New book by longtime advocate describes Milton Wexler’s incomparable contributions to Huntington’s disease research and beyond

 

A new book portrays the largely unexplored personal and psychological context of the quest to understand and defeat Huntington’s disease: a biographical memoir of Milton Wexler (1908-2007), the founder of the Hereditary Disease Foundation (HDF) and key mover in the discovery of the HD gene.

 

In late 2022, Wexler’s daughter, historian Alice Wexler, published The Analyst: A Daughter’s Memoir (Columbia University Press). She is a longtime Huntington’s disease advocate and chronicler of the cause.

 

The Analyst adds unique dimensions to HD history, building on Alice’s groundbreaking work. In 1995 she authored Mapping Fate: a memoir of family, risk, and genetic research (first published by Random House and Times Books, then reissued by the University of California Press). In 2008, she wrote The Woman Who Walked into the Sea: Huntington’s and the Making of a Genetic Disease (Yale University Press).

 

This year marks the 30th anniversary of the discovery of the huntingtin gene, announced in March 1993. Through the HDF and in collaboration with a global team of scientists, Milton and his neuropsychologist daughter Nancy, Alice’s sister, spearheaded the hunt for the gene, as recounted in Mapping Fate. In The Woman Who Walked into the Sea, Alice explored the social and medical history of HD in the 19th and 20th centuries, helping explain the stigma HD families still face.

 

The sisters’ mother Leonore was diagnosed with HD at the age of 53 in 1968. That led Milton to immediately start the HDF, which focused on the development of treatments.

 

In 1993 the discovery of huntingtin “immediately transformed Huntington’s research,” Alice writes in The Analyst. “Suddenly it was possible for researchers to make animal and cell models and study how the gene worked at the cellular and molecular level. They could test drugs and other molecules in mice and sheep, fish and flies, as well as in human beings.”

 

Milton was “ecstatic and also relieved,” Alice recalls. “We even allowed ourselves to imagine that a treatment, and possibly a cure, might be on the horizon.” HDF-sponsored researchers and other scientists around the globe are still striving to achieve that goal.

 

 

Meeting’s life’s difficult challenges

 

Drawing on access to her father’s extensive personal correspondence, her diary, and archival sources enabled Alice, with decades of hindsight, to present her father’s story – in which the fight against HD became his life mission – in intimate detail.

 

Describing Milton, Alice is meticulous, often critical, but always loving – a reflection of the complex relationship of a highly successful professional with daughters that he wanted the best for and whose lives he fought for. She adds a valuable feminist perspective, for example, interpreting her father’s friendships by analyzing masculinity and male intimacy in the 1950s.

 

In addition to Milton’s incomparable contributions to HD research, The Analyst depicts key aspects of American life in the second half of the 20th century. It delves into Jewish life in Brooklyn, which spurred Milton’s ambitions, taking him to Kansas and then to Los Angeles.

 

Portraying her father’s main career as a psychoanalyst, Alice helps to rescue the history of a field that has lost relevance with the emergence of other forms of therapy, though it continues as an intellectual field. Milton saw great value in psychoanalysis’s way of helping people understand their emotions but he increasingly practiced more direct forms of therapy, focused on the here-and-now. As he put it, “insight alone does not change behavior.”

 

Alice demonstrates how much of Milton's early career trying to understand and treat schizophrenia helped him to confront this other knotty problem, HD.

 

In an appendix, The Analyst lists “sayings of Milton Wexler” – including a 1998 note to a President Bill Clinton in crisis – regarding challenges such as the loss of a child, self-defeat, depression, personal identity, loneliness, and risk for a disease such as HD.

 

Milton’s embrace of talk therapy is a key reminder for HD families overwhelmed by the disease's  many social and personal challenges that help is available, and that individual and family therapy can make a difference. He believed that people should not have to struggle on their own.

 

In Los Angeles, Milton became a therapist for many in the arts and entertainment – a practice that he parlayed into significant donations for the HDF.

 

(Click here to read more about my own journey with psychoanalysis as an aid to fighting HD.)

 

‘The nightmare is the children’

 

With new material and perspective, Alice expands on the difficult moments described in Mapping Fate regarding  Leonore’s diagnosis, Milton’s deep fears that his daughters would be affected, and his  “frantic search for information” about HD and scientific contacts that in a matter of weeks spurred the concept of the HDF.

 

Leonore’s diagnosis and HD were “the great poison in my life,” Milton wrote his brother Henry in May 1968 in a letter uncovered by Alice. “But the nightmare is the children.[…] For me there is only dread in the air.”

