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?

Passing on the Huntington’s disease advocacy baton to the next generation

In the fight against Huntington’s disease, a familial condition that can plague generations, each generation must pass on the advocacy baton to the next.

I feel as though I've started my handoff to my daughter Bianca.

HD has profoundly affected my family in multiple ways. My mother was diagnosed with HD in 1995 and died from it in 2006 at age 68. I tested positive for the genetic defect in 1999, and have been racing against the genetic clock ever since. Bianca, thankfully, tested negative in the womb in 2000.

At 57, an age when my mother had chorea (involuntary movements) and severe cognitive loss, I am blessed to have remained symptom-free. However, because HD gene carriers inevitably develop the disorder, I know that, unless scientists discover an effective treatment, I will someday become ill.

HD families must stick together to confront the devastating symptoms, caregiving demands, and difficult challenges the disease brings, but it’s by no means easy.

Avoiding the denial that prevents family solidarity and feeds ignorance about the disease, my wife Regina and I have revealed to Bianca at appropriate moments how HD has impacted our family. We have done so gradually but always honestly. Often, we spoke about HD in response to her questions. (To read more, click here and here.)

Gene Veritas (aka Kenneth P. Serbin) with daughter Bianca and wife Regina (2016 family photo)

A biology assignment

Now 16, Bianca is a healthy and vibrant high school junior. She has frequently read this blog and over the years has participated in several fundraising events for the San Diego chapter of the Huntington’s Disease Society of America (HDSA-San Diego).

Her gene-negative status means that the threat of HD stops with me. Of course, she is concerned about my health, and she is deeply saddened by the plight of juvenile HD patients. She has volunteered for HDSA-San Diego.

Last week she worked on an assignment for her high school biology class titled “A Day in the Life: A Study of Human Genetic Disorders.” From a list of diseases, she chose HD. Drawing on medical and scientific sources, she wrote a four-page summary of the biology of HD, symptoms, its rare status, age of onset, and potential treatments.

Life with HD

For the required creative component of the assignment, Bianca wrote an imaginary patient journal titled “Life with Huntington’s Disease,” from the perspective of this blog, her conversations with me, and her observations over the years.

Bianca captured the sadness, anger, and fear associated with HD. In one excerpt, she wrote:

Today was a bad day. It has been hard lately to ignore HD. I wish I could say I don’t think about it all the time, but I do. Especially now that Mom is getting worse. She can barely walk at this point. Dad helps her eat, shower, use the bathroom, and dress herself. It’s hard for me to see my mom act in a more childish manner than my three-year-old daughter. It’s hard for me to see my mom this way because I know that I will one day experience the same thing. I feel exceptionally lonely nowadays. I know others who struggle or who have struggled to take care of someone with HD, but I somehow feel like my situation is unique, somehow worse than everyone else’s.

However, Bianca also portrayed the strength and hope of HD families and advocates, writing:

Perhaps the best part of having HD is getting to meet so many people who are involved with the cause. The Huntington’s Disease Society of America is one of the most supportive groups of people I have ever worked with. Few know the struggle that accompanies this disease. It’s nice to be able to talk to people who do, people who have lost loved ones, as I have, to this horrible sickness, people who, like me, are at risk.

Bianca Serbin (photo by Gene Veritas)

Honesty and family solidarity

Reading Bianca’s words, I know that HD is forever seared into her consciousness.

I was deeply moved by her decision to write about our family’s struggles with Huntington’s. I am very proud of her.

The experience reinforced the necessity of accurate, patient, and, above all, honest communication within Huntington’s families.

In our conversations last week many powerful memories came to the fore. Bianca told me that one of her earliest recollections was of us visiting my parents’ home in Ohio (she was three) and seeing my father and me help my mother after she fell on the floor.

Bianca learned from me last week how the disease could potentially affect other members of our extended family.

As I looked at her, I felt an immense sense of relief that she is HD-free. I also felt wonderful anticipation: in less than a year she will be applying to college.

‘Don’t worry for now’

At the conclusion of our conversation the night before Bianca turned in the assignment, we discussed the fact that the greater the genetic defect (gene expansion), the earlier the onset.

We inevitably focused on my potential age of onset, ranging from the late forties to the late sixties.

“Hopefully I will get sick only in my late sixties,” I told Bianca.

“Or maybe you’ll get sick even later – or not at all!” Bianca responded optimistically.

We discussed the hope of clinical trials.

A bit later, determined not to let all this hinder her life plans, I told her gently: “Don’t worry about HD for now. That’s something off in the future.”

Bianca and Kenneth Serbin (family photo)

HDSA’s renewed commitment to critical research

After a budgetary crisis that practically eliminated support to HD scientists in recent years, the Huntington’s Disease Society of America (HDSA) has committed itself to reestablishing a program of research projects critical for developing effective treatments.

In a September 28 e-mail message to “HDSA friends,” HDSA CEO Louise Vetter announced the hiring of George Yohrling, Ph.D., to fill the new position of Director of Medical & Scientific Affairs.

“In the past we have relied upon the volunteer support and consultation of physicians and scientists,” Vetter explained in an interview in San Diego on November 16. “We will continue to do so. But based on what the pace of HD research is right now and our vision to have a new research program, we felt it was the right time to bring that expertise in-house.”

Dr. Yohrling, a molecular neuroscientist, has worked in the HD field since 2000.

“His first job was with an HDSA Coalition for the Cure lab,” Vetter said. “He was funded with an HDSA grant, and he has continued to stay in the field.... He has real expertise in HD, which is incredibly important. His primary task is to launch a new research program for the organization.”

