A company called Second Sight made an implant that partially restored vision to people who'd been blind for decades. But when Second Sight pivoted, it stopped servicing its product, leaving many in the dark.
The Argus II uses the implant and a video camera embedded in a special pair of glasses to provide limited vision to those with retinitis pigmentosa, a genetic disease that causes cells in the retina to deteriorate. The camera feeds information to the implant, which sends electrical impulses into the retina to recapitulate what the camera sees. The impulses appear in the Argus II as a 60-pixel grid of blacks, grays and whites in the user’s eye that can render rough outlines of objects and their motion.
Smartphone and computer manufacturers typically stop issuing software upgrades to their devices after two or three years, eventually rendering them bricks. But is the smartphone approach acceptable for a device that helps restore the most crucial sense a human being possesses?
Ross Doerr, a retired disability rights attorney in Maine who received an Argus II in 2019, describes the field of vision as the equivalent of an index card held at arm’s length. Perk often brings objects close to his face to decipher them. Moreover, users must swivel their heads to take in visual data; moving their eyeballs does not work.
Despite its limitations, the Argus II beats the alternative. Perk no longer relies on his guide dog. Doerr was uplifted when he was able to see the outlines of Christmas trees at a holiday show.
“The fairy godmother department sort of reaches out and taps you on the shoulder once in a while,” Doerr says of his implant, which came about purely by chance. A surgeon treating his cataracts was partnered with the son of another surgeon who was implanting the devices, and he was referred.
Doerr had no reason to believe the shower of fairy dust wouldn’t continue. Second Sight held out promises that the Argus II recipients’ vision would gradually improve through upgrades to much higher pixel densities. The ability to recognize individual faces was even touted as a possibility. In the winter of 2020, Doerr was preparing to travel across the U.S. to Second Sight’s headquarters to receive an upgrade. But then COVID-19 descended, and the trip was canceled.
The pandemic also hit Second Sight’s bottom line. Doerr found out about its tribulations only from one of the company’s vision therapists, who told him the entire department was being laid off. Second Sight cut nearly 80% of its workforce in March 2020 and announced it would wind down operations.
Ross Doerr has mostly stopped using his Argus II, the result of combination of fear of losing its assistance from wear and tear and disdain for the company that brought it to market.
Jan Doerr
Second Sight’s implosion left some 350 Argus recipients in the metaphorical dark about what to do if their implants failed. Skeleton staff seem to have rarely responded to queries from their customers, at least based on the experiences of Perk and Doerr. And some recipients have unfortunately returned to the actual dark as well, as reports have surfaced of Argus II failures due to aging or worn-down parts.
Product support for complex products is remarkably uneven. Although the iconic Ford Mustang ceased production in the late 1960s, its parts market is so robust that it’s theoretically possible to assemble a new vehicle from recently crafted components. Conversely, smartphone and computer manufacturers typically stop issuing software upgrades to their devices after two or three years, eventually rendering them bricks. Consumers have accepted both extremes.
But is the smartphone approach acceptable for a device that helps restore the most crucial sense a human being possesses?
Margaret McLean, a senior fellow at the Markkula Center for Applied Ethics at Santa Clara University in California, notes companies like Second Sight have a greater obligation for product support than other consumer product ventures.
“In this particular case, you have a great deal of risk that is involved in using this device, the implant, and the after care of this device,” she says. “You cannot, like with your car, decide that ‘I don’t like my Mustang anymore,’ and go out and buy a Corvette.”
And, whether the Argus II implant works or not, its physical presence can impact critical medical decisions. Doerr’s doctor wanted him to undergo an MRI to assist in diagnosing attacks of vertigo. But the physician was concerned his implant might interfere. With the latest available manufacturer advisories on his implant nearly a decade old, the procedure was held up. Doerr spent months importuning Second Sight through phone calls, emails and Facebook postings to learn if his implant was contraindicated with MRIs, which he never received. Although the cause of his vertigo was found without an MRI, Doerr was hardly assured.
“Put that into context for a minute. I get into a serious car accident. I end up in the emergency room, and I have a tag saying I have an implanted medical device,” he says. “You can’t do an MRI until you get the proper information from the company. Who’s going to answer the phone?”
Second Sight’s management did answer the call to revamp its business. It netted nearly $78 million through a private stock placement and an initial public offering last year. At the end of 2021, Second Sight had nearly $70 million in cash on hand, according to a recent filing with the Securities and Exchange Commission.
And while the Argus II is still touted at length on Second Sight’s home page, it appears little of its corporate coffers are earmarked toward its support. These days, the company is focused on obtaining federal approvals for Orion, a new implant that would go directly into the recipient’s brain and could be used to remedy blindness from a variety of causes. It obtained a $6.4 million grant from the National Institutes of Health in May 2021 to help develop Orion.