 

Milton divorced Leonore but nevertheless cared for her impeccably and guaranteed her financial security. Leonore died in 1978 at 63, ten years after her diagnosis..

 

Providing intellectual fuel

 

With his background in psychology and prior experience as an attorney, Milton advocated for a multidisciplinary approach to solving HD and other neurological disorders. He championed the interplay of psychoanalysis and neuroscience in a move critical for HD research. He also grasped the growing importance of molecular genetics and its potential value for Huntington’s.

 

From this perspective Milton developed unique HDF workshops involving informal, spontaneous discussion – as opposed to dry scientific presentations with slides – as the main driver of the search for the HD gene and the quest for treatments. The first took place in 1971. Held in hotel rooms or at universities, these gatherings typically involved 15 to 20 participants.

 

As Alice reports, Milton believed that real creativity resulted from “casual conversation and carefree association among people in the same or related disciplines.”

 

While finding prestigious veteran scientists for HDF’s advisory board, Milton recruited younger researchers, including women, as the organization’s intellectual fuel.

 

As Alice observes, the HDF formed part of a trend in which “philanthropy assumed an increasingly influential role in funding science and meeting social needs.” Contributions to the HDF swelled. It established an endowment to fund future workshops and critical research grants.

 

The challenges of genetic testing

 

Alice reflects on her family’s monumental role in finding the gene and also the irony that neither she nor her sister chose to get the genetic test – a test which “opened a Pandora’s box of legal, social, and ethical challenges and raised many personal questions for Nancy and me.”

 

The test developed shortly after the 1993 discovery of huntingtin enabled 100 percent accuracy in detecting the HD mutation. Prior to this, research had established that each child of an affected parent has a 50-50 chance of inheriting that mutation. As Alice showed in The Woman Who Walked into the Sea, deep stigma and discrimination increased around HD in the 1900s.

 

“None of us considered the possibility of the genetic test to resolve the uncertainty,” Alice writes, referring to the time when she began noticing subtle changes in Nancy. “For all our knowledge of psychology, we turned to denial, that most primitive of defenses. We worried, we wondered, and then we denied. It simply could not be.”

 

Indeed, to this day, only about ten percent of persons at risk for HD choose to be tested.

 

At 81, Alice has not developed symptoms. In 2020, Nancy revealed her HD diagnosis to the New York Times. At 78, she bravely struggles with HD symptoms yet keeps abreast of the latest scientific developments. She now works with a writer on her memoir.

 

Solidarity and hope

 

Along with Mapping Fate and The Woman Who Walked into the Sea, Alice’s warm portrayal of her father in The Analyst shows how he helped the HD community advance in understanding the disorder and seek anxiously awaited treatments to slow, stop, or reverse the disease.

 

Milton lived a full, fascinating, and challenging life, dying peacefully in 2007 at age 98, at Alice and Nancy’s side. In multiple ways, he serves as a model – especially for the idea that when faced with an enormous and difficult challenge, becoming an activist can be the best form of  therapy.

 

The legacy of the discovery of huntingtin, as well as HDF’s scientific leadership, help build solidarity and hope for a better future for HD and all other neurodegenerative diseases.

 

 

Milton Wexler flanked by daughters Nancy (left) and Alice in 1992 (photo by Mariana Cook)

Lessons from the Maui wildfires for human solidarity and the fight against Huntington’s and other diseases

 

In late June – vacationing in the balmy Hawaiian town of Lahaina – my wife Regina and I snorkeled at Pacific Ocean coral reefs teeming with marvelous aquatic life, dined on succulent seafood, and recharged our emotional batteries after a difficult first half of 2023.

 

We had celebrated our 30th wedding anniversary by traveling to Hawaii for the first time, to the islands of Kona and Oahu, in March 2022. I had never expected to reach my early 60s healthy: I carry the deadly gene for Huntington’s disease, which took my mother at 68. Inspired by the spirit of aloha, we returned with our daughter Bianca in July 2022, this time to Lahaina, on the island of Maui, to celebrate her college graduation.

 

Now, we are alarmed by the massive destruction of Lahaina’s historic core on August 8 by wildfire, and the impact on the rest of Maui. As of August 14, 96 people had succumbed to the fire. This was the deadliest wildfire in the U.S. in over a century, resulting from sweeping long-term human-led changes to the Hawaiian landscape, climate change, and seeming poor preparedness by public officials.

