Please help us feed hungry people by improving  dairy cattle in developing countries.

 12/8/2025  Michael O’Boyle  5 min read

A multidisciplinary collaboration at the University of Illinois Urbana-Champaign has received a $2.5 million award from the National Institutes of Health to develop technology for assessing embryo viability for in vitro fertilization.

The project will combine the microscopy and artificial intelligence expertise of Illinois Grainger Engineering electrical and computer engineering research assistant professor Haohua Tu and associate professor Alexander Gerhard Schwing, respectively, with the embryo production and developmental biology expertise of Illinois animal sciences professor Matthew Wheeler. Researchers will combine the “gentle,” label-free microscopy designed to minimize tissue damage developed by Tu with artificial intelligence developed by Schwing to analyze bovine embryos produced by Wheeler and predict viability rates when transferred in utero.

“In our work, we showed that microscopy based on nonlinear optical processes – a technology that is decades old – can be leveraged to give high-resolution images of biological tissue without damaging it,” Tu said. “For the technology’s entire existence, researchers have assumed that the nonlinear, or multi-photon, absorption damages the molecules it tries to image because of the high energies involved. Our group has shown this is not the case, and the risk of damage can be actively minimized.”

“The idea of the NIH grant is using this microscopy technique to improve in vitro fertilization, since it could allow embryo viability to be assessed before it is implanted,” Wheeler added. “We’re going to use it to study embryos implanted in cows – a good model species for human pregnancy – and see if it can predict which fetuses come to term. If successful, it would be very promising for human IVF.”

This work is made possible by Tu’s development of a nonlinear imaging protocol that achieves high-resolution images of biological tissue while minimizing the risk of tissue damage. He and his collaborators demonstrated that nonlinear, four-photon absorption and emission – the mechanism that makes high-quality imaging possible – is not responsible for molecular-level tissue damage as was previously assumed. The researchers found that low-energy linear absorption is the main mechanism for damage and showed that it is minimized by rapidly scanning light pulses across the sample instead of focusing light on one spot for extended lengths of time.

“We tested our system on several biological systems, including rat brain slices, nematode worms and even chicken breast tissue,” Tu said. “All of our studies support the hypothesis that linear absorption is the primary damage mechanism and can be mitigated by quickly scanning light across the entire sample. This way, the molecule has time to relax between absorption events.”

These results have been published in the journal Advanced Science.

This work formed the basis for the NIH proposal submitted by Tu and Wheeler, the latter of whom is also affiliated with the Department of Bioengineering in the Illinois Grainger Engineering. They believe that this scanning microscopy technique could allow for high-quality images of bovine embryos with minimal toxicity.

“The challenge with trying to image sperm, ova and embryos is that it’s hard to do without disturbing or damaging the system,” Wheeler said. “We took an interest in Professor Tu’s work both because it was shown to minimize damage to biological tissue and because it’s label free. There are no dyes or indicators to worry about disrupting fertilization and development.”

Wheeler and his colleagues will use Tu’s imaging system to monitor implanted bovine embryos as they develop in vitro. They believe that Schwing’s computer vision AI can be used to identify signals that indicate embryo viability, an otherwise difficult task.

“The only available tool for assessing embryo viability right now is the tincture of experience,” Wheeler said. “People spend years practicing it and developing an eye for it by looking at the embryos under an optical microscope. The idea is to combine the new microscopy with AI to detect the parameters that our eyes can’t.”

Wheeler’s animal sciences research group will fertilize 2,500 bovine embryos. Half will be scanned using Tu’s microscopy system, and the other half will be assessed by eye. They will then be shipped to California where they will be implanted in cows. The researchers hope that the combination of nonlinear microscopy and AI will outperform human examination when predicting which implants lead to birth.

Illinois Grainger Engineering Affiliations

Haohua Tu is an Illinois Grainger Engineering research assistant professor of electrical and computer engineering in the Department of Electical and Computer Engineering.

Alexander Gerhard Schwing is and Illinois Grainger Engineering associate professor of electrical and computer engineering in the Department of Electrical and Computer Engineering. He is also affiliated with the Siebel School of Computing and Data Science and the Coordinated Science Laboratory. He holds a W.J. “Jerry” Sanders III – Advanced Micro Devices, Inc. Faculty Fellow appointment.

Matthew B. Wheeler is an Illinois professor of biotechnology and developmental biology in the Department of Animal Sciences. He is also affiliated with the Department of Bioengineering, the Department of Veterinary Clinical Medicine, the Carl R. Woese Institute for Genomic Biology, the Beckman Institute for Advanced Science and Technology and the Carle Illinois College of Medicine.

CHAMPAIGN, Ill. — Three faculty members at the University of Illinois Urbana-Champaign have been named 2024 Fellows of the American Association for the Advancement of Science, the worldʼs largest general scientific society. Animal sciences professor Isaac Cann, chemistry professor Stephan Link and animal sciences professor Matthew B. Wheeler are among the 471 scientists, engineers and innovators chosen by their peers for their scientifically and socially distinguished achievements.

Dr. Matthew B. Wheeler with AAAS President Dr. Theresa A. Maldonado at the AAAS Fellows Reception in Washington, DC in June 2025.

Wheelerʼs research focuses on enhancing global food supply and animal agriculture through biotechnology, especially through livestock reproduction and genetics. His work has implications for human health, not only in addressing hunger and malnutrition, but also in developing better models and tissue-based techniques for studying disease. He was recognized “for distinguished contributions to the field of reproductive biology, particularly the use of transgenic and other biotechnological approaches to improve livestock and animal models of human disease.” Wheeler also is affiliated with the Beckman Institute for Advanced Science and Technology, the Carl R. Woese Institute for Genomic Biology, the Carle Illinois College of Medicine, The Grainger College of Engineering and the College of Veterinary Medicine at the U. of I.

