Hacking humans, upgrading Homo sapiens: the role of the Huntington’s disease community and the consequences for life

An influential book by best-selling historian Yuval Noah Harari, Homo Deus: A Brief History of Tomorrow, looks broadly at potential medical advances, thus providing hope for the Huntington’s disease community’s quest for a cure, but it also warns of the vast consequences for human life caused by the advance of biotechnology and the accumulation and control of data.

A professor in the History Department at the Hebrew University of Jerusalem and holder of a Ph.D. from the University of Oxford, England, Dr. Harari published the international blockbuster Sapiens: A Brief History of Humankind. Sapiens was first published in Hebrew in 2011 and was translated into nearly 50 languages, selling over 10 million copies by 2018.

In Sapiens, Dr. Harari uses macro-history (also known as “big history”) and biological evolution to explain the development of human society over the past several hundred thousand years. He focuses in particular on the “cognitive revolution” that began 70,000 years ago. During this period, the modern human species, Homo sapiens, came to dominate Earth.

“Homo sapiens” is Latin for “wise man.” “Deus” means “god.” In Homo Deus, first published in English in 2016, Dr. Harari projects current trends deep into the 21st century and speculates that humanity could double average life expectancy to 150 years. He also considers the profound changes longer lives would bring such as people in positions of authority stretching out their careers and thus cutting off opportunities for younger individuals.

Ultimately, in this century humanity may seek immortality by developing new biomedical tools and implants, fusing our bodies with high-tech machines, and perhaps also creating non-organic beings.

“You may debate whether it is good or bad,” Dr. Harari writes, “but it seems that […] the twenty-first century will […] involve re-engineering Homo sapiens so that it can enjoy everlasting pleasure. In seeking bliss and immortality humans are in fact trying to upgrade themselves into gods. Not because these are divine qualities, but because in order to overcome old age and misery humans will first have to acquire godlike control of their own biological substratum [bedrock].”

A new scientific dogma: we are algorithms

The idea of ending disease and extending life, even if by only a few years, stirred the depths of my being. The fear of death propels our psyches and civilization. In the Huntington’s community, where the disease’s devastating and fatal symptoms cut off down lives early, the fear of death is ever-present and more acute. I recalled my mother’s death from HD in 2006 at 68 and my condition as an HD gene carrier. At 59, each day without symptoms is a blessing.

Homo Deus also reminded me of my 2010 article “God, Huntington’s disease and the meaning of life,” in which I examined the Catholic Church’s little-known and little-understand acceptance of evolutionary theory and the notion that the Resurrection of Christ could be seen as a genetic mutation.

However, in Homo Deus Dr. Harari also warns that current trends in biotechnology and the gathering and control of data could also lead to the creation of a super-human elite taking control of the rest of humanity, threatening privacy, democracy, and human and civil rights.

“If indeed we succeed in hacking and engineering life, this will be not just the greatest revolution in the history of humanity,” Dr. Harari told the audience at the 2018 World Economic Forum Annual Meeting in Davos, Switzerland. “This will be the greatest revolution in biology since the very beginning of life 4 billion years ago.[…]

“Science is replacing evolution by natural selection with evolution by intelligent design. Not the intelligent design of some god above the clouds, but our intelligent design, and the intelligent design of our clouds, the IBM cloud, the Microsoft cloud. These are the new driving forces of evolution.”

Yuval Noah Harari in 2017 (photo from Wikimedia Commons)

In Homo Deus, Dr. Harari explains that “science is converging on an all-encompassing dogma, which says that organisms are algorithms” – a method or list of instructions for making calculations – “and life is data processing.”

“Humans are algorithms that produce […] copies of themselves,” he adds. The influence of computer algorithms designed by organizations such as Google has grown vastly, taking in fantastic sums of personal data for users of the Internet and personal devices. “Non-conscious but highly intelligent algorithms may soon know us better than we know ourselves.”

In their digital lives, over 2 billion Facebook members have encountered that organization’s problematic algorithm, which a company study found to be a better reader of people’s personalities than even their friends, parents, and spouses, Dr. Harari points out.

Crucial data from HD families

Homo Deus doesn’t mention HD. However, it recognizes the importance of Alzheimer’s disease and the need to prevent it and disease in general. Dr. Harari explains that upgrading humanity would include attempts to expand the abilities of the brain – which, of course, is an organ severely debilitated by HD.