 

We were heartbroken to learn of the deaths and how the fire burned down museums, restaurants, and stores that we had visited on Front Street, the historic main drag dating back to Lahaina’s time as the capital of the Hawaiian kingdom and whaling center in the 1800s. More than 2,000 buildings were destroyed or damaged.

 

We were heartened to see how Hawaiians were coming together, with help from the mainland, to assist one another and express hopes for rebuilding.

 

Such devastation, I believe, is another reminder to strive for human solidarity in the face of global climate change, war, and disease – including devastating neurodegenerative disorders like HD and Alzheimer’s and the threat of future pandemics.

 

Gene Veritas (aka Kenneth P. Serbin) with exhibit of whaling equipment at the Lahaina Heritage Museum in the Old Lahaina Courthouse (photo by Regina Serbin). After the fires, only a shell of the building remains.

 

An overpowering nature

 

With the coronavirus pandemic, the war in Ukraine, and the climate crisis, the history of humanity and the environment may have reached a tipping point.

 

In July, as the world experienced record temperatures, United Nations Secretary-General António Guterres declared that global warming has become “global boiling.”

 

The fires at Lahaina and other parts of Maui reminded Regina and me of the overpowering nature of wildfires in California, which in recent decades have burned ever more acres, taken lives, and forced evacuations.

 

In 2003, during the massive, deadly Cedar Fire, we and thousands of other families were forced to leave our homes in our San Diego residential neighborhood homes; for two long days we wondered whether we would have a home to return to. We saw flames rising 40 or 50 feet into the air as we drove off in our vehicles. Several homes in our neighborhood burned down. Many other neighborhoods also had to evacuate.

 

Significantly, this fire was not restricted to the backcountry but reached into the suburban neighborhoods of the city of San Diego.

 

In Hawaii, a group of youth are suing the state’s Department of Transportation over climate change. In another case involving young people, on August 14 a Montana judge ruled..that the state's failure to consider climate change when approving fossil fuel projects was unconstitutional.

 

Regina and I are exploring ways to lessen our impact on the environment.

 

Keeping the momentum on disease research

 

There is no arguing with nature.

 

With this new reality, as the climate crisis threatens to deepen, societies could have fewer resources for combating disease because of the need to prioritize saving the environment.

 

There is also no arguing with biology. I have endeavored to avoid HD onset through building new avenues of enrichment and building meaning and purpose, including my new interest in the history and culture of Hawaii – stimulated yet further, though in a tragic sense, with Lahaina’s traumas.

 

After our trip to Lahaina, I underwent surgery on my left hand to repair the damage wrought by another biological reality: arthritis and tendonitis. The hand had become painful and weak. I wore a cast for a month, and am now undergoing physical therapy.

 

As with a hip or knee replacement, I am hoping that the operation will restore full use of my hand for many years, and to enable me to work, exercise, and carry out daily activities to reinforce my overall health in the fight against HD.

 

Not having to worry about the hand will also provide an important psychological boost.

 

Our concerns about the environment come precisely as the search for cures for neurodegenerative diseases got some good news: for the first time, the FDA has approved two drugs that have shown efficacy in slowing the progression of Alzheimer’s (click here and here to read more).

 

We need to have that momentum carry over to HD and other diseases. After having to step away from advocacy earlier this year, followed by weeks of inactivity due to my operation, I hope to return to regular reporting of the quest for HD therapies.

 

Gene Veritas recovering from hand surgery (photo by Regina Serbin)

History, Huntington’s disease, and the survival of the human race

 

With thousands of people continuing to die from the COVID pandemic and the planetary climate crisis worsening, the Russian attack on Ukraine and the dictatorial Vladimir Putin’s threats of nuclear war have brought the world to a turning point.

 

Either we strive to end war or, by failing to unite globally to solve environmental and health challenges, we risk destroying ourselves. From biological history we know that millions of species have gone extinct. No one but us prevents our extinction, as well.

 

The war has produced searing images of Ukrainian families living underground or fleeing their country by the hundreds of thousands.

 

While the U.S., the North Atlantic Treaty Organization (NATO) countries, and many other key nations have sought to counteract Putin’s actions without sending in troops, around the world citizens and governments have protested and shown solidarity with the Ukrainian people.

 

As I drove yesterday from my home in San Diego to Palm Springs, CA, for the 17th Annual Huntington’s Disease Therapeutics Conference, I thought once again of how the quest for effective treatments for this devastating disease has embodied fortitude and collaboration.