Presented with a list of written questions by email, Second Sight’s spokesperson, Dave Gentry of the investor relations firm Red Chip Companies, copied a subordinate with an abrupt message to “please handle.” That was the only response from a company representative. A call to Second Sight acting chief executive officer Scott Dunbar went unreturned.
Whether or not the Orion succeeds remains to be seen. The company’s SEC filings suggest a viable and FDA-approved device is years away, and that operational losses are expected for the “foreseeable future.” Second Sight reported zero revenue in 2020 or 2021.
Moreover, the experiences of the Argus II recipients could color the reception of future Second Sight products. Doerr notes that his insurer paid nearly $500,000 to implant his device and for training on how to use it.
“What’s the insurance industry going to say the next time this crops up?” Doerr asks, noting that the company’s reputation is “completely shot” with the recipients of its implants.
Perk, who made speeches to praise the Argus II and is still featured in a video on the Second Sight website, says he also no longer supports the company.
Jeroen Perk, an investigator for the Dutch customs service, cried for joy after partially regaining his sight, but he no longer trusts Second Sight, the company that provided his implant.
Nanda Perk
Nevertheless, Perk remains highly reliant on the technology. When he dropped an external component of his device in late 2020 and it broke, Perk briefly debated whether to remain blind or find a way to get his Argus II working again. Three months later, he was able to revive it by crowdsourcing parts, primarily from surgeons with spare components or other Argus II recipients who no longer use their devices. Perk now has several spare parts in reserve in case of future breakdowns.
Despite the frantic efforts to retain what little sight he has, Perk has no regrets about having the device implanted. And while he no longer trusts Second Sight, he is looking forward to possibly obtaining more advanced implants from companies in the Netherlands and Australia working on their own products.
Doerr suggests that biotech firms whose implants are distributed globally be bound to some sort of international treaty requiring them to service their products in perpetuity. Such treaties are still applied to the salvage rights for ships that sunk centuries ago, he notes.
“I think that in a global tech economy, that would be a good thing,” says McLean, the fellow at Santa Clara, “but I am not optimistic about it in the near term. Business incentives push toward return on share to stockholders, not to patients and other stakeholders. We likely need to rely on some combination of corporately responsibility…and [international] government regulation. It’s tough—the Paris Climate Accord implementation at a slow walk comes to mind.”
Unlike Perk, Doerr has mostly stopped using his Argus II, the result of combination of fear of losing its assistance from wear and tear and disdain for the company that brought it to market. At 70, Doerr says he does not have the time or energy to hold the company more accountable. And with Second Sight having gone through a considerable corporate reorganization, Doerr believes a lawsuit to compel it to better serve its Argus recipients would be nothing but an extremely costly longshot.
“It’s corporate America at its best,” he observes.
Many women want non-hormonal birth control. A 22-year-old's findings were used to launch a company that could, within the decade, bring a new kind of contraceptive to the marketplace.
Now a scientist with NextVivo, Shrestha is not directly involved in the development of the contraceptive that is based on her research. But, back in 2016 when she was going through her own problems with hormonal contraceptives, she “was very personally invested” in her research project, Shrestha says. She was coping with a long list of negative effects from an implanted hormonal IUD. According to the Mayo Clinic, those can include severe pelvic pain, headaches, acute acne, breast tenderness, irregular bleeding and mood swings. After a year, she had the IUD removed, but it took another full year before all the side effects finally subsided; she also watched her sister suffer the “same tribulations” after trying a hormonal IUD, she says.
For contraceptive use either daily or monthly, Shrestha says, “You want the antibody to be very potent and also cheap.” That was her goal when she launched her study.
Shrestha unshelved antibody research that had been sitting idle for decades. It was in the late 80s that scientists in Japan first tried to develop anti-sperm antibodies for contraceptive use. But, 35 years ago, “Antibody production had not been streamlined as it is now, so antibodies were very expensive,” Shrestha explains. So, they shifted away from birth control, opting to focus on developing antibodies for vaccines.
Over the course of the last three decades, different teams of researchers have been working to make the antibody more effective, bringing the cost down, though it’s still expensive, according to Shrestha. For contraceptive use either daily or monthly, she says, “You want the antibody to be very potent and also cheap.” That was her goal when she launched her study.
The problem
The problem with contraceptives for women, Shrestha says, is that all but a few of them are hormone-based or have other negative side effects. In fact, some studies and reports show that millions of women risk unintended pregnancy because of medical contraindications with hormone-based contraceptives or to avoid the risks and side effects. While there are about a dozen contraceptive choices for women, there are two for men: the condom, considered 98% effective if used correctly, and vasectomy, 99% effective. Neither of these choices are hormone-based.