CHAMPAIGN, Ill. — The University of Illinois Urbana-Champaign each year presents Campus Awards for Excellence in Instruction to exceptional faculty and staff members, graduate teaching assistants and advisors campuswide. This year’s recipients are being honored at a ceremony. 

Awardees are cited for sustained excellence and innovation in undergraduate and graduate teaching, undergraduate and graduate advising and mentoring, online teaching and research guidance. The Office of the Provost sponsors the awards.

Matthew B. Wheeler

Photo by Michelle Hassel

Matthew B. Wheeler, a professor of animal sciences, and Qian Chen, a professor of materials science and engineering, are recipients of the Campus Award for Excellence in Graduate Student Mentoring, presented to tenure-system or specialized faculty members at Illinois who have taught on the Urbana-Champaign campus for at least five years. According to their nominators:

Wheeler adopts a hands-on approach to graduate teaching and mentoring. The graduate-level course he taught for many years on advanced animal reproductive physiology allowed students to experience outside the classroom what they learned in lectures. Wheeler is a quintessential professor for a land-grant university, training the next generation of scientists while seamlessly connecting his research program with teaching and outreach activities. He has sustained dedication and enthusiasm for graduate education in reproductive biology throughout his career.

March 13, 2024 Lauren Quinn ANSC / Health / Livestock / Genetics

Matt Wheeler, pictured, helped develop the first transgenic cow to produce human insulin in her milk.

An unassuming brown bovine from the south of Brazil has made history as the first transgenic cow capable of producing human insulin in her milk. The advancement, led by researchers from the University of Illinois Urbana-Champaign and the Universidade de Sao Paulo, could herald a new era in insulin production, one day eliminating drug scarcity and high costs for people living with diabetes.

“Mother Nature designed the mammary gland as a factory to make protein really, really efficiently. We can take advantage of that system to produce a protein that can help hundreds of millions of people worldwide,” said Matt Wheeler, professor in the Department of Animal Sciences, part of the College of Agricultural, Consumer and Environmental Sciences (ACES) at U. of I. He is also affiliated with the Carle Illinois College of Medicine, The Grainger College of Engineering, the College of Veterinary Medicine, the Beckman Institute, and the Carl R. Woese Institute for Genomic Biology.

Wheeler is lead author on a new Biotechnology Journal study describing the development of the insulin-producing cow, a proof-of-concept achievement that could be scaled up aWer additional testing and FDA approval. Wheelerʼs colleagues in Brazil inserted a segment of human DNA coding for proinsulin — the protein precursor of the active form of insulin — into cell nuclei of 10 cow embryos. These were implanted in the uteruses of normal cows in Brazil, and one transgenic calf was born. Thanks to updated genetic engineering technology, the human DNA was targeted for expression — the process whereby gene sequences are read and translated into protein products — in mammary tissue only.

“In the old days, we used to just slam DNA in and hope it got expressed where you wanted it to,” Wheeler said. “We can be much more strategic and targeted these days. Using a DNA construct specific to mammary tissue means thereʼs no human insulin circulating in the cowʼs blood or other tissues. It also takes advantage of the mammary glandʼs capabilities for producing large quantities of protein.”

When the cow reached maturity, the team unsuccessfully attempted to impregnate her using standard artificial insemination techniques. Instead, they stimulated her first lactation using hormones. The lactation yielded milk, but a smaller quantity than would occur after a successful pregnancy. Still, human proinsulin and, surprisingly, insulin were detectable in the milk.

“Our goal was to make proinsulin, purify it out to insulin, and go from there. But the cow basically processed it herself. She makes about three to one biologically active insulin to proinsulin,” Wheeler said. “The mammary gland is a magical thing.”

The insulin and proinsulin, which would need to be extracted and purified for use, were expressed at a few grams per liter in the milk. But because the lactation was induced hormonally and the milk volume was smaller than expected, the team canʼt say exactly how much insulin would be made in a typical lactation.

Conservatively, Wheeler says if a cow could make 1 gram of insulin per liter and a typical Holstein makes 40 to 50 liters per day, thatʼs a lot of insulin. Especially since the typical unit of insulin equals 0.0347 milligrams. “That means each gram is equivalent to 28,818 units of insulin,” Wheeler said. “And that’s just one liter; Holsteins can produce 50 liters per day. You can do the math.”

The team plans to re-clone the cow, and is optimistic theyʼll achieve greater success with pregnancy and full lactation cycles in the next generation. Eventually, they hope to create transgenic bulls to mate with the females, creating transgenic offspring that can be used to establish a purpose-built herd. Wheeler says even a small herd could quickly outcompete existing methods — transgenic yeast and bacteria — for producing insulin, and could do so without having to create highly technical facilities or infrastructure.

“With regard to mass-producing insulin in milk, youʼd need specialized, high-health-status facilities for the cattle, but itʼs nothing too out of the ordinary for our well-established dairy industry,” Wheeler said. “We know what weʼre doing with cows.”

An efficient system to collect and purify insulin products would be needed, as well as FDA approval, before transgenic cows could supply insulin for the worldʼs diabetics. But Wheeler is confident that day is coming. “I could see a future where a 100-head herd, equivalent to a small Illinois or Wisconsin dairy, could produce all the insulin needed for the country,” he said. “And a larger herd? You could make the whole worldʼs supply in a year.

The study, “Human proinsulin production in the milk of transgenic cattle,” is published in Biotechnology Journal [DOI: 10.1002/biot.202300307]. The research was supported by the National Council for Scientific and Technological Development, CNPq [grant no. 245886/2012-5]; the University of Northern Parana, UNOPAR; and the USDA National Institute of Food and Agricultureʼs Multistate Research Fund [project no. W-4171].