 

Along the way I listened to The Tipping Point, the new, long-awaited album by Tears for Fears, one of my favorite bands, and pondered the poignant interview they gave about their album’s relevance to the present moment.

 

What I have termed the “Huntington’s disease movement” has highlighted caregiving, the alleviation of physical and mental suffering, and the harnessing of science for societal good.

 

These sentiments are especially appropriate at the start of the conference, February 28, Rare Disease Day.

HD Therapeutics Conference keynote speaker and journalist Charlotte Raven (seated) and, from left to right, Dr. Ed Wild, Charlotte's daughter Anna, and son John, February 28, 2022 (photo by Gene Veritas, aka Kenneth P. Serbin). Read more below about Charlotte's heartrending but brave presentation.

 

Writing the history of the HD movement

 

As an HD mutation carrier and advocate, I have shifted my focus as a professional historian from the country I consider my second home, Brazil, to the history of science, technology, and medicine.

 

On January 31, I submitted an application for a grant to support new research for a book to be titled “Racing Against the Genetic Clock: A History of the Huntington’s Disease Movement and the Challenges of the Biomedical Revolution.”

 

“Huntington’s disease research stands at the forefront of the biomedical revolution,” I wrote in the application. “The search for the huntingtin gene, finally achieved in 1993, contributed to the concept of the Human Genome Project. Huntingtin was one of the first disease-causing genes discovered. Yet, thirty years later, the experience of living with Huntington’s has not changed dramatically.”

 

In this project, building on my quarter-century of advocacy and tracking of scientific progress, I will seek to chronicle and interpret the HD movement in the period since the huntingtin breakthrough.

 

A visit with scholar Alice Wexler

 

To gather documentation and exchange ideas about the project, on February 21 I traveled to Santa Monica, CA, to meet with the preeminent historian of HD, Alice Wexler, Ph.D., the sister of Nancy Wexler, Ph.D., a key figure in the search for the huntingtin gene.

 

Alice Wexler wrote Mapping Fate, the key historical account about the discovery of the gene. She also authored The Woman Who Walked into the Sea, which describes the of development of medical understanding of HD in the 20th century and the stigma and discrimination associated with the disease.

 

In October, Columbia University Press will publish her latest work, The Analyst, a memoir of her late father Milton Wexler. A psychoanalyst, he founded the Hereditary Disease Foundation (HDF) in 1968 after his wife Leonore was diagnosed with HD.

 

Until the early 2000s, the HDF was the main private funder of HD science. From her personal archive, Dr. Wexler provided me with HDF newsletters, scientific reports, and other important documents.

 

Dr. Wexler also shared with me news clippings and other documents related to the HD movement.

 

Over lunch and then on a long walk along the Santa Monica beach, Dr. Wexler and I bonded over stories of our beloved Latin America (she, too, began her career studying that region), our families’ respective fights against HD, and my goal of building on her work as I embark on my new research.

 

Alice Wexler and Gene Veritas, aka Kenneth P. Serbin, in Santa Monica, CA, February 21, 2022 (personal photo)

 

My eleventh CHDI meeting

 

This will be my eleventh HD Therapeutics Conference, which is sponsored by CHDI Foundation, the nonprofit virtual biotech firm that grew out of the HDF and is dedicated solely to developing HD therapies. I keynoted the 2011 meeting. Because of the pandemic, the 2021 conference was held online. This year the conference will take place in person at its traditional location, the Parker Palm Springs, but under a tent on one of the hotel’s large lawns instead of inside.

 

As a pre-meeting reception on February 27 held by CHDI at the Villa Royale, I saw many veterans of the CHDI staff. I also spent time telling a new CHDI researcher staff member, who was attending her first Therapeutics Conference, about my family’s HD story.

 

I also conversed at length with Daniel Claassen, M.D., M.S., a professor of neurology at the Vanderbilt University Medical Center.

 

I was thrilled to hear Dr. Claassen describe his experience of lecturing via Zoom to about 150 Brazilian neurologists last year about Huntington’s disease, with the assistance of a Portuguese-speaking interpreter.

 

Fighting for human well-being

 

We also discussed the unique interpretations that each HD family can develop about the symptoms, especially in cases such as that involving my family, which had no prior knowledge of HD before it struck my mother.

 

I recalled for Dr. Claassen an especially painful moment from around Christmas of 1989. I had been doing research in Brazil for well over a year and was very happy to see my parents upon visiting their home in Ohio.

 

At one point, I heard my mother on the phone crying and complaining to a friend that she could not stand having me around.

