Tag Archives: Goldman Sachs

Going blind when your neural implant company flirts with bankruptcy (long read)

This story got me to thinking about what happens when any kind of implant company (pacemaker, deep brain stimulator, etc.) goes bankrupt or is acquired by another company with a different business model.

As I worked on this piece, more issues were raised and the scope expanded to include prosthetics along with implants while the focus narrowed to neuro as in, neural implants and neuroprosthetics. At the same time, I found salient examples for this posting in other medical advances such as gene editing.

In sum, all references to implants and prosthetics are to neural devices and some issues are illustrated with salient examples from other medical advances (specifically, gene editing).

Definitions (for those who find them useful)

The US Food and Drug Administration defines implants and prosthetics,

Medical implants are devices or tissues that are placed inside or on the surface of the body. Many implants are prosthetics, intended to replace missing body parts. Other implants deliver medication, monitor body functions, or provide support to organs and tissues.

As for what constitutes a neural implant/neuroprosthetic, there’s this from Emily Waltz’s January 20, 2020 article (How Do Neural Implants Work? Neural implants are used for deep brain stimulation, vagus nerve stimulation, and mind-controlled prostheses) for the Institute of Electrical and Electronics Engineers (IEEE) Spectrum magazine,

A neural implant, then, is a device—typically an electrode of some kind—that’s inserted into the body, comes into contact with tissues that contain neurons, and interacts with those neurons in some way.

Now, let’s start with the recent near bankruptcy of a retinal implant company.

The company goes bust (more or less)

From a February 25, 2022 Science Friday (a National Public Radio program) posting/audio file, Note: Links have been removed,

Barbara Campbell was walking through a New York City subway station during rush hour when her world abruptly went dark. For four years, Campbell had been using a high-tech implant in her left eye that gave her a crude kind of bionic vision, partially compensating for the genetic disease that had rendered her completely blind in her 30s. “I remember exactly where I was: I was switching from the 6 train to the F train,” Campbell tells IEEE Spectrum. “I was about to go down the stairs, and all of a sudden I heard a little ‘beep, beep, beep’ sound.’”

It wasn’t her phone battery running out. It was her Argus II retinal implant system powering down. The patches of light and dark that she’d been able to see with the implant’s help vanished.

Terry Byland is the only person to have received this kind of implant in both eyes. He got the first-generation Argus I implant, made by the company Second Sight Medical Products, in his right eye in 2004, and the subsequent Argus II implant in his left 11 years later. He helped the company test the technology, spoke to the press movingly about his experiences, and even met Stevie Wonder at a conference. “[I] went from being just a person that was doing the testing to being a spokesman,” he remembers.

Yet in 2020, Byland had to find out secondhand that the company had abandoned the technology and was on the verge of going bankrupt. While his two-implant system is still working, he doesn’t know how long that will be the case. “As long as nothing goes wrong, I’m fine,” he says. “But if something does go wrong with it, well, I’m screwed. Because there’s no way of getting it fixed.”

Science Friday and the IEEE [Institute of Electrical and Electronics Engineers] Spectrum magazine collaborated to produce this story. You’ll find the audio files and the transcript of interviews with the authors and one of the implant patients in this February 25, 2022 Science Friday (a National Public Radio program) posting.

Here’s more from the February 15, 2022 IEEE Spectrum article by Eliza Strickland and Mark Harris,

Ross Doerr, another Second Sight patient, doesn’t mince words: “It is fantastic technology and a lousy company,” he says. He received an implant in one eye in 2019 and remembers seeing the shining lights of Christmas trees that holiday season. He was thrilled to learn in early 2020 that he was eligible for software upgrades that could further improve his vision. Yet in the early months of the COVID-19 pandemic, he heard troubling rumors about the company and called his Second Sight vision-rehab therapist. “She said, ‘Well, funny you should call. We all just got laid off,’ ” he remembers. She said, ‘By the way, you’re not getting your upgrades.’ ”

These three patients, and more than 350 other blind people around the world with Second Sight’s implants in their eyes, find themselves in a world in which the technology that transformed their lives is just another obsolete gadget. One technical hiccup, one broken wire, and they lose their artificial vision, possibly forever. To add injury to insult: A defunct Argus system in the eye could cause medical complications or interfere with procedures such as MRI scans, and it could be painful or expensive to remove.

The writers included some information about what happened to the business, from the February 15, 2022 IEEE Spectrum article, Note: Links have been removed,

After Second Sight discontinued its retinal implant in 2019 and nearly went out of business in 2020, a public offering in June 2021 raised US $57.5 million at $5 per share. The company promised to focus on its ongoing clinical trial of a brain implant, called Orion, that also provides artificial vision. But its stock price plunged to around $1.50, and in February 2022, just before this article was published, the company announced a proposed merger with an early-stage biopharmaceutical company called Nano Precision Medical (NPM). None of Second Sight’s executives will be on the leadership team of the new company, which will focus on developing NPM’s novel implant for drug delivery.The company’s current leadership declined to be interviewed for this article but did provide an emailed statement prior to the merger announcement. It said, in part: “We are a recognized global leader in neuromodulation devices for blindness and are committed to developing new technologies to treat the broadest population of sight-impaired individuals.”

It’s unclear what Second Sight’s proposed merger means for Argus patients. The day after the merger was announced, Adam Mendelsohn, CEO of Nano Precision Medical, told Spectrum that he doesn’t yet know what contractual obligations the combined company will have to Argus and Orion patients. But, he says, NPM will try to do what’s “right from an ethical perspective.” The past, he added in an email, is “simply not relevant to the new future.”

There may be some alternatives, from the February 15, 2022 IEEE Spectrum article (Note: Links have been removed),

Second Sight may have given up on its retinal implant, but other companies still see a need—and a market—for bionic vision without brain surgery. Paris-based Pixium Vision is conducting European and U.S. feasibility trials to see if its Prima system can help patients with age-related macular degeneration, a much more common condition than retinitis pigmentosa.

Daniel Palanker, a professor of ophthalmology at Stanford University who licensed his technology to Pixium, says the Prima implant is smaller, simpler, and cheaper than the Argus II. But he argues that Prima’s superior image resolution has the potential to make Pixium Vision a success. “If you provide excellent vision, there will be lots of patients,” he tells Spectrum. “If you provide crappy vision, there will be very few.”

Some clinicians involved in the Argus II work are trying to salvage what they can from the technology. Gislin Dagnelie, an associate professor of ophthalmology at Johns Hopkins University School of Medicine, has set up a network of clinicians who are still working with Argus II patients. The researchers are experimenting with a thermal camera to help users see faces, a stereo camera to filter out the background, and AI-powered object recognition. These upgrades are unlikely to result in commercial hardware today but could help future vision prostheses.

The writers have carefully balanced this piece so it is not an outright condemnation of the companies (Second Sight and Nano Precision), from the February 15, 2022 IEEE Spectrum article,

Failure is an inevitable part of innovation. The Argus II was an innovative technology, and progress made by Second Sight may pave the way for other companies that are developing bionic vision systems. But for people considering such an implant in the future, the cautionary tale of Argus patients left in the lurch may make a tough decision even tougher. Should they take a chance on a novel technology? If they do get an implant and find that it helps them navigate the world, should they allow themselves to depend upon it?

Abandoning the Argus II technology—and the people who use it—might have made short-term financial sense for Second Sight, but it’s a decision that could come back to bite the merged company if it does decide to commercialize a brain implant, believes Doerr.

For anyone curious about retinal implant technology (specifically the Argus II), I have a description in a June 30, 2015 posting.

Speculations and hopes for neuroprosthetics

The field of neuroprosthetics is very active. Dr Arthur Saniotis and Prof Maciej Henneberg have written an article where they speculate about the possibilities of a neuroprosthetic that may one day merge with neurons in a February 21, 2022 Nanowerk Spotlight article,

For over a generation several types of medical neuroprosthetics have been developed, which have improved the lives of thousands of individuals. For instance, cochlear implants have restored functional hearing in individuals with severe hearing impairment.

Further advances in motor neuroprosthetics are attempting to restore motor functions in tetraplegic, limb loss and brain stem stroke paralysis subjects.

Currently, scientists are working on various kinds of brain/machine interfaces [BMI] in order to restore movement and partial sensory function. One such device is the ‘Ipsihand’ that enables movement of a paralyzed hand. The device works by detecting the recipient’s intention in the form of electrical signals, thereby triggering hand movement.

Another recent development is the 12 month BMI gait neurohabilitation program that uses a visual-tactile feedback system in combination with a physical exoskeleton and EEG operated AI actuators while walking. This program has been tried on eight patients with reported improvements in lower limb movement and somatic sensation.

Surgically placed electrode implants have also reduced tremor symptoms in individuals with Parkinson’s disease.

Although neuroprosthetics have provided various benefits they do have their problems. Firstly, electrode implants to the brain are prone to degradation, necessitating new implants after a few years. Secondly, as in any kind of surgery, implanted electrodes can cause post-operative infection and glial scarring. Furthermore, one study showed that the neurobiological efficacy of an implant is dependent on the rate of speed of its insertion.