The history of the search for HD treatments is key to the biotechnological revolution. HD-affected individuals and their families have both witnessed and participated in that revolution, starting with the hunt for the huntingtin gene in the 1970s, 1980s, and 1990s, and since then with a growing number of research studies and clinical trials involving thousands of individuals.

At the start of this decade, CHDI Foundation, Inc., the nonprofit virtual biotech focused on defeating HD, pioneered the use of systems biology, which includes the deciphering of vast amounts of biological data, in disease treatment (click here to read more).

CHDI has also collaborated with IBM to seek deeper understanding of the huntingtin protein’s role in the disease. In this effort, IBM has provided its immense computational power and the tools of big data analytics.

Enroll-HD, the CHDI-sponsored worldwide database of HD-affected individuals and family members, has more than 17,000 participants. Thousands of HD-affected individuals and gene carriers have also participated in the research involving the search for so-called modifier genes that affect the age of onset. The scientists have analyzed millions of small variations in these people’s genes.

Digital monitoring and algorithms

An increasing number of researchers and companies are in effect trying to hack HD’s genetic causes. The most prominent is the gene-silencing drug developed by Ionis Pharmaceuticals, Inc., in collaboration with CHDI and other researchers. On December 19, pharma giant Roche, now the drug’s license-holder, announced the first 26 planned sites for the crucial global Phase 3 trial to test the drug’s efficacy.

In that trial, participants will receive the drug via lumbar puncture (spinal tap), the first time this delivery method is being used extensively in an attempt to treat a neurological disorder.

For the study, Roche has designed an HD Digital Monitoring Platform, which will continually measure participants’ biometric data using smartphones and watches.

“The software is what’s special, and the analytics engine behind it,” Erik Lundgren, the Roche lifecycle leader of the HD team, said in an interview last March. “A tremendous amount of data comes in. The algorithms and how you make sense of that is what our team has been working hard on developing.”

A graphic illustrating the Roche HD Digital Monitoring Platform (source: Roche)

Privacy versus healthcare systems

As Dr. Harari warns, the purpose and uses of technologies and information-gathering techniques originally developed for something positive such as curing a disease could result in unintended, perhaps negative, consequences.

Companies such as Google “want to go much deeper than wearables,” he explains.

“If we give Google and its competitors free access to our biometric devices, to our DNA scans and to our medical records, we will get an all-knowing medical health service that will not only fight epidemics, but will also shield us from cancer, heart attacks and Alzheimer’s,” he writes.

However, he observes, “imagine a system that, in the words of the famous Police song, watches every breath you take, every more you make and every bond you break; a system that monitors your bank account and your heartbeat, your sugar levels and your sexual escapades. It will definitely know you much better than you know yourself.”

Google and these other algorithm-based systems could make decisions for us, from selecting which movie to watch to choosing a spouse to settling on a candidate in the voting booth.

In a world in where the stress on data takes on a religious fervor, the demand for the free and massive flow of information could trump freedom of expression and, by extension, people’s right to control their own information, Dr. Harari asserts. He cites pressure from “Dataist missionaries” for free access to all information, including copyrighted materials.

The danger is that “we will just have to give up the idea that humans are individuals, and that each human has a free will determining what’s good, what’s beautiful and what is the meaning of life.” 

“The big battle over what we today call ‘privacy’ will be between privacy and health,” Dr. Harari asserted at the World Economic Forum. “Do you give access to what is happening inside your body and brain in exchange for far better health care? And my guess is that health will win, hands down.[…] Maybe in many places [people] won’t have a choice. They won’t get insurance if they are unwilling to give access to what is happening inside their body.”

What kind of world are we creating?

Because of the many critical issues it touches on regarding humanity’s future, Homo Deus is a must-read book.

For the HD community, it provides valuable context for the difficult medical, social, and ethical challenges involved in the disease and the quest for treatments.

As many in science strive, in Dr. Harari’s words, to “defeat death and grant humans eternal youth,” the complexities of HD and the close collaboration between HD scientists and families may serve as a reminder that the biotechnological and medical sectors should consult disease communities and the rest of society.

Yes, despite having back problems, to avoid HD onset I would take a drug via recurring spinal taps. I would also wear a data monitor, as do people with type 1 diabetes, for example.  

However, I’m also concerned about the dystopian scenarios outlined by Dr. Harari for this century.