 

At the time, I attributed her reaction to moodiness. In retrospect, as Dr. Claassen and I concluded, my mother’s reaction probably represented the start of the psychiatric and behavioral disorders that are often the first HD symptoms to appear.

 

My mother was diagnosed with HD six years later, in 1995.

 

“It wasn’t my mother’s fault!” I said with great sadness about her emotional difficulties.

 

At the Therapeutics conference, we will all be renewing our commitment to defeat HD and other neurodegenerative conditions.

 

For me, this is our contribution to human well-being.

 

 

Dr. Daniel Claassen (left) and Gene Veritas (photo by Simon Noble, Ph.D., director, scientific communications, CHDI)

 

Charlotte Raven, a brave keynote speaker

 

The conference got under way the evening of February 28 with a profoundly moving presentation by keynote speaker Charlotte Raven, a renowned British journalist, commentator, and author whose work has appeared in The Guardian, New Statesman, and Modern Review.

 

Charlotte is affected by HD. She was the first participant in the Roche GEN-PEAK trial, a small Phase 1 study run in tandem with the Roche Phase 3 GENERATION HD1 trial. These trials sought to measure the effects of the gene silencing drug tominersen.

 

In March 2021, Roche halted dosing in GENERATION HD1 because of lack of efficacy. In January, Roche announced that it will start a new, less ambitious Phase 2 trial to test tominersen’s efficacy (click here to read more).

 

Joined in the presentation by her son John, daughter Anna, and her neurologist, Ed Wild, M.D., Ph.D., Charlotte spoke bravely about her struggles with HD. She echoed the deep sadness and frustration of the HD community in the wake of the March 2021 news.

 

With many of the nearly 300 conference participants crying at the end, Charlotte received a standing ovation.

 

Roche will present two reports on its efforts on the conference’s final day, March 3.

 

A future article will feature Charlotte’s story, including a video of her keynote.

 

Assisted by son John, Charlotte delivers her keynote address (photo by Gene Veritas).

A proud Huntington’s disease gene carrier’s message to his ‘miracle baby’ daughter on her senior year in college

 

When I tested positive for the Huntington’s disease genetic mutation in 1999, at 39, I was convinced I was doomed to repeat my HD-stricken mother’s onset of symptoms in her late 40s.

 

I had tested because my wife Regina and I wanted to plan for children, who, if I had the mutation, would also have a 50-50 chance of inheriting it.

 

We decided to have a child before the availability of preimplantation genetic diagnosis (PGD), which involves in vitro fertilization of embryos without the mutation. So, we had our daughter Bianca tested in the womb. Her negative result in early 2000 was one of the happiest moments of our life. She was our “miracle baby.”

 

Now, 21 years later, Bianca has started her senior year at the University of Pennsylvania, where she is finishing a U.S. history honors thesis. She has flourished in her classes and successfully taken on several leadership roles.

 

Bianca understood from about the age of two that her grandmother was ill with a genetic disease. HD transformed my mother into a mere physical and mental shadow of herself, taking her life at 68 in 2006. Four years later, when Bianca was 9, she learned that I, too, was at risk but that she was not.

 

I have been extremely lucky. I am almost 62 and was found to have no HD symptoms at my recent annual neurological checkup. I have perhaps benefited from the positive action of modifier genes and a far greater opportunity than my mother had – we had never heard of HD prior to her diagnosis – to prepare for the disease.

 

As Bianca navigates the challenges of senior year and prepares for post-college life, I want to provide her with a message of hope, challenge, and some of the wisdom I have picked up along my own life’s journey, including our family’s struggle against Huntington’s. My letter to Bianca follows after the photo below.

 

Regina Serbin (left), Gene Veritas (aka Kenneth P. Serbin), and Bianca Serbin at the Edge sky deck during a visit to New York City in August 2021 to celebrate Bianca's 21st birthday (photo by Devon Riley)

 

Dearest Bianca,

 

When you graduate next May, you and your classmates will come of age at a time of immense challenges.

 

I am impressed with how you (and so many other students of all levels) have shown great fortitude and flexibility when forced into the new reality of online learning and social distancing during the monumental disruptions of the COVID-19 crisis.

 

I was happy to see that this semester Penn has moved students back into the classroom, allowing you to recover some of the lost joy of the college years.

 

With the rapid development of highly effective RNA-based vaccines, many of us are reaping the fruits of the biotechnological breakthroughs of our era. Researchers are also exploring a variety of such genetics-based approaches as potential Huntington’s treatments. Because many of these advances promise to change our very nature, they will pose ethical dilemmas.

