As scientists push for stronger protections for intelligent marine animals, a new generation of Taiwanese biotech startups is developing organ-on-a-chip technology that could transform drug testing — and dramatically reduce reliance on laboratory animals.

Last April, the Ministry of Agriculture received an unusual request through its public email service.

Could the Ministry, the message asked, amend the Animal Protection Act to grant laboratory cephalopods the same protections afforded to vertebrates — animals with backbones, such as mammals and birds? Cephalopods, a class of marine animals that includes octopuses, cuttlefish, and squid, have in recent years gained a reputation for remarkable intelligence.

The author of that email was Chiao Chuan-chin, a distinguished professor of life sciences at National Tsing Hua University (NTHU) in Hsinchu. A few days later, the Ministry responded with a politely worded rejection. Changing the law, officials wrote, would require broad public discussion and consensus. The email closed on an incongruously cheerful note: “Wish you good health and safety!”

Undeterred, Chiao wrote again, repeating the request.

Once again came a courteous rebuff, though this time tinged with a hint of impatience. “You have again suggested that cephalopods be included in the Animal Protection Act… Please refer to the previous letter for relevant content,” it read. The sign-off, though, still wished Chiao “good health and safety!”

Refusing to give up, Chiao sent his request a third time. He wasn’t surprised when another rejection arrived in his inbox, directing him back to the Ministry’s previous replies, thanking him for his concern for animal protection and — once again — wishing him “good health and safety!”

Cuttlefish can feel pain

Article 15 of Taiwan’s Animal Protection Act rules that researchers using vertebrates for lab tests should follow certain guidelines to avoid unnecessary pain and loss of life: Their use should be avoided whenever possible, the number of animals tested kept to the minimum necessary, and every effort made to reduce pain and harm. In Taiwan, none of these safeguards apply to cephalopods, which are classified as invertebrates.

Chiao knows his cuttlefish. He has spent more than 25 years studying the behavior of the curious marine mollusk and is convinced — as are many scientists and several governments around the world — that cephalopods are sentient, capable of feeling pain, and deserving of stronger protections.

Working with scientists overseas, Chiao injected cuttlefish with acetic acid and observed that they groomed the injection site — behavior interpreted as an attempt to soothe pain — but stopped or reduced the response after the area was treated with an anesthetic. He co-wrote a paper on the findings, published in a 2022 issue of Biology, an open-access life sciences journal.

“If we know this animal can suffer pain then we have to do something,” Chiao says. “We can’t just pretend they don’t suffer.”

Some countries have already taken note. Since 2013, the EU has afforded captive cephalopods in laboratories the same protections as vertebrates. In the United States, there is similar guidance, though it is not yet mandatory. As the Ministry’s replies to Chiao make clear, that conversation has not even started in Taiwan.

Human organs on a tiny chip

Even so, Taiwan is making rapid progress in a field that could prove consequential for the welfare of laboratory animals. In recent years, research groups at the country’s leading universities have spun off a handful of start-ups entering the global organs-on-a-chip (OoC) sector — a technology that could reduce, or potentially eliminate, the need for animal testing altogether.

Traditionally, drug discovery begins with in vitro testing, in which human cells are exposed to a pharmaceutical compound in a petri dish. Once a promising candidate is identified, it’s then tested in animals to assess efficacy and toxicity. The process can take a decade or more and carries a failure rate exceeding 90%, meaning most drugs either prove ineffective or produce unacceptable side effects. It also requires the use of large numbers of animals, many of which are subjected to disease and injury during testing.

“There are two problems with the current system — it takes too long and the vast majority of drugs don’t work,” explains Hsu Yu-hsiang, an associate professor with National Taiwan University’s (NTU) Institute of Applied Mechanics. Hsu, who has been involved in OoC research for the past 15 years, runs a laboratory developing OoC systems and devices.

In its simplest form, an OoC device is a thumb-sized piece of silicone or another biocompatible polymer (similar to the material used in contact lenses) on which living human cells are cultured over days or weeks to form tissue resembling parts of a lung, heart, gut, or kidney. Tiny channels within the chip allow fluids to circulate continuously, mimicking the blood flow and pressure changes found in the human body.

OoC technology can trump traditional drug trials in both time and accuracy. Automated OoC drug trials allow tens of thousands of experiments to be conducted simultaneously, accelerating results. Because the systems use living human tissue, they can offer greater predictive accuracy than animal testing, in which drugs that appear safe in laboratory animals may prove ineffective or cause serious side effects in humans. The reverse can also occur: treatments beneficial to people may be discarded because they are toxic to animals, meaning some potential therapies are never pursued. In addition, OoC systems more closely replicate conditions within the human body than conventional in vitro methods.

Hsu notes that using OoCs to test drugs replicate the way the body delivers them — through blood vessels. “Our body doesn’t just soak in the drug, it gets delivered by vessels,” he says. “[In] organ-on-a-chip technology, we try to mimic as closely as we can what really happens in the body.”

Hsu’s laboratory in NTU’s Gongguan campus is packed with gas tanks and state-of-the-art fluorescent microscopes. In a lab inside that lab is where the magic happens. Here the OoCs are fabricated, seeded with living human cells, dosed with drugs, and then stored in refrigerator-like incubators.

This inner lab’s environment must be strictly controlled, incuding humidity, temperature, and oxygen and carbon dioxide concentrations. It’s such a delicate process that anyone who enters must don personal protective equipment (gowns, masks, goggles and/or face shields — familiar sights from the Covid-19 pandemic). The air pressure is kept below atmospheric levels to prevent anything from escaping in the event of a leak.

The rise of OoC in Taiwan

OoC technology has been around for several decades, Hsu explains, but it was the pandemic that truly kickstarted the technology.