What kind of world are we creating for our children and grandchildren?

Reinforcing the global fight against Huntington’s disease: a visit to Brazil and a reminder of our common struggles

The global cooperation necessary to defeat Huntington’s disease requires the bridging of cultural divides. It entails recognition of each country’s unique needs and contributions – but also of the common struggles involved.

With this in mind, last month I embarked on another phase of my own international advocacy by traveling to Brazil, the country I have studied since 1986, to deliver a speech on HD and build new connections for the cause.

The world’s fifth most populous country, with over 190 million people, Brazil occupies a significant place on the world’s HD map. Perhaps 19,000-plus Brazilians suffer from the disease, and tens of thousands are at risk.

Thus, once the global HD clinical trial and research study platform known as Enroll-HD gets under way in Brazil, the country’s potential contributions to the search for effective treatments will increase substantially (click here to read more).

A ‘bi-cultural’ perspective

As I have done almost every year over the past three decades, I visited Brazil primarily to work on my ongoing research in Brazilian history. In all, I have spent nearly seven years there. In 1991, during my Ph.D. research in Rio de Janeiro, I met my wife Regina.

Brazil is my second home. I refer to myself as “bi-cultural.”

Even before I joined the board of the San Diego chapter of the Huntington’s Disease Society of America in 1998, I established contact with Brazilian HD activists who founded the Associação Brasil Huntington (ABH) in 1997.

As a carrier of the HD genetic defect, I spoke in 2013 about my personal strategies for avoiding onset of symptoms at the sixth World Congress on Huntington’s Disease, held in Rio (click here and here to read more).

Gene Veritas (aka Kenneth Serbin) at Ipanema beach in Rio de Janeiro (photo by Regina Serbin)

Combating genetic discrimination

During this most recent trip, I advocated for HD-related issues in my meetings with political leaders.

In 2005, the Brazilian Senate passed a bill protecting citizens against genetic discrimination. However, the Câmara dos Deputados (the House of Representatives), has yet to take up the matter. Until then, the bill cannot become law.

Senator Aloysio Nunes Ferreira Filho, who ran for vice president in the 2014 election on the losing ticket of the opposition Brazilian Social Democracy Party, supports the legislation. During my visit to his office in Brasília, the capital, he phoned a colleague in the Câmara to urge action on the bill.

Senator Aloysio Nunes Ferreira Filho (above, photo by Gene Veritas) and Gene Veritas in the chamber of the Senado Federal in Brasília (below, photo by Lucas Souza) 

Defending the rights of the disabled

Later, in São Paulo, South America’s largest industrial and financial hub, I attended a presentation by the famous liberation theologian Leonardo Boff about the geopolitical state of the world, the threat to the global environment, and the current political crisis in Brazil.

The event was moderated by Paulo de Tarso Vannuchi, who served as Minister of the Special Secretariat for Human Rights from 2005-2011 in the government of the ruling Workers’ Party.

Vannuchi briefly introduced me to leaders of the National Council for the Rights of the Disabled. I committed to furnish them with information about HD and put them in touch with the ABH.

Vannuchi told the audience of 60, which included clergy and grassroots social activists, of my HD advocacy and suggested that the reporters present interview me.

Paulo Vannuchi, former Minister of the Special Secretariat for Human Rights (photo by Gene Veritas)

That same day I gave an interview to the TVT television outlet commenting on the importance of Boff’s speech. (You can see the report on the event, including my commentary, by clicking here).

Shortly after my return from Brazil on July 22, one of the reporters present at the event, São Paulo-based radio broadcaster Marilu Cabañas, interviewed me via phone about HD for her program. Shocked to hear of police detentions of HD-affected individuals in both Brazil and the U.S. because of ignorance about the disease, she headlined her report with that fact.

Bioethical challenges

I gave my speech, “Huntington’s Disease, Bioethics, and the Promise of Biotechnology,” on July 20 at the Universidade Candido Mendes (UCAM) in downtown Rio de Janeiro.

I have known the rector, Candido Mendes, for more than 20 years. My friends and colleagues, UCAM Professor Luiz Alberto Gómez de Souza and his wife Lúcia Ribeiro, both leading scholars and grassroots activists of the Catholic Church, organized the event. (Brazil is the world’s largest Catholic country.)