But what if humans designed a neuroprosthetic, which could bypass the medical glitches of invasive neuroprosthetics? However, instead of connecting devices to neural networks, this neuroprosthetic would directly merge with neurons – a novel step. Such a neuroprosthetic could radically optimize treatments for neurodegenerative disorders and brain injuries, and possibly cognitive enhancement [emphasis mine].

A team of three international scientists has recently designed a nanobased neuroprosthetic, which was published in Frontiers in Neuroscience (“Integration of Nanobots Into Neural Circuits As a Future Therapy for Treating Neurodegenerative Disorders“). [open access paper published in 2018]

An interesting feature of their nanobot neuroprosthetic is that it has been inspired from nature by way of endomyccorhizae – a type of plant/fungus symbiosis, which is over four hundred million years old. During endomyccorhizae, fungi use numerous threadlike projections called mycelium that penetrate plant roots, forming colossal underground networks with nearby root systems. During this process fungi take up vital nutrients while protecting plant roots from infections – a win-win relationship. Consequently, the nano-neuroprosthetic has been named ‘endomyccorhizae ligand interface’, or ‘ELI’ for short.

The Spotlight article goes on to describe how these nanobots might function. As for the possibility of cognitive enhancement, I wonder if that might come to be described as a form of ‘artificial intelligence’.

(Dr Arthur Saniotis and Prof Maciej Henneberg are both from the Department of Anthropology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences; and Biological Anthropology and Comparative Anatomy Research Unit, Adelaide Medical School, University of Adelaide. Abdul-Rahman Sawalma who’s listed as an author on the 2018 paper is from the Palestinian Neuroscience Initiative, Al-Quds University, Beit Hanina, Palestine.)

Saniotis and Henneberg’s Spotlight article presents an optimistic view of neuroprosthetics. It seems telling that they cite cochlear implants as a success story when it is viewed by many as ethically fraught (see the Cochlear implant Wikipedia entry; scroll down to ‘Criticism and controversy’).

Ethics and your implants

This is from an April 6, 2015 article by Luc Henry on technologist.eu,

Technologist: What are the potential consequences of accepting the “augmented human” in society?

Gregor Wolbring: There are many that we might not even envision now. But let me focus on failure and obsolescence [emphasis mine], two issues that are rarely discussed. What happens when the mechanisms fails in the middle of an action? Failure has hazardous consequences, but obsolescence has psychological ones. …. The constant surgical inter­vention needed to update the hardware may not be feasible. A person might feel obsolete if she cohabits with others using a newer version.

T. Are researchers working on prosthetics sometimes disconnected from reality?

G. W. Students engaged in the development of prosthetics have to learn how to think in societal terms and develop a broader perspective. Our education system provides them with a fascination for clever solutions to technological challenges but not with tools aiming at understanding the consequences, such as whether their product might increase or decrease social justice.

Wolbring is a professor at the University of Calgary’s Cumming School of Medicine (profile page) who writes on social issues to do with human enhancement/ augmentation. As well,

Some of his areas of engagement are: ability studies including governance of ability expectations, disability studies, governance of emerging and existing sciences and technologies (e.g. nanoscale science and technology, molecular manufacturing, aging, longevity and immortality, cognitive sciences, neuromorphic engineering, genetics, synthetic biology, robotics, artificial intelligence, automatization, brain machine interfaces, sensors), impact of science and technology on marginalized populations, especially people with disabilities he governance of bodily enhancement, sustainability issues, EcoHealth, resilience, ethics issues, health policy issues, human rights and sport.

He also maintains his own website here.

Not just startups

I’d classify Second Sight as a tech startup company and they have a high rate of failure, which may not have been clear to the patients who had the implants. Clinical trials can present problems too as this excerpt from my September 17, 2020 posting notes,

This October 31, 2017 article by Emily Underwood for Science was revelatory,

“In 2003, neurologist Helen Mayberg of Emory University in Atlanta began to test a bold, experimental treatment for people with severe depression, which involved implanting metal electrodes deep in the brain in a region called area 25 [emphases mine]. The initial data were promising; eventually, they convinced a device company, St. Jude Medical in Saint Paul, to sponsor a 200-person clinical trial dubbed BROADEN.

This month [October 2017], however, Lancet Psychiatry reported the first published data on the trial’s failure. The study stopped recruiting participants in 2012, after a 6-month study in 90 people failed to show statistically significant improvements between those receiving active stimulation and a control group, in which the device was implanted but switched off.

… a tricky dilemma for companies and research teams involved in deep brain stimulation (DBS) research: If trial participants want to keep their implants [emphases mine], who will take responsibility—and pay—for their ongoing care? And participants in last week’s meeting said it underscores the need for the growing corps of DBS researchers to think long-term about their planned studies.”

Symbiosis can be another consequence, as mentioned in my September 17, 2020 posting,

From a July 24, 2019 article by Liam Drew for Nature Outlook: The brain,

“It becomes part of you,” Patient 6 said, describing the technology that enabled her, after 45 years of severe epilepsy, to halt her disabling seizures. Electrodes had been implanted on the surface of her brain that would send a signal to a hand-held device when they detected signs of impending epileptic activity. On hearing a warning from the device, Patient 6 knew to take a dose of medication to halt the coming seizure.

“You grow gradually into it and get used to it, so it then becomes a part of every day,” she told Frederic Gilbert, an ethicist who studies brain–computer interfaces (BCIs) at the University of Tasmania in Hobart, Australia. “It became me,” she said. [emphasis mine]

Symbiosis is a term, borrowed from ecology, that means an intimate co-existence of two species for mutual advantage. As technologists work towards directly connecting the human brain to computers, it is increasingly being used to describe humans’ potential relationship with artificial intelligence. [emphasis mine]

It’s complicated

For a lot of people these devices are or could be life-changing. At the same time, there are a number of different issues related to implants/prosthetics; the following is not an exhaustive list. As Wolbring notes, issues that we can’t begin to imagine now are likely to emerge as these medical advances become more ubiquitous.

Ability/disability?

Assistive technologies are almost always portrayed as helpful. For example, a cochlear implant gives people without hearing the ability to hear. The assumption is that this is always a good thing—unless you’re a deaf person who wants to define the problem a little differently. Who gets to decide what is good and ‘normal’ and what is desirable?

While the cochlear implant is the most extreme example I can think of, there are variations of these questions throughout the ‘disability’ communities.

Also, as Wolbring notes in his interview with the Technologist.eu, the education system tends to favour technological solutions which don’t take social issues into account. Wolbring cites social justice issues when he mentions failure and obsolescence.

Technical failures and obsolescence

The story, excerpted earlier in this posting, opened with a striking example of a technical failure at an awkward moment; a blind woman depending on her retinal implant loses all sight as she maneuvers through a subway station in New York City.

Aside from being an awful way to find out the company supplying and supporting your implant is in serious financial trouble and can’t offer assistance or repair, the failure offers a preview of what could happen as implants and prosthetics become more commonly used.

Keeping up/fomo (fear of missing out)/obsolescence

It used to be called ‘keeping up with the Joneses, it’s the practice of comparing yourself and your worldly goods to someone else(‘s) and then trying to equal what they have or do better. Usually, people want to have more and better than the mythical Joneses.

These days, the phenomenon (which has been expanded to include social networking) is better known as ‘fomo’ or fear of missing out (see the Fear of missing out Wikipedia entry).

Whatever you want to call it, humanity’s competitive nature can be seen where technology is concerned. When I worked in technology companies, I noticed that hardware and software were sometimes purchased for features that were effectively useless to us. But, not upgrading to a newer version was unthinkable.

Call it fomo or ‘keeping up with the Joneses’, it’s a powerful force and when people (and even companies) miss out or can’t keep up, it can lead to a sense of inferiority in the same way that having an obsolete implant or prosthetic could.

Social consequences

Could there be a neural implant/neuroprosthetic divide? There is already a digital divide (from its Wikipedia entry),

The digital divide is a gap between those who have access to new technology and those who do not … people without access to the Internet and other ICTs [information and communication technologies] are at a socio-economic disadvantage because they are unable or less able to find and apply for jobs, shop and sell online, participate democratically, or research and learn.

After reading Wolbring’s comments, it’s not hard to imagine a neural implant/neuroprosthetic divide with its attendant psychological and social consequences.

What kind of human am I?

There are other issues as noted in my September 17, 2020 posting. I’ve already mentioned ‘patient 6’, the woman who developed a symbiotic relationship with her brain/computer interface. This is how the relationship ended,

… He [Frederic Gilbert, ethicist] is now preparing a follow-up report on Patient 6. The company that implanted the device in her brain to help free her from seizures went bankrupt. The device had to be removed.

… Patient 6 cried as she told Gilbert about losing the device. … “I lost myself,” she said.

“It was more than a device,” Gilbert says. “The company owned the existence of this new person.”

Above human

The possibility that implants will not merely restore or endow someone with ‘standard’ sight or hearing or motion or … but will augment or improve on nature was broached in this May 2, 2013 posting, More than human—a bionic ear that extends hearing beyond the usual frequencies and is one of many in the ‘Human Enhancement’ category on this blog.

More recently, Hugh Herr, an Associate Professor at the Massachusetts Institute of Technology (MIT), leader of the Biomechatronics research group at MIT’s Media Lab, a double amputee, and prosthetic enthusiast, starred in the recent (February 23, 2022) broadcast of ‘Augmented‘ on the Public Broadcasting Service (PBS) science programme, Nova.