The hire marks the first step in fulfilling a series of goals outlined in HDSA’s first-ever strategic plan, formulated after broad consultation with the HD community in 2011 and 2012, and launched by Vetter at the annual HDSA convention last June (click here to read a report on the drafting of the plan).

In response to recent criticisms of HDSA because of the drastic decline in research support (click here to read more), Vetter stated that HDSA is working “to have the most impact for the most people and help set the course for the best care and the best treatments as soon as possible.”

(Watch the entirety of my interview with Vetter in the video below.)

Avoiding repetition

In crafting the new research program, HDSA planners took into account the organization’s limited budget (about $8.5 million annually) and strived to avoid duplicating efforts by other HD initiatives focused strictly on research, Vetter added.

Those initiatives include the CHDI Foundation, Inc., which spends tens of millions of dollars annually, and the Hereditary Disease Foundation (HDF). Unlike HDSA, they do not offer support groups, care centers, or other forms of patient outreach.

Both Vetter and Dr. Yohrling emphasized that the new research program will focus on HD research in humans and human cells. This contrasts sharply with – but also necessarily complements – the research conducted on animals.

Focusing on humans

“We’re calling it ‘Human HD Biology Project,’” Dr. Yohrling said in a November 26 interview. “All of the observations will be from human HD patients, and not from a worm or mouse or fly. There’ll be no arguing about the physiological relevance of the data we will acquire.”

Dr. Yorhling explained that the project will function like a post-doctoral or clinical fellowship program. Young scientists will partner with the directors of HDSA’s 21 Centers of Excellence for Family Services and Research, which see patients and other HD family members on a regular basis. It replaces the Coalition for the Cure grant program, which ceased to exist with the onset of the budget crisis.

Dr. George Yohrling (CHDI photo)

The new researchers will focus on tasks such as the search for human biomarkers – specific signs of the disease within bodily fluids or tissues or the brain, for example – that will become crucial for measuring the effects of potential remedies.

“These are studies, not clinical trials, but their outcome could and should help support, drive, and steer clinical trials,” Dr. Yohrling explained, adding that he is currently recruiting HD specialists to serve on the program’s advisory committee, which will review the applications from researchers.

Grants will be relatively modest, Dr. Yorhling indicated. “These won’t be $250,000 jobs,” he said. However, because of the clear emphasis on non-redundancy, “hopefully we’ll get a big bang for our buck,” he added.

HDSA has already raised funds to kick off the project, Dr. Yorhling said, although both he and CEO Vetter recognized the need to increase fundraising to expand support for research.

HDSA hopes to issue its first call for proposals in early 2013, Dr. Yohrling said.

HDSA also will continue to support an important consortium of HD stem cell researchers, he noted.

A pivotal player

Dr. Yohrling’s diverse experience in HD research makes him a pivotal player in the search for treatments.

After receiving his Ph.D. in pharmacology from Wake Forest University in 2000, he became the very first post-doctoral researcher in the lab of Jang-Ho Cha, M.D., Ph.D., at Harvard Medical School/Massachusetts General Hospital. (Dr. Cha is a member of the HDSA Board of Trustees and will chair the HD Human Biology Project Advisory committee.) During his two years under Dr. Cha, he “got to see and interact with HD firsthand.”

“Any human being with a soul in their body” would be motivated to help, Dr. Yohrling recalls of his initial, serendipitous contact with Dr. Cha and the HD team while in Boston searching for a post-doctoral position. “I was hooked. I felt it was my calling.”

Under Dr. Cha, Dr. Yohrling also received an HDF grant.

Dr. Yorhling spent the next five years conducting Alzeimer’s disease research at the pharmaceutical giant Johnson & Johnson, followed by two years at Galleon Pharmaceuticals, Inc., researching respiratory conditions.

In 2009 Dr. Yohrling joined CHDI, which he described as a “dream” of an opportunity to focus fully on HD research in a large, resource-rich organization. There he served as director of target assessment and then director of systems biology-pathway assessment. Working with firms and leading HD scientists, he managed millions of dollars in research contracts. He also led the development of HD Research Crossroads, an online repository of HD-relevant drug target validation data.

Impacting patients with ‘all hands on deck’

CHDI was “more a behind-the-scenes operation,” Dr. Yohrling observed. “HDSA is more of a grassroots, family-oriented foundation. The opportunity to get back to that, while also getting involved in human biology research, was an opportunity too good to ignore.”

Responding to the argument that HDSA should let others concentrate on research while putting funds strictly into social services, Dr. Yohrling observed that the HDSA board and HD families want the organization “back involved in research and not to leave it up to the other entities like CHDI, HDF, and the government,” although his key responsibilities will include maintaining “an open line of communications” with those and other HD research organizations.

“We’re really glad to have someone like George working at HDSA,” said Robi Blumenstein, the president of CHDI Management, Inc., which carries out the day-to-day tasks of CHDI’s mission. “It just furthers our ability to collaborate.”

“I think that HDSA is well-positioned with their centers of excellence around the country,” Dr. Yohrling continued. “This is an incredible resource. It’s a huge benefit that HDSA has over other foundations or organizations, this access and close connection to the patients. A research program, although it might be limited initially, if the money is use properly and thoughtfully, can have a huge impact on the lives of patients.”

“We need all hands on deck,” said Vetter, adding that everybody in the HD community can take small but important steps to help the cause by keeping in touch with attending physicians, learning about HD research, and participating in clinical trials and research studies. “As we look at the dawn of a new time of HD therapeutic development, the only way those drugs are going to come to market is if people get involved. Getting involved is the most important thing that the HD community can do right now.”