During my hour-long presentation in Portuguese, I recalled my family’s long fight against HD, beginning with my mother’s diagnosis in 1995, followed by positive test for the genetic defect in 1999 and the wrenching experience of testing our daughter Bianca in the womb in early 2000.

I felt deep relief after showing the audience pictures of our HD-free “miracle baby” in action as a youth soccer player. I spoke of the “double luck” we currently savor: Bianca will never face the terrible threat of juvenile HD, and I remain symptom-free despite having long passed my mother’s age of onset.

“At 55, my mother […] could no longer drive, she couldn’t work, she couldn't talk,” I said. “By a huge stroke of luck, I am healthy. Each day is a blessing.”

However, I also pointed to the many other bioethical challenges faced by HD families, including discrimination, family and caregiver stress, financial burden, and the lack of adequate facilities and caregiving personnel for late-stage patients.

The room became very quiet as I related how Carol Carr (of Georgia) in 2002 took a gun to the nursing home where her two HD-stricken sons lay helpless in bed and shot them dead to prevent further suffering. Carr spent nearly two years in prison.

“That was extremely sad for our community,” I recalled. “Huntington’s disease is not something easy to speak about.” 

With no effective treatments, such was the degree of hopelessness that has plagued the HD community, I had pointed out earlier.

The hope of clinical trials

“But I came to Brazil not to speak just about sadness,” I continued. “I also came to speak about hope and the promise of biotechnological research.”

The scenario for the HD community has changing radically in recent years with major advances in research and the advent of clinical trials to test potential remedies, I said.

I spoke of the immense potential revealed in the announcement last year of the gene-silencing clinical trial by Isis Pharmaceuticals, Inc. Citing an e-mail from Isis executive Frank Bennett, Ph.D., received the day before the presentation, I confirmed that the trial would start by year’s end.

(Indeed, the morning after my talk, Isis officially announced that it had commenced the trial.)

You can view my talk in the video below.

A Doença de Huntington, a Bioética e a Promessa da Biotecnologia from Gene Veritas on Vimeo.

A local commitment to the cause

During the Q & A, several Brazilian HD-affected individuals and caregivers spoke of their many struggles with the disease.

They also expressed excitement about the Isis clinical trial.

Carmen Paiva, Ph.D., spoke of her lab’s work in HD genetic and epidemiological research among Brazilian HD families. She told the audience of other local researchers and physicians focusing on the disease.

Recognizing common struggles

At the close of the session, Prof. Gómez de Souza evoked a key point of my presentation: the interconnectedness of neurological disease research and the common struggles of the afflicted.

He spoke with profound emotion about his brother, the renowned actor Paulo José Gómez de Souza, who has suffered from Parkinson’s disease for more than two decades but has successfully strived to continue working.

The struggles are shared among diseases – and among nations.

I look forward to celebrating with my Brazilian relatives and friends the defeat of HD, Parkinson's, and other neurological disorders as a result of a truly global effort.

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.

Braving bioethical challenges: the importance of Huntington’s disease

Huntington’s disease, one of the first conditions for which a predictive genetic test was developed, spotlights the psychosocial ramifications of the Genomic Era.

In addition to the profound impact of HD on people’s health and social well-being, the difficult decisions involved in genetic testing have created new ethical challenges.

Over the past few decades, the rapid advance of medical and scientific research has caused ethics – our standards of right and wrong and the study of those standards – to expand into bioethics.

Bioethics is a vast topic. Georgetown University, for example, has an entire library dedicated to research on bioethics, and a number of other universities have centers dedicated to the subject.

Biomedical innovation puts bioethics into a seemingly constant state of flux.

The passage of the Genetic Information Nondiscrimination Act of 2008 (GINA) and the Affordable Care Act of 2010 (Obamacare) are two prominent examples of how society has sought to adapt to new biomedical realities and ethical consequences. GINA seeks to protect individuals from new forms of discrimination made possible by advances in genetics, while Obamacare aims to make health care more inclusive as it undergoes profound transformations.

HD families like mine have lived on the frontier of bioethics, often constructing new, personal solutions to the predicaments posed by the disease.

Understanding our contribution to this historic process helps us appreciate our part in the overall effort to combat disease.

New tools, new challenges

I addressed the topic of HD and bioethics at the invitation of the graduate program in bioethics at the Centro Universitário São Camilo, a private Catholic college, in São Paulo, Brazil, during a presentation on September 21.