 

Our family has lived this in the flesh. The biomedical revolution made it possible for you to know your life will be free of Huntington’s. However, as you have learned, being HD-free does not mean being challenge-free. Far from it!

 

But the freedom from HD has enabled you to plan a life in which you can strive for academic and professional excellence, and to develop your personal qualities.

 

As you venture forth, remember always that you’re not going it alone. You can rely on others, just as you should be available to support others. Life is a collective endeavor, as our family has learned so well from the fight against HD. As I always tell people dealing with the initial shock of discovering Huntington’s in their families, “together we will beat this disease!”

 

In your drive for personal success, cherish the preciousness of time, as I have learned to do in confronting the fears of HD. Use ambition to push ahead, but don’t let it dominate your inner good. Always make time for family and friends.

 

Take time to meditate and cultivate your spirituality, because I believe that we all have such a dimension, independent of any belief system or organized religion. As you have done at Penn, find ways in your life to connect to something larger than you.

 

Bianca, I’m elated with how we have come to share many passions: for writing, the study of history, historical movies (especially war films), music, our dog Lenny, and our family.

 

Because of HD, your grandmother could barely hold you as a baby. Your “HD warrior” caregiver grandfather loved you deeply. I wish they could have shared your college years.

 

I have not wanted you to worry about me getting HD, which is a major reason that I have strived so hard to maintain good health – and to support the search for treatments that could save me from HD’s inevitable though often unpredictable symptoms.

 

You and Mom have joined me at Hope Walks and other fundraisers, and in 2017 you gave up the chance to attend your junior prom to take part in Pope Francis’ special audience with the HD community in Rome. I so deeply appreciated having you by my side during that breathtaking moment.

 

I am thrilled and thankful to have the clarity of mind to enjoy your progress towards graduation. You have made me deeply proud.

 

Because of our and so many other families’ dedication to the HD cause, and also thanks to the researchers, I remain ever hopeful for an HD treatment in my lifetime. If that moment comes, I know that no matter where you are geographically and professionally, we will celebrate with tears of joy.

 

I hope HD strikes me minimally and very late in life, as I have seen in some cases. Together our family has seen many people with HD fight tremendously to overcome the disease, and their caregivers devote every ounce of strength. As it has throughout our journey, the hope for both my good health and the arrival of treatments will continue to sustain us ­– even beyond the start of any symptoms that might occur.

 

No matter what difficulty, please remember that I have always treasured our great moments together and watching you grow as a person.

 

No one knows what tomorrow will bring. In this moment, let’s cherish the positive, including the fact that you, Mom, and I are healthy. As your senior year progresses, I want to celebrate our joy together as you prepare to graduate.

 

Raising you has brought Mom and me greater meaning and purpose – and, above all, lots of love to share.

 

Healthy and ambitious, you are poised, with your generation, to leave your mark on the world.

 

Congratulations on your senior year! Enjoy the ride!

 

Love,

 

Dad

 

 

 

The Serbin Family Team of the Huntington's Disease Society of America San Diego Chapter's  2014 Hope Walk: from left to right, Dory Bertics, Bianca Serbin, Jane Rappoport, Gary Boggs, Yi Sun, Kenneth Serbin, Regina Serbin, and Allan Rappoport (photo by Bob Walker)

Happy Thanksgiving! And hail to the pharmaceutical and biotech industries – and the scientists!

Thanksgiving this year is going to be radically different for many Americans, including my family.

 

I will celebrate my favorite holiday just with my wife Regina, home in San Diego.

 

As it has for many Americans, the COVID-19 pandemic has prevented us from hosting our usual small group of friends.

 

After eating a healthy brunch, we plan to have a Zoom call with our HD-free “miracle” daughter Bianca, a junior history major at the University of Pennsylvania. We are ever thankful that Bianca did not have to face the devastating possibility of juvenile HD. We will miss her, but are reassured knowing that she will spend the day with her boyfriend and his immediate family in the East.

 

We also hope to Zoom with some of our local friends. 

 

However, despite the terrible pall cast by the pandemic over the 2020 holiday season, I feel extremely optimistic that researchers will find a highly effective vaccine for the coronavirus.

 

The announcements of preliminary data by Moderna and the team of Pfizer and BioNTech revealed that their vaccine candidates reduced COVID-19 infections by 95 percent in clinical trials.