I found ‘Augmented’ a little offputting as it gave every indication of being an advertisement for Herr’s work in the form of a hero’s journey. I was not able to watch more than 10 mins. This preview gives you a pretty good idea of what it was like although the part in ‘Augmented, where he says he’d like to be a cyborg hasn’t been included,

At a guess, there were a few talking heads (taking up from 10%-20% of the running time) who provided some cautionary words to counterbalance the enthusiasm in the rest of the programme. It’s a standard approach designed to give the impression that both sides of a question are being recognized. The cautionary material is usually inserted past the 1/2 way mark while leaving several minutes at the end for returning to the more optimistic material.

In a February 2, 2010 posting I have excerpts from an article featuring quotes from Herr that I still find startling,

Written by Paul Hochman for Fast Company, Bionic Legs, iLimbs, and Other Super-Human Prostheses [ETA March 23, 2022: an updated version of the article is now on Genius.com] delves further into the world where people may be willing to trade a healthy limb for a prosthetic. From the article,

There are many advantages to having your leg amputated.

Pedicure costs drop 50% overnight. A pair of socks lasts twice as long. But Hugh Herr, the director of the Biomechatronics Group at the MIT Media Lab, goes a step further. “It’s actually unfair,” Herr says about amputees’ advantages over the able-bodied. “As tech advancements in prosthetics come along, amputees can exploit those improvements. They can get upgrades. A person with a natural body can’t.”

Herr is not the only one who favours prosthetics (also from the Hochman article),

This influx of R&D cash, combined with breakthroughs in materials science and processor speed, has had a striking visual and social result: an emblem of hurt and loss has become a paradigm of the sleek, modern, and powerful. Which is why Michael Bailey, a 24-year-old student in Duluth, Georgia, is looking forward to the day when he can amputate the last two fingers on his left hand.

“I don’t think I would have said this if it had never happened,” says Bailey, referring to the accident that tore off his pinkie, ring, and middle fingers. “But I told Touch Bionics I’d cut the rest of my hand off if I could make all five of my fingers robotic.”

But Bailey is most surprised by his own reaction. “When I’m wearing it, I do feel different: I feel stronger. As weird as that sounds, having a piece of machinery incorporated into your body, as a part of you, well, it makes you feel above human.[emphasis mine] It’s a very powerful thing.”

My September 17, 2020 posting touches on more ethical and social issues including some of those surrounding consumer neurotechnologies or brain-computer interfaces (BCI). Unfortunately, I don’t have space for these issues here.

As for Paul Hochman’s article, Bionic Legs, iLimbs, and Other Super-Human Prostheses, now on Genius.com, it has been updated.

Money makes the world go around

Money and business practices have been indirectly referenced (for the most part) up to now in this posting. The February 15, 2022 IEEE Spectrum article and Hochman’s article, Bionic Legs, iLimbs, and Other Super-Human Prostheses, cover two aspects of the money angle.

In the IEEE Spectrum article, a tech start-up company, Second Sight, ran into financial trouble and is acquired by a company that has no plans to develop Second Sight’s core technology. The people implanted with the Argus II technology have been stranded as were ‘patient 6’ and others participating in the clinical trial described in the July 24, 2019 article by Liam Drew for Nature Outlook: The brain mentioned earlier in this posting.

I don’t know anything about the business bankruptcy mentioned in the Drew article but one of the business problems described in the IEEE Spectrum article suggests that Second Sight was founded before answering a basic question, “What is the market size for this product?”

On 18 July 2019, Second Sight sent Argus patients a letter saying it would be phasing out the retinal implant technology to clear the way for the development of its next-generation brain implant for blindness, Orion, which had begun a clinical trial with six patients the previous year. …

“The leadership at the time didn’t believe they could make [the Argus retinal implant] part of the business profitable,” Greenberg [Robert Greenberg, Second Sight co-founder] says. “I understood the decision, because I think the size of the market turned out to be smaller than we had thought.”

….

The question of whether a medical procedure or medicine can be profitable (or should the question be sufficiently profitable?) was referenced in my April 26, 2019 posting in the context of gene editing and personalized medicine

Edward Abrahams, president of the Personalized Medicine Coalition (US-based), advocates for personalized medicine while noting in passing, market forces as represented by Goldman Sachs in his May 23, 2018 piece for statnews.com (Note: A link has been removed),

Goldman Sachs, for example, issued a report titled “The Genome Revolution.” It argues that while “genome medicine” offers “tremendous value for patients and society,” curing patients may not be “a sustainable business model.” [emphasis mine] The analysis underlines that the health system is not set up to reap the benefits of new scientific discoveries and technologies. Just as we are on the precipice of an era in which gene therapies, gene-editing, and immunotherapies promise to address the root causes of disease, Goldman Sachs says that these therapies have a “very different outlook with regard to recurring revenue versus chronic therapies.”

The ‘Glybera’ story in my July 4, 2019 posting (scroll down about 40% of the way) highlights the issue with “recurring revenue versus chronic therapies,”

Kelly Crowe in a November 17, 2018 article for the CBC (Canadian Broadcasting Corporation) news writes about Glybera,

It is one of this country’s great scientific achievements.

“The first drug ever approved that can fix a faulty gene.

It’s called Glybera, and it can treat a painful and potentially deadly genetic disorder with a single dose — a genuine made-in-Canada medical breakthrough.

But most Canadians have never heard of it.

Here’s my summary (from the July 4, 2019 posting),

It cost $1M for a single treatment and that single treatment is good for at least 10 years.

Pharmaceutical companies make their money from repeated use of their medicaments and Glybera required only one treatment so the company priced it according to how much they would have gotten for repeated use, $100,000 per year over a 10 year period. The company was not able to persuade governments and/or individuals to pay the cost

In the end, 31 people got the treatment, most of them received it for free through clinical trials.

For rich people only?

Megan Devlin’s March 8, 2022 article for the Daily Hive announces a major research investment into medical research (Note: A link has been removed),

Vancouver [Canada] billionaire Chip Wilson revealed Tuesday [March 8, 2022] that he has a rare genetic condition that causes his muscles to waste away, and announced he’s spending $100 million on research to find a cure.

His condition is called facio-scapulo-humeral muscular dystrophy, or FSHD for short. It progresses rapidly in some people and more slowly in others, but is characterized by progressive muscle weakness starting the the face, the neck, shoulders, and later the lower body.

“I’m out for survival of my own life,” Wilson said.

“I also have the resources to do something about this which affects so many people in the world.”

Wilson hopes the $100 million will produce a cure or muscle-regenerating treatment by 2027.

“This could be one of the biggest discoveries of all time, for humankind,” Wilson said. “Most people lose muscle, they fall, and they die. If we can keep muscle as we age this can be a longevity drug like we’ve never seen before.”

According to rarediseases.org, FSHD affects between four and 10 people out of every 100,000 [emphasis mine], Right now, therapies are limited to exercise and pain management. There is no way to stall or reverse the disease’s course.

Wilson is best known for founding athleisure clothing company Lululemon. He also owns the most expensive home in British Columbia, a $73 million mansion in Vancouver’s Kitsilano neighbourhood.

Let’s see what the numbers add up to,

4 – 10 people out of 100,000

40 – 100 people out of 1M

1200 – 3,000 people out of 30M (let’s say this is Canada’s population)\

12,000 – 30,000 people out of 300M (let’s say this is the US’s population)

42,000 – 105,000 out of 1.115B (let’s say this is China’s population)

The rough total comes to 55,200 to 138,000 people between three countries with a combined population total of 1.445B. Given how business currently operates, it seems unlikely that any company will want to offer Wilson’s hoped for medical therapy although he and possibly others may benefit from a clinical trial.

Should profit or wealth be considerations?

The stories about the patients with the implants and the patients who need Glybera are heartbreaking and point to a question not often asked when medical therapies and medications are developed. Is the profit model the best choice and, if so, how much profit?

I have no answer to that question but I wish it was asked by medical researchers and policy makers.

As for wealthy people dictating the direction for medical research, I don’t have answers there either. I hope the research will yield applications and/or valuable information for more than Wilson’s disease.

It’s his money after all

Wilson calls his new venture, SolveFSHD. It doesn’t seem to be affiliated with any university or biomedical science organization and it’s not clear how the money will be awarded (no programmes, no application procedure, no panel of experts). There are three people on the team, Eva R. Chin, scientist and executive director, Chip Wilson, SolveFSHD founder/funder, and FSHD patient, and Neil Camarta, engineer, executive (fossil fuels and clean energy), and FSHD patient. There’s also a Twitter feed (presumably for the latest updates): https://twitter.com/SOLVEFSHD.

Perhaps unrelated but intriguing is news about a proposed new building in Kenneth Chan’s March 31, 2022 article for the Daily Hive,

Low Tide Properties, the real estate arm of Lululemon founder Chip Wilson [emphasis mine], has submitted a new development permit application to build a 148-ft-tall, eight-storey, mixed-use commercial building in the False Creek Flats of Vancouver.

