award 2016

Albinism is an inherited genetic condition that reduces melanin pigment in hair, skin, and eyes. In some areas of Tanzania, infants born albino are believed to be aliens, boding bad fortune to their families. Mothers are pressured to kill them. If allowed to live, albino children are ostracized, physically brutalized, often expelled to segregated camps, suffering dire medical complications without hope, without care.

In the US, a 9 year old female albino gifted basketball player, legally blind, when asked whether she wished her parents had corrected the gene responsible for her blindness before she was born, did not hesitate before answering: "no." Would she ever consider editing the genes of her own future children to help them to see? Again: "no." She was deeply grateful for the drive and ambition she attributed to her "disability."

  • is this disorder a potential candidate for CRISPR?
  • of disorders hypothetically amenable to CRISPR, how do we determine which to tackle first: by complexity of science, prevalence of disease, degree of suffering, political clout of those who suffer?
  • disease has different meaning in different cultures: how will cultural discrepancies be bridged?

limb regeneration

Image © David Jay Photography - "The Unknown Soldier"

Dr. Cliff Tabin described the current devastating epidemic of limb loss, aftermath of diabetes and ravages of war.

Humans and other mammals have extremely limited regenerative capabilities in key body parts such as limbs. No biological therapeutics exist. However, species such as salamanders replace entire lost limbs throughout life. Remarkably, these limbs are anatomically similar to human limbs.

Dr. Tabin explained how human skin cells can be programmed to become embryonic stem cells, capable of transformation into any other cell type in the body, including limb buds. The limb bud is the earliest structure formed during limb development.

Dr. Tabin's lab combines classical methods of experimental embryology with modern molecular and genetic techniques for regulating gene expression during embryogenesis. Dr. Tabin suggested stem cell transplants may guide limb regeneration in mammals within the lifetime of at least the children of the scientists who are currently doing such investigation.

  • what other organs and systems may have similar potential?
  • how does one encourage basic science research in an area of almost science fiction level creativity, complexity, and ingenuity?
  • we can become hyperagents of change, supporting creation of a bold beautiful future we may not live to see ourselves

aggression, apnea, and serotonin

Image © Alia Sultan - "Pursuit of Serotonin"

Dr. Susan Dymecki, termed by the Rita Allen Foundation "The Serotonin Circuit Master," studies a particular class of extraordinary multi-tasker neurons. They are grouped as one entity simply because they all produce the chemical serotonin.

However, serotonin neurons are linked to an array of dramatically different clinical disturbances of mood, behavior, and basic body functions. Disorders involving serotonin include depression, anxiety, eating disorders, aggression, explosive disorders, addiction, autism, lack of empathy, as well as respiratory dysfunction and temperature dysregulation.

Through gene manipulation, Dr. Dymecki has segregated serotonin subtypes, beginning to identify which serotonin neurons are involved with specific clinical disorders. These key steps may reveal previously unknown contributions of the serotonergic neuronal system to disease, inform the development of biomarkers, and lead to more targeted therapies with significant reduction, or even elimination, of undesirable and debilitating side effects.

  • as we learn more about subtypes of neurons and genetic variants that are essential contributors to mood, behavior, and sense of self, how do we prevent development of new bias based simply on genes?
  • will psychological defenses be allowed in the criminal justice system on the basis of "genetic" character "defects"?
  • how will we guide trustees not to rely exclusively on genetic profiles relating to multi-determined behaviors to make decisions about their beneficiaries?

the aging brain needs "REST"

Image © Maya Daniels - "Into Oblivion" (patients behind locked doors in "protected" institution)

Human neurons are functional over an entire lifetime, yet mechanisms which preserve function and protect against neurodegeneration are unknown. Dr. Bruce Yankner has contributed stunning information to the science of aging. His work may fundamentally recast our approach to treatments of Alzheimer's and other dementias.

Amyloid beta plaques and neurofibrillary tangles that are pathological hallmarks of the Alzheimer’s brain appear not to be the whole story. Some subjects with these pathological features do not develop dementia. What protects them?