About 50 people attended the event, including at least a dozen members of the HD community and also Dr. William Saad Hossne, the program’s founder, described by one writer as “the guardian of bioethics” in Brazil. Started in 2004, the program was the first of its kind to receive official sanction.

Gene Veritas speaking at the Centro Universitário São Camilo

Focusing on how the new “tools” of medicine and biotechnology have deepened our understanding of human biology, I explained how my family braved three predictive tests in just five years: my mother’s confirming test for HD in 1995, my own gene-positive result in 1999, and our daughter Bianca’s negative test while still in the womb shortly afterward.

All of these tests brought potentially fatal news: a positive test for the HD mutation meant a 100 percent chance of developing the untreatable disorder.

“Because Regina and I wanted to have children, I also had to think about whether I wanted to get tested,” I told the audience, speaking in Portuguese.

Rather than following my initial impulse to get tested immediately after learning of my mother’s results, I waited for several years. As I explained to the audience, my mother’s geneticist had warned me of the possibility of discrimination by my employer, health plan, or insurance companies.

As demonstrated by the discussion around GINA, discrimination has become a major concern of bioethics.

The risks in having a family

“I did the test, and, unfortunately, I tested positive for Huntington’s,” I continued.

I showed the audience slides illustrating the varying number of CAG repeats (part of the “alphabet” of our DNA) on the huntingin gene. People normally have 10-26 CAG repeats on this gene. An expansion of the gene to 40 repeats signals that a person will develop HD. The tests for both my mother and me showed 40 repeats.

Research shows that the higher the number of repeats, the earlier the disease usually starts, with juvenile onset HD becoming possible if the repeats exceed 80, although even fewer repeats have caused this form of the condition.

Because of the instability of the HD-afflicted male’s huntingtin gene in the reproductive process, he can pass on a much higher number of repeats and possibly trigger juvenile HD.

“Having a family becomes like the Way of the Cross,” I said with pain in my voice. “In our case, because we wanted to have a family – and that’s why I got tested when I did – we faced a third test. First my mom’s. Then mine. Then a third one: of our potential child.

“A low number of repeats: no possibility of having the disease. As the number of repeats rises, the possibility of the disease increases…. The more the repeats, the earlier the disease manifests itself, to the point where five to ten percent of the cases are juvenile Huntington’s.”

I pointed on the slide to a picture of Olivia Ruggiano, a 12-year-old girl who died of juvenile HD in 2012.

“In my case, with 40 repeats, I could pass on to another person 45 or 55,” I continued. “There’s a case where a father has 50 some repeats and the children have 80 or 90 repeats. That’s when juvenile Huntington’s happens.”

Very serious questions

I then delved into the heart of HD and bioethics as I had not done before in such detail in a public presentation.

“A family that faces that situation is suddenly confronted with two very serious questions,” I said. “If they are thinking of the possibility of aborting the fetus, at what number of repeats would they abort? If you’re a couple with the father carrying the gene and the mother gets pregnant, and you’re afraid that the child could have the gene, you can test the child in the uterus to see what type of gene it has, whether it’s normal or abnormal. If it’s abnormal, you can know exactly how many repeats it has.

“And that’s where a question of bioethics is forced upon people. Are you going to have that child – or not? Are you going to face a situation of death at the age of nine or 12? Or are you going to end the pregnancy?”

I explained that, living in California, Regina and I faced the additional burden of raising a potential child without familial support. My father dedicated himself to caring for my mom back in my home state of Ohio, while Regina’s parents lived in far off Rio de Janeiro.

“How would Regina be able to care of me, a sick person in his forties or fifties, and also a child with symptoms or dying early?” I asked, pointing again to the picture of Olivia.

“These were the questions we dealt with and reflected on as we embarked upon the pregnancy,” I observed. “Today there is a method for avoiding that question, with the implantation of healthy embryos. In 1999, that technique didn’t exist. The only way was to get pregnant, then test.”

Fighting on other fronts

The day our geneticist called with the news of Bianca’s negative test in the womb was the happiest of our lives to that moment.

The next slide in the presentation showed two pictures: one of Regina, our gene-negative baby Bianca, and I together in the hospital the day of her birth, another of me clutching our “miracle baby” close to my face.

That terribly difficult and drawn-out part period forms just one part of our journey with HD.