The proposal, designed by local architectural firm Musson Cattell Mackey Partnership, calls for 236,000 sq ft of total floor area, including 105,000 sq ft of general office space, 102,000 sq ft of laboratory space [emphasis mine], and 5,000 sq ft of ground-level retail space. An outdoor amenity space for building workers will be provided on the rooftop.

[next door] The 2001-built, five-storey building at 1618 Station Street immediately to the west of the development site is also owned by Low Tide Properties [emphasis mine]. The Ferguson, the name of the existing building, contains about 79,000 sq ft of total floor area, including 47,000 sq ft of laboratory space and 32,000 sq ft of general office space. Biotechnology company Stemcell technologies [STEMCELL] Technologies] is the anchor tenant [emphasis mine].

I wonder if this proposed new building will house SolveFSHD and perhaps other FSHD-focused enterprises. The proximity of STEMCELL Technologies could be quite convenient. In any event, $100M will buy a lot (pun intended).

The end

Issues I’ve described here in the context of neural implants/neuroprosthetics and cutting edge medical advances are standard problems not specific to these technologies/treatments:

  • What happens when the technology fails (hopefully not at a critical moment)?
  • What happens when your supplier goes out of business or discontinues the products you purchase from them?
  • How much does it cost?
  • Who can afford the treatment/product? Will it only be for rich people?
  • Will this technology/procedure/etc. exacerbate or create new social tensions between social classes, cultural groups, religious groups, races, etc.?

Of course, having your neural implant fail suddenly in the middle of a New York City subway station seems a substantively different experience than having your car break down on the road.

There are, of course, there are the issues we can’t yet envision (as Wolbring notes) and there are issues such as symbiotic relationships with our implants and/or feeling that you are “above human.” Whether symbiosis and ‘implant/prosthetic superiority’ will affect more than a small number of people or become major issues is still to be determined.

There’s a lot to be optimistic about where new medical research and advances are concerned but I would like to see more thoughtful coverage in the media (e.g., news programmes and documentaries like ‘Augmented’) and more thoughtful comments from medical researchers.

Of course, the biggest issue I’ve raised here is about the current business models for health care products where profit is valued over people’s health and well-being. it’s a big question and I don’t see any definitive answers but the question put me in mind of this quote (from a September 22, 2020 obituary for US Supreme Court Justice Ruth Bader Ginsburg by Irene Monroe for Curve),

Ginsburg’s advocacy for justice was unwavering and showed it, especially with each oral dissent. In another oral dissent, Ginsburg quoted a familiar Martin Luther King Jr. line, adding her coda:” ‘The arc of the universe is long, but it bends toward justice,’” but only “if there is a steadfast commitment to see the task through to completion.” …

Martin Luther King Jr. popularized and paraphrased the quote (from a January 18, 2018 article by Mychal Denzel Smith for Huffington Post),

His use of the quote is best understood by considering his source material. “The arc of the moral universe is long, but it bends toward justice” is King’s clever paraphrasing of a portion of a sermon delivered in 1853 by the abolitionist minister Theodore Parker. Born in Lexington, Massachusetts, in 1810, Parker studied at Harvard Divinity School and eventually became an influential transcendentalist and minister in the Unitarian church. In that sermon, Parker said: “I do not pretend to understand the moral universe. The arc is a long one. My eye reaches but little ways. I cannot calculate the curve and complete the figure by experience of sight. I can divine it by conscience. And from what I see I am sure it bends toward justice.”

I choose to keep faith that people will get the healthcare products they need and that all of us need to keep working at making access more fair.

Science events and an exhibition concerning wind in the Vancouver (Canada) area for July 2019 and beyond

it’s not quite the bumper crop of science events that took place in May 2019, which may be a good thing if you’re eager to attend everything. First, here are the events and then, the exhibition.

Nerd Nite at the Movies

On July 10, 2019, a new series is being launched at the Vancouver International Film Festival (VIFF) Centre. Here’s the description from the Nerd Nite Vancouver SciFact vs SciFi: Nerd Nite Goes to the Movies event page,

SciFact vs SciFiction: Nerd Nite Goes to the Movies v1. Animal

This summer we’re trying something a little different. Our new summer series of talks – a collaboration between Nerd Nite and VIFF – examines the pseudo-science propagated by Hollywood, and seeks to sift real insights from fake facts, in a fun, playful but peer-approved format. Each show will feature clips from a variety of movies on a science theme with a featured scientist on hand all done Nerd Nite style with drinks! We begin with biology, and our first presenter is Dr Carin Bondar.

Dr Bondar has been the host of Science Channel’s Outrageous Acts of Science, and she’s the author of several books including “Wild Moms: The Science Behind Mating in the Animal Kingdom”. Tonight she’ll join Kaylee [Byers] and Michael [Unger] from Nerd Nite to discuss the sci-facts in a variety of clips from cinema. We’ll be discussing the science in Planet of the ApesThe BirdsArachnophobiaSnakes on a Plane, and more!

When: July 10 [2019]
Where: Vancouver International Film Centre
When: 7:30 – 8:30 – This talk will be followed by a screening of Alfred Hitchcock’s classic The Birds (9pm). Double bill price: $20
Tickets: Here!

The VIFF Centre’s SciFact vs SciFi: Animals According to Hollywood event page has much the same information plus this,

SciFact vs SciFi: Nerd Nite Goes to the Movies continues:

July 31 [2019] – Dr. Douglas Scott: The Universe According to Hollywood
Aug 14 [2019] – Mika McKinnon: Disaster According to Hollywood
Aug 28 [2019] – Greg Bole: Evolution According to Hollywood

This series put me in mind what was then the New York-based, ‘Science Goes to the Movies’. I first mentioned this series in a March 10, 2016 posting and it seems that since then, the series has lost a host and been embraced by public television (in the US). You can find the latest incarnation of Science Goes To The Movies here.

Getting back to Vancouver, no word as to which movies will accompany these future talks. If I had a vote, I’d love to see Gattaca accompany any talk on genetics.

That last sentence is both true and provides a neat segue to the next event.

Genetics at the Vancouver Public Library (VPL)

Coming up on July 23, 2019, a couple of graduate students at the University of British Columbia will be sharing some of the latest information on genetics. From the VPL events page,

Curiosities of the Natural World: Genetics – the Future of Medicine

Tuesday, July 23, 2019 (7:00 pm – 8:30 pm)
Central Library
Description

Since their discovery over a century ago, diabetes, multiple sclerosis, and Alzheimer’s have seemed like diseases without a cure. The advent of genetic treatments and biomarkers are changing the outcomes and treatments of these once impossible-to-treat conditions.

UBC researchers, Adam Ramzy and Maria-Elizabeth Baeva discuss the potential of genetic therapies for diabetes, and new biomarkers and therapeutics for Alzheimer ’s disease and multiple sclerosis.

This program is part of the Curiosities of the Natural World series in partnership with UBC Let’s Talk Science, the UBC Faculty of Science, and the UBC Public Scholars Initiative

Suitable for: Adults
Seniors

Additional Details:
Alma VanDusen and Peter Kaye Rooms, Lower Level

It’s hard to know how to respond to this as I loathe anything that has ‘future of medicine’ in it. Isn’t there always going to ***be*** ‘a’ future with medicine in it?

Also, there is at least one cautionary tale about this new era of ‘genetic medicine’: Glybera is a gene therapy that worked for people with a rare genetic disease. It is a **treatment**, the only one, and it is no longer available.

Kelly Crowe in a November 17, 2018 article for the CBC (Canadian Broadcasting Corporation) news writes about Glybera,

It is one of this country’s great scientific achievements.

The first drug ever approved that can fix a faulty gene.

It’s called Glybera, and it can treat a painful and potentially deadly genetic disorder with a single dose — a genuine made-in-Canada medical breakthrough.

But most Canadians have never heard of it.

A team of researchers at the University of British Columbia spent decades developing the treatment for people born with a genetic mutation that causes lipoprotein lipase disorder (LPLD).

LPLD affects communities in the Saguenay region of northeastern Quebec at a higher rate than anywhere else in the world.

Glybera was never sold in North America and was available in Europe for just two years, beginning in 2015. During that time, only one patient received the drug. Then it was abandoned by the company that held its European licensing rights.

The problem was the price.

The world’s first gene therapy, a remarkable discovery by a dedicated team of scientists who came together in a Vancouver lab, had earned a second, more dubious distinction:

The world’s most expensive drug.

It cost $1M for a single treatment and that single treatment is good for at least 10 years.

Pharmaceutical companies make their money from repeated use of their medicaments and Glybera required only one treatment so the company priced it according to how much they would have gotten for repeated use, $100,000 per year over a 10 year period. The company was not able to persuade governments and/or individuals to pay the cost.

In the end, 31 people got the treatment, most of them received it for free through clinical trials.

Crowe has written an exceptionally good story (November 17, 2018 article) about Glybera and I encourage you to read in its entirety. I warn you it’s heartbreaking.

I wrote about money and genetics in an April 26, 2019 posting (Gene editing and personalized medicine: Canada). Scroll down to the subsection titled ‘Cost/benefit analysis’ for a mention of Goldman Sachs, an American global investment banking, securities and investment management firm, and its conclusion that personalized medicine is not a viable business model. I wonder if part of their analysis included the Glybera experience.