 

Dr. Anthony Fauci, the director of the National Institutes of Allergies and Infectious Diseases (NIAID), described the Moderna data as “stunningly impressive,” noting that he would have settled for 70-75 percent efficacy in a vaccine.

 

“It is really a spectacular result that I don’t think anybody had anticipated would be this good,” Dr. Fauci said. He had similar praise for the Pfizer/BioNTech data.

 

Both of these trials use genetic approaches: they introduce the virus’s own genes into cells to provoke an immune response.

 

According to the New York Times’ Coronavirus Vaccine Tracker, several dozen other companies have embarked on clinical trial programs using some form of approach based on genetics or other cutting-edge strategies. Only ten projects are making vaccines using the traditional approach of injecting weakened or dead coronaviruses.

 

In all, scientists are testing 54 vaccines in clinical trials, and at least 87 more are under investigation in animals.

 

Genetics-based approaches are familiar to the HD community, where researchers have investigated the potential of gene silencing drugs for more than a decade. Researchers in the lead program, Roche’s historic GENERATION HD1 Phase 3 clinical trial, hope to analyze data in 2022. 

 

When I heard of the initial reports of Moderna’s genetics-based approach, I felt deeply confident that humanity would ultimately defeat the coronavirus. 

 

The potentially record speed in getting a vaccine to the world is testimony to the ingenuity, dedication, and focus of the biotech and pharmaceutical industries, which I have observed with deep interest in my nearly quarter century as an HD advocate and student of the science – and as a writer summarizing the science in simple terms.

 

In October, posting on Facebook an article on the bold Triplet Therapeutics clinical trial program – yet another genetics-based effort – I wrote the following: “Hail to the many imaginative and hard-working companies in America’s pharmaceutical industry!”

 

I also salute the scientists involved, and the many pharmaceutical and biotech firms of other nations engaged in the fight against COVID-19 and HD.

 

Also, we must not forget the millions of doctors, nurses, and other healthcare workers and first responders who have heroically attempted to hold the line against COVID-19, thus giving the researchers the time necessary to develop the vaccines.

 

Thanksgiving is our quintessential American holiday. This year, with the pandemic, it takes on a global significance. Across all cultures and nations, the virus has led us to realize once again our common humanity – and the collective efforts needed to safeguard life for all.

 

 

Photo by Bianca Serbin, taken in fall 2009 at the San Diego Botanic Garden (click here to read more).

Fathoming Huntington’s disease, genetic testing and the biotechnological era in an academic setting

The decision to undergo genetic testing for an inherited, untreatable disease carries the risk of a devastating, life-transforming result. We in the Huntington’s disease community know all too well the medical and social consequences of carrying the genetic mutation for this neurological condition, which produces uncontrollable movements, dementia, and mood and psychiatric disorders.

At the same time, testing positive for a genetic disorder can potentially provide an individual with sufficient advance warning to enable informed decisions regarding planning a family, finances, insurance coverage, career, and other key matters.

I’ve reflected frequently on the perils, benefits, and ethical challenges of genetic testing. In fewer than five years, my family faced three tests: my mother’s positive test (and diagnosis) for HD in 1995, my positive test in 1999, and our daughter’s negative test in the womb in 2000. I have discussed genetic testing in many articles in this blog as well as in the nearly dozen speeches I have made on HD in the past four years.

I prepared practically all of these written and oral accounts for audiences mainly familiar with HD and the issues surrounding genetic testing. Testing was always just one topic among many covered.

As poignant as ever

Recently I was prompted to ponder genetic testing again, but in a different format and setting. At the invitation of Nazin Sedehi, a senior at the University of San Diego (USD), I participated in a video on HD and my family’s experiences with genetic testing.

After exiting the “HD closet” in late 2012 with the publication of an article in The Chronicle of Higher Education, USD placed a feature story and photos of me and my family on its website.

Now, at Sedehi’s behest, I did an interview for two websites aimed at helping a general audience explore the dilemmas of genetic testing and other bioethical challenges.

Sedehi conducted the interview with the benefit of her studies as a pre-med interdisciplinary humanities major. I was distinctly the subject of Sedehi’s research. The interview had a decidedly academic purpose in the broadest, most positive sense of the word: gathering, reflecting upon, and disseminating critical knowledge.

For the first time in an oral presentation, I focused almost exclusively on genetic testing.

Despite having touched often on this topic, it felt as poignant as ever to reflect on it again.

‘You can’t kill the gene’

I met Sedehi after reaching out to her and others at USD who last year set up a new student-designed website called Genetics Generation. The site aims to provide impartial information about genetics-based technologies and engage the general public regarding genetics and ethics.