As I pointed out to the São Paulo audience, HD families live the reality of bioethics in numerous other ways: by combatting the stigma and discrimination associated with the condition, negotiating intra-family conflicts arising from the disease, advocating for new and controversial treatments like stem cells, struggling to obtain various kinds of insurance, facing financial ruin, and dealing with the lack of care facilities and personnel specialized in HD.

Sadly, I also reminded that audience of the high rate of suicide among HD-affected people. Euthanasia is another bioethical issue that comes into sharp focus for HD families.

Emotional testimony

After my 85-minute presentation, the audience offered commentary and questions for another 50 minutes. The emotional testimony from members of HD families and the poignant questions from the audience further underscored the seriousness of the bioethical issues surrounding HD and confirmed their global nature.

One man in his 30s cried as he recalled how his sister, who has the involuntary movements typical of HD, was called a “drunk” by the children at her 12-year-old daughter’s school.

A middle-aged woman told how her brother, a computer programmer, lost his job after his performance declined significantly. Despite his obvious cognitive difficulties and aggressive behavior, two telltale signs of HD, both a caseworker and government psychiatrist working for the Brazilian social security system denied him public benefits.

“The psychiatrist said he was able to work and had no problems whatsoever,” said the woman, who quit her job to care for her brother at home.

The family appealed the decision, but was denied again. They have sued in an attempt to obtain benefits.

At the last hearing in August, held before a federal judge, the caseworker, still unaware of how HD symptoms are manifested, asked whether the HD man drank alcohol.

At my talk, the HD man’s sister referred to government doctors handling the request for benefits as “ignorant” and “stupid.” The case is still pending.

“I’m angry and worn out,” she said, adding that she is attempting to bring the case to the attention of the Brazilian media. “We need help.”

I noted that in the U.S., HD advocates are working towards passage of a federal law to oblige the Social Security Administration to remedy a similar situation in which an inaccurate, outdated definition of the disease has kept many afflicted individuals from obtaining assistance.

Proactive involvement and the hope of treatments

Another, more positive area of bioethics involves participation as subjects in research studies and clinical trials. On this front HD people, gene carriers, untested at-risk individuals, and other family members are taking a proactive approach to contributing to the search for treatments and a cure, usually in a context of high bioethical standards.

Ultimately, allowing HD patients to manage their symptoms with effective remedies, or perhaps someday even curing the disease, will obviate many of the bioethical challenges, although new ones surely will arise – for example, as gene-positive people clamor to try untested drugs.

Our community can and should continue to show leadership on these issues.

For now, as I concluded my presentation, “It’s time to conquer Huntington’s!”

(The many Brazilian readers of this blog can watch my presentation and the Q & A in the videos below.)

 


A Doença de Huntington e a Bioética: Um Estudo de Caso from Gene Veritas on Vimeo.

A Doença de Huntington e a Bioética: Debate sobre a Palestra de Gene Veritas from Gene Veritas on Vimeo.

The Brain Activity Map Project: short- and long-term prospects for Huntington’s disease research

The ambitious, recently announced national effort to map the circuitry of the brain and deepen understanding of its function could bring valuable new knowledge about what goes awry in Huntington’s disease-affected brains. Still, the project likely won’t have a practical impact on the search for effective treatments for years or perhaps even decades.

That’s the initial assessment from three leaders in the search for HD treatments in reaction to reports that the administration of President Barack Obama will include a multi-year, public-private-academic brain mapping project in the next federal budget. The official announcement, following Obama’s February 13 State of the Union remark about the importance of brain mapping, is expected this month, although political wrangling over the budget could cause a delay.

“Anything that teaches us about how the brain works will undoubtedly tell us something about how HD makes the brain dysfunction,” said Simon Noble, Ph.D., the director of scientific communications for CHDI Management, Inc., the firm that furthers the goals of the CHDI Foundation, Inc., the non-profit, multi-million-dollar search for HD treatments. “At the moment, it’s difficult to predict what will come out of this for HD.”

Dr. Simon Noble (photo by Gene Veritas)

Compared by the president and scientists to the $3.8 billion Human Genome Project (1990-2003), which produced a complete map of our genes, the so-called Brain Activity Map Project (BAMP) would aim to record and map the firing of the brain’s 100 billion or so neurons.