Getting back to the July 23, 2019 talk at the VPL’s central branch, I have no doubt the researchers will be discussing some exciting work but the future might not be as rosy as one might hope.

I wasn’t able to find much information about either Adan Ramzy or Maria-Elizabeth Baeva. There’s this for Ramzy (scroll down to Class of 2021) and this for Baeva (scroll down to Scholarships).

WINDS from June 22 to September 29, 2019

This show or exhibition is taking place in New Westminster (part of the Metro Vancouver area) at the Anvil Centre’s New Media Gallery. From the Anvil Centre’s WINDS event page,

WINDS
New Media Gallery Exhibition
June 22  – September 29
Opening Reception + Artist Talk  is on June 21st at 6:30pm
 
Chris Welsby (UK)
Spencer Finch (UK)
David Bowen (USA)
Nathalie Miebach (Germany/USA)
 
Our summer exhibition features four exciting, multi-media installations by four international artists from UK and USA.  Each artist connects with the representation, recreation and manifestation of wind through physical space and time.  Each suggests how our perception and understanding of wind can be created through pressure, sound, data, pattern, music and motion and then further appreciated in poetic or metaphoric ways that might connect us with how the wind influences language, imagination or our understanding of historic events.
 
All the artists use sound as a key element ; to emphasize or recreate the sonic experience of different winds and their effects, to trigger memory or emotion, or to heighten certain effects that might prompt the viewer to consider significant philosophical questions. Common objects are used in all the works; discarded objects, household or readymade objects and everyday materials; organic, synthetic, natural and manmade. The viewer will find connections with past winds and events both recent and distant.  There is an attempt to capture or allude to a moment in time which brings with it suggestions of mortality,  thereby transforming the works into poignant memento-mori.

Dates
June 22 – September 29, 2019

Price
Complimentary

Location
777 Columbia Street. New Media Gallery.

The New Media Gallery’s home page features ‘winds’ (yes, it’s all in lower case),

Landscape and weather have long shared an intimate connection with the arts.  Each of the works here is a landscape: captured, interpreted and presented through a range of technologies. The four artists in this exhibition have taken, as their material process, the movement of wind through physical space & time. They explore how our perception and understanding of landscape can be interpreted through technology. 

These works have been created by what might be understood as a sort of scientific method or process that involves collecting data, acute observation, controlled experiments and the incorporation of measurements and technologies that control or collect motion, pressure, sound, pattern and the like. The artists then take us in other directions; allowing technology or situations to render visible that which is invisible, creating and focussing on peculiar or resonant qualities of sound, light or movement in ways that seem to influence emotion or memory, dwelling on iconic places and events, or revealing in subtle ways, the subjective nature of time.  Each of these works suggest questions related to the nature of illusive experience and how or if it can be captured, bringing inevitable connections to authorship, loss, memory and memento mori

David Bowen
tele-present wind
Image
Biography
Credits

Spencer Finch (USA)
2 hours, 2 minutes, 2 seconds (Wind at Walden Pond, March 12, 2007)
Image
Biography
Credits

Nathalie Miebach (USA)
Hurricane Noel III
Image
Biography
Credits

Chris Welsby (UK)
Wind Vane
Image
Biography
Credits

Hours
10:00am – 5:00pm Tuesday – Sunday
10:00am – 8:00pm Thursdays
Closed Monday

Address
New Media Gallery
3rd Floor Anvil Centre
777 Columbia Street
New Westminster, BC V3M 1B6

If you want to see the images and biographies for the artists participating in ‘winds’, please go here..

So there you have it, science events and an exhibition in the Vancouver* area for July 2019.

*July 23, 2019 Correction: The word ‘and’ was removed from the final sentence for grammatical correctness.

**July 23, 2019 Correction: I changed the word ‘cure’ to ‘treatment’ so as to be more accurate. The word ‘cure’ suggests permanence and Glybera is supposed to be effective for 10 years or longer but no one really knows.

***Added the word ‘be’ for grammatical correctness on Nov. 30, 2020.

Gene editing and personalized medicine: Canada

Back in the fall of 2018 I came across one of those overexcited pieces about personalized medicine and gene editing tha are out there. This one came from an unexpected source, an author who is a “PhD Scientist in Medical Science (Blood and Vasculature” (from Rick Gierczak’s LinkedIn profile).

It starts our promisingly enough although I’m beginning to dread the use of the word ‘precise’  where medicine is concerned, (from a September 17, 2018 posting on the Science Borealis blog by Rick Gierczak (Note: Links have been removed),

CRISPR-Cas9 technology was accidentally discovered in the 1980s when scientists were researching how bacteria defend themselves against viral infection. While studying bacterial DNA called clustered regularly interspaced short palindromic repeats (CRISPR), they identified additional CRISPR-associated (Cas) protein molecules. Together, CRISPR and one of those protein molecules, termed Cas9, can locate and cut precise regions of bacterial DNA. By 2012, researchers understood that the technology could be modified and used more generally to edit the DNA of any plant or animal. In 2015, the American Association for the Advancement of Science chose CRISPR-Cas9 as science’s “Breakthrough of the Year”.

Today, CRISPR-Cas9 is a powerful and precise gene-editing tool [emphasis mine] made of two molecules: a protein that cuts DNA (Cas9) and a custom-made length of RNA that works like a GPS for locating the exact spot that needs to be edited (CRISPR). Once inside the target cell nucleus, these two molecules begin editing the DNA. After the desired changes are made, they use a repair mechanism to stitch the new DNA into place. Cas9 never changes, but the CRISPR molecule must be tailored for each new target — a relatively easy process in the lab. However, it’s not perfect, and occasionally the wrong DNA is altered [emphasis mine].

Note that Gierczak makes a point of mentioning that CRISPR/Cas9 is “not perfect.” And then, he gets excited (Note: Links have been removed),

CRISPR-Cas9 has the potential to treat serious human diseases, many of which are caused by a single “letter” mutation in the genetic code (A, C, T, or G) that could be corrected by precise editing. [emphasis mine] Some companies are taking notice of the technology. A case in point is CRISPR Therapeutics, which recently developed a treatment for sickle cell disease, a blood disorder that causes a decrease in oxygen transport in the body. The therapy targets a special gene called fetal hemoglobin that’s switched off a few months after birth. Treatment involves removing stem cells from the patient’s bone marrow and editing the gene to turn it back on using CRISPR-Cas9. These new stem cells are returned to the patient ready to produce normal red blood cells. In this case, the risk of error is eliminated because the new cells are screened for the correct edit before use.

The breakthroughs shown by companies like CRISPR Therapeutics are evidence that personalized medicine has arrived. [emphasis mine] However, these discoveries will require government regulatory approval from the countries where the treatment is going to be used. In the US, the Food and Drug Administration (FDA) has developed new regulations allowing somatic (i.e., non-germ) cell editing and clinical trials to proceed. [emphasis mine]

The potential treatment for sickle cell disease is exciting but Gierczak offers no evidence that this treatment or any unnamed others constitute proof that “personalized medicine has arrived.” In fact, Goldman Sachs, a US-based investment bank, makes the case that it never will .

Cost/benefit analysis

Edward Abrahams, president of the Personalized Medicine Coalition (US-based), advocates for personalized medicine while noting in passing, market forces as represented by Goldman Sachs in his May 23, 2018 piece for statnews.com (Note: A link has been removed),

One of every four new drugs approved by the Food and Drug Administration over the last four years was designed to become a personalized (or “targeted”) therapy that zeros in on the subset of patients likely to respond positively to it. That’s a sea change from the way drugs were developed and marketed 10 years ago.

Some of these new treatments have extraordinarily high list prices. But focusing solely on the cost of these therapies rather than on the value they provide threatens the future of personalized medicine.

… most policymakers are not asking the right questions about the benefits of these treatments for patients and society. Influenced by cost concerns, they assume that prices for personalized tests and treatments cannot be justified even if they make the health system more efficient and effective by delivering superior, longer-lasting clinical outcomes and increasing the percentage of patients who benefit from prescribed treatments.

Goldman Sachs, for example, issued a report titled “The Genome Revolution.” It argues that while “genome medicine” offers “tremendous value for patients and society,” curing patients may not be “a sustainable business model.” [emphasis mine] The analysis underlines that the health system is not set up to reap the benefits of new scientific discoveries and technologies. Just as we are on the precipice of an era in which gene therapies, gene-editing, and immunotherapies promise to address the root causes of disease, Goldman Sachs says that these therapies have a “very different outlook with regard to recurring revenue versus chronic therapies.”

Let’s just chew on this one (contemplate)  for a minute”curing patients may not be ‘sustainable business model’!”

Coming down to earth: policy

While I find Gierczak to be over-enthused, he, like Abrahams, emphasizes the importance of new policy, in his case, the focus is Canadian policy. From Gierczak’s September 17, 2018 posting (Note: Links have been removed),

In Canada, companies need approval from Health Canada. But a 2004 law called the Assisted Human Reproduction Act (AHR Act) states that it’s a criminal offence “to alter the genome of a human cell, or in vitroembryo, that is capable of being transmitted to descendants”. The Actis so broadly written that Canadian scientists are prohibited from using the CRISPR-Cas9 technology on even somatic cells. Today, Canada is one of the few countries in the world where treating a disease with CRISPR-Cas9 is a crime.