REST, a brain gene transcription factor, plays a key role in protecting neurons of the brain, both in utero and during normal aging. REST is lost in mild cognitive impairment, Alzheimer’s, and other dementias. REST levels during aging are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the aging brain.

The implications for treatment are profound. Although some dementia therapies delay development of certain symptoms or reduce secondary symptoms, such as severe anxiety, depression, and psychosis, currently there are no curative therapies.

Dr. Yankner's work suggests new treatment approaches, alternatives to the present focus on prevention and reduction of amyloid plaque deposition and formation of neurofibrillary tangles. We may seek to develop drugs to increase expression of REST. We may attempt to develop drugs that promote REST transfer to the nucleus and/or suppress its destruction. We may bypass REST to develop drugs that directly promote the expression of antioxidant genes and free radical scavengers.

Early and preventive treatment may become a primary focus of intervention.

  • what are the psychological, social, even financial implications of disclosure of potential future dementia?
  • what is the potential impact on family members?
  • do individuals have a responsibility to inform genetically related family members, even though not all those carrying the variant develop the disease?
  • if an individual has major responsibility in the operation of family business and/or family office, are there obligations to disclose?

a "feature", not a bug

"Sleeping Boy" by Philippe-Laurent Roland, c 1774 Metropolitan Museum of Art

Special Summit guest George Church ascribes his visionary ideas to narcolepsy in a remarkable STAT interview. "It didn’t happen during his appearances on Stephen Colbert’s show or his walk down the red carpet in April as one of Time’s 100 most influential people of 2017. It has happened during meetings, seminars, and panel appearances from Beijing to Boston: the renowned biologist nodded off. It’s no secret that he has narcolepsy, the condition defined by sudden bouts of sleep. He lists it in his personal history (part of the Personal Genomics Project)."

"(Dr. Church) finds inspiration in the many websites that list accomplished people who have had dyslexia, ADHD, OCD, and other forms of neurodiversity. 'I look at them and say that’s really cool,' he said. That and other evidence suggest that 'if you’re different on any axis you’ve got a slight edge in some circumstance. Being different at all allows you to think out of the box. The kind of difference you have maybe determines what direction you’ll take out of the box.'"

  • Dr. Church embraces his "neurodiversity"
  • in your life, with your own family, as well as the families with whom you work, are "differences" embraced?
  • diversity vs disorders: what are implications for potential medical interventions, be they pharmaceutical, or, one day, fundamental alteration of responsible genes?

evolution beyond earth: ting wu at the world science festival

Image © Shutterstock Media by ARENA Creative

Thanks to evolution, our bodies are exquisitely adapted to survive on Earth. But while humanity’s past is firmly grounded on our home planet, humans of the future may live on the moon, Mars, or interstellar ships bound for distant worlds.

Dr. Ting Wu explored with her colleagues at the World Science Festival how living in space affects the human body and how we might tweak our own genome to enhance our ability to live beyond Earth. This is also the focus of work at the Harvard Consortium of Space Genetics, chaired by Dr. Wu, with her colleagues Drs. Tabin, Church, Dymecki, and Yankner.

  • space is a hostile environment: might we harbor illusions of space to avoid grappling with our collision course of growth on a finite planet?
  • JFK might have been speaking about genomics when he advocated space exploration in 1961: "We set sail on this new sea because there is new knowledge to be gained, and new rights to be won, and they must be won and used for the progress of all people. For space science, like nuclear science and all technology, has no conscience of its own. Whether it will become a force for good or ill depends on man."

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Finally, again, deepest appreciation to our Spring Summit 2017Host Committee (Howard Cooper, Judy Green of FFI, Alex Hayward, and pgEd) and to our generous Sponsors, Lazard Asset Management and Asclepius Life Sciences. And, of course, infinite thanks to the extraordinary and generous Faculty and Department of Genetics at Harvard Medical School.

Ronnie S. Stangler, M.D.
Ting Wu, Ph.D.

The science of genomics is progressing at an exponential rate

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