The interview took place in my office at USD, where I have taught since 1993 and chaired the Department of History since 2009. Sedehi produced the video for an independent study supervised by Laura Rivard, Ph.D., an adjunct professor in the USD Department of Biology, with the purpose of generating content for the student-run site and Dr. Rivard’s Genetics Generation blog at Nature Education’s Scitable online teaching/learning portal.

“You know, you can’t just extirpate this thing from your body,” I state at the start of the video, underscoring the genetic nature of HD. “It’s not like a virus that you can hope goes away with time if you take some orange juice, and the cold virus goes away. It’s not like a bacteria, which you can treat with an antibiotic.”

I speak as the juxtaposed images of a normal brain and a shrunken HD brain fill the screen.

A scene from the video comparing a normal with an HD-affected brain

“It’s not even like cancer,” I continue. “In cancer there’s chemotherapy, there’s radiation. You can kill the cancer cells. But you can’t kill the huntingtin gene.”

Sedehi cuts to my response to the question about my reason for getting tested. I explain that I wanted to get tested “immediately” after learning of my mother’s diagnosis. However, on the advice of people familiar with the social risks of genetic testing, I postponed my decision.

Ultimately, I decided to get tested.

“It would be a way for me to fight back,” I declare. “Knowledge is power, and having that knowledge would enable me to care for myself in the best way possible, as a way to avoid the symptoms of the disease.”

Our most difficult experience

Then the interview tackles the most difficult issue my wife and I faced: the testing of our daughter.

“We knew that because I had tested positive for the disease, the potential child had a 50-50 chance of inheriting the mutation,” I say. “We also knew that when a father passes on the disease, he in some instances can pass it on in a far worse form. She was tested in the womb.”

I note that this was before the arrival of preimplantation genetic diagnosis, which couples today use to screen embryos for the HD mutation.

“The happiest day of our lives was learning that she had tested negative for the Huntington’s disease mutation,” I state, adding, however, that the “entire experience was certainly one of the most difficult, if not the most difficult, experience my wife and I went through together.”

No regrets, but a changed life

When Sedehi asks if I ever wish I hadn’t been tested, I respond that I have no regrets. I fantasize about a treatment that would free me and the rest of the community from the scourge of HD.

At the same time, I recognize that HD has profoundly changed my family’s life.

“Life’s not just about Huntington’s disease, but it really did change the way we looked at life,” I recall. “It changed the way we think about money, about career, about whether we should move, about the number of children we should have, whether we can buy a retirement home in South America. … It really made us much more cautious in planning for the future.”

Sedehi wants to know what comes to mind when I hear the words “Huntington’s disease.” I respond instantly: my mother and her utter dependence on my father and other caregivers.

Families of HD people witness two deaths, I add.

“The first death is when the person loses a large part of his or her personality, and cannot talk any more, cannot communicate,” I explain. “It’s as if you’ve lost that person already. The second death is when they die the physical, final death.”

Germinating beneficial ideas

You can read Sedehi and Dr. Rivard’s introduction, watch the video, and participate in an online discussion by clicking here. You can also watch the video below.

Huntington's Disease Interview with Dr. Kenneth Serbin from Know Genetics on Vimeo.

The connections to Sedehi and Dr. Rivard mesh with my HD advocacy and the concomitant expansion of my scholarly research into the history of science, technology, and medicine (click here to read more).

Through our joint efforts, we can help raise awareness about the difficult challenges, as well as the great potential for medical breakthroughs, of the biotechnological era.

Our collaboration reflects the trend towards what academics refer to as “interdisciplinary” research and teaching, where professors from seemingly disparate fields pool knowledge and differing perspectives to understand problems.

Dr. Laura Rivard (photo from Genetics Generation website)

(In a similar vein, on April 3 USD sponsored a well-attended interdisciplinary panel discussion on ethics and genetic testing, with a focus on the highly controversial direct-to-consumer genetic testing service 23andMe. Dr. Rivard organized the event. I plan to write more about it in a future article.)

Ultimately, the interdisciplinary approach can and should seek to solve problems – in this case, the dilemmas of genetic testing and the dire need for treatments for neurological disorders that strain millions of families and the nation’s caregiving system.

Dr. Rivard’s efforts embody the capacity of academic institutions to teach and reflect. Though some criticize higher education and especially the liberal arts for their purported ineffectiveness in preparing young people for the workplace and life, we should recall that the germination of ideas in universities produces numerous benefits for society.