On the other hand, some countries provide little regulatory oversight for editing either germ or somatic cells. In China, a company often only needs to satisfy the requirements of the local hospital where the treatment is being performed. And, if germ-cell editing goes wrong, there is little recourse for the future generations affected.

The AHR Act was introduced to regulate the use of reproductive technologies like in vitrofertilization and research related to cloning human embryos during the 1980s and 1990s. Today, we live in a time when medical science, and its role in Canadian society, is rapidly changing. CRISPR-Cas9 is a powerful tool, and there are aspects of the technology that aren’t well understood and could potentially put patients at risk if we move ahead too quickly. But the potential benefits are significant. Updated legislation that acknowledges both the risks and current realities of genomic engineering [emphasis mine] would relieve the current obstacles and support a path toward the introduction of safe new therapies.

Criminal ban on human gene-editing of inheritable cells (in Canada)

I had no idea there was a criminal ban on the practice until reading this January 2017 editorial by Bartha Maria Knoppers, Rosario Isasi, Timothy Caulfield, Erika Kleiderman, Patrick Bedford, Judy Illes, Ubaka Ogbogu, Vardit Ravitsky, & Michael Rudnicki for (Nature) npj Regenerative Medicine (Note: Links have been removed),

Driven by the rapid evolution of gene editing technologies, international policy is examining which regulatory models can address the ensuing scientific, socio-ethical and legal challenges for regenerative and personalised medicine.1 Emerging gene editing technologies, including the CRISPR/Cas9 2015 scientific breakthrough,2 are powerful, relatively inexpensive, accurate, and broadly accessible research tools.3 Moreover, they are being utilised throughout the world in a wide range of research initiatives with a clear eye on potential clinical applications. Considering the implications of human gene editing for selection, modification and enhancement, it is time to re-examine policy in Canada relevant to these important advances in the history of medicine and science, and the legislative and regulatory frameworks that govern them. Given the potential human reproductive applications of these technologies, careful consideration of these possibilities, as well as ethical and regulatory scrutiny must be a priority.4

With the advent of human embryonic stem cell research in 1978, the birth of Dolly (the cloned sheep) in 1996 and the Raelian cloning hoax in 2003, the environment surrounding the enactment of Canada’s 2004 Assisted Human Reproduction Act (AHRA) was the result of a decade of polarised debate,5 fuelled by dystopian and utopian visions for future applications. Rightly or not, this led to the AHRA prohibition on a wide range of activities, including the creation of embryos (s. 5(1)(b)) or chimeras (s. 5(1)(i)) for research and in vitro and in vivo germ line alterations (s. 5(1)(f)). Sanctions range from a fine (up to $500,000) to imprisonment (up to 10 years) (s. 60 AHRA).

In Canada, the criminal ban on gene editing appears clear, the Act states that “No person shall knowingly […] alter the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants;” [emphases mine] (s. 5(1)(f) AHRA). This approach is not shared worldwide as other countries such as the United Kingdom, take a more regulatory approach to gene editing research.1 Indeed, as noted by the Law Reform Commission of Canada in 1982, criminal law should be ‘an instrument of last resort’ used solely for “conduct which is culpable, seriously harmful, and generally conceived of as deserving of punishment”.6 A criminal ban is a suboptimal policy tool for science as it is inflexible, stifles public debate, and hinders responsiveness to the evolving nature of science and societal attitudes.7 In contrast, a moratorium such as the self-imposed research moratorium on human germ line editing called for by scientists in December 20158 can at least allow for a time limited pause. But like bans, they may offer the illusion of finality and safety while halting research required to move forward and validate innovation.

On October 1st, 2016, Health Canada issued a Notice of Intent to develop regulations under the AHRA but this effort is limited to safety and payment issues (i.e. gamete donation). Today, there is a need for Canada to revisit the laws and policies that address the ethical, legal and social implications of human gene editing. The goal of such a critical move in Canada’s scientific and legal history would be a discussion of the right of Canadians to benefit from the advancement of science and its applications as promulgated in article 27 of the Universal Declaration of Human Rights9 and article 15(b) of the International Covenant on Economic, Social and Cultural Rights,10 which Canada has signed and ratified. Such an approach would further ensure the freedom of scientific endeavour both as a principle of a liberal democracy and as a social good, while allowing Canada to be engaged with the international scientific community.

Even though it’s a bit old, I still recommend reading the open access editorial in full, if you have the time.

One last thing abut the paper, the acknowledgements,

Sponsored by Canada’s Stem Cell Network, the Centre of Genomics and Policy of McGill University convened a ‘think tank’ on the future of human gene editing in Canada with legal and ethics experts as well as representatives and observers from government in Ottawa (August 31, 2016). The experts were Patrick Bedford, Janetta Bijl, Timothy Caulfield, Judy Illes, Rosario Isasi, Jonathan Kimmelman, Erika Kleiderman, Bartha Maria Knoppers, Eric Meslin, Cate Murray, Ubaka Ogbogu, Vardit Ravitsky, Michael Rudnicki, Stephen Strauss, Philip Welford, and Susan Zimmerman. The observers were Geneviève Dubois-Flynn, Danika Goosney, Peter Monette, Kyle Norrie, and Anthony Ridgway.

Competing interests

The authors declare no competing interests.

Both McGill and the Stem Cell Network pop up again. A November 8, 2017 article about the need for new Canadian gene-editing policies by Tom Blackwell for the National Post features some familiar names (Did someone have a budget for public relations and promotion?),

It’s one of the most exciting, and controversial, areas of health science today: new technology that can alter the genetic content of cells, potentially preventing inherited disease — or creating genetically enhanced humans.

But Canada is among the few countries in the world where working with the CRISPR gene-editing system on cells whose DNA can be passed down to future generations is a criminal offence, with penalties of up to 10 years in jail.

This week, one major science group announced it wants that changed, calling on the federal government to lift the prohibition and allow researchers to alter the genome of inheritable “germ” cells and embryos.

The potential of the technology is huge and the theoretical risks like eugenics or cloning are overplayed, argued a panel of the Stem Cell Network.

The step would be a “game-changer,” said Bartha Knoppers, a health-policy expert at McGill University, in a presentation to the annual Till & McCulloch Meetings of stem-cell and regenerative-medicine researchers [These meetings were originally known as the Stem Cell Network’s Annual General Meeting {AGM}]. [emphases mine]

“I’m completely against any modification of the human genome,” said the unidentified meeting attendee. “If you open this door, you won’t ever be able to close it again.”

If the ban is kept in place, however, Canadian scientists will fall further behind colleagues in other countries, say the experts behind the statement say; they argue possible abuses can be prevented with good ethical oversight.

“It’s a human-reproduction law, it was never meant to ban and slow down and restrict research,” said Vardit Ravitsky, a University of Montreal bioethicist who was part of the panel. “It’s a sort of historical accident … and now our hands are tied.”

There are fears, as well, that CRISPR could be used to create improved humans who are genetically programmed to have certain facial or other features, or that the editing could have harmful side effects. Regardless, none of it is happening in Canada, good or bad.

In fact, the Stem Cell Network panel is arguably skirting around the most contentious applications of the technology. It says it is asking the government merely to legalize research for its own sake on embryos and germ cells — those in eggs and sperm — not genetic editing of embryos used to actually get women pregnant.

The highlighted portions in the last two paragraphs of the excerpt were written one year prior to the claims by a Chinese scientist that he had run a clinical trial resulting in gene-edited twins, Lulu and Nana. (See my my November 28, 2018 posting for a comprehensive overview of the original furor). I have yet to publish a followup posting featuring the news that the CRISPR twins may have been ‘improved’ more extensively than originally realized. The initial reports about the twins focused on an illness-related reason (making them HIV ‘immune’) but made no mention of enhanced cognitive skills a side effect of eliminating the gene that would make them HIV ‘immune’. To date, the researcher has not made the bulk of his data available for an in-depth analysis to support his claim that he successfully gene-edited the twins. As well, there were apparently seven other pregnancies coming to term as part of the researcher’s clinical trial and there has been no news about those births.

Risk analysis innovation

Before moving onto the innovation of risk analysis, I want to focus a little more on at least one of the risks that gene-editing might present. Gierczak noted that CRISPR/Cas9 is “not perfect,” which acknowledges the truth but doesn’t convey all that much information.

While the terms ‘precision’ and ‘scissors’ are used frequently when describing the CRISPR technique, scientists actually mean that the technique is significantly ‘more precise’ than other techniques but they are not referencing an engineering level of precision. As for the ‘scissors’, it’s an analogy scientists like to use but in fact CRISPR is not as efficient and precise as a pair of scissors.

Michael Le Page in a July 16, 2018 article for New Scientist lays out some of the issues (Note: A link has been removed),

A study of CRIPSR suggests we shouldn’t rush into trying out CRISPR genome editing inside people’s bodies just yet. The technique can cause big deletions or rearrangements of DNA [emphasis mine], says Allan Bradley of the Wellcome Sanger Institute in the UK, meaning some therapies based on CRISPR may not be quite as safe as we thought.

The CRISPR genome editing technique is revolutionising biology, enabling us to create new varieties of plants and animals and develop treatments for a wide range of diseases.