Fifteen years to a mouse study

This year marks the 20th anniversary of the discovery of the HD gene, a key step in the Human Genome Project. Initially, scientists thought that discovery would lead to potential treatments just a few years later. However, the task has proved far more complex, although a number of clinical trials are in progress or in planning, including cutting-edge gene-therapy approaches made possible by the discovery of the gene.

The scientists behind the BAMP estimate that mapping a significant part of a live mouse brain would be achieved 15 years into the project. Experiments in humans necessarily would take place years later, after testing in non-human primates.

“While the Brain Activity Map is an important and worthy project, I hope it’s irrelevant to Huntington’s disease,” Robi Blumenstein, the president of CHDI Management and a participant in an August 2012 BAMP planning session at the White House Office of Science and Technology Policy, said of the project. “Because mapping the brain is such a hard problem, the BAMP is a complex project on a long-time scale. I hope that we can deliver treatments before it becomes useful to us.”

Scientists say that the large number of neurons and the complexities of the brain, a living organ, will prove far more difficult to measure and map than the much smaller amount of inanimate material in our genes. Furthermore, because HD is a genetic disease, the Genome Project in general and specifically the discovery of the HD gene have been the major, initial breakthroughs in the search for treatments.

In 1923 one scientist referred to the connections among neurons as “impenetrable jungles where many investigators have lost themselves.” Since then, little progress has occurred. In a June 2012 article, six leading scientists identified as leaders of the BAMP likened the current technology of measuring just a few neurons at a time to watching an “HDTV program by looking just at one or a few pixels on a screen.”

Futuristic tools and techniques

“I think it’s exciting,” said George Yohrling, Ph.D., the director of medical and scientific affairs for the Huntington’s Disease Society of America. “The brain is incredibly complex, as we all know. Once we know the details of how all the different neuronal pathways and networks are talking to each other in the normal and diseased states, it could help guide us to effective treatments. In theory, all of the disease areas – Parkinson's, Alzheimer's, HD – will benefit from the successful brain mapping exercise.”

Dr. George Yohrling (CHDI photo)

However, Dr. Yohrling emphasized that the project’s ability to furnish such information will depend on the development of new research tools. At first, such tools cost enormous sums, but come down over time, he said. The first sequencing of the genome cost billions and took more than a decade, whereas today sequencing takes three weeks and will soon cost just $1,000.

"The point of the tools is key," he explained. "We see it every day in science. You can look back 10, 15 years of how we used to do certain things in the lab and think, wow, this is so archaic!"

Indeed, the BAMP scientists’ article pointed out that the project – with the gargantuan goal of imaging “every spike from every neuron” – will require an entirely new set of futuristic tools and techniques resulting from the “convergence of biotechnology and nanotechnology.” They envision such innovations as three-dimensional imaging, biologically inspired computational devices, nanoprobes, DNA molecules acting as sensors, and “small wireless microcircuits, untethered in living brains, for direct monitoring of neural activity.”

Whether nanoscience can shed light on the HD disease process is a “bit of a black box at the moment,” Dr. Noble observed. “A lot of these things will be done in mice first. Working in a human brain is extremely difficult, if not impossible. We’ll have to rely on other systems and post-mortem brains.”

If such technology becomes feasible, it might help “identify early biomarkers (signs)” of HD, Dr. Yorhling said. Biomarkers are crucial for conducting clinical trials of potential treatments.

Keeping HD in the loop

Despite the likely minimal impact of the BAMP on HD research in the short run, both CHDI and HDSA plan to carefully track its progress and seek opportunities to apply its findings and even potential inclusion in some facet of the project.

“CHDI is keeping a close eye on how these grand projects develop and always considering ways that we might be involved,” said Dr. Noble, referring to the BAMP and also a new brain-research initiative co-founded by former Rep. Patrick Kennedy known as One Mind for Research.

As Dr. Noble noted, the idea of brain mapping intersects with CHDI’s new emphasis on systems biology.

“The brain is a system, just as the body is a system,” he said. “Brain mapping is a really difficult problem, but one that’s well worth pursuing. The brain is the final frontier. It’s the least understood system in the human.”

If the BAMP came to include disease-specific mapping, HDSA would advocate for the inclusion of HD, Dr. Yohrling said. He also held out the possibility of the HD research community someday teaming with patients to carry out an HD-specific brain-mapping project, which could become feasible as the techniques advance and become accessible to more researchers.