“Scientists couldn’t find out how Covid was infecting the human body using animal models because animals do not have the same receptor cells as humans,” he says. “But when they used a human lung-on-a-chip they discovered the specific receptor.” That breakthrough ultimately helped in the development of Covid-19 vaccines.

The technology has shown such promise that several governments have launched initiatives to promote its wider adoption alongside other emerging solutions (known as New Approach Methodologies, or NAMs, in the sector’s jargon) such as AI.

In April 2025, the U.S. Food and Drug Administration (FDA) launched a roadmap to pursue NAMs and make animal testing the “exception rather than the norm” for preclinical research within three to five years. And in November last year, the UK published its £75 million (about US$100 million) plan to phase out certain animal tests by adopting alternative methods, with OoCs top of the list.

Taiwan is catching up. “There has been a big push [in Taiwan] in the past two or three years because all the other countries have started to do this,” says Hsu.

While the government has been investing in OoC research and development, leading scientists in the field have been scaling up their university projects into commercial ventures. One of the largest is Pythia Biotech, a startup founded in 2022 by a mechanical engineering professor at NTHU and a research doctor at Taipei Medical University. It provides organ-on-chip and personalized drug screening with a focus on cancer treatments.

Anivance AI, founded in 2024 by Chen Guan-yu, a professor at National Yang Ming Chiao Tung University’s Institute of Biomedical Engineering, has developed around 25 OoCs for different organ and disease models. Its focus is on making automated OoC systems that integrate AI into both drug test design and analysis of results.

“We want our system to be easy to operate… so it’s like ‘plug-and-play’,” explains Chen. In addition to clients in Taiwan, Chen says his company, which employs more than 40 people, has expanded into the Japan, Singapore, South Korea, the UK, and the United States — all within just a year and a half.

He founded Anivance, he says, because he was driven by a simple question: ”Why are we making human health decisions based primarily on non-human biology? Organ-on-a-chip offers a more human-relevant path [going] forward.”

Chen says the sector holds strong growth potential in Taiwan, citing the island’s semiconductor industry and related technical expertise.

“Taiwan’s strengths lie in semiconductor engineering, precision manufacturing, and biomedical research talent — all essential for industrializing organ-on-a-chip systems,” he says. That means it will be quicker, cheaper, and easier to produce what’s needed.

For now, however, one major obstacle remains: standardization.

“There is a lack of international standards for OoC,” says Hsu. “Everyone needs to agree on the geometry [of the chip system] and test protocols.” Without standardization, drug regulatory bodies, such as the FDA and European Medicines Agency (EMA), won’t accept drug trial results using OoCs instead of animal tests.

Taiwan needs to develop a roadmap for standardization so that chips and systems built locally can be regulated domestically and recognized by regulatory authorities overseas, argues Chen. “We would like stronger regulatory alignment programs and better connections to global frameworks such as the FDA and EMA.”

Human-on-a-chip

In addition to vascular models, NTU professor Hsu’s lab develops heart, tumor, artery, and thrombosis chips. He shows me a video of heart chips in which the cells have been cultured in grooves carved in concentric rings. Under magnification, the cells beat just like a real heart, resembling the motion seen in fetal ultrasound images. The circular grooves, Hsu explains, act like guardrails, helping the heart cells line up and beat more synchronously, closer to a real heartbeat.

In other labs across Taiwan and around the world, engineers have put just about every human organ you can think of on a chip. There are chips for neurons, liver, lungs, kidneys, and bone tissue — even an eye-on-a-chip.

“The eye-on-a-chip even has a blinking effect,” says Hsu with a smile. “It can be used to investigate how to repair a damaged cornea.” Some researchers have designed larger chips to link up several organs on the same device.

The ultimate goal is to place all major organs on a single chip.

“The dream is a human-on-a-chip,” says Hsu. One of the main barriers to achieving this goal is determining how large a portion of each organ must be represented so that the system responds in ways comparable to a living person.

Perhaps even more significant than having a human-on-a-chip is using the technology for precision medicine, says Hsu. Precision medicine means tailoring the treatment to the individual patient.

“If you have a disease, we could harvest your cells and then put them on a chip and test [drugs] on them,” Hsu explains. This would be especially powerful for cancer treatments. “We could find the dose and the sequence that’s safe and effective for that individual.”

The science can only continue to improve, Anivance AI’s Chen says. He predicts that, like successive generations of smartphones, OoC technology will steadily become more advanced over time.

Improving soft power with cephalopods

When asked whether OoC could one day replace animal testing entirely, Hsu strikes a cautiously optimistic note.

“I cannot say, but I hope so,” he says, adding: “The reason why I got into this is because I originally wanted to save some animals.”

Chen urges patience. OoC will “not immediately” replace animal testing. “However, it can significantly reduce reliance on animal models, especially in early screening and toxicity studies.” He adds that “its role will expand as regulatory validation increases.”

Back in Hsinchu, Chiao — who does not conduct medical experiments on his cuttlefish — keeps the animals in tanks with opaque sides to minimize stress, allowing them to see only those who peer over the edge.

The palm-sized creatures are floating gently about their tanks, and I am taken aback by their remarkably large and intelligent-looking eyes. Apart from pain response, his team studies cuttlefish emotions, social interactions, and sleep behavior. The latter is tracked using baby monitors (again to minimize stress). While asleep, their skin plays a through kaleidoscope of changing colors, patterns and textures, something scientists say is akin to REM sleep in humans.

“They are smart and lovely animals,” Chiao says fondly.

He says he believes that Taiwan could improve its soft power by changing the law to align with the EU’s inclusion of cephalopods to the protected lab animal list.

“We would be the first in Asia [to do so],” he says. “Just like same gender marriage, Taiwan would be the first. I would be very proud of that.”