When Stephane Castel first met with a group of Maori and other Pacific Islanders in New Zealand to talk about his pharmaceutical company’s plans for genetic research, locals feared he might be trying to profit from community members’ genes without thinking too much.
Instead, Dr. Castel and his colleagues explained, the goal was to strike an unconventional deal: in exchange for trusting them with their genetic heritage, participating communities would receive a share of the company’s revenues. Dr. Castel also promised not to patent any genes – as many other companies had done – but rather the drugs his company would develop from the partnership.
“Many people told us it was a crazy idea and that it wouldn’t work,” Dr. Castel said. But five years after that first conversation at an Indigenous health research conference in March 2019, Dr Castel’s move is starting to pay off for both parties.
On Tuesday, his company, Seattle-based Variant Bio, announced a $50 million collaboration with pharmaceutical company Novo Nordisk to develop drugs for metabolic disorders, including diabetes and obesity, using data collected by indigenous populations. Variant Bio will distribute a portion of these funds to communities it has worked with in nine countries or territories, including Māori, and will seek to make all medicines resulting from its work available to those communities at an affordable price.
Indigenous genetics experts said the deal was a positive step for an industry that has been plagued by allegations of exploitation and a chasm of mistrust.
“In the past, researchers went into indigenous communities with empty promises,” said Krystal Tsosie, a geneticist and bioethicist at Arizona State University who runs a nonprofit genetic repository for indigenous peoples. “Variant Bio is the only company, as far as I know, that has explicitly talked about benefit sharing as part of their mission.”
The idea for Variant Bio was born in a Manhattan bar in August 2018 over drinks between Dr. Castel and Kaja Wasik, who had become friends during their graduate studies in genetics at Cold Spring Harbor Laboratory on Long Island.
Even though their laboratory research kept them under the glare of fluorescent lights, they shared a passion for international travel, which they indulged on backpacking trips together in Peru and Chile. They dreamed of building a company that could take them to remote places.
At the time, drugmakers were establishing partnerships with biological repositories such as the UK Biobank, which contains biological samples and medical records from half a million people living in Britain, in order to look for associations between genes and diseases.
But these databases consist mostly of genes from people of European descent.
“What value is there in sequencing the 500,001st British citizen?” Dr. Castel said. “There are only so many insights to be found by studying the same group of people.”
He and Dr. Wasik were most excited about recent discoveries from underrepresented groups, such as the discovery of new genetic variants affecting metabolism that were first identified in Inuit populations in Greenland.
Such variants may be more common, and consequently easier to identify, in historically isolated populations because they confer some functional benefit on people with a certain diet or lifestyle, or simply because of random events in their history. However, they can also serve as promising pharmaceutical targets that will help a broader segment of the global population.
With $16 million in seed funding from Lux Capital, a New York City venture capital firm, Dr. Castel and Dr. Wasik quit their jobs and began working full time on their startup. Dr. Wasik spanned eight countries across Africa, Asia, Europe and the Pacific in the company’s first year of operation, while Dr. Castel, for the most part, diligently built the software platform from his base in the United States.
They enlisted ethics consultants to develop a benefit-sharing model and went on a listening tour. They knew from the beginning that they would have to proceed with caution.
In 2007, a member of the Karitiana tribe in Brazil told the New York Times that his community had been “tricked, deceived and exploited” by scientists who collected their blood and DNA, which was later sold for $85. to sample. Tribe members, who said they were wooed with the promise of medicine, received nothing.
Ten years later, there was still no consensus on the optimal way to conduct such work. To protect themselves from so-called biopiracy, many countries have ratified the Nagoya Protocol under the United Nations Convention on Biological Diversity, which calls for the “equitable sharing of benefits” arising from genetic resources. But the protocol excluded information on the human genome.
During Dr Castel and Dr Wasik’s trip to New Zealand in 2019, researchers and community members were troubled by a previous attempt by US researchers to patent an obesity risk test based on genetic studies conducted in Samoa . The researchers’ universities did not include their Samoan collaborators in the patent application as co-inventors, nor did they have formal benefit-sharing agreements with local institutions. (The patent application was later abandoned, and the researchers said they always intended to share the benefits with their partners.)
One of Variant’s early advisors was Keolu Fox, an outspoken geneticist at the University of California, San Diego, who had been sharply critical of the Samoan research.
“This is an extension of all these other forms of colonialism,” said Dr. Fox, who is Native Hawaiian and joined Dr. Wasik and Dr. Castel on their outreach trip to New Zealand. He believed Variant could lead by example.
In the company’s benefit-sharing program, up to 10% of a project’s budget is allocated to community programs, typically funding local organizations.
For example, as part of its New Zealand-based study into the genetic causes of kidney disease and other metabolic disorders among Māori and other populations of Pacific descent, the company spent $100,000 funding several local health organizations together to scholarships and scientific conferences for indigenous peoples.
“Before Variant came along, we didn’t do it because we couldn’t afford it,” said Tony Merriman, a gout expert at the University of Alabama at Birmingham who has worked with the company on two projects in the Pacific region. .
Dr Merriman said he also appreciated that the company ensured its findings were shared with the community. In French Polynesia, the company’s research encouraged greater access to gout medications after concluding that the local population was not at high risk of a fatal drug reaction as had been seen in some Asian populations.
The new Novo Nordisk agreement kicks off a second, long-term phase of the benefit-sharing program. Communities will share a 4% slice of Variant’s revenue and, if the company is ever sold or goes public, 4% of its net worth. This percentage is comparable to the royalties that universities receive for licensing their patents.