The CRISPR Cas9 protein works by cutting the DNA of a cell in a specific place. When the cell repairs the damage, a few DNA letters get changed at this spot – an effect that can be exploited to disable genes.

At least, that’s how it is supposed to work. But in studies of mice and human cells, Bradley’s team has found that in around a fifth of cells, CRISPR causes deletions or rearrangements more than 100 DNA letters long. These surprising changes are sometimes thousands of letters long.

“I do believe the findings are robust,” says Gaetan Burgio of the Australian National University, an expert on CRISPR who has debunked previous studies questioning the method’s safety. “This is a well-performed study and fairly significant.”

I covered the Bradley paper and the concerns in a July 17, 2018 posting ‘The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle‘. (The ‘kerfufle’ was in reference to a report that the CRISPR market was affected by the publication of Bradley’s paper.)

Despite Health Canada not moving swiftly enough for some researchers, they have nonetheless managed to release an ‘outcome’ report about a consultation/analysis started in October 2016. Before getting to the consultation’s outcome, it’s interesting to look at how the consultation’s call for response was described (from Health Canada’s Toward a strengthened Assisted Human Reproduction Act ; A Consultation with Canadians on Key Policy Proposals webpage),

In October 2016, recognizing the need to strengthen the regulatory framework governing assisted human reproduction in Canada, Health Canada announced its intention to bring into force the dormant sections of the Assisted Human Reproduction Act  and to develop the necessary supporting regulations.

This consultation document provides an overview of the key policy proposals that will help inform the development of regulations to support bringing into force Section 10, Section 12 and Sections 45-58 of the Act. Specifically, the policy proposals describe the Department’s position on the following:

Section 10: Safety of Donor Sperm and Ova

  • Scope and application
  • Regulated parties and their regulatory obligations
  • Processing requirements, including donor suitability assessment
  • Record-keeping and traceability

Section 12: Reimbursement

  • Expenditures that may be reimbursed
  • Process for reimbursement
  • Creation and maintenance of records

Sections 45-58: Administration and Enforcement

  • Scope of the administration and enforcement framework
  • Role of inspectors designated under the Act

The purpose of the document is to provide Canadians with an opportunity to review the policy proposals and to provide feedback [emphasis mine] prior to the Department finalizing policy decisions and developing the regulations. In addition to requesting stakeholders’ general feedback on the policy proposals, the Department is also seeking input on specific questions, which are included throughout the document.

It took me a while to find the relevant section (in particular, take note of ‘Federal Regulatory Oversight’),

3.2. AHR in Canada Today

Today, an increasing number of Canadians are turning to AHR technologies to grow or build their families. A 2012 Canadian studyFootnote 1 found that infertility is on the rise in Canada, with roughly 16% of heterosexual couples experiencing infertility. In addition to rising infertility, the trend of delaying marriage and parenthood, scientific advances in cryopreserving ova, and the increasing use of AHR by LGBTQ2 couples and single parents to build a family are all contributing to an increase in the use of AHR technologies.

The growing use of reproductive technologies by Canadians to help build their families underscores the need to strengthen the AHR Act. While the approach to regulating AHR varies from country to country, Health Canada has considered international best practices and the need for regulatory alignment when developing the proposed policies set out in this document. …

3.2.1 Federal Regulatory Oversight

Although the scope of the AHR Act was significantly reduced in 2012 and some of the remaining sections have not yet been brought into force, there are many important sections of the Act that are currently administered and enforced by Health Canada, as summarized generally below:

Section 5: Prohibited Scientific and Research Procedures
Section 5 prohibits certain types of scientific research and clinical procedures that are deemed unacceptable, including: human cloning, the creation of an embryo for non-reproductive purposes, maintaining an embryo outside the human body beyond the fourteenth day, sex selection for non-medical reasons, altering the genome in a way that could be transmitted to descendants, and creating a chimera or a hybrid. [emphasis mine]

….

It almost seems as if the they were hiding the section that broached the human gene-editing question. It doesn’t seem to have worked as it appears, there are some very motivated parties determined to reframe the discussion. Health Canada’s ‘outocme’ report, published March 2019, What we heard: A summary of scanning and consultations on what’s next for health product regulation reflects the success of those efforts,

1.0 Introduction and Context

Scientific and technological advances are accelerating the pace of innovation. These advances are increasingly leading to the development of health products that are better able to predict, define, treat, and even cure human diseases. Globally, many factors are driving regulators to think about how to enable health innovation. To this end, Health Canada has been expanding beyond existing partnerships and engaging both domestically and internationally. This expanding landscape of products and services comes with a range of new challenges and opportunities.

In keeping up to date with emerging technologies and working collaboratively through strategic partnerships, Health Canada seeks to position itself as a regulator at the forefront of health innovation. Following the targeted sectoral review of the Health and Biosciences Sector Regulatory Review consultation by the Treasury Board Secretariat, Health Canada held a number of targeted meetings with a broad range of stakeholders.

This report outlines the methodologies used to look ahead at the emerging health technology environment, [emphasis mine] the potential areas of focus that resulted, and the key findings from consultations.

… the Department identified the following key drivers that are expected to shape the future of health innovation:

  1. The use of “big data” to inform decision-making: Health systems are generating more data, and becoming reliant on this data. The increasing accuracy, types, and volume of data available in real time enable automation and machine learning that can forecast activity, behaviour, or trends to support decision-making.
  2. Greater demand for citizen agency: Canadians increasingly want and have access to more information, resources, options, and platforms to manage their own health (e.g., mobile apps, direct-to-consumer services, decentralization of care).
  3. Increased precision and personalization in health care delivery: Diagnostic tools and therapies are increasingly able to target individual patients with customized therapies (e.g., individual gene therapy).
  4. Increased product complexity: Increasingly complex products do not fit well within conventional product classifications and standards (e.g., 3D printing).
  5. Evolving methods for production and distribution: In some cases, manufacturers and supply chains are becoming more distributed, challenging the current framework governing production and distribution of health products.
  6. The ways in which evidence is collected and used are changing: The processes around new drug innovation, research and development, and designing clinical trials are evolving in ways that are more flexible and adaptive.

With these key drivers in mind, the Department selected the following six emerging technologies for further investigation to better understand how the health product space is evolving:

  1. Artificial intelligence, including activities such as machine learning, neural networks, natural language processing, and robotics.
  2. Advanced cell therapies, such as individualized cell therapies tailor-made to address specific patient needs.
  3. Big data, from sources such as sensors, genetic information, and social media that are increasingly used to inform patient and health care practitioner decisions.
  4. 3D printing of health products (e.g., implants, prosthetics, cells, tissues).
  5. New ways of delivering drugs that bring together different product lines and methods (e.g., nano-carriers, implantable devices).
  6. Gene editing, including individualized gene therapies that can assist in preventing and treating certain diseases.

Next, to test the drivers identified and further investigate emerging technologies, the Department consulted key organizations and thought leaders across the country with expertise in health innovation. To this end, Health Canada held seven workshops with over 140 representatives from industry associations, small-to-medium sized enterprises and start-ups, larger multinational companies, investors, researchers, and clinicians in Ottawa, Toronto, Montreal, and Vancouver. [emphases mine]

The ‘outocme’ report, ‘What we heard …’, is well worth reading in its entirety; it’s about 9 pp.

I have one comment, ‘stakeholders’ don’t seem to include anyone who isn’t “from industry associations, small-to-medium sized enterprises and start-ups, larger multinational companies, investors, researchers, and clinician” or from “Ottawa, Toronto, Montreal, and Vancouver.” Aren’t the rest of us stakeholders?

Innovating risk analysis

This line in the report caught my eye (from Health Canada’s Toward a strengthened Assisted Human Reproduction Act ; A Consultation with Canadians on Key Policy Proposals webpage),

There is increasing need to enable innovation in a flexible, risk-based way, with appropriate oversight to ensure safety, quality, and efficacy. [emphases mine]

It reminded me of the 2019 federal budget (from my March 22, 2019 posting). One comment before proceeding, regulation and risk are tightly linked and, so, by innovating regulation they are by exttension alos innovating risk analysis,

… Budget 2019 introduces the first three “Regulatory Roadmaps” to specifically address stakeholder issues and irritants in these sectors, informed by over 140 responses [emphasis mine] from businesses and Canadians across the country, as well as recommendations from the Economic Strategy Tables.

Introducing Regulatory Roadmaps

These Roadmaps lay out the Government’s plans to modernize regulatory frameworks, without compromising our strong health, safety, and environmental protections. They contain proposals for legislative and regulatory amendments as well as novel regulatory approaches to accommodate emerging technologies, including the use of regulatory sandboxes and pilot projects—better aligning our regulatory frameworks with industry realities.

Budget 2019 proposes the necessary funding and legislative revisions so that regulatory departments and agencies can move forward on the Roadmaps, including providing the Canadian Food Inspection Agency, Health Canada and Transport Canada with up to $219.1 million over five years, starting in 2019–20, (with $0.5 million in remaining amortization), and $3.1 million per year on an ongoing basis.