On the non-hormonal side for women, there is the diaphragm which is considered only 87 percent effective. It works better with the addition of spermicides — Nonoxynol-9, or N-9 — however, they are detergents; they not only kill the sperm, they also erode the vaginal epithelium. And, there’s the non-hormonal IUD which is 99% effective. However, the IUD needs to be inserted by a medical professional, and it has a number of negative side effects, including painful cramping at a higher frequency and extremely heavy or “abnormal” and unpredictable menstrual flows.
The hormonal version of the IUD, also considered 99% effective, is the one Shrestha used which caused her two years of pain. Of course, there’s the pill, which needs to be taken daily, and the birth control ring which is worn 24/7. Both cause side effects similar to the other hormonal contraceptives on the market. The ring is considered 93% effective mostly because of user error; the pill is considered 99% effective if taken correctly.
“That’s where we saw this opening or gap for women. We want a safe, non-hormonal contraceptive,” Shrestha says. Compounding the lack of good choices, is poor access to quality sex education and family planning information, according to the non-profit Urban Institute. A focus group survey suggested that the sex education women received “often lacked substance, leaving them feeling unprepared to make smart decisions about their sexual health and safety,” wrote the authors of the Urban Institute report. In fact, nearly half (45%, or 2.8 million) of the pregnancies that occur each year in the US are unintended, reports the Guttmacher Institute. Globally the numbers are similar. According to a new report by the United Nations, each year there are 121 million unintended pregnancies, worldwide.
The science
The early work on antibodies as a contraceptive had been inspired by women with infertility. It turns out that 9 to 12 percent of women who are treated for infertility have antibodies that develop naturally and work against sperm. Shrestha was encouraged that the antibodies were specific to the target — sperm — and therefore “very safe to use in women.” She aimed to make the antibodies more stable, more effective and less expensive so they could be more easily manufactured.
Since antibodies tend to stick to things that you tell them to stick to, the idea was, basically, to engineer antibodies to stick to sperm so they would stop swimming. Shrestha and her colleagues took the binding arm of an antibody that they’d isolated from an infertile woman. Then, targeting a unique surface antigen present on human sperm, they engineered a panel of antibodies with as many as six to 10 binding arms — “almost like tongs with prongs on the tongs, that bind the sperm,” explains Shrestha. “We decided to add those grabbers on top of it, behind it. So it went from having two prongs to almost 10. And the whole goal was to have so many arms binding the sperm that it clumps it” into a “dollop,” explains Shrestha, who earned a patent on her research.
Suruchi Shrestha works in the lab with a colleague. In 2016, her research on antibodies for birth control was inspired by her own experience with side effects from an implanted hormonal IUD.
UNC - Chapel Hill
The sperm stays right where it met the antibody, never reaching the egg for fertilization. Eventually, and naturally, “Our vaginal system will just flush it out,” Shrestha explains.
“She showed in her early studies that [she] definitely got the sperm immotile, so they didn't move. And that was a really promising start,” says Jasmine Edelstein, a scientist with an expertise in antibody engineering who was not involved in this research. Shrestha’s team at UNC reproduced the effect in the sheep, notes Edelstein, who works at the startup Be Biopharma. In fact, Shrestha’s anti-sperm antibodies that caused the sperm to agglutinate, or clump together, were 99.9% effective when delivered topically to the sheep’s reproductive tracts.
The future
Going forward, Shrestha thinks the ideal approach would be delivering the antibodies through a vaginal ring. “We want to use it at the source of the spark,” Shrestha says, as opposed to less direct methods, such as taking a pill. The ring would dissolve after one month, she explains, “and then you get another one.”
Engineered to have a long shelf life, the anti-sperm antibody ring could be purchased without a prescription, and women could insert it themselves, without a doctor. “That's our hope, so that it is accessible,” Shrestha says. “Anybody can just go and grab it and not worry about pregnancy or unintended pregnancy.”
Her patented research has been licensed by several biotech companies for clinical trials. A number of Shrestha’s co-authors, including her lab advisor, Sam Lai, have launched a company, Mucommune, to continue developing the contraceptives based on these antibodies.
And, results from a small clinical trial run by researchers at Boston University Chobanian & Avedisian School of Medicine show that a dissolvable vaginal film with antibodies was safe when tested on healthy women of reproductive age. That same group of researchers earlier this year received a $7.2 million grant from the National Institute of Health for further research on monoclonal antibody-based contraceptives, which have also been shown to block transmission of viruses, like HIV.
“As the costs come down, this becomes a more realistic option potentially for women,” says Edelstein. “The impact could be tremendous.”
