What is Bioengineering?

Bioengineering is the design, construction, or adaptation of living systems to benefit people and the planet.

To be a bioengineer, you have to be two things at once: an engineer and a biologist. You need to understand mass and energy balances, and also the composition and biochemistry of cells. Working at this interface is challenging, but worth it. No major has the potential to impact the health of people and the planet more than ours.

Why be a bioengineer?

Many of the hardest problems facing humanity are biological. Infectious diseases emerge and spread; our own cells grow uncontrolled during cancer; feeding a growing population requires growing plants sustainably in a changing climate.

Being a bioengineer requires judgment. The same tools that a synthetic biologist uses to synthesize a drug to treat malaria can be used to create a toxin. The same sequencing data that guides a diagnosis or allows for statistical inference about how mutations cause disease can be used by an insurance company to deny coverage. The same technology that can correct a debilitating hereditary disease can be used to edit embryos at the earliest stages of a new baby’s life. Bioengineers work at the interface between what we can do and what we should do. Your job will therefore require weighing the societal, ethical, and environmental stakes of your engineering decisions. It includes explaining the complexity of these decisions honestly to people outside the field. We will return to these questions throughout the course.

The first engineers were bioengineers

Humans have been engineering biology before we had a word for it. Our ancestors domesticated animals and crops, turning the wild grass teosinte into maize — a single domestication in southern Mexico roughly 9,000 years ago (Matsuoka et al. 2002), and wolves into hundreds of dog breeds. They learned to ferment milk, grain, and fruit into cheese, bread, beer, and wine by culturing microorganisms. They found and cultivated medicinal plants. In the hills of Meghalaya, in northeast India, people still guide the roots of living Ficus elastica trees across rivers to grow bridges that get stronger as they age; some span more than 50 meters and have stood for centuries (Ludwig et al. 2019).

This was accomplished by taking advantage of natural variation and selecting variants with specific properties. Breeders could not read a genome or edit a gene, but by choosing which plants and animals reproduced, they reshaped species over generations. Modern biology has sharpened the same loop into a laboratory technique called directed evolution, where researchers deliberately generate molecular variation and select (or screen) for a desired function. The approach has been used to engineer new enzymes, and earned Frances Arnold the 2018 Nobel Prize in Chemistry. Through modern genetic engineering tools, bioengineers are also creating new ways to edit cells. These techniques allow them to “correct” for genetic defects, or endow T cells with tumor-targeting receptors (chimeric antigen receptors).

Why engineering biology is different

To design a bridge, an engineer can calculate how thick each beam must be and how much the deck will sag, and be confident the answer is correct. The bridge will not fall down unless the wind blows X mph or an earthquake of magnitude 7.0 occurs. This does not mean that designing the bridge is easy, but it means that static mechanics and the materials science of steel are well established.

Building or measuring something that is alive is different. Bioengineers want to grow a sheet of human skin to heal a wound that won’t close. They want to build a diagnostic that detects small amounts of a hormone from a drop of urine. These problems are different from other engineering disciplines because the complexity of life is massive.

  • There is no datasheet for a cell. A transistor behaves the way it does because a human designed it to. A cell behaves the way it does because it survived billions of years of natural selection. Its parts are not fully understood.
  • Biology is staggeringly complex. A single human cell completes thousands of chemical reactions at once, and those reactions influence one another. Cells are arranged in highly organized structures that dictate their function. Cells interact, migrate, grow, and die in multi-cellular organs. We did not create this organization, and we can’t fully measure it. We do not know all the rules, and most of the rules we do know have exceptions.

The toolkit comes from nature

For the most part, we still cannot build the cells or proteins that we want from scratch. The enzymes, sensors, biomolecules, cancer-targeting drugs, etc that we use are not yet made de novo on a computer. Mostly, they have been found, often by accident, and repurposed. The polymerase chain reaction (PCR), which copies a chosen stretch of DNA millions of times and underlies many diagnostic and sequencing methods, needs an enzyme that keeps copying DNA at the near-boiling temperatures the reaction cycles through. It was purified in 1976 from Thermus aquaticus, a bacterium that lives in the hot springs of Yellowstone, where its DNA polymerase works best near 80 °C (Chien et al. 1976); a decade later that heat-stable enzyme was repurposed for PCR (Saiki et al. 1988), now among the most widely used techniques in biology. This is a familiar story. Restriction enzymes are bacterial defenses against viruses; we use them to cut DNA. Viral ligases paste it back together. CRISPR/Cas9 is another bacterial immune system, now used to make sequence-specific edits in cells. Antibodies made by B cells to fight infection report the result in a home pregnancy test. Green fluorescent protein from a jellyfish lets us see cells under a microscope. The list goes on. Evolution has spent billions of years building molecular machinery tuned to nearly every environment life has reached. We remain far better at finding that machinery and repurposing it than at building it ourselves.

What bioengineering looks like today

Formal bioengineering departments are relatively young — they grew in the twentieth century out of medicine and agriculture, the two fields with the most pressing biological problems at the time. Today the discipline spans a wide range of specialties:

  • Synthetic and systems biology — understanding, designing, and building biological components, devices, and networks from cellular and molecular parts.
  • Cellular, tissue, and genetic engineering — directing and modifying living cells and genetic material to regenerate tissue, treat disease, or build new therapies.
  • Biomaterials and nanotechnology — designing biological and bio-inspired materials, assembled at the scale of proteins and DNA, to repair or interface with living systems.
  • Computational biology and bioinformatics — applying computation and data science approaches to large-scale biological measurements.
  • Bioinstrumentation — inventing tools to observe and manipulate living systems, from imaging machines and biosensors to prosthetics and diagnostics.
NoteFurther reading
  • The Royal Swedish Academy of Sciences, 2018 Nobel Prize in Chemistry — directed evolution of enzymes (Frances Arnold) and phage display of peptides and antibodies.
  • The Royal Swedish Academy of Sciences, 2020 Nobel Prize in Chemistry — CRISPR-Cas9 genome editing (Emmanuelle Charpentier and Jennifer Doudna).
  • National Institute of Biomedical Imaging and Bioengineering, “Science topics” — short overviews of the field’s main areas.

References

Chien, Alice, David B. Edgar, and John M. Trela. 1976. “Deoxyribonucleic Acid Polymerase from the Extreme Thermophile Thermus Aquaticus.” Journal of Bacteriology 127 (3): 1550–57. https://doi.org/10.1128/jb.127.3.1550-1557.1976.
Ludwig, Ferdinand, Wilfrid Middleton, Friederike Gallenmüller, Patrick Rogers, and Thomas Speck. 2019. “Living Bridges Using Aerial Roots of Ficus Elastica – an Interdisciplinary Perspective.” Scientific Reports 9 (1): 12226. https://doi.org/10.1038/s41598-019-48652-w.
Matsuoka, Yoshihiro, Yves Vigouroux, Major M. Goodman, Jesus Sanchez G., Edward Buckler, and John Doebley. 2002. “A Single Domestication for Maize Shown by Multilocus Microsatellite Genotyping.” Proceedings of the National Academy of Sciences 99 (9): 6080–84. https://doi.org/10.1073/pnas.052125199.
Saiki, R. K., D. H. Gelfand, S. Stoffel, et al. 1988. “Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA Polymerase.” Science 239 (4839): 487–91. https://doi.org/10.1126/science.2448875.