In the coming weeks, the Government will be releasing the full Regulatory Roadmaps for each of the reviews, as well as timelines for enacting specific initiatives, which can be grouped in the following three main areas:

What Is a Regulatory Sandbox? Regulatory sandboxes are controlled “safe spaces” in which innovative products, services, business models and delivery mechanisms can be tested without immediately being subject to all of the regulatory requirements.
– European Banking Authority, 2017

Establishing a regulatory sandbox for new and innovative medical products
The regulatory approval system has not kept up with new medical technologies and processes. Health Canada proposes to modernize regulations to put in place a regulatory sandbox for new and innovative products, such as tissues developed through 3D printing, artificial intelligence, and gene therapies targeted to specific individuals. [emphasis mine]

Modernizing the regulation of clinical trials
Industry and academics have expressed concerns that regulations related to clinical trials are overly prescriptive and inconsistent. Health Canada proposes to implement a risk-based approach [emphasis mine] to clinical trials to reduce costs to industry and academics by removing unnecessary requirements for low-risk drugs and trials. The regulations will also provide the agri-food industry with the ability to carry out clinical trials within Canada on products such as food for special dietary use and novel foods.

Does the government always get 140 responses from a consultation process? Moving on, I agree with finding new approaches to regulatory processes and oversight and, by extension, new approaches to risk analysis.

Earlier in this post, I asked if someone had a budget for public relations/promotion. I wasn’t joking. My March 22, 2019 posting also included these line items in the proposed 2019 budget,

Budget 2019 proposes to make additional investments in support of the following organizations:
Stem Cell Network: Stem cell research—pioneered by two Canadians in the 1960s [James Till and Ernest McCulloch]—holds great promise for new therapies and medical treatments for respiratory and heart diseases, spinal cord injury, cancer, and many other diseases and disorders. The Stem Cell Network is a national not-for-profit organization that helps translate stem cell research into clinical applications and commercial products. To support this important work and foster Canada’s leadership in stem cell research, Budget 2019 proposes to provide the Stem Cell Network with renewed funding of $18 million over three years, starting in 2019–20.

Genome Canada: The insights derived from genomics—the study of the entire genetic information of living things encoded in their DNA and related molecules and proteins—hold the potential for breakthroughs that can improve the lives of Canadians and drive innovation and economic growth. Genome Canada is a not-for-profit organization dedicated to advancing genomics science and technology in order to create economic and social benefits for Canadians. To support Genome Canada’s operations, Budget 2019 proposes to provide Genome Canada with $100.5 million over five years, starting in 2020–21. This investment will also enable Genome Canada to launch new large-scale research competitions and projects, in collaboration with external partners, ensuring that Canada’s research community continues to have access to the resources needed to make transformative scientific breakthroughs and translate these discoveries into real-world applications.

Years ago, I managed to find a webpage with all of the proposals various organizations were submitting to a government budget committee. It was eye-opening. You can tell which organizations were able to hire someone who knew the current government buzzwords and the things that a government bureaucrat would want to hear and the organizations that didn’t.

Of course, if the government of the day is adamantly against or uninterested, no amount of persusasion will work to get your organization more money in the budget.

Finally

Reluctantly, I am inclined to explore the topic of emerging technologies such as gene-editing not only in the field of agriculture (for gene-editing of plants, fish, and animals see my November 28, 2018 posting) but also with humans. At the very least, it needs to be discussed whether we choose to participate or not.

If you are interested in the arguments against changing Canada’s prohibition against gene-editing of humans, there’s an Ocotber 2, 2017 posting on Impact Ethics by Françoise Baylis, Professor and Canada Research Chair in Bioethics and Philosophy at Dalhousie University, and Alana Cattapan, Johnson Shoyama Graduate School of Public Policy at the University of Saskatchewan, which makes some compelling arguments. Of course, it was written before the CRISPR twins (my November 28, 2018 posting).

Recaliing CRISPR Therapeutics (mentioned by Gierczak), the company received permission to run clinical trials in the US in October 2018 after the FDA (US Food and Drug Administration) lifted an earlier ban on their trials according to an Oct. 10, 2018 article by Frank Vinhuan for exome,

The partners also noted that their therapy is making progress outside of the U.S. They announced that they have received regulatory clearance in “multiple countries” to begin tests of the experimental treatment in both sickle cell disease and beta thalassemia, …

It seems to me that the quotes around “multiple countries” are meant to suggest doubt of some kind. Generally speaking, company representatives make those kinds of generalizations when they’re trying to pump up their copy. E.g., 50% increase in attendance  but no whole numbers to tell you what that means. It could mean two people attended the first year and then brought a friend the next year or 100 people attended and the next year there were 150.

Despite attempts to declare personalized medicine as having arrived, I think everything is still in flux with no preordained outcome. The future has yet to be determined but it will be and I , for one, would like to have some say in the matter.

Patents as weapons and obstacles

I’m going to start with the phones and finish with the genes. The news article titled Patents emerge as significant tech strategy by Janet I. Tu featured Oct. 27, 2011 on physorg.com provides some insight into problems with  phones and patents,

It seems not a week goes by these days without news of another patent battle or announcement: Microsoft reaching licensing agreements with various device manufacturers. Apple and various handset manufacturers filing suits and countersuits. Oracle suing Google over the use of Java in Android.

After Microsoft and Samsung announced a patent-licensing agreement last month involving Google’s Android operating system, Google issued a statement saying, in part: “This is the same tactic we’ve seen time and again from Microsoft. Failing to succeed in the smartphone market, they are resorting to legal measures to extort profit from others’ achievements and hinder the pace of innovation.”

Microsoft’s PR chief Frank Shaw shot back via Twitter: “Let me boil down the Google statement … from 48 words to 1: Waaaah.”

This was Microsoft’s PR chief??? I do find this to be impressive,but not in a good way. Note: Tu’s article was originally published in The Seattle Times. [Dec.17.11: I’ve edited my original sentence to make the meaning clearer, i. e., I changed it from ‘I don’t find this to be impressive …]

My Sept. 27, 2011 posting focused on the OECD (Organization for Economic Cooperation and Development) and their Science Technology and Industry 2011 Scorecard where they specifically name patenting practices as a worldwide problem for innovation. As both the scorecard and Tu note (from the Tu article),

… technology companies’ patent practices have evolved from using them to defend their own inventions to deploying them as a significant part of competitive strategies …

Tu notes,

Microsoft says it’s trying to protect its investment in research and development – an investment resulting in some 32,000 current and 36,500 pending patents. [emphasis mine] It consistently ranks among the top three computer-software patent holders in the U.S.

One reason these patent issues are being negotiated now is because smartphones are computing devices with features that “are generally in the sweet spot of the innovations investments Microsoft has made in the past 20 years,” said Microsoft Deputy General Counsel Horacio Gutierrez.

There’s no arguing Microsoft is gaining a lot strategically from its patents: financially, legally and competitively.

Royalties from Android phones have become a fairly significant revenue stream.

Investment firm Goldman Sachs has estimated that, based on royalties of $3 to $6 per device, Microsoft will get about $444 million in fiscal year 2012 from Android-based device makers with whom it has negotiated agreements.

Some think that estimate may be low.

Microsoft is not disclosing how much it gets in royalties, but Smith, the company’s attorney, has said $5 per device “seems like a fair price.”

Various tech companies wield patents also to slow down competitors or to frustrate, and sometimes stop, a rival from entering a market. [emphases mine]

It’s not just one industry sector either. Another major player in this ‘patenting innovation to death game’ is the health care industry. Mike Masnick in his Oct. 28, 2011 Techdirt posting (Deadly Monopolies: New Book Explores How Patenting Genes Has Made Us Less Healthy) notes,

A few years ago, David Koepsell, came out with the excellent book, Who Owns You?, with the subtitle, “The corporate gold rush to patent your genes.” It looks like there’s now a new book [Deadly Monopolies] out exploring the same subject, by medical ethicist Harriet Washington.

NPR (National Public Radio) highlights this story in their feature on  Washington’s book,

Restrictive patents on genes prevent competition that can keep the medical cost of treatment down, says Washington. In addition to genes, she also points to tissue samples, which are also being patented — sometimes without patients’ detailed knowledge and consent. Washington details one landmark case in California in which medically valuable tissue samples from a patient’s spleen were patented by a physician overseeing his treatment for hairy-cell leukemia. The physician then established a laboratory to determine whether tissue samples could be used to create various drugs without informing the patient.

“[The patient] was told that he had to come to [the physician’s] lab for tests … in the name of vigilance to treat his cancer and keep him healthy,” says Washington.

The patient, a man named John Moore, was never told that his discarded body parts could be used in other ways. He sued his doctor and the University of California, where the procedure took place, for lying to him about his tissue — and because he did not want to be the subject of a patent. The case went all the way to the California Supreme Court, where Moore lost. In the decision, the court noted that Moore had no right to any share of the profits obtained from anything developed from his discarded body parts.

According to the webpage featuring Deadly Monopolies on the NPR website, this state of affairs is due to a US Supreme Court ruling made in 1980 where the court ruled,

… living, human-made microorganisms could be patented by their developers. The ruling opened the gateway for cells, tissues, genetically modified plants and animals, and genes to be patented.

I gather the US Supreme Court is currently reconsidering their stance on patents and genes. (As for Canada, we didn’t take that route with the consequence that it is not possible to patent a gene or tissue culture here. Of course, things could change.)